Publications by authors named "Kiran Singh"

117 Publications

Oral ulceration in Stüve-Wiedemann syndrome: a new presentation.

BMJ Case Rep 2021 Aug 3;14(8). Epub 2021 Aug 3.

Oral and Maxillofacial Surgery, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Stüve-Wiedemann syndrome (SWS) is a rare, autosomal recessive disorder, causing dysautonomia and multisystem failure. Symptoms include skeletal malformations, restricted joint mobility and desensitisation to pain. Patients with SWS presenting with intraoral lesions are extremely rare and this is probably due to their shortened lifespan. We present a case of a 9-month-old patient who presented to our Oral and Maxillofacial Surgery (OMFS)Unit with a chronic inflamed ulcer affecting the tongue, secondary to trauma from erupting central incisors. We believe that depapillation in conjunction with an increased pain threshold contributed to its development. The patient was successfully treated by extraction of the lower central incisors and intralesional steroid injections under general anaesthetic. This case highlights that patients with SWS can present to the OMFS clinician with oral lesions and that they can be safely managed under general anaesthesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2020-241530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336181PMC
August 2021

Estradiol correlates with the accumulation of Monocytic Myeloid-Derived Suppressor Cells in Pre-term birth: A possible explanation of immune suppression in pre-term babies.

J Reprod Immunol 2021 Sep 19;147:103350. Epub 2021 Jul 19.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address:

Synergistic interplay of immune endocrine interaction is prerequisite for an effective maternal fetal tolerance. Pre-term birth (PTB) may be a consequence of altered immune-endocrine crosstalk during third trimester resulting in early breakdown of this tolerance. Myeloid derived suppressor cells (MDSCs), a heterogenous population of immature immune cells are increased in pregnant women and healthy newborns, but their role in PTB still remains obscure. We now report that granulocytic MDSCs (G-MDSCs) is decreased in women delivering prematurely, suggesting their potential role in maintaining maternal fetal tolerance. Interestingly, in contrast statistically significant increase in MDSCs and monocytic MDSCs (M-MDSCs) along with positive correlation with cord serum estradiol (E2), and overexpressed ER-α in placental tissue suggested E2 mediated accumulation of M-MDSCs in PTB babies. MDSCs mediated immune suppression is accompanied with subsequent decline in total T cells and its subtypes: Th and Tc in PTB babies, which signifies their potential contribution towards the impaired immune system of PTB babies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jri.2021.103350DOI Listing
September 2021

Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses.

Nutr Res 2021 07 24;91:57-66. Epub 2021 May 24.

Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India. Electronic address:

One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P < .01, P < .05, respectively) and meta-analysis as well (P < .001, P < .05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nutres.2021.05.002DOI Listing
July 2021

Comparison of Expression of Chemokine Receptor 4 in Maternal Decidua and Chorionic Villi in Women with Spontaneous Miscarriages and Women Opting for Termination of Viable Pregnancies.

J Hum Reprod Sci 2021 Jan-Mar;14(1):68-72. Epub 2021 Mar 30.

Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Background: Early pregnancy losses can be a distressing experience both for the parents and the treating clinician. We aim to explore the role of chemokine receptor 4 (CXCR4) in early pregnancy losses by comparing its expression among patients with spontaneous miscarriages and patients undergoing termination of viable pregnancies for unwanted pregnancies.

Aim: The aim of the study was to investigate the expression of CXCR4 in early pregnancy losses and correlate the various clinical parameters with differential expression of the above receptor in the chorionic villi and maternal decidua.

Study And Setting: The present study is a case-"control study done in a tertiary care center.

Methodology: Fifty patients attending outdoor and antenatal clinic of the hospital aged 18-40 years with spontaneous miscarriage under 20 weeks of gestational age were included as cases and compared with fifty females of comparable age group (18-40 years) seeking medical termination of pregnancy as controls. Chorionic villi and decidua obtained from the cases and controls were analyzed for CXCR4 expression.

Statistical Analysis: The results were analyzed using mean ± standard deviation, percentiles values, Chi-square test, and value to determine the association of CXCR4 expression in decidua and chorionic villi of cases versus controls.

Results: CXCR4 expression was significantly downregulated in cases as compared to the controls with < 0.001. The mean normalized ratio of CXCR4 expression to housekeeping gene (β Actin) expression in the case group was 1.607 ± 1.108 and in the control group, it was 2.506 ± 1.457. There was a strong correlation between the expression of CXCR4 and maternal age. With increasing age, the expression of CXCR4 was more downregulated in both the cases and control groups ( < 0.001). The expression of CXCR4 was elevated in controls as compared to cases in <30 years age group ( = 0.009). CXCR4 expression was higher in primigravida than in multigravida ( = 0.001), and as the number of previous miscarriages increased, the expression of CXCR4 was found to be decreased ( = 0.021).

Conclusion: CXCR4 expression is significantly reduced in women with spontaneous miscarriages in comparison with viable pregnancies. and possibly, therapies targeted at increasing the expression of CXCR4 can be used as a treatment modality for management of spontaneous miscarriages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jhrs.JHRS_64_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057149PMC
March 2021

A Novel Ensemble-based Classifier for Detecting the COVID-19 Disease for Infected Patients.

Inf Syst Front 2021 Apr 25:1-17. Epub 2021 Apr 25.

Department of Computer Science, Government Bikram College of Commerce, Punjabi University, Patiala, Punjab India.

