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1.
Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.
Monangi, NK, Xu, H, Fan, YM, Khanam, R, Khan, W, Deb, S, Pervin, J, Price, JT, Kaur, L, , , et al
The American journal of clinical nutrition. 2024;(1):221-231
Abstract
BACKGROUND Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). OBJECTIVES This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. METHODS Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. RESULTS The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. CONCLUSIONS Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.
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2.
Unveiling the impact of Aging on BBB and Alzheimer's disease: Factors and Therapeutic implications.
Jha, NK, Kumar Nelson, V, Nuli, MV, Kanna, S, Gahtani, RM, Hani, U, Singh, AK, Gupta, S, Abomughaid, MM, Abomughayedh, AM, et al
Ageing research reviews. 2024;:102224
Abstract
Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble β-amyloid peptide (Aβ) and neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD.
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3.
Psychedelics for alzheimer's disease-related dementia: Unveiling therapeutic possibilities and pathways.
Sinha, JK, Trisal, A, Ghosh, S, Gupta, S, Singh, KK, Han, SS, Mahapatra, M, Abomughaid, MM, Abomughayedh, AM, Almutary, AG, et al
Ageing research reviews. 2024;:102211
Abstract
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly dementia, have not been fully explored. In recent years, studies have revealed the modulatory and beneficial effects of psychedelics in the context of dementia, specifically Alzheimer's disease (AD)-related dementia, which lacks a definitive cure. Psychedelics such as N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and Psilocybin have shown potential in mitigating the effects of this debilitating disease. These compounds not only target neurotransmitter imbalances but also act at the molecular level to modulate signalling pathways in AD, including the brain-derived neurotrophic factor signalling pathway and the subsequent activation of mammalian target of rapamycin and other autophagy regulators. Therefore, the controlled and dose-dependent administration of psychedelics represents a novel therapeutic intervention worth exploring and considering for the development of drugs for the treatment of AD-related dementia. In this article, we critically examined the literature that sheds light on the therapeutic possibilities and pathways of psychedelics for AD-related dementia. While this emerging field of research holds great promise, further studies are necessary to elucidate the long-term safety, efficacy, and optimal treatment protocols. Ultimately, the integration of psychedelics into the current treatment paradigm may provide a transformative approach for addressing the unmet needs of individuals living with AD-related dementia and their caregivers.
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4.
Effectiveness of peer-led intervention in control of non-communicable diseases in rural areas of Khordha district: study protocol for a cluster randomized controlled trial.
Behera, P, Patro, BK, Singh, AK, Dora, S, Bandhopadhyay, D, Saharia, GK, Dey, A, Behera, SM, Subba, SH
Trials. 2024;(1):22
Abstract
BACKGROUND The main contributors to death and disability from chronic illnesses in developing nations are elevated blood pressure (hypertension), blood sugar (diabetes mellitus), and blood cholesterol (dyslipidaemia). Even though there are affordable treatments, the treatment gap for these conditions is still significant. Few pilot studies from industrialized nations discuss the value of peer-led interventions for achieving community-level management of blood pressure and blood sugar. This study aims to evaluate the effectiveness of peer-led intervention compared to standard care in achieving control of selected non-communicable diseases (NCDs) in Indian context at 1 year of intervention among people of 30-60 years with hypertension and/or diabetes mellitus and/or dyslipidaemia. METHODS A cluster-randomized controlled trial will be conducted in villages of two rural blocks of the Khordha district of Odisha from August 2023 to December 2024. A total of 720 eligible participants (360 in the intervention group and 360 in the control group) will be recruited and randomized into two study arms. The participants in the intervention arm will receive a peer-led intervention model for 6 months in addition to standard care. The sessions will be based on the six domains of NCDs - self-care, follow-up care, medication, physical activity, diet, limiting substance use, mental health and co-morbidities. The mean reduction in blood pressure, HbA1C, and blood cholesterol in the intervention arm compared to the standard care arm will be the main outcome. DISCUSSION The increasing burden of NCDs demands for newer strategies for management. Peer-led interventions have proven to be useful at the international level. Incorporating it in India will have remarkable results in controlling NCDs. TRIAL REGISTRATION Clinical Trial Registry of India (CTRI) CTRI/2023/02/050022. Registered on 23 February 2023.
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5.
Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity.
