Background: Observational studies have reported an association between immune cells and digestive diseases. We sought to assess the relationship between immune cells and the risk of gastric malignancy by two-way two-sample Mendelian randomisation (MR) analysis.

Methods: This study used a comprehensive two-sample Mendelian randomisation (MR) analysis to determine the causal relationship between immune cells and gastric malignancy (GC). Based on publicly available genetic data, we explored the causal relationship between 731 immune cell signatures and GC risk. We performed Mendelian randomisation (MR) analyses using genetic variants strongly associated with neutrophil, lymphocyte, eosinophil, basophil and monocyte counts as instrumental variables (IVs). Comprehensive sensitivity analyses were used to verify the robustness, heterogeneity and horizontal pleiotropy of the results.

Results: Two-sample MR analysis revealed that multiple immune cell phenotypes were significantly associated with the risk of gastric malignancy. Among the phenotypes with low uncorrected p-values, including CD14- CD16- AC (p < 0.001; OR = 0.9730; 95% CI = 0.9598–0.9863); DN (CD4- CD8-) AC (p < 0.001; OR = 1.1483; 95% CI = 1.0607–1.2432); IgD on IgD+ (p < 0.001; OR = 0.8883; 95% CI = 0.8289–0.9520). Meanwhile, we used Simple mode, Weight median, and Weight mode, all of which led to the same conclusion. Moreover, in our further analysis, gastric malignancy also had a causal effect on the above immune cell types when gastric malignancy was used as an exposure factor, and the results were statistically significant.

Conclusion: The study underscores the crucial role of immune cells in GC development, providing key insights for future research. The statistically significant associations between specific immune cell phenotypes and gastric malignancy risk highlight potential targets for therapeutic interventions aimed at modulating the immune response in GC, thereby opening avenues for precision medicine approaches in the treatment of this disease.

Background: Rhamnazin is a natural dimethoxyflavonoid compound and Rhamnazin has been reported to have antitumor activity. This work is performed to study the function of Rhamnazin in prostate cancer (PCa) cells and its mechanism.

Methods: Rhamnazin (20 μM) was used to treat 22Rv1 and C4-2B cells, and the cells treated with dimethyl sulfoxide (DMSO) were set as the control group. To investigate the role of dipeptidyl peptidase 4 (DPP4) in mediating the biological effects of Rhamnazin, DPP4 overexpression plasmids were transfected into the PCa cell lines. Cell counting kit-8 method was employed to detect the proliferation; apoptosis and cell cycle were detected by flow cytometry. the target genes of Rhamnazin were predicted in Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of target genes of Rhamnazin was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID database). Human Protein Atlas database was utilized to identify genes associated with poor PCa prognosis. GEPIA database was used to validate the expression and prognosis of DPP4 in PCa. The LinkedOmics database was used to analyze the signaling pathway related to DPP4 in PCa. Quantitative polymerase chain reaction was performed to detect DPP4 mRNA levels. Western blot assays were performed to detect the expression levels of DPP4, phosphorylated (p-) Janus kinase 1 (JAK1) and p-signal transducer and activator of transcription 3 (STAT3).

Results: Functional assays confirmed that Rhamnazin inhibited the proliferation of PCa cells (p < 0.05), and promoted apoptosis (p < 0.05) and blocked the cell cycle progression (p < 0.05). In addition, Rhamnazin significantly inhibited the expression of DPP4 (p < 0.05), and up-regulating DPP4 reversed the effects of Rhamnazin (p < 0.05). It was further found that DPP4 was associated with JAK/STAT signaling and Rhamnazin inhibited the expression of p-JAK1 (p < 0.05) and p-STAT3 (p < 0.05) through DPP4.

Conclusion: Rhamnazin has the potential to kill PCa cells via DPP4/JAK/STAT axis.

Background: Hepatocellular carcinoma (HCC) is a common human malignancy. In recent years, the study of biomarkers for HCC progression has become a hot topic. This study focused on identifying the key gene protein Z (PROZ) associated with the tumorigenesis of HCC by bioinformatics methods, and exploring its function and regulatory mechanism.

Methods: Differentially expressed genes (DEGs) in HCC cells under hypoxia condition and normoxia condition were analyzed with the data of GSE15366 and GSE41666. The genes associated with the prognosis of HCC patients were analyzed in the Human Protein Atlas (HPA) database and intersected with hypoxia-related DEGs in HCC to obtain key genes. Gene Expression Profiling Interactive Analysis database was used to analyze the relationship between expressions of the above key genes in HCC and the prognosis of patients. The mRNA expression level of PROZ was analyzed by qPCR. Immunohistochemical staining results of PROZ in HCC were obtained from the HPA database. The cell viability and apoptosis were testified by CCK-8 and TUNEL methods. The glucose consumption and lactic acid production of cells were also detected. LinkedOmics database was used to analyze the relevant signaling pathways regulated by PROZ in HCC. Western blot was adopted to detect expressions of Hexokinase 2 (HK2) protein, cyclin D1 (cyclin B1) and Notch signaling pathway-related proteins including notch receptor 1 (Notch1) and Hes family BHLH transcription factor 1 (Hes1).

Results: PROZ was greatly down-regulated in HCC cells (HepG2 and Hep3B) in hypoxia condition. PROZ overexpression in HepG2 cell lines inhibited cell proliferation and glycolysis, and promoted apoptosis; PROZ knockdown worked oppositely. In terms of mechanism, PROZ inhibited the expression levels of cell cycle-related proteins, Notch1 and Hes1.

Conclusions: PROZ inhibits HCC cell proliferation and glycolysis, and promotes apoptosis by inhibiting cell cycle and Notch signaling pathways. PROZ could be a potential biomarker/therapy target for HCC.

Background: This article mainly analyzed the influence of obesity constitution on the failure of cemented total hip replacement.

Methods: By collecting body mass index (BMI) data of patients with hip joint and bone mineral density (BMD) of femur, the age, gender and number of patients were statistically analyzed, and the influence of body weight on postoperative implant force was analyzed by finite element method modeling analysis.

Results: Studies have found that obesity and BMI reaching overweight or obesity standards will aggravate the symptoms of hip patients, and the effects will be different between different genders. The effects of body weight on hip replacement, fracture of bone cement stem, sinking of prosthesis stem and loosening of bone cement-stem interface were analyzed in detail.

Conclusions: It was proved that BMI had a great correlation with postoperative failure. In addition, the effect of weight loss drugs on postoperative rehabilitation immune system was discussed.

Background: Esophageal squamous cell carcinoma (ESCC) is a strongly metastatic and fatal cancer. Currently, the mechanisms underlying the pathogenesis of ESCC are poorly understood. Lysine-specific demethylase 6B (KDM6B) plays a key role in the occurrence and development of various human diseases, such as cancers, immune diseases and developmental diseases. Studies have confirmed that KDM6B may exhibit both tumour-suppressive and oncogenic activities in different cancer types. However, the expression and role of KDM6B in ESCC remain unclear.

