Search

BackgroundThe impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown.MethodsWe analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 ​mmHg or diastolic blood pressure of ≥90 ​mmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 ​mmHg or diastolic blood pressure of ≥80 ​mmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000-2025).ResultsAmong 180,335 participants (33.2% women), the mean age was 40.6 ​± ​14.9 years (41.1 ​± ​15.0 and 39.7 ​± ​14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18-19, 20-44, 45-54, 55-64, 65-74 and ​≥ ​75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines.ConclusionAccording to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.

Introduction: Human Immunodeficiency Virus (HIV) has become an epidemic causing Acquired Immunodeficiency Syndrome (AIDS). Highly Active Antiretroviral Therapy (HAART) consists of Nucleoside Reverse Transcriptase Inhibitors (NRTIS), Nucleotide Reverse Transcriptase Inhibitors (NtRTIS), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIS) with HIV Protease Inhibitors (HIV PIs). However, the emergence of resistant strains of NNRTIS necessitates the search for better HIV-1-RT inhibitors., Methods: In this study, a series of novel imidazoles (SP01-SP30) was designed using molecular docking inside the Non-nucleoside Inhibitory Binding Pocket (NNIBP) of the HIV-1-RT (PDB ID-1RT2) using Glide v13.0.137, AutoDock Vina, and FlexX v2.1.3. Prime MMGBSA was used to study the free energy of binding of the inhibitors with the target enzyme. Molecular dynamics simulation studies were carried out to discover the dynamic behavior of the protein as well as to unveil the role of the essential amino acids required for the better binding affinity of the inhibitor within the NNIBP of the enzyme. The QikProp software module of Schrodinger and online SwissADME were also used to evaluate the drug-likeliness of these compounds., Results: The imidazole derivative SP08 is predicted to be the most promising design compound that can be considered for further synthetic exploitations to obtain a molecule with the highest therapeutic index against HIV-1-RT., Conclusion: The results of the current study demonstrate the robustness of our in silico drug design strategy that can be used for the discovery of novel HIV-1-RT inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: A series of benzylidene derivatives of fenobam and its thio analogues (1-22) have been evaluated for their cytotoxicity against breast cancer (MCF-7, MDA-MB-231), ovarian cancer (A2780, SKOV-3) and cervical cancer (HELA) cell lines., Method: These compounds (1-22) exhibited 72-83% inhibition of Erk activity against the ovarian cancer cell line (A2780). Compounds 3 and 20 showed the highest DNA damage effect in Comet Assay against the A2780 cancer cell line as compared to the other tested analogues (4, 8, 11, 12, and 13) by using % Tail DNA and OTM. Compounds 3, 4, and 11 showed significant activities and selectivity towards COX-2 with 78%, 97%, and 89% inhibition, as compared to 17%, 57%, and 26% inhibition against COX-1 isoenzyme, respectively., Results: Interestingly, molecular docking scores were also in very good agreement with the experimental results regarding discriminating the selectivity index of the tested compounds against COX-1 & COX-2 enzymes. Further molecular dynamics (MD) simulation study revealed that the most selective compound, 13, binds with the COX-2 enzyme in a similar fashion to that of Rofecoxib, which was further supported by their MD-based free binding energies (MM-GBSA) of -49.76 ± 4.27 kcal/mol, and -44.84 ±3.78 kcal/mol, respectively., Conclusion: Moreover, in silico ADMET predictions showed adequate properties for these compounds, making them promising leads worthy of further optimization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background : Breast cancer influences more than 2 million women worldwide annually. Since apoptotic dysregulation is a cancer hallmark, targeting apoptotic regulators encompasses strategic drug development for cancer therapy. One such class of apoptotic regulators is inhibitors of apoptosis proteins (IAP) which are a class of E3 ubiquitin ligases that actively function to support cancer growth and survival. Methods : The current study reports design, synthesis, docking analysis (based on binding to IAP-BIR3 domains), anti-proliferative and anti-tumor potential of the azomethine derivative, 1-(4-chlorophenyl)-N-(4-ethoxyphenyl)methanimine ( BCS3 ) on breast cancer (in vitro and in vivo) and its possible mechanisms of action. Results : Strong selective cytotoxic activity was observed in MDA-MB-231, MCF-7, and MDA-MB-468 breast cancer cell lines that exhibited IC50 values, 1.554 µM, 5.979 µM, and 6.462 µM, respectively, without affecting normal breast cells, MCF-10A. For the evaluation of the cytotoxic potential of BCS3 , immunofluorescence, immunoblotting, and FACS (apoptosis and cell cycle) analyses were conducted. BCS3 antagonized IAPs, thereby causing MDM2-p53 and Bcl-2-Caspase-mediated intrinsic and extrinsic apoptosis. It also modulated p53 expression causing p21-CDK1/cyclin B1-mediated cell cycle arrest at S and G2/M phases. The in vitro findings were consistent with in vivo findings as observed by reduced tumor volume and apoptosis initiation (TUNEL assay) by IAP downregulation. BCS3 also produced potent synergistic effects with doxorubicin on tumor inhibition. Conclusions : Having witnessed the profound anti-proliferative potential of BCS3 , the possible adverse effects related to anti-cancer therapy were examined following OECD 407 guidelines which confirmed its systemic safety profile and well tolerability. The results indicate the promising effect of BCS3 as an IAP antagonist for breast cancer therapy with fewer adverse effects.

