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Risk of Cancer Recurrence in Patients With Immune-Mediated Diseases With Use of Immunosuppressive Therapies: An Updated Systematic Review and Meta-Analysis.
Gupta, A, Peyrin-Biroulet, L, Ananthakrishnan, AN
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;(3):499-512.e6
Abstract
BACKGROUND & AIMS There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments. METHODS We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent. RESULTS Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation. CONCLUSIONS In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.
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Phase 3 efficacy and safety trial of proposed liraglutide biosimilar for reduction of glycosylated hemoglobin (HbA1c) in patients with Type 2 diabetes mellitus.
Krishnan, K, Raman, S, Anand Moses, CR, Rajesh, RP, Gupta, A, Mudaliar, V, Vimal, J
Diabetes research and clinical practice. 2024;:111034
Abstract
Liraglutide is indicated for glycaemic control in adults with Type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. A proposed biosimilar of liraglutide (Levim Liraglutide) was investigated for efficacy & safety in a phase 3 study against the originator reference liraglutide (Victoza®) manufactured by Novo Nordisk A/S, Denmark. Patients aged 18-65 years of age with glycosylated hemoglobin (HbA1c) between 7 and 10 %, among other criteria, were included in the study. Patients were randomized 1:1 to receive daily doses of either Levim liraglutide or reference liraglutide for 24 weeks. The least square mean (standard error, SE) for the primary efficacy endpoint of reduction in HbA1c% at Week 24 was -1.09 (0.15)% for Levim liraglutide group and -1.04 (0.14)% for reference liraglutide. The upper bound of the confidence interval for treatment difference was less than the non-inferiority margin of 0.4 % at one-sided alpha of 0.025 (P-value = 0.0003). The secondary endpoints for proportion of patients achieving reduction in HbA1c, glycaemic level and weight, changes in cardiovascular parameters and the overall safety profiles of the study drugs were comparable. Levim liraglutide demonstrated non-inferior efficacy and similar safety to reference liraglutide and may be an option in treatment of T2DM (CTRI.nic.in, no. CTRI/2022/02/040261).
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Tinospora cordifolia (Giloy): An insight on the multifarious pharmacological paradigms of a most promising medicinal ayurvedic herb.
Gupta, A, Gupta, P, Bajpai, G
Heliyon. 2024;(4):e26125
Abstract
Medicinal herbs are being widely accepted as alternative remedies for preventing various diseases especially in India and other Asian countries. However, most plant-based herbal medicines are not yet being scientifically accepted worldwide. "Tinospora cordifolia (Willd.) Miers ex Hook.F. & Thomson", one of the most promising plant species of Tinospora known as "Giloy" or Guduchi that is used in several traditional medicines in treating diseases e.g., metabolic and immune disorders, diabetes, heart diseases, cancer, and infectious diseases, has been widely investigated. Varieties of bioactive phytochemical constituents isolated from the stem, root and whole plant of T. cordifolia have been identified. In the last two decades, the diverse pharmacological activities of T. cordifolia have been continuously studied. Due to its therapeutic efficacy in immune modulation, it could be effective in viral and other diseases treatment as well. A medicinal plant could be well-suited not only for the treatment of target site but also for boosting the body's immune system. As an alternate source of medication, medicinal herbs are continuously showing better compatibility with the human body with minimal side effects than other therapies. Keeping this in mind, the present review highlights the pharmacological potential of T. cordifolia against various diseases.
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Alginate based biomaterials for hemostatic applications: Innovations and developments.
