Publications by authors named "Md Sahab Uddin"

143 Publications

Neuroinflammatory Signaling in the Pathogenesis of Alzheimer's Disease.

Curr Neuropharmacol 2021 Aug 26. Epub 2021 Aug 26.

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah. Saudi Arabia.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.
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http://dx.doi.org/10.2174/1570159X19666210826130210DOI Listing
August 2021

Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma.

Front Pharmacol 2021 27;12:703761. Epub 2021 Aug 27.

Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah, Saudi Arabia.

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling.
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http://dx.doi.org/10.3389/fphar.2021.703761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429794PMC
August 2021

Candidate antiviral drugs for COVID-19 and their environmental implications: a comprehensive analysis.

Environ Sci Pollut Res Int 2021 Sep 12. Epub 2021 Sep 12.

Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

Emerging from Wuhan, China, SARS-CoV-2 is the new global threat that killed millions of people, and many are still suffering. This pandemic has not only affected people but also caused economic crisis throughout the world. Researchers have shown good progress in revealing the molecular insights of SARS-CoV-2 pathogenesis and developing vaccines, but effective treatment against SARS-CoV-2-infected patients are yet to be found. Several vaccines are available and used in many countries, while many others are still in clinical or preclinical studies. However, this involves a long-term process, considering the safety procedures and requirements and their long-term protection capacity and in different age groups are still questionable. Therefore, at present, the drug repurposing of the existing therapeutics previously designed against other viral diseases seems to be the only practical approach to mitigate the current situation. The safety of most of these therapeutic agents has already been tested. Recent clinical reports revealed promising therapeutic efficiency of several drugs such as remdesivir, tenofovir disoproxil fumarate, azithromycin, lopinavir/ritonavir, chloroquine, baricitinib, and cepharanthine. Besides, plasma therapies were used to treat patients and prevent fatal outcomes. Thus, in this article, we have summarized the epidemiological and clinical data from several clinical trials conducted since the beginning of the pandemic, emphasizing the efficiency of the known agents against SARS-CoV-2 and their harmful side effects on the human body as well as their environmental implications. This review shows a clear overview of the current pharmaceutical perspective on COVID-19 treatment.
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http://dx.doi.org/10.1007/s11356-021-16096-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435122PMC
September 2021

Plasmalogens ensure the stability of non-neuronal (microglial) cells during long-term cytotoxicity.

Environ Sci Pollut Res Int 2021 Aug 7. Epub 2021 Aug 7.

Physiology Department, Faculty of Veterinary Medicine, South Valley University, Qena, 83523, Egypt.

Microglia (MG) are resident phagocytes in the brain responsible for neuronal maintenance. The regulation of MG necroptosis is required for protecting neurons during neurodegenerative diseases. Therefore, this study proposed to elucidate the molecular mechanisms underlying microglia necroptosis during long-time apoptotic stimuli (lipopolysaccharide, LPS). The protective role of plasmalogens (PLS) was also investigated against LPS insult in MG cells (including BV2 and MG6 cell lines). LPS produced time-dependent decreases in the survival of BV2 and MG6 cells mediated by the caspase signaling pathway. Interestingly, MG death was mediated by caspase-8 and 9 signaling pathways suggesting that MG necroptosis was actively attributed to long-time LPS treatment through intrinsic and extrinsic pathways. Notably, caspase signaling was markedly inhibited in the PLS-pretreated cells; thereby, PLS were capable of maintaining the MG cell population and inhibit the MG necroptosis against the longtime of LPS administration via its antioxidant and anti-inflammatory properties.
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http://dx.doi.org/10.1007/s11356-021-15773-7DOI Listing
August 2021

Honokiol: A review of its pharmacological potential and therapeutic insights.

Phytomedicine 2021 Sep 16;90:153647. Epub 2021 Jul 16.

K.G. Razumovsky Moscow State University of Technologies and Management (the First Cossack University), 109004, Moscow, Russian Federation.

Background: Honokiol is a pleiotropic compound which been isolated from Magnolia species such as Magnolia grandiflora and Magnolia dealbata. Magnolia species Magnolia grandiflora is used in traditional medicine for the treatment of various diseases.

Purpose: The objective of this review is to summarize the pharmacological potential and therapeutic insights of honokiol.

Study Design: Honokiol has been specified as a novel alternative to treat various disorders such as liver cancer, neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties and others. Therefore, this study designed to represent the in-depth therapeutic potential of honokiol.

Methods: Literature searches in electronic databases, such as Web of Science, Science Direct, PubMed, Google Scholar, and Scopus, were performed using the keywords 'Honokiol', 'Health Benefits' and 'Therapeutic Insights' as the keywords for primary searches and secondary search terms were used as follows: 'Anticancer', 'Oxidative Stress', 'Neuroprotective', 'Antimicrobial', 'Cardioprotection', 'Hepatoprotective', 'Anti-inflammatory', 'Arthritis', 'Reproductive Disorders'.

