20 December 2017, Volume 31 Issue 4
    

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  • Editorial
    I. Robuffo, E. Toniato, L. Tettamanti, F. Mastrangelo, G. Ronconi, I. Frydas, Al. Caraffa, S. K. Kritas, P. Conti
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 837-842.
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    Innate immunity consists of physical and chemical barriers which provide the early defense against infections. Innate immunity orchestrates the defense of the host with cellular and biochemical proteins. Mast cells (MCs) are involved in innate and adaptive immunity and are the first line of defense which generates multiple inflammatory cytokines/chemokines in response to numerous antigens. MC-activated antigen receptor Fc-RI provokes a number of important biochemical pathways with secretion of numerous vasoactive, chemoattractant and inflammatory compounds which participate in allergic and inflammatory diseases. MCs can also be activated by Th1 cytokines and generate pre-formed and de novo inflammatory mediators, including TNF. IL-37 is an anti-inflammatory cytokine which binds IL-18R-alpha chain and reduces the production of inflammatory IL-1 family members. IL-37 down-regulates innate immunity by inhibiting macrophage response and its accumulation and reduces the cytokines that mediate inflammatory diseases. Here, we discuss the relationship between MCs, innate immunity, and pro-inflammatory and anti-inflammatory cytokines.

  • Article
    L. Jiang, H. Li, N. Zhao
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 843-853.
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    The prevalence of neurodegenerative diseases worldwide has increased dramatically in the last decades. Hypoxia and oxidative stress play a central role in the pathogenesis of neurodegenerative diseases. Thymoquinone (TQ) is a monoterpenoid hydrocarbon compound that possesses potent antioxidant activity. In the current study, we investigated the neuroprotective effects of TQ against CoCl2, a widely used hypoxia-inducing agent. We found that TQ inhibited CoCl2-indcued cytotoxicity in vitro, as reflected by an increase of cell viability and decrease of apoptosis in CoCl2-treated PC12 cells. TQ exhibited a potent protective effect against CoCl2-induced neurotoxicity in vivo, as evidenced by decreased time spent to find the platform site in the Probe trials, reduced escape latencies, decreased traveling distance and reduction of apoptotic cell death in brains in CoCl2-treated rats. CoCl2-resulted decrease of glutathione (GSH) and increase of malondialdehyde (MDA) levels were significantly inhibited by TQ. Inhibition of GSH synthesis by buthionine sulphoximine (BSO) significantly attenuated TQ-induced neuroprotective effects against CoCl2 in rats and in PC12 cells. TQ could upregulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLc) and Nrf2/glutamate-cysteine ligase modifier subunit (GCLm) pathway which contributed to antioxidant and neuroprotective effects of TQ. In summary, we found that TQ exhibited protective effects against neurotoxicity via upregulation of Nrf2/GCL signaling. Upregulation of Nrf2/GCL signaling promoted the synthesis of GSH and contributed to attenuation of oxidative stress, neuronal cell apoptosis and neurotoxicity. These data have appointed a new path toward the understanding of the neuroprotective activities of TQ.

  • Article
    M. Dyszkiewicz-Konwińska, A. Bryja, K. Jopek, J. Budna, R. Khozmi, M. Jeseta, D. Bukowska, P. Antosik, M. Bruska, M. Nowicki, M. Zabel, B. Kempisty
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 855-864.
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    Recently, using experimental animal model, we demonstrated that porcine buccal pouch mucosal cells reflect increased proliferation capability during primary cultivation in vitro. Although the histological structure and morphogenesis in oral cavity is well recognized, the molecular mechanisms which regulate this process still need further investigation. This study was aimed to analyze the molecular marker expression profile involved in morphogenesis and differentiation capacity of porcine buccal pouch mucosal cells during their long-term primary cultivation in vitro. The experiment was performed on buccal pouch mucosal cells isolated from 80 pubertal crossbred Landrace gilts. After collection, the cells were treated enzymatically and transferred into a primary in vitro culture (IVC) system and cultured for 30 days. The cells were collected for RNA isolation after 7, 15 and 30 days of IVC and were checked for their real-time proliferative status using the RTCA system. We found an increased expression of FN1 and SOX9 genes when calculated against ACTB after 7, and 30 days of IVC, (P less than 0.01, P less than 0.001, respectively). The CXCL12 mRNA was down-regulated after 7, 15 and 30 days of IVC, but not statistically significant. Similar expression profile was observed when calculated against HPRT, however, DAB2 was found to be higher expressed at day 15 of IVC, (P less than 0.05). The cell index measured during real-time cell proliferation was substantially increased between 96 h and 147h of IVC and reached the log phase. Since FN1 and SOX9 revealed significant increase of expression after long-term culture in vitro, it is suggested that expression of these differentiation and stemness genes is accompanied by cell proliferation. Moreover, FN1 and SOX9 might be recognized as new markers of buccal pouch mucosal cell proliferation and differentiation in pigs in in vitro primary culture model

  • Article
    A. Gerges Geagea, M. Rizzo, A. Eid, I. Hajj Hussein, Z. Zgheib, M. N. Zeenny, R. Jurjus, M. L. Uzzo, G. F. Spatola, G. Bonaventura, A. Leone, L. Massaad-Massade, A. Jurjus
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 865-877.
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    It is well documented that nutraceuticals, in general, and Green tea catechins, in particular, possess a potential therapeutic value in inflammatory bowel diseases (IBD) due to their anti-oxidative and anti-inflammatory effects. This study aimed to investigate the possible mechanism of action of catechins in a rat model of colitis induced by 2.4.6 trinitrobenzene sulfonic acid (TNBS). Thirty-five young adult Sprague-Dawley rats were divided into four groups: normal control (n=5), catechins (n=9), TNBS (n=9) and TNBS plus catechins (n=12) treated. Catechin in the form of Epigallocatechin-3-gallate (EGCG) was administered daily by intraperitoneal injection, 1 week before the induction date of UC. Biopsies of the descending colon were collected on days 3, 10 and 17, and partly frozen for molecular studies or fixed for light microscopy. The status of intestinal tissue alterations and mast cells number were also assessed, as well as the mRNA expressions of IL-6, TNF-a and NF-kB, and determination of ROS expression. Histological data depicted a significant amelioration in the TNBS- and EGCG-treated rats compared to the non-treated animals. Catechin expressed strong anti-inflammatory and anti-oxidant effects, ameliorated ulcerative colitis and stabilized mast cells. The mechanism of action occurred basically through the NF-kB pathway and possibly through a crosstalk with other pathways.

  • Article
    X H. Wang, Y N. Liu, K. Tian, C X. Yao, L M. Li, Y Q. Zheng, Z M. Shi
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 879-887.
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    The aim of this study was to detect the differential expression of Artemin (ARTN) and matrix metallopeptidase protein 9 (MMP-9) in endometrial carcinoma (EC) and to assess their clinical significance in order to provide insight into the pathological mechanism of tumor infiltration and metastasis in EC. A total of 48 patients who had undergone surgery for EC at the School of Medicine and Affiliated Hospital of HeBei University of Engineering between July 2015 and July 2016 were included in the study. The 48 patients were classified into 3 groups according to tumor stage: 27 patients with EC stage I, 12 patients with EC stage II and 9 patients with EC stage III. The samples collected from each patient included fresh normal endometrial tissue, endometrial simple hyperplastic tissue and endometrial atypical hyperplastic tissue. The transcription levels of ARTN and MMP-9 mRNA in each group were investigated using RT-PCR. The expression levels of ARTN and MMP-9 protein in each group were examined using Western blotting. Spearman's correlation analysis was used to analyze the correlation between the expression levels of ARTN and MMP-9 proteins and EC tissue type. RT-PCR and Western blotting assays revealed that the expression levels of ARTN and MMP-9 were increased in normal endometrial tissue, simple hyperplastic tissue, atypical hyperplastic tissue and EC of stages I, II and III. The differences noted were statistically significant (P less than 0.05). Furthermore, Western blot analysis indicated that the expression levels of ARTN and MMP-9 proteins in lymphatic metastatic tissues were higher than those in non-lymphatic metastatic tissues (P less than 0.05). The expression levels in the infiltration tissues of the deep muscular layer were higher than those noted in the light muscular layer (P less than 0.05). The expression levels of ARTN and MMP-9 proteins were positively correlated (P less than 0.05). The data suggest that ARTN and MMP-9 are involved in the occurrence, development, invasion and metastasis of EC, and play a synergistic role in the development of EC and lymphatic metastasis.