The recently discovered coronavirus, SARS-CoV-2, which was detected in Wuhan, China, has spread worldwide and is still being studied at the end of 2019. Detection of COVID-19 at an early stage is essential to provide adequate healthcare to affected patients and protect the uninfected community. This paper aims to design and develop a novel ensemble-based classifier to predict COVID-19 cases at a very early stage so that appropriate action can be taken by patients, doctors, health organizations, and the government. In this paper, a synthetic dataset of COVID-19 is generated by a dataset generation algorithm. A novel ensemble-based classifier of machine learning is employed on the COVID-19 dataset to predict the disease. A convex hull-based approach is also applied to the data to improve the proposed novel, ensemble-based classifier's accuracy and speed. The model is designed and developed through the python programming language and compares with the most popular classifier, i.e., Decision Tree, ID3, and support vector machine. The results indicate that the proposed novel classifier provides a more significant precision, kappa static, root means a square error, recall, F-measure, and accuracy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10796-021-10132-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068562PMC
April 2021

MTHFR 1298A>C Substitution is a Strong Candidate for Analysis in Recurrent Pregnancy Loss: Evidence from 14,289 Subjects.

Reprod Sci 2021 Mar 19. Epub 2021 Mar 19.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.

We undertook meta-analyses on MTHFR 1298A>C substitution for critically evaluating its association with recurrent pregnancy loss (RPL). MTHFR genotype data for 5888 cases and 8401 controls from 39 studies were pooled to perform this meta-analyses. Genotype data were screened, scrutinized, pooled, analysed and subjected to sensitivity analysis to carefully evaluate the association between MTHFR 1298A>C and recurrent pregnancy loss. Genetic associations were sought using dominant, recessive and co-dominant models of genetic testing with odds ratio and 95% Confidence interval (CI) as the effect measures. Further analyses were undertaken by classifying the studies into Caucasian and East Asian sub-groups. Genetic heterogeneity was tested before pooling the data across studies. For assessing publication bias, Egger's intercept test was undertaken. We found a significant association of 1298A>C substitution with increased risk of RPL in the dominant (P=0.000; OR = 1.58; 95% CI =1.25-1.99) as well as recessive (P=0.000; OR = 1.66; 95% CI =1.25-2.20) models. In sub-group analysis, we observed a significant association of the polymorphism with RPL in the Caucasian populations using dominant (P=0.000; OR = 1.98; 95% CI =1.42-2.76) and recessive (P=0.000; OR = 2.20; 95% CI =1.49-3.24) models. However, this substitution showed no association with RPL in the East Asian populations (P=0.149; OR = 1.187; 95% CI =0.94-1.50). MTHFR 1298A>C substitution shows association with the risk of recurrent pregnancy loss. The association is in a population-specific manner with the substitution being a strong risk factor only in the Caucasian populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-021-00530-5DOI Listing
March 2021

Environment, Lifestyle, and Female Infertility.

Reprod Sci 2021 03 3;28(3):617-638. Epub 2020 Aug 3.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, UP, 221005, India.

Lifestyle factors, which include the practices we adopt in our daily life, have a significant role in shaping our overall health. These lifestyle choices are mainly centered on personal preferences and our surrounding social environment. In addition to lifestyle factors, we continuously interact with our environment, which impacts physiology. Several factors have been claimed to affect women's fertility; lifestyle-related factors, in particular, have received great attention in the last decade. Due to societal and professional pressure, childbearing age in women has gradually shifted to the 30s. Delayed age of childbearing along with modern lifestyle offers a wider window of opportunity for various lifestyle and genetic perturbations to penetrate to affect fertility. While clinical studies have strengthened a direct correlation between lifestyle, environment, and female reproductive health; experimental studies on animal models have investigated their mechanism of action. In most instances, these factors target the neuroendocrine pathways, resulting in metabolic derangements. This review aims to dissect the plausible interconnection of lifestyle and environmental factors with various neuroendocrine pathways and to discuss how it can affect the female physiology in the long-term, resulting in reproductive incompetence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-020-00279-3DOI Listing
March 2021

Impact of socio-demographic variables on antenatal services in eastern Uttar Pradesh, India.

Health Care Women Int 2021 23;42(4-6):580-597. Epub 2020 Jul 23.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India.

We investigated the impact of socio-demographic variables on antenatal care (ANC) utilization and the low birth weight of a child. Data were collected from 300 pregnant females. Only 22.5% of females received full antenatal care (≥4 visits). Our results showed that female's age at marriage and education plays a significant role in improving ANC. We observed an overall decrease in the utilization of services provided during each antenatal visit. ANC visits from the first trimester decrease the risk of having a baby with low birth weight. Awareness programs and educating families about pregnancy care are recommended to improve ANC utilization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07399332.2020.1789643DOI Listing
July 2020

Leishmania donovani Infection with Atypical Cutaneous Manifestations, Himachal Pradesh, India, 2014-2018.

Emerg Infect Dis 2020 08;26(8):1864-1869

We conducted a molecular study of parasite sequences from a cohort of cutaneous leishmaniasis patients in Himachal Pradesh, India. Results revealed atypical cutaneous disease caused by Leishmania donovani parasites. L. donovani variants causing cutaneous manifestations in this region are different from those causing visceral leishmaniasis in northeastern India.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3201/eid2608.191761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392404PMC
August 2020

Structural correlations in the enhancement of ferroelectric property of Sr doped BaTiO.

J Phys Condens Matter 2020 Jul 7;32(44):445402. Epub 2020 Jul 7.

UGC-DAE Consortium for Scientific Research, University Campus, Khandwa Road, Indore, 452001, India.

