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1.
The Impact of Salinity on Crop Yields and the Confrontational Behavior of Transcriptional Regulators, Nanoparticles, and Antioxidant Defensive Mechanisms under Stressful Conditions: A Review.
Ahmed, M, Tóth, Z, Decsi, K
International journal of molecular sciences. 2024;(5)
Abstract
One of the most significant environmental challenges to crop growth and yield worldwide is soil salinization. Salinity lowers soil solution water potential, causes ionic disequilibrium and specific ion effects, and increases reactive oxygen species (ROS) buildup, causing several physiological and biochemical issues in plants. Plants have developed biological and molecular methods to combat salt stress. Salt-signaling mechanisms regulated by phytohormones may provide additional defense in salty conditions. That discovery helped identify the molecular pathways that underlie zinc-oxide nanoparticle (ZnO-NP)-based salt tolerance in certain plants. It emphasized the need to study processes like transcriptional regulation that govern plants' many physiological responses to such harsh conditions. ZnO-NPs have shown the capability to reduce salinity stress by working with transcription factors (TFs) like AP2/EREBP, WRKYs, NACs, and bZIPs that are released or triggered to stimulate plant cell osmotic pressure-regulating hormones and chemicals. In addition, ZnO-NPs have been shown to reduce the expression of stress markers such as malondialdehyde (MDA) and hydrogen peroxide (H2O2) while also affecting transcriptional factors. Those systems helped maintain protein integrity, selective permeability, photosynthesis, and other physiological processes in salt-stressed plants. This review examined how salt stress affects crop yield and suggested that ZnO-NPs could reduce plant salinity stress instead of osmolytes and plant hormones.
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2.
Food environment research in Canada: a rapid review of methodologies and measures deployed between 2010 and 2021.
Vaillancourt, C, Ahmed, M, Kirk, S, Labonté, MÈ, Laar, A, Mah, CL, Minaker, L, Olstad, DL, Potvin Kent, M, Provencher, V, et al
The international journal of behavioral nutrition and physical activity. 2024;(1):18
Abstract
Numerous research methodologies have been used to examine food environments. Existing reviews synthesizing food environment measures have examined a limited number of domains or settings and none have specifically targeted Canada. This rapid review aimed to 1) map research methodologies and measures that have been used to assess food environments; 2) examine what food environment dimensions and equity related-factors have been assessed; and 3) identify research gaps and priorities to guide future research. A systematic search of primary articles evaluating the Canadian food environment in a real-world setting was conducted. Publications in English or French published in peer-reviewed journals between January 1 2010 and June 17 2021 and indexed in Web of Science, CAB Abstracts and Ovid MEDLINE were considered. The search strategy adapted an internationally-adopted food environment monitoring framework covering 7 domains (Food Marketing; Labelling; Prices; Provision; Composition; Retail; and Trade and Investment). The final sample included 220 articles. Overall, Trade and Investment (1%, n = 2), Labelling (7%, n = 15) and, to a lesser extent, Prices (14%, n = 30) were the least studied domains in Canada. Among Provision articles, healthcare (2%, n = 1) settings were underrepresented compared to school (67%, n = 28) and recreation and sport (24%, n = 10) settings, as was the food service industry (14%, n = 6) compared to grocery stores (86%, n = 36) in the Composition domain. The study identified a vast selection of measures employed in Canada overall and within single domains. Equity-related factors were only examined in half of articles (n = 108), mostly related to Retail (n = 81). A number of gaps remain that prevent a holistic and systems-level analysis of food environments in Canada. As Canada continues to implement policies to improve the quality of food environments in order to improve dietary patterns, targeted research to address identified gaps and harmonize methods across studies will help evaluate policy impact over time.
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3.
Computational and experimental strategies for combating MBL P. aeruginosa (MBLPA) biofilms using phytochemicals: Targeting the quorum sensing network.
