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From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease.
Kumari, N, Kumari, R, Dua, A, Singh, M, Kumar, R, Singh, P, Duyar-Ayerdi, S, Pradeep, S, Ojesina, AI, Kumar, R
Molecular nutrition & food research. 2024;(6):e2300688
Abstract
The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like β-glucuronidases and β-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders.
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Post-operative chyle leak following nephrectomy: Inference from tertiary care center and review of literature.
Sarangi, SS, Bhirud, DP, Sandhu, AS, Aggarwal, A, Singh, M, Navriya, SC, Choudhary, GR
Urologia. 2024;(1):33-41
Abstract
OBJECTIVES Lymphatic channels (LC) are not as prominent as blood vessels, so they tend to get damaged during surgical procedures. It can present with chyle leak in the postoperative period. We aimed to study the occurrence of chyle leak in patients undergoing nephrectomy and its management. METHODS During the period of January 2021 and January 2023, 158 adult patients underwent nephrectomy for various reasons like non-functioning kidney, donor nephrectomy, and malignancy. We retrospectively analyzed data of patients who had chyle leak after nephrectomies. RESULTS Eight patients out of the 158 patients (5.06%) undergoing nephrectomy developed chyle leak. One out of these eight patients underwent nephrectomy by open approach while seven underwent laparoscopic approach. All eight patients who had chyle leak undergone left sided nephrectomy. Six patients of chyle leak could be managed with dietary modification while two patients needed octreotide therapy for treatment. Higher Body Mass Index (BMI; p-value = 0.012), left sides nephrectomy (p-value = 0.013), h/o pyelonephritis (p-value = 0.005) were associated with higher incidence of chyle leak on univariate analysis. While on multivariate analysis no factor was found to be independently associated with chyle leak. Hospital stay was significantly prolonged in patients with chyle leak (p-value = 0.007). CONCLUSION Chyle leak is not a very rare complication after nephrectomy. Patients with higher BMI, who undergo left sided nephrectomies and patients who had history of pyelonephritis or infectious complications had higher incidence of chyle leak. Most cases can be managed with conservative management (CM). Chyle leak is associated with a prolonged hospital stay.
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The role of the mitochondrial trans-sulfuration in cerebro-cardio renal dysfunction during trisomy down syndrome.
Pushpakumar, S, Singh, M, Sen, U, Tyagi, N, Tyagi, SC
Molecular and cellular biochemistry. 2024;(4):825-829
Abstract
One in 700 children is born with the down syndrome (DS). In DS, there is an extra copy of X chromosome 21 (trisomy). Interestingly, the chromosome 21 also contains an extra copy of the cystathionine beta synthase (CBS) gene. The CBS activity is known to contribute in mitochondrial sulfur metabolism via trans-sulfuration pathway. We hypothesize that due to an extra copy of the CBS gene there is hyper trans-sulfuration in DS. We believe that understanding the mechanism of hyper trans-sulfuration during DS will be important in improving the quality of DS patients and towards developing new treatment strategies. We know that folic acid "1-carbon" metabolism (FOCM) cycle transfers the "1-carbon" methyl group to DNA (H3K4) via conversion of s-adenosyl methionine (SAM) to s-adenosyl homocysteine (SAH) by DNMTs (the gene writers). The demethylation reaction is carried out by ten-eleven translocation methylcytosine dioxygenases (TETs; the gene erasers) through epigenetics thus turning the genes off/on and opening the chromatin by altering the acetylation/HDAC ratio. The S-adenosyl homocysteine hydrolase (SAHH) hydrolyzes SAH to homocysteine (Hcy) and adenosine. The Hcy is converted to cystathionine, cysteine and hydrogen sulfide (H2S) via CBS/cystathioneγ lyase (CSE)/3-mercaptopyruvate sulfurtransferase (3MST) pathways. Adenosine by deaminase is converted to inosine and then to uric acid. All these molecules remain high in DS patients. H2S is a potent inhibitor of mitochondrial complexes I-IV, and regulated by UCP1. Therefore, decreased UCP1 levels and ATP production can ensue in DS subjects. Interestingly, children born with DS show elevated levels of CBS/CSE/3MST/Superoxide dismutase (SOD)/cystathionine/cysteine/H2S. We opine that increased levels of epigenetic gene writers (DNMTs) and decreased in gene erasers (TETs) activity cause folic acid exhaustion, leading to an increase in trans-sulphuration by CBS/CSE/3MST/SOD pathways. Thus, it is important to determine whether SIRT3 (inhibitor of HDAC3) can decrease the trans-sulfuration activity in DS patients. Since there is an increase in H3K4 and HDAC3 via epigenetics in DS, we propose that sirtuin-3 (Sirt3) may decrease H3K4 and HDAC3 and hence may be able to decrease the trans-sulfuration in DS. It would be worth to determine whether the lactobacillus, a folic acid producing probiotic, mitigates hyper-trans-sulphuration pathway in DS subjects. Further, as we know that in DS patients the folic acid is exhausted due to increase in CBS, Hcy and re-methylation. In this context, we suggest that folic acid producing probiotics such as lactobacillus might be able to improve re-methylation process and hence may help decrease the trans-sulfuration pathway in the DS patients.