The effect of Sr doping in BaTiO (BTO) with nominal compositions BaSrTiO (BSTO) have been explored on its structural, lattice vibration, dielectric, ferroelectric and electrocaloric properties. The temperature dependent dielectric results elucidate the enhancement in dielectric constant and exhibit three frequency independent transitions around 335, 250 and 185 K, which are related to different structural transitions. All these transitions occur at lower temperature as compared with pristine BTO, however; remnant electric polarization (P ) of BSTO is much higher than in BTO. The value of P is ∼5 μC cm at room temperature and the maximum P ∼ 8 μC cm is observed at tetragonal to orthorhombic and orthorhombic to rhombohedral transitions. The electro-caloric effect shows the maximum adiabatic change in temperature ΔT ∼ 0.24 K at cubic to tetragonal transition. The temperature dependent synchrotron x-ray diffraction and Raman results show correlations between P , crystal structure and lattice vibrations. Our results demonstrate the enhancement in ferroelectric properties of BTO with Sr doping. The origin of the enhancement in ferroelectric property is also discussed in correlations with the appearance of superlattice peak around room temperature due to TiO octahedral distortion. These enhanced properties would be useful to design lead free high quality ferroelectric and piezoelectric materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-648X/aba384DOI Listing
July 2020

Excess iodine impairs spermatogenesis by inducing oxidative stress and perturbing the blood testis barrier.

Reprod Toxicol 2020 Jun 25;96:128-140. Epub 2020 Jun 25.

Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh -226031, India. Electronic address:

Approximately 2 billion people worldwide are susceptible to iodine deficiency. Iodine deficiency has largely been tackled by iodine fortification in salt; however indiscriminate use of iodine raises the risk of iodine toxicity. In this study, we aimed to investigate the molecular mechanisms underlying adverse effect of excess iodine on spermatogenesis. Sprague Dawley (SD) rats were orally administered with 0.7 mg potassium iodide (KI)/100 g Bw and 3.5 mg potassium iodide (KI)/100 g Bw for a period of 60 days. This resulted in significant loss of sperm count and motility. Molecular investigations provided evidence for the generation of oxidative stress with high SOD levels, reduced Nrf2, HO-1 and increased NF-kB and Follistatin. Further investigations showed increased apoptosis evidenced by reduced expression of anti-apoptotic (BCL-2, Survivin), increased expression of pro-apoptotic (Bid, Bax) markers, and increased expression of p53 and other modulators/effectors of apoptosis (cytochrome c, cleaved PARP, caspase3 and caspase9). Analysis of the blood testis barrier proteins showed reduced expression of tight junction (JAM-A, Tricellulin), ectoplasmic specialization (Integrin- β1), adherens junction (N-Cadherin, E-cadherin, β-catenin) proteins, and reduced expression of other junction protein coding genes (Claudin1, Claudin 5, Occludin, ZO-1, Testin, Fibronectin, CAR-F). Focal adhesion kinase (FAK) and key regulators of spermatogenesis (c-Kit receptor, androgen receptor) were also parallelly decreased. Further investigation showed reduced expression of germ cell proliferation and differentiation markers (PCNA, Cyclin D1, c-Kit, Cdk-4). These findings collectively explain the loss of spermatogenesis under excess iodine conditions. In conclusion, excess iodine causes loss of spermatogenesis by inducing oxidative stress and disrupting the blood testis barrier and cytoskeleton.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.reprotox.2020.06.012DOI Listing
June 2020

Enhancement of magnetoelectric coupling in Cr doped MnO.

J Phys Condens Matter 2020 Jul;32(29):295703

UGC-DAE Consortium for Scientific Research, University Campus, Khandwa Road, Indore, 452001, India.

The effect of Cr doping has been undertaken to investigate its effect on the structural, magnetic, dielectric and magnetoelectric properties of newly discovered multiferroics material α-MnO. The Cr doping modifies the room temperature crystal symmetry i.e. transforms from orthorhombic to cubic symmetry. Similar to α-MnO, two magnetic transitions have been observed in all Cr doped samples. The effect of Cr doping manifested on the low temperature transition. The lower magnetic transition shifted toward higher temperature (25 K for pristine to 40 K for Cr = 10%) whereas the high temperature transition decreases slightly with increasing Cr content. A clear frequency independent transition is observed in temperature dependent complex dielectric measurements for Mn Cr O (0 ⩽ x ⩽ 0.10) samples around high temperature magnetic ordering ∼80 K which corroborate the magnetoelectric coupling in these samples. Interestingly, the magnetodielectric value enhanced significantly with Cr doping and a maximum increase of ∼21% is observed for 10% Cr doped sample at 5 K around 70 kOe magnetic field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-648X/ab7fdcDOI Listing
July 2020

AZF deletions in Indian populations: original study and meta-analyses.

J Assist Reprod Genet 2020 Feb 9;37(2):459-469. Epub 2020 Jan 9.

Division of Endocrinology, Central Drug Research Institute, Lucknow, India.

Purpose: To identify the frequency of Y chromosome microdeletions in Indian populations and to quantitatively estimate the significance of association between these deletions and male infertility.

Methods: A total of 379 infertile males (302 azoospermic and 77 oligozoospermic infertile males) and 265 normozoospermic fertile males were evaluated for Y chromosome microdeletions (YCD) using PCR amplification and gel electrophoresis. Meta-analyses were performed on AZFa (2079 cases and 1217 controls), AZFb (2212 cases and 1267 controls), AZFc (4131 cases and 2008 controls), and AZFb+c (1573 cases and 942 controls) deletions data to quantitatively estimate the significance of association between these deletions and male infertility in Indian populations.

Results: The results revealed that out of 379 infertile azoospermic and oligozoospermic males, 38 (10.02%) had AZF deletions. No deletion was found in control samples. The highest percentage of deletions was observed in the AZFc region, followed by AZFa and AZFb. Qualitative analysis showed that AZF deletions were present in 0.59 to 32.62% (average 13.48%) of infertile cases in Indian populations. Meta-analysis revealed a significant association of AZFa (OR = 6.74, p value = 0.001), AZFb (OR = 4.694, p value = 0.004), AZFc (OR = 13.575, p value = 0.000), and AZFb+c (OR = 5.946, p value = 0.018) deletions with male infertility.

