Owing to crucial role played by MicroRNA-126 (miR-126) in vascular development and regulation of vascular endothelial growth factor (VEGFA), this study determined the role of miR-126 and its target gene VEGFA in the pathogenesis of recurrent pregnancy loss (RPL) in women against healthy controls. A total of 40 samples were collected from women who had experienced consecutive RPL at 20 weeks of gestation when compared to healthy controls with full-term successful pregnancies. The relative expression of miR-126 and VEGFA in plasma was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). miR-126 expression was significantly up regulated in RPL patients compared to controls (p < 0.0001), with a median fold change of 3.13 (IQR: 1.25–5.78). Conversely, VEGFA mRNA expression was significantly down regulated in RPL patients (p < 0.0001), with a median fold change of 0.29 (IQR: 0.12–0.67). Moreover, no substantial differences were found in relative expression of miR-126 and VEGFA mRNA among categories of various variables in RPL group respectively. Correlation analysis revealed a negative association between miR-126 and VEGFA expression in RPL cases (r = -0.165). In healthy controls, the miR-126 expression was positively correlated with expression levels of VEGFA mRNA with correlation coefficient (r) = 0.925; p < 0.01. However, the correlation between miR-126 and VEGFA mRNA was not statistically significant in the RPL group. Our findings suggest that dysregulation of miR-126 and VEGFA is associated with RPL. These markers may serve as potential diagnostic and prognostic tools for idiopathic RPL. Furthermore, restoring the normal expression of these molecules could represent a novel therapeutic approach for this condition.

Esophageal cancer (EC) is an aggressive malignancy characterized by poor survival outcomes and strong links to chronic inflammatory signaling. Interleukin-11 (IL-11) has emerged as a cytokine of interest in tumorigenesis and therapy resistance. This study investigated the expression, prognostic implications and functional relevance of IL-11 signaling in EC. IL-11 pathway components were analyzed in 50 surgically resected EC and adjacent normal tissues using RT-qPCR and immunohistochemistry (IHC). Histological subtype-stratified analyses were performed for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Functional assays in KYSE-410 cells evaluated the effect of IL-11 neutralization on viability, migration, and pathway activation. RNA-sequencing, reverse-phase protein array (RPPA), clinical, and survival data from the TCGA-ESCA cohort were analyzed to validate pathway activation and prognostic associations. Additionally, murine RNA-sequencing datasets following anti-IL-11 or anti-IL-11 receptor treatment were examined to assess downstream transcriptional effects. IL-11, COX-2, and STAT3 mRNA levels were significantly upregulated in tumors compared with matched normal epithelium (p < 0.05) accompanied by increased nuclear phosphorylation of STAT3 (Tyr705). TCGA analyses confirmed elevated expression of IL-11 pathway components in EC. Elevated IL11 expression showed a trend toward reduced overall survival and was significantly associated with poorer disease-free survival. While IL11, STAT3, and PTGS2 expression did not differ significantly between EAC and ESCC, receptor-level signaling components IL6ST (gp130) and JAK1 were significantly higher in EAC, with RPPA data demonstrating increased pSTAT3 (Tyr705) and e-cadherin levels in this subtype. Downstream transcriptional analyses revealed subtype-specific STAT3 programs, with proliferation and invasion genes enriched in ESCC and survival-associated mediators elevated in EAC. Neutralization of IL11 significantly reduced cell viability (IC50 = 1 µg/mL), impaired migration, and suppressed pSTAT3 activation. These findings identify the IL-11/IL6ST/JAK1/STAT3/COX-2 axis as a central inflammatory signaling pathway in esophageal cancer. Although ligand expression is comparable across subtypes, receptor-level signaling in EAC suggests pathway sensitization rather than ligand abundance as a key determinant of signaling intensity. Functional inhibition of IL-11 attenuates tumor-promoting phenotypes, supporting IL-11 signaling as a biologically relevant and potentially pan-histologic therapeutic target in esophageal cancer.