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A randomized controlled trial of an oral probiotic to reduce antepartum group B Streptococcus colonization and gastrointestinal symptoms.
Hanson, L, VandeVusse, L, Forgie, M, Malloy, E, Singh, M, Scherer, M, Kleber, D, Dixon, J, Hryckowian, AJ, Safdar, N
American journal of obstetrics & gynecology MFM. 2023;5(1):100748
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Plain language summary
Streptococcus agalactiae (or group B Streptococcus [GBS]) is an encapsulated, gram-positive, beta-haemolytic anaerobe that asymptomatically colonizes the genitourinary tract. Vertical transmission of GBS during normal vaginal birth can lead to neonatal colonization and risk for early-onset GBS disease. The aim of this study was to present the findings of a phase II, double-blind, randomised, placebo-controlled trial of an antenatal probiotic intervention to reduce GBS colonization. A secondary aim was to determine if the probiotic intervention reduces gastrointestinal (GI) symptoms of pregnancy. Participants (n=107) were randomly assigned to one of the two groups: probiotic intervention (n=55) or placebo group (n=54). Results show that: - there weren’t any significant differences between the groups in demographic characteristics, perinatal or neonatal outcomes, or intrapartum antibiotic prophylaxis doses. - there wasn’t any significant difference between groups in the presence of the probiotic bacteria on the rectal swabs, whereas the vaginal swabs showed a trend toward greater presence in probiotic group participants. - more probiotic participants took antenatal antibiotics (5/39) compared with controls (1/44). Authors conclude that probiotic bacteria colonisation of the genitourinary tract occurred more in the intervention group than in the control group and significantly reduced GI symptoms of pregnancy.
Abstract
BACKGROUND Probiotics have been suggested as a strategy to reduce antenatal group B Streptococcus colonization. Although probiotics are known to improve gastrointestinal symptoms, this has not been studied during pregnancy. OBJECTIVE This study aimed to evaluate the efficacy of a probiotic to reduce: (1) standard-of-care antenatal group B Streptococcus colonization and colony counts and (2) gastrointestinal symptoms of pregnancy. STUDY DESIGN In a double-blind fashion, 109 healthy adult pregnant people were randomized to Florajen3 probiotic or placebo capsules once daily from 28 weeks' gestation until labor onset. Baseline vaginal and rectal study swabs for group B Streptococcus colony-forming units and microbiome analysis were collected at 28 and 36 weeks' gestation. Standard-of-care vaginal to rectal group B Streptococcus swabs were collected from all participants at 36 weeks' gestation and determined the need for intrapartum antibiotic prophylaxis. Data collection included solicitation of adverse events, demographic information, Antepartum Gastrointestinal Symptom Assessment score, yogurt ingestion, sexual activity, and vaginal cleaning practices. RESULTS A total of 83 participants completed the study to 36 weeks' gestation with no adverse events. Standard-of-care group B Streptococcus colonization was 20.4% in the control group and 15.4% in probiotic group participants (-5%; P=.73). The relative risk for positive standard-of-care vaginal-rectal group B Streptococcus colonization was 1.33 (95% confidence interval, 0.5-3.40) times higher in the control group than in the probiotic group (P=.55). There were no differences in median vaginal (P=.16) or rectal (P=.20) group B streptococcus colony-forming units at baseline or at 36 weeks (vaginal P>.999; rectal P=.56). Antepartum Gastrointestinal Symptom Assessment scores were similar at baseline (P=.19), but significantly decreased in probiotic group participants at 36 weeks (P=.02). No covariates significantly altered group B Streptococcus colonization. Significantly more Florajen3 bacteria components were recovered from the vaginal-rectal samples of probiotic group participants (32%; P=.04) compared with controls. CONCLUSION The findings of this study provided insufficient evidence for the clinical application of the Florajen3 probiotic intervention to reduce standard-of-care vaginal-rectal group B Streptococcus colonization. The prevalence of group B Streptococcus was lower than expected in the study population, and intervention adherence was poor. Probiotic bacteria colonization of the genitourinary tract occurred more in intervention group participants than in controls and significantly reduced gastrointestinal symptoms of pregnancy.