Conclusion: AZF deletions were seen in 10.02% of azoospermic and oligozoospermic cases with the highest frequency of AZFc deletions. Pooled analysis for all studies showed deletion frequency from 0.59 to 32.62% (average = 13.48%). Meta-analysis showed significant association of AZFa, AZFb, and AZFb+c deletions with male infertility. Analysis of Y chromosome microdeletions should be reckoned as an essential testing for diagnostic and therapeutic purposes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-019-01661-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056782PMC
February 2020

Increased DNA methylation in the spermatogenesis-associated (SPATA) genes correlates with infertility.

Andrology 2020 05 2;8(3):602-609. Epub 2020 Jan 2.

Division of Endocrinology, Central Drug Research Institute, Lucknow, India.

Background: Spermatogenesis-associated (SPATA) family of genes plays important roles in spermatogenesis, sperm maturation or fertilization. The knockout studies in mice have demonstrated that SPATA genes are crucial for fertility. Gene expression and genetic polymorphism studies have further suggested their correlation with infertility; however, methylation analysis of SPATA genes in human male infertility has not yet been undertaken.

Objectives: To analyze the methylation status of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic male infertility.

Materials And Methods: In the present study, we have analyzed DNA methylation pattern in the promoter regions of SPATA4, SPATA5 and SPATA6 genes in oligozoospermic patients and compared it with normozoospermic fertile controls. Semen samples were obtained from 30 oligozoospermic infertile and 19 normozoospermic fertile controls, and DNA methylation levels of the target gene promoters were analyzed by amplicon based deep sequencing methylation analysis using MiSeq.

Results: SPATA4 (P < 0.0008), SPATA5 (P = 0.009) and SPATA6 (Promoter, P < 0.0005; Exon 1, P = 0.0128) genes were significantly hypermethylated in oligozoospermic patients in comparison to controls. This is the first study reporting a higher methylation in the promoters of SPATA4, SPATA5 and SPATA6 in oligozoospermic infertile individuals in comparison to the normozoospermic fertile controls.

Discussion: Altered methylation of SPATA genes would affect pathways involved in sperm production or affect various processes linked to sperm fertility.

Conclusion: In conclusion, hypermethylation in the SPATA4, SPATA5 and SPATA6 genes correlates with oligozoospermic infertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/andr.12742DOI Listing
May 2020

Altered cord serum 25-hydroxyvitamin D signaling and placental inflammation is associated with pre-term birth.

Am J Reprod Immunol 2020 02 17;83(2):e13201. Epub 2019 Nov 17.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.

Problem: Vitamin D is well-known for having anti-inflammatory and immunomodulatory properties. Impaired maternal vitamin D status has been known to increase the risk of adverse pregnancy outcomes like pre-term birth. The present study aims to evaluate the impact of fetal cord serum 25-hydroxyvitamin D-mediated signaling in mediating inflammatory responses in placenta during pre-term birth.

Method Of Study: For the above purpose, cord serum 25 hydroxyvitamin D 25(OH)D were measured in term (n = 20) and pre-term (n = 20) born babies using ELISA. Vitamin D downstream signaling has also been checked in placenta (VDR, CYP27B1, cathelicidin LL37) along with expression of inflammatory markers (S100A8, HMGB1, TLR2, p-NF-kappaB) using Western blotting and immunohistochemistry. Pearson correlation model was used to do correlation study.

Results: Compared with term born babies (59.31 ± 3.476), decline in cord serum 25(OH)D levels is observed in pre-term born babies (22.26 ± 1.083, P = <0.0001) that showed strong positive correlation with gestational age (r = .9368***) and birthweight (r = .9559***). On the other hand, vitamin D signaling markers were found to be downregulated and inflammatory markers were upregulated in placental tissue of pre-term born babies.

Conclusion: Thus, our study demonstrated that insufficient cord 25(OH)D levels may disturb the homeostasis of inflammation in placenta. Altered cord serum 25(OH)D mediated anti-inflammatory signaling may be acting as trigger signals in modulating inflammatory responses in placenta and eliciting premature activation of spontaneous labor in pre-term birth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13201DOI Listing
February 2020

Duplications in 19p13.3 are associated with male infertility.

J Assist Reprod Genet 2019 Oct 16;36(10):2171-2179. Epub 2019 Aug 16.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, 221005, India.

Purpose: To identify genomic imbalances and candidate loci in idiopathic male infertility.

Methods: Affymetrix CytoScan 750K Array was used to analyze genomic imbalances and candidate loci in 34 idiopathic infertile cases of different phenotypes (hypo-spermatogenesis, n = 8; maturation arrest, n = 7; and Sertoli cell-only syndrome, n = 13, severe oligozoospermia, n = 6, and 10 normozoospermic fertile men). Ten ethnically matched controls were screened for comparison.

Results: The cytogenetic array analysis detected a genomic gain at the 19p13.3 region in 9 (26.47%) cases, with the highest frequency in patients with Sertoli cell-only syndrome (SCOS) (38%). Its complete absence in the control group suggests its likely pathogenic nature. In addition to Y-classical, micro, and partial deletions, the duplication in 19p13.3 could serve as a unique biomarker for evaluation of infertility risk. The common region across the individuals harboring the duplication identified STK11, ATP5D, MIDN, CIRBP, and EFNA2 genes which make them strong candidates for further investigations. The largest duplicated region identified in this study displayed a major network of 7 genes, viz., CIRBP, FSTL3, GPX4, GAMT, KISS1R, STK11, and PCSK4, associated with reproductive system development and function. The role of chance was ruled out by screening of ethnically matched controls.

