20 June 2022, Volume 36 Issue 3

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  • Review
    Minglong Yao, Jia Liu, Boyan Pan, Hongtao Yu, Ning Bao
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 437-444. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.51
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    The most common and serious complication of hysteroscopy is operative hysteroscopy intravascular absorption (OHIA). Bipolar plasma cutting systems are widely used in clinical practice because of their advantages, such as less bleeding, no current through the body, etc. The electrolyte-containing distension solutions can be used with bipolar current electrosurgical devices to avoid hyponatremia. However, complications (e.g., acute heart failure (AHF) and pulmonary edema (PE)) due to excessive absorption of dilating media have been frequently reported. The present study aimed to review the working principle of plasma bipolar hysteroscopy, discuss factors influencing the risk of fluid overload, and compare the absorption of uterine distension fluid during hysteroscopy with the values of B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) in the diagnosis of fluid overload in bipolar hysteroscopy. Real-time bedside ultrasound, which is a reliable and non-invasive method to identify cardiac function and pulmonary hyperemia, can make early diagnosis of fluid overload in bipolar hysteroscopy of patients with AHF and PE, and even move the diagnostic threshold forward. We also described inferior vena cava (IVC) ultrasound and volume reactivity, systolic and diastolic functions of the left heart, peak velocity and velocity time integral of aorta, size of the right heart, systolic function of the right heart, diastolic function recognition, and their relationship with PE in AHF caused by fluid overload. In summary, combination of cardiopulmonary ultrasound and IVC ultrasound can be a sensitive indicator for the early diagnosis of AHF and PE caused by fluid overload in bipolar hysteroscopy, while further clinical experiments need to be conducted to verify this conclusion.

  • Review
    Li Wen
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 445-453. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.52
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    Hearing loss is caused by a variety of genetic and environmental factors, with inherited causes assumed to account for 50% to 60%. Mutations in mitochondrial DNA (mtDNA) 12S rRNA, especially the m.1555A>G mutation, are the most common molecular cause for nonsyndromic sensorineural hearing loss and aminoglycoside-induced deafness. The spectra of this gene varies among different ethnic populations. In current review, the m.1555A>G mutation of 12S rRNA decoding gene was compared in different populations for ethnic-specific allele frequency and their contribution to genetic hearing loss. Differences in the distribution of mutation to diverse regions of the world showed that it occurred from the ancestors of each ancestral generation and in immigrant populations at different time periods. Furthermore, we also include the functional studies of this mtDNA variation in the etiologies of aminoglycoside-induced hearing loss. Carriers of the mutation (m.1555A>G) should avoid aminoglycosides and use alternatives for antibiotic therapy to avoid the possibility of drug-induced hearing loss. Comprehensive summary of the m.1555A>G mutation can help provide scientific basis for disease diagnosis and consultation for hearing loss and develop optimal therapeutic strategies for deaf patients.

  • Review
    Xiangnan Chen, Lihua Zhu, Linlin Chen, Fenghua Zhang, Hui Wang, Yanjun Yang, Wenfeng Ye
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 455-461. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.53
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    Objective: The presence of caveolin-1(cav1) has been known for years. The aim of this narrative review was to investigate the expression of cav1 in normal and pathological pregnancy.

    Method: This review was carried out by two authors from the databases including PubMed and web of science. This review included all published studies about the role of cav1 in pregnancy-related diseases, including miscarriage of unknown cause, preeclampsia, gestational diabetes mellitus (GDM) and pregnancy in women with high body mass index (BMI).

    Results: The review showed that there were difference between the expression of cav1 of normal pregnancy and that of pathological pregnancy. The expression of cav1 is down-regulated in placenta of the group with unexplained spontaneous miscarriage in comparison with normal pregnancy. The level of cav1 in preeclampsia cases are lower than that of women in normal pregnancy. The expression of cav1 protein and mRNA in placenta of macrosomia induced by GDM was down-regulated and rats fed with HFHC had a decreased uterine expression of cav1 in the stage of labor.

    Conclusions: It can therefore be concluded that the caveolin-1 gene may be a potential susceptibility gene in pathological pregnancy.

  • Article
    Wenhao Ji, Rongjie Zhao, Xin Lin, Shengpeng Shao, Si Lu, Ruyun Cai, Hang Yu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 463-472. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.54
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    Background: Lymph node involvement in T3M0 colorectal cancer (CRC) results in different treatments and prognoses, although the underlying mechanisms are still unclear. This study aimed to investigate the role of competing endogenous RNAs (ceRNA) in the mechanism.

    Methods: Differentially expressed genes were identified by comparing the transcription profiling in 83 T3N0M0 versus 83 T3N+M0 CRC. The ceRNA network was constructed based on the regulation of lncRNA-miRNA and miRNA-mRNA recorded in databases. Functional enrichment and overall survival analysis were then performed. Protein-Protein Interaction (PPI) Network was established to screen out hub genes and related ceRNA regulation axis. The correlation between the hub genes and immune infiltration was calculated.

    Results: A total of 595 DEmRNAs were identified, which were significantly enriched in cell adhesion, migration, and differentiation-associated biological processes. The similar method was used to identify 157 DElncRNAs and 15 DEmiRNAs, and a ceRNA network consisting of 17 DElncRNAs, four DEmiRNAs, and 36 DEmRNAs was constructed. The ceRNA network was associated with the regulation of homophilic cell adhesion via plasma membrane adhesion molecules, cell differentiation, and communication. A total of 13 members of the ceRNA network were associated with the outcomes of T3 CRC patients. DRD1 and MYH11 not only participated in the ceRNA network but were hub genes. External validation cohort GSE39582 confirmed that DRD1 was up-regulated explicitly in T3 CRC but not in T2 and T4. Additionally, hub genes DRD1 and MDM2 may induce an immunosuppressive microenvironment by reducing the infiltration of CD8+T cells and cytotoxic cells.

    Conclusions: The ceRNA network, especially for DRD1-related lncRNAs-miRNAs, modulates T3 CRC lymph node involvement by affecting the adhesion and migration processes and the immune microenvironment.

  • Article
    Meng Wei, Fang Wang, Lihong Shang, Ting Hao, Yu e Yang, Chunfang Ha
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 473-481. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.55
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    Objectives: The aim of this study is to investigate the relationship between the Nuclear factor-kappa B (NF-κBp65) and RAS/MEK/ERK signaling cascade and their influence on the proliferation and invasion of endometrial stromal cells.

    Design: A prospective case control study was carried out. The endometriotic ovarian cyst wall was examined as a case whereas endometrial tissue obtained during endometrial curettage and non-endometriotic ovarian cyst wall were examined as controls (n = 15).

    Methods: To explore the relationship between RAS/MEK/ERK and NF-κB pathway, we firstly detected the expression of RAS, MEK, ERK and NF-κBp65 in the control endometrium and eutopic/ectopic endometrium with endometriosis. Then their affection on the proliferative and invasive abilities of endometrial stromal cells was analyzed by CCK-8 and Trans-well and verified the upstream and downstream relationship between RAS/MEK/ERK and NF-κB signaling pathway cascade by Western blot.