Swertia chirayita is a popular hepatoprotective herb according to 'Ayurveda'. This study characterises the phytochemicals of S. chirayita responsible for hepatoprotective properties was executed using targeted metabolomics approach. Different fractions of hydro-alcoholic extract of S. chirayita were subjected to assess in-vitro antioxidant and hepatoprotective properties in HepG2 cells. Furthermore, active fraction was further subjected to UPLC-QTOF-MS based targeted metabolomics to identify the phytochemicals linked to bioactivity. A complementary in-silico experiment was also performed to understand the interactions of identified molecules with CYP2E1 enzyme. It was observed that, n-butanol fraction deciphers significant ( p  < .05) and maximum antioxidant and hepatocyte protection compared to other fractions. UPLC-QTOF-HRMS analysis reveals that it contains 17 secondary metabolites various classes. Identified molecules showed potential interactions with the crucial amino acid residues in the active site of CYP2E1 protein indicate the possibility of inhibition which may counter APAP induced toxicity in HepG2 cells.

Non-coding RNAs (lncRNAs) play critical roles in various cellular processes, including a novel form of regulated cell death known as disulfidptosis, characterized by accumulating protein disulfide bonds and severe endoplasmic reticulum stress. This review highlights the therapeutic potential of lncRNAs in regulating disulfidptosis for cancer treatment, emphasizing their influence on key pathway components such as GPX4, SLC7A11, and PDIA family members. Recent studies have demonstrated that targeting specific lncRNAs can sensitize cancer cells to disulfidptosis, offering a promising approach to cancer therapy. The regulation of disulfidptosis by lncRNAs involves various signaling pathways, including oxidative stress, ER stress, and calcium signaling. This review also discusses the molecular mechanisms underlying lncRNA regulation of disulfidptosis, the challenges of developing lncRNA-based therapies, and the future potential of this rapidly advancing field in cancer research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

A novel series of 7-(trifluoromethyl)indolizine derivatives (4a-4n) was synthesized using a 1,3-Dipolar cycloaddition reaction. Structure elucidation of the synthesized compounds was done using various spectroscopic techniques. Compounds were assessed for their larvicidal activity against Anopheles arabiensis. Exposure of Anopheles arabiensis larvae to a series of 7-(trifluoromethyl)indolizine at 4 µg/mL for 24 and 48 h resulted in moderate to high larval mortality rates. Among them, compounds 4b, 4a, 4g, and 4m exhibited the most promising larvicidal activities, with mortality rates of 94.4%, 93.3%, 80.00%, and 85.6%, respectively, compared to controls, Acetone and Temephos. The structural activity relationship analysis of the evaluated compounds revealed that substitution with halogens or electron-withdrawing groups (CN, F, Cl, Br) at the para position of the benzoyl group is crucial for achieving promising larvicidal activity. Molecular docking studies were carried out involving six potential larvicidal target proteins to predict how the tested compounds might work. Compounds 4a and 4b showed strong binding to the Mosquito Juvenile Hormone-Binding Protein (5V13). Molecular dynamics (MD) simulations confirmed the stability of the protein-ligand complexes over the simulation period, reinforcing the reliability of the docking results. Compounds 4a and 4b also exhibited favourable ADMET profiles, showing high oral bioavailability, good permeability, moderate distribution, low plasma protein binding, sufficient metabolic stability, efficient renal clearance and low toxicity. Given the crucial role of Juvenile Hormone in regulating gene expression and developmental pathways through receptor interactions, compounds 4a and 4b show promise as inhibitors of this protein. Inhibiting this process could hinder larval growth and reproduction, presenting a promising approach for early-stage mosquito larvicidal activity. Therefore, compounds 4a and 4b represent lead candidates for further optimization and the development of new larvicidal agents., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In the current study, two sets of compounds: (E)-1-(2-(4-substitutedphenyl)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium derivatives (3a-3e); and (E)-3-(substitutedbenzoyl)-7-((hydroxyimino)methyl)-2-substitutedindolizine-1-carboxylate derivatives (5a-5j), were synthesized and biologically evaluated against two strains of Mycobacterial tuberculosis (ATCC 25177) and multi-drug resistant (MDR) strains. Further, they were also tested in vitro against the mycobacterial InhA enzyme. The in vitro results showed excellent inhibitory activities against both MTB strains and compounds 5a-5j were found to be more potent, and their MIC values ranged from 5 to 16 μg/mL and 16-64 μg/mL against the M. tuberculosis (ATCC 25177) and MDR-TB strains, respectively. Compound 5h with phenyl and 4-fluorobenzoyl groups attached to the 2- and 3-position of the indolizine core was found to be the most active against both strains with MIC values of 5 μg/mL and 16 μg/mL, respectively. On the other hand, the two sets of compounds showed weak to moderate inhibition of InhA enzyme activity that ranged from 5 to 17 % and 10-52 %, respectively, with compound 5f containing 4-fluoro benzoyl group attached to the 3-position of the indolizine core being the most active (52 % inhibition of InhA). Unfortunately, there was no clear correlation between the InhA inhibitory activity and MIC values of the tested compounds, indicating the probability that they might have different modes of action other than InhA inhibition. Therefore, a computational investigation was conducted by employing molecular docking to identify their putative drug target(s) and, consequently, understand their mechanism of action. A panel of 20 essential mycobacterial enzymes was investigated, of which β-ketoacyl acyl carrier protein synthase I (KasA) and pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (BioA) enzymes were revealed as putative targets for compounds 3a-3e and 5a-5j, respectively. Moreover, in silico ADMET predictions showed adequate properties for these compounds, making them promising leads worthy of further optimization., Competing Interests: Declaration of competing interest Authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Malaria is one of the most known vector-borne diseases caused by female Anopheles mosquito bites. According to WHO, about 247 million cases of malaria and 619,000 deaths were estimated worldwide in 2021, of which 95% of the cases and 96% of deaths occurred in the African region. Sadly, about 80% of all malaria deaths were of children under five years old. Despite the availability of different insecticides used to control this disease, the emergence of drug-resistant mosquitoes threatens public health. This, in turn, highlighted the need for new larvicidal agents that are effective at different larval life stages. This study aimed to identify novel larvicidal agents. To this end, a series of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates 8a-i was synthesized using a three-step chemical synthetic approach via a Biginelli reaction employed as a key step. All title compounds were screened against Anopheles arabiensis to determine their larvicidal activities. Among them, two derivatives, ethyl 2-((4-bromophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8b and ethyl 2-((4-bromo-2-cyanophenyl)amino)-4-(4-fluorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate 8f , showed the highest larvicidal activity, with mortality of 94% and 91%, respectively, and emerged as potential larvicidal agents. In addition, computational studies, including molecular docking and molecular dynamics simulations, were carried out to investigate their mechanism of action. The computational results showed that acetylcholinesterase appears to be a plausible molecular target for their larvicidal property.Communicated by Ramaswamy H. Sarma.

