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1.
Berberine: Pharmacological Features in Health, Disease and Aging.
Gasmi, A, Asghar, F, Zafar, S, Oliinyk, P, Khavrona, O, Lysiuk, R, Peana, M, Piscopo, S, Antonyak, H, Pen, JJ, et al
Current medicinal chemistry. 2024;(10):1214-1234
Abstract
BACKGROUND Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. OBJECTIVE This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. METHODS Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. RESULTS Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. CONCLUSION Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.
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2.
Sleep, Dietary Melatonin Supplementation, and COVID-19.
Gasmi, A, Semenova, Y, Noor, S, Benahmed, AG, Bjørklund, G
Current medicinal chemistry. 2024;(11):1298-1314
Abstract
BACKGROUND During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home confinement. Melatonin is a popular anti-inflammatory and antioxidant molecule sold as an over-the-counter dietary supplement. OBJECTIVE This review discusses the indications for using melatonin in the context of the COVID-19 pandemic, including treatment. METHODS A comprehensive search of publications was conducted in electronic databases focusing on the administration of melatonin in COVID-19. RESULTS Stress has a huge negative impact on sleep routines and the quality of life of individuals. Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The administration of melatonin protects against viral and other pathogens and speeds clinical recovery. CONCLUSION In patients admitted to intensive care units, melatonin decreases the risks of severe complications, such as thrombosis and sepsis, and mortality rates. In addition, it is efficacious in lowering vessel permeability, depression, and sedation, and improving the quality of sleep, which could also help COVID-19 patients achieve better clinical outcomes.
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3.
The role of serum and glucocorticoid-regulated kinase 1 in cellular signaling: Implications for drug development.
Gulzar, M, Noor, S, Hasan, GM, Hassan, MI
International journal of biological macromolecules. 2024;(Pt 1):128725
Abstract
Serum and glucocorticoid-regulated kinase 1 (SGK1) is a ubiquitously expressed protein belonging to the Ser/Thr kinase family. It regulates diverse physiological processes, including epithelial sodium channel activity, hypertension, cell proliferation, and insulin sensitivity. Due to its significant role in the pathogenesis of numerous diseases, SGK1 can be exploited as a potential therapeutic target to address challenging health problems. SGK1 is associated with the development of obesity, and its overexpression enhances the sodium-glucose co-transporter 1 activity, which absorbs intestinal glucose. This review highlighted the detailed functional significance of SGK1 signaling and role in different diseases and subsequent therapeutic targeting. We aim to provide deeper mechanistic insights into understanding the pathogenesis and recent advancements in the SGK1 targeted drug development process. Small-molecule inhibitors are being developed with excellent binding affinity and improved SGK1 inhibition with desired selectivity. We have discussed small molecule inhibitors designed explicitly as potent SGK1 inhibitors and their therapeutic implications in various diseases. We further addressed the therapeutic potential and mechanism of action of these SGK1 inhibitors and provided a strong scientific foundation for developing effective therapeutics.
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4.
Risk of Bleeding Following Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase.
Tsai, TY, Liu, YC, Huang, WT, Tu, YK, Qiu, SQ, Noor, S, Huang, YC, Chou, EH, Lai, EC, Huang, HK
JAMA internal medicine. 2024;(1):37-45
Abstract
IMPORTANCE Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). OBJECTIVE To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. DESIGN, SETTING, AND PARTICIPANTS This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. EXPOSURES NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. MAIN OUTCOMES AND MEASURES The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. RESULTS Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. CONCLUSIONS AND RELEVANCE In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.
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5.
Decoding the multifaceted interventions between human sirtuin 2 and dynamic hepatitis B viral proteins to confirm their roles in HBV replication.
