Myeloid-derived suppressor cells in cancer: Current knowledge and future perspectives.

MDSCs (myeloid-derived suppressor cells) are crucial for immune system evasion in cancer. They accumulate in peripheral blood and tumor microenvironment, suppressing immune cells like T-cells, natural killer cells and dendritic cells. They promote tumor angiogenesis and metastasis by secreting cytokines and growth factors and contribute to a tumor-promoting environment. The accumulation of MDSCs in cancer patients has been linked to poor prognosis and resistance to various cancer therapies. Targeting MDSCs and their immunosuppressive mechanisms may improve treatment outcomes and enhance immune surveillance by developing drugs that inhibit MDSC function, by preventing their accumulation and by disrupting the tumor-promoting environment. This review presents a detailed overview of the MDSC research in cancer with regulation of their development and function. The relevance of MDSC as a prognostic and predictive biomarker in different types of cancers, along with recent advancements on the therapeutic approaches to target MDSCs are discussed in detail.

Trends in hypertension prevalence, awareness, treatment, and control: an 8-year follow-up study from rural North India.

Hypertension is a major contributor to global CVD burden. LMICs including India is challenged with rising hypertension prevalence, yet limited studies are available on temporal change and incidence among community-cohorts. This study aimed to describe trends in hypertension prevalence, awareness, treatment, and control over 8 years among a rural community-cohort from Haryana, India. The study also lends towards an analysis of incidence. Adults ≥ 30 years (N = 1542) recruited during baseline cross-sectional study between 2011 and 2014 were followed up after a median 8.1 years. At endline, demographic/lifestyle characteristics and blood pressure were re-examined. Overall median SBP significantly increased from 120 mmHg at baseline to 125.5 mmHg at endline (p < 0.001), while hypertension prevalence increased from 34.4% (95% CI 32.0-36.9) to 40.4% (95% CI 37.5-43.4) (p = 0.002). Age-standardized hypertension incidence was 30.2% (95% CI 26.7-35.2) over 8 years. Among hypertensive group, awareness, treatment, and control increased from 9.6, 8.8 and 5.0% to 31.8, 27.3 and 9.6% (p < 0.05), respectively. Increasing trend in SBP and hypertension prevalence was observed as the cohort ages. This increase is supported by the high incidence of hypertension. Nevertheless, our study highlights positive trends in hypertension care cascade but poor control, suggesting that this trend may not be adequately impactful to reduce hypertension burden.

Incidence and determinants of hysterectomy among North Indian women: An 8-year follow-up study.

Background: Despite indications of a rapid increase in the number of hysterectomies performed in India, very few studies have methodically investigated the rate and determinants of the incidence of hysterectomy. The present study aims to estimate the rate of incidence of hysterectomy and identify predictors/determinants of incident hysterectomy in a cohort of North Indian women. Methods: In the present study, a cohort of 1,009 ever-married North Indian women (aged 30-75 years) was followed up after a median of 8.11 years. Those hysterectomized at the baseline (63) were excluded; and of the rest 946 participants, 702 (74.2%) could be successfully followed-up. During the baseline assessment, data about sociodemographic variables, reproductive history, menopausal status, physiological health, and selected blood biochemicals were collected. During the end-line assessment, data about sociodemographic variables, current menopausal status, and incident hysterectomy were recorded. Results: The overall rate of incidence of hysterectomy was found to be 11.59 per 1,000 women-years, in the study population. Interestingly, the incidence rates were found to be similar among pre- and post-menopausal women. Further, while late age at menarche was found to be negatively associated with incident hysterectomy, folate repletion and high triglyceride (TG) at the baseline were found to be positively associated. Conclusions: High rate of incident hysterectomy in the studied population points toward the huge burden of gynecological morbidity and the unavailability of non-invasive protocols. Such a situation warrants immediate policy intervention. Further, maintaining TG and folate within normal physiological ranges may be beneficial in gynecological ailments necessitating hysterectomy.

Association of ACE I/D gene polymorphism and related risk factors in impaired fasting glucose and type 2 diabetes: a study among two tribal populations of North-East India.

BACKGROUND: Type 2 diabetes is a serious public health concern in India, even the indigenous tribal populations are not left unaffected. The present study aims to understand the association of major risk factors i.e. obesity, hypertension, dyslipidemia, ACE I/D polymorphism with impaired fasting glucose (IFG) and type 2 diabetes (T2D) among two different Mendelian populations of North East India. METHODS: Demographic, somatometric, physiological variables along with fasting blood samples were collected from 609 individuals. The participants were screened for ACE I/D polymorphism. RESULTS: ACE I/D polymorphism was found to follow HWE among Liangmai tribe but not among Mizo tribe. Distribution of DD genotype/D allele was found to be significantly higher for T2D among Mizo tribe. Significant association were observed between DD genotype/D allele of ACE I/D polymorphism and TC as well as LDL with both IFG and T2D only in Mizo tribe. CONCLUSIONS: The present study is an example of gene-environment interaction where DD genotype or D allele and dyslipidemia (high TC and high LDL) are posing risk for IFG and T2D both independently and in combination only among Mizo tribe with relatively less physical activity attributed to their residence in less hilly terrain however Liangmai tribe which resides in high hilly terrain shows no such association.

Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India.

BACKGROUND: Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15µM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. METHODS: We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. RESULTS: Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04]. CONCLUSIONS: High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

Differential distribution and association of FTO rs9939609 gene polymorphism with obesity: A cross-sectional study among two tribal populations of India with East-Asian ancestry.

The fat mass and obesity associated (FTO) rs9939609 gene polymorphism is most widely studied in terms of obesity in various populations. Recently, the prevalence of obesity has been reported to be very high among the North-Eastern State of India. The major aim of the present study is to understand the extent of FTO rs9939609 gene polymorphism and its association with obesity among the two North-East Indian tribal populations with similar East Asian ancestry. Somatometric data and fasting blood sample were collected from 521 tribal individuals (258 Liangmai and 263 Mizo) of Manipur after obtaining written informed consent. Genotyping of FTO rs9939609 single nucleotide polymorphism (SNP) was done using restriction fragment length polymorphism method for PCR-amplified fragments. Both the presently studied populations were not following Hardy-Weinberg law. The prevalence of obesity and minor allele frequency of FTO rs9939609 polymorphism was found to be significantly higher among the Mizo tribe compared to that of Liangmai. The selected polymorphism was found to be significantly associated with obesity (BMI) only among the Liangmai tribe (Odds ratio-3.0; 95% CI-1.4, 6.4; p-0.003), after adjusting for age and occupation. Age-cohort wise distribution and absolute fitness analysis indicated the lower fitness of minor allele in the higher age group among the Liangmai tribe. To the best of the author's knowledge this is the first study, associating FTO rs9939609 gene polymorphism and obesity in the North-eastern Indian tribal populations with East-Asian ancestry. This study revealed the FTO rs9939609 polymorphism is observed to be associated with obesity only among the Liangmai tribe not among the Mizo tribe. The differential distribution and association observed in the two selected tribes, inhabited in a similar geographical region, could be attributed to differences in their migratory histories in terms of both route and time of settlement.