Introduction Recently, the expression of metallophosphoesterase-domain-containing protein 2 (MPPED2) was identified in cervical cancer. However, its precise role and correlation with other tumor suppressor proteins, such as p16INK4A, is not well studied in high-risk human papillomavirus (HPV) integrated human cervical carcinoma. Hence, in the present study, we try to see the expression of MPPED2 in human cervical carcinoma and its correlation with age and p16INK4A protein expression level. Methods The prospective study consists of 200 samples of 150 known cervical carcinoma and 50 controls. Histopathological evaluation, immunohistochemical staining, and semi-quantitative scoring of the intensity of proteins were performed. Statistical analysis was performed with the Shapiro-Wilk test, Spearman's rho correlation sig. (two-tailed), and Student's t-test. Results The data show that among the 150 cases, 136 (68.0%) cervical carcinoma tissues express the presence of high-risk HPV viral genome integration in the host cell. The expression of p16INK4A protein is higher in those tissues identified with high-risk HPV viral genomes. In contrast, the expression of MPPED2 protein is lesser or absent in those cervical tissues that have the higher expression of p16INK4A protein and vice versa. There is a significant correlation (p=0.000) between age and p16INK4A protein expression but not with MPPED2. A significant linear correlation (p=0.000) is found between the p16INK4A and MPPED2 proteins. Conclusion It may support the therapeutic application of MPPED2 protein to prevent cervical carcinoma progression in the near future.
Aim Study the effect of coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), on the placenta and in turn study its effects on pregnancy and newborn outcomes. Methods In this cross-sectional study, which was conducted in the term pregnant women who underwent delivery, their placentas were collected after delivery along with the mothers’ blood and cord blood. Results Among the 212 pregnant women recruited, the prevalence of marginal cord insertion (MCI) in the placentas after delivery, was found to be 23% (n=48). Among these 48 cases (n=48) with MCI, 58.33% (n=28) were COVID-19 positive. The placentas with MCI had significantly lower minimum placental circumference (probability value/p value=0.04) and significantly longer umbilical cord (p-value=0.05). COVID-19 antibodies transfer from the mother to the umbilical cord (C/M antibodies ratio) was observed to be lower, albeit insignificantly. Both the weight of newborns (p value=0.03) and their COVID-19 antibodies levels (p-value=0.05) were observed to be significantly lower in the MCI group. Univariate analysis shows that a body mass index (BMI) ≥ 23 of the mothers was significantly associated with abnormal MCI. Conclusion The prevalence of MCI was observed to be high in COVID-19-affected mothers in our study. MCI was associated with lower placental size, newborn weight, lesser transfer of COVID-19 antibodies from the mother to the fetus across the umbilical cord, and lower antibody levels in the cord blood when compared to maternal blood.
