Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.

miRNA expression in PCOS: unveiling a paradigm shift toward biomarker discovery.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects a substantial percentage of women, estimated at around 9-21%. This condition can lead to anovulatory infertility in women of childbearing age and is often accompanied by various metabolic disturbances, including hyperandrogenism, insulin resistance, obesity, type-2 diabetes, and elevated cholesterol levels. The development of PCOS is influenced by a combination of epigenetic alterations, genetic mutations, and changes in the expression of non-coding RNAs, particularly microRNAs (miRNAs). MicroRNAs, commonly referred to as non-coding RNAs, are approximately 22 nucleotides in length and primarily function in post-transcriptional gene regulation, facilitating mRNA degradation and repressing translation. Their dynamic expression in different cells and tissues contributes to the regulation of various biological and cellular pathways. As a result, they have become pivotal biomarkers for various diseases, including PCOS, demonstrating intricate associations with diverse health conditions. The aberrant expression of miRNAs has been detected in the serum of women with PCOS, with overexpression and dysregulation of these miRNAs playing a central role in the atypical expression of endocrine hormones linked to PCOS. This review takes a comprehensive approach to explore the upregulation and downregulation of various miRNAs present in ovarian follicular cells, granulosa cells, and theca cells of women diagnosed with PCOS. Furthermore, it discusses the potential for a theragnostic approach using miRNAs to better understand and manage PCOS.

Emerging tendencies for the nano-delivery of gambogic acid: a promising approach in oncotherapy.

Despite the advancements in cancer therapies during the past few years, chemo/photo resistance, severe toxic effects, recurrence of metastatic tumors, and non-selective targeting remain incomprehensible. Thus, much effort has been spent exploring natural anticancer compounds endowed with biosafety and high effectiveness in cancer prevention and therapy. Gambogic acid (GA) is a promising natural compound in cancer therapy. It is the major xanthone component of the dry resin extracted from the Garcinia hanburyi Hook. f. tree. GA has significant antiproliferative effects on different types of cancer, and it exerts its anticancer activities through various pathways. Nonetheless, the clinical translation of GA has been hampered, partly due to its water insolubility, low bioavailability, poor pharmacokinetics, rapid plasma clearance, early degradation in blood circulation, and detrimental vascular irritation. Lately, procedures have been invented demonstrating the ability of nanoparticles to overcome the challenges associated with the clinical use of natural compounds both in vitro and in vivo. This review sheds light on the recent emerging trends for the nanodelivery of GA to cancer cells. To the best of our knowledge, no similar recent review described the different nanoformulations designed to improve the anticancer therapeutic activity and targeting ability of GA.

Vitamin D deficiency and the vitamin D receptor (VDR) gene polymorphism rs2228570 (FokI) are associated with an increased susceptibility to hypertension among the Bangladeshi population.

Vitamin D receptor (VDR) gene is implicated in hypertension vulnerability due to its role in regulating the renin-angiotensin system (RAS) and blood pressure. In this case-control study, a carefully selected cohort of 111 hypertensive individuals and 100 healthy controls underwent serum analysis using HPLC to measure 25-hydroxy vitamin D levels. Polymorphic variations in the VDR gene were detected and characterized using the PCR-RFLP method. At first, lower 25-hydroxy vitamin D levels were observed in hypertensive individuals compared to controls (p<0.001). The genotype frequency of the VDR gene TaqI showed no significant difference between cases and controls (p>0.05). Similarly, no significant difference was found in the VDR gene BsmI genotype frequency between hypertensive patients and controls (p>0.05). However, a statistically significant distinction was observed in the VDR gene FokI genotype frequency between cases and controls (p<0.01). The odds ratios for FokI genotypes (CC, CT, TT, and CT+TT) were 1.0, 0.590, 1.566, and 0.963, respectively. Furthermore, serum 25-hydroxy vitamin D levels were significantly higher in control subjects compared to hypertensive patients across all genotypes of VDR (p<0.001). Hypertensive patients, excluding those with the FokI VDR gene CC genotype, exhibited significantly higher systolic blood pressure levels compared to the control group (p<0.05). Similarly, hypertensive subjects displayed elevated diastolic blood pressure levels compared to the control group (p<0.001). Overall, the results suggest the presence of a potential inverse correlation between serum 25-hydroxy vitamin D levels and hypertension. The association analysis conducted indicated that there is no significant association between TaqI and bsmI genotypic variants and the risk of developing hypertension. However, it was observed that VDR gene polymorphisms do have a clear association with hypertension susceptibility, as evidenced by the significantly higher occurrence of FokI genotypic variants in hypertensive patients. Our study therefore introduces the possibility of utilizing 25-hydroxy vitamin D deficiency and VDR gene polymorphisms as a biomarker for hypertension.