    Results: The results revealed that the expression levels of MAPK kinase-dependent molecules RAS, MEK, ERK and NF-κBp65 in eutopic/ectopic endometrial stromal cells of patients with endometriosis were significantly higher than those in the control group (p < 0.05). When the expression of MEK, ERK and NF-κBp65 were respectively silenced, the proliferation and invasion of eutopic endometrial stromal cells were all significantly suppressed. They all participated in the progress of endometriosis. Of note, the expression of NF-κBp65 protein was obviously inhibited after respectively suppressing ERK, MEK and RAS/MEK/ERK signaling pathway (p < 0.05). However, the expression of RAS, MEK and ERK has no change after NF-κBp65 was silenced by small interfering RNA (p > 0.05).

    Conclusions: The NF-κBp65 is regulated by the RAS/MEK/ERK signal pathway to promote the proliferation and invasion of eutopic endometrial stromal cells. Its inhibitors provide the selection of multiple potential targets and different joint intervention approaches for non-hormonal therapy for endometriosis.

  • Article
    Zhenting Wu, Haobo Sun, Yanan Liu, Xuehang Wang, Lihua Hu, Ying Liu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 483-493. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.56
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    Oxidative stress plays an important role on the occurrence and development of acute alcoholic liver injury. Therefore, it is necessary to explore the role and related mechanism of antioxidant Glutathione (GSH) in acute alcoholic liver injury. The animal model of acute alcoholic liver injury in mice was established and divided into different groups, i.e., drug treatment and observation. The body weight and liver weight of mice in each group were recorded, the liver index was calculated, and the pathological changes of liver tissue were observed. The contents of AST, ALT and ALP in serum of mice were detected by automatic analyzer. Liver tissues were extracted to detect oxidative stress indexes such as Superoxide Dismutase (SOD), Glutathione peroxidase (GSH-Px), Catalase (CAT), Malondialdehyde (MDA) and liver function indexes such as TC, TG. TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect hepatocyte apoptosis in each group, and Western blot (WB) and Real time quantitative PCR (qPCR) were used to detect the expression of related pathway proteins and apoptotic proteins. Serum Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-1β (IL-1β) were detected by Enzyme linked immunosorbent assay (ELISA) kit. In addition, we also applied Lipopolysaccharide (LPS) to establish the model of liver injury, and detected that the liver function indexes related to liver injury, apoptosis. The level of oxidative stress and the level of inflammatory factors were used to explore the relationship between GSH and Lipopolysaccharide binding protein (LBP) signal pathway. Results showed that GSH could reduce the indexes of liver function, oxidative stress and the level of inflammatory factors, and also reduce the LPS-induced liver injury in mice. GSH may alleviate alcohol-induced liver injury by inhibiting LPS/LBP-TNF-α signal pathway.

  • Article
    Junjie Ni, Pu Wu, Lutong Liu, Miaomiao Jin, Changzhen Lei, Chaoyang Xu, Zhongwu Hong
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 495-506. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.57
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    Background: Gastric cancer (GC) is the number five most prevalent malignancy globally and the third deadliest, and GC patients have a poor prognosis. Necroptosis is a kind of regulatory cell death, mainly controlled by MLKL, RIP1, and RIP3. In tumor immunotherapy, necroptosis has been shown to be related to antitumor immune responses.

    Methods: Molecular subtypes of GC tissue in TCGA database was identified based upon necroptosis-associated mRNAs through a ConsensusClusterPlus analysis. Prognosis and tumor immune microenvironment differences were assessed between subtypes. Based on the molecular subtypes, Cox and LASSO regression analyses were employed to identify a prognostic gene model. Patients with stomach adenocarcinoma (STAD) were separated into different risk groups using the model. An established predictive model was assessed via Kaplan–Meier survival analyses and ROC curve analysis. Function enrichment and immunity analysis were conducted to gain additional relevance regarding the mechanistic roles and clinical relevance of the genes. External validation was performed using a GEO dataset.

    Results: mRNA expression profiles of necroptosis revealed two molecular subtypes (cluster1, cluster2) with distinct prognostic and tumor immune features. A prognostic signature consisting of 11 genes was constructed to separate patients into high- and low-risk subgroups. The C2 subtype and high-risk subgroup not only exhibited worse prognosis but also had universally significantly increased immune cell infiltration and immune-related pathway activation relative to the C1 subtype and low-risk subgroup. The AUCs for 1-, 3-, and 5-year OS were 0.669, 0.692, and 0.747 in the TCGA cohort and 0.548, 0.588, and 0.600 in the GEO cohort. Age, T and N stage, and riskScore were all independent predictors of patient outcomes in both cohorts. Functional analyses revealed that differentially expressed genes (DEGs) between these two risk subgroups were mostly involved in metastasis-related pathways.

    Conclusions: This study identified two necroptosis-related molecular subtypes exhibiting distinct prognoses and tumor immunological characteristics. Moreover, a 11-gene risk signature was identified, with which patients were separated into low- and high-risk subgroups, which could help clinicians make decisions and personalize treatment.

  • Article
    Jianhui Li, Jingyi Zhao
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 507-515. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.58
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    Objective: This study evaluated the predictive value of key genes in response to treatment with infliximab of patients with Crohn’s disease (CD).

    Methods: Four datasets on CD treated with infliximab were downloaded from the GEO database. We integrated these datasets and analyzed the characteristics of differentially expressed genes, immune infiltration, and weighted gene co-expression network between the non-response and response groups of patients treated with infliximab. The key genes that could predict the infliximab response were determined using support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) regression. The receiver operating characteristic (ROC) curve, concordance index (C index), and GiViTi calibration band were used to evaluate the diagnostic performance of these genes. In addition, functional annotation and pathway enrichment analysis of key genes were performed. Finally, the correlation between key genes and immune cells was analyzed.

    Results: Seven genes with a high predictive value for infliximab response in patients with CD were selected from four integrated datasets. The area under the curve (AUC > 0.8), c-index (>0.8), and GiViTi calibration bands (p > 0.05) of the 7-gene signature showed its ability to predict the infliximab response in patients with CD. Differences existed in monocytes between non-response and response groups of infliximab in patients with CD. Three genes (SPP1, CHN1, and GAS1) were negatively proportional to the number of monocytes.

    Conclusion: The results indicated that the 7-gene signature could serve as a candidate biomarker for predicting the response to infliximab treatment in patients with CD.

  • Article
    Ruixiao Song, Xiaoya Bao, Zun Li, Jing Xi, Chen Qian, Yaqin Ding, Xiaolong Yu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 517-522. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.59
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    Objective: To evaluate the predictive value of meniscus echo homogeneity and medial meniscus extrusion (MME) in non-load-bearing condition for the occurrence and development of knee osteoarthritis (KOA).

    Methods: One hundred fourteen patients with KOA were selected as the study group from 2018 to 2019. Two hundred four healthy volunteers were included as the control group during the same period. The covariates between the two groups were balanced by a 1:1 propensity score matching (PSM). Logistic regression analysis was performed to analyze the independent risk factors, and the value of the auxiliary diagnosis was evaluated using the receiver operating characteristic (ROC) curve.

