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Developmental Impacts of Epigenetics and Metabolism in COVID-19.
Naik, N, Patel, M, Sen, R
Journal of developmental biology. 2024;(1)
Abstract
Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host's immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host's metabolism, causing damage to the host's organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.
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Navigating the Gut-Cardiac Axis: Understanding Cardiovascular Complications in Inflammatory Bowel Disease.
Sinha, T, Zain, Z, Bokhari, SFH, Waheed, S, Reza, T, Eze-Odurukwe, A, Patel, M, Almadhoun, MKIK, Hussain, A, Reyaz, I
Cureus. 2024;(2):e55268
Abstract
Inflammatory bowel disease (IBD) presents a complex interplay of chronic inflammation in the gastrointestinal tract and is associated with various extraintestinal manifestations, including cardiovascular complications (CVCs). IBD patients face an elevated risk of CVCs, including coronary artery disease, heart failure, arrhythmias, stroke, peripheral artery disease, venous thromboembolism, and mesenteric ischemia, necessitating comprehensive cardiovascular risk assessment and management. The intricate interplay between chronic inflammation, genetic predisposition, environmental factors, and immune dysregulation likely contributes to the development of CVCs in IBD patients. While the exact mechanisms linking IBD and CVCs remain speculative, potential pathways may involve shared inflammatory pathways, endothelial dysfunction, dysbiosis of the gut microbiome, and traditional cardiovascular risk factors exacerbated by the chronic inflammatory state. Moreover, IBD medications, particularly corticosteroids, may impact cardiovascular health by inducing hypertension, insulin resistance, and dyslipidemia, further amplifying the overall CVC risk. Lifestyle factors such as smoking, obesity, and dietary habits may also exacerbate cardiovascular risks in individuals with IBD. Lifestyle modifications, including smoking cessation, adoption of a heart-healthy diet, regular exercise, and optimization of traditional cardiovascular risk factors, play a fundamental role in mitigating CVC risk. Emerging preventive strategies targeting inflammation modulation and gut microbiome interventions hold promise for future interventions, although further research is warranted to elucidate their efficacy and safety profiles in the context of IBD. Continued interdisciplinary collaboration, advanced research methodologies, and innovative interventions are essential to address the growing burden of CVCs in individuals living with IBD and to improve their long-term cardiovascular outcomes.
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3.
Is Coffee and Tea a Threat or Ally to Cardiovascular Health?
Mendpara, V, Garg, S, Shah, P, Bhavsar, J, Anamika, F, Patel, M, Munjal, RS, Gupta, V, Garg, N, Jain, R
Cureus. 2023;(12):e49991
Abstract
Tea and coffee have become ingrained in our daily lives and have become the most widely consumed drinks after water. Their effects vary on an individual basis depending upon the amount of daily consumption, genetic polymorphisms, and the presence of comorbidities. Non-habitual individuals experience an initial, brief increase in blood pressure due to caffeine's vasoactive effects. Caffeine also appears to be protective against arrhythmias and heart failure. Along with having a generally cardioprotective profile, they have also demonstrated to have a favorable impact on insulin resistance and reduced risk of diabetes mellitus. Physicians often practice caution and advise patients with known cardiovascular diseases to refrain from drinking caffeine; however, studies have shown that drinking two to three cups a day has either no or some beneficial effects on both patients with or without cardiac disorders like arrhythmias. This article focuses on the effects of tea and coffee on the cardiovascular system as well as the potential mechanisms involved.
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4.
