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1.
Prognostic factors in resolution of nonalcoholic fatty liver disease post bariatric surgery in adolescents.
Bacha, F, Gupta, R, Jenkins, TM, Brandt, ML, Inge, TH, Kleiner, DE, Xanthakos, SA, ,
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2024;(4):367-375
Abstract
BACKGROUND The long-term effect of bariatric surgery on adolescent non-alcoholic fatty liver disease is not clear. OBJECTIVES To evaluate longitudinal change in serum alanine aminotransferase (ALT) levels and to determine the factors independently associated with this change over 2 years after bariatric surgery in adolescents with severe obesity. SETTING An observational prospective cohort from the Teen-LABS Consortium. METHODS We examined the relationship of longitudinal change in serum ALT (% change and normalization) to change in body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), high- (HDL) and low-density lipoprotein cholesterol, A1C and fasting glucose, accounting for age, sex, race-ethnicity, blood pressure, and baseline BMI in 219 adolescents during the first 2 years post-surgery. RESULTS Mean BMI declined from a baseline of 52.6 to 37.2 kg/m2 at 2 years (P < .01). Alanine aminotransferase decreased significantly from baseline (36.5 [95% CI: 31.4, 41.7]) to 6 months (30.5 [95% CI: 25.4, 35.6]), and remained stable at 12 and 24 months, all P < .01 versus baseline. After adjustment, improvement in BMI, fasting glucose, HOMA-IR, triglycerides, TG/HDL ratio, and HDL were independently associated with reduced ALT at 6 months. These remained significantly associated with a decline in ALT after adjusting for BMI change. The %participants with elevated ALT decreased from 71% at baseline to 42% and 36% at 1 and 2 years post-surgery. CONCLUSIONS Bariatric surgery resulted in significant and sustained improvement in ALT levels over 2 years. Although associated with weight loss, this decline was also associated with improved metabolic indices, independent of weight loss.
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2.
Karanjin, A Promising Bioactive Compound Possessing Anti-cancer Activity against Experimental Model of Non-small Cell Lung Cancer Cells.
Kumar, G, Pandey, DM, Ghosh, M, Dall'Acqua, S, Gupta, R, Tiwari, NP, Siddique, UM, Vishwakrama, L, Guleri, SK, Lal, UR, et al
Anti-cancer agents in medicinal chemistry. 2024;(5):317-333
Abstract
AIMS: The aim of this study is to isolate the Millettia pinnata (Karanj) leaf extract for pure compound with anticancer properties and to study the molecular target of the isolates in non-small cell lung cancer cell lines. BACKGROUND In our earlier research Millettia pinnata leaf extract has demonstrated potential anticancer activities. Thus, in pursuit of the bioactive compounds, the most potential active extract from our previous study was purified. Furthermore, the anticancer properties of the isolated compound karanjin was studied and aimed for apoptosis and restraining growth. METHODS A novel method was developed through column chromatography for isolation and purification of the compound karanjin from leaf chloroform extract. The purified component was then characterised using FTIR, mass spectrometry, and NMR. An MTT-based cytotoxicity assay was used to analyse cell cytotoxicity, whereas fluorescence staining was used for apoptosis and reactive oxygen species inhibition quantification. Furthermore, the real-time PCR assay was used to determine the molecular mechanism of action in cells causing cytotoxicity induced by karanjin dosing. RESULTS The anticancer activity of karanjin in A549 cell line exhibited prominent activity revealing IC50 value of 4.85 μM. Conferring the predicted molecular pathway study, karanjin restrains the proliferation of cancer cells through apoptosis, which is controlled by extrinsic pathway proteins FAS/FADD/Caspases 8/3/9. Downregulation of KRAS and dependent gene expression also stopped cell proliferation. CONCLUSION Karanjin has been identified as a compound with potential effect in non-small cell lung cancer cells. Molecular mechanism for apoptosis and inhibition of reactive oxygen species induced through H2O2 were observed, concluding karanjin have medicinal and antioxidant properties.
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3.
The intricate role of lipids in orchestrating plant defense responses.
Seth, T, Asija, S, Umar, S, Gupta, R
Plant science : an international journal of experimental plant biology. 2024;:111904
Abstract
Plants are exposed to a variety of pests and pathogens that reduce crop productivity. Plants respond to such attacks by activating a sophisticated signaling cascade that initiates with the recognition of pests/pathogens and may culminate into a resistance response. Lipids, being the structural components of cellular membranes, function as mediators of these signaling cascades and thus are instrumental in the regulation of plant defense responses. Accumulating evidence indicates that various lipids such as oxylipins, phospholipids, glycolipids, glycerolipids, sterols, and sphingolipids, among others, are involved in mediating cell signaling during plant-pathogen interaction with each lipid exhibiting a specific biological relevance, follows a distinct biosynthetic mechanism, and contributes to specific signaling cascade(s). Omics studies have further confirmed the involvement of lipid biosynthetic enzymes including the family of phospholipases in the production of defense signaling molecules subsequent to pathogen attack. Lipids participate in stress signaling by (1) mediating the signal transduction, (2) acting as precursors for bioactive molecules, (3) regulating ROS formation, and (4) interacting with various phytohormones to orchestrate the defense response in plants. In this review, we present the biosynthetic pathways of different lipids, their specific functions, and their intricate roles upstream and downstream of phytohormones under pathogen attack to get a deeper insight into the molecular mechanism of lipids-mediated regulation of defense responses in plants.
