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Viruses pose a significant challenge and threat to human health, as demonstrated by the current COVID-19 pandemic. Neurodegeneration, particularly in the case of Alzheimer's disease (AD), is significantly influenced by viral infections. AD is a neurodegenerative disease that affects people of all ages and poses a significant threat to millions of individuals worldwide. The precise mechanism behind its development is not yet fully understood; however, the emergence and advancement of AD can be hastened by various environmental factors, such as bacterial and viral infections. There has been a longstanding suspicion that the herpes simplex virus-1 (HSV-1) may have a role to play in the development or advancement of AD. Reactivation of HSV-1 could potentially lead to damage to neurons, either by direct means or indirectly by triggering inflammation. This article provides an overview of the connection between HSV-1 infections and immune cells (astrocytes, microglia, and oligodendrocytes) in the progression of AD. It summarizes recent scientific research on how HSV-1 affects neurons, which could potentially shed light on the clinical features and treatment options for AD. In addition, the paper has explored the impact of HSV-1 on neurons and its role in various aspects of AD, such as Aβ secretion, tau hyperphosphorylation, metabolic dysregulation, oxidative damage, apoptosis, and autophagy. It is believed that the immune response triggered by HSV-1 reactivation plays a role in the development of neurodegeneration in AD. Despite the lack of a cure for AD, researchers have made significant efforts to study the clinical and pathological aspects of the disease, identify biomarkers, and gain insight into its underlying causes. The goal is to achieve early diagnosis and develop treatments that can modify the progression of the disease. The current article discusses the most promising therapy for combating the viral impacts, which provides additional evidence for the frequent reactivations of latent HSV-1 in the AD brain. However, further research is still required to establish the molecular and cellular mechanisms underlying the development of AD through the reactivation of HSV-1. This could potentially lead to new insights in drug development aimed at preventing HSV-1 reactivation and the subsequent development and progression of AD., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The endocannabinoid system has garnered attention as a potential therapeutic target in a range of pathological disorders. Cannabinoid receptors type 2 (CB2) are a class of G protein-coupled receptors responsible for transmitting intracellular signals triggered by both endogenous and exogenous cannabinoids, including those derived from plants (phytocannabinoids) or manufactured synthetically (synthetic cannabinoids). Recent recognition of the role of CB2 receptors in fibrosis has fueled interest in therapeutic targeting of CB2 receptors in fibrosis. Fibrosis is characterized by the alteration of the typical cellular composition within the tissue parenchyma, resulting from exposure to diverse etiological factors. The pivotal function of CB2 agonists has been widely recognized in the regulation of inflammation, fibrogenesis, and various other biological pathologies. The modulation of CB2 receptors, whether by enhancing their expression or activating their function, has the potential to provide benefits in numerous conditions, particularly by avoiding any associated adverse effects on the central nervous system. The sufficient activation of CB2 receptors resulted in the complete suppression of gene expression related to transforming growth factor β1 and its subsequent fibrogenic response. Multiple reports have also indicated the diverse functions that CB2 agonists possess in mitigating chronic inflammation and subsequent fibrosis development in various types of tissues. While currently in the preclinical stage, the advancement of CB2 compounds has garnered significant attention within the realm of drug discovery. This review presents a comprehensive synthesis of various independent experimental studies elucidating the pivotal role of identified natural and synthetic CB2 agonists in the pathophysiology of organ fibrosis, specifically in the cardiac, hepatic, and renal systems., (© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Mentha aquatica L., or water mint, is an important member of the Mentha genus, and has long been used in traditional medicine, mainly to treat respiratory diseases such as the common cold. Nevertheless, although over the years many studies have shown that it's potential grows beyond this use, a review that highlights M. aquatica L.'s true potential is still lacking. Thus, the main purpose of the present article is to provide a thorough and multidisciplinary critical review of M. aquatica L., including its phytochemical characterization, main bioactivities, and current marketed cosmetic products. Many compounds have been identified as part of M. aquatica L. composition, such as terpenes, phenolic acids, phenols, and terpenoids, which have been linked to a vast therapeutic potential, namely anti-inflammatory, antioxidant, antibacterial, antifungal, antiobesity, and hepatoprotection bioactivities, with additional anticancer potential for several types of tumors (breast, lung, and skin), and psycho and neuroactive potential in depression, or Alzheimer's or Parkinson's disease. Additionally, it has been proven to be suitable for cosmetic application since several cleansing, hydrating, protecting, and/or odor masking products containing it are already available, with the main functions attributed to M. aquatica including refreshing/cooling effects, calming/soothing/relaxing effects, and purifying effects, properties closely related to its anti-inflammatory and antioxidant bioactivities. Hence, M. aquatica is an extremely versatile plant, with its extracts and essential oils having great therapeutic and cosmetic potential. With many marketed cosmetic products, future studies should focus on this plant's medicinal aspects, so that 1 day it can be part of therapeutic regimens., (© 2024 John Wiley & Sons Ltd.)

