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  1. Fulltext Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro
    Paudel KR, Clarence DD, Panth N, Manandhar B, De Rubis G, Devkota HP, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Apr;397(4):2465-2483.
    PMID: 37851060 DOI: 10.1007/s00210-023-02760-7
    The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
  2. Fulltext Alleviation of diabetic nephropathy by zinc oxide nanoparticles in streptozotocin-induced type 1 diabetes in rats
    Alomari G, Al-Trad B, Hamdan S, Aljabali AAA, Al Zoubi MS, Al-Batanyeh K, et al.
    IET Nanobiotechnol, 2021 Jul;15(5):473-483.
    PMID: 34694755 DOI: 10.1049/nbt2.12026
    This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-β1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.
  3. WITHDRAWN: Trace metals translocation from soil to plants: Health risk assessment via consumption of vegetables in the urban sprawl of a developing country
    Haque KS, Islam MS, Ahmed S, Rahman MZ, Hemy DH, Islam MT, et al.
    Food Chem Toxicol, 2024 Mar 11.
    PMID: 38467293 DOI: 10.1016/j.fct.2024.114580
    This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.
  4. Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases
    Chan Y, Raju Allam VSR, Paudel KR, Singh SK, Gulati M, Dhanasekaran M, et al.
    Crit Rev Food Sci Nutr, 2023;63(19):3302-3332.
    PMID: 34613853 DOI: 10.1080/10408398.2021.1986467
    Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.
  5. Nuclear factor-kappa B (NF-κB) inhibition as a therapeutic target for plant nutraceuticals in mitigating inflammatory lung diseases
    Alharbi KS, Afzal O, Almalki WH, Kazmi I, Javed Shaikh MA, Thangavelu L, et al.
    Chem Biol Interact, 2022 Feb 25;354:109842.
    PMID: 35104489 DOI: 10.1016/j.cbi.2022.109842
    Nutraceuticals are dietary supplements that are used to improve health, postpone aging, prevent illnesses, and maintain the human body's correct functioning. Nutraceuticals are now garnering a lot of interest because of their nutritional and therapeutic benefits. The research indicating the relevance of nutraceuticals as a possible therapeutic candidate against inflammatory lung disease was covered in this review. Nowadays, inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pneumonia, lung cancer, becoming highly dreadful because of their associated fatality. Inflammation is one of the cores and common factors of these diseases which is mainly associated with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, NF-κB p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation, and initiation of the signaling pathway of the NF-κB. The secondary metabolites from natural sources are the active component that attenuates NF-κB and the associated pathway that inhibits inflammation in lung diseases. Nutraceuticals belonging to the chemical category polyphenols, alkaloids, terpenoids, flavonoids, tannins have the potential to combat the NF-κB pathway. Accordingly, this review discusses the medical value of nutraceuticals briefly and their ability to mitigate various inflammatory lung diseases through targeting inhibition of NF-κB.
  6. Fulltext Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations
    Jha NK, Ojha S, Jha SK, Dureja H, Singh SK, Shukla SD, et al.
    J Mol Neurosci, 2021 Nov;71(11):2192-2209.
    PMID: 33464535 DOI: 10.1007/s12031-020-01767-6
    The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
  7. Proteostasis disruption and senescence in Alzheimer's disease pathways to neurodegeneration
    Thapa R, Ahmad Bhat A, Shahwan M, Ali H, PadmaPriya G, Bansal P, et al.
    Brain Res, 2024 Dec 15;1845:149202.
    PMID: 39216694 DOI: 10.1016/j.brainres.2024.149202
    Alzheimer's Disease (AD) is a progressive neurological disease associated with behavioral abnormalities, memory loss, and cognitive impairment that cause major causes of dementia in the elderly. The pathogenetic processes cause complex effects on brain function and AD progression. The proper protein homeostasis, or proteostasis, is critical for cell health. AD causes the buildup of misfolded proteins, particularly tau and amyloid-beta, to break down proteostasis, such aggregates are toxic to neurons and play a critical role in AD pathogenesis. The rise of cellular senescence is accompanied by aging, marked by irreversible cell cycle arrest and the release of pro-inflammatory proteins. Senescent cell build-up in the brains of AD patients exacerbates neuroinflammation and neuronal degeneration. These cells senescence-associated secretory phenotype (SASP) also disturbs the brain environment. When proteostasis failure and cellular senescence coalesce, a cycle is generated that compounds each other. While senescent cells contribute to proteostasis breakdown through inflammatory and degradative processes, misfolded proteins induce cellular stress and senescence. The principal aspects of the neurodegenerative processes in AD are the interaction of cellular senescence and proteostasis failure. This review explores the interconnected roles of proteostasis disruption and cellular senescence in the pathways leading to neurodegeneration in AD.