Methods: KDM6B expression was analysed using The Cancer Genome Atlas (TCGA) database, and the correlation between KDM6B mRNA expression and prognosis was analysed. The expression of KDM6B in Eca109 and TE11 ESCC cells and ESCC tissues was evaluated using immunohistochemical (IHC) and Quantitative Real-time PCR (RT‒qPCR) analyses. In vitro assays were further performed to reveal the functions and characterize the upstream and downstream regulation of KDM6B expression.

Results: KDM6B was overexpressed in stage T3/T4 as well as N2/N3 ESCC tissues relative to stage T1/T2 and N1/N2 ESCC tissues, respectively, and this overexpression was linked to worse prognosis of ESCC. Inhibiting KDM6B expression significantly impaired the proliferation and metastasis of ESCC cells. Lactate dehydrogenase isoform A (LDHA) plays a critical role in tumour aerobic glycolysis. The expression of LDHA was inhibited in ESCC cells to assess its role in ESCC proliferation. In this study, KDM6B knockdown suppressed not only LDHA expression but also ESCC cell proliferation.

Conclusions: Based on these results, we speculate that KDM6B might be a novel therapeutic target for ESCC.

Background: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Histone deacetylases (HDACs) play a crucial role in the onset and development of PF. Changes in HDACs 1–10 expression levels occur during PF development, and their specific roles remain unclear. Therefore, we elucidated changes in the gene and protein levels of HDACs 1–10. Furthermore, we selectively knocked down HDAC2 to explore the molecular mechanism underlying the regulatory role of HDAC2 in epithelial-mesenchymal transition (EMT) during the development of PF.

Methods: Lewis lung carcinoma (LLC) cells were stimulated with transforming growth factor-β1 (TGF-β1) (5 ng/mL) to establish a lung fibrosis cell model. Additionally, C57BL/6 mice received bleomycin through single intratracheal instillation at a 3.5 mg/kg volume, diluted in 0.7 mL saline. Furthermore, EMT-related gene and protein expression levels were assessed using quantitative PCR (qPCR) and Western blotting, respectively.

Results: We observed that HDAC2 expression levels were significantly increased in both the in vitro and in vivo PF models. HDAC2 knockdown significantly decreased the expression levels of fibrosis indicators such as collagen type I (Col-I) and collagen type IV (Col-IV), and EMT indicator α-smooth muscle actin (α-SMA) was observed. Conversely, it increased the expression of EMT indicator E-cadherin (E-cad). Hematoxylin and eosin (H&E) and Masso staining revealed that HDAC2 knockdown substantially reduced the degree of pulmonary fibrosis. These findings suggest that lowering HDAC2 expression inhibits EMT and reduces PF. Moreover, in a TGF-β1-induced lung fibrosis cell model, HDAC2 knockdown significantly reduced epithelial growth factor receptor levels, which inhibited mitogen-activated protein kinases (MAPK) signaling and decreased the protein expression of p38 and c-Jun N-terminal kinase (JNK).

Conclusions: HDAC2 knockdown effectively impedes EMT and diminishes PF severity, impacting the JNK/p38 MAPK signaling pathway, which may serve an inhibitory function.

Background: Unsatisfactory prognosis of glioma partly arises from its resistance to temozolomide (TMZ). This work will focus on whether luteolin sensitize glioma cells to TMZ and explore its regulatory mechanism.

Methods: The viability, cell cycle progression and programmed death of TMZ-resistant glioma cells were evaluated by CCK-8 assay, flow cytometry, and TUNEL assay. Additionally, the cell migration and invasion were examined by Transwell assay. The expression of PI3K/AKT signaling pathway-related proteins was probed by Western blot. The target genes of luteolin, and those related to gliomas were identified by bioinformatics.

Results: In vitro experiments suggested that luteolin could impede the malignant biological behaviors including viability and aggressiveness of TMZ-resistant glioma cells. Bioinformatics analysis implied the target genes of luteolin and glioma were associated with the PI3K/AKT signaling pathway. Luteolin significantly inhibited p-PI3K and p-AKT proteins' expression in TMZ-resistant glioma cells.

Conclusion: Luteolin could sensitize TMZ-resistant cells to TMZ, at least partly via modulating the PI3K/AKT signaling.

Background: Lobar pneumonia seriously endangers children's respiratory tract health and affects their growth and development, so it is very important to identify pathogenic microorganisms and use appropriate antibiotics early.

Objective: To analyze the significance of pathogenic detection of alveolar lavage fluid in children with lobar pneumonia.

Methods: The clinical data of 80 children with lobar pneumonia who were hospitalized from March 2019 to March 2022 were analyzed for pathogenic characteristics in bronchoalveolar lavage fluid (BALF) detected by fluorescence quantitative PCR (FQ-PCR), and serum mycoplasma pneumoniae-specific antibody (MP-IgM) levels were measured by enzyme-linked immunosorbent assay (ELISA). The differences in clinical lung infections in children with different age groups, mycoplasma pneumoniae (MP) pneumonia versus non-MP pneumonia, and mixed versus single infections were compared.

Results: There were 15 cases of pathogenic MP infection in the 1–3 years old group, 34 cases of MP infection in the 4–6 years old group, and 6 cases of pathogenic MP infection in the 7–14 years old group. Statistically significant differences were observed in the detection rate of MP between each age group (p < 0.001), and the highest MP detection rate was found in the 7–14 years old group. The differences in the detection rates of single and mixed infections between the age groups did not come up to the statistical standard (p > 0.05). The mean age of patients with a single infection was slightly older than that of patients with mixed infection, but no statistical difference was found between the groups (p > 0.05). The duration of disease was shorter than that of patients with mixed infection, but the difference between the two groups was not statistically significant (p > 0.05). The positive rate of MP detection in BALF by FQ-PCR (55, 73.75%) was higher than that of serum MP-IgM detection (38, 47.5%).

Conclusion: The detection rate of MP was the highest in children with lobar pneumonia, followed by Streptococcus pneumoniae (SP) and adenovirus (ADV), and the pathogens of infection varied in different age groups. MP is the main pathogen of most mixed infections, and mixed infections are more prone to severe or refractory cases. Further studies are required prior to clinical promotion.

Background: miRNAs are involved in the process of tumorigenesis and metastasis as tumor suppressor genes or oncogenes. This work aims to explore the effect of miR-140 in the proliferation and invasion as well as metastasis of gastric cancer cells, as well as to provide new target for the diagnosis and therapy for gastric cancer.