Background SARS-CoV-2 infection during pregnancy may cause adverse maternal, neonatal and placental outcomes. While tissue hypoxia is often reported in COVID-19 patients, pregnant women with anemia are suspected to be more prone to placental hypoxia-related injuries. Methods This hospital-based cross-sectional study was conducted between August-November 2021, during COVID-19 second wave in India. Term pregnant women (N=212) admitted to hospital for delivery were enrolled consecutively. Since hospital admission mandated negative RT-PCR test for SARS-CoV-2 virus, none had active infection. Data on socio-demography, COVID-19 history, maternal, obstetric, and neonatal outcomes were recorded. Pre-delivery maternal and post-delivery cord blood samples were tested for hematological parameters and SARS-CoV-2 IgG. Placentae were studied for histology. Results Of 212 women, 122 (58%) were seropositive for SARS-CoV-2 IgG, but none reported COVID-19 history; 134 (63.2%) were anemic. In seropositive women, hemoglobin ( p =0.04), total WBC ( p =0.009), lymphocytes ( p =0.005) and neutrophils ( p =0.02) were significantly higher, while ferritin was high, but not significant and neutrophils to lymphocytes ( p =0.12) and platelets to lymphocytes ratios ( p =0.03) were lower. Neonatal outcomes were similar. All RBC parameters and serum ferritin were significantly lower in anemic mothers but not in cord blood, except RDW that was significantly higher in both, maternal ( p =0.007) and cord ( p =0.008) blood from seropositive anemic group compared to other groups. Placental histology showed significant increase in villous hypervascularity ( p =0.000), dilated villous capillaries ( p =0.000), and syncytiotrophoblasts ( p =0.02) in seropositive group, typically suggesting placental hypoxia. Maternal anemia was not associated with any histological parameters. Univariate and multivariate logistic regression analyses of placental histopathological adverse outcomes showed strong association with SARS-CoV-2 seropositivity but not with maternal anemia. When adjusted for several covariates, including anemia, SARS-CoV-2 seropositivity emerged as independent risk factor for severe chorangiosis (AOR 8.74, 95% CI 3.51-21.76, p <0.000), dilated blood vessels (AOR 12.74, 95% CI 5.46-29.75, p <0.000), syncytiotrophoblasts (AOR 2.86, 95% CI 1.36-5.99, p =0.005) and villus agglutination (AOR 9.27, 95% CI 3.68-23.32, p <0.000). Conclusion Asymptomatic COVID-19 during pregnancy seemed to be associated with various abnormal placental histopathologic changes related to placental hypoxia independent of maternal anemia status. Our data supports an independent role of SARS-CoV-2 in causing placental hypoxia in pregnant women.
Background and aim: In India, total vitamin B12 (Vit B12) and its active form (active B12) have not been studied in mother’s blood and cord blood. We hypothesized that total and active B12 levels are sufficiently maintained in cord blood despite low levels in mothers. Methods: Two hundred term pregnant mother's blood and cord blood was collected and analyzed for total Vit B12 (radioimmunoassay method) and active B12 levels (enzyme-linked immunosorbent assay). Mean values of constant or continuous variables (hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV), white blood cells (WBC), and Vit B12) were compared in mother's blood and newborn cord blood using Student's t-test and multiple comparisons within the groups were carried out with ANOVA. Spearman's correlation (Vit B12) and multivariable backward regression analyses (height, weight, education, body mass index (BMI) and Hb, PCV, MCV, WBC, and Vit B12 levels) were also performed. Results: Total Vit 12 deficiency was highly prevalent at 89% and active B12 deficiency was 36.7% in mothers. Cord blood showed total Vit B12 deficiency prevalence of 53% and active B12 deficiency being 9.3%. Total Vit B12 ( p<0.001) and active B12 ( p<0.001) levels were significantly higher in cord blood when compared to mother's blood. In multivariate analysis, higher total and active B12 levels in mother's blood predicted higher levels of total and active B12 levels in cord blood. Conclusion: Our study showed higher prevalence of total and active Vit B12 deficiency in mothers compared to cord blood thus indicating their transfer to fetus irrespective of mother's status. Maternal Vit B12 levels affected cord blood Vit B12 levels.
Patients with comorbidities of obesity and diabetes are recognized to be at high risk of breast cancer development and face worse breast cancer outcomes. Though several reports showed the reinforced link between obesity, diabetes, and prediabetes with breast cancer, the underlying molecular mechanisms are still unknown. The present study aimed to investigate the underlying molecular link between increased risks of breast cancer due to coincident diabetes or obesity using a spontaneous obese rat model with impaired glucose tolerance (WNIN/GR-Ob rat). A single dose of solubilized DMBA suspension (40 mg/kg body weight) was orally administered to the animals at the age of 60 days to induce breast tumors. The tumor incidence, latency period, tumor frequency, and tumor volume were measured. Histology, immunohistochemistry, and immunoblotting were performed to evaluate the tumor morphology and expression levels of signal molecules. The development of mammary tumors in GR-Ob rats was characterized by early onset and shorter latency periods compared to control lean rats. While 62% of obese rats developed breast tumors, tumor development in lean rats was only 21%. Overexpression of ER, PR, Ki67, and p53 markers was observed in tumor tissues of obese rats in comparison with lean rats. The levels of the hallmarks of cell proliferation and angiogenesis involved in IGF-1/PI3K/Akt/GSK3β/β-catenin signaling pathway molecules were upregulated in obese rat breast tumors compared to lean rats. Furthermore, obesity with prediabetes is associated with changes in IGF-1 signaling and acts on PI3K/Akt/GSK3β/β-catenin signaling, which results in rapid cell proliferation and development of breast tumors in obese rats than the lean rats. These results indicate that tumor onset and development were faster in spontaneous obese rat models with impaired glucose tolerance than in their lean counterparts.