  • Article
    N. N. Omar, A. H. El-Tawdi, R. F. Tash, Y. Shoukry, N. A. Mahmoud, W. El Bakly
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 889-899.
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    Platelet-rich plasma (PRP) has been recognized as an effective strategy for tissue regeneration, how-ever, the safety of PRP in wound healing in terms of tumorigenicity has not yet been addressed. Therefore, the aim of this study was to examine the impact of PRP administration on the expression of the inflammatory marker, tenascin-C (TnC) and the myofibroblast markers, α-smooth muscle actin (α-SMA) and vimentin. The immune suppressive response was examined by determining the level of forkhead box protein 3 (Foxp3). PRP was administered for both long-term (two times weekly for four weeks) and short-term (for the fourth week only) post-wounding. Collagen I (col1) and lysyl oxidase (LOX) were used to indicate complete healing, after which any increase in the myofibroblast or in the inflammatory markers would suggest tumor potential. Collagen III (col3), a marker for granulation tissue, was used to remark non-healing. Quantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR) and Western blot showed that after long-term administration of PRP, the expression of TnC, α-SMA and vimentin was barely detected, while being markedly expressed in the wounded non-treated group and in the short-term administration group. Moreover, the active expression of α-SMA in the two groups was associated positively with the expression of col3 and negatively with the expression of col1. The low expression of Foxp3 after short-term administration relative to the control group indicated active immunity against tumor development. In conclusion, these findings indicate that PRP can be safely used in short- and long-term administration without tumorigenesis concern.

  • Article
    S. Cantore, A. Ballini, D. De Vito, F. S. Martelli, I. Georgakopoulos, M. Almasri, V. Dibello, V. Altini, G. Farronato, G. Dipalma, D. Farronato, F. Inchingolo
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 901-910.
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    Dental tissues represent an alternative and promising source of post-natal Mesenchymal stem cells (MSCs) for tissue engineering. Furthermore, dental stem cells from apical papilla (SCAPs) cells can be obtained from the wisdom tooth which is unnecessary for human masticatory function and frequently extracted for orthodontic reasons or dysodontiasis. More precisely, apical papilla is the immature, mostly uncalcified, precursor of the tooth root, therefore is composed of more undifferentiated cells than dental pulp. In addition, tooth extraction, especially by piezosurgery technique, can be considered less invasive in comparison to bone marrow or other tissues biopsy. Our work is aimed to investigate the safety of and predictable procedure on surgical immature third molar extraction and to provide new insight on SCAP research for future biomedical applications. The isolated cells were examined for stem cell properties by analyzing their colony-forming efficiency, differentiation characteristics and the expression of MSC markers

  • Article
    G. Di Spigna, M. Iannone, P. Ladogana, S. Salzano, M. Ventre, B. Covelli, E. De Marinis, L. Postiglione
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 911-921.
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    Myocardial infarction is the leading cause of morbidity and mortality in developed countries. It causes a left ventricular dysfunction, mainly due to the loss of functional tissue, resulting in heart failure. New therapies are being developed, using a tissue engineering approach, with the ultimate goal of restoring cardiac function by regenerating and repairing the damaged myocardium. In the present study we investigated the behaviour of a specific population of c-kit positive human cardiac stem cells, called Multipotent Adult Stem Cells (MASCs), grown within three-dimensional collagen scaffolds (3D), to establish whether they could be used in post-infarction cardiac regeneration. We also evaluated the expression levels of the Granulocyte Macrophage-Colony Stimulating Factor Receptor (GM-CSFR) and endoglin, a component of the Transforming Growth Factor beta (TGF-ß) receptor complex. Finally, we also evaluated the expression of the α2β1integrin. MASCs cultured within 3D collagen matrices are able to proliferate and migrate even in the absence of chemotactic agents and express high levels of factors involved in cell proliferation and migration, such as GM-CSFRα chain and integrins. They therefore represent a promising approach to tissue engineering aimed to restore cardiac function. Our results also suggest a role of GM-CSF in cell proliferation, while TGF-β does not seem to be relevant

  • Letter
    M. Bednarczyk, M. Muc-Wierzgoń, D. Waniczek, E. Fatyga, K. Klakla, U. Mazurek, J. Wierzgoń
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 923-927.
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    There is evidence that autophagy can play a dual role in tumor cells-as a tumor suppressor, and a process involved in tumor cell survival. The aim of this work was to assess the expression of the genes engaged in the autophagy process in biopsies taken from the colon, confirmed as adenocarcinoma, and normal tissue and to relate them to the clinical stage of the tumor. A total of 20 pairs of surgically removed tumors and healthy (marginal) tissue samples from colorectal cancer patients at clinical stages (CS) I-IV were analyzed. Gene expression profile analysis was performed using HG-U133A microarrays. Differentially expressed genes were identified, using the PL-Grid Infrastructure. Only for CSI, there were two specific genes: FOXO1 and BNIP1; further in CSII-LAMP2, MET and BCL2L, in CSIII-HIF1A and 2 ID mRNAs for HGF and 18 genes were specific for CSIV in comparison to controls. PINK1 is the only gene that differentiates all transcriptome groups from controls. Furthermore, examination of the expression of genes associated with the autophagy process may allow for better knowledge and understanding of the processes occurring during the development of colon cancer. The presented genes may be used as prognostic markers of clinical stages of colorectal cancer, contributing to the development of new lines of therapy focused on reducing metastasis of the primary tumor.

  • Letter
    K. Walkiewicz, E. Nowakowska-Zajdel, J. Strzelczyk, S. Dzięgielewska-Gęsiak, M. Muc-Wierzgoń
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 929-934.
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    Colorectal cancer is the third most common cancer in the world. Our study analyzed the potential significance of serum levels of selected adamalysines (ADAM10, ADAM12, ADAM17, ADAM28) in colorectal cancer patients. The study was performed on a group of 85 colorectal cancer patients (48 men, 37 women). Serum protein concentrations were measured by ELISA. The ADAMs serum level changes were analyzed according to selected clinical parameters (BMI, sex, age, clinical stage of disease). The following ranges of concentration of analyzed proteins were obtained: ADAM10 min=1.7, max=321.8 [ng/ml]; ADAM12 min=0.6, max=26.7 [ng/ml]; ADAM17 min=0.4, max=9.8 [ng/ml]; ADAM28 min=17.1, max=1545.8 [ng/ml]. In addition, it was stated that there is a relationship between the serum level of ADAM28 and the degree of the clinical stage (p less than 0.04). The obtained results could be the starting point for further research into the role of adamalysines in the development of colorectal cancer, as well as the potential predictive and prognostic value of these proteins.