    Results: After PSM, MME was higher in the study group than in the control group, and the peripheral joint space was smaller in the study group than in the control group; the differences were statistically significant (both, p < 0.01). Multivariate logistic analysis showed that MME, and inhomogeneous echo of the medial meniscus were independent risk factors of KOA. According to the ROC curve, 2.8 mm was the optimal cutoff value for MME in the auxiliary diagnosis of KOA.

    Conclusion: Medial meniscal extrusion and uneven echo are independent risk factors for knee osteoarthritis.

  • Article
    Hui Song, Liang Wang, Yufei Liang, Qingqing Wang, Yingying Liu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 523-533. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.60
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    Background: The present research sought to figure out the expression features and role of transmembrane p24 trafficking protein 5 (TMED5), a novel oncogene, in gastric cancer (GC).

    Materials and Methods: Firstly, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB) were implemented to monitor the TMED5 level in GC tissues and paracancerous non-tumor tissues and the link between the TMED5 profile and clinical-pathological parameters of the patients was probed. Secondly, TMED5 knockdown models were established in AGS and MKN-45 cells. Then, the cell counting kit-8 (CCK-8) and colony formation experiments were utilized to check cell proliferation. Afterward, the expression of apoptosis-related proteins and the hypoxia-inducible factor-1alpha (HIF-1α)/Wnt/β-catenin axis were gauged by WB. Subsequently, Transwell assay monitored cell invasion.

    Results: TMED5 was highly expressed in GC tissues versus adjacent paracancerous tissues, and the high TMED5 expression was strongly linked to undesirable GC prognosis. Knocking down TMED5 choked GC cell proliferation and invasion and facilitated apoptosis. In vivo, the tumorigenic ability of GC cells knocking down TMED5 was obviously dampened. Mechanism studies have confirmed that knocking down TMED5 notably inactivated the HIF-1α/Wnt/β-catenin axis. Moreover, the TMED5 knockdown-mediated anti-tumor effect was largely abated after attenuating the HIF-1α pathway by LW6.

    Conclusions: This study substantiated that TMED5 is up-regulated in GC tissues and affects GC advancement by modulating the HIF-1α/Wnt/β-catenin pathway.

  • Article
    Jian Zhao, Xianfei Xie, Bo Xia, Peng Ning, Yong Xu, Qiang Zhao
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 535-545. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.61
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    Background: This study investigated autophagy-related genetic biomarkers to understand the occurrence and distant metastasis in osteosarcoma.

    Methods: Microarray or mRNA sequencing data obtained from the gene expression omnibus (GEO) database was analyzed to identify the differentially expressed genes (DEGs). Comprehensive pan-cancer analyses were performed based on the cancer genome atlas (TCGA) database, and the Hallmarks and Kyoto of genes and genomes (KEGG) pathway enrichment analyses were conducted using gene set enrichment analysis (GSEA). Further, estimation of stromal and immune cells in malignant tumors using the expression data (ESTIMATE) algorithm was done to estimate the relationship between the tumor microenvironment (TME) of the osteosarcoma and potential biomarker genes.

    Results: Commonly known autophagy-related DEG serpin family member 1 (SERPINA1) was found up-regulated in osteosarcomas with distal metastasis. It was a potential oncogene with prognostic value and was associated with an immune microenvironment in pan-cancer. It was also involved in the progression and metastasis of osteosarcoma.The pathway’s response to autophagy and immune response were also enriched in the high expression of the SERPINA1 group. Otherwise, SERPINA1 was associated with tumor immune cell infiltration in the osteosarcoma.

    Conclusions: The autophagy-related gene, SERPINA1, holds great promise to monitor the association between autophagy and the occurrence and metastasis of osteosarcoma.

  • Article
    Xiaoqing Wu, Wenping Lu, Cuihong Jiang, Yanan Wang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 547-556. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.62
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    Cervical cancer has the highest incidence rate among gynaecological cancers. The treatment of advanced and recurrent cervical cancer is limited. Therefore, it is imperative to find new prognostic indicators and therapeutic targets. The main purpose of this study was to identify gene sets or pathways related to prognosis and explore their underlying mechanism. The samples were taken from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Gene Set Variation Analysis (GSVA) was used to score gene sets in tumor tissue and normal cervical tissue, and the samples were then grouped according to score and overall survival. A prognostic model with lasso regression was then undertaken. Gene Set Enrichment Analysis (GSEA) was used to analyse the function and pathway of gene sets. The Timer 2.0 database was used to explore the relationship between the expression of the gene set and the immune microenvironment. The Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database was used to verify the above results and showed the difference in the expression of hub genes in the gene set between cervical cancer and normal cervical tissue. Our study analysed 4922 gene sets, which were compared between 306 tumor tissue and 13 normal cervical tissue samples. The samples were divided into three subtypes, and the tumor grade was closely related to the subtypes. Hallmark-epithelial esenchymal (HR: 38.13; 95% CI: 2.13-681.35; p = 0.013), Hallmark-angiogenesis (HR: 521.78; 95% CI: 13.47-20210.87; p = 0.001) and GSE36888_untreated vs IL-2 treated STAT A/B T-cell IL-2 (HR: 1828.94; 95% CI: 4.59-728605.07; p = 0.014) were found to be significant pathways related to prognosis through GSVA. In GSEA, the gene sets were enriched in response to lipopolysaccharide, response to molecule of bacterial origin and cytokine receptor binding, cytokine-cytokine receptor interaction, chemokine signaling pathway, IL-17 signaling pathway and viral protein interaction. We further analysed the IL-2-STAT5-Foxp3 pathway. The hub genes of this pathway were significantly enriched in regulatory T cells (Tregs), p < 0.05. IL-2R and Foxp3 were upregulated in cancer tissue compared to normal cervix (p < 0.01). In conclusion, IL-2-STAT5-Foxp3 may regulate Tregs in the immune environment, affecting the prognosis of cervical cancer.

  • Article
    Xianping Huang, Jiajia Chen, Huiqiu Xiang, Xiaoting Yu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 557-563. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.63
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    Background: Cervical cancer occurs in middle-aged and elderly women, which is one of the most common cancers in women. Unfortunately, there is still no effective treatment for cervical cancer patients of terminal stages. Maslinic acid, a pentacyclic triterpene acid exhibits various bioactivities. However, the effect of Maslinic acid in cervical cancers remain unclear.

    Methods: The bioactivity of Maslinic acid have investigated using qRT-PCR, flow cytometry, cell migration assay, western blot and immunofluorescence in order to explore the mechanism of anticancer effects of on cervical cancer cells (HeLa).

    Results: The proliferation of HeLa cells was suppressed by Maslinic acid treatment. Moreover, the abilities of migration and invasion were suppressed after Maslinic acid treatment. Furthermore, Maslinic acid could induce mitochondria dysfunction in HeLa cells.

    Conclusions: The proliferation ability was suppressed and the apoptosis was increased by Maslinic acid treatment. Additionally, p53-dependent and Bcl related pathway influence the capacity of migration and invasion in Hela cells, which could be regulated by Maslinic acid. It could be a promising effective agent and underlying mechanism for cervical cancer treatment.

  • Article
    Junchi Cheng, Rong Wang, Xiaohong Wang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 565-573. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.64
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    Background: Although endometrial cancer (EC) has adverse effect on the survivors’ quality of life, risks of death from non-cancer causes in EC survivors remain poorly understood. The present study aimed to identify the change in risk for specific causes of death after EC diagnosis, when compared with the risk in the general population.