Rana, HK, Singh, AK, Kumar, R, Pandey, AK
Naunyn-Schmiedeberg's archives of pharmacology. 2024;(3):1251-1273
Abstract
Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium which causes tuberculosis (TB). TB control programmes are facing threats from drug resistance. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains need longer and more expensive treatment with many medications resulting in more adverse effects and decreased chances of treatment outcomes. The World Health Organization (WHO) has emphasised the development of not just new individual anti-TB drugs, but also novel medication regimens as an alternative treatment option for the drug-resistant Mtb strains. Many plants, as well as marine creatures (sponge; Haliclona sp.) and fungi, have been continuously used to treat TB in various traditional treatment systems around the world, providing an almost limitless supply of active components. Natural products, in addition to their anti-mycobacterial action, can be used as adjuvant therapy to increase the efficacy of conventional anti-mycobacterial medications, reduce their side effects, and reverse MDR Mtb strain due to Mycobacterium's genetic flexibility and environmental adaptation. Several natural compounds such as quercetin, ursolic acid, berberine, thymoquinone, curcumin, phloretin, and propolis have shown potential anti-mycobacterial efficacy and are still being explored in preclinical and clinical investigations for confirmation of their efficacy and safety as anti-TB medication. However, more high-level randomized clinical trials are desperately required. The current review provides an overview of drug-resistant TB along with the latest anti-TB medications, drug-induced hepatotoxicity and oxidative stress. Further, the role and mechanisms of action of first and second-line anti-TB drugs and new drugs have been highlighted. Finally, the role of natural compounds as anti-TB medication and hepatoprotectants have been described and their mechanisms discussed.
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6.
Cadmium toxicity: its' uptake and retaliation by plant defence system and ja signaling.
Kaushik, S, Ranjan, A, Sidhu, A, Singh, AK, Sirhindi, G
Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2024
Abstract
Cadmium (Cd+2) renders multifarious environmental stresses and highly toxic to nearly all living organisms including plants. Cd causes toxicity by unnecessary augmentation of ROS that targets essential molecules and fundamental processes in plants. In response, plants outfitted a repertory of mechanisms to offset Cd toxicity. The main elements of these are Cd chelation, sequestration into vacuoles, and adjustment of Cd uptake by transporters and escalation of antioxidative mechanism. Signal molecules like phytohormones and reactive oxygen species (ROS) activate the MAPK cascade, the activation of the antioxidant system andsynergistic crosstalk between different signal molecules in order to regulate plant responses to Cd toxicity. Transcription factors like WRKY, MYB, bHLH, bZIP, ERF, NAC etc., located downstream of MAPK, and are key factors in regulating Cd toxicity responses in plants. Apart from this, MAPK and Ca2+signaling also have a salient involvement in rectifying Cd stress in plants. This review highlighted the mechanism of Cd uptake, translocation, detoxification and the key role of defense system, MAPKs, Ca2+ signals and jasmonic acid in retaliating Cd toxicity via synchronous management of various other regulators and signaling components involved under stress condition.
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7.
Efficacy and safety of imeglimin in type 2 diabetes: A systematic review and meta-analysis of randomized placebo-controlled trials.
Singh, AK, Singh, A, Singh, R, Misra, A
Diabetes & metabolic syndrome. 2023;(2):102710
Abstract
BACKGROUND & AIMS Imeglimin is a novel new oral compound recently approved for treating type 2 diabetes (T2D) in India. We conducted a systematic review and meta-analysis to evaluate the efficacy of imeglimin in people with T2D in the approved dose of 1000 mg twice daily (BID). METHODS We systematically searched the database of PubMed until December 20, 2022, and retrieved all published double-blind, randomized, placebo-controlled trials (RCTs) conducted with imeglimin 1000 mg BID, using appropriate keywords and MeSH terms. A meta-analysis was conducted to study the HbA1c lowering effect of imeglimin 1000 mg BID in people with T2D using the Comprehensive meta-analysis (CMA) software Version 3, Biostat Inc. Englewood, NJ, USA. RESULTS Of the seven Phase 2 studies and three Phase 3 studies conducted so far, only three published double-blind RCTs have reported the efficacy and safety of imeglimin 1000 mg BID against the placebo. Our meta-analysis using the random-effects model from two monotherapy studies (n = 360) showed imeglimin 1000 mg BID reduce HbA1c significantly (Δ -0.9%, 95% Confidence Interval [CI], -1.1 to -0.74%; P < 0.0001) against the placebo, without any heterogeneity (I2 = 0%). The pooled meta-analysis from all three RCTs (n = 574) found a significant reduction in HbA1c with imeglimin 1000 mg BID (Δ -0.79%; 95% CI, -1.00 to -0.59%; P < 0.0001) compared to placebo with high heterogeneity. CONCLUSIONS This meta-analysis found a significant HbA1c lowering effect of imeglimin in people with T2D with an acceptable tolerability profile. Still, larger and longer studies are needed.
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8.
Non-sugar sweeteners and health outcomes in adults without diabetes: deciphering the WHO recommendations in the Indian context.