Conclusion: The result clearly indicates the significance of 19p13.3 duplication in infertile men with severe testicular phenotypes. The present study underlines the utility and significance of whole genomic analysis in the cases of male infertility which goes undiagnosed due to limitations in the conventional cytogenetic techniques and for identifying genes that are essential for spermatogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-019-01547-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823329PMC
October 2019

Array-based DNA methylation profiling reveals peripheral blood differential methylation in male infertility.

Fertil Steril 2019 07 15;112(1):61-72.e1. Epub 2019 May 15.

Division of Endocrinology, Central Drug Research Institute, Lucknow, India. Electronic address:

Objective: To study peripheral blood DNA differential methylation in oligozoospermic infertile men in comparison with normozoospermic fertile controls.

Design: Case-control study.

Setting: Reproductive biology laboratory.

Patients(s): Azoospermic and oligozoospermic infertile patients (n = 6) and normozoospermic fertile controls (n = 6) in the discovery phase, and oligo/asthenozoospermic infertile men (n = 11) and normozoospermic fertile controls (n = 10) in the validation phase.

Intervention(s): Blood samples drawn from all participants, DNA isolation and methylation analysis.

Main Outcome Measure(s): DNA methylation values analyzed using genomewide methylation 450K BeadChip array, followed by deep sequencing of selected regions for methylation analysis in the neighborhood regions of differentially methylated CpGs.

Result(s): We found 329 differentially methylated CpG spots, out of which 245 referred to the genes, representing 170 genes. Deep-sequencing analysis confirmed the methylation pattern suggested by 450K array. A thorough literature search suggested that 38 genes play roles in spermatogenesis (PDHA2, PARP12, FHIT, RPTOR, GSTM1, GSTM5, MAGI2, BCAN, DDB2, KDM4C, AGPAT3, CAMTA1, CCR6, CUX1, DNAH17, ELMO1, FNDC3B, GNRHR, HDAC4, IRS2, LIF, SMAD3, SOD3, TALDO1, TRIM27, GAA, PAX8, RNF39, HLA-C, HLA-DRB6), are testis enriched (NFATC1, NMNAT3, PIAS2, SRPK2, WDR36, WWP2), or show methylation differences between infertile cases and controls (PTPRN2, RPH3AL).

Conclusion(s): We found a statistically significant correlation between peripheral blood DNA methylation and male infertility, raising the hope that epigenome-based blood markers can be used for screening male infertility risk. The study also identified new candidates for spermatogenesis and fertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2019.03.020DOI Listing
July 2019

S100 proteins: An emerging cynosure in pregnancy & adverse reproductive outcome.

Indian J Med Res 2018 12;148(Suppl):S100-S106

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India.

S100 proteins are calcium (Ca)-binding proteins and these have an important function in progression, manifestation and therapeutic aspects of various inflammatory, metabolic and neurodegenerative disorders. Based on their involvement in intracellular or extracellular regulatory effects, S100 proteins are classified into three subgroups: one subgroup is specialized in exerting only intracellular effects, other performs both intracellular and extracellular functions and the third subgroup members only display extracellular regulatory effects. S100 proteins are expressed particularly in vertebrates and have cell-specific expression. Functionally, S100 proteins act through their surface receptors and regulate cell functions in autocrine or paracrine mode. Receptor for advanced glycation end products (RAGEs) and toll-like receptor 4 are the main surface receptors. S100 proteins participate in the regulation of cellular differentiation, proliferation, apoptosis and inflammation along with Ca homeostasis, energy metabolism and cellular migration, and perform the respective functions through their interaction with transcription factors, nucleic acids, enzymes, receptors, cytoskeleton system, etc. Currently, their role in adverse pregnancy outcomes and compromised reproductive health is being explored. These proteins are present in amniotic fluid, endometrium tissue and foetal brain; therefore, it is quite likely that alterations in the expression levels of S100 family members will be affecting the particular function they are involved in and ultimately affecting the pregnancy in adverse manner. The current review discusses about an association of S100 proteins in pregnancy disorders such as endometriosis, intrauterine growth retardation and miscarriage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijmr.IJMR_494_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469379PMC
December 2018

XRCC1 deficiency correlates with increased DNA damage and male infertility.

Mutat Res Genet Toxicol Environ Mutagen 2019 Mar 15;839:1-8. Epub 2019 Jan 15.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India. Electronic address:

High fidelity DNA repair is critical to sustain the genomic integrity and quality of developing germ cells. Deficiencies in DNA repair machinery may result in increased DNA damage in germ cell leading to abnormal spermatogenesis and infertility. X-ray repair cross-complementing group 1 (XRCC1) is a testis enriched protein that plays a crucial role in the DNA base excision repair (BER) pathway. The aim of this study was to analyze the level of XRCC1 transcript and protein in infertile men and its association with DNA damage in sperm. A total of eighty infertile patients with different infertile phenotypes (Azoospermia, n = 30; Severe oligozoospermia, n = 25; Severe oligoasthenozoospermia, n = 25) and age-matched controls (normal spermatogenesis [NS], n = 15 and fertile controls, n = 10) were recruited. γ-H2 AX protein levels were analyzed to estimate the DNA damage in sperm. XRCC1 transcript levels in cases and controls were determined by qRT-PCR. XRCC1 and γ-H2 AX proteins were immunohistochemically analyzed in testicular biopsy sections obtained from NOA patients and OA controls. The determination of XRCC1 and γ-H2 AX protein levels was performed with Western blots. The results revealed reduced expression of XRCC1 mRNA and protein in infertile individuals as compared to controls (p < 0.001). γ-H2 AX levels were significantly increased in infertile cases as compared to controls, indicating increased DNA damage in infertile men. The results indicate decreased expression of the XRCC1 gene in infertile patients which may be one of the factors associated with impaired spermatogenesis and infertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mrgentox.2019.01.004DOI Listing
March 2019

Azoospermic infertility is associated with altered expression of DNA repair genes.