Results: This promising bioactive compound presented an wide range of therapeutic and biological activities which include liver cancer, neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties, and others. Its pharmacokinetics has been established in experimental animals, while in humans, this is still speculative. Some of its mechanism for exhibiting its pharmacological effects includes apoptosis of diseased cells, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6), amelioration of impaired hepatic enzymes and reversal of morphological alterations, among others.

Conclusion: All these actions displayed by this novel compound could make it serve as a lead in the formulation of drugs with higher efficacy and negligible side effects utilized in the treatment of several human diseases.
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http://dx.doi.org/10.1016/j.phymed.2021.153647DOI Listing
September 2021

Exploring ER stress response in cellular aging and neuroinflammation in Alzheimer's disease.

Ageing Res Rev 2021 09 31;70:101417. Epub 2021 Jul 31.

Neuromodulation Laboratory, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Electronic address:

One evident hallmark of Alzheimer's disease (AD) is the irregular accumulation of proteins due to changes in proteostasis involving endoplasmic reticulum (ER) stress. To alleviate ER stress and reinstate proteostasis, cells undergo an integrated signaling cascade called the unfolded protein response (UPR) that reduces the number of misfolded proteins and inhibits abnormal protein accumulation. Aging is associated with changes in the expression of ER chaperones and folding enzymes, leading to the impairment of proteostasis, and accumulation of misfolded proteins. The disrupted initiation of UPR prevents the elimination of unfolded proteins, leading to ER stress. In AD, the accumulation of misfolded proteins caused by sustained cellular stress leads to neurodegeneration and neuronal death. Current research has revealed that ER stress can trigger an inflammatory response through diverse transducers of UPR. Although the involvement of a neuroinflammatory component in AD has been documented for decades, whether it is a contributing factor or part of the neurodegenerative events is so far unknown. Besides, a feedback loop occurs between neuroinflammation and ER stress, which is strongly associated with neurodegenerative processes in AD. In this review, we focus on the current research on ER stress and UPR in cellular aging and neuroinflammatory processes, leading to memory impairment and synapse dysfunction in AD.
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http://dx.doi.org/10.1016/j.arr.2021.101417DOI Listing
September 2021

Antioxidant and Signal-Modulating Effects of Brown Seaweed-Derived Compounds against Oxidative Stress-Associated Pathology.

Oxid Med Cell Longev 2021 10;2021:9974890. Epub 2021 Jul 10.

Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

The biological and therapeutic properties of seaweeds have already been well known. Several studies showed that among the various natural marine sources of antioxidants, seaweeds have become a potential source of antioxidants because of their bioactive compounds. Most of the metabolic diseases are caused by oxidative stress. It is very well known that antioxidants have a pivotal role in the treatment of those diseases. Recent researches have revealed the potential activity of seaweeds as complementary medicine, which have therapeutic properties for health and disease management. Among the seaweeds, brown seaweeds (Phaeophyta) and their derived bioactive substances showed excellent antioxidant properties than other seaweeds. This review focuses on brown seaweeds and their derived major bioactive compounds such as sulfated polysaccharide, polyphenol, carotenoid, and sterol antioxidant effects and molecular mechanisms in the case of the oxidative stress-originated disease. Antioxidants have a potential role in the modification of stress-induced signaling pathways along with the activation of the oxidative defensive pathways. This review would help to provide the basis for further studies to researchers on the potential antioxidant role in the field of medical health care and future drug development.
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http://dx.doi.org/10.1155/2021/9974890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289617PMC
July 2021

Therapeutic potential of indole alkaloids in respiratory diseases: A comprehensive review.

Phytomedicine 2021 Sep 15;90:153649. Epub 2021 Jul 15.

Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo - Ourense Campus, E32004 Ourense, Spain. Electronic address:

Background: Indole alkaloids are very promising for potential therapeutic purposes and appear to be particularly effective against respiratory diseases. Several experimental studies have been performed, both in vivo and in vitro, to evaluate the effectiveness of indole alkaloids for the management of respiratory disorders, including asthma, emphysema, tuberculosis, cancer, and pulmonary fibrosis.

Purpose: The fundamental objective of this review was to summarize the in-depth therapeutic potential of indole alkaloids against various respiratory disorders.

Study Design: In addition to describing the therapeutic potential, this review also evaluates the toxicity of these alkaloids, which have been utilized for therapeutic benefits but have demonstrated toxic consequences. Some indole alkaloids, including scholaricine, 19-epischolaricine, vallesamine, and picrinine, which are derived from the plant Alstonia scholaris, have shown toxic effects in non-rodent models.