Background: Clerodendrum glandulosum Lindl. is an important ethnomedicinal shrub of Northeast India, used by traditional healers to control various ailments like diabetes, hypertension, arthritis, etc. OBJECTIVES: The present study was conducted to explore the anti-hyperglycemic and antioxidative effects of the polyphenol-rich fraction (PRF) of C. glandulosum leaf extract and identification of its major bioactive compounds. Further, an in-silico molecular docking study was also performed to understand the molecular interactions of the identified major compounds with some target proteins associated with diabetic complications., Materials and Methods: PRF was purified from the hydromethanolic (80% MeOH) extract of leaves and subjected to assessment of in-vitro antioxidant and anti-diabetic properties. It was also subjected to evaluate the ameliorative effect during streptozotocin-nicotinamide-induced hyperglycemia in Wistar albino rats. An in-silico molecular docking study was also performed to complement the in-vitro/in-vivo studies., Results: Chemical analysis of PRF showed the presence of phenolics like caffeic acid, verbascoside, isoverbascoside, and apigenin, of which verbascoside (598.14 ± 1.24 mg/g) was found to be the principal compound. In-vitro studies showed potent antioxidant (IC 50 of DPPH:32.45 ± 2.16 μg/mL; ABTS:39.08 ± 0.53 μg/mL) properties and excellent aldose reductase inhibition potential (IC 50 2.18 ± 0.10 μg/mL). Treatment with PRF showed reduced blood glucose levels and increased plasma insulin levels. The results also indicate an improvement of endogenous antioxidants and suppression of inflammatory cytokines (IL-6 and TNF-α) comparable to the standard. Molecular docking studies predicted promising interactions between the identified molecules and the crucial amino acid residues of the enzymes involved in the development of hyperglycemia., Conclusion: This study revealed the antihyperglycemic and antioxidant potential of partially purified fraction PRF of C. glandulosum leaves., Competing Interests: Conflict of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rajlakshmi Devi reports financial support and administrative support were provided by Institute of Advanced Study in Science and Technology. Rajlakshmi Devi reports a relationship with Institute of Advanced Study in Science and Technology that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is caused by the aging process and manifested by cognitive deficits and progressive memory loss. During aging, several conditions, including hypertension, diabetes, and cholesterol, have been identified as potential causes of AD by affecting Sonic hedgehog (Shh) signalling. In addition to being essential for cell differentiation and proliferation, Shh signalling is involved in tissue repair and the prevention of neurodegeneration. Neurogenesis is dependent on Shh signalling; inhibition of this pathway results in neurodegeneration. Several protein-protein interactions that are involved in Shh signalling are implicated in the pathophysiology of AD like overexpression of the protein nexin-1 inhibits the Shh pathway in AD. A protein called Growth Arrest Specific-1 works with another protein called cysteine dioxygenase (CDO) to boost Shh signalling. CDO is involved in the development of the central nervous system (CNS). Shh signalling strengthened the blood brain barrier and therefore prevent the entry of amyloid beta and other toxins to the brain from periphery. Further, several traditional remedies used for AD and dementia, including Epigallocatechin gallate, yokukansan, Lycium barbarum polysaccharides, salvianolic acid, and baicalin, are known to stimulate the Shh pathway. In this review, we elaborated that the Shh signalling exerts a substantial influence on the pathogenesis of AD. In this article, we have tried to explore the various possible connections between the Shh signalling and various known pathologies of AD., Competing Interests: Declaration of Competing Interest Declaration from the authors that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

According to WHO, in 2021, there was an estimation of 247 million malaria cases from 84 malaria-endemic countries. Globally an estimated count of 2 billion malaria cases and 11.7 million deaths due to malaria were recorded in the past two decades. Further, the emergence of drug-resistant mosquitos threatens mankind. Therefore, the development of newer larvicidal agents is the need of the hour. This research identifies a new series of variably substituted indolizines for their effectiveness in controlling Anopheles arabiensis larvae through larvicidal activity. The series of Ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues (4a-j) were synthesized by reacting 4-(piperidin-1-yl)pyridine, phenacyl bromides with ethyl propiolate via 1, 3-dipolar cycloaddition and the green metrics of the process are reported. All the newly synthesized compounds were characterized by spectroscopic techniques such as 1 H NMR, 13 C NMR, FT-IR, and HRMS. The larvicidal effectiveness of the newly synthesized compounds was assessed against Anopheles arabiensis . Among the compounds studied, namely 4c , 4d , 4e , and 4f , displayed the most notable larval mortality rates within the series, reaching 73%, 81%, 76%, and 71% respectively, in contrast with the negative control acetone. In comparison, the standard Temephos exhibited a mortality rate of 99% at the same concentration. Furthermore, computational approaches including molecular docking and molecular dynamics simulations identified the potential targets of the series compounds as the larval Acetylcholinesterase (AChE) enzyme and the Sterol Carrier Protein-2 (SCP-2) protein. However, it is essential for these computational predictions to undergo experimental validation.Communicated by Ramaswamy H. Sarma.