DNA Repair (Amst) 2019 03 24;75:39-47. Epub 2019 Jan 24.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India. Electronic address:

Compelling evidence suggest that germs cells are predominantly sensitive to DNA damaging agents in comparison to other cells. High fidelity DNA repair in testicular cells thus becomes indispensable to preserve the genomic integrity for passing on to the progeny. Compromised DNA repair machinery in the testicular cells may result in impaired spermatogenesis and infertility. It remains unclear if the alterations in the expression of DNA repair genes correlate with azoospermia and male infertility. In the present study, 54 non-obstructive azoospermic infertile patients with hypospermatogenesis (HS, n = 26), maturation arrest (MA, n = 15), Sertoli cell only syndrome (SCOS, n = 13) and 14 controls with obstructive azoospermia, but normal spermatogenesis were recruited. Expression profiling of 84 DNA repair genes in testicular biopsy samples was performed using PCR array. Out of 84 genes, 27, 64 and 28 genes showed >5 fold down-regulation in the HS, MA and SCOS groups, respectively. On the basis of differential expression and their functional significance in spermatogenesis, ten genes (MSH2, BRIP1, CCNH, LIG4, MGMT, NTHL1, PMS1, DMC1, POLB and XPA) were selected for validation of transcript levels in a higher number of cases using RT-PCR, which corroborated the findings of array. Four genes (MSH2, LIG4, PMS1 and DMC1) were analyzed for protein levels using immunohistochemistry, which further validated the loss of DNA repair gene expression. Caspase-3 immunostaining showed that the loss of DNA repair correlated with increased testicular apoptosis in patients. Maturation arrest showed the highest apoptotic index with maximum number of downregulated genes. We conclude that the loss of DNA repair genes expression in testis correlates with increased apoptosis, azoospermia and infertility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dnarep.2019.01.006DOI Listing
March 2019

Altered crosstalk of estradiol and progesterone with Myeloid-derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal-fetal tolerance.

Am J Reprod Immunol 2019 02 28;81(2):e13081. Epub 2019 Jan 28.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, India.

Problem: Decline in myeloid-derived suppressor cells (MDSCs) and Th2 cytokines levels lead to early miscarriage (EM) but how the hormonal milieu of the body regulates MDSCs and Th1/Th2 cytokine balance is still a matter of investigation.

Method Of Study: Peripheral blood and decidua samples were collected from 20 EM patients, and 20 healthy pregnant women opted for elective abortion. MDSCs and G-MDSCs levels were analyzed in peripheral blood mononuclear cells, and Th1/Th2 cytokines levels were determined in serum via flow cytometry. Estrogen (E2), Progesterone (P4), and Testosterone levels were measured via ELISA. Further, proliferation and apoptosis in decidual samples were checked via immunoblot/immunohistochemistry of estrogen receptor -α (ER-α), STAT-3/pSTAT-3, and caspase-3, respectively.

Results: Our results clearly indicate that in EM patients; decline in E2 and P4 significantly correlates with decline in MDSCs, particularly with subtype granulocytic MDSCs (G-MDSCs) and skewness of the Th1/Th2 cytokines balance toward Th1 response. Downregulation of ER- α and increased caspase-3 expression in endometrium decidua signifies poor endometrial receptivity in EM. STAT-3 activation regulates proliferation, differentiation and suppressive potency of MDSCs. In decidua of EM, significantly lower expression of pSTAT-3 indicates that these processes pertaining to MDSCs are compromised.

Conclusion: Altogether, this unfavorable systemic milieu may drive toward early breakdown of maternal-fetal tolerance in EM. Therefore, regulated crosstalk of E2, P4 with MDSCs and balanced Th1/Th2 cytokines is prerequisite for successful pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13081DOI Listing
February 2019

The Yin and Yang of Myeloid Derived Suppressor Cells.

Front Immunol 2018 28;9:2776. Epub 2018 Nov 28.

Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.

In recent years, most of our knowledge about myeloid derived suppressor cells (MDSCs) has come from cancer studies, which depicts Yin side of MDSCs. In cancer, inherent immunosuppressive action of MDSCs favors tumor progression by inhibiting antitumor immune response. However, recently Yang side of MDSCs has also been worked out and suggests the role in maintenance of homeostasis during non-cancer situations like pregnancy, obesity, diabetes, and autoimmune disorders. Continued work in this area has armored the biological importance of these cells as master regulators of immune system and prompted scientists all over the world to look from a different perspective. Therefore, explicating Yin and Yang arms of MDSCs is obligatory to use it as a double edged sword in a much smarter way. This review is an attempt toward presenting a synergistic coalition of all the facts and controversies that exist in understanding MDSCs, bring them on the same platform and approach their "Yin and Yang" nature in a more comprehensive and coherent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2018.02776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280921PMC
October 2019

SNPs in ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway and risk of male infertility in the Asian populations: association study, meta-analysis, and trial sequential analysis.

J Assist Reprod Genet 2019 Jan 3;36(1):79-90. Epub 2018 Nov 3.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, 221005, India.

Purpose: We investigated if substitutions in the ERCC1, ERCC2, and XRCC1 genes of the DNA repair pathway correlate with non-obstructive azoospermia and male infertility.