  8. Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome
    Corrie L, Singh H, Gulati M, Vishwas S, Chellappan DK, Gupta G, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Sep;397(9):6721-6743.
    PMID: 38507103 DOI: 10.1007/s00210-024-03029-3
    The gut microbiome is involved in the pathogenesis of many diseases including polycystic ovarian syndrome (PCOS). Modulating the gut microbiome can lead to eubiosis and treatment of various metabolic conditions. However, there is no proper study assessing the delivery of microbial technology for the treatment of such conditions. The present study involves the development of guar gum-pectin-based solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing curcumin (CCM) and fecal microbiota extract (FME) for the treatment of PCOS. The optimized S-SNEDDS containing FME and CCM was prepared by dissolving CCM (25 mg) in an isotropic mixture consisting of Labrafil M 1944 CS, Transcutol P, and Tween-80 and solidified using lactose monohydrate, aerosil-200, guar gum, and pectin (colon-targeted CCM solid self-nanoemulsifying drug delivery system [CCM-CT-S-SNEDDS]). Pharmacokinetic and pharmacodynamic evaluation was carried out on letrozole-induced female Wistar rats. The results of pharmacokinetic studies indicated about 13.11 and 23.48-fold increase in AUC of CCM-loaded colon-targeted S-SNEDDS without FME (CCM-CT-S-SNEDDS (WFME)) and CCM-loaded colon-targeted S-SNEDDS with FME [(CCM-CT-S-SNEDDS (FME)) as compared to unprocessed CCM. The pharmacodynamic study indicated excellent recovery/reversal in the rats treated with CCM-CT-S-SNEDDS low and high dose containing FME (group 13 and group 14) in a dose-dependent manner. The developed formulation showcasing its improved bioavailability, targeted action, and therapeutic activity in ameliorating PCOS can be utilized as an adjuvant therapy for developing a dosage form, scale-up, and technology transfer.
  9. Retraction Note: Polysaccharide-fecal microbiota-based colon-targeted self-nanoemulsifying drug delivery system of curcumin for treating polycystic ovarian syndrome
    Corrie L, Singh H, Gulati M, Vishwas S, Chellappan DK, Gupta G, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Nov 20.
    PMID: 39565398 DOI: 10.1007/s00210-024-03635-1
  10. Fulltext Hypoglycaemic Molecules for the Management of Diabetes Mellitus from Marine Sources
    Chellappan DK, Chellian J, Rahmah NSN, Gan WJ, Banerjee P, Sanyal S, et al.
    Diabetes Metab Syndr Obes, 2023;16:2187-2223.
    PMID: 37521747 DOI: 10.2147/DMSO.S390741
    Diabetes mellitus (DM) is a chronic metabolic disorder recognized as a major health problem globally. A defective insulin activity contributes to the prevalence and expansion of DM. Treatment of DM is often hampered by limited options of conventional therapies and adverse effects associated with existing procedures. This has led to a spike in the exploration for potential therapeutic agents from various natural resources for clinical applications. The marine environment is a huge store of unexplored diversity of chemicals produced by a multitude of organisms. To date, marine microorganisms, microalgae, macroalgae, corals, sponges, and fishes have been evaluated for their anti-diabetic properties. The structural diversity of bioactive metabolites discovered has shown promising hypoglycaemic potential through in vitro and in vivo screenings via various mechanisms of action, such as PTP1B, α-glucosidase, α-amylase, β-glucosidase, and aldose reductase inhibition as well as PPAR alpha/gamma dual agonists activities. On the other hand, hypoglycaemic effect is also shown to be exerted through the balance of antioxidants and free radicals. This review highlights marine-derived chemicals with hypoglycaemic effects and their respective mechanisms of action in the management of DM in humans.
  11. Berberine-loaded engineered nanoparticles attenuate TGF-β-induced remodelling in human bronchial epithelial cells
    De Rubis G, Paudel KR, Liu G, Agarwal V, MacLoughlin R, de Jesus Andreoli Pinto T, et al.
    Toxicol In Vitro, 2023 Oct;92:105660.
    PMID: 37591407 DOI: 10.1016/j.tiv.2023.105660
    Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.
  12. Fulltext Expert consensus statement on the science of HIV in the context of criminal law
    Barré-Sinoussi F, Abdool Karim SS, Albert J, Bekker LG, Beyrer C, Cahn P, et al.
    J Int AIDS Soc, 2018 Jul;21(7):e25161.
    PMID: 30044059 DOI: 10.1002/jia2.25161
    INTRODUCTION: Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence.

    DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant.

    CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.

  13. Fulltext Berberine-loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Mehta M, Yin GHS, Yen LL, Malyla V, Patel VK, et al.
    Environ Sci Pollut Res Int, 2022 Jul;29(31):46830-46847.
    PMID: 35171422 DOI: 10.1007/s11356-022-19158-2
    Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung cancer. Berberine is an isoquinoline alkaloid which offers a broad range of therapeutical and pharmacological actions against cancer. However, extremely low water solubility and poor oral bioavailability have largely restricted its therapeutic applications. To overcome these limitations, we formulated berberine-loaded liquid crystalline nanoparticles (LCNs) and investigated their in vitro antiproliferative and antimigratory activity in human lung epithelial cancer cell line (A549). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue staining, and colony forming assays were used to evaluate the anti-proliferative activity, while scratch wound healing assay and a modified Boyden chamber assay were carried out to determine the anti-migratory activity. We also investigated major proteins associated with lung cancer progression. The developed nanoparticles were found to have an average particle size of 181.3 nm with spherical shape, high entrapment efficiency (75.35%) and have shown sustained release behaviour. The most remarkable findings reported with berberine-loaded LCNs were significant suppression of proliferation, inhibition of colony formation, inhibition of invasion or migration via epithelial mesenchymal transition, and proliferation related proteins associated with cancer progression. Our findings suggest that anti-cancer compounds with the problem of poor solubility and bioavailability can be overcome by formulating them into nanotechnology-based delivery systems for better efficacy. Further in-depth investigations into anti-cancer mechanistic research will expand and strengthen the current findings of berberine-LCNs as a potential NSCLC treatment option.
  14. Emerging applications and prospects of NFκB decoy oligodeoxynucleotides in managing respiratory diseases
    Datsyuk JK, Paudel KR, Rajput R, Kokkinis S, El Sherkawi T, Singh SK, et al.
    Chem Biol Interact, 2023 Nov 01;385:110737.
    PMID: 37774998 DOI: 10.1016/j.cbi.2023.110737
    Chronic respiratory diseases like asthma and Chronic Obstructive Pulmonary Disease (COPD) have been a burden to society for an extended period. Currently, there are only preventative treatments in the form of mono- or multiple-drug therapy available to patients who need to utilize it daily. Hence, throughout the years there has been a substantial amount of research in understanding what causes inflammation in the context of these diseases. For example, the transcription factor NFκB has a pivotal role in causing chronic inflammation. Subsequent research has been exploring ways to block the activation of NFκB as a potential therapeutic strategy for many inflammatory diseases. One of the possible ways through which this is probable is the utilisation of decoy oligodeoxynucleotides, which are synthetic, short, single-stranded DNA fragments that mimic the consensus binding site of a targeted transcription factor, thereby functionally inactivating it. However, limitations to the implementation of decoy oligodeoxynucleotides include their rapid degradation by intracellular nucleases and the lack of targeted tissue specificity. An advantageous approach to overcome these limitations involves using nanoparticles as a vessel for drug delivery. In this review, all of those key elements will be explored as to how they come together as an application to treat chronic inflammation in respiratory diseases.
  15. Fulltext Zerumbone-incorporated liquid crystalline nanoparticles inhibit proliferation and migration of non-small-cell lung cancer in vitro
    Manandhar B, Paudel KR, Clarence DD, De Rubis G, Madheswaran T, Panneerselvam J, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Jan;397(1):343-356.
    PMID: 37439806 DOI: 10.1007/s00210-023-02603-5
    Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.
  16. A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer
    Shamsudin NF, Leong SW, Koeberle A, Suriya U, Rungrotmongkol T, Chia SL, et al.
    Future Med Chem, 2024 Aug 02;16(15):1499-1517.
    PMID: 38949858 DOI: 10.1080/17568919.2024.2363668
    Aim: Chromones are promising for anticancer drug development.Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC50 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 μM). It suppressed colony formation, induced cell cycle arrest and triggered apoptotic cell death, confirmed by staining and apoptosis markers. Cell death was accompanied by enhanced reactive oxygen species formation and modulation of the autophagic machinery (autophagy marker light chain 3B (LC3B); adenosine monophosphate-activated protein kinase (AMPK); protein kinase B (PKB); UNC-51-like kinase (ULK)-1; and ULK2). Molecular docking and dynamic simulations revealed that compound 8 directly binds to ULK1.Conclusion: Compound 8 is a promising lead for autophagy-modulating anti-colon cancer drugs.
  17. Fulltext Autoantibodies and autoimmune disorders in SARS-CoV-2 infection: pathogenicity and immune regulation
    Darmarajan T, Paudel KR, Candasamy M, Chellian J, Madheswaran T, Sakthivel LP, et al.
    Environ Sci Pollut Res Int, 2022 Aug;29(36):54072-54087.
    PMID: 35657545 DOI: 10.1007/s11356-022-20984-7
    Coronavirus disease 2019 (COVID-19) is an infectious disease associated with the respiratory system caused by the SARS-CoV-2 virus. The aim of this review article is to establish an understanding about the relationship between autoimmune conditions and COVID-19 infections. Although majority of the population have been protected with vaccines against this virus, there is yet a successful curative medication for this disease. The use of autoimmune medications has been widely considered to control the infection, thus postulating possible relationships between COVID-19 and autoimmune diseases. Several studies have suggested the correlation between autoantibodies detected in patients and the severity of the COVID-19 disease. Studies have indicated that the SARS-CoV-2 virus can disrupt the self-tolerance mechanism of the immune system, thus triggering autoimmune conditions. This review discusses the current scenario and future prospects of promising therapeutic strategies that may be employed to regulate such autoimmune conditions.
  18. Theoretical investigation of selective inhibitory activity of chromone-based compounds against monoamine oxidase (MAO)-A and -B
    Putri IS, Shamsudin NF, Abdullah MA, Nurcholis M, Imran S, Yu CX, et al.
    J Biomol Struct Dyn, 2024 Dec 05.
    PMID: 39633610 DOI: 10.1080/07391102.2024.2436553
    Monoamine oxidase (MAO) is crucial for the breakdown of monoamine neurotransmitters, making it a promising target for treating neurodegenerative disorders, such as depression, Alzheimer's disease, and Parkinson's disease. In this study, we investigated the selective inhibitory activity of chromone-based compounds against MAO-A and MAO-B for neurodegenerative disease treatment. In literary sources, thirty chromone derivatives have been identified as potential ligands for MAO-A and MAO-B inhibitors. We utilized molecular docking to evaluate how the most active compound interacted with the targeted MAO-A and MAO-B. Compound 2 g, the most active for MAO-A, demonstrated a lower CDOCKER energy compared to the co-crystallized ligand. Meanwhile, compound 2f, the most active for MAO-B, showed a CDOCKER energy similar to the co-crystallized ligand and exhibited similar binding patterns. Furthermore, we constructed a quantitative structure-activity relationship (QSAR) model to predict the properties and estimate IC50 values for 30 chromone derivatives functioning as MAO-A and MAO-B inhibitors. The model predictions were validated against experimental measurements. Our 2D QSAR model demonstrated robustness, with a statistically significant non-cross-validated coefficient (r2 < 0.9), cross-validated correlation coefficient (q2 < 0.6), and predictive squared correlation coefficient (r2pred < 0.8). Additionally, MD simulations confirmed the stable binding of compounds 2 g and 2f with MAO-A and MAO-B, respectively, displaying substantial binding energy. The most effective pharmacophore model identified key features, such as hydrogen bond acceptors and hydrophobic interactions, that contribute significantly to inhibitory potency. This study offers valuable insight into the selection of compounds with improved selectivity for MAO inhibition.
  19. Association between vascular endothelial growth factor and atrial fibrillation: a systematic review
    Sharma N, Khatib MN, Roopashree R, Kaur M, Srivastava M, Barwal A, et al.
    BMC Cardiovasc Disord, 2025 Jan 06;25(1):5.
    PMID: 39757193 DOI: 10.1186/s12872-024-04460-3
    BACKGROUND: Atrial fibrillation (AF) is the most prevalent form of sustained cardiac arrhythmia, with vascular endothelial growth factor (VEGF) increasingly recognized for its potential role in the pathogenesis of AF through mechanisms involving atrial remodeling, inflammation, and fibrosis. This systematic review aims to synthesize available evidence on the association between VEGF and AF, exploring the implications of VEGF as a biomarker and therapeutic target.