OBJECTIVE:Recurrent Pregnancy Loss (RPL) is a significant pregnancy complication with a multifactorial aetiology and is a vital reproductive health concern that globally affects 2-5% of women. Polymorphic gene variation causes alteration in FOXP3 gene that impairs the Treg cells which leads to complications in pregnancy outcome. Thus, we aimed to study an association between FOXP3 polymorphic variations (rs3761548 and rs3761549) and RPL. MATERIAL AND METHODS:This case control study comprised of 120 RPL cases and 150 healthy multiparous women as control group with at least one full term pregnancy and no history of pregnancy loss matched to cases according to age and geographic origins. Genotyping for FOXP3 was analyzed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). RESULTS:Significantly higher frequency of FOXP3 -3279 C/A (rs 3761548)heterozygous AC and homozygous AA was found in RPL cases than controls (63.3% vs. 46%, O.R = 2.53): p = 0.0006 and (11.7% vs. 8%; O.R 2.68): p = 0.03 respectively. Moreover, the dominant model (AC +AA) and allele A were seen implicated more in RPL cases vs. healthy control (75% vs. 54%; O.R = 2.5): p = 0.0005 and (43.3% vs. 31%; O.R = 1.7): p = 0.003. For FOXP3 -2383 C/T (rs 3761548), homozygous genotype TT was significantly higher in RPL cases than the control group against the wild type CC genotype with O. R= 3.49 (p = 0.04). Further, FOXP3 (rs 3761548) genotypes AC+AA were significantly associated between cases and control in terms of women without any known family history (p = 0.0009) and consanguinity (p = 0.0002), respectively. CONCLUSION:The study concludes that both the variants of FOXP3 gene, C/A (-3279) and C/T (-2383) are significantly associated with an increased risk for recurrent pregnancy losses.

INTRODUCTION:The human telomerase reverse transcriptase (hTERT) upregulation is a common feature in many cancers. While telomerase activity is often linked to gene expression, the relationship between promoter methylation and hTERT levels can be complex. This study aimed to investigate the association between hTERT promoter hypermethylation and its expression for prognosis and pathogenesis of bladder cancer. METHODS:A total of 50 histologically confirmed bladder cancer tissue samples and matched adjacent normal controls were evaluated in a single-center prospective study. Promoter methylation was assessed by methylation-specific PCR (MS-PCR) targeting the CpG-rich hTERT promoter region, while protein expression was analyzed by immunohistochemistry using standardized scoring criteria. For validation, TCGA-BLCA data were analyzed for TERT mRNA expression, promoter methylation (TSS1500 and gene body regions), copy-number alterations (CNA), and survival outcomes. Correlation analyses and Kaplan-Meier plots were used for integrative assessment. RESULTS:Promoter hypermethylation of hTERT was detected in 90% of bladder cancers, with 80% showing high hTERT protein expression. A strong positive association between promoter hypermethylation and high protein expression was observed (P = 0.04). This was corroborated by TCGA data showing a significant upregulation of TERT mRNA in bladder tumors. The expression of hTERT was at its strongest at stage IV, though this trend was not significant in the larger TCGA cohort (P = 0.256) The large-scale survival analysis revealed no significant association between TERT expression with OS (P = 0.76), PFS (0.95), DFS (P = 0.88) and pan-cancer analysis. TERT amplification was linked to markedly higher expression levels, but weak correlation between methylation and expression at selected CpG loci and methylation at TSS1500 or gene body regions and expression CONCLUSION: Our findings demonstrate that hTERT promoter hypermethylation is paradoxically associated with increased protein expression in bladder cancer, possibly through disruption of repressor binding within the THOR region. Although hTERT expression lacks prognostic value, its consistent upregulation suggests potential use as a screening biomarker and supports exploration of telomerase-targeted therapeutic strategies.

Background: Venous thromboembolism (VTE) is a significant global health concern, with an annual incidence of approximately 1–2 per 1000 individuals. VTE is a major cause of morbidity and mortality worldwide, leading to substantial healthcare costs due to hospitalizations, long-term anticoagulation therapy, recurrent thrombotic events and the need for lifelong clinical management. The burden of VTE is particularly pronounced in aging populations, with incidence rates increasing exponentially after the age of 50. Despite its significant impact, the genetic underpinnings of VTE remain incompletely understood. This study investigates the association of Lp(a) gene polymorphisms (93C > T and 121G > A) and Lp(a) expression with VTE risk. Methods: A case-control study was conducted, enrolling 101 VTE cases and 110 healthy, age- and gender-matched controls. Genotyping was performed using PCR-RFLP, and serum Lp(a) levels were quantified using ELISA. Genotype distribution and their association with VTE risk was determined by statistical analyses. Results: The +121 G > A polymorphism exhibited a significant protective effect, with the GA genotype more prevalent in controls than cases (OR = 0.41, 95 % CI = 0.23–0.73, p = 0.002). Additionally, the combined GA + AA genotypes were significantly associated with a lower VTE risk (OR = 0.44, p = 0.003). Serum Lp(a) levels were elevated in VTE cases (mean VTE 36.41 mg/dl) compared to controls (mean 32.00 mg/dl, p < 0.84). Notably, this difference was most pronounced in the 30–70 mg/dl subgroup (p < 0.01). D-Dimer was significantly elevated in VTE (p < 0.001) and GA + AA genotype was significantly more frequent in control subjects with D-Dimer levels <500 ng/ml (OR = 0.23, 95 % CI = 0.05–0.95, p = 0.04. LP (a)+121 G > A variant genotype was significantly higher in controls for males, smokers and BMI ≤25 than VTE cases (p < 0.05). No significant difference was found in LP(a) +93C > T with VTE risk. Conclusion: Our study concludes the inverse role of Lp(a) polymorphic variation +121 G > A in the pathogenesis of VTE. +93C > T variant and serum lipoprotein (a) levels did not increase the risk of pathogenesis of VTE. However, gender specific impact of LP(a) on VTE is plausible.

