Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice.

PURPOSE: Radiation triggers cell death events through signaling proteins, but the combined mechanism of these events is unexplored The Wnt canonical pathway, on the other hand, is essential for cell regeneration and cell fate determination. AIM: The relationship between the Wnt pathway's response to radiation and its role in radiotoxicity is overlooked, even though it is a critical molecular control of the cell. The Wnt pathway has been predicted to have radioprotective properties in some reports, but the overall mechanism is unknown. We intend to investigate how this combined cascade works throughout the radiation process and its significance over radiotoxicity. MATERIALS AND METHODS: Thirty adult mice were irradiated with electron beam radiation, and 5 served as controls. Mice were sacrificed after 24 h and 30 days of irradiation. We assessed DNA damage studies, oxidative stress parameters, mRNA profiles, protein level (liver, kidney, spleen, and germ cells), sperm viability, and motility. OBSERVATION: The mRNA profile helps to understand how the combined cascade of the Wnt pathway and NHEJ work together during radiation to combat oxidative response and cell survival. The quantitative examination of mRNA uncovers unique critical changes in all mRNA levels in all cases, particularly in germ cells. Recuperation was likewise seen in post-30 day's radiation in the liver, spleen, and kidney followed by oxidative stress parameters, however not in germ cells. It proposes that reproductive physiology is exceptionally sensitive to radiation, even at the molecular level. It also suggests the suppression of Lef1/Axin2 could be the main reason for the permanent failure of the sperm function process. Post-irradiation likewise influences the morphology of sperm. The decrease in mRNA levels of Lef1, Axin2, Survivin, Ku70, and XRCC6 levels suggests radiation inhibits the Wnt canonical pathway and failure in DNA repair mechanisms in a coupled manner. An increase in Bax, Bcl2, and caspase3 suggests apoptosis activation followed by the decreased expression of enzymatic antioxidants. CONCLUSION: Controlled several interlinked such as the Wnt canonical pathway, NHEJ pathway, and intrinsic apoptotic pathway execute when the whole body is exposed to radiation. These pathways decide the cell fate whether it will survive or will go to apoptosis which may further be used in a study to counterpart and better comprehend medication focus on radiation treatment.

Association of DAZL polymorphisms and DAZ deletion with male infertility: a systematic review and meta-analysis.

BACKGROUND: Various populations have been investigated for the occurrence of two key DAZL polymorphisms, 260A > G (rs11710967) and 386A > G (rs121918346), as well as complete DAZ cluster deletion, with conflicting results. OBJECTIVE: The purpose of the current meta-analysis was to investigate if there is an association between DAZL polymorphisms and complete deletion of the DAZ cluster gene with male infertility. METHODS: Up until September 2022, a thorough search was conducted in the Pubmed and Google scholar databases. For 260A > G polymorphism, 8 studies with 2077 cases and 1398 controls, 13 studies for 386A > G polymorphism (4343 cases and 3727 controls) and 17 studies of DAZ deletion (2820 cases and 1589 controls) were included in the pooled analysis. All of the studies were statistically analysed by Review Manager 5.4, and publication bias was evaluated with JASP 0.16.2.0 software utilising funnel plots and Egger's linear regression test. RESULTS: The meta analysis result for pooled data indicated no association between 260A > G and 386A > G polymorphisms and male infertility in any of the genetic models or ethnicities. However, there was a definite correlation between complete deletion of the DAZ gene cluster and male infertility, with an OR = 13.23, 95% confidence interval (6.63-26.39), and p < 0.00001. In the stratified analysis by ethnicity, Caucasians and Asian ethnic groups showed the similar relationship. CONCLUSION: In order to arrive at more definitive conclusions, further study should be conducted, including studies from a larger range of nations and nationalities.

Linking Depressive and Anxiety Symptoms with Diet Quality of University Students: A Cross-Sectional Study during the COVID-19 Pandemic in India.