Methods: miR-140 mimics and miR-140 inhibitors were transfected to the SGC-7901 gastric cancer cells, the expression of miR-140 and histone deacetylase4 (HDAC4) in human gastric cancer and normal gastric tissues was evaluated by quantitative reverse transcription-PCR (qRT-PCR), the HDAC4 protein level was evaluated by western blot method. The effects of miR-140 upregulation and downregulation on the invasion and metastasis ability of SGC-7901 cells were investigated by Transwell cell model. The samples were classified into control group by adding lipofectamine 2000, negative control group by adding miRNA unrelated sequence and lipofectamine 2000, miRNA up-regulated transfection group by adding miR-140 mimics and lipofectamine 2000 were added, as well as miRNA down-regulated transfection group by adding miR-140 inhibitors and lipofectamine 2000.

Results: The effects of up and down regulation of miR-140 on the invasion and metastasis ability of SGC-7901 cells were determined by Transwell chamber model. The expression of miR-140 in gastric cancer cells was significantly lower than that of normal gastric tissue (p < 0.05). The invasion and metastasis ability of SGC-7901 cells in miR-140 mimics and miR-140 inhibitor groups were significantly lower and higher when compared with negative control (NC) and control groups, respectively. HDAC protein was significant up-expressed in miR-140 inhibitor group when compared with NC and control groups. All these differences were of statistical significance (p < 0.05).

Conclusion: The expression level of miR-140 are associated with the invasive and metastatic properties of gastric cancer cells, which may serve as new target for the clinical treatment of gastric cancer.

Aim: This study is targeted at investigating the effects of Celastrus orbiculatus extract (COE) on non-small cell lung cancer (NSCLC) cells.

Methods: At 24, 48 and 72 h after different concentrations of COE were applied to treat NSCLC cells, MTT method, 5-Ethynyl-2′-deoxyuridine (EdU) assay, Transwell assay and flow cytometry were conducted to explore the effects of COE at different concentrations on the phenotypes of NSCLC cells. The expression of apoptosis-associated proteins and PI3K/AKT/mTOR-associated proteins were examined via Western blot.

Results: COE inhibited NSCLC cell multiplication, migration and invasion and facilitated the apoptosis, and this effect was dose-dependent. Additionally, also in a dose-dependent manner, COE suppressed Bcl-2 expression and facilitated Bax expression. After COE treatment, the phosphorylation levels of AKT, mTOR and PI3K were noticeably decreased.

Conclusion: COE suppresses the malignancy of NSCLC cells, probably via inhibiting PI3K/AKT/mTOR signaling.

Objective: To explore the biological functions and the mechanisms of ETS transcription factor ELK1 (ELK1) in esophageal squamous cell carcinoma (ESCC) cells.

Methods: ELK1 expression in ESCC samples/cells was analyzed by the UALCAN database. ELK1 mRNA expression in ESCC tissue samples and cells was detected utilizing quantitative real-time PCR. Cell counting kit-8 method, BrdU assay and Transwell assays were employed for examining ESCC cell proliferation, migration, and invasion. The PROMO database was adopted to predict the binding sites of ELK1 and the cyclin-dependent kinase 4 (CDK4) promoter region. The binding status of ELK1 and CDK4 was predicted and verified by dual-luciferase reporter gene assay and chromatin co-immunoprecipitation qPCR assay. The effect of ELK1 on CDK4 expression was examined via western blot. The possibly related signaling pathways to CDK4 were predicted by the gene set enrichment analysis in the LinkedOmics database.

Results: In ESCC tissues and cells, ELK1 was up-regulated and was associated with short survival of patients. Upregulating ELK1 promoted malignant phenotypes of ESCC cells; ELK1 knockdown exerted the opposite effect. ELK1 bound to the CDK4 promoter region; ELK1 overexpression facilitated CDK4 expression, whereas ELK1 knockdown inhibited CDK4 expression. CDK4 is enriched in the Wnt signaling pathway, and ELK1 overexpression boosted β-catenin expression.

Conclusion: ELK1 promotes of CDK4 transcription, and activates Wnt/β-catenin pathway, thereby facilitating the ESCC malignant progression.

Background: Hydrogen peroxide (H₂O₂) can induce oxidative injury, protein damage and DNA breaks in osteoblasts. The purpose of this study was to investigate the effect of heme oxygenase-1 (HO-1) on the biological behavior and oxidative stress damage of H₂O₂-treated osteoblasts.

Methods: The skull osteoblasts were isolated and divided into three groups: negative control group (without H₂O₂ or transfection of HO-1 protein), positive control group (with H₂O₂ but without transfection of HO-1 protein) and experimental group (with H₂O₂ and transfection of HO-1 protein). After 24 h of intervention, the apoptosis, cell proliferation, levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD), protein levels of B-cell lymphoma-2 (Bcl-2), Caspase-3, Tartrate resistant acid phosphatase (TRAP) and cytokinin (CTK), as well as protein and mRNA levels of bone gla-protein (BGP) and Runt related transcription factor 2 (Runx2) were detected.

Results: Compared with the negative control group, the positive control group and the experimental group had lower levels of SOD, lower protein and mRNA expressions of BGP and Runx2, higher cell proliferation inhibition rate, apoptosis rate, levels of MDA and ROS levels, and protein levels of Bcl-2, Caspase-3, TRAP and CTK after intervention (all p < 0.05). The experimental group showed the opposite results when comparing with the positive control group (all p < 0.05).

Conclusions: HO-1 can inhibit the oxidative stress damage of osteoblasts induced by H₂O₂, as well as promote the proliferation and inhibit the apoptosis of osteoblasts.

Background: The Long noncoding RNAs (lncRNAs) have been recognized as pivotal regulators in the development of colorectal cancer (CRC). In this study, we aim to evaluate the impact of lncRNA matrilin 1 (MATN1)-Antisense RNA 1 (AS1)/micro RNA (miRNA, miR)-200c-3p/hyaluronan synthase-2 (HAS-2) axis on CRC cells and in vivo CRC model.

Methods: The expression levels of LncRNA MATN1-AS1 in CRC tissues were assessed utilizing the Gene Expression Profiling Interactive Analysis (GEPIA) platform. The expressions of LncRNA MATN1-AS1 and miR-200c-3p were validated through reverse transcription quantitative polymerase chain reaction, while HAS-2 protein and epithelial-mesenchymal transition (EMT)-related protein expressions were examined using western blot analysis. The enrichment of lncRNA MATN1-AS1 and miR-200c-3p was evaluated using RNA Binding Protein Immunoprecipitation (RIP). The binding sites between miR-200c-3p and lncRNA MATN1-AS1 or HAS-2 were predicted by StarBase and confirmed through dual-luciferase reporter assay. Additionally, colony formation assay was performed to assess CRC cell proliferation. Transwell migration assay and invasion assay were conducted to evaluate the migratory and invasive abilities of CRC cells. An in vivo model was established by subcutaneous injection in BALB/c nude mice, while lung metastasis models were created through caudal vein injection. Immunohistochemistry was employed for the detection of HAS-2 protein in vivo.