    Methods: Data was obtained from the SEER database between 2000 and 2015. Standardized mortality ratios for various causes of death were subsequently calculated in comparison with the US general population.

    Results: A total of 44,485 (29.0%) EC patients were recorded as having died during follow-up from 2000–2015. The number of EC-specific deaths decreased as time passed, while the risk of death due to non-cancer causes increased yearly. Compared with the general US population, EC survivors displayed a dramatically higher risk of death due to heart disease within one year of diagnosis (SMR = 1.58, 95% CI [1.47–1.70]), as well as after more than 10 years (SMR = 1.14, 95% CI [1.07–1.22]). The risk of death from cerebrovascular disease among EC survivors was also increased, with a SMR equal to 1.35 (95% CI [1.16–1.56]) within one year, and 1.15 (95% CI [1.01–1.30]) ten years after diagnosis. Additionally, results also showed that women with EC are at increased risk of death from diabetes, in all surveyed time periods, following their cancer diagnosis.

    Conclusions: Although EC accounted for the most common cause of death during follow-up, causes other than cancer contributed to a great number of deaths among EC survivors. Our findings may assist clinicians in counseling EC survivor regarding to future health risks during long-term follow-up.

  • Article
    Xuefeng Jin, Shufan Hu, Dengxia You, Weihong Tang, Shanshan Pan
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 575-582. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.65
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    Objective: Nontyphoidal Salmonella (NTS) Infection is the most common food-borne disease. Among all groups, young children are the most vulnerable group to NTS. With the increase in the incidence of NTS infection and the development of multi-drug resistance, public health especially children health has had a major impact. In order to characterize the changes of antibiotic resistance of NTS in children in Hangzhou, China, and to provide references for the rational use of drugs for NTS infections in this area.

    Methods: Three hundred and thirty-one hospitalized children with NTS infections in Hangzhou Children’s Hospital from 2014 to 2020 were included. The clinical data and antibiotic susceptibility test results were retrospectively reviewed and analyzed.

    Results: Among these 331 children infected by NTS, 190 cases were male and 141 were female. The youngest age of onset was only 18 days, and the median age was 15 months. In Hangzhou, NTS infections mostly occurred in infants and young children from 6 months to 2 years, and often occurred in the summer and Fall. The dominant bacterial types in this region were Salmonella Typhimurium (42.30%) and Salmonella Enteritidis (13.60%). The distribution of the remaining serotypes was relatively scattered. From 2014 to 2020, NTS were completely susceptible to imipenem/ertapenem; its susceptibility and resistance to penicillins and cephalosporins remained relatively stable. The high rates of antibiotic susceptibility were recorded in relation to piperacillin/tazobactam (93.05%), ceftriaxone (70.69%), ceftazidime (78.25%), and cefepime (87.01%). However, the susceptibility to quinolones had decreased significantly, only 37.17% in 2020. The multi-drug resistant (MDR) rate of 331 NTS isolates was 29.61% (98/331). Among them, Salmonella Typhimurium was more prone to MDR.

    Conclusions: The overall antibiotic resistance rates remained at a high level in Hangzhou, and antibiotic susceptibility rates of NTS to quinolones decreased significantly. The surveillance of antibiotic resistance in NTS and control measures should be further strengthened. For children who need antibacterial drugs due to NTS infection in Hangzhou, the use of piperacillin, tazobactam, ceftazidime or ceftriaxone is recommended until antibiotic susceptibility test results are available.

  • Article
    Nan Wang, Mingyu Wang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 583-592. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.66
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    Background: The common inhalational anaesthetuc sevoflurane has been implicated in tumorigenesis. This study explored its effect on proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) in MCF-7 human breast cancer cells.

    Methods: MCF-7 cell lines were treated with different gradient concentrations of sevoflurane for 6 h. EdU-based proliferation assay and detection by immunoblotting of several proliferation-associated proteins including p21, proliferating cell nuclear antigen (PCNA), and cyclinD1, were employed to determine the influence of sevoflurane on proliferation. Flow cytometry assay and immunoblotting assay were used to analyze cellular apoptosis and apoptosis-relevant proteins; containing Bcl-2, Bax, cleaved-caspase-3, cleaved-caspase-9, as well as cleaved-PARP1, EMT-associated markers contain N-cadherin, E-cadherin, β-catenin, vimentin and discoidin domain receptor 2 (DDR2) as well as janus kinase 2 (JAK2), p-JAK2, signal transducer and activator of transcription-3 (STAT3) and p-STAT3. Transwell assay was conducted to evaluate the cells invasion.

    Results: The results suggested that sevoflurane restrained the proliferation and EMT, but promoted the apoptosis of MCF-7 cells. Besides, sevoflurane treatment contributes to the downregulation of the JAK2/STAT3 pathway. RO8191 (a JAK2 activator) weakened the effects of sevoflurane on proliferation, apoptosis, and EMT in MCF-7 cells.

    Conclusions: To sum up, sevoflurane suppresses proliferation and EMT and promotes apoptosis by repressing the JAK2/STAT3 pathway in MCF-7 cells.

  • Article
    Chunying Guo, Zhuren Luo, Xiongjie Zhuang, Yiming You, Zhen Yang, Cen Yue
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 593-597. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.67
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    Objective: To explore the relationship between FLAIR vascular hyperintensities (FVH) and the early neurofunctional status of patients with acute middle cerebral artery infarction after intravenous thrombolysis.

    Methods: One hundred and seventeen patients divided into FVH-positive (n = 86) and FVH-negative groups (n = 31). We compared the demographics, cerebrovascular disease risk factors, neurological examinations and imaging examinations between the two groups, and analyzed the relationship between the changes of the National Institutes of Health Stroke Scale (NIHSS) scores and the incidence of FVH.

    Results: In the FVH-positive group, the decline of the average NIHSS scores obtained 24 hours after intravenous thrombolytic therapy were significantly less than that of the FVH-negative group. Also, the average 24-hour follow-up NIHSS scores were significantly higher in the FVH-positive group than that of the negative group. There were no significant differences between the FVH-positive group and the FVH-negative group in age, gender, risk factors for cerebrovascular disease, length of hospitalization, the baseline NIHSS scores and the NIHSS scores at discharge.

    Conclusions: FVH can be applied to predict the short-term clinical efficacy of intravenous thrombolytic therapy in patients with acute middle cerebral infarction, which would help to assist in the selection of patients who might benefit more from thrombolytic therapy.

  • Article
    Jian Ding, Tianxing Ni
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 599-609. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.68
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    Background: Thoracic aortic aneurysm (TAA) is a fatal condition result from weakening of the thoracic aorta wall. This study aims to reveal promising prognostic biomarkers and the potential molecular mechanism associated with TAA.

    Method: The differentially expressed genes (DEGs) were explored between TAA samples (TAA group) and normal samples (control group). The enrichment analysis and protein-protein interaction (PPI) network analysis for DEGs were performed to explore diagnostic hub genes. The receiver operating characteristic curve (ROC) analysis was performed on each hub gene to evaluate the diagnostic effect of hub genes. Finally, the associations of hub gene with immune cells were investigated.