Objective: Our objective was to study the levels and relation between CD320 receptors in anaemic mothers in their last trimester of pregnancy and their newborns after birth. Methods: Association between CD320, VitB12, active B12 levels in mothers with anaemia were analysed before they underwent labor and in blood collected from their newborns after labor. Regression analysis was performed in order to assess the relation between the mothers and their neonatal vitamin CD320 levels in relation to their Vit B12 status. Results: Among the 200 pregnant mothers recruited, 59% were anaemic. CD320 levels were significantly higher in anaemic mothers (414.09 ±10.75 pg/ml) when compared with cord blood (372.25 ± 7.81 pg/ml). CD320 levels were higher in both mother and cord blood with Vit B12 deficiency, however, were lower in mothers with active B12 deficiency. CD320 levels in cord blood were positively associated with haemoglobin (r value 0.8, p value 0.42) of mothers and negatively with serum folate (r value -0.15; p value 0.23), Vit B12(r value -0.21; p value0.28) and active Vit B12 levels (r value -0.25; p value0.03) in mothers. Conclusion: CD320 levels in cord blood positively correlated with haemoglobin of mothers and negatively with folic acid and B12 status. A negative trend (p=0.0024) was observed between maternal and neonatal CD320 levels.
Introduction: Iron deficiency anemia is the most prevalent nutritional deficiency disorder in pregnant women. During pregnancy, nutrients, including iron, are transferred from the mother to the fetus through the placenta, in which the placental transport protein Ferroportin1 (FPN1) plays a crucial role. It has been frequently observed that developing fetus is immune to anemia despite the presence of anemia in the mother, the mechanisms underlying which have not been identified. We, therefore, planned the present study to explore the effect of maternal iron deficiency anemia on the expression of FPN1 in the placenta. Material and Methods: Two hundred pregnant women recruited were divided into anemic and nonanemic groups based on their predelivery hemoglobin levels (<11 g/dl and ≥11 g/dl, respectively). After delivery, placental expression of FPN1 was studied by immunohistochemistry and mRNA analysis, and neonatal anthropometry was performed. Results: Of the 200 women, 59% were anemic. FPN1 protein immunohistochemical staining in placenta showed a statistically significant increase with increasing severity of anemia. Similarly, placental mRNA expression levels of the FPN1 gene were observed to be higher in anemic mothers when compared with nonanemic mothers. Discussion and Conclusion: Thus, our study for the first time shows that maternal iron deficiency increases placental FPN1 protein and mRNA expression, thereby probably facilitating increased transport of iron from the mother to the fetus.