Methods: This review also discusses clinical studies exploring the therapeutic efficacy of indole alkaloids, which have confirmed the promising benefits observed in vivo and in vitro.

Results: The indole alkaloidal compounds have shown efficacy in subjects with respiratory diseases.

Conclusion: The available data established both preclinical and clinical studies confirm the potential of indole alkaloids to treat the respiratory disorders.
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http://dx.doi.org/10.1016/j.phymed.2021.153649DOI Listing
September 2021

Natural Products for Neurodegeneration: Regulating Neurotrophic Signals.

Oxid Med Cell Longev 2021 21;2021:8820406. Epub 2021 Jun 21.

Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.

Neurodegenerative disorders (NDs) are heterogeneous groups of ailments typically characterized by progressive damage of the nervous system. Several drugs are used to treat NDs but they have only symptomatic benefits with various side effects. Numerous researches have been performed to prove the advantages of phytochemicals for the treatment of NDs. Furthermore, phytochemicals such as polyphenols might play a pivotal role in rescue from neurodegeneration due to their various effects as anti-inflammatory, antioxidative, and antiamyloidogenic agents by controlling apoptotic factors, neurotrophic factors (NTFs), free radical scavenging system, and mitochondrial stress. On the other hand, neurotrophins (NTs) including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT4/5, and NT3 might have a crucial neuroprotective role, and their diminution triggers the development of the NDs. Polyphenols can interfere directly with intracellular signaling molecules to alter brain activity. Several natural products also improve the biosynthesis of endogenous genes encoding antiapoptotic Bcl-2 as well as NTFs such as glial cell and brain-derived NTFs. Various epidemiological studies have demonstrated that the initiation of these genes could play an essential role in the neuroprotective function of dietary compounds. Hence, targeting NTs might represent a promising approach for the management of NDs. In this review, we focus on the natural product-mediated neurotrophic signal-modulating cascades, which are involved in the neuroprotective effects.
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http://dx.doi.org/10.1155/2021/8820406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241508PMC
June 2021

Synthesis and Toxicity of Graphene Oxide Nanoparticles: A Literature Review of and Studies.

Biomed Res Int 2021 10;2021:5518999. Epub 2021 Jun 10.

Laboratory of Water, Biodiversity & Climate Change, Cadi Ayyad University, B.P. 2390, 40000 Marrakech, Morocco.

Nanomaterials have been widely used in many fields in the last decades, including electronics, biomedicine, cosmetics, food processing, buildings, and aeronautics. The application of these nanomaterials in the medical field could improve diagnosis, treatment, and prevention techniques. Graphene oxide (GO), an oxidized derivative of graphene, is currently used in biotechnology and medicine for cancer treatment, drug delivery, and cellular imaging. Also, GO is characterized by various physicochemical properties, including nanoscale size, high surface area, and electrical charge. However, the toxic effect of GO on living cells and organs is a limiting factor that limits its use in the medical field. Recently, numerous studies have evaluated the biocompatibility and toxicity of GO and . In general, the severity of this nanomaterial's toxic effects varies according to the administration route, the dose to be administered, the method of GO synthesis, and its physicochemical properties. This review brings together studies on the method of synthesis and structure of GO, characterization techniques, and physicochemical properties. Also, we rely on the toxicity of GO in cellular models and biological systems. Moreover, we mention the general mechanism of its toxicity.
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http://dx.doi.org/10.1155/2021/5518999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213470PMC
June 2021

Nanotechnology-Based Approaches and Investigational Therapeutics against COVID-19.

Curr Pharm Des 2021 Jul 1. Epub 2021 Jul 1.

Department of Pharmacy, Southeast University, Dhaka. Bangladesh.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus which is currently responsible for the global pandemic since December 2019. This class of coronavirus has affected 217 countries around the world. Most of the countries have taken some non-remedial preventive actions like country lockdown, work from home, travel bans, and the most significant one is social isolation. Pharmacists, doctors, nurses, technologists, and all other healthcare professionals are playing a pivotal role during this pandemic. Unluckily, there is no specific drug that can treat patients who are confirmed with COVID-19, though favipiravir and remdesivir have appeared as favorable antiviral drugs. Some vaccines have already developed, and vaccination has started worldwide. Different nanotechnologies are in the developing stage in many countries for preventing SARS-COV-2 and treating COVID-19 conditions. In this article, we review the COVID-19 pandemic situation as well as the nanotechnology-based approaches and investigational therapeutics against COVID-19.
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http://dx.doi.org/10.2174/1381612827666210701150315DOI Listing
July 2021

Effects of Alcoholic Extracts of Bangladeshi Mangrove Linn. (Acanthaceae) Leaf and Stem on Atherogenic Model of Wistar Albino Rats.

Evid Based Complement Alternat Med 2021 30;2021:7539037. Epub 2021 May 30.