  • Letter
    S. Y. Liu, L. Zhang, Y. Zhang, Y. Zhen, Y. F. Wu
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 935-941.
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    We aimed to identify important genes associated with septic shock and then explore the possibly significant mechanisms of this disease. We downloaded GSE26440 expression data of samples from 98 children with septic shock and 32 normal controls from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in samples from patients with septic shock were analyzed in comparison with those in samples from normal controls using a limma package. Functional enrichment analysis for DEGs was performed using DAVID, and a protein-protein interaction (PPI) network was constructed. Upstream transcription factors for DEGs were predicted using the CHIPBase database, and a transcriptional regulation network was constructed. A total of 383 significantly DEGs, including 141 downregulated and 242 upregulated genes, were obtained in the sepsis shock group compared with the normal group. The top five nodes in the PPI network were lysine (K)-specific demethylase 6B (KDM6B), histone deacetylase 2 (HDAC2), V-Myc avian myelocytomatosis viral oncogene homolog (MYC), heat-shock protein 90 kDa alpha (cytosolic), class B member 1 (HSP90AB1), and poly (A)-binding protein, cytoplasmic 1 (PABPC1). Nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) was the transcription factor targeted by most genes, and it regulated the expression of KDM6B, HDAC2, MYC, HSP90AB1, and PABPC1. In conclusion, KDM6B, HDAC2, MYC, HSP90AB1, and PABPC1 may play important roles in the development of septic shock. Furthermore, NFκB may be involved in septic shock by regulating the expression of KDM6B, HDAC2, MYC, HSP90AB1, and PABPC1

  • Letter
    J. Marti, F. López, I. Gascón, J. Julve
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 943-950.
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    Currently, treatment for acute rhinitis (AR) is symptomatic but no clear agreement exists to control its development. Propolis extract may appear as a promising natural treatment for AR, but its beneficial effects have not yet been fully tested. Forty children suffering from AR and common cold symptoms aged between 2-12 years were enrolled in a prospective epidemiological multicentre study. A 7-day treatment with propolis nasal spray (3 times/day) was applied and a comparison of symptomatology, subjective global improvement and quality of life (QoL) between baseline (day 1) and final (day 7) visits were performed. The main goal was to evaluate the changes in symptom intensity using the Jackson's scoring test. After 7 days of treatment there was a significant decrease of symptoms both in the total score (p less than 0.0001) and in regard to each AR symptom (p less than 0.01). On the whole, the sample reported no symptoms by day 7, and the resolution of symptoms occurred approximately at day 4. Furthermore, there was no need for supplementary treatment. Both the subjective global improvement impression and the QoL of patients appeared to significantly improve after treatment. No adverse events (AEs) were found globally. It can be concluded that propolis nasal spray effectively improves recovery from infectious AR and common cold symptoms in children and is an optimal alternative in the treatment of this disease without need for any adjuvant treatment

  • Letter
    M. B. Khawar, N. Sheikh
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 951-956.
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    Obesity is a commonly growing life-threatening problem of the modern world. The present study was aimed to assess alterations in transaminase levels as well as leptin and hepcidin levels of sera through ELISA after high fat diet consumption for sixteen weeks by albino rats (n=5). Three groups were established: experimental groups 1 and 2 and a control group. Group 1 was fed on a high fat diet having a composition of 33% rat chow +33% sucrose +33% milk powder. Similarly, group 2 was fed with another high fat diet with a mixture of rat chow and milk powder ad libitum. The control group was fed on normal rat chow and water ad libitum. After sixteen weeks, the rats were euthanized and blood was collected for serum separation. Serum levels of alanine aminotransferase showed a positive significant increase (P=0.0325) while a significant negative change (P=0.0006) was noted in aspartate aminotransferase levels in both the experimental groups compared to the control group. Serum leptin levels were found to be increased up to 10.06-fold in Group 1 and 6.11-fold in Group 2 when compared to controls. On the other hand, serum hepcidin levels showed up to 1-fold and 2.59-fold changes in Group 1 and Group 2, respectively, compared to controls. Taken together, from these results it can be concluded that a high fat diet not only disturbs normal metabolism, but it also leads to liver inflammation which is obvious by the changes in transaminase activity as well as leptin and hepcidin levels

  • Letter
    A. Kasperska-Zajac, A. Grzanka, A. Damasiewicz-Bodzek, K. Bieniek, A. Skrzypulec-Frankel, K. Stencel-Gabriel, A. Sikora-Zydek
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 957-961.
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    Chronic spontaneous urticaria (CSU) is associated with activation of acute phase response. Questions arise regarding its association with other inflammatory mediators. To determine plasma IL-8 concentration in CSU patients and its association with C-reactive protein (CRP) concentration, a nonspecific inflammatory marker of the disease activity, concentrations of plasma IL-8 and serum CRP were measured in CSU patients and compared with healthy controls. IL-8 and CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects. In addition, there were significant differences in IL-8 and CRP concentrations between CSU patients with moderate-severe symptoms and the healthy subjects. Plasma IL-8 and serum CRP concentrations showed a significant correlation with urticaria activity score (UAS). Additionally, a significant positive correlation was observed between IL-8 and CRP concentrations. Up-regulations of IL-8 and its association with the marker of clinical and inflammatory activity suggest a role of this cytokine in the pathogenesis of CSU.

  • Letter
    M. Khalid, M. Bilal, D. Hassani, H. M. N. Iqbal, D. Huang
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 963-969.
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    In this study, Aerva javanica was used to extract the essential oil with notable medicinal activities. The chemical composition was investigated by high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC-MS). Ten major chemical compounds were identified as flavonoids derivatives, dihydroxylated and glycosylated metabolites. The antimicrobial, antioxidant, and cytotoxicity activities were tested using agar well-diffusion assay, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free-radical scavenging and linoleic acid oxidation assays and hemolytic assay against human erythrocytes (RBCs), respectively. Plant extracts exhibited different extents of antimicrobial activities against selected bacterial and fungal strains; however, the essential oil displayed potent antimicrobial activity against all the tested strains. The percentage inhibition of linoleic acid oxidation and inhibitory concentration (IC50) were recorded to be in the range of 42.45-96.21% and 14.21-38.18 μg/mL, respectively. Cytotoxicity profile of A. javanica extracts and essential oil was found in the range of 5.82 to 14.47%. In conclusion, A. javanica essential oil could be a potential alternative to chemical additives in the food and pharmaceutical industries

  • Letter
    M. Shu, BY. Wang, J. Zhang, CY. Guo, XH. Wang
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 971-976.
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    To analyze the nursing effect on the respiratory function of thoracotomy patients, sixty thoracotomy hospitalized patients were studied. The subjects were divided into a normal group (A) and an observation group (B). The patients in group A received routine nursing only, while those in group B received chest physiotherapy as well as routine nursing. Afterwards, the respiratory function indicators of the two groups were compared and a data analysis was performed. The results showed that the partial pressure of oxygen (PO2) value of the patients in group B was greater than that of the patients in group A while the partial pressure of carbon dioxide (PCO2) value in group B was smaller than that in group A, and there was a significant difference between the two groups (p less than 0.05). The vital capacity under normal circumstances and forced breathing of group B were greater than that of group A and the difference was statistically significant (p less than 0.05). The incidence of complications (atelectasis, respiratory infections, pleural effusion) was statistically significant between the two groups (p less than 0.05). The degree of autonomic respiratory dysfunction in group B was lower than that in group A, and there was a significant difference (p less than 0.05), suggesting that the respiratory function in patients receiving chest physiotherapy improved significantly.