There is an increase in the incidence and prevalence of type-2 diabetes and obesity which leads to the structural and functional changes in myocardium leading to a lethal complication called diabetic cardiomyopathy (DCM). In the present study, we investigated the preventive effect of cinnamon (3% of Cinnamomum zeylanicum bark powder in AIN-93 diet for 3 months) feeding on DCM and the concerned mechanisms in a rodent model. Experimental diabetes was induced by a single intraperitoneal injection of 40 mg/kg b.w streptozotocin (STZ), 15 min after the ip administration of 60 mg/kg b.w of nicotinamide (NA) in Wistar-NIN (WNIN) male rats. The oxidative stress parameters were investigated by assessing superoxide dismutase (SOD), glutathione-s-transferase (GST) enzyme activity, protein carbonyls and malondialdehyde (MDA) levels. The histopathology of myocardium was analyzed by H&E and Masson's trichrome staining, and scanning electron microscopy. The changes in diabetic rat heart involved the altered left ventricular parietal pericardium, structural changes in myocardial cells, enhanced oxidative stress. Masson's trichrome and H&E staining have shown increased fibrosis, and perinuclear vacuolization in NA-STZ induced diabetic rat myocardium. Cinnamon feeding prevented the oxidative stress and myocardial alterations in the heart of diabetic rats. Taken together, these results suggest that cinnamon can effectively prevent the metabolic and structural changes in NA-STZ induced diabetic cardiomyopathy.
Introduction Cervical cancer is the fourth most frequent cancer in women worldwide, and it continues to be a big issue in developing countries. The current case-control study sought to determine the presence of high-risk human papillomaviruses (hr-HPV) in the development of cervical cancer, as well as their relationship with the cell cycle inhibitor gene p16INK4A in cervical cancer. Methods The association between p16INK4A protein and the presence of hr-HPV DNA in cervical lesions was explored in this study, which included 150 cervical cancer patients and 100 normal cervix samples. The immunohistochemistry approach was used to identify the expression of the p16INK4A protein, while the semi-quantitative polymerized chain reaction (PCR) method was used to identify the genomic identity of hr-HPV. Results About 90.67% (n=136) of the 150 case samples were found to be hr-HPV positive. Within the 136 HPV-positive samples, 45 (33.08%) show moderate expression of the p16INK4A protein, whereas 91 (66.91%) show overexpression, which is statistically significant (0.05). Among the 136 HPV-positive samples, 22.08% (N=30) were classified as having cervical intraepithelial neoplasia (CIN), with 56.66% (n=17) having CIN3, 36.66% (n=11) having CIN2, and 6.67% (n=2) having CIN1. Conclusion Based on the semi-quantitative immune staining scoring method of p16INK4A protein, genomic expression of HPV demonstrates that the expression of p16INK4A protein increases with the infectious load of the hr-HPV genome in the host cell. The result directly shows that immunostaining of the p16INK4A protein, in conjunction with the assessment of high-risk HPV in the host genome, will aid in the identification of cervical cancer in the cervix.
The CYP2R1 gene express the enzyme 25-hydroxylase, involved in the synthesis of major circulating vitamin D metabolite 25-hydroxyvitaminD [25(OH)D]. CYP2R1 gene variants have been reported to be associated with altered 25(OH)D level and associated with the development of active disease including tuberculosis (TB). The aim of the present study was to understand the association of rs10741657 (G/A) and rs2060793(A/G) CYP2R1 gene polymorphisms with tuberculosis susceptibility/protection in 104 Healthy controls (HCs) and 105 pulmonary tuberculosis (PTB) patients and to understand the influence of gene variants on 25(OH)D levels in South Indian population. Genotyping was performed by polymerase chain reaction trailed by restriction fragment length polymorphism (PCR-RFLP) method. Plasma samples were used for 25(OH)D level estimation by ELISA method. In rs10741657, under a dominant model (GG vs AG + AA), “AG” and “AA” genotypes as well as in rs2060793 under an overdominant model (GA vs GG + AA), “GA” genotype were significantly associated with protection to pulmonary tuberculosis. Based on sex, rs10741657 “AG” was significantly associated with protection and “GG” was significantly associated with susceptibility to TB in males. A sufficient vitamin D level was found with rs10741657 “AA” and “AG” genotypes and “GG” genotype associated with 81.8% of vitamin D deficiency in PTB individuals. In conclusion, rs10741657 “AG” and “AA” genotypes were associated with higher 25(OH)D levels and protection to TB. The lower 25(OH)D levels associated with rs10741657 “GG” genotype individuals may be recommended for higher vitamin D supplementation for better outcome from the disease. Further studies with large sample size are needed to confirm this study finding.