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Targeting monocarboxylate transporters (MCTs) in cancer: How close are we to the clinics?
Singh, M, Afonso, J, Sharma, D, Gupta, R, Kumar, V, Rani, R, Baltazar, F, Kumar, V
Seminars in cancer biology. 2023;:1-14
Abstract
As a result of metabolic reprogramming, cancer cells display high rates of glycolysis, causing an excess production of lactate along with an increase in extracellular acidity. Proton-linked monocarboxylate transporters (MCTs) are crucial in the maintenance of this metabolic phenotype, by mediating the proton-coupled lactate flux across cell membranes, also contributing to cancer cell pH regulation. Among the proteins codified by the SLC16 gene family, MCT1 and MCT4 isoforms are the most explored in cancers, being overexpressed in many cancer types, from solid tumours to haematological malignancies. Similarly to what occurs in particular physiological settings, MCT1 and MCT4 are able to mediate lactate shuttles among cancer cells, and also between cancer and stromal cells in the tumour microenvironment. This form of metabolic cooperation is responsible for important cancer aggressiveness features, such as cell proliferation, survival, angiogenesis, migration, invasion, metastasis, immune tolerance and therapy resistance. The growing understanding of MCT functions and regulation is offering a new path to the design of novel inhibitors that can be foreseen in clinical practices. This review provides an overview of the role of MCT isoforms in cancer and summarizes the recent advances in their pharmacological targeting, highlighting the potential of new potent and selective MCT1 and/or MCT4 inhibitors in cancer therapeutics, and anticipating its inclusion in clinical practice.
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Effectiveness of Nurse-led Lifestyle Modification Intervention on Obesity Among Young Women in India.
Shaji, P, Singh, M, Sahu, B, Arulappan, J
SAGE open nursing. 2023;:23779608231186705
Abstract
BACKGROUND Obesity management in young women necessitates interventions that include dietary modification and physical exercise. High-intensity lifestyle modification is effective in managing obesity in young women. OBJECTIVES The study determined the effectiveness of a nurse-led lifestyle modification intervention (NLLMI) on obesity among young women in India. METHODS The study adopted a quasi-experimental pre- and post-interventional control group research design. The study was conducted among obese young women in the communities of Jabalpur, Madhya Pradesh, India. The participants were selected using convenient sampling technique. The sample included 150 women in the study group and 150 in the control group. The NLLMI comprising of exercises and dietary modifications were taught to the participants for 30 min three times a week for 24 weeks. Thereafter, they were encouraged to follow the diet and perform the exercises on their own for the next 12 weeks. Practice diary was maintained by the participants and they were encouraged to continue the intervention through the phone. The participants in the control group did not engage in the NLLMI until the post-test. However, they did receive the same NLLMI after the trial was over. RESULTS There was a high statistically significant difference (p = 0.001) between the study group and the control group the after 12th and 24th weeks of NLLMI. The study group had a significant reduction in BMI after the intervention. CONCLUSIONS Young obese women may benefit from a NLLMI if they regularly follow the healthy eating habits and physical exercise.