Fakhar, M, Ahmed, M, Nasim Sabri, A
Saudi journal of biological sciences. 2024;(6):104001
Abstract
Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, ubiquitously found in nature and causative agent in many infections. Due to increased antibiotic resistance, there is a need to develop more robust antibacterial agents from natural sources. In this study, we worked on two metallo-β-lactamase (MBL) producing Pseudomonas aeruginosa strains and targeted the Quorum Sensing mechanism (QS) of these bacteria to combat antibiotic resistance. Our study aimed at using phytochemicals which have been used since centuries in herbal medicine. We used fifteen commercially available phytochemicals and check their effects on biofilm formation, quorum sensing and inter-related mechanisms. Sub-inhibitory concentration of isoliquiritin inhibited biofilm formation 55 % in P8 at day 6 and 48 % in P6 at day 6; quorum sensing 83 % in P6 and 61 % in P8 whereas sub-inhibitory concentration of 6-gingerol suppressed biofilm formation by 48 % in P8 at day 6 and 44 % in P6 at day 6; quorum sensing 69 % in P6 and 48 % in P8, respectively. The results indicated isoliquiritin, epigallocatechin gallate, eugenol, luteolin and chrysin to be the potential candidates in inhibiting QS and related mechanisms. Isoliquiritin which was never been used before against biofilm and QS related studies, showed remarkable results and found to be more efficient in inhibiting QS than 6-gingerol -a known QS inhibitor. For examining the molecular interaction between phytochemicals and QS, In-silico molecular docking was performed between phytoligands and four QS proteins (Las I, Las R, RhlI and Rhl R). In-silico docking analysis revealed that isoliquiritin showed strong bond with amino acids (Trp34, Asp35, Asp35, Tyr105, Arg104, Val138, Thr140) present at the active site of RhlI with binding energy value of -8.4 kcal/mol as compared to that of 6-gingerol with Rhl1 (-7.3 kcal/mol). In conclusion, our study may help in controlling nosocomial infections caused by carbapenem-resistant metallo beta-lactamase P. aeruginosa (MBL-PA) by utilizing these phytochemicals in biofilms disruption and quorum sensing inhibition. Moreover their synergism with antibiotics may help in lowering the MIC of carbapenem antibiotics against such Multi-drug resistant strains.
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4.
Caveolin-1 and lipids: Association and their dualism in oncogenic regulation.
Bhowmick, S, Biswas, T, Ahmed, M, Roy, D, Mondal, S
Biochimica et biophysica acta. Reviews on cancer. 2023;(6):189002
Abstract
Caveolin-1 (Cav-1) is a structural protein of caveolae that functions as a molecular organizer for different cellular functions including endocytosis and cellular signaling. Cancer cells take advantage of the physical position of Cav-1, as it can communicate with extracellular matrix, help to organize growth factor receptors, redistribute cholesterol and glycosphingolipids, and finally transduce signals within the cells for oncogenesis. Recent studies emphasize the exceeding involvement of Cav-1 with different lipid bodies and in altering the metabolism, especially lipid metabolism. However, the association of Cav-1 with different lipid bodies like lipid rafts, lipid droplets, cholesterols, sphingolipids, and fatty acids is remarkably dynamic. The lipid-Cav-1 alliance plays a dual role in carcinogenesis. Both cancer progression and regression are modified and affected by the type of lipid molecule's association with Cav-1. Accordingly, this Cav-1-lipid cooperation exemplifies a cancer-type-specific treatment strategy for a better prognosis of the disease. In this review, we first present Cav-1 as an oncogenic molecule and its communication via lipid raft. We discussed the involvement of Cav-1 with lipid droplets, Cholesterol, sphingolipids, gangliosides, and ceramides. Further, we describe the Cav-1-mediated altered Fatty acid metabolism in cancer and the strategic therapeutic approaches toward Cav-1 targeting.
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5.
Cognitive development among children in a low-income setting: Cost-effectiveness analysis of a maternal nutrition education intervention in rural Uganda.