Department of Biochemistry and Molecular Biology, Trust University, Barishal, Ruiya, Nobogram Road, Barishal 8200, Bangladesh.

Linn. (Acanthaceae) is a popular mangrove ethnomedicinal plant that cures several ailments, including asthma, diabetes, cancer, and many others. Our experiment was aimed at evaluating the anti-atherogenic effect of (leaf and stem) on a high-fat diet-induced atherogenic rat model. Atherosclerosis was developed in 12 weeks. Treatment with the standard drug (3 mg/kg b.w./day, p.o. of Simvastatin), separate doses of methanolic and ethanolic extracts of leaf (250 and 500 mg/kg b.w./day, p.o.), and stem (200 and 400 mg/kg b.w./day, p.o.) was subsequently conducted for additional 15 days. The anti-atherogenic effect was evaluated by estimating the change in body weight, systolic blood pressure, and lipid profile. Histopathology of aorta, liver, and kidney of atherogenic models was done for further evaluation. The antioxidant effect of different extracts was performed via DPPH (2,2-diphenyl-1-picrylhydrazyl) assay using ascorbic acid as standard. The anticoagulant effect was determined after 15 days of treatment with the same doses of the plant extracts and the standard Warfarin (2 mg/kg b.w./day, p.o.). When compared with atherogenic control, treatment with significantly reduced ( < 0.01) body weight, systolic blood pressure, and serum lipid levels while it elevated HDL (high-density lipoprotein) level in a dose-dependent manner. Moreover, bleeding and clotting time was significantly decreased ( < 0.01) under the treatment of plant extracts. The histopathological data showed considerable improvement in tissue morphology after treatment. Our study evidenced that the alcoholic extracts of leaf and stem have anti-atherogenic properties and may be recommended as a potential herbal remedy for preventing cardiovascular diseases.
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http://dx.doi.org/10.1155/2021/7539037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184344PMC
May 2021

Exploring the Role of Monoamine Oxidase Activity in Aging and Alzheimer's Disease.

Curr Pharm Des 2021 Jun 11. Epub 2021 Jun 11.

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah. Saudi Arabia.

Monoamine oxidases (MAOs) are a family of flavin adenine dinucleotide-dependent enzymes that exert a crucial role in the metabolism of neurotransmitters of the central nervous system. The impaired function of MAOs is associated with copious brain diseases. The alteration of monoamine metabolism is a characteristics feature of aging. MAO plays a crucial role in the pathogenesis of Alzheimer's disease (AD) - a progressive neurodegenerative disorder associated with an excessive accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles (NFTs). Activated MAO has played a critical role in the development of amyloid plaques from Aβ, as well as the formation of the NFTs. In the brain, MAO mediated metabolism of monoamines is the foremost source of reactive oxygen species formation. The elevated level of MAO-B expression in astroglia has been reported in the AD brains adjacent to amyloid plaques. Increased MAO-B activity in the cortical and hippocampal regions is associated with AD. This review describes the pathogenic mechanism of MAOs in aging as well as the development and propagation of Alzheimer's pathology.
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http://dx.doi.org/10.2174/1381612827666210612051713DOI Listing
June 2021

Potential health benefits of carotenoid lutein: An updated review.

Food Chem Toxicol 2021 Aug 8;154:112328. Epub 2021 Jun 8.

Green Biotechnologies Research Centre of Excellence, University of Limpopo, Private Bag X1106, Polokwane, Sovenga, 0727, South Africa. Electronic address:

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with β-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed.
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http://dx.doi.org/10.1016/j.fct.2021.112328DOI Listing
August 2021

Therapeutic Potential of Polyphenols in the Management of Diabetic Neuropathy.

Evid Based Complement Alternat Med 2021 13;2021:9940169. Epub 2021 May 13.

Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, Besançon, France.

Diabetic neuropathy (DN) is a common and serious diabetes-associated complication that primarily takes place because of neuronal dysfunction in patients with diabetes. Use of current therapeutic agents in DN treatment is quite challenging because of their severe adverse effects. Therefore, there is an increased need of identifying new safe and effective therapeutic agents. DN complications are associated with poor glycemic control and metabolic imbalances, primarily oxidative stress (OS) and inflammation. Various mediators and signaling pathways such as glutamate pathway, activation of channels, trophic factors, inflammation, OS, advanced glycation end products, and polyol pathway have a significant contribution to the progression and pathogenesis of DN. It has been indicated that polyphenols have the potential to affect DN pathogenesis and could be used as potential alternative therapy. Several polyphenols including kolaviron, resveratrol, naringenin, quercetin, kaempferol, and curcumin have been administered in patients with DN. Furthermore, chlorogenic acid can provide protection against glutamate neurotoxicity via its hydrolysate, caffeoyl acid group, and caffeic acid through regulating the entry of calcium into neurons. Epigallocatechin-3-gallate treatment can protect motor neurons by regulating the glutamate level. It has been demonstrated that these polyphenols can be promising in combating DN-associated damaging pathways. In this article, we have summarized DN-associated metabolic pathways and clinical manifestations. Finally, we have also focused on the roles of polyphenols in the treatment of DN.
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http://dx.doi.org/10.1155/2021/9940169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137294PMC
May 2021

Disposal Practices of Unused and Leftover Medicines in the Households of Dhaka Metropolis.