    Result: A total of 702 DEGs were revealed between TAA and control groups. These DEGs such as FOXP3 were mainly assembled in functions like regulation of cell adhesion. PPI network analysis explored 20 hub genes including CCL19, SOCS3, and IL10. Moreover, compared with normal samples, the cell infiltration in monocytes was significant in TAA samples. Finally, the correlation analysis between hub genes and immune cells showed that monocytes were negatively correlated with hug genes including IL7R.

    Conclusions: A total of 20 hub genes including CCL19 and IL10 were revealed as potential diagnostic biomarkers for TAA. FOXP3 might take part in the progression of TAA via regulating cell adhesion. Furthermore, the inhibition of monocytes via promoting IL7R expression may contribute to the clinical treatment of TAA.

  • Article
    Xiaobo Ling
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 611-623. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.69
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    Background: Considering the crucial role epithelial-to-mesenchymal transition (EMT) plays to promote pulmonary fibrosis, it has hence become the objective to reveal the effects of breviscapine on EMT of transforming growth factor-β1 (TGF-β1)-induced human pulmonary fibrosis model.

    Methods: During the experiments, A549 cells were used to establish a cellular pulmonary fibrosis model in vitro, which were mimicked by TGF-β1 intervention and further treated with breviscapine, or the PI3K activator insulin-like growth factor-1 (IGF-1). The following assays, including MTT (viability), wound healing (migration) and Transwell (invasion) were carried out as appropriate. The morphology of pulmonary fibrosis cells was observed under the microscope. The expressions of EMT-, TGF-β1/Smad pathway-, and PI3K/AKT/GSK3β pathway-related proteins were quantified based on the tests of RT-qPCR and western blot as needed.

    Results: Corresponding, the results here highlighted that TGF-β1 down-regulated the level of E-cadherin and up-regulated those of N-cadherin and Fibronectin in A549 cells. Breviscapine abrogated the promoting effects of TGF-β1 on the malignant phenotypes of A549 cells and on EMT-related factors. However, IGF-1 offset the effects of breviscapine on regulating the migration, invasion, and the expression levels of factors related to EMT and TGF-β1/Smad pathway in A549 cells with the treatment of TGF-β1.

    Conclusions: Breviscapine has the suppressive effects on the proliferation, migration, invasion, EMT, and TGF-β1/Smad signaling of TGF-β1-treated pulmonary fibrotic cells in vitro by blocking PI3K/AKT/GSK3β pathway, and possesses great potential as a feasible candidate for pulmonary fibrosis.

  • Article
    Haifeng Zhou, Peiyue Jiang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 625-633. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.70
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    Objective: FOXO3a has been reported to be involved in regulating decidual formation. This research aimed to probe into the role and mechanism of miR-155-5p/FOXO3a in the decidualization of endometrial stromal cells.

    Methods: Human endometrial stromal cells (hESCs) were cultured and decidualization induced in vitro. An immunofluorescence assay was utilized to monitor cell morphology. Quantitative RT-PCR (qRT-PCR) was applied to monitor the expression of microRNA-155-5p (miR-155-5p) in the decidualization model in vitro, ELISA was utilized to detect the levels of prolactin and Insulin-like growth factor binding protein 1 (IGFBP1). The levels of prolactin, IGFBP1, decorin (DCN), and Forkhead box O3 (FOXO3a) were detected by western blot. Dual-luciferase reporter gene assay was applied to detect the binding between miR-155-5p and FOXO3a.

    Results: The expression of miR-155-5p was downregulated in the process of decidualization. Herein, overexpression of miR-155-5p attenuated decidualization of hESCs in vitro. Compared with normal decidualized cells, the decidualization markers (prolactin, IGFBP1, and DCN) in miR-155-5p mimic-transfected cells were also inhibited. Furthermore, bioinformatics analysis and luciferase reporter analysis proved that FOXO3a was the direct target of miR-155-5p. The rescue experiment confirmed that FOXO3a could partially reverse the inhibition of miR-155-5p on decidualization.

    Conclusions: This study confirmed the regulatory function of miR-155-5p in the inhibition of FOXO3a-mediated decidualization. This may provide some understanding for the treatment of planting-related diseases and infertility.

  • Article
    Yong-Ming Liu, Yuan-Yu Liang, Ning-Zi Zang, Ling-Yun Zhu, Lin-Lin Wang, Li Yang, Tian-Jiao Wang, Rui Jiao, Si-Meng Xie, Yan-Tong Liu, Li-Jian Pang, Xiao-Dong Lv
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 635-646. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.71
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    Purpose: To identify key biomarkers associated with the diagnosis, prognosis, and treatment of idiopathic pulmonary fibrosis (IPF), as well as to establish miRNA-mRNA regulatory networks in this disease.

    Methods: Differentially expressed microRNAs (DEMs) and differentially expressed genes (DEGs) were identified from the publicly-available microarray datasets GSE27430, GSE32537, and GSE24206. The transcription factors and target genes of DEMs were further predicted by FunRich and miRNet respectively. The miRNA-mRNA regulatory networks were constructed by overlapping identified target genes for DEMs and DEGs, and the output was depicted using Cytoscape software. The Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted using OmicShare tools and R software.

    Results: 16 DEMs and 120 DEGs were identified within the GSE27430, GSE32537, and GSE24206 datasets. miRNA-mRNA regulatory networks were constructed with 28 miRNA gene pairs, consisting of 11 miRNAs (hsa-mir-154-5p, hsa-mir-382-5p, hsa-mir-410, hsa-mir-432-5p, hsa-mir-299-5p, hsa-mir-493-5p, hsa-mir-127-3p, hsa-mir-409-3p, hsa-mir-487b, hsa-mir-203a-3p, and hsa-mir-375) and 22 genes (C12orf75, CCDC113, CD24, GXYLT2, IL13RA2, KLHL13, MXRA5, PSD3, SPATA18, ST6GALNAC1, VCAM1, MNS1, OGN, ACSL1, ADM, HHIP, MATN3, NECAB1, PTX3, SERPINE1, SULT1B1, and THBS1). GO and KEGG analysis showed most candidate genes were enriched in pathways associated with the extracellular matrix, collagen, and platelet function.

    Conclusions: In this study, the miRNA-mRNA regulatory networks with 11 miRNAs and 22 mRNAs provide potential biomarkers, and may highlight novel strategies for diagnosis and treatment in IPF.

  • Article
    Niccolò Cenzato, Loris Marcolongo, Solanlly Sanchez, Cinzia Maria Norma Maspero
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 647-653. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.72
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    Background: The aim of the study is to evaluate the different composition and oral microflora and bacterial plaque present in patients treated with clear aligners and fixed appliances.

    Methods: The study was conducted on 16 patients, 7 males and 9 females aged between 7 and 35 years were selected as study sample. 8 of them have been treated by fixed orthodontic appliances and 8 with clear aligners. The bleeding index was detected and a plaque sample was taken at the level of the lingual surface of the first lower right molar (46) with a sterile loop, to analyze the composition of the gram bacteria.