ObjectivesStudies have investigated miR-125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3. MethodsThe present study included 40 cases of women with at least two RPLs in <= 20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR-125a was conducted by quantitative real-time PCR (qPCR). ResultsThe expression of miR-125a was significantly lower in the plasma of RPL cases (P = 0.0001) and showed a significantly increased mean expression level in product of conception (2.56-fold, P < 0.0001). Among the target gene of miR-125a, ERBB2 and STAT3 gene expression level was significantly increased (2.58-fold, P = 0.04; 1.87-fold, P = 0.025), respectively in RPL cases while the LIFR gene revealed comparable expression (P = 0.64). Furthermore, expression analysis of ERBB2 gene with respect to its regulatory miR-125a cases depicted a significant association (P = 0.0005). Kaplan-Meier survival analysis revealed cases with low miR-125a expression had significantly shorter time to miscarriages, (log-rank P = 0.02). Also, decreased expression of miR-125a significantly conferred >2-fold increased risk for RPL (HR = 2.34: P < 0.05). ConclusionThe overall conclusion of the study was that altered miR-125a expression may cause deregulation in target genes LIFR, ERBB2 and STAT3 resulting in adverse consequence in the outcome of pregnancy. The impact of altered miR-125a expression causes deregulation in target genes LIFR, ERBB2 and STAT3 that result in deleterious effect in the outcome of the pregnancy.

In this article, we carried out the temperature dependent UV-Visible (UV-Vis) spectroscopy, differential scanning calorimetry (DSC), and electrical studies for normal and cancerous (glioma) DNA samples of single patient. Based on this method, we were able to monitor the denaturation process and thermal stability in these molecules. From the temperature dependent optical absorption data, we calculated various optical parameters for these two types of samples. The optical band gap of these samples were also estimated and discussed as per the experimental conditions. The various optical parameters calculated indicate that mutated (tumor) DNA is less stable than the normal one. From the DSC data, clear melting peaks were observed for the tumor and normal samples. Also various thermodynamic parameters like change in enthalpy (ΔH), entropy (ΔS), and specific heat (Cp) were estimated. From the thermal study, it seems that the tumor DNA is less stable. Further from the electrical or current-voltage (I-V) characteristics data, the resistance for normal DNA decreases with temperature. But for tumor sample, it show anomalous behavior (like decreasing and then increasing trend) with temperature. For electrical transport, small polaron hopping could be the possible transport mechanism in the current sample. Here from these studies, the tumor sample seems more disordered, and structural fluctuations due to the speculated structure could be the best reason for this behavior. If such kind of molecular (at nano scale range) studied are done more vividly, then these calculated parameters of the molecule could be explored for further confirmation/diagnostics of the diseases in addition to clinical investigations.

Abstract Background Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). Methods A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. Results FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (− 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). Conclusion The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Background and objectivesHLA-G gene harbors certain polymorphic variations that can potentially impact its biological activity, and therefore, may confer a risk for recurrent pregnancy loss (RPL). This study aimed to analyze whether HLA-G polymorphic variations (G*0103, G*0104, and G0105N) are related to the risk of RPL in women from Kashmir, North India.