Background: Metabolic disorder is characterized as chronic low-grade inflammation which elevates the systemic inflammatory markers. The proposed hypothesis behind this includes occurrence of hypoxia due to intake of high fat diet leading to oxidative stress and mitochondrial dysfunction., Aim: In the present work our aim was to elucidate the possible mechanism of action of hydroethanolic fraction of M. longifolia leaves against the metabolic disorder., Method and Results: In the present investigation, effect of Madhuca longifolia hydroethanolic fraction (MLHEF) on HFD induced obesity and diabetes through mitochondrial action and selective GLUT expression has been studied. In present work, it was observed that HFD (50% of diet) on chronic administration aggravates the metabolic problems by causing reduced imbalanced oxidative stress, ATP production, and altered selective GLUT protein expression. Long term HFD administration reduced (p < 0.001) the SOD, CAT level significantly along with elevated liver function marker AST and ALT. MLHEF administration diminishes this oxidative stress. HFD administration also causes decreased ATP/ADP ratio owing to suppressed mitochondrial function and elevating LDH level. This oxidative imbalance further leads to dysregulated GLUT expression in hepatocytes, skeletal muscles and white adipose tissue. HFD leads to significant (p < 0.001) upregulation in GLUT 1 and 3 expression while significant (p < 0.001) downregulation in GLUT 2 and 4 expressions in WAT, liver and skeletal muscles. Administration of MLHEF significantly (p < 0.001) reduced the LDH level and also reduces the mitochondrial dysfunction., Conclusion: Imbalances in GLUT levels were significantly reversed in order to maintain GLUT expression in tissues on the administration of MLHEF., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Icacinaceae, an Angiospermic family comprising 35 genera and 212 accepted species, including trees, shrubs, and lianas with pantropical distribution, is one of the most outshining yet least explored plant families, which despite its vital role as a source of pharmaceuticals and nutraceuticals has received a meagre amount of attraction from the scientific community. Interestingly, Icacinaceae is considered a potential alternative resource for camptothecin and its derivatives, which are used in treating ovarian and metastatic colorectal cancer. However, the concept of this family has been revised many times, but further recognition is still needed. The prime objective of this review is to compile the available information on this family in order to popularize it in the scientific community and the general population and promote extensive exploration of these taxa. The phytochemical preparations or isolated compounds from the Icacinaceae family have been centrally amalgamated to draw diverse future prospects from this inclusive plant species. The ethnopharmacological activities and the associated endophytes and cell culture techniques are also depicted. Nevertheless, the methodical evaluation of the Icacinaceae family is the only means to preserve and corroborate the folkloristic remedial effects and provide scientific recognition of its potencies before they are lost under the blanket of modernization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colorectal cancer (CRC) is the most frequent form of gastrointestinal cancer and one of the major causes of human mortality worldwide. Many of the current CRC therapies have limitations due to multidrug resistance and/or severe side effects. Quinazoline derivatives are promising lead compounds with a wide range of pharmacological actions. In this study, the effect of seven synthesized 2,3-dihydroquinazolin-4(1H)-one analogues as potential anticancer agents against two CRC cell lines (HCT116 and SW480) was investigated using cell viability proliferation, migration, adhesion and invasion assays. A liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics approach was used to identify the underlying biochemical pathways disturbed in treated-HCT116 cells. Cell viability proliferation assay revealed that four compounds (C2, C3, C5, and C7) had IC 50 < 10 µM with C5 displaying the most potent cytotoxic effect (IC 50 1.4 and 0.3 µM against HCT116 and SW480, respectively). Additionally, the compounds showed suppression of wound closure after 72 h, and both C2 and C5 significantly decreased the number of adherent cells and suppressed HCT116 cells invasion. Metabolomics study revealed that C5 induced significant perturbations in the level of several metabolites including spermine, polyamines, glutamine, creatine and carnitine, and altered biochemical processes essential for cell proliferation and progression such as amino acids biosynthesis and metabolism, redox homeostasis, energy related processes (e.g., fatty acid oxidation, second Warburg like effect) and one-carbon metabolism. Our findings indicate that 2,3-dihydroquinazolin-4(1H)-one analogues, particularly C5, have promising anticancer properties, and shed light on the role of metabolomics in identifying new therapeutic targets and providing better understanding of the pathways altered in treated cancer cells., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Malaria is a serious worldwide medical issue that results in substantial annual death and morbidity. The availability of treatment alternatives is limited, and the rise of resistant parasite types has posed a significant challenge to malaria treatment. To prevent a public health disaster, novel antimalarial agents with single-dosage therapies, extensive curative capability, and new mechanisms are urgently needed. There are several approaches to developing antimalarial drugs, ranging from alterations of current drugs to the creation of new compounds with specific targeting abilities. The availability of multiple genomic techniques, as well as recent advancements in parasite biology, provides a varied collection of possible targets for the development of novel treatments. A number of promising pharmacological interference targets have been uncovered in modern times. As a result, our review concentrates on the most current scientific and technical progress in the innovation of new antimalarial medications. The protein kinases, choline transport inhibitors, dihydroorotate dehydrogenase inhibitors, isoprenoid biosynthesis inhibitors, and enzymes involved in the metabolism of lipids and replication of deoxyribonucleic acid, are among the most fascinating antimalarial target proteins presently being investigated. The new cellular targets and drugs which can inhibit malaria and their development techniques are summarised in this study., (© 2023 Naveen Kumar Reddy Chinnappanna et al., published by Sciendo.)