Pharmacy (Basel) 2021 May 20;9(2). Epub 2021 May 20.

Department of Biochemistry and Molecular Biology, Trust University, Barishal, Ruiya, Nobogram Road, Barishal 8200, Bangladesh.

This fact-finding study aimed to attain an overall idea and knowledge about medicine disposal practices in Dhaka Metropolitan households. This mixed study (both quantitative and qualitative) was orchestrated to inspect the household leftover medicine disposal pattern's governing status. A cross-sectional survey was conducted following a structured questionnaire and key informant interview with a household person and in-depth interviews with the top pharmaceutical and government officials. Findings disclose that, for most of the key informants, the terms "drug disposal" and "drug pollution" were unknown; more precisely, 67% and 74% of key informants even did not hear these two terms. Almost all (87%) households faced undesired incidents due to the insecure storage of medicines. People disposed of excess and expired medication in regular dustbins (47%), threw out of the window (19%), flushed within commode (4%), burnt in fire (2%), and reused (4%). A good percentage of people (21%) returned unexpired drugs to the pharmacy and bought other medicines on a need basis. A total of 72% wanted a medicine take-back program, and 100% agreed on mass education on this issue. Officials of pharmaceuticals conferred mixed opinion: top-ranked pharmaceuticals will adopt leftover medicine disposal practices; middle and low-ranked pharmaceutical companies are reluctant, merely denied mentioning the less important issue. The absence of mass awareness and standard laws and policies may explain these existing aberrant practices.
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http://dx.doi.org/10.3390/pharmacy9020103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162525PMC
May 2021

Multi-Omics Approach in the Identification of Potential Therapeutic Biomolecule for COVID-19.

Front Pharmacol 2021 12;12:652335. Epub 2021 May 12.

Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has a disastrous effect on mankind due to the contagious and rapid nature of its spread. Although vaccines for SARS-CoV-2 have been successfully developed, the proven, effective, and specific therapeutic molecules are yet to be identified for the treatment. The repurposing of existing drugs and recognition of new medicines are continuously in progress. Efforts are being made to single out plant-based novel therapeutic compounds. As a result, some of these biomolecules are in their testing phase. During these efforts, the whole-genome sequencing of SARS-CoV-2 has given the direction to explore the omics systems and approaches to overcome this unprecedented health challenge globally. Genome, proteome, and metagenome sequence analyses have helped identify virus nature, thereby assisting in understanding the molecular mechanism, structural understanding, and disease propagation. The multi-omics approaches offer various tools and strategies for identifying potential therapeutic biomolecules for COVID-19 and exploring the plants producing biomolecules that can be used as biopharmaceutical products. This review explores the available multi-omics approaches and their scope to investigate the therapeutic promises of plant-based biomolecules in treating SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fphar.2021.652335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149611PMC
May 2021

Mesoporous Carbon: A Versatile Material for Scientific Applications.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.

Mesoporous carbon is a promising material having multiple applications. It can act as a catalytic support and can be used in energy storage devices. Moreover, mesoporous carbon controls body's oral drug delivery system and adsorb poisonous metal from water and various other molecules from an aqueous solution. The accuracy and improved activity of the carbon materials depend on some parameters. The recent breakthrough in the synthesis of mesoporous carbon, with high surface area, large pore-volume, and good thermostability, improves its activity manifold in performing functions. Considering the promising application of mesoporous carbon, it should be broadly illustrated in the literature. This review summarizes the potential application of mesoporous carbon in many scientific disciplines. Moreover, the outlook for further improvement of mesoporous carbon has been demonstrated in detail. Hopefully, it would act as a reference guidebook for researchers about the putative application of mesoporous carbon in multidimensional fields.
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http://dx.doi.org/10.3390/ijms22094498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123390PMC
April 2021

Anti-Alzheimer's Molecules Derived from Marine Life: Understanding Molecular Mechanisms and Therapeutic Potential.

Mar Drugs 2021 Apr 28;19(5). Epub 2021 Apr 28.

Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo, Ourense Campus, E32004 Ourense, Spain.