  • Letter
    Q. Wang, J. Wang, D. Gao, J. Li
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 977-983.
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    Bortezomib (BTZ) is generally used as a chemotherapeutic agent for the treatment of multiple myeloma; however, one of the significant limiting complications of BTZ is painful peripheral neuropathy observed during BTZ therapy. There is a lack of drugs which can prevent and/or treat the painful symptoms induced by BTZ, as the underlying molecular mechanism leading to neuropathic pain remains largely unclear. In the present study, we examined engagement of proteinase-activated receptor 2 (PAR2) and transient receptor potential ankyrin 1 (TRPA1) in neuropathic pain induced by BTZ in rats. Our results demonstrated that systemic injection of BTZ increased mechanical pain and cold sensitivity as compared with control animals (P less than 0.05 vs control rats). Our data further showed that blocking respective PAR2 and TRPA1 attenuated mechanical pain and cold sensitivity observed in control rats and BTZ rats (P less than 0.05 vs vehicle control). Notably, the attenuating effect of blocking PAR2 and TRPA1 on mechanical pain and cold sensitivity was significantly less in BTZ rats than that in control rats. In addition, protein expression of PAR2 and TRPA1 was upregulated in the lumbar dorsal root ganglion of BTZ rats, and inhibition of PAR2 decreased the levels of TRPA1 and attenuated its downstream pathways (namely, PKCɛ and PKA). Overall, we revealed specific signaling pathways leading to neuropathic pain induced by chemotherapeutic BTZ and that blocking PAR2 and TRPA1 in sensory nerves is beneficial to improve neuropathic pain during BTZ intervention.

  • Letter
    M.H. Abbasi, S. Fatima, M.B. Khawar, N. Naz, K.A. Mujeeb, T. Akhtar, N. Sheikh
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 985-989.
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    Many studies have been carried out in order to determine the toxicity of medicinal plants. The objective of this study was to compare and analyze the hepatic response against two doses of Nerium oleander, (N. oleander) “kaner” leaf decoction. Aqueous leaf decoction was injected intramuscularly into both hind limbs of male rats (200∓10g), assigned into three categories (n=4): control group with no treatment; group I, injected with 5 ml/ kg; and group II injected with 10 ml/ kg of leaf decoction, respectively. Animals were sacrificed 6 h after administration and hepato-histological changes were then observed. The decoction induced an acute phase reaction reflected by a more significant recruitment of inflammatory cells in group II than in group I and controls, as observed by histological studies. These results indicated that both doses can induce an acute-phase condition. Hence, traditional practice of medicinal plants without preliminary dose assessment must not be administered.

  • Letter
    JK. Li, C. Wang, HD. Gong, HZ. Li
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 991-996.
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    The aim of this study was to analyze the changes in coagulation in meningioma patients treated with different injections using the method of acute hypervolemic hemodilution (AHH). One hundred fifty hindbrain membrane meningioma patients were randomly divided into 5 groups, 30 per group. The first group were injected 40ml/time with Danhong after anesthesia induction; the second group were injected with 40ml~60ml/time Kangai and combined with interventional chemotherapy and embolization procedure; the third group of AHH were injected with polygeline 15ml/kg; the fourth group were injected with hydroxyethyl starch (130/0.4) sodium chloride in doses of 15ml/kg; the control group underwent basic treatment for lowering blood pressure and lowering blood fat. The changes of coagulation index were recorded before and after surgery and before and after the injection of different medications. Compared to the control group, for the first group of AHH, after being treated for 10 days and 30 days, the concentrations of bone specific alkaline phosphatase (BALP), bone Gla protein (BGP) and pro-collagen carboxy-terminal propeptide (PICP) were higher than that of the control group, the levels of endotoxin (ET) and C-reactive protein (CRP) were decreased compared to the control group (p less than 0.05); for the second group of AHH, after being treated for 10 days, the index of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg) were not significantly changed, but the related level of vascular endothelial growth factor (VEGF) significantly decreased (p less than 0.05). Comparing the coagulation function index after surgery in the third and fourth groups, there were no significant changes in mean arterial pressure (MAP) level, heart rate (HR) value presented a low decrease, central venous pressure (CVP) level increased and the level of interleukin IL-6 showed a steady state after increasing. Analyzing the levels of interleukin IL-8 and tumor necrosis factor-α (TNF-α) after surgery, it was seen that in the third group they increased and in the fourth group they decreased (p less than 0.05). Danhong injection improved the coagulation function and microcirculation of patients, Kangai injection and interventional chemotherapy and embolization restrained the appearance of tumor angiogenesis, AHH operation with polygeline injection and hydroxyethyl starch (130/0.4) sodium chloride kept blood flow in normal parameters

  • Letter
    X. Du, J. Jiao, X. Cheng, L. Wang, K. Li, H. Liu, C. Wang, C. Arena, K. Zhurakivska, G. Guglielmi, L. Lo Muzio
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 997-1003.
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    Quantitative Computed Tomography (QCT) was used to investigate age-related changes in trabecular bones of the mandible. The volumetric Bone Mineral Density (vBMD) of mandibles was found to be increasing with aging in the 20-29, 30-39, 40-49 age groups, while resulted decreasing in the 50~ years age group in a Chinese population. The aim of this study was to validate QCT as a reliable method to measure the vBMD of the mandible and to assess vBMD of the mandible in a Chinese population. A total of seven hundred and eighteen volunteers (299 males, 419 females), ranging from 20 to 63 years of age, previously enrolled in another study, were included for vBMD measurements by QCT. A total of 50 subjects were enrolled for the validation of QCT measurement. Basic information (age, height and weight), and vBMD of the mandible (middle, body and angle) were recorded. Comparisons among age and sex groups were analyzed using the Mann-Whitney test. Linear correlation analysis between vBMD and age was performed. The mandibular vBMD was twice measured with QCT by one operator and resulted highly repeatable (ICC 0. 97, P 0. 05). The vBMD in the middle of the mandible was the highest, followed by that in the body and at the angle of mandible. In each age group, the mean vBMD increased with aging except for the 50~ years age group (P less than 0.05) in which it decreased. The mean mandibular vBMD was higher in females than males in each age group (P less than 0.05). Correlation between vBMD and age was statistically significant (r=0.15, P less than 0.01). QCT shows high precision for the measurement of BMD in the mandible. The present study provides normative data of the mandible in an age- and sex-stratified manner, which can be helpful in clinical practice

  • Letter
    Q. Lin, X-Y. Hong, D. Zhang, H-J. Jin
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1005-1012.
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    The zygomatico-maxillary complex functions as the principle buttress of the face and is the cornerstone to an individual's aesthetic appearance. Its fracture not only creates cosmetic deformities owing to its position and facial contour, but can also cause disruption of ocular and mandibular functions. The aim of this study was to evaluate the quality, efficacy and impact of internal fixation of zygomatic complex fractures on functional and cosmetic outcomes. A prospective study was carried out on 100 patients who were divided according to the classification and the severity of injury. Subjective evaluation was submitted based on the patient's perception of signs and symptoms in the preoperative and postoperative periods. Intraoperative and postoperative assessment of bone reduction quality was made according to the type of the fracture and related difficulties; also, the difference between these groups was observed as functional and esthetic outcome. To optimize the treatment of zygomatic bone fractures, a pre-designed questionnaire was used for subjective evaluation of symptoms and treatment outcome. In 70% of cases, ophthalmologic consultation was taken and was most common in type VII fractures (100% cases). Neurosensory disturbance was the most common finding (60%), followed by diplopia (56R%), pain upon mouth opening (54%) and malar depression (50%). Out of all possible 400 fracture sites in 100 patients of zygomatic complex fractures, 266 (66.5%) fractures were detected by clinical examination, in contrast to 330 (82.5%) on radiological examination, which were highest at zygomatic-maxillary buttress (93%) followed by infraorbital rim (91%) and almost equal among fronto-zygomatic site (72%) and zygomatic arch (74%). The scores from the questionnaire for annoyance were significantly higher for paraesthesia (23%) than for trismus (10%), pain (8.5%), or deformity (8.25%). Residual deformity and pain significantly influenced the total satisfaction. Conclusively, there are many treatment modalities available for zygomatic complex fractures, and the preferred methods should be selected on the basis of fracture type, fracture severity, pre-operative signs and symptoms. Regarding the requirements of fracture site exposure and actual fixation, one priority should be to minimize postoperative complications, morbidity and residual deformities.

