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1.
Metabolic engineering for enhanced terpenoid production: Leveraging new horizons with an old technique.
Kumari, M, Checker, VG, Kathpalia, R, Srivastava, V, Singh, IK, Singh, A
Plant physiology and biochemistry : PPB. 2024;:108511
Abstract
Terpenoids are a vast class of plant specialized metabolites (PSMs) manufactured by plants and are involved in their interactions with environment. In addition, they add health benefits to human nutrition and are widely used as pharmaceutically active compounds. However, native plants produce a limited amount of terpenes restricting metabolite yield of terpene-related metabolites. Exponential growth in the plant metabolome data and the requirement of alternative approaches for producing the desired amount of terpenoids, has redirected plant biotechnology research to plant metabolic engineering, which requires in-depth knowledge and precise expertise about dynamic plant metabolic pathways and cellular physiology. Metabolic engineering is an assuring tool for enhancing the concentration of terpenes by adopting specific strategies such as overexpression of the key genes associated with the biosynthesis of targeted metabolites, controlling the modulation of transcription factors, downregulation of competitive pathways (RNAi), co-expression of the biosynthetic pathway genes in heterologous system and other combinatorial approaches. Microorganisms, fast-growing host plants (such as Nicotiana benthamiana), and cell suspension/callus cultures have provided better means for producing valuable terpenoids. Manipulation in the biosynthetic pathways responsible for synthesis of terpenoids can provide opportunities to enhance the content of desired terpenoids and open up new avenues to enhance their production. This review deliberates the worth of metabolic engineering in medicinal plants to resolve issues associated with terpenoid production at a commercial scale. However, to bring the revolution through metabolic engineering, further implementation of genome editing, elucidation of metabolic pathways using omics approaches, system biology approaches, and synthetic biology tactics are essentially needed.
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2.
Dietary Influences on Skin Health in Common Dermatological Disorders.
Sharma, N, Chaudhary, SM, Khungar, N, Aulakh, SK, Idris, H, Singh, A, Sharma, K
Cureus. 2024;(2):e55282
Abstract
The role of diet in the development of skin disorders is well-established, with nutritional deficiency often identified as a risk factor for skin diseases. Imbalances in the skin can be caused by nutritional deficiencies, excessive intake, insufficient nutrients, and hazardous ingredients. Patients frequently inquire about the impact of dietary patterns on skin health when consulting dermatologists in clinical settings. Simultaneously, the popularity of using nutritional supplements containing vitamins, minerals, and nutraceutical blends has been on the rise. It is crucial for dermatologists, primary care physicians, and other healthcare providers to be acquainted with evidence-based dietary interventions, distinguishing them from those that are more market-driven than truly efficacious. This review explores the modification of diet, encompassing both dietary exclusion and supplementation, as a therapeutic approach for conditions such as psoriasis, atopic dermatitis, bullous disease, vitiligo, and alopecia areata. A comprehensive literature search, utilizing the PubMed/Medline, Google Scholar, and Medscape databases, was conducted to investigate the relationship between each nutrient and various inflammatory skin diseases. The findings emphasize the significance of a well-balanced and thoughtfully planned diet in supplying adequate amounts of proteins, vitamins, and minerals to support optimal skin health. Additionally, this comprehensive review navigates through various dietary recommendations, offering insights into their multifaceted impacts on the immune system, gut microbiome, and skin health. The goal is to pave the way for informed and targeted dietary interventions for individuals dealing with food allergies and associated skin conditions.
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Changes in microbial community structure and yield responses with the use of nano-fertilizers of nitrogen and zinc in wheat-maize system.
Upadhyay, PK, Dey, A, Singh, VK, Dwivedi, BS, Singh, RK, Rajanna, GA, Babu, S, Rathore, SS, Shekhawat, K, Rai, PK, et al
Scientific reports. 2024;(1):1100
Abstract
The growing popularity of nano-fertilization around the world for enhancing yield and nutrient use efficiency has been realized, however its influence on soil microbial structure is not fully understood. The purpose of carrying out this study was to assess the combined effect of nano and conventional fertilizers on the soil biological indicators and crop yield in a wheat-maize system. The results indicate that the at par grain yield of wheat and maize was obtained with application of 75% of recommended nitrogen (N) with full dose of phosphorus (P) and potassium (K) through conventional fertilizers along with nano-N (nano-urea) or nano-N plus nano-Zn sprays and N100PK i.e. business as usual (recommended dose of fertilizer). Important soil microbial property like microbial biomass carbon was found statistically similar with nano fertilizer-based management (N75PK + nano-N, and N75PK + nano-N + nano-Zn) and conventional management (N100PK), during both wheat and maize seasons. The experimental data indicated that the application of foliar spray of nano-fertilizers along with 75% N as basal is a sustainable nutrient management approach with respect to growth, yield and rhizosphere biological activity. Furthermore, two foliar sprays of nano-N or nano-N + nano-Zn curtailed N requirement by 25%, furthermore enhanced soil microbial diversity and the microbial community structure. The specific microbial groups, including Actinobacteria, Bacteroidia, and Proteobacteria, were present in abundance and were positively correlated with wheat and maize yield and soil microbial biomass carbon. Thus, one of the best nutrient management approaches for sustaining productivity and maintaining sound microbial diversity in wheat-maize rotation is the combined use of nano-fertilizers and conventional fertilizers.