This study examines the association of depressive and anxiety symptoms with diet quality among university students while controlling for different demographic and other health and lifestyle factors. This cross-sectional study was carried out between April 2021 and June 2021 among a total of 440 (unweighted) university students. Diet quality was assessed using a 10-item mini-dietary assessment index tool. The depressive and anxiety symptoms of participants were measured using the validated Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder (GAD-7) scale, respectively. Multivariable logistic regression and mediation analyses were performed. In this study, 61.1% (95% CI: 56.6% to 65.7%) of university students' diet quality was good during the COVID-19 pandemic. Being a post-graduate student, an urban resident, having no depressive (AOR = 2.15, 95% CI: 1.20 to 3.84) and anxiety symptoms (AOR = 1.96, 95% CI: 1.07 to 3.59), no changes or improvement in appetite, and no changes in sleep duration were significantly associated with good diet quality among our study participants. Depressive and anxiety symptoms during COVID-19 had a significant effect on the diet quality of university students. Future public health policies need to be focused on improving the mental health and well-being of students particularly during pandemic situations to enhance their diet quality.

Visceral Adiposity Index and Lipid Accumulation Product as diagnostic markers of Metabolic Syndrome in South Indians with Polycystic Ovary Syndrome.

BACKGROUND: Cardiovascular disease (CVD) is one of the debilitating consequences of polycystic ovary syndrome (PCOS). Early diagnosis of metabolic syndrome (MetS) with a simple but accurate method can reduce the risk of progression to CVD in PCOS. AIMS: This study aimed to determine the accuracy of various anthropometric indices and lipid accumulation product (LAP), in assessing the risk of MetS in PCOS. SETTINGS AND DESIGN: This is a cross-sectional study including 150 PCOS women and 100 control subjects. MATERIALS AND METHODS: Anthropometric parameters were measured and calculated. Lipid profile, fasting plasma glucose (FPG), and insulin were estimated. MetS was detected according to the International Diabetes Federation criteria. STATISTICAL ANALYSIS: Logistic regression and receiver operating characteristic curve analysis were applied to determine the potential association of anthropometric indices such as body mass index, waist circumference (WC), waist-to-hip ratio, waist-to-height ratio, conicity index (CI), visceral adiposity index (VAI), abdominal volume index (AVI), body adiposity index (BAI), and a body shape index (ABSI) and LAP with MetS. RESULTS: In our study of PCOS women of the south Indian population, the prevalence of MetS was 59.3%, which was higher than other populations and the cutoff values of VAI and LAP were 6.05 and 53, respectively. VAI showed the strongest association with MetS, followed by diastolic blood pressure BP, FPG, and LAP. CONCLUSIONS: We recommend VAI and LAP as new indices for MetS diagnosis. As these indices exhibit population specificity, it is imperative that independent cutoffs are determined for every demographic population.

Assessment and Establishment of Correlation between Reactive Oxidation Species, Citric Acid, and Fructose Level in Infertile Male Individuals: A Machine-Learning Approach.

BACKGROUND: Biochemical complexity of seminal plasma and obesity has an important role in male infertility (MI); so far, it has not been possible to provide evidence of clinical significance for all of them. AIMS: Our goal here is to evaluate the correlation between biochemical markers with semen parameters, which might play a role in MI. STUDY SETTING AND DESIGN: We enlisted 100 infertile men as patients and 50 fertile men as controls to evaluate the sperm parameters and biochemical markers in ascertaining MI. MATERIALS AND METHODS: Semen analyses, seminal fructose, citric acid, and reactive oxidation species (ROS) were measured in 100 patients and 50 controls. STATISTICAL ANALYSIS: Descriptive statistics, an independent t-test, Pearson correlation, and machine-learning approaches were used to integrate the various biochemical and seminal parameters measured to quantify the inter-relatedness between these measurements. RESULTS: Pearson correlation results showed a significant positive correlation between body mass index (BMI) and fructose levels. Citric acid had a positive correlation with sperm count, morphology, motility, and volume but displayed a negative correlation with BMI and basal metabolic rate (BMR). However, BMI and BMR had a positive correlation with ROS. Sperm count, morphology, and motility were negative correlations with ROS. The machine-learning approach detected that pH was the most critical parameter with an inverse effect on citric acid, and BMI and motility were the most critical parameter for ROS. CONCLUSION: We recommend that evaluation of biochemical markers of seminal fluid may benefit in understanding the etiology of MI based on the functionality of accessory glands and ROS levels.

