Postaxial polydactyly (PAP) is characterized by the development of extra digits at the fifth finger. It can occur as an isolated disease or a part of a syndrome. The genetic basis of nonsyndromic PAP has been linked to sequence variants in different genes. The aim of the present study was to identify the causative genetic variants in four Pakistani families demonstrating PAP. Causative genetic variants were identified using whole-exome sequencing and microsatellite mapping, followed by validation through Sanger sequencing. Further analysis was carried out through conservation, structural modeling, and 100-ns molecular dynamic simulations of GLI1. Whole-exome and targeted sequencing in four families (A, B, C, and D) identified novel variants in the (c.1013G>T; p.Cys338Phe), and (c.2003C>T; p.Pro668Leu and c.4564delG; p.Ala1522ProfsTer2), and a recurrent variant in genes (c.895_904del; p.Val301SerfsTer8) linked to 7p22.3. All the variants were highly conserved across different species. Comparative analysis of the GLI1 and GLI1 proteins revealed domain fluctuations leading to the loss of structurally and functionally important inter- and intramolecular interactions. The three-dimensional structural analysis of the GLI3 protein showed that the missense variant p. (Pro668Leu) disturbed the protein folding and intra-residue interaction, while the frameshift variant p. (Ala1522ProfsTer2) led to the loss of the C-terminus of the protein. Similarly, the IQCE structural analysis confirmed the loss of protein function due to frameshift and C-terminal deletion. This study has broadened the phenotypic and allelic spectrum of the genes associated with isolated PAP and strengthened the role of these genes in regulating limb development.

Genetic polymorphisms in microRNA binding sites (mir-SNPs) may affect rheumatic diseases risk. We genotyped two mir-SNPs in the 3' UTR of (rs16917496) and (rs3660) in ankylosing spondylitis (AS) patients to assess their association with AS risk. DNAs were extracted from blood samples for polymerase chain reaction analysis. Western blot was used to detect protein expression. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology. We found that CC genotype had an increased chance of developing AS than the TT + CT genotype carrier (odds ratio, 5.378; 95% confidence interval, 1.130-25.593; = 0.019). Moreover, the CC genotype displayed a lower expression of SET8 than the TT genotype. Additionally, increased ROS generation in AS patients was observed compared with controls (23859.055 ± 12283.038 vs. 14758.330 ± 5854.946, < 0.001). Furthermore, the AS-susceptible CC genotype was associated with high ROS levels (35062.000 ± 17748.785 vs. 22629.463 ± 11002.181, = 0.033). Our study revealed that the SNP rs16917496 located in the miR-502 binding site in the 3' UTR of could be used as a biomarker to predict AS risk. Importantly, SNP rs16917496 could participate in the pathogenesis of AS by regulating the expression of SET8, thereby promoting oxidative stress levels.

This study aims to investigate whether elevated human neutrophil peptides 1-3 (HNP 1-3) levels in cerebrospinal fluid (CSF) are associated with disease severity and clinical outcomes in patients with intracerebral hemorrhage (ICH). HNP 1-3 levels were measured in CSF samples collected within 3 days after hemorrhage onset in ICH patients and control subjects. HNP 1-3 levels were significantly higher in ICH patients with moderate-severe coma and hematoma volume >30 mL group. Univariate and multivariate logistic regression analyses demonstrated that CSF HNP 1-3 levels were associated with unfavorable outcomes. Receiver operating characteristic analysis revealed that CSF HNP 1-3 concentrations >466.95 ng/mL could distinguish ICH patients at risk for an unfavorable prognosis. HNP 1-3 exhibit satisfactory diagnostic efficiency for predicting the prognosis of ICH patients.