Prostate cancer (PC) is the second most common tumor in males worldwide. The lack of effective medication and the development of multidrug resistance towards current chemotherapeutic agents urge the need to discover novel compounds and therapeutic targets for PC. Herein, seven synthesized 2,3-dihydroquinazolin-4(1H)-one analogues were evaluated for their anticancer activity against PC3 and DU145 cancer cell lines using MTT, scratch-wound healing, adhesion and invasion assays. Besides, a liquid chromatography mass spectrometry (LC-MS)-based metabolomics approach was followed to identify the biochemical pathways altered in DU145 cancer cells upon exposure to dihydroquinazolin derivatives. The seven compounds showed sufficient cytotoxicity and significantly suppressed DU145 and PC3 migration after 48 and 72 h. C2 and C5 had the most potent effect with IC 50  < 15 µM and significantly inhibited PC cell adhesion and invasion. Metabolomics revealed that C5 disturbed the level of metabolites involved in essential processes for cancer cell proliferation, progression and growth including energy production, redox homeostasis, amino acids and polyamine metabolisms and choline phospholipid metabolism. The data presented herein highlighted the importance of these compounds as potential anticancer agents particularly C5, and pointed to the promising role of metabolomics as a new analytical approach to investigate the antiproliferative activity of synthesized compounds and identify new therapeutic targets., (© 2022. The Author(s).)

Environmental sustainable analytical methods were developed by mathematical modification of UV absorption spectra for quality control study of multicomponent formulations consisting of remogliflozin (REM) and teneligliptin (TEN), with good sensitivity and selectivity. Then analytes were quantified by measuring the peak amplitude of the first derivative spectra at zero crossing points at 230.2 nm and 213.8 nm for REG and TEN in the first derivative method. The second method involves the formation of ratio spectra and taking the absorption difference at two selected wavelengths of peak and trough of a spectrum. In the ratio first derivative method peak amplitudes were measured at 235.2 nm and 259.1 nm for simultaneous quantification of REM and TEN respectively. The fourth method was based on the measurement of the peak amplitude of zero-order spectra of analytes generated from the mixture spectrum by subtraction of a constant from the ratio spectrum followed by multiplication with divisor spectrum, Further, the proposed methods were validated systematically to confirm the linearity, precession, accuracy, sensitivity, and selectivity. Finally, validated UV spectroscopic methods were applied for simultaneous quantification of REM and TEN from formulation, and laboratory mixed solutions and statistically compared with the reported HPLC method. Further, recently developed AGREE, Hexagonal greenness and white analytical chemistry, a whiteness evaluation tools were applied to the proposed UV spectroscopic methods and found to be safer analytical methods, compared to the reported expensive, time-consuming and toxic HPLC method. Hence, proposed UV spectroscopic methods could be used for routine quality control of formulations containing REM and TEN., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This Study aimed to characterise the phenolic compounds in Garcinia pedunculata extract and assess their potential antioxidant activity as well as its cardioprotective potential in isoproterenol-induced cardiac hypertrophy in an experimental animal model. In vitro antioxidant properties were determined using DPPH, ABTS, FRAP, PMD assays. In vitro lipid peroxidation experiment was also performed with heart tissues. Cardioprotective and cardiotoxicity effects were determined using the cell line studies. The cardioprotective effect of GP was assessed in a rat model of isoproterenol-(ISO-) induced cardiac hypertrophy by subcutaneous administration. Heart weight/tail length ratio and cardiac hypertrophy indicators were reduced after oral administration of GP. Additionally, GP reduced oxidative stress and heart inflammation brought on by ISO. In H9c2 cells, the antihypertrophic and anti-inflammatory effects of the extract of GP were seen in the presence of ISO, which were further supported by the in vivo observations. This study makes a compelling case for the possibility that supplementing with dried GP fruit can prevent heart hypertrophy by reducing oxidative stress and inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhattacharjee, Elancheran, Dutta, Deb and Devi.)

Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes mellitus occurring primarily in tropical countries like Bangladesh and has distinct characteristics. The present study aimed to describe the demographic, clinical and biochemical characteristics of patients with FCPD. This cross-sectional study was conducted at Mymensingh Medical College Hospital, Bangladesh, from January 2019 to December 2021. All patients with FCPD (previously or newly diagnosed) admitted to the inpatient Endocrinology department of the hospital were evaluated. Out of the 15 patients, 73.3% were aged 10-29 years at diagnosis, the male: female ratio was 11:4, rural: urban ratio was 9:6, 20.0% had FCPD in the first-degree family members, 73.3% were underweight, none were overweight/obese or central obese and one of them was hypertensive. Diabetes was uncontrolled in all, with a mean HbA1c of 10.5±1.9%. All but one had low C-peptide and all required insulin to manage diabetes. Although their average (mean or median) lipid parameters were normal, 73.3% of them had dyslipidemia. Among diabetic complications, diabetic nephropathy (66.7%) and neuropathy (66.7%) were more frequent, whereas diabetic retinopathy (6.7%), ischemic heart disease (6.7%) and peripheral vascular disease (6.7%) were less frequently observed; 13.3% had a history of diabetic ketoacidosis. Malnutrition manifested as abnormal skin and hair conditions and anemia was also common in the study subjects. Patients with FCPD are usually young males from rural residences. Microvascular diabetic complications are common, but macrovascular complications and DKA can occur in FCPD.

This study reports the influence of seasonality on the accumulation of verbascoside as a principal phenolic compound in Clerodendrum glandulosum Lindl. leaves along with possible alteration of antioxidant potentials. Leaves were collected during winter (December 2018), spring (February 2019), summer (May 2019), monsoon (July 2019), autumn (October 2019), and extracted with 95% aqueous methanol by cold maceration. The total phenolic content and antioxidant capacities (DPPH, ABTS and FRAP) were estimated by spectrophotometric technique, and verbascoside content was estimated by HPLC-PDA. Results indicate that the leaves collected during summer and winter both exhibited the highest total phenolic content verbascoside accumulation and antioxidant potentials which are significantly different ( p  < 0.05) than other seasons. Correlation studies further demonstrated that the total polyphenol and verbascoside contents were directly proportional to the antioxidant potentials. Thus, the study concludes that winter and summer are the best seasons for collecting leaves from this plant to obtain maximum antioxidant potential.