Alzheimer's disease (AD) is a devastating neurodegenerative disease and the most common cause of dementia. It has been confirmed that the pathological processes that intervene in AD development are linked with oxidative damage to neurons, neuroinflammation, tau phosphorylation, amyloid beta (Aβ) aggregation, glutamate excitotoxicity, and cholinergic deficit. Still, there is no available therapy that can cure AD. Available therapies only manage some of the AD symptoms at the early stages of AD. Various studies have revealed that bioactive compounds derived from marine organisms and plants can exert neuroprotective activities with fewer adverse events, as compared with synthetic drugs. Furthermore, marine organisms have been identified as a source of novel compounds with therapeutic potential. Thus, there is a growing interest regarding bioactive compounds derived from marine sources that have anti-AD potentials. Various marine drugs including bryostatin-1, homotaurine, anabaseine and its derivative, rifampicins, anhydroexfoliamycin, undecylprodigioisin, gracilins, 13-desmethyl spirolide-C, and dictyostatin displayed excellent bioavailability and efficacy against AD. Most of these marine drugs were found to be well-tolerated in AD patients, along with no significant drug-associated adverse events. In this review, we focus on the drugs derived from marine life that can be useful in AD treatment and also summarize the therapeutic agents that are currently used to treat AD.
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http://dx.doi.org/10.3390/md19050251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146595PMC
April 2021

Phytochemicals from Plant Foods as Potential Source of Antiviral Agents: An Overview.

Pharmaceuticals (Basel) 2021 Apr 19;14(4). Epub 2021 Apr 19.

Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy.

To date, the leading causes of mortality and morbidity worldwide include viral infections, such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review focuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioavailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these reasons, a continuous systematic exploration of plant foods and their phytochemicals is necessary for the development of new antiviral agents capable of saving lives and improving their well-being.
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http://dx.doi.org/10.3390/ph14040381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073840PMC
April 2021

Molecular Mechanisms of Astaxanthin as a Potential Neurotherapeutic Agent.

Mar Drugs 2021 Apr 3;19(4). Epub 2021 Apr 3.

Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Food Science and Technology, University of Vigo-Ourense Campus, E32004 Ourense, Spain.

Neurological disorders are diseases of the central and peripheral nervous system that affect millions of people, and the numbers are rising gradually. In the pathogenesis of neurodegenerative diseases, the roles of many signaling pathways were elucidated; however, the exact pathophysiology of neurological disorders and possible effective therapeutics have not yet been precisely identified. This necessitates developing multi-target treatments, which would simultaneously modulate neuroinflammation, apoptosis, and oxidative stress. The present review aims to explore the potential therapeutic use of astaxanthin (ASX) in neurological and neuroinflammatory diseases. ASX, a member of the xanthophyll group, was found to be a promising therapeutic anti-inflammatory agent for many neurological disorders, including cerebral ischemia, Parkinson's disease, Alzheimer's disease, autism, and neuropathic pain. An effective drug delivery system of ASX should be developed and further tested by appropriate clinical trials.
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http://dx.doi.org/10.3390/md19040201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065559PMC
April 2021

A deep neural network-based approach for prediction of mutagenicity of compounds.

Environ Sci Pollut Res Int 2021 Sep 24;28(34):47641-47650. Epub 2021 Apr 24.

Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

We are exposed to various chemical compounds present in the environment, cosmetics, and drugs almost every day. Mutagenicity is a valuable property that plays a significant role in establishing a chemical compound's safety. Exposure and handling of mutagenic chemicals in the environment pose a high health risk; therefore, identification and screening of these chemicals are essential. Considering the time constraints and the pressure to avoid laboratory animals' use, the shift to alternative methodologies that can establish a rapid and cost-effective detection without undue over-conservation seems critical. In this regard, computational detection and identification of the mutagens in environmental samples like drugs, pesticides, dyes, reagents, wastewater, cosmetics, and other substances is vital. From the last two decades, there have been numerous efforts to develop the prediction models for mutagenicity, and by far, machine learning methods have demonstrated some noteworthy performance and reliability. However, the accuracy of such prediction models has always been one of the major concerns for the researchers working in this area. The mutagenicity prediction models were developed using deep neural network (DNN), support vector machine, k-nearest neighbor, and random forest. The developed classifiers were based on 3039 compounds and validated on 1014 compounds; each of them encoded with 1597 molecular feature vectors. DNN-based prediction model yielded highest prediction accuracy of 92.95% and 83.81% with the training and test data, respectively. The area under the receiver's operating curve and precision-recall curve values were found to be 0.894 and 0.838, respectively. The DNN-based classifier not only fits the data with better performance as compared to traditional machine learning algorithms, viz., support vector machine, k-nearest neighbor, and random forest (with and without feature reduction) but also yields better performance metrics. In current work, we propose a DNN-based model to predict mutagenicity of compounds.
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http://dx.doi.org/10.1007/s11356-021-14028-9DOI Listing
September 2021

Deciphering the Interacting Mechanisms of Circadian Disruption and Alzheimer's Disease.