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School-based physical activity interventions: which intervention characteristics are associated with participation and retention? A meta-analysis.
van der Wurff, I, Kirschner, M, Golsteijn, R, de Jonge, M, Berendsen, B, Singh, A, Savelberg, H, de Groot, R
Preventive medicine. 2024;:107925
Abstract
OBJECTIVE Many school-based intervention studies are conducted to increase students' physical activity (PA). Recruitment and retention problems potentially impact the robustness of RCT findings. We conducted a meta-analysis to summarize recruitment and retention rates in long-term secondary school-based PA intervention studies and examined associated participant and intervention characteristics. METHODS Web of Science, Pubmed, Medline, and PsychInfo were searched until March 20th 2023. We included studies on secondary school-based PA interventions ≥12 weeks, aimed at typically developing adolescents. We abstracted number of schools and students invited, randomized, and participating at follow-up to calculate pooled recruitment and retention rates; participant and intervention characteristics were abstracted to execute subgroup or meta-regression analyses. RESULTS Recruitment rates were 51% for invited schools and 80% for invited students, the retention for schools was almost 100% and for students 91%. Interventions with fixed and flexible components, executed in Asia and South America, and from later publication years had higher student recruitment rates. Students' retention rates were lower for interventions which had flexible components, were theory/model-based, used an accelerometer, had a longer intervention duration, and included more females. CONCLUSION Recruitment and retention rates in school-based PA interventions are high. Some participant and intervention characteristics influence these rates: flexibility of the intervention, theory/model-based intervention, accelerometer use, intervention duration, continent, and number of females. Researchers should consider these characteristics in intervention development to achieve optimal balance between intervention effectiveness, recruitment, and retention.
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Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).
Singh, A, Rastogi, A, Puri, GD, Ganesh, V, Naik, NB, Kajal, K, Kahlon, S, Soni, SL, Kaloria, N, Saini, K, et al
Journal of public health (Oxford, England). 2024
Abstract
BACKGROUND efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.
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Zinc oxide nanoparticles influence on plant tolerance to salinity stress: insights into physiological, biochemical, and molecular responses.
Singh, A, Rajput, VD, Lalotra, S, Agrawal, S, Ghazaryan, K, Singh, J, Minkina, T, Rajput, P, Mandzhieva, S, Alexiou, A
Environmental geochemistry and health. 2024;(5):148
Abstract
A slight variation in ecological milieu of plants, like drought, heavy metal toxicity, abrupt changes in temperature, flood, and salt stress disturbs the usual homeostasis or metabolism in plants. Among these stresses, salinity stress is particularly detrimental to the plants, leading to toxic effects and reduce crop productivity. In a saline environment, the accumulation of sodium and chloride ions up to toxic levels significantly correlates with intracellular osmotic pressure, and can result in morphological, physiological, and molecular alterations in plants. Increased soil salinity triggers salt stress signals that activate various cellular-subcellular mechanisms in plants to enable their survival in saline conditions. Plants can adapt saline conditions by maintaining ion homeostasis, activating osmotic stress pathways, modulating phytohormone signaling, regulating cytoskeleton dynamics, and maintaining cell wall integrity. To address ionic toxicity, researchers from diverse disciplines have explored novel approaches to support plant growth and enhance their resilience. One such approach is the application of nanoparticles as a foliar spray or seed priming agents positively improve the crop quality and yield by activating germination enzymes, maintaining reactive oxygen species homeostasis, promoting synthesis of compatible solutes, stimulating antioxidant defense mechanisms, and facilitating the formation of aquaporins in seeds and root cells for efficient water absorption under various abiotic stresses. Thus, the assessment mainly targets to provide an outline of the impact of salinity stress on plant metabolism and the resistance strategies employed by plants. Additionally, the review also summarized recent research efforts exploring the innovative applications of zinc oxide nanoparticles for reducing salt stress at biochemical, physiological, and molecular levels.