In the current article, we did characterizations like Fourier Transform Infrared (FT-IR) Spectroscopy, UV-Visible (UV–vis) spectroscopy, Photoluminescence (PL) spectroscopy, Cyclic Voltammetry (CV), Electrochemical Impedance Spectroscopy (EIS), Current-Voltage (I-V) characteristics, dielectric spectroscopy, and transient time spectroscopy on normal and cancerous (esophagus) DNA samples. FT-IR confirms the associated functional groups of DNA. Also a significant change in these groups with mutations is observed. From the analysis of UV data, the various optical parameters like optical band gap, disorder energy were estimated and discussed. PL data demonstrate the various emissions and are described as per the existing structure of the molecule. From the CV plots, the energy levels, like highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were also calculated. The EIS data interpretations show well developed changes in various parameters related with nature of the present molecules. Also from I-V characteristics, visible variations were observed and discussed. From the dielectric spectroscopy, a drastic change in the data were seen and described. Dynamic measurements like transient time demonstrates a vital impact on charge storage and hence on the rise and fall time of the molecules. The various calculated parameters related with these methods show changes with normal and mutated DNA. These observed properties shown by these techniques could be explored for further confirmation of the diagnostic of the disease.

BACKGROUND:Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma. AIM:To examine genetic variations of EGFR T rs712829 (216G/T) and rs712830 (191C>A) with respect to glioma risk. MATERIALS AND METHODS:129 confirmed glioma cases were genotyped against 180 malignancy-free healthy controls by polymerase chain reaction-restriction fragment length polymorphism technique (RFLP). RESULTS:The frequency of the TT homozygous variant of the EGFR -216 G/T genotype differed significantly between cases and controls (49.6% vs. 23.0%) (p < 0.0001). The EGFR -216 G>T allele 'T' was found significantly more frequently in cases (0.56 vs. 0.33 in controls; p < 0.0001). The EGFR -191C>A homozygous 'AA' genotype was implicated significantly more frequently in cases than in controls (p < 0.0001). The distribution of the 'A' variant allele was also more frequent in cases (41.9%) than in controls (14.0%) (0.55 vs. 0.30; p < 0.0001). TC and TA haplotypes showed varied frequency in cases and controls. CONCLUSION:EGFR -216 G>T and -191 C>A variants and haplotypes (TA and TC) of the EGFR gene are very strong risk factors in the development of glioma in the Kashmiri population.

BACKGROUND:Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease.METHOD:Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein.RESULTS:Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05).CONCLUSION:Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.

Background: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. Method: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. Results: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (-75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. Conclusion: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

Obesity is a complex, multifactorial, lifestyle-related disorder which affects nearly one-third of the global population. In more than one way, obesity classifies as a potential indicator or contributing factor of various clinical conditions, subsequently leading to poor health outcomes and compromised quality of life (QoL). The high prevalence and reporting rate of obesity is irrespective of geographical difference, ethnicity and gender, however, they most often serve as predisposing risk factors for obesity. Additionally, environmental changes, availability & affordability of low nutrition, yet palatable food, hormonal disbalance and variation at the genetic level, prominently exacerbates the condition of obesity and its related effects. Clinically, obesity, may either lead to other pathophysiological conditions as well, such as liver dysfunction, polycystic ovarian syndrome, hypertension, coronary artery diseases and psychological impairment or vice-versa. Henceforth, to cope with the challenges of obesity and related conditions, a healthy lifestyle, personal care & social well-being is of prime importance. Additionally, a customized strategy to address the economic expenditure and newer therapeutic perspectives should be implemented to control the widespread damage of human population by this condition. The present review focuses on providing a brief knowledge about nutritional, biochemical, genetic and psychological aspects of obesity and its epidemiology.

Background:The polymorphic variations of human telomerase reverse transcriptase (hTERT) gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of hTERT gene.Materials and methods:Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of hTERT rs2736098 and rs2736100.Results:hTERT rs2736098 homozygous variant AA genotype frequency was observed to significantly differ 2-fold between cases and controls (26.15% vs. 13.5%) (p = 0.02). In addition, rare 'A' allele significantly differed among two groups (cases: 47% versus controls: 39%: p = 0.03). hTERT rs2736098 was observed to be presented significantly more in high stage tumors (p = 0.02). hTERT rs2736100 genotype AA or variant allele A showed no significant difference between cases and controls. Haplotype CA displayed significantly different pattern of frequency as 0.5 in cases as compared to 0.16 in controls (p < 0.0001). Combination of variant A/G haplotype frequency implicated more in cases than in controls (0.34 vs. 0.14, p = 0.001).Conclusions:It is concluded that hTERT rs2736098 polymorphic variant has a vital role to confer a strong risk to bladder cancer in our population. Further, hTERT haplotypes CA and AG inhTERT could prove to be a promising tool to screen the risk for bladder cancer.