  • Letter
    A. Goren, J. Shapiro, T. Naccarato, M. Situm, M. Kovacevic, N. Lonky, T. Lotti, J. McCoy
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1013-1016.
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    In recent years, dermatologists have observed an increase in the incidence of male androgenetic alopecia (AGA). In a survey of 41 dermatologists, 88% reported an increase in incidence of AGA in men younger than 30 years. This phenomenon has no apparent explanation. However, due to the strong genetic inheritance component of AGA, a social or environmental factor which favours the inheritance of genes that increase the risk of developing AGA is suspected. To date, the strongest predictor of AGA in men has been the length of the CAG repeat located in the androgen receptor gene (AR gene) on the X chromosome. The same genetic variant in women is associated with ovulation at a later age, higher antral follicle count, and lower risk for premature ovarian failure. This led us to theorize that, due to social pressure to conceive later in life, women carriers of the short CAG repeat in the AR gene would have a selective advantage to conceive later in life and would thus favour male offspring exhibiting AGA

  • Letter
    Y-Z. Deng, L-G. Xu, L. Chen, D. Zhou, Y. Liu
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1017-1022.
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    Cervical spondylosis is the most common type of spinal pathology which is more common in middle-aged or senile populations with a high potential to affect physical and mental health. This study evaluates the effectiveness of acupuncture in the management of cervical spondylosis. After a detailed literature search in electronic databases, the required data were acquired from selected research articles and meta-analyses were performed to obtain the percent cure, failure and total effectiveness rates under random effects model. Meta-regression was performed to identify the factors affecting the efficacy. Twenty-seven studies were selected for data acquisition (2,853 patients; average age 46.2±9.5; 51.7±12.5% males). Acupuncture alone had 33.41% (25.50, 41.24) cure rate but in combination with other therapies it rose to 53.36% (41.9, 64.8). Similarly, total effectiveness rate was 87.01% (83.40, 90.62) with acupuncture alone and 93.62% (89.85, 97.38) with acupuncture in combination with other therapies. Age was inversely associated with the percent cure rate and the number of combination therapies with acupuncture was positively associated with the cure rate. In conclusion, acupuncture therapy alone can provide cure and total effectiveness rates of 33% and 87%, respectively, but acupuncture with additional therapies can improve the cure and total effectiveness rates to 53% and 94%, respectively. Age inversely affects efficacy and the number of additional therapies improves the efficacy.

  • Letter
    I.M. Tahir, T. Iqbal, A. Jamil, M. Saqib
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1023-1027.
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    B-Cell Lymphoma protein-2 (BCL-2) is one of the most studied proteins with substantial regulatory potential for both apoptosis and autophagy. BCL-2 confer chemoresistance through influencing cancer pathophysiology. Serum level of lactate dehydrogenase (LDH) predicts increased anaerobic glycolysis and is associated with metabolic modulation in cancer cells. In the present research, the interplay of BCL-2, total oxidative status (TOS) and LDH was investigated in patients with acute lymphoblastic leukemia (ALL). The studied parameters, BCL-2 protein (p less than 0.001), TOS (p less than 0.001) and LDH (p less than 0.001) were significantly elevated in the ALL group compared to the normal group (N-group). However, the total antioxidant status (TAS) was reduced significantly (p less than 0.01) in ALL patients. In the ALL group, the TOS had significant negative correlation with TAS (p less than 0.01). Furthermore, non-significant positive correlations were found between BCL-2 and LDH, BCL-2 and TAS and LDH and TAS (each with; p>0.05). However, a negative non-significant correlation was observed between BCL-2 and TOS and LDH and TOS (each with; p<0.05)

  • Letter
    C.Y. Chen, J. Chen, C.C. Xia, Z.X. Huang, B. Song
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1029-1036.
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    The aim of this study was to investigate the value of Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase (HBP) imaging and T1 mapping sequence in the differentiation of hepatocellular carcinoma (HCC). A total of 45 patients with HCC who were to undergo a resection were enrolled in this study. Gd-EOB-DTPA-enhanced magnetic resonance examination was performed prior to resection. T1 mapping was performed before and 20 min after injection of Gd-EOB-DTPA. T1 values of the lesions were measured on pre-contrast (T1p) and during HBP (T1-HBP) on T1 maps. The signal intensity, the diameter and the margin of HCC lesions on HBP images were analyzed. The reduction in T1 value (T1d) and the reduction rate (ΔT1%) of T1 mapping between pre-contrast and HBP were calculated. The Edmondson-Steiner classification of each lesion was made after surgery. The SPSS software package was used for statistical analysis and the analysis of receiver operator characteristic (ROC) curve and area under the curve (AUC) were carried out by using MedCalc software package. Mean values of T1p and T1-HBP were 1935.4±730.8 ms and 1257.1±529.1 ms, respectively. T1p accuracy (AUC = 0.685, p = 0.037) in predicting pathological grading was similar to that of T1-HBP (AUC = 0.751, p = 0.005). A T1p of 1648.2 ms or greater had a sensitivity and specificity of 85.19% and 61.11%, respectively. A T1-HBP of 1006 ms or greater had a sensitivity and specificity of 81.84% and 61.11%, respectively. The number of HCCs with a non-smooth tumor margin was 20 (44.4%), and a non-smooth tumor margin correlated moderately with the Edmondson-Steiner grade (Spearman r = 0.491, p = 0.041). There was no significant correlation between T1d, ΔT1%, HCC signal intensity on HBP image and lesion diameter with pathologic grading. T1 mapping in pre-contrast and HBP of Gd-EOB-DTPA-enhanced MRI, a non-smooth tumor margin in the HBP of Gd-EOB-DTPA-enhanced MRI, are useful in predicting the pathologic grading of HCC

  • Letter
    T. Jagmag, M. Tirant, T. Lotti
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1037-1041.
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    Depression and mood disorders often develop after dermatological conditions which could be primary or secondary to dermatological pathology. The oxidative and psychological stress cause physiological changes in the body. Shift in the methylation pathway, elevated cortisol, lowered neurotransmitter levels and lowered immune system allow infection to penetrate the body and lead to anxiety and depression. Here, a case report of a 20 year old male patient is presented to show how infectious skin lesions, unresponsive to the usual treatment plan, were treated after using a multipronged approach of addressing systemic infection of Escherichia coli, elevated cortisol levels and nutritional imbalances