Nutritional intervention is a key strategy in the control and management of non-communicable diseases. Here, initially, we evaluated the effects of carrot juice (CJ) on some of the physical and biochemical parameters in rats fed with high-fructose diet, then in type 2 diabetic subjects. For the animal study, weanling male Wistar rats were given control (n = 6) or high fructose (HFr; n = 24) diet for 8 weeks. Then, the HFr group rats were subdivided into 4 groups (n = 6 in each) and continued either on HFr diet or shifted to control diet, with or without CJ (0.3 mg β-carotene) ingestion orally for 8 weeks. At the end, the ingestion of CJ reversed the HFr-induced adiposity (23 ± 1.6 vs 18 ± 1.1, P = .038), hypertriglyceridemia (182 ± 18.2 vs 90 ± 10.5 mg/dL, P <0.001), and hyperinsulinemia (81 ± 14.7 vs 40 ± 7.5 µU/mL, P = .014), while increased the retinol levels in liver (240 ± 38.4 vs 492 ± 61.2 µg/g, P = .002) and adipose tissue (1.8 ± 0.09 vs 2.5 ± 0.18 µg/g, P = .026). On the other hand, in the diabetic subjects (7 males and females each, n = 14) compared to their baseline, the daily consumption of 50 mL CJ (~2400 µg β-carotene) for 6 weeks significantly reduced the body weight (69.4 ± 4.13 vs 69.0 ± 4.09 kg, P = .014), BMI (27.4 ± 1.07 vs 27.2 ± 1.06 kg/m 2 , P = .007), and fat% (33.4 ± 1.87 vs 31.9 ± 2.13, P = .029) with an increase in plasma β-carotene levels (0.21 ± 0.045 vs 0.45 ± 0.089 µmol/L, P = .044). Although CJ increased the glucose (145 ± 10.4 vs 165 ± 11.4 mg/dL, P = .039), insulin, and glycated hemoglobin levels remained unaltered. In conclusion, the consumption of carrot juice reversed the HFr-induced metabolic abnormalities in a rat model and decreased body weight and BMI of diabetic subjects.
Background: During pregnancy, iron is transferred from mother to fetus with placental iron transport proteins (Transferrin receptor, Divalent metal transporter/DMT1, ferroportin/FPN1 and Zyklopen). The aim of the study was to evaluate the effect of maternal iron deficiency anemia on placental iron transporters. Study Design: Two hundred pregnant women, in third trimester of pregnancy were divided into anemic (Hemoglobin/Hb < 11g/dl) and non-anemic groups (Hb >= 11 g/dl). After delivery, placental expression of iron transport proteins were studied by immunohistochemistry and by mRNA analysis. Results: Of the 200 subjects, 59% were anemic. All 3 placental proteins showed statistically significant increase in immunohistochemical expression, proportionate to the severity of maternal anemia. The mRNA expression of DMT-1 gene was only significantly elevated in placentas of anemic mothers. Conclusion: Although in our study mRNA expression of only the DMT-1 gene was significantly high, immunohistochemically however all the 3 proteins showed significantly higher expression in placentas of anemic mothers.