Piracha, ZZ, Saeed, U, Piracha, IE, Noor, S, Noor, E
Frontiers in cellular and infection microbiology. 2023;:1234903
Abstract
The human sirtuin 2 gene (SIRT2) encodes a full-length Sirt2 protein (i.e., the Sirt2 isoform 1), which primarily functions as a cytoplasmic α-tubulin deacetylase, and which promotes the growth of hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) replication itself, or HBV X (HBx) protein-mediated transcriptional transactivation, enhances Sirt2.1 expression; therefore, Sirt2.1 itself is capable of positively increasing HBV transcription and replication. Sirt2.1 is linked to liver fibrosis and epithelial-to-mesenchymal transition and, consequently, augments the risk of HCC. The Sirt2.1 protein enhances the HBV replication cycle by activating the AKT/glycogen synthase kinase 3 beta (GSK3β)/β-catenin pathway. It also activates the transcription of the viral enhancer I/HBx promoter (EnI/Xp) and enhancer II/HBc promoter (EnII/Cp) by targeting the transcription factor p53. The Sirt2 isoform 2 (Sirt2.2) is mainly localized in the cytoplasm, and the N-terminus is shorter by 37 amino acids than that of Sirt2.1. Despite the truncation of the N-terminal region, Sirt2.2 is still capable of enhancing HBV replication and activating the AKT/GSK3β/β-catenin signaling pathway. The Sirt2 isoform 5 (Sirt2.5) is primarily localized to the nucleus, it lacks a nuclear export signal (NES), and the catalytic domain (CD) is truncated. Upon HBV replication, expression of the Sirt2 isoforms is also enhanced, which further upregulates the HBV replication, and, therefore, supports the vicious cycle of viral replication and progression of the disease. Sirt2 diversely affects HBV replication such that its isoform 1 intensely augments HBV replication and isoform 2 (despite of the truncated N-terminal region) moderately enhances HBV replication. Isoform 5, on the other hand, tends to protect the cell (for smooth long-term continued viral replication) from HBV-induced extreme damage or death via a discrete set of regulatory mechanisms impeding viral mRNAs, the hepatitis B core/capsid protein (HBc), core particles, replicative intermediate (RI) DNAs, and covalently closed circular DNA (cccDNA) levels, and, consequently, limiting HBV replication. In contrast to Sirt2.1 and Sirt 2.2, the Sirt2.5-mediated HBV replication is independent of the AKT/GSK3β/β-catenin signaling cascade. Sirt2.5 is recruited more at cccDNA than the recruitment of Sirt2.1 onto the cccDNA. This recruitment causes the deposition of more histone lysine methyltransferases (HKMTs), including SETDB1, SUV39H1, EZH2, and PR-Set7, along with the respective corresponding transcriptional repressive markers such as H3K9me3, H3K27me3, and H4K20me1 onto the HBV cccDNA. In HBV-replicating cells, Sirt2.5 can also make complexes with PR-Set7 and SETDB1. In addition, Sirt2.5 has the ability to turn off transcription from cccDNA through epigenetic modification via either direct or indirect interaction with HKMTs.
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6.
Nutritional and surgical aspects in prostate disorders.
Gasmi, A, Bjørklund, G, Noor, S, Semenova, Y, Dosa, A, Pen, JJ, Menzel, A, Piscopo, S, Wirth, N, Costea, DO
Critical reviews in food science and nutrition. 2023;(21):5138-5154
Abstract
Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.
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7.
Chemopreventive role of probiotics against cancer: a comprehensive mechanistic review.
Noor, S, Ali, S, Riaz, S, Sardar, I, Farooq, MA, Sajjad, A
Molecular biology reports. 2023;(1):799-814
Abstract
Probiotics use different mechanisms such as intestinal barrier improvement, bacterial translocation and maintaining gut microbiota homeostasis to treat cancer. Probiotics' ability to induce apoptosis against tumor cells makes them more effective to treat cancer. Moreover, probiotics stimulate immune function through an immunomodulation mechanism that induces an anti-tumor effect. There are different strains of probiotics, but the most important ones are lactic acid bacteria (LAB) having antagonistic and anti-mutagenic activities. Live and dead probiotics have anti-inflammatory, anti-proliferative, anti-oxidant and anti-metastatic properties which are useful to fight against different diseases, especially cancer. The main focus of this article is to review the anti-cancerous properties of probiotics and their role in the reduction of different types of cancer. However, further investigations are in progress to improve the efficiency of probiotics in cancer treatment.
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8.
Physical activity and obesity spectrum disorders in post-bariatric surgery patients: A systematic review and Meta-analysis.