Ahmed, M, Muhoozi, GKM, Atukunda, P, Westerberg, AC, Iversen, PO, Wangen, KR
PloS one. 2023;(8):e0290379
Abstract
Inadequate nutrition and insufficient stimulation in early childhood can lead to long-term deficits in cognitive and social development. Evidence for policy and decision-making regarding the cost of delivering nutrition education is lacking in low and middle-income countries (LMIC). In rural Uganda, we conducted a cluster-randomized controlled trial (RCT) examining the effect of a maternal nutrition education intervention on developmental outcomes among children aged 6-8 months. This intervention led to significantly improved cognitive scores when the children reached the age of 20-24 months. When considering the potential for this intervention's future implementation, the desired effects should be weighed against the increased costs. This study therefore aimed to assess the cost-effectiveness of this education intervention compared with current practice. Health outcome data were based on the RCT. Cost data were initially identified by reviewing publications from the RCT, while more detailed information was obtained by interviewing researchers involved in processing the intervention. This study considered a healthcare provider perspective for an 18-months' time horizon. The control group was considered as the current practice for the future large-scale implementation of this intervention. A cost-effectiveness analysis was performed, including calculations of incremental cost-effectiveness ratios (ICERs). In addition, uncertainty in the results was characterized using one-way and probabilistic sensitivity analyses. The ICER for the education intervention compared with current practice was USD ($) 16.50 per cognitive composite score gained, with an incremental cost of $265.79 and an incremental cognitive composite score of 16.11. The sensitivity analyses indicated the robustness of these results. The ICER was sensitive to changes in cognitive composite score and the cost of personnel. The education intervention can be considered cost-effective compared with the current practice. The outcome of this study, including the cost analysis, health outcome, cost-effectiveness, and sensitivity analysis, can be useful to inform policymakers and stakeholders about effective resource allocation processes in Uganda and possibly other LMIC.
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6.
A computational odyssey: uncovering classical β-lactamase inhibitors in dry fruits.
Javid, A, Ahmed, M
Journal of biomolecular structure & dynamics. 2023;:1-27
Abstract
In the antibacterial arsenal, β-lactams have held a prominent position, but increasing resistance due to unauthorized use and genetic factors requires new strategies. Combining β-lactamase inhibitors with broad-spectrum β-lactams proves effective in combating this resistance. ESBL producers demand new inhibitors, leading to the exploration of plant-derived secondary metabolites for potent β-lactam antibiotics or alternative inhibitors. Using virtual screening, molecular docking, ADMET analysis, and molecular dynamic simulation, this study actively analyzed the inhibitory activity of figs, cashews, walnuts, and peanuts against SHV-1, NDM-1, KPC-2, and OXA-48 β-lactamases. Using AutoDock Vina, the docking affinities of various compounds for target enzymes were initially screened, revealing 12 bioactive compounds with higher affinities for the target enzymes compared to Avibactam and Tazobactam. Top-scoring metabolites, including Oleanolic acid, Protocatechuic acid, and Tannin, were subjected to MD simulation studies to further analyze the stability of the docked complexes using WebGro. The simulation coordinates, in terms of RMSD, RMSF, SASA, Rg, and hydrogen bonds formed, showed that these phytocompounds are stable enough to retain in the active sites at various orientations. The PCA and FEL analysis also showed the stability of the dynamic motion of Cα residues of phytochemical-bound enzymes. The pharmacokinetic analysis of the top phytochemicals was performed to analyze their bioavailability and toxicity. This study provides new insights into the therapeutic potential of phytochemicals of selected dry fruits and contributes to future experimental studies to identify βL inhibitors from plants.Communicated by Ramaswamy H. Sarma.
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7.
Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
Amare, A, Thalamuthu, A, Schubert, KO, Fullerton, J, Ahmed, M, Hartmann, S, Papiol, S, Heilbronner, U, Degenhardt, F, Tekola-Ayele, F, et al
Research square. 2023
Abstract
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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8.
Bone Health in People Living with HIV/AIDS: An Update of Where We Are and Potential Future Strategies.
Ahmed, M, Mital, D, Abubaker, NE, Panourgia, M, Owles, H, Papadaki, I, Ahmed, MH
Microorganisms. 2023;(3)
Abstract
The developments in Human Immunodeficiency Virus (HIV) treatment and in the care of people living with HIV (PLWHIV) and Acquired Immunodeficiency Syndrome (AIDS) over the last three decades has led to a significant increase in life expectancy, on par with HIV-negative individuals. Aside from the fact that bone fractures tend to occur 10 years earlier than in HIV-negative individuals, HIV is, per se, an independent risk factor for bone fractures. A few available antiretroviral therapies (ARVs) are also linked with osteoporosis, particularly those involving tenofovir disoproxil fumarate (TDF). HIV and hepatitis C (HCV) coinfection is associated with a greater risk of osteoporosis and fracture than HIV monoinfection. Both the Fracture Risk Assessment Tool (FRAX) and measurement of bone mineral density (BMD) via a DEXA scan are routinely used in the assessment of fracture risk in individuals living with HIV, as bone loss is thought to start between the ages of 40 and 50 years old. The main treatment for established osteoporosis involves bisphosphonates. Supplementation with calcium and vitamin D is part of clinical practice of most HIV centers globally. Further research is needed to assess (i) the cut-off age for assessment of osteoporosis, (ii) the utility of anti-osteoporotic agents in PLWHIV and (iii) how concomitant viral infections and COVID-19 in PLWHIV can increase risk of osteoporosis.