Prevalence and knowledge of polycystic ovary syndrome (PCOS) and health-related practices among women of Syria: a cross-sectional study.

Polycystic Ovarian Syndrome (PCOS) is a prevalent metabolic and hormonal disorder affecting women of reproductive age. Limited data exists on Syrian women's PCOS awareness and health behaviors. This study aimed to gauge PCOS prevalence, knowledge, awareness, and health-related practices among Syrian women. A cross-sectional online survey was conducted from 11 February to 27 October 2022, targeting Syrian women aged 18-45. Collaborators from specific medical universities distributed a questionnaire adapted from a Malaysian paper through social media platforms. Out of 1840 surveyed Syrian women, 64.2% were aged 21-29, and 69.6% held bachelor's degrees. Those with a bachelor's degree exhibited the highest mean knowledge score (12.86), and women previously diagnosed with PCOS had a higher mean knowledge score (13.74) than those without. Approximately 27.4% were confirmed PCOS cases, and 38.9% had possible cases. Women with PCOS were 3.41 times more likely to possess knowledge about the condition. The findings suggest a moderate level of PCOS knowledge and health-related practices among Syrian women, emphasizing the need for increased awareness. Consistent local PCOS screening programs, in collaboration with obstetrics and gynecology professionals, are crucial for improving understanding and clinical symptom recognition of this condition among Syrian women.

Anterior Nutcracker syndrome in a young male patient: a case report and review of literature.

Introduction and importance: The left renal vein (LRV) is affected by a venous compression syndrome called Nutcracker syndrome (NCS). This syndrome is characterized by extrinsic compression of the LRV, which usually occurs between aorta and superior mesenteric artery. It is a rare and under-diagnosed condition, more prevalent in females and that, if left untreated, can lead to severe problems. There are no clear guidelines regarding management. Therefore, the authors report this rare case and its symptoms in male patient and they display current management options. Case presentation: NCS was observed during computer tomography in a male patient presented with persistent left flank pain and associated haematuria. Ultrasound for left scrotum demonstrated left moderate-sized varicocele. The left varicocele testis unit was 1.6 mm and during the Valsalva manoeuvre in the supine position the testis unit was 2 mm. LRV compression between abdominal aorta and superior mesenteric artery was identified by computer tomography imaging and therefore, diagnosis of NCS was confirmed. Clinical discussion: The actual prevalence is unclear, and incidence rates have been observed to fluctuate among age group and more prevalent in women. Main symptoms include haematuria, left flank discomfort, varicocele in men, proteinuria and anaemia. Depending on severity of symptoms, management might range from conservative care to surgery. Conclusion: This treatment strategy was effective in reducing the symptoms of the patients. In young patients, conservative treatment is advised for a fair amount of time. However, more studies on how much the authors should wait before considering surgery is important.

Evaluation of Forkhead BOX M1 (FOXM1) gene expression in colorectal cancer.

Forkhead Box M1 (FOXM1)-a key cell cycle regulator is a member of the Forkhead transcription factor family. It plays a key role in embryogenesis and cell proliferation and has been strongly linked to various solid tumors. We sought to understand the regulation of FOXM1 in colorectal cancer (CRC), as well as if and to what extent other clinicopathological characteristics are associated with FOXM1. The investigation comprised 98 CRC samples and normal tissues (controls). All colon cancer patients had a colonoscopy and targeted biopsy. All rectal cancer patients had a CT and MRI. Real-time PCR, Immunohistochemistry, and Western blotting were used to evaluate FOXM1 expression, and the findings were analyzed using SPSS (v.26). FOXM1 mRNA and protein expression were substantially upregulated in tumor tissues, with the majority of these proteins localized in nucleo-cytoplasm. Elevated protein levels of FOXM1 were strongly correlated with lower education level, larger tumor size, lymph node status, lymphovascular invasion (LVI), perineural invasion (PNI), lymph node metastasis (LNM), tumor invasion depth (subserosal and serosal invasion), late stage (III and IV), localization (nucleo-cytoplasmic), intensity (strong) and recurrence. Based on survival analysis, FOXM1 overexpression and nucleo-cytoplasmic localization were associated with shorter disease-free survival while stage and PNI were linked to poorer overall and disease-free survival. According to the results of the Cox regression analysis, stage and PNI were significant predictors of prognosis in CRC patients. FOXM1 expression was elevated in CRC and was linked to reduced disease-free survival. These findings support prior reports and hence FOXM1 can be an important prognostic marker for CRC and a promising therapeutic target. Additionally, we found a link between poor disease-free survival and FOXM1's nucleo-cytoplasmic localization. However, since the sample size of this study was small, further research is needed to validate our findings.