In the present study, we investigated the effect of maternal iron deficiency anaemia (IDA) on expression of the newly discovered iron transporter, Zyklopen in term placenta, in 200 pregnant women. Placental expression of Zyklopen was studied by mRNA analysis and immunohistochemistry for the protein. In addition neonatal anthropometric parameters were also analysed. 58.8% of 200 subjects were anaemic. Both Zyklopen mRNA as well as protein expression in the placenta showed a statistically significant increase with increasing severity of anaemia. Although all the neonatal anthropometric parameters were lower in newborns of anaemic mothers, none showed any statistical significance. Zp mRNA levels did not show any significant correlation with newborn and placental parameters (except newborn skinfold thickness and head circumference). Similar to mRNA expression, Zp IHC expression correlated positively, albiet non-significantly, with newborn length and Hb levels, the correlation was however negative with birth weight, head circumference, mid-arm circumference unlike the mRNA expression, where it positively correlated with the above parameters. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both mRNA and protein levels in term placenta, in maternal IDA.IMPACT STATEMENTWhat is already known on this subject? Iron deficiency anaemia (IDA) in a pregnant mother can lead to anaemia in the developing foetus; which is frequently observed to be of lesser severity than that in the mother. Recently a copper-containing oxidase called Zyklopen was discovered which was involved in iron efflux in BeWo cells. The gene encoding Zyklopen has been identified with a putative C-terminal membrane-spanning sequence and high sequence identitical to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate multicopper ferroxidase (MCF). Protein expression of this new MCF was observed in multiple diverse mouse tissues, including placenta and mammary gland.What do the results of this study add? Zyklopen protein immunohistochemical expression showed a statistically significant increase with increasing severity of anaemia. Similarly, placental mRNA expression of the Zyklopen gene was observed to be higher in anaemic mothers when compared to non-anaemic mothers. Our study for the first time demonstrated a definite increase in expression of Zyklopen at both protein and mRNA levels in term placenta, in maternal IDA.What are the implications of these findings for clinical practice and/or further research? This study will help us to understand better, the increased potential for influx of iron from mother to foetus in the condition of maternal iron deficiency. This study will help to determine how placental iron transport proteins can be regulated in response to maternal and neonatal iron status and will further our existing knowledge on relationships between maternal and neonatal iron status and mechanisms by which placental iron transport is modified in relation to these parameters.
Background DNA repair systems play an important role in maintaining the integrity of the human genome. Deficiency in the repair capacity due to either mutations or inherited polymorphisms in DNA repair genes may contribute to variations in the DNA repair capacity and subsequently susceptibility to cancer. Objectives This study aimed to investigate the association between Excision repair cross-complementation groups 2 (ERCC2) single nucleotide polymorphisms (SNPs rs1799793 and rs13181) and the response to platinum-based chemotherapy among patients with oral squamous cell carcinoma (OSCC). Methodology Polymerase chain reaction‐based restriction fragment length polymorphism analysis was used to determine the polymorphism from a total of 150 OSCC patients and 150 normal tissues of same patients were collected as controls for this study. Results ERCC2 GA (Asp312Asn) AC (Lys751Gln) genotypes were significantly associated (p = 0.0001 and p = 0.0004, respectively) with OSCC patients, when compared with the controls. These findings suggest that potentially functional SNPs in ERCC2 may contribute to OSCC risk. This study highlights the genetic variant that might play a role in mediating susceptibility to OSCC in this population. An understanding of DNA repair gene polymorphisms might not only enable risk assessment, but also response to therapy, which target the DNA repair pathway.
Introduction:Iron deficiency anemia (IDA) is the most prevalent nutritional deficiency disorder in pregnant women. During pregnancy, placental transport protein Divalent metal transporter1 (DMT1) plays a crucial role in transit of iron across placenta. The developing fetus is observed to be immune to anemia despite presence of anemia in the mother. Hence, we planned the present study to explore the effect of maternal IDA on the expression of DMT1 in the placenta. Materials and methods:Two hundred pregnant women recruited, were divided into anemic and nonanemic groups based on their predelivery hemoglobin levels (<11 g/dL and >= 11 g/dL respectively). After delivery, placental expression of DMT1 was studied by immunohistochemistry and mRNA analysis and neonatal anthropometry was performed. Results:Of the 200 women recruited, 58.8% were anemic with 60.35% having moderate anemia. Most of the red cell parameters were observed to be higher in cord blood than mothers. DMT1 protein immunohistochemical expression showed a statistically significant increase with increasing severity of anemia. Similarly, placental mRNA expression levels of DMT1 gene were observed to be higher in anemic mothers in comparison with nonanemic mothers. Conclusion:Our study thus demonstrated a definite increase in expression of DMT1 at both protein and mRNA levels in term placenta, in maternal IDA.