Results: The expression of LncRNA MATN1-AS1 was found to be upregulated in both CRC tissues and cells. Subsequently, dual-luciferase reporter assay was performed to demonstrate the interaction between miR-200c-3p and lncRNA MATN1-AS1, which was further confirmed by RNA immunoprecipitation (RIP) assay. Suppression of miR-200c-3p rescued low CRC cell proliferation, migratory and invasive abilities. EMT caused by the knockdown of lncRNA MATN1-AS1. HAS-2 is identified as a target that is negatively regulated by miR-200c-3p, highlighting a critical interaction within the CRC molecular landscape. As for in vivo detections, tumor weight and volume were suppressed via the downregulation of lncRNA MATN1-AS1. Additionally, lncRNA MATN1-AS1 downregulation inhibited lung metastasis and suppressed HAS-2 protein levels.

Conclusion: The MATN1-AS1/miR-200c-3p/HAS-2 axis was shown to regulate CRC cell proliferation, invasiveness, migration, EMT, and tumorigenesis in vivo.

Background: How long non-coding RNA (lncRNA) functions in cancer biology has attracted extensive attention recently. Various lncRNAs interfere with the advancement of non-small cell lung cancer (NSCLC). This work focused on how lncRNA LINC00174 functions in NSCLC.

Methods: The analysis of LINC00174 expressions in NSCLC was performed with quantitative real-time PCR (qRT-PCR). The multiplication, migration, aggressiveness and apoptosis of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8), Transwell assays and Flow cytometry. The binding relationship between LINC00174 and E1A-binding protein p300 (EP300) was verified by RNA immunoprecipitation experiment. The binding of EP300 to the promoter region of the nuclear factor of activated T cells 5 (NFAT5) was detected by dual luciferase reporter gene assay and immunocoprecipitation assay.

Results: The expression of LINC00174 was increased in NSCLC, which impaired the overall survival time in patients with NSCLC. Knocking down LINC00174 curbed the multiplication, migration and aggressiveness of cancer cells and promoted apoptosis. LINC00174 was directly combined with EP300. Knocking down LINC00174 inhibited the binding of EP300 and NFAT5 promoter region, thereby curbing NFAT5 transcription. In addition, NFAT5 overexpression facilitated cancer cell malignancy, which could be reversed by knockdown of LINC00174.

Conclusions: This study indicates that LINC00174 promotes NFAT5 transcription by recruiting the EP300 to NFAT5 promoter region, thereby accelerating the progression of NSCLC.

Background: It has recently been shown that concomitant medication, such as proton pump inhibitors (PPIs), can modulate the microbiome and has effect on the clinical outcome among advanced-stage cancer patients following immune checkpoint inhibitors (ICIs). Whether such relationship is associative or causative in advanced non-small cell lung cancer (NSCLC) is content of investigation. The current meta-analysis was conducted to explore the impact of proton pump inhibitors (PPIs) on ICIs treatment in NSCLC.

Methods and Materials: The electronic databases were searched until September, 2022. Researches investigating the predictive role of PPIs in NSCLC following ICIs were included. Then, the meta-analysis was aim to reveal the influence of PPI use on survival efficacy.

Results: 8 researches were finally included. For all interested outcomes, the between-study heterogeneity was low. Our results showed that the concomitant PPI use has a negative effect on the survival of NSCLC receiving ICIs. The pooled HRs of progression-free survival (PFS) and overall survival (OS) were HR = 1.33 (95% CI 1.21 to 1.46, p < 0.00001) and HR = 1.46 (95% CI 1.32 to 1.62, p < 0.00001) when compared to those without PPIs.

Conclusion: The impact of PPI use is related to poor survival efficacy and may attenuate the anti-cancer activity of ICI. The underlying biological mechanisms of the relation between PPI and the efficacy of ICI treatment should be elucidate through further researches.

Background & Objective: Colchicine improves cardiovascular outcomes in patients with coronary heart disease, but the underlying mechanisms remain incompletely elucidated. The aim of this study was to evaluate the effects of colchicine on systemic inflammation, peripheral blood CD4⁺ T cell subsets, and oxidative stress after percutaneous coronary intervention in patients with coronary heart disease combined with gout from the perspective of population study.

Methods: From January 2019 to June 2022, a total of 128 patients with coronary heart disease combined with gout who underwent percutaneous coronary intervention (PCI) at our hospital were retrospectively collected and divided into colchicine group (n = 64) and control group (n = 64) according to whether colchicine was routinely used or not. Systemic inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and hypersensitivity C-reactive protein (hs-CRP)), peripheral blood CD4⁺ T cell subsets (Th1 cells, Th17 cells, and regulatory T cells), and oxidative stress indicators (serum superoxide dismutase (SOD) and malondialdehyde (MDA)) were compared between the two groups after PCI. hs-CRP ≥2 mg/L was defined as a patient at risk of residual inflammatory. Logistic regression was used to analyze the association between colchicine treatment and the risk of residual inflammation.

Results: There was no significant difference between the two groups in terms of age, gender, smoking history, disease history, body mass index (BMI), time from symptom onset to PCI, blood pressure, hypersensitivity troponin I (hs-TnI), neutrophils, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), serum creatinine, and the equilibrium was comparable (p > 0.05). After PCI treatment, TNF-α and IL-6 levels were significantly decreased in both groups, and the levels of TNF-α and IL-6 in the colchicine group were significantly lower than control group (TNF-α: 22.5 ± 4.9 vs 41.6 ± 4.1 μg/L; IL-6: 21.3 ± 12.8 vs 40.9 ± 17.5 ng/L; both p < 0.001). Patients in the colchicine group had a significantly proportion of risk of residual inflammation compared with controls (37.5% vs 62.5%, p = 0.005). Logistic regression showed that, using the control group as a reference, we still found that colchicine use was independently associated with a reduced risk of residual inflammation when corrected for other confounders (odds ratio [OR], 0.372; 95% confidence interval [CI], 0.156–0.889; p = 0.026). Regarding peripheral blood CD4⁺ T cell subsets, Th1 cell, Th17 cell, and regulatory T cell counts were significantly higher in the colchicine group than control group after PCI treatment (p < 0.01). As for oxidative stress indicators, SOD levels were significantly higher and MDA levels were significantly lower in the colchicine group after PCI treatment compared with the control group (p < 0.001).

Conclusions: Colchicine administration was associated with reduced systemic inflammatory indexed, promoted proliferation of peripheral blood CD4⁺ T cells, and improved oxidative stress levels in patients with coronary heart disease combined with gout after PCI.