Numerous genetic factors influence the severity and susceptibility to COVID-19. The renin-angiotensin system has a role in the genesis of COVID-19. This study aims to investigate the genetic polymorphisms of Angiotensin-Converting Enzyme Insertion/Deletion (ACE I/D) and ACE2 rs2285666 in patients with COVID-19 and their association with mild, severe, and critical disease symptoms. This study included 300 patients with COVID-19, categorized as mild, severe, and critical. Genotypes for the I/D polymorphism of ACE1 and the rs2285666 polymorphism of ACE2 were determined in all samples using polymerase chain reaction (PCR) and restriction fragment length polymorphism-PCR methodologies, respectively. This study revealed a significant association between the ACEI/D genotype and the severity of COVID-19 ( < 0.001). A strong association was seen between the frequency of ACEI/D alleles and the severity of COVID-19, with the D allele being more prevalent in the severe and critical cohorts compared with the mild cohort ( < 0.001). A significant association was found between the ACE2 rs2285666 polymorphism and disease severity in both male and female groups ( < 0.05). The frequency of G/A alleles linked to the ACE2 polymorphism exhibited a significant association with disease severity, as the G allele was more common in the severe and critical groups than in the mild group ( = 0.004). Individuals with the homozygous ACE D/D genotype have an increased susceptibility to severe COVID-19, while the presence of allele I may provide a preventive advantage against severe disease symptoms. The ACE2 rs2285666 variant is associated with disease severity, while the ACE2 G/G genotype is linked to an increased severity of COVID-19.

Methyltransferase proteins, including SET Domain Containing 7 (), play an important role in the initiation of carcinogenesis through epigenetic mechanisms. Due to the reduced chance of survival in colorectal cancer (CRC), it is necessary to find molecular methods to detect CRC in the early stages. This study aimed to investigate the expression of in metastatic and nonmetastatic tumor tissues in CRC compared with healthy tissue in order to evaluate its potential as a biomarker for the diagnosis of CRC in the early stages. In this study, the expression level of the gene in primary colon adenocarcinoma was analyzed using the UALCAN database. To confirm the bioinformatics data, gene expression was investigated in 80 colorectal tumor tissues (metastatic and nonmetastatic) and adjacent normal tissues using RT-qPCR. According to the results obtained from the UALCAN database, expression is significantly increased in tumor tissues compared with normal tissues, which was confirmed by the RT-qPCR results. We showed that although the expression level in colorectal tumor tissues was higher than in adjacent normal tissues ( = 0.0001), this increase was only statistically significant in nonmetastatic tumor tissues ( = 0.0001). Based on receiver operating characteristic (ROC) analysis, increased gene expression can be used as a good biomarker to distinguish tumor tissue from normal tissue in the early stages (area under the ROC curve = 0.85). Increased gene expression can be used as an epigenetic marker in tissue-based prognosis and screening of CRC in the early tumor stages.

Noncoding RNAs (ncRNAs) comprise a significant portion of the transcriptome and contribute to various cellular and molecular processes and disease development. Although many functional roles for ncRNAs have been discovered, the regulatory functions of many require further elucidation. Intervertebral disk degeneration (IDD) is a leading cause of lower back pain and represents a major social and financial challenge worldwide. This review summarizes the literature on long ncRNAs and circular RNAs as novel regulators in IDD development. IDD diminishes quality of life, underscoring the importance of research on its pathogenesis and the identification of novel therapeutic targets. The definitive cellular and molecular mechanisms underlying IDD pathogenesis remain unidentified, and no effective treatment is available. Both genetic and environmental or lifestyle factors are associated with IDD development. Therefore, understanding the exact molecular mechanisms of IDD could yield novel therapeutic targets.

Familial exudative vitreoretinopathy (FEVR) is a rare inherited ocular disorder characterized by abnormal peripheral retinal vascular development. variants are known to cause autosomal dominant FEVR, but novel pathogenic variants remain to be identified. This study aimed to identify a novel causative variant of FEVR and provide evidence for genetic counseling. Whole-exome sequencing was performed on members of a Chinese family with FEVR. Rare variants with a gnomAD allele frequency <0.1% in East Asian and general populations were prioritized. Sanger sequencing was used for validation, and bioinformatic analyses (including Combined Annotation Dependent Depletion [CADD] score and cross-species conservation analysis) were conducted to assess pathogenicity. A novel heterozygous frameshift variant c.1239_1240del (p.V414Sfs*9) was identified in the proband, his brother, and his mother. This variant, absent from public databases (1000 Genomes, ExAC, gnomAD), had a CADD score of 26.9 and affected a highly conserved residue, suggesting disruptive effects on protein structure. The proband's mother showed macular involvement. The novel frameshift variant (c.1239_1240del p.V414Sfs*9) identified in a Chinese family expands the mutation spectrum of autosomal dominant FEVR, with macular involvement aiding clinical prognostic assessment.