Singh, AK, Singh, A, Singh, R, Joshi, SR, Misra, A
Diabetes & metabolic syndrome. 2023;(8):102829
Abstract
BACKGROUND AND AIMS A systematic review and meta-analysis conducted by the World Health Organization (WHO) assessed the health outcomes of non-sugar sweeteners (NSS) in randomized controlled trials (RCTs) and prospective cohort studies (PCSs) and reported conflicting findings. We aim to decipher these conflicting findings in RCTs and PCSs by critically reviewing their results, comparing them with previous meta-analyses, and providing a simplified interpretation including the Indian perspective. METHODS We critically reviewed the 210-page dossier of WHO including the full text of most of the key studies of NSS included in this meta-analysis and subsequently compared it with previous meta-analyses to identify similarities and differences to address a few key questions pertaining to health outcomes associated with NSS use in adults. RESULTS Poor health outcomes are often associated with excess sugar intake. While NSS are typically consumed as a sugar replacement, benefits are conflicting. While RCTs found some benefits in the short term, PCSs found harm associated with NSS use in the long term. CONCLUSION The 2022 WHO meta-analysis that assessed the health outcomes of NSS is the most robust and critically analyzed document available to date. Despite the absence of any strong conclusion that suggests NSS consumption increases the risk of cardio-metabolic disorders, no firm evidence also rejects this statement. NSS could be an attractive replacement for sugar in overweight/obese people in the short term, but long-term harm cannot be fully ruled out. We suggest avoiding consuming sugar and restricting NSS intake wherever possible until long-term studies confirm or refute these findings.
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9.
Surface activity, mechanisms, kinetics, and thermodynamic study of adsorption of malachite green dye onto sulfuric acid-functionalized Moringa oleifera leaves from aqueous solution.
Dixit, U, Singh, K, Mohan, S, Singh, AK, Kumar, A
Environmental monitoring and assessment. 2023;(1):78
Abstract
In the present study, activated carbon prepared from H2SO4-functionalized Moringa oleifera leaves (ACMOL) was used as a potential adsorbent for the effective removal of malachite green (MG) dye from aqueous media. FT-IR, SEM, EDS, Zeta potential, XRD, BET, proximate, and CHNS analysis techniques were used for surface characterization of the ACMOL. The adsorption efficiency of the ACMOL was investigated as a function of varying adsorbent dosage (0.02-0.2 g/100 mL), pH (3.0-9.0), ionic strength (0.1-0.5 M KCl), urea concentration (0.1-0.5 M), contact time (30-210 min), and temperature (303-323 K). The representative adsorption isotherms belong to the typical L-type. Maximum percentage removal was found to be 84% (124.40 mg/g) for MG dye concentration (30 mg/L) at pH 7.0 and 303 K with ACMOL dose 0.02 g/100 mL. The adsorption kinetics and equilibrium experimental data of MG dye adsorption on the ACMOL were well explained by the pseudo-second-order kinetics (R2 = 0.99) and Langmuir isotherm model (R2 = 0.99), respectively. The value of adsorption and desorption coefficient was found to be 0.036 min-1 and 0.025 mg min-1/L, respectively. Thermodynamic study showed the spontaneous (ΔG° = - 31.33, - 31.92, and - 32.49 kJ/mol at temperatures 303 K, 313 K, and 323 K, respectively) and exothermic (ΔH° = - 13.7 kJ/mol) nature of the adsorption with some structural changes occurring on the ACMOL surface (ΔS° = 58.198 J/K·mol).
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10.
Meta-QTL analysis in wheat: progress, challenges and opportunities.
Sharma, D, Kumari, A, Sharma, P, Singh, A, Sharma, A, Mir, ZA, Kumar, U, Jan, S, Parthiban, M, Mir, RR, et al
TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik. 2023;(12):247
Abstract
Wheat, an important cereal crop globally, faces major challenges due to increasing global population and changing climates. The production and productivity are challenged by several biotic and abiotic stresses. There is also a pressing demand to enhance grain yield and quality/nutrition to ensure global food and nutritional security. To address these multifaceted concerns, researchers have conducted numerous meta-QTL (MQTL) studies in wheat, resulting in the identification of candidate genes that govern these complex quantitative traits. MQTL analysis has successfully unraveled the complex genetic architecture of polygenic quantitative traits in wheat. Candidate genes associated with stress adaptation have been pinpointed for abiotic and biotic traits, facilitating targeted breeding efforts to enhance stress tolerance. Furthermore, high-confidence candidate genes (CGs) and flanking markers to MQTLs will help in marker-assisted breeding programs aimed at enhancing stress tolerance, yield, quality and nutrition. Functional analysis of these CGs can enhance our understanding of intricate trait-related genetics. The discovery of orthologous MQTLs shared between wheat and other crops sheds light on common evolutionary pathways governing these traits. Breeders can leverage the most promising MQTLs and CGs associated with multiple traits to develop superior next-generation wheat cultivars with improved trait performance. This review provides a comprehensive overview of MQTL analysis in wheat, highlighting progress, challenges, validation methods and future opportunities in wheat genetics and breeding, contributing to global food security and sustainable agriculture.