Positive association of sperm dysfunction in the pathogenesis of recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) is one of the most frustrating and difficult areas in reproductive medicine, because the aetiology is often unknown and there are few evidence-based diagnostic and treatment strategies. RPL diagnosis is mainly focused on the female partner. The male factor contributing in evaluation of RPL has been less investigated, it is restricted to karyotype and basic semen analysis, assessment of functionality of sperm is largely ignored. AIM AND OBJECTIVE: To investigate the role of sperm factors in RPL through regular semen analysis preceded with sperm function tests. MATERIALS AND METHODS: We performed a case control study of 95 males whose partner has experienced two or more pregnancy loss as case and 37 volunteers who had fathered child/children without the history of RPL as control group. Basic semen analysis and sperm function test (Nuclear chromatin decondensation {NCD}, Hypo osmotic swelling {HOS} and Acrosome intactness test {AIT} was performed. The results were analysed by performing Independent-sample t-test using SPSS (version 14.0). RESULTS: One individual had anatomical abnormality which was confirmed through trans-rectal ultrasound scanning and RPL group showed statistically significant (p<0.05) value for NCD, HOS and AIT and 36.8% of RPL individuals had reduced score for sperm count and motility. Less than 4% normal morphology was recorded in 16.8% individuals of RPL group. CONCLUSION: Our study revealed that the positive association of sperm dysfunction in RPL cases, hence male may be considered for a routine part of the evaluation along with his partner in the near future in order to achieve desirable outcome.

Role of phenylthiocarbamide as a genetic marker in predicting the predisposition of disease traits in humans.

The main objective of this study is to find out the genetic variation and predisposition of overweight/obese, smoking/alcoholism and thyroid disease traits among tasters and non-tasters in Mysore population, South India. Bitter-taste perception for phenylthiocarbamide (PTC) is a classically variable trait both within and between human populations. Many studies have reported that in world population, approximately 30% of them are PTC non-tasters and 70% are tasters. This investigation was conducted during the year 2009-2010 involving a total 1352 study subjects and divided into three different groups, considering the age ranging from 13 to 50 years. Phenylthiocarbamide taste sensitivity was measured by administering a freshly prepared 0.025% of phenylthiocarbamide solution using the Harris and Kalmus method with a slight modification and the results were recorded. In the first group of 100 obese/overweight children, 28% are taster and 72% are non-taster and among 100 control group 67% are tasters and 43% are non-tasters. In second group, out of 1152 individuals 710 (61.63%) are tasters and 442 (38.37%) are non-tasters including both males and females. In the third group, out of each 100 thyroid patients and the control group, tasters are significantly more frequent (61.41%) than the non-tasters (38.58%) in the control group, but a higher proportion of non-tasters are recorded among individuals with thyroid problems (68%) compared to tasters (32%). There is a significant higher incidence of PTC tasters than non-tasters among general population in this study. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of multifactorial disease and disorders.

Evaluation of acrosome intactness status in male infertility in Mysore, South India.

BACKGROUND AND OBJECTIVE: The objective of this study is to determine the status of acrosome intactness in different infertile conditions among men who have attended the Mediwave Fertility Research Center, Mysore, South India. MATERIALS AND METHODS: A total of 70 infertile and 20 control subjects were employed in the study. Infertile subjects were classified into different conditions according to the WHO protocol. The data obtained was statistically analyzed. RESULTS: In the present study, seven different infertile conditions were reported. For the acrosome intactness test, except oligospermia, all other conditions recorded a statistically significant value (P < 0.05) compared with the control group. CONCLUSIONS: The present study shows the decreased acrosomal enzyme activity in infertile males compared with fertile males. If diagnosed and treated earlier, it may help in the success of the in vitro fertilization technique.