Breast cancer is a common cancer in women, often linked to reduced survival in advanced stages. Recently, lncRNAs have gained attention as potential biomarkers for early detection. Among them, lncRNA AC073352.1 and its target protein Y-box 1 (YBX1) are associated with breast cancer progression and are promising diagnostic tools for early-stage detection. This study included 45 newly diagnosed breast cancer patients and 45 healthy controls from Shafa Hospital. Serum was separated from the collected blood samples, and total RNA was extracted and reverse-transcribed into cDNA. Expression levels of lncRNA AC073352.1 and YBX1 were quantified using SYBR Green-based real-time polymerase chain reaction. Their diagnostic performance was assessed by ROC curve analysis. The study demonstrated that the expression levels of lncRNA AC073352.1 and YBX1 were significantly higher in breast cancer patients compared to the control group. ROC curve analysis indicated that AC073352.1 and YBX1 had suitable sensitivity and specificity for breast cancer detection. Additionally, a significant positive correlation was found between the expression of these two markers in patients, suggesting the possibility of a shared regulatory pathway. lncRNA AC073352.1 and YBX1 are promising biomarkers for early breast cancer detection, potentially enhancing diagnostic accuracy when used in combination with other methods.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with a high rate of germline predisposition. Although multigene panel testing (MGPT) using next-generation sequencing (NGS) is widely adopted globally, its clinical application in Japan remains limited. Methods: We developed a custom amplicon-based NGS panel targeting 12 established PPGL susceptibility genes. Germline analysis was performed in 23 Japanese patients with confirmed PPGL to evaluate sequencing quality and variant detection. Sequencing quality was consistently high (Q30 > 96%, mapping rate >99%, on-target rate >80%), with nearly all exons (148/149) achieving >1,000× coverage. Pathogenic or likely pathogenic variants were found in 21.7% (5/23), including , , and . In addition, variants of uncertain significance (VUS) were found in 17.4% (4/23), including novel missense variants in , , and . This study demonstrates the feasibility and clinical utility of amplicon-based MGPT for PPGL in a real-world Japanese setting and highlights the importance of ongoing VUS reclassification to improve clinical interpretation. The findings support its diagnostic value, reflect underlying clinical demand, and contributed to its non-insured clinical adoption at certified laboratories in Japan.

Coiled-coil-helix-coiled-coil-helix domain containing 1 (CHCHD1) is a mitochondrial protein involved in oxidative phosphorylation and mitochondrial protein synthesis. While its functions have been explored in basic mitochondrial biology, the role of this process in hepatocellular carcinoma (HCC) remains poorly understood. We performed transcriptomic analysis on 272 HCC and 50 normal liver tissue samples to assess CHCHD1 expression. Correlations with clinical features were analyzed using Pearson coefficients. Prognostic relevance was evaluated using receiver operating characteristic analysis. Functional studies in SMMC-7721 cells included transwell migration/invasion assays, as well as western blotting, to assess epithelial-mesenchymal transition (EMT) markers and transforming growth factor (TGF)-β1 signaling. Gene set enrichment analysis (GSEA), single-cell RNA sequencing (scRNA-seq), and immune infiltration analyses were conducted to investigate immunoregulatory functions. CHCHD1 expression was significantly upregulated in HCC tissues (1.38-fold, < 0.001) and correlated positively with tumor size ( = 0.45), vascular invasion ( = 0.56), and advanced Barcelona Clinic Liver Cancer stage ( = 0.62; all < 0.001). High CHCHD1 predicted shorter progression-free survival (area under the curve = 0.938; 95% confidence interval 0.910-0.965; = 0.039). Overexpression of CHCHD1 enhanced cell migration and invasion, promoted EMT (downregulation of E-cadherin and upregulation of vimentin), and activated TGF-β1 signaling. GSEA linked CHCHD1 to immune-related pathways. scRNA-seq localized CHCHD1 to myeloid-derived suppressor cells, showing potential interactions with TGF-β receptor 1. CHCHD1 expression correlated with Th2 cell infiltration ( = 0.57, = 0.025) and programmed cell death 1 expression ( = 0.027). CHCHD1 promotes EMT and immune evasion in HCC via TGF-β1 signaling, implicating it as a promising biomarker and therapeutic target.