Background: Esophageal squamous cell carcinoma (ESCC) represents a prevalent malignancy within the digestive tract, often diagnosed at advanced stages, leading to treatment challenges and poor prognosis. Despite its essential roles in biosynthesis, antioxidation, and energy metabolism, the involvement of lysine in cancer pathogenesis remains poorly understood. This study aimed to elucidate the significance of lysine-associated genes in ESCC, potentially enhancing treatment outcomes.

Methods: mRNA expression data for ESCC were retrieved from The Cancer Genome Atlas (TCGA) for limma differential expression analysis. Lysine-related genes were extracted from the GeneCards database and overlapped with differentially expressed genes. Lysine levels were quantified using single-sample Gene Set Enrichment Analysis (ssGSEA), followed by metabolic pathway analysis comparing high and low lysine levels. The random survival forest (RSF) algorithm identified lysine-related genetic signatures associated with poor prognosis of ESCC. Further analysis encompassed drug susceptibility profiling and assessment of immune cell infiltration. Subsequently, single-cell analysis was conducted using data from the Gene Expression Omnibus (GEO) database (GSE196756) to validate key lysine-related genes.

Results: Ubiquitination Factor E4A (UBE4A) and Apolipoprotein C1 (APOC1) were identified as key lysine-associated genes in ESCC. Functional enrichment analysis revealed that the lysine-related genes remarkably enriched lysine-regulated pathways, including histone modification, histone lysine methylation, and lysine degradation pathways. Moreover, these lysine-related differentially expressed genes (DEGs) served as independent prognostic factors, and a nomogram incorporating these genes and clinical factors accurately predicted 1- and 2-year survival rates in ESCC patients. Drug databases highlighted AICAR, BI.D1870, MS.275, and lapatinib as potential therapeutic agents. Immunemicroenvironment infiltration analysis indicated that UBE4A was actively connected with T cells CD4 memory resting and passively connected with B cells memory. APOC1 was actively linked to macrophages M2, T cells CD4 memory activated, T cells CD8, and was passively linked to the activated Dendritic cells, T cells CD4 memory resting and Eosinophils. We further performed single-cell analysis, and 21 subtypes were obtained by t-Distributed Stochastic Neighbor Embedding (tSNE) algorithm. The total clusters were labeled to tissue stem cells, neurons, epithelial cells, B cells, neutrophils, monocytes, T cells, smooth muscle cells, NK cells, and endothelial cells.

Conclusions: Our findings underscore the pivotal role of lysine-related gene regulation in ESCC. The identified lysine-related genes hold promise as prognostic indicators for ESCC patients, shedding light on potential mechanisms underlying poor prognosis and facilitating the search for targeted therapeutics to enhance the success rate of ESCC treatment.

Background: Colorectal cancer, an invasive tumor originating in the mucosal lining of the large intestine and rectum, represents a prevalent form of gastrointestinal malignancy. Although extensive investigations have been conducted on colorectal cancer, the precise molecular mechanisms underlying this neoplasm remain uncharacterized. Alterations in the genetic material have been linked to colorectal cancer progression. To analyze the prognosis of individuals with colorectal cancer, it is crucial to identify new biomarkers. Using integrated bioinformatics analysis, this study successfully identified and confirmed the fundamental gene linked to colorectal cancer.

Methods: Bioinformatics software tools were employed to assess the mRNA expression level of Erythroferrone (ERFE) by analyzing the Cancer Genome Atlas (TCGA) dataset, which included 647 tumor samples and 51 control samples. In order to verify the findings, a comparison was conducted with data available on the Gene Expression Omnibus (GEO). In order to determine the clinical significance and expression level of ERFE, a bioinformatics investigation was carried out using logistic regression analysis. To assess survival rates in both high- and low-expression ERFE groups, univariate and multivariate Cox proportional hazards model (Cox) regression analyses were conducted. To validate the expression of ERFE at both the gene and protein levels in colorectal cancer (CRC) cells (HCT116 and Lovo) and normal epithelial cells, reverse transcription quantitative polymerase chain reaction and western blot experiments were performed. The knock-down efficiency of ERFE in HCT116 and LoVo cell lines was assessed using western blot experiments. The effect of ERFE gene function was compared and analyzed through various assays such as cell counting kit-8 (CCK-8), Transwell, and scratch tests before and after ERFE knock-down in HCT116 and LoVo cell lines.

Results: An analysis of data obtained from TCGA and GEO databases unveiled a remarkable increase in the expression of ERFE mRNA in CRC tissue compared to both normal and paracancerous tissues (p < 0.001). Furthermore, it was discovered that the overexpression of ERFE was linked to an unfavorable prognosis and had the potential to act as an independent prognostic indicator for predicting overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) among colorectal cancer patients. Additionally, a positive correlation was found between heightened ERFE expression, infiltration of numerous immune cells, and levels of immune checkpoint molecules. Experimental evaluations, including the CCK-8 assay, scratch assay, and transwell assay, provided compelling evidence demonstrating a significant reduction in the proliferative, migratory, and invasive capabilities of colorectal cancer cells upon knocking down ERFE.

Conclusions: In summary, ERFE, functioning as a pro-oncogene in CRC, is linked to the initiation and advancement of cancer, and can serve as a standalone marker for unfavorable prognosis among CRC patients.

Background: Intrahepatic cholangiocarcinoma (ICC) is a prevalent type of cancer originating from epithelial cells of the bile duct within the liver. The molecular mechanisms underlying ICC proliferation, invasion, and metastasis remain unclear. Recently, N6-methyladenosine (m6A) RNA methylation has been associated with tumor progression. Methyltransferase 3 (METTL3) is a crucial methyltransferase for m6A. However, its biological significance and the regulatory mechanisms underlying ICC invasion and metastasis remain poorly understood. Therefore, we aimed to explore the role of METTL3 in ICC progression and its potential mechanisms.

Methods: We analyzed the expression of METTL3 in ICC using bioinformatics, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and immunohistochemistry analysis. Furthermore, we evaluated the impact of METTL3 on ICC cell proliferation and metastasis in vivo and in vitro. For mechanistic studies, we used RNA-Seq to screen the crucial downstream targets of METTL3 in ICC cells. Furthermore, we examined the regulatory impact of METTL3 on the phenotype of ICC cells through S100 calcium-binding protein A4 (S100A4) using qRT-PCR, Western blot, and rescue experiments. Finally, we assessed the effect of METTL3 on S100A4 stability by mediating m6A modification using the methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) and messenger RNA (mRNA) degradation experiments.

Results: The expression of METTL3 was upregulated in patients with ICC (p < 0.05). Moreover, METTL3 knockdown inhibited the proliferation, migration, and invasion ability of ICC cells (p < 0.05). Mechanistically, METTL3 mediated m6A modification of S100 calcium-binding protein A4 (S100A4) mRNA and inhibited S100A4 mRNA decay in an m6A-dependent manner (p < 0.05), thus promoting the proliferation and metastasis of ICC.