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Quality Standards and Pharmacological Interventions of Natural Oils: Current Scenario and Future Perspectives.
Ali, S, Ekbbal, R, Salar, S, Yasheshwar, , Ali, SA, Jaiswal, AK, Singh, M, Yadav, DK, Kumar, S, Gaurav,
ACS omega. 2023;(43):39945-39963
Abstract
Medicinal plants are rich sources of natural oils such as essential and fixed oils used traditionally for nutritive as well as medicinal purposes. Most of the traditional formulations or phytopharmaceutical formulations contain oil as the main ingredient due to their own therapeutic applications and thus mitigating several pathogeneses such as fungal/bacterial/viral infection, gout, psoriasis, analgesic, antioxidant, skin infection, etc. Due to the lack of quality standards and progressive adulteration in the natural oils, their therapeutic efficacy is continuously deteriorated. To develop quality standards and validate scientific aspects on essential oils, several chromatographic and spectroscopic techniques such as HPTLC, HPLC, NMR, LC-MS, and GC-MS have been termed as the choices of techniques for better exploration of metabolites, hence sustaining the authenticity of the essential oils. In this review, chemical profiling and quality control aspects of essential or fixed oils have been explored from previously reported literature in reputed journals. Methods of chemical profiling, possible identified metabolites in essential oils, and their therapeutic applications have been described. The outcome of the review reveals that GC-MS/MS, LC-MS/MS, and NMR-based chromatographic and spectroscopic techniques are the most liable, economic, precise, and accurate techniques for determining the spuriousness or adulteration of oils based on their qualitative and quantitative chemical profiling studies. This review occupies the extensive information about the quality standards of several oils obtained from natural sources for their regulatory aspects via providing the detailed methods used in chemoprofiling techniques. Hence, this review helps researchers in further therapeutic exploration as well as quality-based standardization for their regulatory purpose.
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Neutrophil Extracellular Traps and NLRP3 Inflammasome: A Disturbing Duo in Atherosclerosis, Inflammation and Atherothrombosis.
Singh, P, Kumar, N, Singh, M, Kaur, M, Singh, G, Narang, A, Kanwal, A, Sharma, K, Singh, B, Napoli, MD, et al
Vaccines. 2023;(2)
Abstract
Atherosclerosis is the formation of plaque within arteries due to overt assemblage of fats, cholesterol and fibrous material causing a blockage of the free flow of blood leading to ischemia. It is harshly impinging on health statistics worldwide because of being principal cause of high morbidity and mortality for several diseases including rheumatological, heart and brain disorders. Atherosclerosis is perpetuated by pro-inflammatory and exacerbated by pro-coagulatory mediators. Besides several other pathways, the formation of neutrophil extracellular traps (NETs) and the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contribute significantly to the initiation and propagation of atherosclerotic plaque for its worst outcomes. The present review highlights the contribution of these two disturbing processes in atherosclerosis, inflammation and atherothrombosis in their individual as well as collaborative manner.
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Ocular manifestations of common pulmonary diseases: a narrative review.
Singh, M, Deokar, K, Sinha, BP, Keena, M, Desai, G
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace. 2023;(1)
Abstract
Several pulmonary disorders can cause ocular involvement. Understanding these manifestations is critical for early diagnosis and treatment. Hence, we set out to examine the most common ocular manifestations of asthma, chronic obstructive pulmonary disease (COPD), sarcoidosis, obstructive sleep apnea (OSA), and lung cancer. Allergic keratoconjunctivitis and dry eye are two ocular manifestations of bronchial asthma. The inhaled corticosteroids used to treat asthma can cause cataract formation. COPD is associated with ocular microvascular changes as a result of chronic hypoxia and systemic inflammation spillover into the eyes. Its clinical significance, however, is unknown. Ocular involvement is common in sarcoidosis, occurring in 20% of cases of pulmonary sarcoidosis. It can affect nearly any anatomical structure of the eye. Obstructive sleep apnea has been linked to floppy eye syndrome, glaucoma, non-arteritic anterior ischemic optic neuropathy, keratoconus, retinal vein occlusion, and central serous retinopathy, according to research. However, while an association has been established, causality has yet to be established. The effect of positive airway pressure (PAP) therapy used to treat OSA on the aforementioned ocular conditions is unknown. PAP therapy can cause eye irritation and dryness. Lung cancer can affect the eyes through direct nerve invasion, ocular metastasis, or as part of a paraneoplastic syndrome. The goal of this narrative review is to raise awareness about the link between ocular and pulmonary disorders in order to aid in the early detection and treatment of these conditions.