Sharma, A, Verma, C, Singh, P, Mukhopadhyay, S, Gupta, A, Gupta, B
International journal of biological macromolecules. 2024;(Pt 2):130771
Abstract
Development of the efficient hemostatic materials is an essential requirement for the management of hemorrhage caused by the emergency situations to avert most of the casualties. Such injuries require the use of external hemostats to facilitate the immediate blood clotting. A variety of commercially available hemostats are present in the market but most of them are associated with limitations such as exothermic reactions, low biocompatibility, and painful removal. Thus, fabrication of an ideal hemostatic composition for rapid blood clot formation, biocompatibility, and antimicrobial nature presents a real challenge to the bioengineers. Benefiting from their tunable fabrication properties, alginate-based hemostats are gaining importance due to their excellent biocompatibility, with >85 % cell viability, high absorption capacity exceeding 500 %, and cost-effectiveness. Furthermore, studies have estimated that wounds treated with sodium alginate exhibited a blood loss of 0.40 ± 0.05 mL, compared to the control group with 1.15 ± 0.13 mL, indicating its inherent hemostatic activity. This serves as a solid foundation for designing future hemostatic materials. Nevertheless, various combinations have been explored to further enhance the hemostatic potential of sodium alginate. In this review, we have discussed the possible role of alginate based composite hemostats incorporated with different hemostatic agents, such as inorganic materials, polymers, biological agents, herbal agents, and synthetic drugs. This article outlines the challenges which need to be addressed before the clinical trials and give an overview of the future research directions.
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Identification of potent BRD4-BD1 inhibitors using classical and steered molecular dynamics based free energy analysis.
Gupta, A, Purohit, R
Journal of cellular biochemistry. 2024;(3):e30532
Abstract
In the present work a combination of traditional and steered molecular dynamics based techniques were employed to identify potential inhibitors against the human BRD4 protein (BRD4- BD1); an established drug target for multiple illnesses including various malignancies. Quinoline derivatives that were synthesized in-house were tested for their potential as new BRD4-BD1 inhibitors. Initially molecular docking experiments were performed to determine the binding poses of BRD4-BD1 inhibitors. To learn more about the thermodynamics of inhibitor binding to the BRD4-BD1 active site, the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) free energy calculations were conducted afterwards. The findings of the MM-PBSA analysis were further reinforced by performing steered umbrella sampling simulations which revealed crucial details about the binding/unbinding process of the most potent quinoline derivatives at the BRD4-BD1 active site. We report a novel quinoline derivative which can be developed into a fully functional BRD4-BD1 inhibitor after experimental validation. The identified compound (4 g) shows better properties than the standard BRD4-BD1 inhibitors considered in the study. The study also highlights the crucial role of Gln78, Phe79, Trp81, Pro82, Phe83, Gln84, Gln85, Val87, Leu92, Leu94, Tyr97, Met105, Cys136, Asn140, Ile146 and Met149 in inhibitor binding. The study provides a possible lead candidate and key amino acids involved in inhibitor recognition and binding at the active site of BRD4-BD1 protein. The findings might be of significance to medicinal chemists involved in the development of potent BRD4-BD1 inhibitors.
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Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.
Charchar, FJ, Prestes, PR, Mills, C, Ching, SM, Neupane, D, Marques, FZ, Sharman, JE, Vogt, L, Burrell, LM, Korostovtseva, L, et al
Journal of hypertension. 2024;(1):23-49
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Abstract
Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.
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In silico identification and validation of phenolic lipids as potential inhibitor against bacterial and viral strains.
Khatana, K, Gupta, A, Ghosal, A, Dey, P, Zafar, F, Srivastava, A, Verma, P
Journal of biomolecular structure & dynamics. 2024;(5):2525-2538
Abstract
The recurrence of coronavirus disease and bacterial resistant strains has drawn attention to naturally occurring bioactive molecules that can demonstrate broad-spectrum efficacy against bacteria as well as viral strains. The drug-like abilities of naturally available "anacardic acids" (AA) and their derivatives against different bacterial and viral protein targets through in-silico tools were explored. Three viral protein targets [P DB: 6Y2E (SARS-CoV-2), 1AT3 (Herpes) and 2VSM (Nipah)] and four bacterial protein targets [P DB: 2VF5 (Escherichia coli), 2VEG (Streptococcus pneumoniae), 1JIJ (Staphylococcus aureus) and 1KZN (E. coli)] were selected to evaluate the activity of bioactive AA molecules. The potential ability to inhibit the progression of microbes has been discussed based on the structure, functionality and interaction ability of these molecules on the selected protein targets for multi-disease remediation. The number of interactions, full-fitness value and energy of the ligand-target system were determined from the docked structure in SwissDock and Autodock Vina. In order to compare the efficacy of these active derivatives to that of commonly used drugs against bacteria and viruses, a few of the selected molecules were subjected to 100 ns long MD simulations. It was found that the phenolic groups and alkyl chains of AA derivatives are more likely to bind with microbial targets, that could be responsible for the improved activity against these targets. The results suggest that the proposed AA derivatives have demonstrated potential to become active drug ingredients against microbial protein targets. Further, experimental investigations are essential for clinical verification of the drug-like abilities of AA derivatives.Communicated by Ramaswamy H. Sarma.