Evolution of phenylthiocarbamide taster trait in Mysore, South India.

BACKGROUND: The ability to taste phenylthiocarbamide (PTC), a bitter chemical has long been known to be a heritable trait, which is being widely used for both genetic and anthropological studies. The frequency of taster and non-taster allele is found to vary in different populations. AIMS AND OBJECTIVE: To investigate the frequency of taster trait in Mysore, South India. MATERIALS AND METHODS: The present investigation was conducted in Mysore, South India during 2002 - 2003. About 3282 subjects irrespective of age, sex, religion, food habits, socio-economic status were randomly selected from various parts of the city and a total of 180 families, which included Christian (50), Hindu (61) and Muslim (69) were screened from different localities of the city. Harris and Kalmus method was used to assess the PTC taster and nontaster phenotype. RESULTS: It was found that tasters were significantly more frequent than nontasters in all the four categories. The incidence of tasters was more in unbiased category (85%) and less in Muslim category (58%). Investigations on PTC tasting in the families of three different religious groups revealed that the tasters were significantly more frequent than nontasters. It was also found that heterozygous father or mother for the taster genes with nontaster partner had taster and nontaster progenies in the ratio 1.0: 1.54 indicating the deviation in the segregation pattern of test cross. CONCLUSION: In Mysore, tasters are more frequent than nontasters. Variation in the frequency of nontaster allele in the religious groups could be due to inbreeding.

Possible risk factors for Down syndrome and sex chromosomal aneuploidy in Mysore, South India.

BACKGROUND: Down syndrome (DS) and sex chromosomal aneuploidy (SA) are common chromosomal anomalies causing congenital malformations and mental retardation in humans. The well-established risk factor, advanced maternal age, was not found in many of the DS and SA cases in India, while the other possible risk factors have not been well studied. In view of this, the present study has been made. MATERIALS AND METHODS: During the last 5 years, 150 clinically suspected DS and 25 SA cases were referred to our laboratory for chromosome investigation from major hospitals of Mysore city. Chromosome preparations were made from these patients after informed consent was obtained. Well-spread G-banded metaphase plates were analyzed by automated LEICA KARYO software. Two hundred and 100 randomly selected families belonging to different religions were used as controls for the DS and SA cases, respectively. Statistical analysis was carried out using logistic regression RESULTS: Out of the 150 cases of DS, 122 had free trisomy 21, two were mosaic trisomy 21, and one had translocation. Logistic regression of case-control study of DS children revealed that the odds ratio of uncle-niece marriages, or second cousin marriages, or parents lived in rural region, or exposure of the parents to chemicals, or parents education status, or habits (tobacco/ alcohol used) of father, or mother not undergone prenatal scanning, or mothers with previous abortions were significant when all the variables of that category were used one at a time. Exposure of the parents to chemicals, parents' educational status, habits (tobacco/alcohol use) of the father, mother not undergone prenatal scanning, and history of previous abortions were significant when all the variables of that category were used one at a time. Similarly, except for consanguinity, history of previous abortions, and mother not undergone prenatal scanning, all other factors showed significant odds ratios in SA cases. CONCLUSION: Besides the known risk factors, consanguinity, region (rural/urban) of residence of parents, exposure of parents to chemicals, educational status of parents, habits of father, prenatal scanning, and reproductive performance of mother are possible risk factors for chromosomal aneuploidy.

Influence of advanced age of maternal grandmothers on Down syndrome.

BACKGROUND: Down syndrome (DS) is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92-95%), mosaic trisomy 21 (2-4%) and translocation (3-4%). Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction. METHODS: We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression. RESULTS: Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years) born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds) of birth of DS baby increases by 30%. CONCLUSION: Besides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.