    Results: Patients with clear aligners presented a bleeding index less than 9%, while patients with fixed appliance it was ranging from 12% to 20%. In addition, patients with fixed appliances, compared to patients with clear aligners presented less than 25% Gram+ cocci; more than 50% of Gram- cocci; more than 40% of Gram+ bacilli; more than 12% of Gram- bacilli.

    Conclusions: Patients treated with clear aligners can maintain better oral hygiene and the composition of the bacterial flora is less pathogenic than patients treated with fixed appliances. It would therefore be appropriate to evaluate different bacterial plaque control strategies between the two orthodontic methods.

  • Article
    Zhaonan Ban, Ying Wang, Lei Xu, Xingtian Lan, Shuxing Xing, Yongjie Ye, Bing Xu, Qiang Huang, Xin He, Hang Zhong, Wanquan Cao, Jing Quan, Qian Tang, Zhengjiang Li
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 655-666. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.73
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    Background: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with autoimmune features, but its molecular mechanism(s) remain unclear.

    Methods: We analyzed differentially expressed genes (DEGs) using GSE55235, GSE55457, and GSE1919 datasets downloaded from the Gene Expression Omnibus database. We analyzed co-expressed DEGs in GSE55235 and GSE55457 using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and a protein-protein interaction (PPI) network of the co-expressed DEGs constructed using STRING and Cytoscape. The top20 hub genes were screened, and targeted miRNAs were identified using TargetScan v. 7.1. The relative expression of hub genes in clinical specimens and in TNF-α-stimulated synovial cells was analyzed by real-time PCR.

    Results: We extracted 1123 and 333 DEGs in GSE55235 and GSE55457, respectively based on cutoff criteria of |log2 (FC)| > 1 and adjusted p < 0.05. We found 174 overlapping genes comprising 137 upregulated and 37 downregulated DEGs in patients with RA. Gene Set Enrichment Analysis (GSEA) revealed activated cytokine-cytokine receptor interaction and chemokine signaling pathway cell adhesion molecules (CAMS) in RA lesions. RT-PCR analysis revealed significantly upregulated expression of the hub genes, cluster of differentiation (CD)2, cell division cycle protein 20 homolog (CDC20), and kinesin family member 11 (KIF11) in patients with RA compared with controls and in the GSE1919 dataset. Moreover, miR-106a-5p, miR-20a-5p, and miR-17-5p might negatively regulate the relative expression of ribonucleotide reductase regulatory subunit M2 (RRM2) during RA progression.

    Conclusions: We identified and validated hub gene expression in RA pathogenesis, and found that the key miRNAs, miR-106a-5p, miR-20a-5p, and miR-17-5p might negatively regulate RRM2 expression during RA progression. These novel hub genes might help to clarify the RA pathogenesis and lead to novel strategies for RA treatment.

  • Article
    Lei Zhang, Gengming Wang, Xiaojun Li, Zhen Tang, Chao Song, Yang Geng, Wei Wang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 667-676. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.74
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    Objective: The study aimed to investigate the role of general transcription factor 2B (GTF2B) in proliferation and apoptosis of human lung adenocarcinoma A549 cells.

    Methods: The expression of GTF2B in human lung cancer cell lines (H460, A549, H1299 and PC9) was detected by the qRT-PCR. A549 cells were infected by lentivirus carrying shRNA targeting GTF2B (shGTF2B) and control shRNA (shCtrl) for GTF2B knockdown, and the knockdown efficiency was verified by qPCR and Western blot. Cell proliferation was determined by CCK-8 assay and colony formation assay. The induction of apoptosis was detected by flow cytometry, and the related proteins were examined by Western blot.

    Results: GTF2B showed the highest expression in A549 cell among human lung cancer cell lines. shGTF2B efficiently reduced the mRNA and protein levels of GTF2B. Upon GTF2b silencing, cell proliferation was significantly impaired and the colony formation ability was decreased. GTF2B silencing caused a G1/S arrest in A549 cells, and led to an increased of apoptotic events, as well as the increased levels of pro-apoptotic proteins. Western blot results showed that C-JUN and mTOR protein levels in shGTF2B group were decreased, and P53, TNF-α and PTEN protein levels were increased upon GTF2B silencing.

    Conclusions: Taken together, our data suggest that GTF2B is required for the proliferation and survival of non-small cell lung cancer A549 cells, which may serve as a candidate for therapeutic intervention.

  • Article
    Jianming Mo, Ping Xu, Hui Han, Yazhou Cai, Xiang Long
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 677-688. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.75
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    Background: Considering the oncogenic role of long non-coding RNA (lncRNA) LMCD1-AS1 in various cancers and its dim association with lung cancer (LC), we commence the research to unveil such association.

    Methods: LMCD1-AS1, let-7b-5p and SP1 expressions in LC cells were predicted by starBase and calculated via quantitative reverse-transcription PCR (qRT-PCR). The targeting relationships were predicted with bioinformatics and further verified using dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. The effects of LMCD1-AS1 on cell viability (cell counting kit-8), migration, invasion (Transwell assay) and epithelial-mesenchymal transition (EMT, Western blot) were determined with the help of loss- and gain-of-function assay. The regulation of the LMCD1-AS1/let-7b-5p axis on the aforementioned malignant biological behaviors of LC cells and the activation of PI3K/AKT pathway was detected by rescue experiments.

    Results: LMCD1-AS1 was highly expressed in LC. The malignant biological behaviors and EMT of LC cells were promoted following the overexpression of LMCD1-AS1, but were inhibited by silencing of LMCD1-AS1. SP1 activated the transcription of LMCD1-AS1, and let-7b-5p was the target miRNA of LMCD1-AS1. LMCD1-AS1 regulated the malignant biological behaviors of LC cells and activated PI3K/AKT pathway by targeting let-7b-5p.

    Conclusions: SP1 mediates LMCD1-AS1 overexpression and promotes the progression of LC by targeting let-7b-5p.

  • Article
    Liqing Yang, Jiqing Cao, Yongqiang Wang, Cheng Zhang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 689-698. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.76
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    Background: Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively affects motor neurons. Vascular endothelial growth factor (VEGF) and adipose-derived stem cells (ADSCs) have shown therapeutic efficacy in ALS. VEGF has a combinatorial effect on the proliferation and differentiation of ADSCs in vitro; however, its effects in vitro remain unclear.

    Methods: A method involving transplantation of ADSCs with or without VEGF through the fourth ventricle was used. An ALS mouse model (G93A-SOD1 transgenic mice) was used to explore the effects of this combination therapy on ALS. The onset of ALS and survival times of G93A-SOD1 mice were noted, compromised, motor function was assessed using a rotating rod experiment, and immunohistochemical and Nissl staining were used to assess neuronal changes, particularly motor neurons. The expression levels of key proteins were analyzed by western blotting.

    Results: The transplantation of GFP-rADSCs and VEGF-rADSCs in G93A-SOD1 mice delayed the onset of ALS, enhanced the survival and motor function of mice, improved the structure and number of neuronal cells, inhibited the hyperplasia of astrocytes, and upregulated the expression of VEGF and glutamate transporter-1 (GLT-1) protein.

    Conclusions: Combination therapy may protect motor neurons by promoting the expression of VEGF and GLT-1, thereby reducing astrocyte hyperplasia, improving motor function, delaying the onset of ALS, and prolonging the lifespan of G93A-SOD1 mice.