The nitric oxide (NO) synthase 3 () 894G>T (p.Glu298Asp) variant has been associated with an elevated risk of neural tube defects (NTDs) in Caucasians. This association suggests a link between the NO and folic acid pathways. This study aimed to evaluate the (p.Glu298Asp) variant as a potential genetic risk factor in infants with isolated open and closed NTDs (CNTDs) from Western Mexico. The studied population included 114 live-born infants with open and CNTDs (cases) and 155 neonates without major birth defects (controls). Genotyping of the 894G>T (p.Glu298Asp) variant was performed by PCR amplification and direct Sanger sequencing. Data were analyzed using logistic regression analysis. The 894T allele (adjusted odds ratio [aOR] = 2.1; 95% confidence interval [95% CI]: 1.3-3.4), the 894GT (aOR = 2.3; 95% CI: 1.3-4.1), and the 894GT/TT (aOR = 2.6; 95% CI: 1.4-4.7) genotypes were significantly associated with open NTDs (ONTDs). There was no association between the 894G>T gene variants and CNTDs. This study indicates that the 894G>T (p.Glu298Asp) variant is associated with an increased risk of ONTDs in the studied Mexican patients.

Male patients with prolactinomas exhibit greater invasiveness, resistance to dopamine agonists, making treatment more challenging. This study aims to explore the potential different genes contributing to sex disparities in prolactinomas. Weighted gene co-expression network analysis and differential expressed genes analysis were performed to identify sex-related hub genes. In addition, bioinformatics analyses were conducted to understand gene localization on chromosomes, gene regulatory networks, signaling pathways, and their relationship with immune function, which was verified in 21 human prolactinoma samples. A total of 21 sex-related hub genes were identified. The hub genes in males included nine Y chromosome genes and six autosomal genes, while females had six specific genes. Further predictions using the NetworkAnalyst online tool suggested that transcription factors (REST, androgen receptor) and microRNAs (miR-27a-3p, miR-146a-5p) may be involved in regulating the above sex-related hub genes. CIBERSORT analysis revealed that prolactinomas in males showed significant infiltration of resting dendritic cells and naive CD4 T cells. Correlation analysis between sex-related hub genes and immune checkpoint genes indicated that male hub genes were positively correlated with and , while showing a strong negative correlation with , , and . Finally, similar changes of gene expression in our surgical prolactinoma samples were confirmed by RT-qPCR. In prolactinomas, the male hub genes and female hub genes are identified by our bioinformatics analysis. Our findings suggest that , , , and serve as potential biomarkers for male prolactinomas, while , , and may serve as potential biomarkers for female prolactinoma, providing a theoretical basis for targeted therapy.

This study aimed to investigate the association between the single nucleotide polymorphism (SNP: rs1805127; T>C transition; S38G substitution) and atrial fibrillation (AF) in the Mazandaran population of northern Iran. To conduct this case-control study, 120 blood samples from healthy individuals and 120 from individuals with AF were collected over an 11-month period. All participants underwent electrocardiogram analysis by a cardiologist. In addition, they completed a questionnaire that included questions about their medical history, lifestyle factors, and current medications. Genotyping of -rs1805127 was performed using the restriction fragment length polymorphism method. The impact of -rs1805127 on protein stability, function, and mRNA secondary structure was assessed using SIFT, I-Mutant, MetaRNN, and RNAsnp servers. The results revealed a significant association of the CC genotype and C allele with AF (CC genotype: value = 0.035; C allele: value = 0.042). Furthermore, an association was observed between smoking ( value = 0.018), hypertension ( value = 0.046), and thyroid disorders ( value = 0.040) and AF. predictions indicated that -rs1805127 may impair protein function, reduce stability, and alter mRNA secondary structure. Based on the results obtained, -rs1805127 may increase the risk of AF, particularly in the presence of risk factors such as smoking, hypertension, and thyroid disorders. Notably, predictions from computational tools validate this observed impact. Given the role of the gene in modulating ion channels and cardiac electrophysiology, we suggest that further research on and its SNPs could provide valuable insights into its role in the pathogenesis of cardiac arrhythmias, particularly AF.