  • Letter
    H. Mou, L. Yu, X. Zheng, Q. Liao, X. Hou, Y. Wu, L. Yu
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1043-1047.
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    The aim of this study was to assess the importance of p16 gene expressions in pancreatic cancer tissue for early diagnosis and treatment. Two groups were included in the study: an experimental group of 35 pancreatic cancer tissue specimens and a control group of 35 pancreatic cancer adjacent tissues collected during surgery. The expression of p16 gene in the two groups was observed using the immunohistochemical streptavidin peroxidase conjugated (S-P) method. The results were statistically interpreted using SPSS22.0 software. The positive expression rate of p16 in the experimental group was lower than that of the control group (p less than 0.05). Comparing the intensity of p16 gene expression, differentiation degree, clinical stage and metastases of nearby lymph nodes the differences had statistical significance (p less than 0.05). The intensity of p16 gene expression in high and medium differentiated pancreatic cancer group was higher than that of the low differentiated group. p16 gene expression in stages III and IV groups was lower than that in stages I and II groups. Differentiation degree, clinical stage, metastases of nearby lymph nodes and distant metastasss were negatively related with p16 gene expression (p less than 0.05). There was no correlation between age or gender and p16 gene expression. The decreased expression of p16 gene in pancreatic cancer tissue was negatively correlated with differentiation degree and clinical stage. Our results indicated that p16 can be used as a cue signal for diagnosing advanced pancreatic cancer.

  • Letter
    A. Goren, T. Naccarato, M. Situm, M. Kovacevic, T. Lotti, J. McCoy
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1049-1053.
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    Topical minoxidil is the only topical drug approved by the US Food and Drug Administration (FDA) for the treatment of androgenetic alopecia. However, the exact mechanism by which minoxidil stimulates anagen phase and promotes hair growth is not fully understood. In the late telegen phase of the hair follicle growth cycle, stem cells located in the bulge region differentiate and re-enter anagen phase, a period of growth lasting 2-6 years. In androgenetic alopecia, the anagen phase is shortened and a progressive miniaturization of hair follicles occurs, eventually leading to hair loss. Several studies have demonstrated that minoxidil increases the amount of intracellular Ca2+, which has been shown to up-regulate the enzyme adenosine triphosphate (ATP) synthase. A recent study demonstrated that ATP synthase, independent of its role in ATP synthesis, promotes stem cell differentiation. As such, we propose that minoxidil induced Ca2+ influx can increase stem cell differentiation and may be a key factor in the mechanism by which minoxidil facilitates hair growth. Based on our theory, we provide a roadmap for the development of a new class of drugs for the treatment of androgenetic alopecia

  • Letter
    ZM. Shi, YN. Liu, B. Fu, YF. Shen, LM. Li
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1053-1059.
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    The aim of the present study was to provide a novel method for the diagnosis, prevention and treatment of endometrial cancer by the determination of the characteristic expression of the eukaryotic translation initiation factor 4E (eIF4E) and the enzyme matrix metalloproteinase 9 (MMP9) in endometrial cancer tissue. Three types of endometrial tissue specimens were selected (including 20 cases of normal endometrial tissue specimens, 15 cases of hyperplastic endometrial tissue specimens and 45 cases of endometrial cancer tissue specimens). The expression of eIF4E and MMP9 in the specimens was examined by immunohistochemistry and their corresponding levels were statistically analyzed. The positive expression rates of eIF4E and MMP9 in endometrial cancer specimens were 64.44% and 66.67% respectively, which were higher than those noted in hyperplastic endometrial tissue specimens and normal endometrial tissue specimens (p less than 0.05). The comparisons between the groups indicated that the expression levels of eIF4E and MMP9 in the endometrial cancer specimens were increased compared with those noted in the normal endometrial tissue specimens (p less than 0.0167). In endometrial cancer specimens, the positive expression rates of eIF4E and MMP9 were related to the endometrial cancer stages as determined by the International Federation of Gynecology and Obstetrics (FIGO), tumor cell differentiation degree and lymphatic metastasis (p less than 0.05) classifications. eIF4E expression was positively related to MMP9 expression in endometrial cancer specimens. High expression levels of eIF4E and MMP9 proteins were noted in endometrial cancer specimens, which were correlated with FIGO stages, histological grade and degree of lymphatic metastasis. Thus, endometrial cancer and malignant biological behavior may be connected to the high expression of eIF4E and MMP9. The positive correlation between eIF4E and MMP9 expression in endometrial cancer specimens suggests their potential up-regulation during carcinogenesis

  • Letter
    T. Akhtar, N. Sheikh, T. Shan, R. Ghazanfar
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1061-1066.
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    Transplantation has evolved into an accepted treatment for end-stage organ failure. The major limitation for solid organ transplantation is organ rejection, which is an adaptive immune response caused by the activation of T-cells. Immunosuppressant drugs are used to overcome this problem. Tacrolimus is a powerful immunosuppressive drug which is used to minimize the risk of organ rejection. The present study was designed to find the toxic effects of tacrolimus on lungs and kidneys. Wistar rats were divided into 4 experimental groups and one control group (n=9). Each rat of the experimental group was orally given the aqueous suspension of tacrolimus powder (3mg/ml) and dissected after 6, 12, 24 and 48 hours of tacrolimus suspension dose. Lungs and kidneys were excised and processed for histopathological and histochemical alterations. Kidney tissues presented signs of toxic potential on tissue architecture such as increased interstitial spaces, necrosis, especially acute tubular necrosis, glomerular shrinkage, dilated blood vessels and enlargement of Bowman’s capsule. Lung sections also confirmed the toxic potential, characterized by bronchiolar wall thickening, alveolar cells necrosis, collapsing of alveolar spaces and interstitial round cell infiltrate. Results of Prussian blue iron staining showed no iron deposition in kidney architecture while in lung sections, iron accumulation was evident. Taken together from these observations we can conclude that tacrolimus may induce toxicity to a certain extent with structural distortion of the kidneys and lungs

  • Letter
    GT. Liu, C. Shen, XH. Ren, L. Yang, YM. Yu, YX. Xiu, RH. Li, L. Jiang, CL. Zhang, YW. Li
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1067-1072.
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    Esophageal squamous cell carcinoma is the most common type of esophageal cancer in Eastern Europe and Asia, being the 6th most common cause of cancer deaths worldwide. The aim of this study was to analyze the expression of transmembrane serine protein in esophageal squamous cell carcinoma, and to correlate it with the clinical biological features of esophageal cancer. The expression of transmembrane protease serine 4 (TMPRSS4) mRNA and protein in carcinoma tissues and corresponding adjacent tissues and non-tumorous esophageal tissues was determined using PCR (qRT-PCR). The results show that both TMPRSS4 mRNA and protein expression were remarkably lower in adjacent normal tissues than in tumorous tissues. TMPRSS4 protein expression in esophageal carcinoma was correlated with patient demographic characteristics, tumor type, high TNM stages and overall survival (OS). Based on the experimental results, we conclude that TMPRSS4 is closely related to the occurrence, development and metastasis of esophageal squamous cell carcinoma