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7.
Mitophagy Activation by Urolithin A to Target Muscle Aging.
Faitg, J, D'Amico, D, Rinsch, C, Singh, A
Calcified tissue international. 2024;(1):53-59
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Abstract
The age-related loss of skeletal muscle function starts from midlife and if left unaddressed can lead to an impaired quality of life. A growing body of evidence indicates that mitochondrial dysfunction is causally involved with muscle aging. Muscles are tissues with high metabolic requirements, and contain rich mitochondria supply to support their continual energy needs. Cellular mitochondrial health is maintained by expansing of the mitochondrial pool though mitochondrial biogenesis, by preserving the natural mitochondrial dynamic process, via fusion and fission, and by ensuring the removal of damaged mitochondria through mitophagy. During aging, mitophagy levels decline and negatively impact skeletal muscle performance. Nutritional and pharmacological approaches have been proposed to manage the decline in muscle function due to impaired mitochondria bioenergetics. The natural postbiotic Urolithin A has been shown to promote mitophagy, mitochondrial function and improved muscle function across species in different experimental models and across multiple clinical studies. In this review, we explore the biology of Urolithin A and the clinical evidence of its impact on promoting healthy skeletal muscles during age-associated muscle decline.
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Oxidative treatment of micropollutants present in wastewater: A special emphasis on transformation products, their toxicity, detection, and field-scale investigations.
Singh, A, Majumder, A, Saidulu, D, Bhattacharya, A, Bhatnagar, A, Gupta, AK
Journal of environmental management. 2024;:120339
Abstract
Micropollutants have become ubiquitous in aqueous environments due to the increased use of pharmaceuticals, personal care products, pesticides, and other compounds. In this review, the removal of micropollutants from aqueous matrices using various advanced oxidation processes (AOPs), such as photocatalysis, electrocatalysis, sulfate radical-based AOPs, ozonation, and Fenton-based processes has been comprehensively discussed. Most of the compounds were successfully degraded with an efficiency of more than 90%, resulting in the formation of transformation products (TPs). In this respect, degradation pathways with multiple mechanisms, including decarboxylation, hydroxylation, and halogenation, have been illustrated. Various techniques for the analysis of micropollutants and their TPs have been discussed. Additionally, the ecotoxicity posed by these TPs was determined using the toxicity estimation software tool (T.E.S.T.). Finally, the performance and cost-effectiveness of the AOPs at the pilot scale have been reviewed. The current review will help in understanding the treatment efficacy of different AOPs, degradation pathways, and ecotoxicity of TPs so formed.
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In-Silico Aided Screening and Characterization Results in Stability Enhanced Novel Roxadustat Co-Crystal.
Muthusamy, AR, Singh, A, Sundaram, MSS, Wagh, Y, Jegorov, A, Jain, AK
Journal of pharmaceutical sciences. 2024;(5):1190-1201
Abstract
Roxadustat (RXD) is an approved drug substances for the treatment of renal anemia. It has poor aqueous solubility and photochemical stability. This study employs a comprehensive approach to enhance the stability and physicochemical properties RXD through coformer selection and characterization. The investigation integrates delta pKa analysis, molecular complementary assessment, molecular electrostatic potential surface analysis, and machine learning techniques to predict potential co-crystal formation and binding interactions between drug molecules and coformers. The co-crystal screening which lead to in a novel RXD-nicotinamide co-crystal (RXD-NA). Experimental characterization underscores the physical and chemical stability of the co-crystals. To elucidate the supramolecular synthons and understand the intermolecular interactions in the RXD-NA co-crystal, Hirshfeld surfaces analysis, quantum theory of atoms in molecules (QTAIM) analysis and non-covalent interaction (NCI) analysis were performed. Computational analysis of photo-isomer formation aligns with experimental observations, further enhancing our understanding of RXD-coformer interactions. RXD-NA co-crystal was found photo-chemically stable as compared to free base API drug substance. This integrated methodology provides a systematic framework for informed co-crystal design, holding promise for optimizing RXD formulations based on molecular interactions and stability considerations. Consequently, this study contributes valuable insights to the field of rational drug design and formulation optimization.
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Impact of delay in the diagnosis on the severity of celiac disease.
Mehta, S, Agarwal, A, Pachisia, AV, Singh, A, Dang, S, Vignesh, D, Ahmed, A, Chaudhari, BR, Prasad, S, Goyal, RM, et al
Journal of gastroenterology and hepatology. 2024;(2):256-263
Abstract
BACKGROUND AND AIM Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.