Neurochem Res 2021 Jul 19;46(7):1603-1617. Epub 2021 Apr 19.

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Alzheimer's disease (AD) is one of the crucial causative factors for progressive dementia. Neuropathologically, AD is characterized by the extracellular accumulation of amyloid beta plaques and intracellular neurofibrillary tangles in cortical and limbic regions of the human brain. The circadian system is one of the many affected physiological processes in AD, the dysfunction of which may reflect in the irregularity of the sleep/wake cycle. The interplay of circadian and sleep disturbances inducing AD progression is bidirectional. Sleep-associated pathological alterations are frequently evident in AD. Understanding the interrelation between circadian disruption and AD may allow for earlier identification of AD pathogenesis as well as better suited approaches and potential therapies to combat dementia. In this article, we examine the existing literature related to the molecular mechanisms of the circadian clock and interacting mechanisms of circadian disruption and AD pathogenesis.
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http://dx.doi.org/10.1007/s11064-021-03325-xDOI Listing
July 2021

Synaptotagmin-1: A Multi-Functional Protein that Mediates Vesicle Docking, Priming, and Fusion.

Curr Protein Pept Sci 2021 Mar 25. Epub 2021 Mar 25.

King Fahd Medical Research Center, King Abdul-Aziz University, Jeddah. Saudi Arabia.

The fusion of secretory vesicles with the plasma membrane depends on the assembly of v-SNAREs (VAMP2/synaptobrevin2) and t-SNAREs (SNAP25/syntaxin1) into the SNARE complex. Vesicles go through several upstream steps, referred to as docking and priming, to gain fusion competence. The vesicular protein synaptotagmin-1 (Syt-1) is the principal Ca2+ sensor for fusion in several central nervous system neurons and neuroendocrine cells and part of the docking complex for secretory granules. Syt-1 binds to the acceptor complex such as synaxin1, SNAP-25 on the plasma membrane to facilitate secretory vesicle docking, and upon Ca2+-influx promotes vesicle fusion. This review assesses the role of the Syt-1 protein involved in the secretory vesicle docking, priming, and fusion.
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http://dx.doi.org/10.2174/1389203722666210325110231DOI Listing
March 2021

Reconsidering and Reforming the Amyloid Cascade Hypothesis.

Curr Protein Pept Sci 2021 Mar 22. Epub 2021 Mar 22.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah. Saudi Arabia.

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http://dx.doi.org/10.2174/1389203722666210322151627DOI Listing
March 2021

Dissecting Sex-Related Cognition between Alzheimer's Disease and Diabetes: From Molecular Mechanisms to Potential Therapeutic Strategies.

Oxid Med Cell Longev 2021 5;2021:4572471. Epub 2021 Mar 5.

Department of Biological Sciences, University of Limerick, Limerick, Ireland.

The brain is a sexually dimorphic organ that implies different functions and structures depending on sex. Current pharmacological approaches against different neurological diseases act distinctly in male and female brains. In all neurodegenerative diseases, including Alzheimer's disease (AD), sex-related outcomes regarding pathogenesis, prevalence, and response to treatments indicate that sex differences are important for precise diagnosis and therapeutic strategy. Pathogenesis of AD includes vascular dementia, and in most cases, this is accompanied by metabolic complications with similar features as those assembled in diabetes. This review discusses how AD-associated dementia and diabetes affect cognition in relation to sex difference, as both diseases share similar pathological mechanisms. We highlight potential protective strategies to mitigate amyloid-beta (A) pathogenesis, emphasizing how these drugs act in the male and female brains.
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http://dx.doi.org/10.1155/2021/4572471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960032PMC
May 2021

Evaluation of the anti-diarrheal effects of the whole plant extracts of Roxb in pigeons.

Toxicol Rep 2021 23;8:395-404. Epub 2021 Feb 23.

Department of Chemistry, The University of Jordan, Amman, 11942, Jordan.

Background: (dodder) belonging to the family Convolvulaceae has many ethno-medicinal uses such as antidiarrheal and antiemetic. This plant has been employed to treat diarrhea, where the antidiarrheal use of this plant is well established in different communities around the world without scientific bases. In addition, the antibacterial, anthelmintic, anticholinergic, and antihistaminic effects of this parasitic vine are partly responsible for the folkloric antidiarrheal use of this plant. In the present study, the antidiarrheal activity was evaluated in pigeons () using the juice (JCR), aqueous (CRAE), and methanol (CRME) extracts.