Conclusions: METTL3 promotes ICC proliferation and metastasis by mediating S100A4 mRNA degradation, suggesting that METTL3 may be a potential target for treating ICC.

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) globally, characterized by increased albuminuria and reduced glomerular filtration rate. Recent evidence points to inflammation as a vital contributor to the development and progression of DKD, involving interactions among immune cells, cytokines, and chemokines. Our study focused on uncovering inflammation-related genes in DKD to understand its mechanisms and developed an inflammation-centric predictive model. We aimed to bridge molecular insights with immune interactions, paving the way for innovative treatments.

Methods: This study involves comprehensive data collection from gene expression omnibus (GEO) datasets (GSE1009 and GSE30528) to identify differentially expressed genes (DEGs) between patients with DKD and healthy controls (HC). Using the ComBat method for batch effect removal, R package Limma for DEGs identification, and Metascape for enrichment analysis, we focused on the interplay between inflammation-associated genes and immune cell infiltration. We developed a predictive model for DKD using the least absolute shrinkage and selection operator (LASSO) regression, centered on six potential candidate genes: chitinase-3-like protein 1 (CHI3L1), coagulation factor V (F5), decay-accelerating factor (CD55), insulin-like growth factor 1 (IGF1), vascular endothelial growth factor A (VEGFA), and 15-hydroxyprostaglandin dehydrogenase (HPGD), within a training cohort. This model was subsequently validated in a test cohort utilizing data extracted from the GEO dataset GSE96804. Immune cell infiltration was determined using CIBERSORT, followed by Pearson correlation analysis to elucidate the interactions between hub genes, immune cells, and chemokines.

Results: We identified 349 DEGs, including 99 upregulated and 250 downregulated genes, highlighting the significant role of inflammation in DKD. Through weighted gene co-expression network analysis (WGCNA), a module consisting of 784 genes strongly associated with DKD was identified. Within this module, six inflammatory-related genes were identified as crucial for the predictive model, achieving an area under the receiver operating characteristic curve (AUC) of 1 in training and 0.76 in validation. Analysis of immune cells revealed significant differences between DKD patients and controls, while Pearson correlation analysis highlighted key associations with immune infiltration and regulation.

Conclusions: Our study provides novel insights into the genetic and inflammatory landscape of DKD, establishing a predictive model with high accuracy compared to existing models. We pinpoint significant correlations between hub genes and immune cell dynamics, potentially opening avenues for new therapeutic strategies. Our findings underscore the promise of precision medicine in diagnosing and treating DKD.

Alzheimer's disease (AD), a catastrophic disorder that commonly affects the elderly, causes extracellular plaques to form in the hippocampus, leading to slow, progressive loss of brain function. The Blood Brain Barrier poses a significant challenge for conventional drug delivery in AD therapeutics. Therefore, introducing novel strategies such as nanotechnology-based drug delivery offers promising potential. This paper highlights the significance of nanotechnology based drug delivery in AD with respect to its pathophysiology and discusses the current situation and future prospects of the same in diagnosis and therapy. Data collection involved scientific databases such as PubMed, Science Direct, and Google Scholar. The keywords searched were AD, neurodegenerative, nanotechnology, Amyloid-beta protein, tau protein and patents. A total of 146 papers were obtained. The pathophysiology of AD with respect to the Amyloid- and tau hypotheses were found to have significant therapeutic potential. It was also found that nanotechnology systems were able to offer enhanced site-specific action, offering a low toxicity profile in areas where conventional drug delivery systems had difficulty to act on. Delivery systems that were found to have potential were nanoparticles (NPs) including inorganic NPs and magnetic NPs, Quantum Dots, liposomes, dendrimers, Micelles, etc. Thus, our work suggests that NP-based drug delivery systems are able to overcome the challenges faced by conventional systems to achieve therapeutic efficacy with substantial levels of evidence, initiating the much-needed discussions on their potential use in AD therapeutics.

Cancer, characterized by uncontrolled cell division and potential tissue spread, remains a significant health problem, with breast cancer being the most common in women, accounting for 25% of all cancer cases. Natural compounds have recently gained attention as they can improve the efficacy of cancer treatment. The aim of this study is to shed light on the potential benefits of polyunsaturated fatty acids in the treatment of breast cancer. Overexpression of tyrosine kinase receptors and mutations in the breast cancer gene-1 (BRCA1) and BRCA2 genes lead to breast cancer in women. Based on the findings of papers published in various scientific search engines, n-3 polyunsaturated fatty acid (PUFA) may reduce the likelihood of developing breast cancer due to their anti-inflammatory properties. According to several studies, women who consume more n-3 polyunsaturated fatty acids have a lower risk of breast cancer. n-3 polyunsaturated fatty acids regulate breast cancer by controlling the inflammatory mediators, gene expression transcription factor and signal transducer, peroxisome proliferator-activated receptor-gamma, B-cell lymphoma-2 (Bcl-2) associated X protein or B-cell lymphoma-2, Phosphatidylinositol 3-kinase or Protein kinase B, Nuclear factor-κB, and toll-like receptor-4. Polyunsaturated fatty acids are considered a successful treatment for breast cancer patients when combined with chemotherapy drugs. Doxorubicin is a first-line drug for the treatment of triple-negative breast cancer. Giving doxorubicin and polyunsaturated fatty acids together makes chemotherapy treatments for triple-negative breast cancer work better in the MDA-MB-468 and MDA-MB-231 cell lines. This review highlights the role of PUFAs in modulating cancer-related pathways, offering valuable insights for researchers, clinicians and the pharmaceutical industry in the fight against breast cancer.

Background: Organophosphate poisoning poses a significant health burden due to the absence of specific pharmacological antidotes. To address this issue, we explored the potential of nanoparticles for organophosphate detoxification, focusing on biomimetic nanoparticles with natural cell membrane coatings.

Methods: We developed membrane-cloaked oil nano-sponges by combining red blood cell (RBC) membranes and oil to create a dual-model detoxification system for organophosphates. The oil component non-specifically absorbed organophosphate poisons, while the membrane-bound acetylcholinesterase enzyme is specifically bound to the toxic molecules, preserving intrinsic acetylcholinesterase function. We evaluated the detoxification capacity of this system using chlorpyrifos as a model insecticide in a rabbit model.

Results: The prepared oil nano-sponge exhibited potent antidote capabilities against organophosphate poisoning and demonstrated efficacy in poisoning prevention. The safety evaluation revealed no adverse effects on the gross appearance or histopathological sections of the liver, kidneys, spleen, lungs, and heart.