A systematic review and meta-analysis of urinary biomarkers in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Taccori, A, Maksoud, R, Eaton-Fitch, N, Patel, M, Marshall-Gradisnik, S
Journal of translational medicine. 2023;(1):440
Abstract
BACKGROUND Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness that affects many body systems including the immune, nervous, endocrine, cardiovascular, and urinary systems. There is currently no universal diagnostic marker or targeted treatment for ME/CFS. Urine is a non-invasive sample that provides biomarkers that may have the potential to be used in a diagnostic capacity for ME/CFS. While there are several studies investigating urine-based biomarkers for ME/CFS, there are no published systematic reviews to summarise existing evidence of these markers. The aim of this systematic review was to compile and appraise literature on urinary-based biomarkers in ME/CFS patients compared with healthy controls. METHODS Three databases: Embase, PubMed, and Scopus were searched for articles pertaining to urinary biomarkers for ME/CFS compared with healthy controls published between December 1994 to December 2022. The final articles included in this review were determined through application of specific inclusion and exclusion criteria. Quality and bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. A meta-analysis according to Cochrane guidelines was conducted on select studies, in particular, those that investigate urinary free cortisol levels in ME/CFS patients compared to healthy controls using the program STATA 17. RESULTS Twenty-one studies were included in this review. All of the studies investigated urinary-based markers in ME/CFS patients compared with healthy controls. The reported changes in urinary outputs include urinary free cortisol (38.10%), carnitine (28.6%), iodine (4.76%), and the metabolome (42.86%). In most cases, there was minimal overlap in the main outcomes measured across the studies, however, differences in urinary free cortisol between ME/CFS patients and healthy controls were commonly reported. Seven studies investigating urinary free cortisol were included in the meta-analysis. While there were significant differences found in urinary free cortisol levels in ME/CFS patients, there was also substantial heterogeneity across the included studies that makes drawing conclusions difficult. CONCLUSIONS There is limited evidence suggesting a consistent and specific potential urinary-based biomarker for ME/CFS. Further investigations using more standardised methodologies and more stringent case criteria may be able to identify pathophysiological differences with diagnostic potential in ME/CFS patients compared with healthy controls.
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A Systematic Review Exploring the Cardiovascular and Renal Effects of Empagliflozin in Patients With Heart Failure With Reduced Ejection Fraction.
Athiyaman, S, Randhi, B, Gutlapalli, SD, Pu, J, Zaidi, MF, Patel, M, Atluri, LM, Gonzalez, NA, Sakhamuri, N, Venugopal, S
Cureus. 2022;(10):e29896
Abstract
The major cause of death in the United States is heart disease. The global burden of illness and mortality from heart failure is substantial. Despite recent innovations in the treatment of heart failure, the prognosis is still poor. To identify, evaluate, and summarize the findings of all relevant studies of a drug that is equally efficacious but rather cost-effective, empagliflozin compared to the other sodium-glucose cotransporter-2 (SGLT2) inhibitors was studied. It is licensed by the Food and Drug Administration (FDA), acts by preventing the reabsorption of glucose from the kidney, and exhibits promising advantages in heart failure. We systematically explored PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE) for randomized controlled trials (RCTs) and observational studies related to cardiovascular and renal outcomes of empagliflozin in patients with heart failure with reduced ejection fraction (HFrEF). After performing scoping search and search strategy, studies were screened for quality assessment using the Cochrane risk of bias assessment tool. We screened 60 articles by titles, abstract, and exclusion and inclusion criteria, after which eight final randomized controlled trials (RCTs) with 18,659 participants treated with empagliflozin and placebo were used for the systematic review. This systematic review's objective is to investigate and explore the full range of empagliflozin's effects and advantages on cardiac structure, function, and hemodynamics and renal function in patients with heart failure with reduced ejection fraction (EF) in order to better understand the drug's effects and related mechanisms.
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6.
Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta-analysis.
Kastora, S, Patel, M, Carter, B, Delibegovic, M, Myint, PK
Endocrinology, diabetes & metabolism. 2022;(3):e00338
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Abstract
INTRODUCTION To date, COVID-19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID-19 infection. Whether that holds true across world regions uniformly has not been previously assessed. METHODS This study offers the first umbrella systematic review and meta-analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID-19 hospitalization outcomes, were included. This meta-analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta-analysis reported, (2) no confirmed COVID-19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). RESULTS Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53-65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID-19-related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East-originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID-19 mortality, whilst the inverse was true for concurrent insulin use. CONCLUSIONS Whilst diabetes constitutes a poor prognosticator for various COVID-19 infection outcomes, variability across world regions is significant and may skew overall trends.
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Oral Cavity and Candida albicans: Colonisation to the Development of Infection.
Patel, M
Pathogens (Basel, Switzerland). 2022;(3)
Abstract
Candida colonisation of the oral cavity increases in immunocompromised individuals which leads to the development of oral candidiasis. In addition, host factors such as xerostomia, smoking, oral prostheses, dental caries, diabetes and cancer treatment accelerate the disease process. Candida albicans is the primary causative agent of this infection, owing to its ability to form biofilm and hyphae and to produce hydrolytic enzymes and candialysin. Although mucosal immunity is activated, from the time hyphae-associated toxin is formed by the colonising C. albicans cells, an increased number and virulence of this pathogenic organism collectively leads to infection. Prevention of the development of infection can be achieved by addressing the host physiological factors and habits. For maintenance of oral health, conventional oral hygiene products containing antimicrobial compounds, essential oils and phytochemicals can be considered, these products can maintain the low number of Candida in the oral cavity and reduce their virulence. Vulnerable patients should be educated in order to increase compliance.