  • Letter
    J. Wang, LJ. Ren, XL. Chen, L. Ma, BJ. Chen, SJ. Ran, S. Lu
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1073-1079.
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    Colon cancer is a common malignant tumor with particularly high morbidity and mortality. The aim of this study was to compare the effect of quick rehabilitation nursing and routine nursing in postoperative recovery of patients with colon cancer after laparoscopic surgery. Two hundred forty patients with colon cancer were classified into four random groups (A, B, C and D, with 60 patients in each group). All patients underwent surgery to remove the colon tumor by laparoscopy under general anesthesia. Patients in groups A and B received quick rehabilitation nursing for post-surgery recovery. In group C patients, local anesthesia associated with quick rehabilitation nursing for post-surgery recovery was used. Group D was used as control group and the patients were treated based on routine nursing. Time to get out of bed, first bowel movement time and the average time of hospitalisation in group A was lower than group D (p less than 0.05), postoperative leukocyte level as well as the occurrence rate of nausea and vomiting, ankylenteron and pelvic adhesion was decreased in group A compared to group D (p less than 0.05), but the postoperative albumin and total protein level was higher than group D (p less than 0.05). The serum level of C-Reactive Protein (CRP) and interleukin 6 (IL-6) in group A was decreased compared to group D several days after surgery (p less than 0.05); group B had 4 cases of intestinal obstruction after surgery that could be cured through conservative treatment, while group D had 10 cases of intestinal obstruction, 8 of which could be cured through conservative treatment and two needed surgery (p less than 0.05); VAS for pain degree of group C in active state was clearly lower at 1h, 5h, 7h, 15h, 30h and 42h after surgery, and side effects of postoperative analgesia were clearly reduced. Time to get out of bed was obviously decreased, while there was no evident effect on postoperative dosage, chronic pain and complications. Adopting quick rehabilitation nursing can effectively reduce occurrence of complications and postoperative pain, speed up the recovery of gastrointestinal function, shorten the length of stay, and improve patients’ satisfaction.

  • Letter
    . Vicenti, V. Pesce, D. Bizzoca, V. Nappi, F. Palmiotto, M. Carrozzo, B. Moretti
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1081-1086.
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    Presepsin (sCD14-ST) is an emerging biomarker in the diagnosis of sepsis. In the field of orthopaedics, it could be useful in the diagnosis and management of periprosthetic joint infections (PJI). The aim of this study is to define the normal perioperative plasmatic levels of presepsin in patients undergoing primary cementless total hip replacement (THR) or primary cemented total knee replacement (TKR). For this purpose, 50 patients (19 male, 31 female, mean age= 64.04±8.88) were recruited. The patients were divided into two groups: Group A patients underwent cementless THR, whereas Group B patients underwent cemented TKR. On recruitment, anthropometric data, smocking status, osteoarthritis stage according to Kellgren and Lawrence, Harris Hip Score (HHS) for Group A patients and Knee Society Score (KSS) for Group B patients, drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS), C-reactive protein (CRP) and procalcitonin (PCT) 24 hours before arthroplasty (T0) and at 24 (T1), 48 (T2), 72 (T3) and 96 (T4) hours postoperatively. Body temperature (θ) was recorded every six hours in the time lapse T0-T4. Presepsin plasmatic concentration was comparable at baseline in both groups. After surgery, however, a significant increase of presepsin was observed in Group A, whereas in Group B no significant changes of presepsin were recorded. A comparable trend of this biomarker was found in the two groups, i.e. presepsin increased from T0 to T3, when it reached its maximum value, and its decrease started at T4. Finally, presepsin resulted more accurate than CRP in the evaluation of perioperative inflammatory response in patients undergoing THR or TKR. These data will be helpful in defining a reference interval for presepsin in patients with prosthetic joint implants, and a cut-off of this biomarker for the diagnosis of PJI

  • Letter
    V. Musolino, M. Gliozzi, C. Carresi, J. Maiuolo, R. Mollace, F. Bosco, F. Scarano, M. Scicchitano, A. Maretta, E. Palma, M. Iannone, V.M. Morittu, S. Gratteri, C. Muscoli, M. Fini, V. Mollace
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1087-1093.
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    Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

  • Letter
    G. Varvara, S. Bernardi, T. Cutilli, S. Bianchi, B. Sinjari, M. Piattelli
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1095-1099.
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    Oral surgery procedures involve traumatization of mucosal and bony tissues, and lengthy interventions can lead to inflammatory post-operative sequelae. In the bony tissues in particular, the inflammatory processes can affect healing. Modern drug therapies provide valid support for lowering the risk of occurrence of post-operative inflammatory signs. The two main types of agents used are nonsteroidal anti-inflammatory drugs and/or corticosteroids, which act on two different molecular pathways in the inflammatiory process. The aim of this systematic review is to examine the different corticosteroids used in oral surgery procedures, their indications for use, and their route of administration, to provide the clinician with a useful scheme for correct pharmacological management of post-operative inflammation. To identify studies eligible for inclusion in this systematic review, we performed a literature search up to April 2017 of the electronic databases, considering published papers from 2007 to 2017. The search terms included steroids, third molar, oral surgery, RCT [randomized controlled trial], human, and clinical trial. Only articles in English language were considered.

  • Letter
    E. Sinagra, V. Guarnotta, D. Raimondo, F. Mocciaro, S. Dolcimascolo, C.A. Rizzolo, F. Puccia, N. Maltese, R. Citarrella, M. Messina, M. M Spada, G. Tomasello, F. Cappello, A. Leone, F. Rossi, R. Di Mitri, G.C. Morreale, S. Marasà, M. Midiri, F. Midiri, D. Sinagra
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1101-1107.
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    Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 - 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 - 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion

  • Letter
    V. De Iuliis, V. Dadorante, A. Marino, I. Griffo, A. Pennelli, V. Breda, I. Robuffo, S. Ursi, S. Martinotti, S. Caputi, E. Toniato
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1109-1113.
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    Cardiac surgery is accompanied by an important immune response that is poorly understood. This inflammatory response is caused by several stimuli: surgical trauma, cardiopulmonary bypass apparatus, aortic-cross clamping, reperfusion injury and hypothermia. The aim of the present study is to investigate the cytokine level profile involved in the inflammatory pathway of patients undergoing cardiac surgery. One hundred and two patients undergoing elective cardiac surgery utilizing cardiopulmonary bypass (CPB) apparatus were enrolled in the study. In the hematological and biochemical profiles investigated, we observed a significant increase of WBC and blood glucose concentration and a strong decrease of RBC, HB, HCT and PLT 24 h post-surgery compared to baseline and immediately after surgery groups. Furthermore, we found a modulation of cytokine levels mostly for IL-10 and an increase of IL-6, detected at 6 h post-surgery, IL-8 at 6 and 24 h, and TNFα only at 24 h post-surgery. In conclusion, these findings evidence a time course profile on cytokine levels and a balance between pro- and anti-inflammatory cytokine activation during and after cardiac surgery. In fact, IL-6 and IL-10, a pro- and an anti-inflammatory cytokine, respectively, increased immediately after surgery. The plasma level of TNF-α could be inhibited by the high concentration of IL-10 up to 6 h post-surgery. An IL-10 reduction at baseline level, after 24 h post-surgery, could explain a rise of TNF-α plasma concentration. On the other hand, considering the dual role of IL-6 on inflammation acting both as an activator of inflammatory cascade or an anti-inflammatory agent, the increased IL-6 levels 24 h after surgery could be related to the negative feedback action on TNFα activity.