Conclusions: In summary, our novel membrane-cloaked oil nano-sponge proved to be a safe and effective antidote for organophosphate poisoning in rabbits. These findings have the potential for extrapolation to other species, offering a promising solution to mitigate inadvertent organophosphate poisoning.

Background: The role of Recombinant Nucleophosmin 1 (NPM1) in the development of lung adenocarcinoma (LUAD) has been recognized, however, the precise mechanism underlying this involvement remains unclear. Therefore, this study aimed to assess the mechanism of NPM1 in LUAD progression.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting assays were used to detect the expression level of NPM1. Furthermore, Cell Counting Kit-8 (CCK-8) assay, Transwell migration, Transwell invasion, and flow cytometry assays were conducted to evaluate the role of NPM1 in the proliferation, migration, invasion, and apoptosis in LUAD cell lines. Moreover, glycolysis-related indicators were determined using corresponding kits. Additionally, the mechanism of NPM1 involvement was further evaluated through NPM1 silencing experiments.

Results: NPM1 was upregulated in two human LUAD cell lines (p < 0.001). Glycolysis was enhanced in LUAD cell lines (p < 0.05). After inhibiting the expression of NPM1, the proliferation, migration, and invasion were significantly reduced in LUAD cell lines but the apoptosis was increased (p < 0.05). Furthermore, a substantial reduction in glycolytic flux and an elevation in mitochondrial respiration were observed (p < 0.05).

Conclusion: These findings reveal that NPM1 promotes LUAD progression by mediating glycolysis, offering a novel therapeutic target for treating LUAD.

Background: Zinc finger (ZNF) proteins play pivotal roles in the initiation, progression, and metastasis of various cancer types. Nevertheless, the precise mechanism of ZNF genes (ZNFGs) in the prognosis and treatment of gastric cancer (GC) patients remains unclear.

Methods: Transcriptomic data and clinical information related to GC, as well as ZNFG-related data, were retrieved from publicly available databases. Initially, differentially expressed ZNFGs (DE-ZNFGs) were identified through comparative analysis between GC and normal tissue samples. Subsequently, univariate and multivariate regression analyses, and the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm were utilized to identify potential biomarkers and formulate a risk assessment model. Furthermore, Kaplan-Meier survival curve analysis was conducted to analyze the correlation between the risk score and overall survival of GC patients, while the receiver operating characteristic (ROC) curve analysis was performed to evaluate the reliability of the model. Moreover, Gene Set Enrichment Analysis (GSEA) was performed to elucidate Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, comprehensive investigations were conducted to assess immune infiltration, immune checkpoints, and the immunophenoscore of distinct risk groups.

Results: A total of 165 DE-ZNFGs were identified, from which, five genes (zinc finger protein 36 (ZFP36), zinc finger protein 121 (ZNF121), ZNF131, ZNF22, and Replication initiator 1 (REPIN1) were selected as biomarkers to construct the risk model. This model demonstrated high predictive accuracy for the prognosis of GC patients, with an area under the curve (AUC) exceeding 0.6 for 1-, 3- and 5-year survival rates. Both the risk score and patient age were observed to independently predict prognosis in GC. Moreover, GSEA results showed that high risk group exhibited enrichment in pathways related to mitogen-activated protein kinase (MAPK), calcium signaling, neuroregulation, cellular connections, and cytoskeletal regulation, while low risk group was characterized by pathways associated with metabolic processes, transcription of genetic information, and stringent regulation of genetic stability. Immune analysis revealed significantly elevated stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) composite scores in high-risk patients. Additionally, there was a notable difference in the expression levels of 19 immune cells and 13 immune checkpoints between the two groups, suggesting significant immunological differences.

Conclusions: Our ZNFG-related risk model can be used to predict the survival of GC patients and may have potential guiding implications for GC treatment.

Background: Immune dysregulation is one of the hypotheses brought up to explain autism spectrum disorder (ASD). Interleukine-17A (IL-17A), a proinflammatory cytokine, has been demonstrated to be a major mediator of immune-related neurodevelopmental impairment of social behavior, including ASD. Chrysin (CHN) is a naturally occurring hydroxylated flavonoid with antioxidant, anti-inflammatory, anti-asthmatic, anticancer, cardioprotective, and neuroprotective activities. The current study investigated the effects of CHN against Polyinosinic:polycytidylic acid (Poly (I:C))-induced autism-like behavior by modulating the fetal serotonin and IL-17A levels in fetal and offspring brains in C57BL/6J mice.

Methods: Pregnant C57BL/6J mice (n = 6) were randomly selected. After the confirmation of pregnancy, female mice were divided into two different experimental groups (n = 3 female/group = 4–8 littermates/group). The pups were randomly divided into 5 experimental groups, namely, control (group I), Poly (I:C) (group II), CHN25 (group III) & CHN50 (group IV), and fluoxetine (group V). Group I and II pregnant mice were pre-treated orally with saline for 12 consecutive days (Estrus Day 0.5 (E0.5) to E12.5) and then challenged with saline (group I) and Poly (I:C) [20 mg/kg Body Weight (BW)] (group II) intraperitoneally on the 12th day (E12.5). Group III, IV & V pregnant mice were administered orally with CHN (25 mg/kg & 50 mg/kg BW) and fluoxetine (10 mg/kg, BW), respectively, for 12 consecutive days (E0.5 to E12.5) and then challenged with Poly (I:C) (20 mg/kg BW) intraperitoneally on 12th day (E12.5). In one set of studies, 1 pregnant mouse from each group was sacrificed after 4 h of Poly (I:C) injection to measure the fetal 5-Hydroxytrptophane (5-HT) and IL-17A levels in fetal brains using enzyme-linked immunosorbent assay (ELISA) kits. In the second set of experiments, the remaining pregnant mice were allowed to deliver the pups. Offspring were subjected to different behavior tests, including marble burying test (MBT), rotarod test, social interaction test (SIT) and sucrose preference test (SPT) at the age of 6, 7 and 12 weeks to investigate the autistic-like behaviors and associated symptoms. Following behavioral studies, the mice were sacrificed to isolate the prefrontal cortex (PFC), hippocampus (HC) and amygdala (AMG) tissues to measure the IL-17A levels through an ELISA kit.

Results: The findings of the present study demonstrated that Poly (I:C) administration to pregnant mice resulted in maternal immune activation (MIA), as evidenced by the significant increase in IL-17A (p < 0.05) and decrease in 5-HT levels (p < 0.001) in fetal brains. Pre-treatment of CHN and fluoxetine altered the fetal 5-HT and IL-17A levels significantly (p < 0.001). Offspring of Poly (I:C) injected pregnant mice showed autistic-like behaviors and associated symptoms as evidenced by an increased number of marbles buried in MBT and decreased fall in time in the Rotarod test, sucrose preference in SPT, and social preference in SIT significantly (p < 0.001) which were ameliorated by the chronic pre-treatment of CHN (both the dosages i.e., 25 & 50 mg) and fluoxetine significantly (p < 0.001). Further, results showed the significant elevation of IL-17A levels in PFC (p < 0.001), HC (p < 0.001) and AMG (p < 0.05) of offspring of Poly (I:C) injected pregnant mice, which were attenuated significantly by the chronic pre-treatment of CHN (both the dosage i.e., 25 & 50 mg) and fluoxetine (p < 0.001).