Genetic variations of long noncoding RNAs are potential biomarkers for gastric cancer (GC). However, reports on the association between single nucleotide polymorphisms (SNPs) in antisense noncoding RNA in the INK4 locus () and GC risk are few. This case-control study aimed to evaluate the association between SNPs in , GC risk, and subgroups in a Korean population. The TaqMan genotyping assay of six SNPs in was performed in 419 patients with GC and 348 controls. After adjusting for age and gender, the following significant associations were identified: rs2157719 in the dominant model (TC+CC vs. TT) with decreased GC risk in the lymph node metastasis (LNM)-negative subgroup ( = 0.045, adjusted odds ratio [AOR] = 0.65, 95% confidence interval [CI] = 0.43-0.99); rs1333040 in the recessive model (CC vs. TT+TC) with increased risk in the undifferentiated subgroup ( = 0.032, AOR = 1.92, 95% CI = 1.06-3.50); and rs4977574 in the dominant model (AG+GG vs. AA) with decreased risk in the LNM-positive, tumor stage III (A+B+C), and undifferentiated subgroups ( = 0.007, AOR = 0.58, 95% CI = 0.39-0.86; = 0.028, AOR = 0.63, 95% CI = 0.42-0.95; and = 0.049, AOR = 0.63, 95% CI = 0.40-1.00, respectively). Our findings suggest that these SNPs in are associated with GC risk and influence GC development. Further studies are needed to confirm our results in different ethnic groups and larger populations.

Vitamin D deficiency influences the pathogenicity and severity of coronavirus disease 2019 (COVID-19), suggesting that polymorphisms in the vitamin D receptor may impact disease susceptibility and outcomes. This study aims to examine the relationship between the rs7975232 SNP and susceptibility to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection. This study compared 138 COVID-19 patients with 136 healthy individuals at Shohada-ye Ashayer Hospital in Khorramabad. The PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method was employed to ascertain the genotypes following the collection of blood samples. The results of PCR-RFLP method were confirmed by sequencing. IBM SPSS and SNPStats software were utilized to compare genotypes and allele frequencies, as well as to conduct odds ratio analysis. This study's results did not demonstrate a significant association between the rs7975232 polymorphism and COVID-19 susceptibility ( = 0.58). Subsequent analysis revealed that individuals with low lymphocyte levels and the CC genotype exhibited increased susceptibility to COVID-19 (OR = 3.45, 95%CI: 1.18-10.11). A significant association was observed between creatinine ( < 0.0001), neutrophils ( = 0.02), and NLR (Neutrophil to Lymphocyte Ratio) ( = 0.0015) with rs7975232. In a comparison of AA/AC genotype cases, individuals with normal levels of ALT, CPK, creatinine, blood sugar, and hemoglobin exhibited an increased likelihood of infection. In CC genotype cases, individuals with normal neutrophil levels exhibited a reduced chance of COVID-19. The current study did not demonstrate a significant association between the examined SNP and COVID-19. The findings indicated that the standard levels of various laboratory parameters influence the likelihood of the disease. Additional studies involving larger and more diverse populations can yield more valid results.