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Phytochemical-loaded liposomes for anticancer therapy: an updated review.
Chavda, VP, Vihol, D, Mehta, B, Shah, D, Patel, M, Vora, LK, Pereira-Silva, M, Paiva-Santos, AC
Nanomedicine (London, England). 2022;(8):547-568
Abstract
The major obstacles observed in current chemotherapy are severe adverse effects, narrow therapeutic indexes and multidrug resistance. Anticancer phytochemicals are extracted and purified from natural plants, providing alternative therapeutic approaches with recognized biomedical benefits. However, poor bioavailability, high dose requirements and non-specific targeting have made those molecules less effective. To tackle those issues, liposomal nanovesicles for phytochemical delivery are taken into consideration for improving the therapeutic effectiveness by increasing transportation across cell barriers and conferring attractive cancer-specific targeting capabilities. In the present review, the liposomal approaches of anticancer phytochemicals are discussed, and recent advances in these formulations applied to cancer phytotherapy are further reviewed by an informed approach.
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A Systematic Review of Mixed Studies Exploring the Effects of Probiotics on Gut-Microbiome to Modulate Therapy in Children With Autism Spectrum Disorder.
Patel, M, Atluri, LM, Gonzalez, NA, Sakhamuri, N, Athiyaman, S, Randhi, B, Gutlapalli, SD, Pu, J, Zaidi, MF, Khan, S
Cureus. 2022;(12):e32313
Abstract
Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder characterized by social deficits, repetitive typical behaviors, insistence on the same routines, and communication impairments. The prevalence of ASD has increased in the past decade. While we are aware that there is no cure for ASD, attempts are being made to reduce its symptoms and improve the learning, overall growth, and well-being of ASD patients. Gastrointestinal (GI) symptoms are frequent occurrences in patients with ASD, but the underlying mechanisms are unknown. Recent studies show that the microbiota-gut-brain axis is the key modulator of neuropsychiatric health. Although fecal transplants have shown positive outcomes in treating dysbiosis and symptoms of autism, lifestyle modifications such as dietary intervention will prevent and treat this disorder without causing major adverse effects. Probiotics enhance the microbiome to provide necessary metabolites, which help in gut permeability, cognitive function, and immunity. In some studies, children with increased GI symptoms have also shown increased behavioral disturbances. In this study, a systematic review of mixed studies is conducted to obtain more robust and conclusive results. We included randomized controlled studies with larger sample sizes and specifications on probiotics.
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Current status and strategic possibilities on potential use of combinational drug therapy against COVID-19 caused by SARS-CoV-2.
Siddiqui, AJ, Jahan, S, Ashraf, SA, Alreshidi, M, Ashraf, MS, Patel, M, Snoussi, M, Singh, R, Adnan, M
Journal of biomolecular structure & dynamics. 2021;(17):6828-6841
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Abstract
The spread of new coronavirus infection starting December 2019 as novel SARS-CoV-2, identified as the causing agent of COVID-19, has affected all over the world and been declared as pandemic. Approximately, more than 8,807,398 confirmed cases of COVID-19 infection and 464,483 deaths have been reported globally till the end of 21 June 2020. Until now, there is no specific drug therapy or vaccine available for the treatment of COVID-19. However, some potential antimalarial drugs like hydroxychloroquine and azithromycin, antifilarial drug ivermectin and antiviral drugs have been tested by many research groups worldwide for their possible effect against the COVID-19. Hydroxychloroquine and ivermectin have been identified to act by creating the acidic condition in cells and inhibiting the importin (IMPα/β1) mediated viral import. There is a possibility that some other antimalarial drugs/antibiotics in combination with immunomodulators may help in combatting this pandemic disease. Therefore, this review focuses on the current use of various drugs as single agents (hydroxychloroquine, ivermectin, azithromycin, favipiravir, remdesivir, umifenovir, teicoplanin, nitazoxanide, doxycycline, and dexamethasone) or in combinations with immunomodulators additionally. Furthermore, possible mode of action, efficacy and current stage of clinical trials of various drug combinations against COVID-19 disease has also been discussed in detail.Communicated by Ramaswamy H. Sarma.