Unraveling the relationship between the renin-angiotensin system and endometrial cancer: a comprehensive review.

Endometrial cancer (EC), the most common adenocarcinoma, represents 90% of uterine cancer in women with an increased incidence of occurrence attributed to age, obesity, hypertension, and hypoestrogenism. Being the most common gynecological malignancy in women, it shows a relation with the activation of different components of the renin-angiotensin system (RAS), which is predominantly involved in maintaining blood pressure, salt, water, and aldosterone secretion, thereby playing a significant role in the etiology of hypertension. The components of the RAS, i.e., ACE-I, ACE-II, AT1R, AT2R, and Pro(renin) receptor, are widely expressed in both glandular and stromal cells of the endometrium, with varying levels throughout the different phases of the menstrual cycle. This causes the endometrial RAS to implicate angiogenesis, neovascularization, and cell proliferation. Thus, dysfunctioning of the endometrial RAS could predispose the growth and spread of EC. Interestingly, the increased expression of AngII, AGTR1, and AGTR2 showed advancement in the stages and progression of EC via the prorenin/ATP6AP2 and AngII/AGTR1 pathway. Therefore, this review corresponds to unraveling the relationship between the progression and development of endometrial cancer with the dysfunction in the expression of various components associated with RAS in maintaining blood pressure.

Nanotube breakthroughs: unveiling the potential of carbon nanotubes as a dual therapeutic arsenal for Alzheimer's disease and brain tumors.

Alzheimer's disease (AD) and brain tumors are debilitating neurological conditions that pose significant challenges in current medical practices. Existing treatment options for AD primarily focus on symptom management, and brain tumors often require aggressive therapeutic approaches. Novel disease-modifying strategies and therapeutic agents are urgently needed to address the underlying causes of AD pathogenesis and improve brain tumor management. In recent years, nanoparticles (NPs) have shown promise as valuable tools in diagnosing and managing various brain disorders, including AD. Among these, carbon nanotubes (CNTs) have garnered attention for their unique properties and biomedical potential. Their ability to cross the blood-brain barrier (BBB) with ease opens up new possibilities for targeted drug delivery and neuroprotection. This literature review aims to explore the versatile nature of CNTs, which can be functionalized with various biomolecules or substances due to their sp2 hybridization. This adaptability enables them to specifically target cells and deliver medications under specific environmental conditions. Moreover, CNTs possess an exceptional capacity to penetrate cell membranes, making them valuable tools in the treatment of AD and brain tumors. By delving into the role of CNTs in biomedicine, this review sheds light on their potential in managing AD, offering a glimpse of hope for effective disease-modifying options. Understanding the mechanisms of CNTs' action and their capabilities in targeting and delivering medication to affected cells will pave the way for innovative therapeutic strategies that can improve the lives of those afflicted with these devastating neurological conditions. The exploration of CNTs as a dual therapeutic arsenal for both brain tumors and Alzheimer's disease holds great promise and may usher in a new era of effective treatment strategies for these challenging conditions.

Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers.

BACKGROUND: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. AIM: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. METHODS: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19-9) in CRC patients. RESULTS: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUCRDW+PLR+NLR = 0.91, 95% CI: 0.86-0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). CONCLUSION: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels.

Knowledge toward ovarian cancer symptoms among women in Syria: Cross-sectional study.

BACKGROUND: Ovarian cancer is the second most prevalent malignancy in women over 40, especially in low-income nations. For every 100,000 women in Syria, 473 new cases of ovarian cancer are diagnosed. This study aims to investigate the knowledge of ovarian cancer symptoms among Syrian women and determine the factors associated with good knowledge. METHODS: An online cross-sectional was performed between July 29 and August 17, 2022. The inquired participants in the study were Syrian females above 18 years. The questionnaire consists of 41 questions organized into three sections: sociodemographic information, Confidence in recognizing ovarian cancer symptoms, and women's Awareness of the symptoms of ovarian cancer. RESULTS: This research included 557 Syrian women, and the average age was 23. Only 20.5% of involved women demonstrated a good knowledge of the symptoms of ovarian cancer. The participants who agreed that abdominal pain and pelvic pain are ovarian cancer symptoms formed (36.8%), and (63.9%), respectively. Regarding the additional presenting symptoms of ovarian cancer, "extreme generalized fatigue" was the most often reported symptom (66.1%). Divorced women showed greater knowledge scores than other marital status groups (7.13 ± 3.31, P-value<0.05), while public sector participants scored higher than other occupational groups (6.38 ± 2.5, P-value<0.05). CONCLUSION: Our findings indicate that Syrian females have inadequate knowledge regarding ovarian cancer symptoms. More ovarian cancer awareness programs for Syrian women of all ages are needed to increase the early identification of this illness.