    METHODS: We conducted a comprehensive search across PubMed, Embase, and Web of Science until November 10 2024, selecting studies based on pre-defined criteria that involve adults with AF and measurements of VEGF levels. The selected studies included observational and experimental designs, excluding non-English and methodologically insufficient publications. Narrative synthesis was used for summarising the results.

    RESULTS: Eight studies met the inclusion criteria. The studies show a general trend of elevated VEGF levels in AF patients compared to controls, with significant heterogeneity in findings across studies. VEGF subtypes such as VEGF-A and VEGF-D demonstrated stronger associations with AF risk compared to VEGF-C. These variations point to the complex role of VEGF in AF, influencing factors like angiogenesis, endothelial function, and inflammatory responses.

    CONCLUSION: VEGF is potentially a significant contributor to AF pathophysiology, with its levels reflecting disease activity. The variability observed across studies suggests a need for standardized measurement approaches and further investigation into VEGF subtypes. Future research should focus on longitudinal studies to better understand the causal relationships and the potential of VEGF as a therapeutic target and biomarker in AF management.

    CLINICAL TRIAL NUMBER: Not applicable.

  20. The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region
    Elghazaly H, Aref AT, Anderson BO, Arun B, Yip CH, Abdelaziz H, et al.
    Int J Cancer, 2021 08 01;149(3):505-513.
    PMID: 33559295 DOI: 10.1002/ijc.33506
    In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.
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