In this article, we propose a smart bedsheet-i-Sheet-for remotely monitoring the health of COVID-19 patients. Typically, real-time health monitoring is very crucial for COVID-19 patients to prevent their health from deteriorating. Conventional healthcare monitoring systems are manual and require patient input to start monitoring health. However, it is difficult for the patients to give input in critical conditions as well as at night. For instance, if the oxygen saturation level decreases during sleep, then it is difficult to monitor. Furthermore, there is a need for a system that monitors post-COVID effects as various vitals get affected, and there are chances of their failure even after the recovery. i-Sheet exploits these features and provides the health monitoring of COVID-19 patients based on their pressure on the bedsheet. It works in three phases: 1) sensing the pressure exerted by the patient on the bedsheet; 2) categorizing the data into groups (comfortable and uncomfortable) based on the fluctuations in the data; and 3) alerting the caregiver about the condition of the patient. Experimental results demonstrate the effectiveness of i-Sheet in monitoring the health of the patient. i-Sheet effectively categorizes the condition of the patient with an accuracy of 99.3% and utilizes 17.5 W of the power. Furthermore, the delay involved in monitoring the health of patients using i-Sheet is 2 s which is very diminutive and is acceptable.

Despite tremendous advancements in technologies and resources, drug discovery still remains a tedious and expensive process. Though most cells are cultured using 2D monolayer cultures, due to lack of specificity, biochemical incompatibility, and cell-to-cell/matrix communications, they often lag behind in the race of modern drug discovery. There exists compelling evidence that 3D cell culture models are quite promising and advantageous in mimicking in vivo conditions. It is anticipated that these 3D cell culture methods will bridge the translation of data from 2D cell culture to animal models. Although 3D technologies have been adopted widely these days, they still have certain challenges associated with them, such as the maintenance of a micro-tissue environment similar to in vivo models and a lack of reproducibility. However, newer 3D cell culture models are able to bypass these issues to a maximum extent. This review summarizes the basic principles of 3D cell culture approaches and emphasizes different 3D techniques such as hydrogels, spheroids, microfluidic devices, organoids, and 3D bioprinting methods. Besides the progress made so far in 3D cell culture systems, the article emphasizes the various challenges associated with these models and their potential role in drug repositioning, including perspectives from the COVID-19 pandemic.

The introduction of selective COX-2 inhibitors (so-called 'coxibs') has demonstrated tremendous commercial success due to their claimed lower potential of serious gastrointestinal adverse effects than traditional NSAIDs. However, following the repeated questioning on safety concerns, the coxibs 'controversial me-too' saga increased substantially, inferring to the risk of cardiovascular complications, subsequently leading to the voluntary withdrawal of coxibs (e.g., rofecoxib and valdecoxib) from the market. For instance, the makers (Pfizer and Merck) had to allegedly settle individual claims of cardiovascular hazards from celecoxib and valdecoxib. Undoubtedly, the lessons drawn from this saga revealed the flaws in drug surveillance and regulation, and taught science to pursue a more integrated translational approach for data acquisition and interpretation, prompting science-based strategies of risk avoidance in order to sustain the value of such drugs, rather than their withdrawal. Looking forward, coxibs are now being studied for repurposing, given their possible implications in the management of a myriad of diseases, including cancer, epilepsy, psychiatric disorders, obesity, Alzheimer's disease, and so on. This article briefly summarizes the development of COX-2 inhibitors to their market impression, followed by the controversy related to their toxicity. In addition, the events recollected in hindsight (the past lessons), the optimistic step towards drug repurposing (the present), and the potential for forthcoming success (the future) are also discussed.

A series of 2,3-dihydroquinazolin-4(1 H )-one derivatives ( 3a - 3m ) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 3l and 3m with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound 3k with an imidazole ring at the 2-position of the dihydroquinazolin-4(1 H )-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively. The computational results revealed the mycobacterial pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (BioA) enzyme as the potential target for the tested compounds. In vitro, ADMET calculations and cytotoxicity studies against the normal human dermal fibroblast cells indicated the safety and tolerability of the test compounds 3k - 3m . Thus, compounds 3k - 3m warrant further optimization to develop novel BioA inhibitors for the treatment of drug-sensitive H37Rv and drug-resistant MTB.

Cigarette smoking has been responsible for causing many life-threatening diseases such as pulmonary and cardiovascular diseases as well as lung cancer. One of the prominent health implications of cigarette smoking is the oxidative damage of cellular constituents, including proteins, lipids, and DNA. The oxidative damage is caused by reactive oxygen species (ROS, oxidants) present in the aqueous extract of cigarette smoke (CS). In recent years, there has been considerable interest in the potential health benefits of dietary polyphenols as natural antioxidant molecules. Epidemiological studies strongly suggest that long-term consumption of diets (fruits, vegetables, tea, and coffee) rich in polyphenols offer protective effects against the development of cancer, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. For instance, green tea has chemopreventive effects against CI-induced lung cancer. Tea might prevent CS-induced oxidative damages in diseases because tea polyphenols, such as catechin, EGCG, etc., have strong antioxidant properties. Moreover, apple polyphenols, including catechin and quercetin, provide protection against CS-induced acute lung injury such as chronic obstructive pulmonary disease (COPD). In CS-induced health problems, the antioxidant action is often accompanied by the anti-inflammatory effect of polyphenols. In this narrative review, the CS-induced oxidative damages and the associated health implications/pathological conditions (or diseases) and the role of diets rich in polyphenols and/or dietary polyphenolic compounds against various serious/chronic conditions of human health have been delineated.