Background: Bladder cancer (BC) is the most common malignancy of the urinary tract caused by the uncontrollable division of cells lining the bladder. The clinicopathological characteristics of BC determine largely the prognosis and aid in the treatment and management of disease. Aim: The aim of the study was to analyze the incidence of BC in our region. Materials and methods: The study prospectively screened all the patients who were diagnosed with BC between 2018 and 2020. Detailed history of 235 patients was taken and Kaplan-Meier survival analysis of 137 BC patients was also performed to evaluate any possible association between various clinico-pathological characteristics, with respect to overall survival (OS) and recurrence in terms of disease free survival (DFS). Results: Among BC cases, 78.72% (185) patients were males and 21.27% (50) were females with a male: female ratio of 3.7:1. The frequency of BC was observed to be 36.17% (85) in cases that belonged to the age group of <50 years whereas 63.82% (150) cases belonged to ≥50 years. Of all cases 67.65% (159) patients were active smokers. The pathological characteristics of BC cases included 59.14% (139) cases of low stage (pTa/pT1) versus 40.86% (96) of the high stage (pT2/higher). Moreover, non-smokers, females and patients exhibiting low grade and stage had significant and better OS and DFS than the rest (Log rank P < 0.05). Conclusion: BC remains one of the leading cancers in our region despite absence of many occupational exposures except smoking.

Cytokines are potent molecules produced mainly by specific activated immune cells to control inflammatory responses besides other biologic processes. Although active participation of cytokines provides defense against carcinogenesis on the other hand, deregulation at the genetic level influences their activity to promote tumor development. Among many aspects, constitutional polymorphic sequence variations are key factors that derange the cytokine expression to lead an individual’s propensity to risk for different cancers. Cytokine polymorphisms are now believed to alter these critical molecules that have a dual face in carcinogenesis as, when implicated in the activation of the immune response, these molecules check the cancer development while their persistent inflammatory reaction can envisage the development of malignancy and tumor growth. We have given ample evidence of case-control studies in a range of cancers where substantial evidence, as reported in this chapter, links polymorphism of cytokine gene susceptibility with numerous cancers. Cytokine gene polymorphism is vital to be significant bimolecular genetic determinants of susceptibility and prognosis of cancer. A strong need is felt for more case-control association studies in cytokine candidate genes involved in specific pathways for particular cancer in bigger powered sample sizes involving additional variables to disclose their factual risk for cancer.

Pregnancy is controlled by several types of genes and the regulation of their expression is tightly controlled by miRNAs. The present study was carried out to explore the association between miR-125a polymorphic sequence variation and its expression and recurrent pregnancy loss (RPL) compared to full-term healthy controls. A total of 150 women that had experienced two or more RPLs and 180 healthy controls (two or more full-term pregnancies) were recruited, along with 50 product of conception (POC) samples from the corresponding RPL patients, and evaluated for miR-125a SNPs by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), which was confirmed by high resolution melting (HRM)/DNA sequencing. Additionally, the expression of miR-125a was quantified with q–PCR in the maternal plasma of 40 corresponding RPL patients against healthy controls. The frequency of variant genotype CC was significantly higher in RPL cases (19.3%) than controls (10.5%), with an odds ratio of >2 (p = 0.025). The expression levels of miR-125a were markedly decreased in RPL cases compared to healthy controls (p < 0.05). Variant genotype CC was found significantly more often in RPL cases than controls (0.34 vs. 0.20; p < 0.05).In this study, miR-125a rs12976445 C/T revealed that the homozygous CC genotype and C allele were associated with the risk of RPL and significant expression indicates that miR-125a has an important role in RPL etiopathogenesis.

Bladder cancer is a heterogeneous disease and ranks as 10th most common cancer worldwide. Urothelial carcinoma (UC) is the most common histologic type of BC and majority constitute of papillary tumors that are well-differentiated (low-grade). Several genetic changes may occur in bladder cancer, but hTERT promoter mutations and its expression has been detected in most cases of transitional cell carcinoma. Numerous researches have led to the findings which suggest that the hTERT promoter mutations in conjunction with the common polymorphism and hTERT expression have potential of being used as clinical biomarkers in bladder cancer. Further studies need to explore the potential use of hTERT gene in bladder cancer detection, diagnosis and prognosis. This review focuses on the role of hTERT in bladder tumors in the backdrop of various studies published.