Endometrial cancer (EC) is a malignancy of the inner epithelial lining of the uterus, with an increasing incidence and disease-associated mortality worldwide. Inflammation and lipid metabolism contribute to EC risk. Differential expression genes (DEGs) in EC and normal samples were analyzed based on the TCGA-UCEC database, and DEGs associated with inflammation and lipid metabolism were screened out to be candidate genes. Prognosis-related genes were analyzed using Cox regression and LASSO regression, and a prognostic model was established. Receiver operating characteristic curves and Kaplan-Meier survival analysis were performed to assess the predictive performance of the prognostic model. Gene Set enrichment analysis, immune infiltration analysis, and gene set variation analysis were performed. Expression of prognostic genes in local tissues was examined by Reverse Transcription Quantitative PCR (RT-qPCR) and immunohistochemistry. Methylthiazolyldiphenyl-tetrazolium bromide assay, migration assay, and wound-healing assay were applied to examine the role of CKMT1B on cell proliferation and migration in EC cell lines. A prognostic model based on six prognosis-related genes (CKMT1B, NTS, NSG2, H3C1, MAL, ELOA2) was established in EC, and this model had a favorable predictive performance. Respective different pathways and immune cell infiltration were associated with prognostic genes. 5/6 prognostic genes were highly expressed in local EC tissues compared with normal tissues. Knockdown of CKMT1B significantly suppressed cell proliferation and metastasis in EC cell lines. CKMT1B, NTS, NSG2, H3C1, MAL, and ELOA2 (especially CKMT1B) were important factors in human EC and could be potentially used for risk stratification and prognosis prediction in EC.

Obstructive sleep apnea syndrome (OSAS) is a kind of sleep disturbance in which breathing is reduced or stopped for a short time and, if left untreated, can lead to long-term dangerous complications such as heart attack and obesity. Previous studies have shown that leptin receptor (LEPR) gene polymorphisms correlate with obesity and OSAS. This study aimed to measure the correlation of LEPR K109R and Q223R gene polymorphisms with OSAS in the Kurd population of Kermanshah, Iran. This study's population includes 100 patients with OSAS and 100 healthy individuals. Polysomnography diagnostic tests were performed on both patient and control groups. Polymerase chain reaction-restriction fragment length polymorphism was used to check the association between OSAS and LEPR gene polymorphisms. Significant differences were observed in the allelic frequencies and genotype distributions of the LEPR K109R single nucleotide polymorphism (SNP) between the patients with OSAS and those of the healthy controls, whereas no such differences were found in the allelic and genotype frequencies of LEPR gene Q223R polymorphism. Additionally, the genotypic distribution of patients did not correspond to the severity of the disease. The results indicate an association between K109R and OSAS, with no such relation between Q223R and OSAS. Neither of the SNPs showed a link with the disease severity level.

To check the correlation between the MAGE Family Member C1 ( gene variant rs176036 and ovarian cancer risk among the Jammu and Kashmir population. A case-control association study of the gene variant rs176036 (G > A) and ovarian cancer. The variation was identified through whole exome sequencing, and the selected variant was genotyped in 111 patients with ovarian cancer and 107 healthy controls belonging to the Jammu and Kashmir region of North India using Sanger sequencing to confirm its association with the ovarian cancer. Odds ratio (OR) and other statistical values were calculated using standard tools. The allelic frequency distribution was found to be similar between cases and controls, with the dominant allele (G) present in 89.6% of cases and 90.2% of controls ( = 0.84). The allelic OR for the dominant allele was 1.08 (0.55-2.11), which is nonsignificant ( = 0.83). The present study suggests that the rs176036 variant does not confer any increased risk of ovarian cancer among population of Jammu and Kashmir.