  • Article
    Ruizhu Lin, Jianfeng Xu, Xinbao Tian, Yundong Chen, Jian Liu, Yujuan Liu, Yue Wang, Kaibin Wang, Jie Zhang, Lei Wang, Ning Zhu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 699-709. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.77
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    Background: Our previous study has shown that Hui Medicine moxibustion (HMm) can improve the steroid-induced avascular necrosis of the femoral head (SANFH) at the early stage. The primary purpose of this study was to explore the therapeutic effect and underlying molecular mechanisms of HMm treatment in rats with SANFH.

    Methods: We established SANFH rat models, which were treated with HMm alone and with Fas activating antibody. Hematoxylin and eosin (H & E) staining was applied to assess the effects of HMm intervention on the altered pathological features of subchondral bone. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, western blotting, immuno-histochemistry, and RT-PCR were performed to detect the expression of proteins related to Fas-mediated apoptosis.

    Results: We found that HMm treatment significantly reduced bone resorption, damage, and loss of subchondral bone. Cell apoptosis in trabecular bone and marrow significantly decreased in Hui/SANFH group after treatment for four weeks with HMm. Compared to the SANFH group, the levels of Fas, FasL, FADD, c-Caspase-8, and c-Caspase-3 dramatically reduced in the Hui/SANFH group. However, HMm intervention significantly decreased the mRNA levels of MMP-1 and MMP-3. Also, it increased Runx-2 expression and the ratio of OPG/RANKL, whereas the anti-Fas antibody treatment abolished the effect of HMm intervention.

    Conclusions: The study strongly demonstrates for the first time that HMm treatment may play an important role in improving SANFH via downregulating the Fas/FasL signal pathway.

  • Article
    Xuexin Wang, Lingling Jiang
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 711-720. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.78
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    Background: Programmed cell death 10 (PDCD10) is associated with cell apoptosis and inflammation, but its role in uterine ischemia/reperfusion injury (IRI) is unclear. The aim of this study was to evaluate the role of PDCD10 in uterine IRI in rats.

    Methods: A uterine IRI model was induced by using a microvascular clamp at the distal end of the abdominal aorta, followed by silencing smallinterfering (si) RNA-PDCD10 transfection. Histologic examinations including hematoxylin, eosin staining and Masson trichrome staining were performed. Enzyme-linked immunosorbent assays were used to determine the expression of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-a. The protein levels of PDCD10, Bcl-2, caspase-3, collagen 1, α-smooth muscle actin (α-SMA), fibroblast growth factor 2 (FGF2), IL-β, IL-6, and TNF-α were determined by western blot analysis.

    Results: The expression of PDCD10 was significantly increased in a time-dependent manner after induction of IRI, while siRNA-PDCD10 downregulated its expression. Silencing PDCD10 thickened the endometrium; thinned the myometrium; attenuated expression of collagen 1, α-SMA, and FGF2; repressed the expression of IL-1β, IL-6, and TNF-α; and suppressed apoptosis by activating Bcl-2 and inhibiting Bax and caspase-3 in the uterus following IRI.

    Conclusions: Silencing PDCD10 ameliorated uterine IRI through inhibition of fibrosis, inflammation and apoptosis, and may serve as a promising management tool for women with uterine IRI.

  • Article
    Kaining Jia, Hongyan Zhang, Yiwen Na, Dan Zhu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 721-733. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.79
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    Background: Diabetes is a common immune-metabolic disease, and it has become the third non-communicable disease threatening human health and life after cardiovascular disease and tumor. Among them, type 2 diabetes is a more common condition. Inflammation is closely related to the pathogenesis and complications of diabetes. Type 2 diabetes-related risk factors such as inflammation and high glucose have been shown to induce pyroptosis, but it is still unclear whether pyroptosis is involved in the pathogenesis of type 2 diabetes.

    Methods: This study aimed to explore whether pyroptosis is involved in the pathogenesis of type 2 diabetes by bioinformatics analysis of transcriptomic data of tissue samples from patients with type 2 diabetes and healthy control samples from the GEOs dataset.

    Results: Differential gene expression analysis showed that five pyroptosis-related genes, NLRP3, ELANE, IL-6, SCAF11 and CASP1, were differentially expressed in patients with type 2 diabetes. Cluster analysis found that there were two types of pyrop-tosis in diabetic patients. PCA and pathway enrichment analysis revealed different gene expression profiles in the two patterns. The CIBERSORT algorithm assessed immune cell composition and found that patients with different patterns exhibited different immune cell infiltrations. The network analysis results of key genes showed that the above five pyroptosis-related genes have targeted miRNAs and transcription factors, except for the SCAF11 gene. The SCAFII gene has no predicted target drugs in the DGIdb database, but the other four genes have targeted drugs.

    Conclusions: Our results suggest that pyroptosis is involved in the pathogenesis of type 2 diabetes and may regulate the immune response in type 2 diabetes.

  • Article
    Jing Chen, Ligang Ren, Kaisen Liao, Chao Feng, Wei Shen
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 735-745. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.80
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    Background: Long non-coding RNAs (lncRNAs) are involved in various physiological and pathological processes. This study aimed to investigate the role of long non-coding RNA myocardial infarction associated transcript (lncRNA MIAT)-mediated miR-34a-5p/KLF4 axis in the phenotypic transformation of corpus cavernosum smooth muscle cells (CCSMCs) in diabetes mellitus erectile dysfunction (DMED) rats.

    Methods: We constructed a DMED rat model and observed the pathological changes and apoptosis of cavernous tissues using HE/Masson and TUNEL staining. The expressions of lncRNA MIAT, miR-34a-5p, and KLF4 in cavernous tissues were detected by qRT-PCR or immunohistochemistry. Immunohistochemistry assay was used to identify the isolated CCSMCs, and cell vitality and migration were examined using CCK-8 and wound healing. The binding of miR-34a-5p and KLF4 was determined by a dual-luciferase report assay. Oxidative stress levels were detected by ELISA. The expressions of lncRNA MIAT, miR-34a-5p, KLF4, α-SMA, SM-MHC, and OPN were detected by immunofluorescence, qRT-PCR or western blot.

    Results: LncRNA MIAT and KLF4 were up-regulated in the cavernous tissues of DMED rats. MiR-34a-5p mimic decreased KLF4-3′UTR-WT luciferase activity. High glucose (HG) induction promoted the proliferation and migration of CCSMCs. LncRNA MIAT and KLF4 silencing inhibited the proliferation, migration, surface transformation and oxidative stress of HG-CCSMCs compared to miR-34a-5p inhibition. KLF4 silencing neutralized the positive effect by miR-34-5p inhibition.

    Conclusions: LncRNA MIAT facilitates phenotypic transformation and oxidative stress of CCSMCs in DMED rats via mediating the miR-34a-5p/KLF4 axis.

  • Article
    Hai-jia Ma, Xiao-dan Zhou, Li-yu Zhang, Ling Wang, Jin Chen, Hui-ying Qiu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 747-754. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.81
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    Background: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by inflammation, articular cartilage degradation, joint discomfort, and limited function. So far, there is a lack of effective treatments for OA. This study aimed to investigate the function of hub genes and the potential mechanisms of regulation.