Non-steroidal anti-inflammatory drugs and biomarkers: A new paradigm in colorectal cancer.

Colorectal cancer is a sporadic, hereditary, or familial based disease in its origin, caused due to diverse set of mutations in large intestinal epithelial cells. Colorectal cancer (CRC) is a common and deadly disease that accounts for the 4th worldwide highly variable malignancy. For the early detection of CRC, the most common predictive biomarker found endogenously are KRAS and ctDNA/cfDNA along with SEPT9 methylated DNA. Early detection and screening for CRC are necessary and multiple methods can be employed to screen and perform early diagnosis of CRC. Colonoscopy, an invasive method is most prevalent for diagnosing CRC or confirming the positive result as compared to other screening methods whereas several non-invasive techniques such as molecular analysis of breath, urine, blood, and stool can also be performed for early detection. Interestingly, widely used medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) to reduce pain and inflammation have reported chemopreventive impact on gastrointestinal malignancies, especially CRC in several epidemiological and preclinical types of research. NSAID acts by inhibiting two cyclooxygenase enzymes, thereby preventing the synthesis of prostaglandins (PGs) and causing NSAID-induced apoptosis and growth inhibition in CRC cells. This review paper majorly focuses on the diversity of natural and synthetic biomarkers and various techniques for the early detection of CRC. An approach toward current advancement in CRC detection techniques and the role of NSAIDs in CRC chemoprevention has been explored systematically. Several prominent governing mechanisms of the anti-cancer effects of NSAIDs and their synergistic effect with statins for an effective chemopreventive measure have also been discussed in this review paper.

Assessing Syrian women's knowledge of breast cancer risk factors, warning signs, and barriers to preventive measures: A cross-sectional study.

BACKGROUND: This study aims to investigate the knowledge of Syrian women about breast cancer risk factors, warning signals, and barriers. Breast cancer is the most common cancer worldwide and the leading cause of cancer death among women. It develops when cells in the breast tissue grow uncontrollably, forming a tumor that can spread to other parts of the body. MATERIALS AND METHODS: This survey was conducted online from September 3 to September 27, 2022, and focused on Syrian women over the age of 18. It was divided into two sections, one focusing on sociodemographic characteristics and the other on breast cancer risk factors, warning signals, and barriers. RESULTS: This study found that the majority of the 1305 participants had inadequate knowledge of breast cancer risk factors, warning signs, and barriers. Those with higher levels of education, such as Ph.D. students, had the highest overall scores. The sample was mostly made up of housewives, married women, and women with moderate monthly incomes. CONCLUSION: This research found that Syrian women have inadequate knowledge about breast cancer, including risk factors, warning signs, and barriers. To reduce mortality rates, increase survival rates, and improve early diagnosis, local health organizations should provide awareness courses to emphasize the importance of annual breast exams.

ABO and Rhesus blood group markers as predictors in colorectal cancer: A prospective observational study.

Numerous research studies have investigated the relationship between ABO and Rhesus (Rh) blood groups and the risk of various cancers, yielding diverse findings. While these blood groups have been established as prognostic factors in some cancers, their relevance to colorectal cancer (CRC) remains uncertain. This research aims to determine the link between CRC and the ABO and Rh blood groups and explore any potential implications for disease survival. A hospital-based prospective observational study was conducted from March 2019 to March 2022 at the Sher-I-Kashmir Institute of Medical Sciences in Srinagar, India. A total of 246 patients with confirmed colorectal cancer were enrolled in the study. Our study observed that blood type B (33.74%) and Rh-positive (91.87%) blood types were the most prevalent, surpassing other blood groups. No statistically significant associations were identified between the blood groups and the studied xenobiotic-metabolizing enzyme gene variants. The study observed a heightened risk of CRC in patients with advanced cancer stages and lymphovascular invasion (P-value < .05). On follow-up, there were no statistically significant differences in 3-year survival rates observed between ABO and Rh blood groups. This study's findings suggest that ABO and Rh blood groups are not associated with the risk of CRC or overall survival among CRC patients. Further clinical studies are needed to establish the precise relationship between blood groups and CRC risks, as well as their implications for the prognosis of CRC patients.

