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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.
Perspectives on Iron Deficiency as a Cause of Human Disease in Global Public Health.
Bjørklund, G, Semenova, Y, Hangan, T, Pen, JJ, Aaseth, J, Peana, M
Current medicinal chemistry. 2024;(12):1428-1440
Abstract
Iron (Fe) is a necessary trace element in numerous pathways of human metabolism. Therefore, Fe deficiency is capable of causing multiple health problems. Apart from the well-known microcytic anemia, lack of Fe can cause severe psychomotor disorders in children, pregnant women, and adults in general. Iron deficiency is a global health issue, mainly caused by dietary deficiency but aggravated by inflammatory conditions. The challenges related to this deficiency need to be addressed on national and international levels. This review aims to summarize briefly the disease burden caused by Fe deficiency in the context of global public health and aspires to offer some hands-on guidelines.
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3.
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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4.
Coenzyme Q10 in aging and disease.
Gasmi, A, Bjørklund, G, Mujawdiya, PK, Semenova, Y, Piscopo, S, Peana, M
Critical reviews in food science and nutrition. 2024;(12):3907-3919
Abstract
Coenzyme Q10 (CoQ10) is an essential component of the electron transport chain. It also acts as an antioxidant in cellular membranes. It can be endogenously produced in all cells by a specialized mitochondrial pathway. CoQ10 deficiency, which can result from aging or insufficient enzyme function, has been considered to increase oxidative stress. Some drugs, including statins and bisphosphonates, often used by older individuals, can interfere with enzymes responsible for endogenous CoQ10 synthesis. Oral supplementation with high doses of CoQ10 can increase both its circulating and intracellular levels and several clinical trials observed that its administration provided beneficial effects on different disorders such as cardiovascular disease and inflammation which have been associated with low CoQ10 levels and high oxidative stress. Moreover, CoQ10 has been suggested as a promising therapeutic agent to prevent and slow the progression of other diseases including metabolic syndrome and type 2 diabetes, neurodegenerative and male infertility. However, there is still a need for further studies and well-designed clinical trials involving a large number of participants undergoing longer treatments to assess the benefits of CoQ10 for these disorders.
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Linking Environmental Chemicals to Neuroinflammation and Autism Spectrum Disorder: Mechanisms and Implications for Prevention.
Bjørklund, G, Mkhitaryan, M, Sahakyan, E, Fereshetyan, K, Meguid, NA, Hemimi, M, Nashaat, NH, Yenkoyan, K
Molecular neurobiology. 2024
Abstract
This article explores the potential link between endocrine-disrupting chemicals (EDCs), neuroinflammation, and the development of autism spectrum disorder (ASD). Neuroinflammation refers to the immune system's response to injury, infection, or disease in the central nervous system. Studies have shown that exposure to EDCs, such as bisphenol A and phthalates, can disrupt normal immune function in the brain, leading to chronic or excessive neuroinflammation. This disruption of immune function can contribute to developing neurological disorders, including ASD. Furthermore, EDCs may activate microglia, increasing pro-inflammatory cytokine production and astroglia-mediated oxidative stress, exacerbating neuroinflammation. EDCs may also modulate the epigenetic profile of cells by methyltransferase expression, thereby affecting neurodevelopment. This article also highlights the importance of reducing exposure to EDCs and advocating for policies and regulations restricting their use. Further research is needed to understand better the mechanisms underlying the link between EDCs, neuroinflammation, and ASD and to develop new treatments for ASD.
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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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Structural modeling of protein ensembles between E3 RING ligases and SARS-CoV-2: The role of zinc binding domains.