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10.
Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia.
Das, RR, Singh, M, Naik, SS
The Cochrane database of systematic reviews. 2023;(1):CD011597
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Abstract
BACKGROUND Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases children's risk of developing pneumonia. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited. This is an update of a Cochrane Review first published in 2018. OBJECTIVES To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, and two trial registries on 28 December 2021. We applied no language restrictions. SELECTION CRITERIA We included randomised controlled trials (RCTs) that compared vitamin D supplementation with placebo in children (aged one month to five years) hospitalised with acute community-acquired pneumonia, as defined by the World Health Organization (WHO) acute respiratory infection guidelines. For this update, we reappraised eligible trials according to research integrity criteria, excluding RCTs published from April 2018 that were not prospectively registered in a trials registry according to WHO or Clinical Trials Registry - India (CTRI) guidelines (it was not mandatory to register clinical trials in India before April 2018). DATA COLLECTION AND ANALYSIS Two review authors independently assessed trials for inclusion and extracted data. For dichotomous data, we extracted the number of participants experiencing the outcome and the total number of participants in each treatment group. For continuous data, we used the arithmetic mean and standard deviation (SD) for each treatment group together with number of participants in each group. We used standard methodological procedures expected by Cochrane. MAIN RESULTS In this update, we included three new trials involving 468 children, bringing the total number of trials to seven, with 1601 children (631 with pneumonia and 970 with severe or very severe pneumonia). We categorised three previously included studies and three new studies as 'awaiting classification' based on the research integrity screen. Five trials used a single bolus dose of vitamin D (300,000 IU in one trial and 100,000 IU in four trials) at the onset of illness or within 24 hours of hospital admission; one used a daily dose of oral vitamin D (1000 IU for children aged up to one year and 2000 IU for children aged over one year) for five days; and one used variable doses (on day 1, 20,000 IU in children younger than six months, 50,000 IU in children aged six to 12 months, and 100,000 IU in children aged 13 to 59 months; followed by 10,000 IU/day for four days or until discharge). Three trials performed microbiological diagnosis of pneumonia, radiological diagnosis of pneumonia, or both. Vitamin D probably has little or no effect on the time to resolution of acute illness (mean difference (MD) -1.28 hours, 95% confidence interval (CI) -5.47 to 2.91; 5 trials, 1188 children; moderate-certainty evidence). We do not know if vitamin D has an effect on the duration of hospitalisation (MD 4.96 hours, 95% CI -8.28 to 18.21; 5 trials, 1023 children; very low-certainty evidence). We do not know if vitamin D has an effect on mortality rate (risk ratio (RR) 0.69, 95% CI 0.44 to 1.07; 3 trials, 584 children; low-certainty evidence). The trials reported no major adverse events. According to GRADE criteria, the evidence was of very low-to-moderate certainty for all outcomes, owing to serious trial limitations, inconsistency, indirectness, and imprecision. Three trials received funding: one from the New Zealand Aid Corporation, one from an institutional grant, and one from multigovernment organisations (Bangladesh, Sweden, and UK). The remaining four trials were unfunded. AUTHORS' CONCLUSIONS Based on the available evidence, we are uncertain whether vitamin D supplementation has important effects on outcomes of acute pneumonia when used as an adjunct to antibiotics. The trials reported no major adverse events. Uncertainty in the evidence is due to imprecision, risk of bias, inconsistency, and indirectness.