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Unraveling the Role of Maternal Serum Ferritin Levels in Preterm Delivery: A Comprehensive Review.
Dande, A, Pajai, S, Gupta, A, Dande, S, Sethi, N
Cureus. 2024;(2):e54515
Abstract
Preterm delivery remains a critical global health concern, with numerous adverse consequences for both neonate and healthcare systems. Understanding the relationship between maternal ferritin levels, as a marker of iron status, and the risk of preterm birth is the focal point of this comprehensive review. We provide insights into the multifaceted nature of this connection, highlighting factors that influence maternal ferritin levels, including dietary intake, genetic and physiological variations, comorbidities, and iron supplementation. While evidence suggests an association between low maternal ferritin levels and preterm birth, causality remains elusive, necessitating further research with robust study designs. The potential mechanisms linking maternal iron status to preterm birth, such as inflammation, infection, and oxidative stress, are explored, underscoring the need for in-depth investigations. This comprehensive review emphasizes the clinical importance of assessing and monitoring maternal ferritin levels in prenatal care and advocates for public health initiatives to raise awareness and provide targeted interventions, particularly in high-risk populations. As we strive to address these unanswered questions and embark on innovative research directions, the aim is to ultimately enhance our understanding of the complex relationship between maternal iron status and preterm birth, leading to improved maternal and child health outcomes.
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Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?
Ross, FC, Mayer, DE, Horn, J, Cryan, JF, Del Rio, D, Randolph, E, Gill, CIR, Gupta, A, Ross, RP, Stanton, C, et al
Nutritional neuroscience. 2024;:1-19
Abstract
Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.
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Impact of induced mutation-derived genetic variability, genotype and varieties for quantitative and qualitative traits in Mentha species.
Prasad, P, Gupta, A, Singh, V, Kumar, B
International journal of radiation biology. 2024;(2):151-160
Abstract
PURPOSE The genus Mentha spp. is an aromatic herb from the family 'Lamiaceae'. It is extensively predominant in temperate and sub-temperate regions of the world. The essential oil of this species is enriched with broad aroma constituents extensively utilized in food, beverages, flavor, cosmetics, perfumery, and pharmaceutical enterprises. With the global menthol market size estimated to be worth USD 765 million in 2022, India (accompanied by China and Brazil) is the world's primary manufacturer, consumer, and exporter of Mentha oil. Despite prominent global demand, the crucial bottleneck in mint cultivation is the need for more superior commercial cultivars. Predominant vegetative propagation mode with difficulties in manual emasculation, differential blooming times, sterile/sub-sterile hybrids, and low seed viability are the primary containment in creating genetic variability by classical breeding approaches. Therefore, genetic complications encountered in conventional breeding have led the breeders to apply mutation breeding as an alternative crop improvement approach in Mentha spp. These attempts at mutation breeding have produced some distinctive mutants as genetic pools for plant breeding programs, and some novel mutant mint cultivars have been made available for commercial cultivation. CONCLUSIONS The prime strategy in mutation-based breeding has proven an adept means of encouraging the expression of recessive genes and producing new genetic variations. The present review comprises a significant contribution of mutation breeding approaches in the development of mutant mint species and its effects on physiological variation, photosynthetic pigment, essential oil content and composition, phytochemical-mediated defense response, pathogen resistivity, and differential expression of genes related to terpenoid biogenesis. Development and diversification have led to the release of varieties, namely Todd's Mitcham, Murray Mitcham, Pranjal, Tushar, and Kukrail in M. piperita L., Mukta, and Pratik in M. cardiaca Baker, Neera in M. spicata L., Kiran in M. citrata Ehrh., and Rose mint in M. arvensis L. that have revolutionized and uplifted mint cultivation leading to economic gain by the farmers and entrepreneurs.