Methods: A total of 548 azoospermic infertile males and 410 fertile controls were genotyped for XRCC1 399A > G, 280G > A, and ERCC1 C > A 3' UTR and 541 azoospermic infertile males and 416 fertile controls were genotyped for ERCC2 751A > C using iPLEX Gold Assay. Meta-analyses were performed on XRCC1 399A > G (1022 cases and 1004 controls), ERCC1 C > A 3' UTR (879 cases and 1059 controls), and ERCC2 751A > C (914 cases and 850 controls) polymorphisms to quantitatively estimate the significance of the association between these polymorphisms and the risk of infertility.

Results: Statistically significant association between ERCC2 751A > C SNP and male infertility was found using the codominant model (p = 0.03). Results of meta-analysis suggested a lack of correlation with male infertility risk, which could be due to pooling of studies from different ethnic populations. Due to limited the number of studies, a stratified analysis for different ethnic groups could not be performed.

Conclusion (s): In conclusion, AA genotype of 751A > C SNP in ERCC2 correlated with a higher risk of male infertility and may contribute to an increased risk of azoospermia and male infertility in Indian men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10815-018-1339-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338593PMC
January 2019

Genome-wide differential methylation analyses identifies methylation signatures of male infertility.

Hum Reprod 2018 12;33(12):2256-2267

Division of Endocrinology, Central Drug Research Institute, Lucknow, India.

Study Question: Do methylation changes in sperm DNA correlate with infertility?

Study Answer: Loss of spermatogenesis and fertility was correlated with 1680 differentially-methylated CpGs (DMCs) across 1052 genes.

What Is Known Already: Methylation changes in a number of genes have been correlated with reduced sperm count and motility.

Study Design, Size, Duration: This case-control study used spermatozoal DNA from 38 oligo-/oligoastheno-zoospermic infertile patients and 26 normozoospermic fertile men.

Participants/materials, Settings, Methods: Genome-wide methylation analysis was undertaken using 450 K BeadChip on spermatozoal DNA from six infertile and six fertile men to identify DMCs. This was followed by deep sequencing of spermatozoal DNA from 32 infertile patients and 20 fertile controls.

Main Results And The Role Of Chance: A total of 1680 DMCs were identified, out of which 1436 were hypermethylated and 244 were hypomethylated. Classification of DMCs according to the genes identified BCAN, CTNNA3, DLGAP2, GATA3, MAGI2 and TP73 among imprinted genes, SPATA5, SPATA7, SPATA16 and SPATA22 among spermatogenesis-associated genes, KDM4C and JMJD1C, EZH2 and HDAC4 among genes which regulate methylation and gene expression, HLA-C, HLA-DRB6 and HLA-DQA1 among complementation and immune response genes, and CRISPLD1, LPHN3 and CPEB2 among other genes. Genes showing significant differential methylation in deep sequencing, i.e. HOXB1, GATA3, EBF3, BCAN and TCERG1L, are strong candidates for further investigations. The role of chance was ruled out by deep sequencing of select genes.

Large-scale Data: N/A.

Limitations, Reason For Caution: Genome-wide analyses are fairly accurate, but may not be exactly validated in replication studies across all DMCs. We used the 't' test in the genome-wide methylation analysis, whereas other tests could provide a more robust and powerful analysis.

Wider Implications Of The Findings: DMCs can serve as markers for inclusion in infertility screening panels, particularly those in the genes showing differential methylation consistent with previous studies. The genes validated by deep sequencing are strong candidates for investigations of their roles in spermatogenesis.

Study Funding/competing Interest(s): The study was funded by the Council of Scientific and Industrial Research (CSIR), Govt. of India with grant number BSC0101 awarded to Rajender Singh. None of the authors has any competing interest to declare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/humrep/dey319DOI Listing
December 2018

Urban green space availability in Bathinda City, India.

Environ Monit Assess 2018 Oct 24;190(11):671. Epub 2018 Oct 24.

Department of Geography and Geology, School of Environment and Earth Sciences, Central University of Punjab, Mansa Road, Bathinda, India.

This paper aims to investigate and map the spatial distribution of urban green spaces (UGSs) in Bathinda City, India. Since urban green spaces affect the quality of life and provide various ecological, socio-cultural and economic benefits to a city, the spatial distribution of UGSs and per capita availability deserve greater consideration in urban planning and research. The UGSs are extracted from freely available Sentinel 2 image with spatial resolutions of 10 m (blue, green, red, and near infrared bands). The result indicates that the planned urban setups have higher area under UGSs as compared to the rest of the city. Analysis and intra-city comparison (ward wise) of distribution of green spaces and per capita availability indicate that there is an inequitable distribution of UGSs in Bathinda City. The study also attempts to accentuate the scope of green initiatives in the various wards of the city to ensure the well-being of people.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10661-018-7053-0DOI Listing
October 2018

Decline in seminal quality in Indian men over the last 37 years.

Reprod Biol Endocrinol 2018 Oct 23;16(1):103. Epub 2018 Oct 23.

Male Reproductive Biology Laboratory, Division of Endocrinology, Central Drug Research Institute, Lucknow, UP, India.

Background: Since the first report of a decline in semen quality in 1974, there have been several reports of similar declines across populations. Despite some scattered reports of declining semen quality in the Indian sub-continent, comprehensive studies analyzing semen quality over the last few decades have not been undertaken. We undertook the present study to investigate the temporal trend in semen parameters in Indian populations over a period of 37 years (1979-2016).