Gasmi, A, Boukhmis, B, Bjørklund, G, Elkhidir, IH, Semenova, Y, Dosa, A, Piscopo, S, Temitope, AH, Noor, S, Costea, DO
Critical reviews in food science and nutrition. 2023;(26):8161-8172
Abstract
OBJECTIVES This systematic review and meta-analysis is based on randomized controlled trials evaluating the effect of physical activity on weight loss in adults undergoing bariatric surgery. The study compared certain biomarkers for individuals with and without physical activity after bariatric surgery. Secondary, the study identified potential successful interventions for the target population. METHOD PubMed, Embase, OVID, CINAHL, and Cochrane Library were searched from January 2000 to December 2020. Intervention studies on the effect of physical activity in adults after bariatric surgery were selected, included, and analyzed following the PRISMA guidelines. The primary outcome was weight loss followed by selected biomarkers. RESULTS Two independent reviewers extracted data and conducted quality assessments. Of the 11 studies included, six reported BMI, two reported fat-free mass, three reported fat mass, two reported waist-hip ratio, and two reported waist circumference. Six studies measuring change from baseline BMI reported a significant intervention effect: SMD = -0.93 (-1.65;-0.20) with high heterogeneity of included trials (I2 = 72%). There was no significant difference between control and intervention groups for other outcomes. CONCLUSION BMI as a measure of physical activity positively impacts the target population. Large-scale studies with better criteria and a longer evaluation follow-up may finalize pronounced outcomes.
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9.
Toxic Metals Exposure and APOE4 Gene Variant in Cognitive Decline Disorders.
Gasmi, A, Menzel, A, Piscopo, S, Noor, S
Archives of Razi Institute. 2022;(1):1-10
Abstract
Neurodegenerative disorders are those which affect cognitive functions. Misfolding of proteins especially apolipoprotein E is a key genetic factor involved in several cognitive impairments. Increasing evidence also described the toxic effects of metals, generated by both nature and humans, on the development of neurological disorders. Understanding of interaction between toxic metals and apolipoprotein E protein in cognitive decline diosrders would provide alternative treatment options. Google Scholar and PubMed database were used to search the articles using different search terms like 'toxic metals', 'cognitive decline', 'Apolipoprotein E', "neurodegenerative disorders" and "metals neurotoxicity". Only those papers were included that discussed the metal exposure-apolipoprotein association in the development of cognitive decline disorders. Heavy metals are particularly recognized as a major source of neurotoxicity. These toxic metals can interact with genetic factors and play important role in disease etiology. Understanding the underlying mechanism of this interaction could provide tremendous benefits to treat cognitive decline disorders. In this study, the role of the apolipoprotein E4 gene in the development of cognitive disease conditions and their phenotypes has been discussed thoroughly which leads to the accumulation of amyloid-beta fibrils. This exploratory study revealed novel hypothetical findings which might contribute to the understanding of the neurotoxic effects of chronic toxic metals exposure and possibly improve our knowledge on the molecular mechanisms linking metal exposure to cognitive decline disorder risk.
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10.
Neurotransmitters Regulation and Food Intake: The Role of Dietary Sources in Neurotransmission.
Gasmi, A, Nasreen, A, Menzel, A, Gasmi Benahmed, A, Pivina, L, Noor, S, Peana, M, Chirumbolo, S, Bjørklund, G
Molecules (Basel, Switzerland). 2022;(1)
Abstract
Neurotransmitters (NTs) are biologically active chemicals, which mediate the electrochemical transmission between neurons. NTs control numerous organic functions particularly crucial for life, including movement, emotional responses, and the physical ability to feel pleasure and pain. These molecules are synthesized from simple, very common precursors. Many types of NTs have both excitatory and inhibitory effects. Neurotransmitters' imbalance can cause many diseases and disorders, such as Parkinson's disease, depression, insomnia, increased anxiety, memory loss, etc. Natural food sources containing NTs and/or their precursors would be a potential option to help maintain the balance of NTs to prevent brain and psychiatric disorders. The level of NTs could be influenced, therefore, by targeting dietary habits and nutritional regimens. The progressive implementation of nutritional approaches in clinical practice has made it necessary to infer more about some of the nutritional NTs in neuropsychiatry. However, the importance of the intake of nutritional NTs requires further understanding, since there are no prior significant studies about their bioavailability, clinical significance, and effects on nerve cells. Interventional strategies supported by evidence should be encouraged.