  • Letter
    P. Ciappetta, S. Taurone, M. Spoletini, M. Artico
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1115-1118.
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    Tumors anteriorly situated to the medullary conus are rarely encountered and represent a true surgical challenge. We examined the literature on this topic, concluding that there are no previous reports on alternative surgical techniques different to the traditional one. We report two cases of intradural extramedullary tumor operated on by a technique performed through a window opened between the spinal roots, which allows an easy, effective and useful resection. We describe a new operative technique which ensures a complete removal of these tumors and discuss clinical implications in the light of the available literature on this topic

  • Letter
    E. Sinagra, D. Raimondo, G. Pompei, G. Fusco, F. Rossi, G. Tomasello, A. Leone, F. Cappello, G. C. Morreale, F. Midiri, M. Midiri, A. G. Rizzo
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1119-1125.
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    The term focal active colitis (FAC) is conventionally used to describe the presence of isolated cryptitis, characterized by an inflammatory infiltrate consisting of intraepithelial neutrophils and/or neutrophils invading the lumen of the criptae, with no other microscopic alteration of the colonic mucosa and, in particular, without the presence of signs of chronic inflammation. To date, only four studies, including one conducted in a pediatric population, have been performed to evaluate the clinical significance of this disease. The aim of this retrospective study on prospectively-collected data is to evaluate the clinical implications of the focal active colitis, since there still remains a marked uncertainty regarding this topic and about how often such a diagnosis will presage a diagnosis of inflammatory bowel disease (IBD). Clinical, endoscopic, and pathological data were retrospectively reviewed from 30 patients with focal active colitis, who had no other diagnostic findings on colorectal biopsy and no history of chronic inflammatory bowel disease. The histological findings were correlated with clinical diagnoses. Thirty patients (11 males, 19 females; age 24-80 years, median 56 years) (0.5%) out of 5,600 undergoing colonoscopy between January 2012 and December 2016 presented a definitive diagnosis of FAC. Follow-up ranged from 6 to 60 months (median 24 months). At endoscopy, 19 patients (63%) had mild and non-specific changes, such as mild mucosal erythema, while 11 (37%) had normal findings. Eight patients were documented as having irritable bowel syndrome, while nine cases could be attributed to the effects of drugs, five presented FAC as incidental finding, one a diagnosis of infectious colitis, and seven a diagnosis of IBD (4 with Crohn's disease). FAC was confirmed to be a more significant predictor of IBD than the previous literature would indicate, even if larger prospective studies, targeted to study this relationship, are needed to understand more clearly its clinical significance.

  • Letter
    R. Celletti, S. Fanali, C.U. Laici, C. Santori, P. Pignatelli, B. Sinjari
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1127-1131.
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    When splinting multiple implants passive fit of the framework should be achieved to avoid excessive force distribution on the implants. Recently, a protocol was suggested for immediate loading of multiple implants by welding a titanium bar to implant abutments directly in the oral cavity so as to create a customized, precise and passive metal-reinforced provisional restoration. The intraoral welding technique subsequently proves to be a successful option in the full-arch immediate restorations of the mandible and maxilla. The aim of this article is to present a case report in which a new prosthetic approach, using trans-mucosal implants, is described. Dental implants are instantly loaded with a provisional prosthesis supported by an intraoral welded titanium framework to obtain a precise passive fit of the immediate loaded prosthesis

  • Letter
    E. Rosato, A. Gigante, M. Liberatori, ML. Gasperini, B. Barbano, A. Amoroso, L. Tubani, A. Laviano
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1133-1138.
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    Autonomic nervous system is involved in body weight regulation. Gastrointestinal manifestations of systemic sclerosis (SSc) can influence patients' nutritional status and facilitate the development of protein'energy malnutrition. The aim of the study is to assess the nutritional status of SSc patients and to explore its possible correlation with autonomic dysfunction using heart rate variability (HRV). We enrolled 19 SSc subjects and 19 healthy subjects as controls. Body mass index (BMI) and body surface area (BSA) were collected and recorded in all patients. HRV was measured and the domains of low frequencies (LF, index of the sympathetic modulation) and high frequencies (HF, index of the parasympathetic modulation) were recorded. As assessed by the LF/HF RATIO, sympathovagal balance is altered in SSc patients because of increased sympathetic modulation and reduced parasympathetic activity. BMI positively correlates with LF (r=0.57; p less than 0.01) and LF/HF RATIO during daytime (r= 0.46; p less than 0.05). Similarly, BSA positively correlates with LF (r= 0.51; p less than 0.05), LF day time (r= 0.53; p less than 0.05) and LF/HF RATIO night time (r=-0.51; p less than 0.05). In SSc patients the autonomic dysfunction is characterized by increased sympathetic modulation. We observed a correlation between autonomic dysfunction and nutritional status in SSc patients.

  • Letter
    M. Abate, V. Salini
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1139-1145.
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    Osteoarthritis (OA) is a progressively degenerative joint disease, with a very high prevalence rate that is expected to increase worldwide with the ageing of the population. Considering that OA requires long-term treatment, therapies with minimal side effects and which can be repeated as needed are warranted. Hyaluronic acid (HA), a natural glycosaminoglycan with viscoelastic properties, is a major component of synovial fluid and the extracellular matrix of the joint cartilage, and plays key roles in maintaining synovial fluid viscosity and the bio-mechanical integrity of healthy cartilage. Intra-articular administration of exogenous HA has therefore been used to successfully improve the viscoelastic properties of the joint to improve lubrication, modulate inflammation and modify the catabolic micro-environment. Sinovial®/GELSYN-3TM is a sterile, non-pyrogenic formulation of highly purified, chemically unmodified HA of bio-fermentative origin, which has been introduced in several different concentrations in clinical use within the European market. This expert opinion reports on the published data regarding the efficacy and tolerability of first and multiple injection series of Sinovial®-based product formulations. The data regarding the tolerability of Sinovial® in patients with knee osteoarthritis were analyzed, showing that this formulation, beside favourable therapeutic effects, has a very good tolerability profile, with only mild, transient, and easily managed, local injection-site reactions and absence of systemic reactions. In particular, repetitive cycles of HA have been shown to yield positive results in terms of both efficacy and safety and therefore should be offered to patients who had undergone a successful first course of therapy when their symptoms reoccur.

  • Letter
    V. Sargentini, D. Collepardo, M.D. Alessandro, G. Petralito, G. Ceccarelli, F. Alessandri, A. Piciocchi, A. Angeloni, M. Venditti, A. Bachetoni
    Journal of Biological Regulators and Homeostatic Agents. 2017, 31(4): 1147-1154.
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    This study measured Procalcitonin (PCT), Presepsin (PRE-S) and pro-Adrenomedullin (pro-ADM) in intensive care unit (ICU) patient's blood to assess their contribution to accurate diagnosis of sepsis and potential predictive impact on prognosis. The final aim was to improve the use of infection biomarkers for optimizing the impact of laboratory medicine on clinical outcomes, focusing on the good management of resources designed to produce maximum effectiveness and efficiency. Sixty-four adult patients were studied during their hospitalization in ICU; blood samples were collected and categorized according to their clinical diagnosis and illness severity, and sepsis marker levels were measured on automated immunoassay platforms. PCT, PRE-S and pro-ADM infection markers were significantly lower in controls than in sepsis or septic shock groups. The area under the curve, by ROC curve analysis, was 0.945 for PCT, 0.756 for PRE-S and 0.741 for pro-ADM. Sepsis diagnostic accuracy was not improved by combining PCT, PRE-S and pro-ADM measures. Preliminary data demonstrated that, despite PRE-S and pro-ADM being able to differentiate between septic and non-septic patients with accuracy, PCT remains the most reliable marker available. The results obtained still do not allow us to consider a combination of markers, because it would merely increase laboratory costs without improving diagnostic performance. Furthermore, the results confirm a possible prognostic role of pro-ADM in septic states, but no correlation between biomarker levels and survival at 48 h was detected. Hence PCT, PRE-S, nor pro-ADM can be used to predict short-term prognosis