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4.
Plant hormones and secondary metabolites under environmental stresses: Enlightening defense molecules.
Kumari, S, Nazir, F, Maheshwari, C, Kaur, H, Gupta, R, Siddique, KHM, Khan, MIR
Plant physiology and biochemistry : PPB. 2024;:108238
Abstract
The climatic changes have great threats to sustainable agriculture and require efforts to ensure global food and nutritional security. In this regard, the plant strategic responses, including the induction of plant hormones/plant growth regulators (PGRs), play a substantial role in boosting plant immunity against environmental stress-induced adversities. In addition, secondary metabolites (SMs) have emerged as potential 'stress alleviators' that help plants to adapt against environmental stressors imposing detrimental impacts on plant health and survival. The introduction of SMs in plant biology has shed light on their beneficial effects in mitigating environmental crises. This review explores SMs-mediated plant defense responses and highlights the crosstalk between PGRs and SMs under diverse environmental stressors. In addition, genetic engineering approaches are discussed as a potential revenue to enhance plant hormone-mediated SM production in response to environmental cues. Thus, the present review aims to emphasize the significance of SMs implications with PGRs association and genetic approachability, which could aid in shaping the future strategies that favor agro-ecosystem compatibility under unpredictable environmental conditions.
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5.
Recent advances in the treatment of primary and secondary progressive Multiple Sclerosis.
Sriwastava, S, Elkhooly, M, Amatya, S, Shrestha, K, Kagzi, Y, Bhatia, D, Gupta, R, Jaiswal, S, Lisak, RP
Journal of neuroimmunology. 2024;:578315
Abstract
BACKGROUND The article highlights upcoming potential treatments, which target different phases of inflammation and offer remyelinating strategies as well as direct and indirect neuroprotective and oligodendrocyte protective effects, providing a hopeful outlook for patients with primary and secondary progressive multiple sclerosis (PPMS and SPMS). OBJECTIVES The review aims to identify potential treatments and ongoing clinical trials for PPMS and SPMS, and compare their mechanisms of action, efficacy, and side effects with current treatments. METHODS We reviewed ongoing clinical trials for PPMS and SPMS on the NIH website, as well as articles from PubMed, Embase, and clinicaltrails.gov since 2010. RESULTS BTKIs like, tolebrutinib, and fenebrutinib are being explored as potential PMS treatments. Vidofludimus calcium, an orally available treatment, has shown a reduction of active and new MRI lesions. Other treatments like simvastatin, N-acetylcysteine (NAC), and alpha-lipoic acid are being explored for their antioxidant properties. AHSCT and mesenchymal stem cell therapy are experimental options for younger patients with high inflammatory activity. CONCLUSIONS SPMS and PPMS are being studied for new treatments and future trials should consider combination therapies targeting inflammation, demyelination, and neuronal death, as the pathogenesis of PMS involves complex factors.
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6.
Comparative safety review of antithrombotic treatment options for patients with atrial fibrillation undergoing percutaneous coronary intervention.
Erbay, MI, Pyrpyris, N, Susarla, S, Ulusan, S, Mares, AC, Wilson, TP, Lee, D, Sood, A, Gupta, R
Expert opinion on drug safety. 2024;(2):149-160
Abstract
INTRODUCTION Balancing antithrombotic therapy for atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) remains a clinical challenge due to coexisting thrombogenic risks. This review emphasizes the delicate balance required to prevent ischemic events while minimizing bleeding complications, particularly in the context of risk assessment. AREAS COVERED This review spans from 2010 to October 2023, exploring the complexities of antithrombotic management for AF patients undergoing PCI. It stresses the need for personalized treatment decisions to optimize antithrombotic therapies effectively. EXPERT OPINION The evolving evidence supports double antithrombotic therapy (DAT) over triple antithrombotic therapy (TAT) for these patients, showcasing a more favorable safety profile without compromising efficacy. Non-vitamin K antagonist oral anticoagulant (NOAC)-based DAT strategies exhibit superiority in reducing major bleeding events while effectively preventing ischemic events. Recommendations from the 2023 European Society of Cardiology (ESC) Guidelines advocate for NOAC-based DAT post-PCI, endorsing safer antithrombotic profiles.Challenges persist for specific patient categories requiring both oral anticoagulants and antiplatelets, necessitating personalized approaches. Future advances in intravascular imaging and novel coronary stent technologies offer promising avenues to optimize outcomes and influence antithrombotic strategies in AF-PCI patients.
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7.
Laboratory evaluation of lipid parameters in clinical practice.