Gout is the most common arthritis, and it is associated with monosodium urate (MSU) crystal deposits in articulations, kidney, and soft tissue. The MSU crystal deposit initiates an inflammatory response, mediated by inflammasome, with the release of interleukin-1beta. Toll-like receptor 4 () is involved in this response. The association of single nucleotide polymorphisms (SNPs) and gout risk is controversial, with different results according to different populations. In the present study, we aimed to investigate the association between gene rs2770150, rs4986790, rs4986791, and rs7873784 SNPs and hyperuricemia (HUA) and primary gout in males of Bai minority in Dali Prefecture, Yunnan Province, Southwest China. In total, 600 male patients with primary gout and 720 male patients with HUA of Bai minority were collected from the First Affiliated Hospital of Dali University and the Affiliated Hospital of Traditional Chinese Medicine of Dali University from 2022 to 2024. Nine hundred and eighty-eight men of Bai minority (without HUA and primary gout) received the health examination in the physical examination center of the hospital during the same period were recruited in the healthy control group. The four SNPs of rs2770150, rs4986790, rs4986791, and rs7873784 in receptor were compared among the three groups. There were no statistically significant differences in the genotype and allele frequency of rs4986790, rs4986791, and rs7873784 among the three groups (all > 0.05). The difference in distribution of rs2770150 was statistically significant between HUA group and gout group ( < 0.05). There were 714 cases (99.2%) of AA type and 6 cases (0.8%) of GA type in HUA group, while there were 580 cases (96.7%) of AA type and 20 cases (3.3%) of GA type in primary gout group. Our study demonstrated that patients with HUA with gene rs2770150 carrying GA type may be more likely to develop gout in males of Bai minority from Dali Prefecture of Yunnan Province, Southwest China.

Genetic predisposition is an important factor related to the enhancement of inflammation or immune responses in COVID-19 patients. This study aimed to explore the association between the IL-6 (rs1800795) polymorphism and COVID-19 severity in the southwest of Iran. We evaluated these variants in 100 patients with moderate and 100 patients with severe COVID-19 using an (Amplification Refractory Mutation System Polymerase Chain Reaction) ARMS-PCR assay. In addition, we collected clinical characteristics of patients to assess their association with the severity of COVID-19. Statistically, the significance in the present evaluation was < 0.05. Our findings showed a significant association with the SNP-174G/C of the IL-6 gene between the moderate and severe groups of COVID-19 patients under the dominant and codominant genetic models ( = 0.02 and 0.03, respectively). The frequency of the G allele was notably higher in the severe group compared to the moderate group ( = 0.02). Also, the rs1800795 genotypes, as well as the patients' age and gender ( = 0.13 and 0.31, respectively), were detected. Additionally, we confirmed a significant correlation between clinical data known as risk factors for COVID-19 severity. Taken together, understanding the risk factors associated with the increased severity of COVID-19 may provide the opportunity for early and useful intervention in individuals at higher risk.

Herein, we addressed the clinical challenge of high lymph node metastasis rates despite the lack of reliable diagnostic biomarkers in papillary thyroid carcinoma (PTC) by employing bioinformatics approaches to identify key biomarkers, aiming to provide new strategies for clinical diagnosis and treatment. Through bioinformatics analysis, plasminogen activator urokinase () was identified as a key biomarker for lymph node metastasis in PTC. Immunohistochemistry (IHC) was performed to validate expression in tumor and adjacent normal tissues and its correlation with clinicopathological features. cellular expression was further confirmed by immunocytochemistry (ICC), Western blotting, and quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 and Transwell assays were used to assess its role in PTC tumor cell proliferation, migration, and invasion. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on -related genes; immune cell infiltration in PTC was evaluated using the TIMER database and CIBERSORT algorithm. Bioinformatics analysis showed that expression was significantly elevated in the PTC lymph node metastasis group [area under the receiver operating characteristic curve, 75.3%]. IHC results demonstrated significantly elevated expression in tumor tissues. Clinicopathological correlation analysis indicated that was associated with lymph node metastasis, particularly lateral cervical lymph node involvement. ICC, qRT-PCR, and Western blotting confirmed that was highly expressed in PTC tumor cells. After transient knockdown of , proliferation, migration, and invasion of PTC tumor cells were significantly reduced. GO and KEGG enrichment analyses showed that -related genes were primarily involved in signal transduction, inflammatory response, and P53, PI3K-Akt, and Mitogen-activated protein kinase (MAPK) signaling pathways. Immune cell infiltration was significantly higher in PTC tissues than in adjacent normal tissues; expression positively correlated with B and CD8 T cell infiltration and Programmed cell death protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression. enhances PTC cell proliferation, migration, and invasion while promoting immune escape through the Th1/Th2 imbalance and PD-1/CTLA-4 upregulation, serving as a potential biomarker for lymph node metastasis in PTC.