    Methods: The whole data of microarray datasets, consist of 12 control groups of OA patients’ chondrocyte and 12 groups of OA patients’ chondrocyte with COT from GSE75181. Differentially expressed genes (DEGs), Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed. Protein-Protein Interaction (PPI) network and Gene Set Enrichment Analysis (GSEA) were performed. Cytoscape was used to identify central genes. Finally, the CCK-8 cell proliferation assay was used to verify the role of the gene HSPA4 in OA by down-regulating the expression of HSPA4.

    Result: A total of 274 up-regulated and 164 down-regulated genes were identified in this study, 438 DEGs were related to OA patients treated with COT mixture in the dataset. DEGs in OA patients treated with COT mixture was enriched in unfolded protein, MAPK signaling pathway and Extracellular matrix organization. GSEA indicated that Dorsal spinal cord development, Regulation of presynaptic cytosolic calcium ion concentration, sinus bradycardia and prolonged qtc interval were related to the tumorigenesis of OA patients treated with COT mixture. Finally, 6 hub genes (HSPA4, MYC, HSPA8, COL1A1, COL3A1 and CTGF) were determined through the Cytoscape plugin. The CCK-8 cell proliferation assay showed that HSPA4 gene knockdown could inhibit the proliferation of VSMC.

    Conclusions: Our study results suggest a potential mechanism by which HSPA4 affects the occurrence and progression of OA. The results may help the understanding on the biological system of OA patients treated with COT cocktails and on the development of novel treatments for OA.

  • Case Report
    Jing-feng Chen, Yi-shuo Wang, Yong-jun Chen, Wen-dan Zhang, Chuan Cheng, Li-ping Yan, Peng Gao, Xin-wu Mao, Jian-ping Wang, Chu-xiao Shao, Jie Xu
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 755-764. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.82
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    Synchronous colorectal carcinoma (sCRC) is defined as multiple malignant colorectal tumors that occur simultaneously or in a heterochronous manner. In comparison to patients with solitary colorectal carcinoma (CRC), the incidence of sCRC is rare. At present, the literature presenting case reports of patients with SC remains limited. Here, we present three cases of sCRC. The first patient was admitted because of a 5-month history of abdominal pain associated with difficult defecation. PET-CT and colonoscopy revealed a mass lesion of the splenic flexure of colon, and another mass in the sigmoid colon. Postoperative pathology confirmed that there are malignant characteristics in both lesions. The second patient suffered from with fatigue for more than two years. Abdominal contrast enhanced CT showed irregular thickening of the ascending colon wall, and colonoscopy revealed a tumor in the patient’s rectum and many polyps in the sigmoid colon. Postoperative pathology confirmed a moderately differentiated adenocarcinoma of the rectum and ascending colon. The third patient exhibited hematochezia for one year. Both rectal magnetic resonance imaging (MRI) and colonoscopy indicated the presence of two lesions in the rectum. Postoperative pathology confirmed two malignant tumors in the rectum. The literature review provided in this manuscript summarizes the available information on sCRC prevalence, clinical manifestation, diagnosis, pathology, treatment, and the molecular mechanism features of sCRC. At present, serrated adenoma, hyperplastic polyps, ulcerative colitis, and Crohn’s disease are considered to be closely related to sCRC. Microsatellite instability and gene mutation are two molecular mechanisms that give rise to sCRC.

  • Case Report
    Antonio Scarano, Gianluca Martino Tartaglia, Felice Lorusso, Francesco Inchingolo
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 765-768. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.83
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    Background: The dental implant displacement into nasal and paranasal cavity represent a very rare complications in the clinical practice.

    Case Description: The present investigation reported a case of a 68-year-old female subject affected by a dental implant displaced into the inferior nasal meatus.

    Conclusions: The present study findings reported a particular case that did not required intervention procedure, while the dental implant migrated into the nasal cavity resulted in a spontaneous resolution by ingestion into the digestive tract.

  • Case Report
    Paola Emilia Ferrara, Dario Mattia Gatto, Ilaria Bastoni, Paolo Zordan, Gioia Stefinlongo, Roberta Marini, Fiorella Evangelista, Antonio Leone, Gianpaolo Ronconi
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 769-774. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.84
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    Background: Posteromedial bowing of the tibia (CPMBT) is a rare congenital lower extremity disorder typically associated with calcaneovalgus foot deformity and extreme ankle dorsiflexion that can lead to leg length discrepancy (LLD) later in life. The management of CPMBT includes several therapeutic options, but the treatment of choice remains controversial. Given the tendency to spontaneous leg bowing correction, some authors suggest an initial conservative treatment consisting of manipulation, serial casting, orthoses and shoe lifts during the first four years of life, leaving surgical limb equalization closer to skeletal maturity.

    Methods: An Asian girl born at 38 weeks of gestational age, affected by left congenital posteromedial bowing of the tibia and ipsilateral calacaneo valgus deformity was exclusively treated with conservative orthopedic management and rehabilitation physiotherapy.

    Results: The integrated approach of serial casting and splinting in conjunction with early physiotherapy was effective to resolve the calcaneo valgus foot deformity and to significantly correct the left leg bowing and LLD. Moreover, adequate gross motor development was achieved as evidenced by periodic AIMS score assessment.

    Conclusions: Conservative management with intermittent plaster casting and rehabilitation treatment during the first years of life can significantly improve congenital leg bowing, calcaneo valgus deformity and leg length discrepancy. We believe that our experience can contribute to build up a standardized rehabilitation protocol to minimize the need for surgery in CPMBT patients. Future studies should compare the motor skill development of children with CPMBT that underwent conservative orthopedic management and rehabilitation treatment with children who only underwent conservative orthopedic management.

  • Case Report
    Yanzhen Zhang, Lidan Zhang, Sufang Sun, Li Wen, Yongmiao Pan
    Journal of Biological Regulators and Homeostatic Agents. 2022, 36(3): 775-781. https://doi.org/10.23812/j.biol.regul.homeost.agents.20223603.85
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    Background: This study aimed to identify potential pathogenic gene variations associated with Bardet-Biedl syndrome type 12 (BBS12) in a Chinese family.

    Case Description: Single nucleotide polymorphism microarray (SNP-Array) and whole exome sequencing were performed to identify pathogenic gene variations associated with BBS12, which was phenotypically characterised with antenatal ultrasonography and post-natal examination. Antenatal SNP-Array analysis revealed a 107.8 Kb deletion in the 4q27 segment of chromosome 4. An initial whole exome sequencing detected a homozygous mutation on the BBS12 gene in the family: there was one de novo mutation inherited from the mother while another gene mutation was from the father. After five years follow-up, whole exome sequencing identified a heterozygous BBS12 mutation, c.337_339del (p.V113del) inherited from the father, accompanied with a heterozygous deletion of chr4: 123653861–123748536 inherited from the mother.

    Conclusions: BBS is a rare autosomal recessive disorder, usually caused by a pathogenic homozygous mutation or compound heterozygous mutation in the BBS gene. This article reports a novel case of BBS12 that resulted from both a heterozygous mutation and heterozygous deletion for the first time.

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