Background and Objectives: Cisplatin is one of the major drugs that used in the treatment of oral cancer.Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink caused by platinum-based treatment. The aim of this study was to investigate the association between polymorphisms in ERCC1 (C118T & C8092A) genes and the response to cisplatin-based chemotherapy. Methods: ERCC1polymorphisms (C118T & C8092A) were studied using PCR-RFLP method from 150 OSCC patients as cases as well as 150 normal tissues from the same patients were collected as controls for this study. Results: Frequencies of ERCC1 C118C, C118T and T118T genotypes were 60%, 28% and 12% in OSCC patients and 78%, 19% and 3% in the controls, respectively. The C118T & T118T genotype had a 1.69 and 4.97 -folds increased risk for OSCC. Frequencies of ERCC1 C8092C, C8092A and A8092A were 78%, 18% and 4% in the OSCC patients and 89%, 10%, amd 1% in the controls, respectively. The C8092A genotype showed a 1.97-fold increased risk for OSCC. Interpretation & Conclusions: In conclusion, this study highlights the DNA repair gene polymorphisms that might play a role in mediating susceptibility to oral squamous cell carcinoma and cisplatin therapy. Our data suggest that the ERCC1 C118T, T118T and ERCC1 C8092A genotypes are genetic risk factors for Oral squamous cell carcinoma and ERCC1 118 C/T and C8092A polymorphisms have significant influence on clinical outcome.
Vitamin D deficiency is often associated with tuberculosis susceptibility. Variants of vitamin D binding protein gene are reported to be associated with blood circulating concentration of 25(OH)D levels. The aim of the present study was to understand the association of rs7041 (G/T) and rs4588 (C/A) polymorphisms with tuberculosis susceptibility/protection in 125 Healthy controls (HCs) and 125 pulmonary tuberculosis (PTB) patients and to understand whether the gene variants have any influence on 25(OH)D levels in South Indian population. The genotyping for both the polymorphisms were done by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) method. 25(OH)D levels were estimated by ELISA method. The results revealed that under codominant model, rs4588 'CA' genotype significantly associated with TB susceptibility [OR: 1.47 (0.85-2.55); p = 0.049] and associated with 47.4% 25(OH)D deficiency in PTB patients. Whereas, under recessive model ('AA' vs 'CC' + 'CA') rs4588 'AA' genotype significantly associated with TB protection [OR: 0.14 (0.02-1.29); p = 0.042]. Whereas in rs7041 polymorphism, under overdominant model ('TG' vs 'GG+'TT'), no association was found. Increased 25(OH)D levels were found with rs7041 "GG", and rs4588 "CC" genotype in HCs and PTB patients. Haplotypes 'TA' and 'TC' associated with susceptibility to TB in males compared with females ['TA' OR: 4.18 (1.84-9.49); 'TC' OR: 3.63 (1.34-9.84)]. The results suggest that the heterozygous genotype rs4588 "CA" significantly associated with susceptibility while rs4588 "AA" genotype significantly associated with TB protection. Gene variants with 25(OH)D deficiency revealed no significant association due to limited sample size. However, in rs7041 "TG" and rs4588 "CA" genotype was associated with 61.1% and 47.4% 25(OH)D deficiency (OR > 2.0) in PTB patients. Future studies with larger sample size are needed to confirm this study finding.