Methods: Publications providing semen analysis details for fertile and infertile men from the Indian sub-continent were collected by a thorough literature search. Semen quality data for 6466 normal fertile or presumptive normal men (from 119 studies/data sets) and 7020 infertile men (from 63 studies/data sets) published between 1979 and 2016 were retrieved. We undertook systematic review and quantitative analysis of mean sperm count, motility, normal morphology and other available parameters. Data were analyzed to estimate semen parameters reference values for Indian men and to assess temporal trends in infertile, fertile and all subjects.

Results: Seminal quality shows a decreasing temporal trend and the decrease is higher in infertile than fertile males. In pooled analysis for all individuals, significant (p < 0.05 or < 0.001) declines in sperm concentration and normal morphology are observed; however, isolated analysis for each group shows declines without statistical significance. The mean (± SD) semen volume, sperm concentration, total motility, rapid linear progressive motility, normal sperm morphology and sperm viability for Indian fertile men are 2.88 ± 0.77 ml, 81.08 ± 29.21 million/ml, 66.37 ± 10.95%, 52.64 ± 15.78%, 56.68 ± 20.23% and 72.63 ± 8.31%, respectively, whereas in infertile these are 3.07 ± 1.27 ml, 37.94 ± 26.41 million/ml, 40.22 ± 13.76%, 26.79 ± 15.47%, 36.41 ± 21.66% and 55.25 ± 11.99%, respectively. The mean seminal parameter values were significantly lower (p < 0.001) in infertile as compared to fertile men, except semen volume.

Conclusions: Semen parameters in Indian men have declined with time and the deterioration is quantitatively higher in the infertile group. The study also provides reference values for semen parameters in Indian men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-018-0425-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199708PMC
October 2018

Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent.

PLoS Negl Trop Dis 2018 09 27;12(9):e0006659. Epub 2018 Sep 27.

Department of Biochemistry and Microbial Sciences, Central University of Punjab, Bathinda, Punjab, India.

Background: Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent.

Methods And Findings: A literature review based on endemic areas, the nature of disease manifestation, and underlying causative parasite was performed with data collected from WHO reports for each country. Searches on PubMed included the term ''leishmaniasis" and "leishmaniasis epidemiology" alone and in combination with each of the endemic countries, Leishmania species, cutaneous, visceral, endemic, non-endemic, typical, classical, atypical, and unusual with no date limit and published in English up to September 2017. Our findings portray a scenario with a wider distribution of the disease in new endemic foci, with new discoveries of parasite-driven atypical disease manifestations in different regions of the world. Unlike the classical picture, some Leishmania species are associated with more than one disease presentation, e.g., the L. donovani complex, generally associated with the visceral form, is now also associated with a cutaneous disease presentation, while L. tropica species complex, known to cause cutaneous disease, can cause viscerotropic disease. This phenomenon points towards the discovery of novel parasite variants as etiologic agents of atypical disease manifestations and represents an excellent opportunity to identify and study genes that control disease virulence and tropism.

Conclusions: The increased recognition of atypical leishmaniasis as an outcome of parasite variants has major implications for leishmaniasis control and elimination. Identifying molecular correlates of parasite isolates from distinct regions associated with different disease phenotypes is required to understand the current epidemiology of leishmaniasis in regions with atypical disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0006659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159859PMC
September 2018

High Level of APOA1 in Blood and Maternal Fetal Interface Is Associated With Early Miscarriage.

Reprod Sci 2019 05 13;26(5):649-656. Epub 2018 Jul 13.

1 Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India.

Early miscarriage (EM) is one of the most devastating obstetrical complications globally affecting the quality of women's life. In the present study, we aimed to identify proteins that correlate with and could act as biomarkers for EM. We performed 2-dimensional gel electrophoresis in chorionic villi samples followed by mass spectrometry for identification of differential protein expression with EM. Proteomic studies detected a total 124 protein spots, out of which 83 spots were differentially expressed between EM and controls in chorionic villi samples. Matrix assisted laser desorbtion/ionization-time of flight (MALDI-TOF) mass spectrometry analysis revealed Apolipoprotein A1 (APOA1) to be the most upregulated protein in the EM group that was validated by Western blotting and Enzyme-linked immunosorbent assay (ELISA) . We found low but not statistically significant level of APOA1 on 21st day of menstruation in comparison to the 7th day. APOA1 level was observed to be the lowest in the first trimester. Hence, this study suggests that low APOA1 expression is critical in establishing pregnancy and elevated APOA1 expression in chorionic villi correlates with EM. Similar observation in serum samples suggests its potential as a marker for the risk of EM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1933719118783266DOI Listing
May 2019

Association of functional SNP-1562C>T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients.

J Diabetes Complications 2017 Dec 26;31(12):1648-1651. Epub 2017 Aug 26.

Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi 221005, India. Electronic address:

Objective: Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C>T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C>T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population.

Methods: This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C>T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results.

Results: T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p<0.0001 by T allele; p=0.002 by TT and p<0.0001 by CT genotype).

Conclusions: The present study suggests that the functional SNP-1562C>T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdiacomp.2017.08.010DOI Listing
December 2017

Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation.

Sci Rep 2017 05 15;7(1):1885. Epub 2017 May 15.

Division of Endocrinology, CSIR-Central Drug Research Institute, Sector-10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, U.P., India.

Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst first interacts with the luminal endometrial epithelial cells during its implantation; therefore, we have investigated the signaling of ITGB8 via FAK and VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5, 0500 h) stages of endometrial receptivity period in the mouse. Integrins downstream molecule FAK has demonstrated an increased expression and phosphorylation (Y397) in the endometrium as well as in the isolated endometrial epithelial cells during receptive and post-receptive stages. Integrin beta8 can functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK, and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1 signaling axis via FAK to facilitate the endometrial epithelial cell receptivity for the attachment of blastocyst.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-01764-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5432530PMC
May 2017
-->