Chasapis, CT, Perlepes, SP, Bjørklund, G, Peana, M
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2023;:127089
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Abstract
BACKGROUND The ubiquitin system is a modification process with many different cellular functions including immune signaling and antiviral functions. E3 ubiquitin ligases are enzymes that recruit an E2 ubiquitin-conjugating enzyme bound to ubiquitin in order to catalyze the transfer of ubiquitin from the E2 to a protein substrate. The RING E3s, the most abundant type of ubiquitin ligases, are characterized by a zinc (II)-binding domain called RING (Really Interesting New Gene). Viral replication requires modifying and hijacking key cellular pathways within host cells such as cellular ubiquitination. There are well-established examples where a viral proteins bind to RING E3s, redirecting them to degrade otherwise long-lived host proteins or inhibiting E3's ubiquitination activity. Recently, three binary interactions between SARS-CoV-2 proteins and innate human immune signaling Ε3 RING ligases: NSP15-RNF41, ORF3a-TRIM59 and NSP9-MIB1 have been experimentally established. METHODS In this work, we have investigated the mode of the previous experimentally supported NSP15-RNF41, ORF3a,-TRIM59 and NSP9-MIB1 binary interactions by in silico methodologies intending to provide structural insights of E3-virus interplay that can help identify potential inhibitors that could block SARS-CoV-2 infection of immune cells. CONCLUSION In silico methodologies have shown that the above human E3 ligases interact with viral partners through their Zn(II) binding domains. This RING mediated formation of stable SARS-CoV-2-E3 complexes indicates a critical structural role of RING domains in immune system disruption by SARS-CoV-2-infection. DATA AVAILABILITY The data used to support the findings of this research are included within the article and are labeled with references.
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Dietary supplements and bariatric surgery.
Gasmi, A, Bjørklund, G, Mujawdiya, PK, Semenova, Y, Dosa, A, Piscopo, S, Pen, JJ, Gasmi Benahmed, A, Costea, DO
Critical reviews in food science and nutrition. 2023;(25):7477-7488
Abstract
Bariatric surgery or weight loss surgery has been in practice for achieving significant weight loss in patients who have failed to achieve weight loss after pharmacological interventions. The rising cases of obesity are a triggering factor for more bariatric surgeries worldwide. Interestingly, sustained weight loss achieved post-bariatric surgery offers metabolic advantages, and patients show improved glucose and lipid metabolisms. Bariatric surgery is directly linked to higher incidences of vitamin, mineral, and trace element deficiencies, thus making patients susceptible to anemia, osteoporosis, and cardiomyopathy. Reduced nutrient absorption capacity, dietary changes, dietary restriction, and altered gastrointestinal tract morphology are some reasons for nutritional deficiency observed in post-bariatric surgery procedures. Micro-and-macronutrient deficiency observed in patients during the postoperative phase requires continuous monitoring of nutritional parameters. Therefore, adequate multivitamin and mineral supplements become essential to prevent/overcome micronutrient deficiencies. Bariatric surgery also raises the risk of small for gestational age (SGA) babies. Hence, a 12 - 24 months gap is recommended between bariatric surgery and pregnancy to achieve desired weight loss targets. The topic of this review is the impact of bariatric surgery procedures on vitamin and mineral absorption and the role of dietary supplements in maintaining a healthy nutritional balance during the postoperative phase.
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Metal-induced autoimmunity in neurological disorders: A review of current understanding and future directions.
Bjørklund, G, Đorđević, AB, Hamdan, H, Wallace, DR, Peana, M
Autoimmunity reviews. 2023;(3):103509
Abstract
Autoimmunity is a multifaceted disorder influenced by both genetic and environmental factors, and metal exposure has been implicated as a potential catalyst, especially in autoimmune diseases affecting the central nervous system. Notably, metals like mercury, lead, and aluminum exhibit well-established neurotoxic effects, yet the precise mechanisms by which they elicit autoimmune responses in susceptible individuals remain unclear. Recent studies propose that metal-induced autoimmunity may arise from direct toxic effects on immune cells and tissues, coupled with indirect impacts on the gut microbiome and the blood-brain barrier. These effects can activate self-reactive T cells, prompting the production of autoantibodies, inflammatory responses, and tissue damage. Diagnosing metal-induced autoimmunity proves challenging due to nonspecific symptoms and a lack of reliable biomarkers. Treatment typically involves chelation therapy to eliminate excess metals and immunomodulatory agents to suppress autoimmune responses. Prevention strategies include lifestyle adjustments to reduce metal exposure and avoiding occupational and environmental risks. Prognosis is generally favorable with proper treatment; however, untreated cases may lead to autoimmune disorder progression and irreversible organ damage, particularly in the brain. Future research aims to identify genetic and environmental risk factors, enhance diagnostic precision, and explore novel treatment approaches for improved prevention and management of this intricate and debilitating disease.
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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.