Conclusion: Findings of the study demonstrated that chronic pre-treatment of CHN attenuated autistic-like behavior by altering fetal 5-HT and IL-17A in fetal brain, PFC, HC, and AMG of offspring of MIA pregnant C57BL/6J mice. However, further investigation is required to establish the therapeutic applicability of CHN in ASD.

Background: Prostate cancer (PC) is one of the most common malignant tumors, and the effect of celastrol on squalene synthase (SQS) in PC is unknown. This study aimed to investigate the effect of celastrol on SQS in PC.

Methods: The protein expression was detected by Western blot. Cell proliferation capacity was detected by cell counting kit-8 (CCK-8) kit (450 nm optical density values). Cell scratch (wounding healing rate) and transwell assays (migration cells number) detected the cells' migration abilities. Messenger RNA (mRNA) expression was detected using a real-time polymerase chain reaction test.

Results: Celastrol decreased the expression of SQS in PC cells, and the knockdown of the SQS-encoding gene farnesyl-diphosphate farnesyltransferase 1 (fdft1) with and without celastrol treatment decreased PC cell proliferation and migration abilities. Furthermore, overexpression of the fdft1 gene attenuated the proliferation and migration abilities of PC-3 cells. Treatment with celastrol with fdft1 gene overexpression can still decrease the proliferation and migration abilities of PC-3 cells.

Conclusion: This study verified that celastrol decreases the proliferation and migration abilities of PC-3 and Lymph Node Carcinoma of the prostate (LNCaP) cells and revealed that celastrol reduces SQS expression. The results indicate that the inhibitory effect of celastrol on the malignant phenotypes of PC cells is partly dependent on SQS, and SQS is involved in the malignant behaviour of PC cells. Furthermore, there may be a dual effect dependent on the SQS protein expression level on the malignant phenotypes of PC cells.

Background: Differentiated Thyroid Carcinoma (DTC) presents diverse patient outcomes, highlighting the need to identify reliable prognostic biomarkers. This study focuses on the role of interleukins, particularly interleukin18 (IL18), in predicting survival rates and treatment responses among DTC patients.

Methods: We conducted a comprehensive analysis of the association between various pyroptosis-related genes (IL18, IL1A, IL6, Granzyme A (GZMA), and Neutrophil elastase (ELANE)) and overall survival in DTC. The study employed univariate and multivariate Cox models to assess the prognostic value of these cytokines. Additionally, a nomogram model was created, integrating clinical characteristics to improve the precision of predicting patient outcomes. IL18 expression levels in DTC tissues compared to normal tissues were examined, along with their association with patient survival and response to radioactive iodine (RAI) therapy.

Results: IL18 emerged as a significant protective factor associated with better survival outcomes, exhibiting higher expression levels in DTC tissues compared to normal tissues. However, its expression was notably lower in RAI-refractory or high-risk groups. This study also identified axitinib as a potential therapeutic agent for high-risk DTC cases, supported by drug prediction analysis. Furthermore, immune cell analysis linked high IL18 expression with an abundance of specific T cells, indicating its involvement in regulating the immune response and influencing the effectiveness of RAI treatment.

Conclusions: IL18 holds promise as a prognostic biomarker in DTC, offering valuable insights into patient survival and potential treatment pathways. This study emphasizes the importance of combining molecular and clinical data to improve prognostic models and therapeutic strategies, highlighting the need for further research into the mechanisms of action of IL18 in DTC.

Background: Migraine is one of the most common neurological disorders occurring globally and its treatment is currently based on synthetic drugs. Due to undesired effects associated with these agents, some of the patients might prefer natural compounds-based therapies that are cost-effective, efficacious, have more patient compliance and less adverse effects. Hence, this systematic review was conducted to evaluate the effects of natural compounds (single/combination) used for the prophylaxis or acute treatment of migraine.

Method: Five electronic databases (PubMed, Scopus, Cochrane Library, Cumulated Index to Nursing and Allied Health Literature (CINAHL) library and Web of Science) were searched from 1 March 2020–31 January 2024. We included studies that evaluated the effects of natural compounds on migraine through randomized clinical trials (RCTs) that reported the duration of migraine headache, severity and frequency of attacks as primary outcomes. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist was used to report the study while Cochrane Collaboration's Risk of Bias (ROB) 2 tool was used to assess the ROB in included studies. The review protocol was registered on PROSPERO (CRD42023454998).

Results: Twelve RCTs with 889 participants were included. Seven RCTs had low ROB and two RCTs had high ROB, while three RCTs expressed “some concerns”. It was observed that natural compounds including curcumin, topical basil, cinnamon, ginger, Vitamin D3 (Vit D3), zinc (Zn), magnesium (Mg) and cobalamin significantly reduced the severity of migraine headache. In addition, the duration of migraine attacks was significantly decreased by curcumin, cinnamon, ginger, Vit D3, Mg and cobalamin. Further, curcumin, topical basil, cinnamon, Vit D3, Zn, Mg and cobalamin exhibited significant beneficial effect on migraine frequency. In contrast, nanocurcumin and jodeungsan showed no significant results.

Conclusion: The current findings suggest that natural compounds including cinnamon, Vit D3, Zn, Mg and cobalamin might mitigate migraine attacks and serve as interesting alternate therapies. Nonetheless, further large scale studies are highly desired.

A variety of events, including infection, traumatic brain damage, neurodegenerative illnesses, and autoimmune disorders, can cause neuroinflammation, a complicated biological reaction in the central nervous system. Glial cells, especially microglia and astrocytes, are activated as part of this complex event, which also results in the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. In this review, the role of microglia and astrocytes in neuroinflammation, as well as the important neuroinflammatory factors including their pathways, and positive and negative aspects of neuroinflammation are discussed. It was earlier documented that microglial cells and astrocytes play a notable role in immune and inflammatory diseases. Various pro-apoptotic pathways like nuclear factor kappa B (NF-κB), cytokines, cyclooxygenases, reactive oxygen species (ROS), and mitogen-activated protein kinase (MAPK) are responsible for the induction of neuroinflammation. Neuroinflammation may also lead to many neurodegenerative diseases like Alzheimer's disease, multiple sclerosis, and Parkinson's disease. It has also been reported that inflammasomes and multi-protein oligomers are also responsible for neuroinflammation.