Methods: The antidiarrheal effect of was evaluated using different reported research models, with few modifications. In pigeons, diarrhea was induced by administration of castor oil (6 mL/kg, PO), ampicillin (250 mg/kg, IP), magnesium sulfate (2 gm/kg, PO), and cisplatin (6 mg/kg, IV). In these experiments, loperamide (2 mg/kg, IM) was used as a positive control, whereas JCR (1 mL/kg (1%) and 1 mL/kg (2%), CRAE (50, 100 and 200 mg/kg) and CRME (50, 100 and 200 mg/kg) were administered intramuscularly at different doses into each pigeon in the test groups.

Results: In addition to cisplatin-induced diarrhea, all paradigms tested gave significant results ( < 0.01). The JCR, at different doses, exhibited a significant ( < 0.01) a dose-dependent antidiarrheal effect on both the frequency and the onset of diarrhea. Similarly, CRAE and CRME, at doses of 100 and 200 mg/kg, showed considerable ( < 0.001) inhibition against the onset and frequency of diarrhea. On the other hand, JCR, CRAE, and CRME exerted significant effects ( < 0.001) on the percentage inhibition (PI) of diarrhea and gastrointestinal charcoal transit in a dose-dependent manner. In this respect, the maximum PI ( < 0.01) of JCR, CRAE, and CRME in different experimental paradigms was 43.13, 49.14, and 55.99 %, respectively.

Conclusions: Taken all together, results from this study reveal that the juice, aqueous, and methanol extract of exhibit significant anti-motility and anti-secretory potential. These findings may explain the medicinal use of folk medicine as an antidiarrheal medicinal plant.
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http://dx.doi.org/10.1016/j.toxrep.2021.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921875PMC
February 2021

Impaired Quality Control of Mitochondria Underlying the Pathogenesis of Alzheimer's Disease.

Curr Drug Targets 2021 Mar 8. Epub 2021 Mar 8.

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah. Saudi Arabia.

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http://dx.doi.org/10.2174/1389450122666210309105326DOI Listing
March 2021

Hutchinson-Gilford Progeria Syndrome: An Overview of the Molecular Mechanism, Pathophysiology and Therapeutic Approach.

Curr Gene Ther 2021 ;21(3):216-229

Department of Pharmacy, Southeast University, Dhaka, Bangladesh.

Lamin A/C encoded by the LMNA gene is an essential component for maintaining the nuclear structure. Mutation in the lamin A/C leads to a group of inherited disorders is known as laminopathies. In the human body, there are several mutations in the LMNA gene that have been identified. It can affect diverse organs or tissues or can be systemic, causing different diseases. In this review, we mainly focused on one of the most severe laminopathies, Hutchinson-Gilford progeria syndrome (HGPS). HGPS is an immensely uncommon, deadly, metameric ill-timed laminopathies caused by the abnormal splicing of the LMNA gene and production of an aberrant protein known as progerin. Here, we also presented the currently available data on the molecular mechanism, pathophysiology, available treatment, and future approaches to this deadly disease. Due to the production of progerin, an abnormal protein leads to an abnormality in nuclear structure, defects in DNA repair, shortening of telomere, and impairment in gene regulation which ultimately results in aging in the early stage of life. Now some treatment options are available for this disease, but a proper understanding of the molecular mechanism of this disease will help to develop a more appropriate treatment which makes it an emerging area of research.
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http://dx.doi.org/10.2174/1566523221666210303100805DOI Listing
January 2021

COVID-19: Epidemiology, Pathology, Diagnosis, Treatment, and Impact.

Curr Pharm Des 2021 Feb 24. Epub 2021 Feb 24.

Molecular Pharmacology and Herbal Drug Research Laboratory, Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000. Bangladesh.

The pandemic, well-known as COVID-19, has been brought about by the coronavirus SARS-CoV-2 and it has distinct characteristics from other coronavirus-related epidemics. This pandemic has been ravaging the whole world for more than a year now and no drugs or vaccines have been found to eliminate this virus from the infected people effectively; only physical measures like social distancing, hand washing and face-mask wearing have been taken to reduce its spreading and very recently Veklury (remdesivir) has been permitted by the USFDA to manage the critical patients. This disease can be asymptomatic but when it is symptomatic, it presents with respiratory problems and cold- or flu-like symptoms which can be diagnosed with a chest CT and confirmed with RT-PCR tests. In this review, the taxonomy and structure of SARS-CoV-2 and history, transmission, epidemiology, pathology, clinical features and impacts of the COVID-19 have been discussed. A summary of possible drug targets, attempted physical and chemical measures, as well as vaccine candidates, have also been provided. How this coronavirus is different from other coronaviruses, the obstacles in managing this disease and the possibility of a second wave have also been reviewed. This review represents a wide range of information regarding COVID-19 and intends to be used as a comprehensive overview in this regard.
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http://dx.doi.org/10.2174/1381612827666210224142446DOI Listing
February 2021
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