Pancholia, AK, Kabra, NK, Gupta, R
Indian heart journal. 2024;(Suppl 1):S29-S32
Abstract
Accurate measurement of various lipids- total cholesterol, cholesterol lipoproteins and triglycerides- is important for coronary artery disease (CAD) prevention and management. Over the years many technologies have developed for their accurate measurements and in recent years the assays have been internationally standardised. Most of the guidelines recommend measurement of non fasting levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and triglycerides (TG) for risk estimation and guiding treatment. Measurement of lipid profile in clinics and emergency departments can lead to earlier estimation of CAD risk and rapid initiation of lipid lowering therapy. CAD risk and baseline levels of LDL-C guide intensity of lipid lowering therapies. The LDL-C targets according to CAD risk are detailed in this review. There is an urgent need for standardization of lipid estimation in medical laboratories across the country so that every eligible individual can receive evidence-based lipid lowering interventions.
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8.
Expanding Indications of Nonvitamin K Oral Anticoagulants Beyond Nonvalvular Atrial Fibrillation and Venous Thromboembolism: A Review of Emerging Clinical Evidence.
Hajra, A, Ujjawal, A, Ghalib, N, Chowdhury, S, Biswas, S, Balasubramanian, P, Gupta, R, Aronow, WS
Current problems in cardiology. 2024;(1 Pt A):102017
Abstract
Direct oral anticoagulants (DOAC) have emerged as a new therapy for patients who need and can tolerate oral anticoagulation. DOACs were initially approved for nonvalvular atrial fibrillation (NVAF) and treatment for deep vein thrombosis (DVT) and pulmonary embolism (PE). Ease of administration, no requirement of bridging with other anticoagulants, and less frequent dosing have made DOACs preferable choice for anticoagulation. Studies are showing promising results regarding use of DOACs beyond the common indications. Studies have been done to show the potential benefit of DOACs in valvular atrial fibrillation, heart failure, acute coronary syndrome, stroke, and peripheral arterial disease. Data have shown safety as well as comparable bleeding incidences with DOACs compared to vitamin K antagonist anticoagulants. Naturally interest is growing to see the use of DOACs apart from the NVAF, DVT, or PE. Authors have highlighted various study results to show the potential beneficial role of DOACs in the above-mentioned situations.
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9.
Calcium mediated static and dynamic allostery in S100A12: Implications for target recognition by S100 proteins.
Wang, Q, DiForte, C, Aleshintsev, A, Elci, G, Bhattacharya, S, Bongiorno, A, Gupta, R
Protein science : a publication of the Protein Society. 2024;(4):e4955
Abstract
Structure and functions of S100 proteins are regulated by two distinct calcium binding EF hand motifs. In this work, we used solution-state NMR spectroscopy to investigate the cooperativity between the two calcium binding sites and map the allosteric changes at the target binding site. To parse the contribution of the individual calcium binding events, variants of S100A12 were designed to selectively bind calcium to either the EF-I (N63A) or EF-II (E31A) loop, respectively. Detailed analysis of the backbone chemical shifts for wildtype protein and its mutants indicates that calcium binding to the canonical EF-II loop is the principal trigger for the conformational switch between 'closed' apo to the 'open' Ca2+ -bound conformation of the protein. Elimination of binding in S100-specific EF-I loop has limited impact on the calcium binding affinity of the EF-II loop and the concomitant structural rearrangement. In contrast, deletion of binding in the EF-II loop significantly attenuates calcium affinity in the EF-I loop and the structure adopts a 'closed' apo-like conformation. Analysis of experimental amide nitrogen (15 N) relaxation rates (R1 , R2 , and 15 N-{1 H} NOE) and molecular dynamics (MD) simulations demonstrate that the calcium bound state is relatively floppy with pico-nanosecond motions induced in functionally relevant domains responsible for target recognition such as the hinge domain and the C-terminal residues. Experimental relaxation studies combined with MD simulations show that while calcium binding in the EF-I loop alone does not induce significant motions in the polypeptide chain, EF-I regulates fluctuations in the polypeptide in the presence of bound calcium in the EF-II loop. These results offer novel insights into the dynamic regulation of target recognition by calcium binding and unravels the role of cooperativity between the two calcium binding events in S100A12.
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10.
Evolution of reactive oxygen species cellular targets for plant development.
Singh, VP, Jaiswal, S, Wang, Y, Feng, S, Tripathi, DK, Singh, S, Gupta, R, Xue, D, Xu, S, Chen, ZH
Trends in plant science. 2024
Abstract
Reactive oxygen species (ROS) are the key players in regulating developmental processes of plants. Plants have evolved a large array of gene families to facilitate the ROS-regulated developmental process in roots and leaves. However, the cellular targets of ROS during plant evolutionary development are still elusive. Here, we found early evolution and large expansions of protein families such as mitogen-activated protein kinases (MAPK) in the evolutionarily important plant lineages. We review the recent advances in interactions among ROS, phytohormones, gasotransmitters, and protein kinases. We propose that these signaling molecules act in concert to maintain cellular ROS homeostasis in developmental processes of root and leaf to ensure the fine-tuning of plant growth for better adaptation to the changing climate.