For many decades, the thiazole moiety has been an important heterocycle in the world of chemistry. The thiazole ring consists of sulfur and nitrogen in such a fashion that the pi (π) electrons are free to move from one bond to other bonds rendering aromatic ring properties. On account of its aromaticity, the ring has many reactive positions where donor-acceptor, nucleophilic, oxidation reactions, etc., may take place. Molecules containing a thiazole ring, when entering physiological systems, behave unpredictably and reset the system differently. These molecules may activate/stop the biochemical pathways and enzymes or stimulate/block the receptors in the biological systems. Therefore, medicinal chemists have been focusing their efforts on thiazole-bearing compounds in order to develop novel therapeutic agents for a variety of pathological conditions. This review attempts to inform the readers on three major classes of thiazole-bearing molecules: Thiazoles as treatment drugs, thiazoles in clinical trials, and thiazoles in preclinical and developmental stages. A compilation of preclinical and developmental thiazole-bearing molecules is presented, focusing on their brief synthetic description and preclinical studies relating to structure-based activity analysis. The authors expect that the current review may succeed in drawing the attention of medicinal chemists to finding new leads, which may later be translated into new drugs.

Neuropathic pain affects more than one million people across the globe. The quality of life of people suffering from neuropathic pain has been considerably declining due to the unavailability of appropriate therapeutics. Currently, available treatment options can only treat patients symptomatically, but they are associated with severe adverse side effects and the development of tolerance over prolonged use. In the past decade, researchers were able to gain a better understanding of the mechanisms involved in neuropathic pain; thus, continuous efforts are evident, aiming to develop novel interventions with better efficacy instead of symptomatic treatment. The current review discusses the latest interventional strategies used in the treatment and management of neuropathic pain. This review also provides insights into the present scenario of pain research, particularly various interventional techniques such as spinal cord stimulation, steroid injection, neural blockade, transcranial/epidural stimulation, deep brain stimulation, percutaneous electrical nerve stimulation, neuroablative procedures, opto/chemogenetics, gene therapy, etc. In a nutshell, most of the above techniques are at preclinical stage and facing difficulty in translation to clinical studies due to the non-availability of appropriate methodologies. Therefore, continuing research on these interventional strategies may help in the development of promising novel therapies that can improve the quality of life of patients suffering from neuropathic pain.

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis , a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure-activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules' potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis , 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.

Antibiotic resistance continues to be a most serious threat to public health. This situation demands that the scientific community increase their efforts for the discovery of alternative strategies to circumvent the problems associated with conventional small molecule therapeutics. The Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report (published in June 2021) discloses the rapidly increasing number of bacterial infections that are mainly caused by antimicrobial-resistant bacteria. These concerns have initiated various government agencies and other organizations to educate the public regarding the appropriate use of antibiotics. This review discusses a brief highlight on the timeline of antimicrobial drug discovery with a special emphasis on the historical development of antimicrobial resistance. In addition, new antimicrobial targets and approaches, recent developments in drug screening, design, and delivery were covered. This review also discusses the emergence and roles of various antibiotic adjuvants and combination therapies while shedding light on current challenges and future perspectives. Overall, the emergence of resistant microbial strains has challenged drug discovery but their efforts to develop alternative technologies such as nanomaterials seem to be promising for the future.

Dietary polyphenols including phenolic acids, flavonoids, catechins, tannins, lignans, stilbenes, and anthocyanidins are widely found in grains, cereals, pulses, vegetables, spices, fruits, chocolates, and beverages like fruit juices, tea, coffee and wine. In recent years, dietary polyphenols have gained significant interest among researchers due to their potential chemopreventive/protective functions in the maintenance of human health and diseases. It is believed that dietary polyphenols/flavonoids exert powerful antioxidant action for protection against reactive oxygen species (ROS)/cellular oxidative stress (OS) towards the prevention of OS-related pathological conditions or diseases. Pre-clinical and clinical evidence strongly suggest that long term consumption of diets rich in polyphenols offer protection against the development of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases (CVDs), cancer, diabetes, inflammatory disorders and infectious illness. Increased intake of foods containing polyphenols (for example, quercetin, epigallocatechin-3-gallate, resveratrol, cyanidin etc.) has been claimed to reduce the extent of a majority of chronic oxidative cellular damage, DNA damage, tissue inflammations, viral/bacterial infections, and neurodegenerative diseases. It has been suggested that the antioxidant activity of dietary polyphenols plays a pivotal role in the prevention of OS-induced human diseases. In this narrative review, the biological/pharmacological significance of dietary polyphenols in the prevention of and/or protection against OS-induced major human diseases such as cancers, neurodegenerative diseases, CVDs, diabetes mellitus, cancer, inflammatory disorders and infectious diseases have been delineated. This review specifically focuses a current understanding on the dietary sources of polyphenols and their protective effects including mechanisms of action against various major human diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rudrapal, Khairnar, Khan, Dukhyil, Ansari, Alomary, Alshabrmi, Palai, Deb and Devi.)

Rheumatic Fever (RF)/ Rheumatic Heart Disease (RHD) is the result of autoimmune response triggered by group A Beta-haemolytic streptococcal pharyngitis leading to immune-inflammatory injury to cardiac valves. It is practically disappeared in developed countries. However, it continues to be a major cause of disease burden among children, adolescents, and young adults in low-income countries and even in high-income countries with socioeconomic inequalities. For decades, many cases of Acute Rheumatic Fever (ARF) and RHD were missed and were denied the secondary prophylaxis, as a result these patients used to end up with complications and untimely death. Advanced understanding of the echocardiography can prevent both under diagnosis and over diagnosis and thus help in management strategy. Another new advancement in recent past is the mitral valve repair, which is technically demanding, and the results are acceptable in experienced cardiac surgical units. Whenever feasible, valve repair should be preferred over valve replacement since it precludes the need for anticoagulation and future risks of prosthesis dysfunction., (© Journal of the Association of Physicians of India 2011.)