Obstructive sleep apnea is an outcome of obesity, resulting from abnormal upper airway structures. Our main objective was to assess the fat infiltration into the tongue of calorie-restricted rats and its consequences on upper airway obstruction in comparison with lean and obese rats. A total of 24 adults lean, obese and CR obese rats were included in the study. Body fat and lean body mass were determined by TOBEC, DXA measured fat depositions around the neck region, and radiographs of upper airway structure were analysed by digital X-ray. Ex vivo biochemistry was carried out for leptin, and lipids in blood/tissues, and fat infiltration by ORO staining. The tongue, masseter muscle fat, fibre and taste bud morphology was assessed by SEM. Body composition analysis showed higher body fat and low lean body mass in obese animals; DXA results showed excess fat around the neck region of obese rats. Higher triglyceride and reduced leptin levels were observed in CR obese rats compared to lean and obese rats. ORO and SEM analysis showed varying degree of fat accumulation among the groups. Tongue muscle fibres of obese rats showed rugged abnormal folding with an increase in width in comparison with calorie-restricted obese rats. The distance and width between the taste buds of calorie-restricted obese rats were reduced to the levels of lean rats. The calorie restriction in obese rats reduced the fat deposition around the neck and improves the upper airway structures, the morphology of tongue fibre and increased the stiffness of the tongue, thereby reducing the risk of obstructive sleep apnea.
Background: Food allergy (FA) is a chronic condition of emerging global concern. Surveys have been conducted in numerous countries to assess physician knowledge, attitude, and practices (KAP) pertaining to FA and anaphylaxis, and substantial deficits in their KAP were identified. Objective: To assess the KAP of medical clinicians in Hyderabad, India, with respect to FA and anaphylaxis. Methods: A regionally representative sample of 570 physicians including 113 general practitioners, 123 pediatricians, 110 pulmonologists, 113 dermatologists, and 111 gastroenterologists were recruited from all major institutions in Hyderabad, India. A validated questionnaire was used to assess their KAP. Results: Overall, 90% of questions were correctly answered and differences emerged with respect to specific items, namely the following: (1) the lateral thigh being the preferred location for epinephrine administration (P = .001); (2) a positive skin prick test or radioallergosorbent test is sufficient for FA diagnosis (P = .04); and (3) the appropriate epinephrine dose for a 27-kg child (P = .006). Approximately 95% of the participants in each group were confident in their ability to care for patients with FA, yet 91% desired additional periodic FA training sessions. Conclusion: Survey findings suggest that although FA knowledge among South Indian clinicians seems high across all major specialties who care for patients with FA, there are differences in the level of knowledge among them, which in turn reflects the differences in attitude and approach toward their patients. These FA care providers still desire to further participate in continuing medical education efforts in the field of food allergy. Efforts to provide periodic training and education for all FA clinical care providers remain vital in South India. (C) 2020 Published by Elsevier Inc. on behalf of American College of Allergy, Asthma & Immunology.
Retinopathy is one of the micro vascular complications of diabetes and can also be observed in pre-diabetic state. However, there are only limited studies available on the pathophysiology of retinopathy in pre-diabetic state and its preventive strategies. In this study, we investigated the retinal functional, structural and molecular alterations using high fructose (HF) induced pre-diabetic rat model and also the protective role of garlic. Feeding of HF to Wistar NIN (WNIN) rats had developed insulin resistance (IR) and impaired glucose tolerance (IGT) by three months, while retinal functional abnormalities by ten months as evidenced by decrease of Electroretinogram (ERG) scotopic, photopic b-wave amplitudes, oscillatory potentials (OPs) when compared to controls. Supplementation of garlic (3%) to HF+G group rats had marginally protected these changes. Elevated expression of glial fibrillary acidic protein (GFAP), vascular endothelial growth factor (VEGF), aldose reductase (AR) and decreased rhodopsin (Rho) in HF group rats as evidenced by immunohistochemistry, immunoblot methods, which were further supported by gene expression studies, indicate the initiation of retinal abnormalities. Increased immunefluorescence signal of carboxymethyl lysine (CML-KLH) and 4-hydroxynanoenol (4-HNE) in retina of HF group rats indicate the association of glycation and oxidative stress, respectively. Early intervention of garlic to HF+G group rats attenuated retinal functional, structural, and molecular abnormalities.