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9.
A Systematic Review Looking at the Current Best Practices as well as Primary Care Practitioner's Views on the Diagnosis and Treatment of Childhood Obesity.
Ahmed, U, Mahmood, MS, Parsons, M, O'callaghan, H, Pawlik, O, Chaudhary, S, Ahmed, M
Cureus. 2023;(1):e34346
Abstract
Childhood obesity is a significant and growing issue, with the WHO recognising worldwide childhood obesity rates as an epidemic. Primary care is often the first point for monitoring a child's development over time, hence could play an integral part in recognising and addressing childhood obesity. As a result, our systematic review has two objectives. The primary objective is to review the current evidence on best practices in diagnosing and treating childhood obesity. The secondary objective is to review recent qualitative studies looking into the view of primary care practitioners on the treatment and diagnosis of childhood obesity. The rationale for this is to help determine what opportunities there are in primary care in the NHS to tackle childhood obesity. Using searches in MEDLINE, EMBASE, PSYCHINFO, HMIC and NHS evidence over a five-year period from March 2014 to March 2019, a total of 37 studies were eligible for inclusion in the review. Out of these, 25 studies identified exploring the diagnosis and treatment of childhood obesity. A few key themes in these studies were identified, including motivational interviewing, m-health, tools and resources used in consultations, the use of dieticians in the primary care team and factors concerned with the identification of obesity in children. The rest of the 12 qualitative studies involved eliciting the views of direct stakeholders about the diagnosis and treatment of obesity in children. Eight of the studies investigated providers' views towards the role of primary care practitioners in treating childhood obesity, two investigated the parents of obese children's perspectives and the other two investigated general practitioners' (GPs) views towards specific tools and resources. Regarding our primary objective, our findings showed many studies looking at interventions to reduce the BMI in obese children fail to do so in a statistically significant way. However, a few interventions have been more consistent in reducing BMI and obesogenic behaviours. Those interventions include ones utilising the motivational interviewing technique and those targeting families, rather than children. Another key finding was that tools and resources available to primary care providers can significantly impact their ability to diagnose and treat obesity, particularly when looking at the detection. Finally, evidence regarding the clinical effectiveness of e-health is limited, with views on their use also mixed. Regarding our secondary objective, the qualitative research identified demonstrated many common views from GPs across different countries. It showed healthcare providers (HCPs) perceiving the parents as lacking in motivation to address the issue, HCPs not wanting to damage the relationship with their patients due to it being a sensitive topic to bring up, and a lack of time, training and confidence. However, some of these views may not be generalisable to the UK due to cultural and system differences.
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10.
Emerging Promise of Therapeutic Approaches Targeting Mitochondria in Neurodegenerative Disorders.
Rahman, MM, Tumpa, MAA, Rahaman, MS, Islam, F, Sutradhar, PR, Ahmed, M, Alghamdi, BS, Hafeez, A, Alexiou, A, Perveen, A, et al
Current neuropharmacology. 2023;(5):1081-1099
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Abstract
Mitochondria are critical for homeostasis and metabolism in all cellular eukaryotes. Brain mitochondria are the primary source of fuel that supports many brain functions, including intracellular energy supply, cellular calcium regulation, regulation of limited cellular oxidative capacity, and control of cell death. Much evidence suggests that mitochondria play a central role in neurodegenerative disorders (NDDs) such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Ongoing studies of NDDs have revealed that mitochondrial pathology is mainly found in inherited or irregular NDDs and is thought to be associated with the pathophysiological cycle of these disorders. Typical mitochondrial disturbances in NDDs include increased free radical production, decreased ATP synthesis, alterations in mitochondrial permeability, and mitochondrial DNA damage. The main objective of this review is to highlight the basic mitochondrial problems that occur in NDDs and discuss the use mitochondrial drugs, especially mitochondrial antioxidants, mitochondrial permeability transition blockade, and mitochondrial gene therapy, for the treatment and control of NDDs.