TEAD4 nuclear localization and regulation by miR-4269 and miR-1343-3p in colorectal carcinoma.

BACKGROUND AND AIMS: TEAD4 transcription factor belonging to TEAD-family, is a key downstream element of the Hippo Signalling pathway and is very important for YAPinduced tumor progression. YAP-TEAD interaction is required to promote tumor progression and metastasis in various cancers. This study aims to investigate the role of TEAD4 in CRC progression and to compare the TEAD4 expression with different clinicopathological parameters of the study population. We also aim to explore the expression pattern of miR-4269 and miR-1343-3p and their functional role in TEAD4 mediated CRC progression. Furthermore, we intend to evaluate the prognostic significance of TEAD4, miR-4269, and miR-1343-3p in colorectal carcinoma. METHODS: Real-time PCR, Immunohistochemical Staining, and Western Blotting were performed on 71 human CRC tissue specimens and their adjacent normal tissues to evaluate the TEAD4 expression and the results were statistically analyzed against the clinicopathological variables of patient data and also with survival data using STATA software. miRNA expression was analyzed by quantitative real-time PCR. RESULTS: TEAD4 expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with TNM stage, Duke Stage, tumor grade, invasion depth, node status, necrosis of tumor tissue, lymphovascular and perineural invasion. As per the cox-regression model and classification tree analysis, TNM stage and perineural invasion were important predictors for TEAD4 expression and prognosis of CRC patients. Survival analysis indicated that TEAD4 overexpression was associated with poorer overall and disease-free survival. miR-4269 and miR-1343-3p were downregulated in CRC tumors and showed a negative correlation with TEAD4. The nuclear overexpressed TEAD4 and downregulated miR-4269 and miR-1343-3p evaluated for the first time in CRC, are believed to serve as important prognostic markers in CRC. CONCLUSION: Expression of TEAD4 was increased in CRC and was negatively regulated by miR-4269 and miR-1343-3p. The overexpression of TEAD4 is linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus TEAD4 may be a possible prognostic marker in CRC.

Association of -675 4G/5G PAI-1 and -2518A/G MCP-1 genetic polymorphisms with polycystic ovary syndrome in Kashmiri women: A case control study.

Background: Polycystic ovarian syndrome (PCOS) is a highly prevalent endocrine disorder among females of fertile age. It has been speculated to be associated with low-grade chronic inflammation like other inflammatory response-driven multifactorial illnesses such as diabetes mellitus (DM) and cancer. Monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) are biomarkers of inflammation and endothelial dysfunction, respectively. These have been found to be elevated in PCOS patients. The current research reveals that single nucleotide polymorphisms (SNPs) in their genes are strongly associated with the elevation of these biomarkers. The goal of this study was to see if there was a link between PAI-1 -675 4G/5G and MCP-1 -2518 A/G polymorphisms with the occurrence of PCOS. Material and Method: This study included 220 PCOS participants and 220 healthy controls. The allele-specific polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to investigate PAI-1-675 4G/5G and MCP-1 -2518A/G SNPs, respectively. Results: The -675 4G/5G SNP in the PAI-1 gene was strongly linked to PCOS. The odds ratio (OR) for the 4G/4G genotype was (OR = 3.2; P = 0.001), whereas the OR for the 4G/5G genotype was (OR = 2.39; P = 0.001). The carriers with the 4G/4G and 4G/5G genotypes showed significantly increasing trends in the triglyceride levels (P < 0.05). The genotypic frequency of the -2518 A/G MCP-1 SNP differed significantly between the PCOS patients and healthy controls; the GG genotype remained a strong predictor of PCOS (OR = 8.7; P = 0.01) and the AG genotype (OR = 2.40; P = 0.01), indicating an elevated risk of predisposing women to PCOS. There was a significant variation in the glucose 2-h levels between -2518A/G MCP-1 genotypes with AG heterozygous and GG mutant genotype showing increasing trends of glucose 2-h levels (P < 0.05). Conclusion: Both PAI-1 -675 4G/5G and MCP-1 -2518A/G polymorphisms are associated with predisposition to PCOS and its complications in Kashmiri women.

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer.

BACKGROUND: Connective tissue growth factor (CTGF) is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling, inflammatory processes and fibrosis in various illnesses including cancer. AIM: To investigate the role of CTGF in colorectal cancer (CRC) progression and to compare the CTGF expression with different clinicopathological parameters. METHODS: Real-time polymerase chain reaction, immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16. RESULTS: CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, and both lymphovascular and perineural invasion. As per the cox regression model and classification tree analysis, tumor-node-metastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients. Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival. CONCLUSION: Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.