Noonan syndrome is a genetic disorder of autosomal dominant inheritance that prevents normal development in various parts of the body. A spontaneous mutation without any family history may also result in the condition. Noonan syndrome can affect normal growth. Birth weight may be normal, but growth slows over time. The growth spurt usually seen during the teenage years may be delayed, and bone maturity also is delayed. In this case A 13 year's male admitted inpatient Department of Endocrinology, Mymensingh Medical College Hospital in April 2021 with not attaining appropriate height and delayed development of secondary sexual characteristics. His birth weight was normal; gestational and neonatal history was uneventful. He was diagnosed with severe pulmonary stenosis at four years and underwent cardiac surgery at his four and eleven years. He was noted to have growth failure from the age of 9 years onward. He had no family history of such type of disease. On examination, he was short statured, underweight, having an upper: lower segment ratio of 1.05 with an arm span of 126cm. He had craniosynostosis, high arched palate, the thick helix of ears (outer rim), small, upturned nose, depressed broad nose, deeply grooved philtrum, keratosis pilaris of the face and upper arm, slant eyes with proptosis, keloid scar over mid-chest, widely spaced nipple, shield chest, pectus excavatum and cubitus valgus. His sexual maturation score was A1, P1, B1. He had pulmonary stenosis with pulmonary hypertension. He had mild microcytic anemia with normal liver, renal, blood glucose, and calcium profile. His bone age was delayed (9 years), thyroid function was normal. The growth hormone dynamic test after clonidine stimulation was normal. His karyotype was 46XY. We have considered giving recombinant growth hormone therapy to accelerate his height.

The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstituted-1,2,4-oxadiazole derivatives ( 3a-3i ) were tested against H37Rv, MDR and XDR strains of MTB. Of which, compound 3a with para-trifluorophenyl substituted oxadiazole showed excellent activity against the susceptible H37Rv and MDR-MTB strain with a MIC values of 8 and 16 µg/ml, respectively.To understand the mechanism of action of these compounds ( 3a-3i ) and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, in silico ADMET predictions showed satisfactory properties for these compounds, collectively, making them, particularly compound 3a , promising leads worthy of further optimisation.

A series of 1,2,3-trisubstituted indolizines ( 2a-2f, 3a-3d , and 4a-4c ) were screened for in vitro whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 2b-2d , 3a-3d , and 4a-4c were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines 4a-4c, with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16-64 µg/mL). In silico docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines. The X-ray diffraction analysis of the compound 4b was also carried out. Further, a safety study ( in silico and in vitro ) demonstrated no toxicity for these compounds. Thus, the indolizines warrant further development and may represent a novel promising class of InhA inhibitors and multi-targeting agents to combat drug-sensitive and drug-resistant MTB strains.

Chemoresistance poses a major hurdle to cancer treatments. Andrographolide-derived SRJ09 and SRJ23 were reported to exhibit potent, selective inhibitory activities against colon and prostate cancer cells, respectively. In this study, previously developed resistant colon (HCT-116 rst09 ) and prostate (PC-3 rst23 ) cancer cell lines were used to elucidate the molecular mechanisms contributing to chemoresistance. Cytotoxic effects of SRJ09 and SRJ23 on both parental and resistant cells were investigated. Cell cycle distributions in HCT-116 rst09 cells following SRJ09 treatment were analysed using flow cytometry. Whole-genome microarray analysis was performed on both parental and resistant cells to obtain differential gene expression profiles. Microarray data were subjected to protein-protein interaction network, functional enrichment, and pathway analyses. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the changes in expression levels of selected genes. Besides morphological changes, HCT-116 rst09 cells showed 7.0-fold resistance to SRJ09 while PC-3 rst23 cells displayed a 5.5-fold resistance to SRJ23, as compared with their respective parental cells. G 0 /G 1 -phase cell cycle arrest was observed in HCT-116 rst09 cells upon SRJ09 treatment. Collectively, 77 and 21 genes were found differentially modulated in HCT-116 rst09 and PC-3 rst23 cells, respectively. Subsequent bioinformatics analysis revealed several genes associated with FGFR4 and PI3K pathways, and cancer stemness, were chemoresistance mediators in HCT-116 rst09 cells. RT-PCR confirmed the HMOX1 upregulation and ATG12 downregulation protected the PC-3 rst23 cells from SRJ23 cytotoxicity. In conclusion, acquired chemoresistance to SRJ09 and SRJ23 in colon and prostate cancer cells, respectively, could be attributed to the alterations in the expression of genes such as those related to PI3K and autophagy pathways., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: Studies on the changes in the presentation and management of acute myocardial infarction (AMI) during the COVID-19 pandemic from low- and middle-income countries are limited. We sought to determine the changes in the number of admissions, management practices, and outcomes of AMI during the pandemic period in India., Methods & Results: In this two-timepoint cross-sectional study involving 187 hospitals across India, patients admitted with AMI between 15th March to 15th June in 2020 were compared with those admitted during the corresponding period of 2019. We included 41,832 consecutive adults with AMI. Admissions during the pandemic period (n = 16414) decreased by 35·4% as compared to the corresponding period in 2019 (n = 25418). We observed significant heterogeneity in this decline across India. The weekly average decrease in AMI admissions in 2020 correlated negatively with the number of COVID cases (r = -0·48; r 2  = 0·2), but strongly correlated with the stringency of lockdown index (r = 0·95; r 2  = 0·90). On a multi-level logistic regression, admissions were lower in 2020 with older age categories, tier 1 cities, and centers with high patient volume. Adjusted utilization rate of coronary angiography, and percutaneous coronary intervention decreased by 11·3%, and 5·9% respectively., Conclusions: The magnitude of reduction in AMI admissions across India was not uniform. The nature, time course, and the patient demographics were different compared to reports from other countries, suggesting a significant impact due to the lockdown. These findings have important implications in managing AMI during the pandemic., Competing Interests: Declaration of competing interest Nothing to declare for all the authors., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)