Plants and their derived phytochemicals have a long history of treating a wide range of illnesses for several decades. They are believed to be the origin of a diverse array of medicinal compounds. One of the compounds found in kudzu root is puerarin, a isoflavone glycoside commonly used as an alternative medicine to treat various diseases. From a biological perspective, puerarin can be described as a white needle crystal with the chemical name of 7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4-one-8-D-glucopyranoside. Besides, puerarin is sparingly soluble in water and produces no color or light yellow solution. Multiple experimental and clinical studies have confirmed the significant therapeutic effects of puerarin. These effects span a wide range of pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, immunomodulation, anticancer properties, anti-diabetic properties, anti-osteoporosis properties, and more. Puerarin achieves these effects by interacting with various cellular and molecular pathways, such as MAPK, AMPK, NF-κB, mTOR, β-catenin, and PKB/Akt, as well as different receptors, enzymes, and growth factors. The current review highlights the molecular mechanism of puerarin as a neuroprotective agent in the treatment of various neurodegenerative and neurological diseases. Extensive cellular, animal, and clinical research has provided valuable insights into its effectiveness in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, cerebral stroke, depression, and more., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oxidative stress, fibrosis, and inflammasome activation from advanced glycation end product (AGE)-receptor of advanced glycation end product (RAGE) interaction contribute to diabetic cardiomyopathy (DCM) formation and progression. Our study revealed the impact of β -caryophyllene (BCP) on activating cannabinoid type 2 receptors (CB2Rs) against diabetic complication, mainly cardiomyopathy and investigated the underlying cell signaling pathways in mice. The murine model of DCM was developed by feeding a high-fat diet with streptozotocin injections. After the development of diabetes, the animals received a 12-week oral BCP treatment at a dose of 50 mg/kg/body weight. BCP treatment showed significant improvement in glucose tolerance and insulin resistance and enhanced serum insulin levels in diabetic animals. BCP treatment effectively reversed the heart remodeling and restored the phosphorylated troponin I and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a expression. Ultrastructural examination showed reduced myocardial cell injury in DCM mice treated with BCP. The preserved myocytes were found to be associated with reduced expression of AGE/RAGE in DCM mice hearts. BCP treatment mitigated oxidative stress by inhibiting expression of NADPH oxidase 4 and activating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Also, BCP suppressed cardiac fibrosis and endothelial-to-mesenchymal transition in DCM mice by inhibiting transforming growth factor β (TGF-β)/suppressor of mothers against decapentaplegic (Smad) signaling. Further, BCP treatment suppressed nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation in DCM mice and alleviated cellular injury to the pancreatic tissues evidenced by significant elevation of the number of insulin-positive cells. To demonstrate a CB2R-dependent mechanism of BCP, another group of DCM mice were pretreated with AM630, a CB2R antagonist. AM630 was observed to abrogate the beneficial effects of BCP in DCM mice. Taken together, BCP demonstrated the potential to protect the myocardium and pancreas of DCM mice mediating CB2R-dependent mechanisms. SIGNIFICANCE STATEMENT: BCP, a CB2R agonist, shows protection against DCM. BCP attenuates oxidative stress, inflammation, and fibrosis in DCM via activating CB2Rs. BCP mediating CB2R activation favorably modulates AGE/RAGE, PI3K/AKT/Nrf2 β and TGF- β /Smad and (NLRP3) inflammasome in diabetic cardiomyopathy., (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)

The complex pathophysiology of Alzheimer's disease (AD) poses challenges for the development of therapies. Recently, neuroinflammation has been identified as a key pathogenic mechanism underlying AD, while inflammation has emerged as a possible target for the management and prevention of AD. Several prior studies have demonstrated that medications modulating neuroinflammation might lessen AD symptoms, mostly by controlling neuroinflammatory signaling pathways such as the NF-κB, MAPK, NLRP3, etc, and their respective signaling cascade. Moreover, targeting these inflammatory modalities with inhibitors, natural products, and metabolites has been the subject of intensive research because of their anti-inflammatory characteristics, with many studies demonstrating noteworthy pharmacological capabilities and potential clinical applications. Therefore, targeting inflammation is considered a promising strategy for treating AD. This review comprehensively elucidates the neuroinflammatory mechanisms underlying AD progression and the beneficial effects of inhibitors, natural products, and metabolites in AD treatment., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cancer, a multifaceted and pernicious disease, continuously challenges medicine, requiring innovative treatments. Brain cancers pose unique and daunting challenges due to the intricacies of the central nervous system and the blood-brain barrier. In this era of precision medicine, the convergence of neurology, oncology, and cutting-edge technology has given birth to a promising avenue - targeted cancer therapy. Furthermore, bioinspired microrobots have emerged as an ingenious approach to drug delivery, enabling precision and control in cancer treatment. This Keynote review explores the intricate web of neurological insights into brain-targeted cancer therapy and the paradigm-shifting world of bioinspired microrobots. It serves as a critical and comprehensive overview of these evolving fields, aiming to underscore their integration and potential for revolutionary cancer treatments., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's Disease (AD) is a challenging neurodegenerative condition, with overwhelming implications for affected individuals and healthcare systems worldwide. Animal models have played a crucial role in studying AD pathogenesis and testing therapeutic interventions. Remarkably, studies on the genetic factors affecting AD risk, such as APOE and TREM2, have provided valuable insights into disease mechanisms. Early diagnosis has emerged as a crucial factor in effective AD management, as demonstrated by clinical studies emphasizing the benefits of initiating treatment at early stages. Novel diagnostic technologies, including RNA sequencing of microglia, offer promising avenues for early detection and monitoring of AD progression. Therapeutic strategies remain to evolve, with a focus on targeting amyloid beta (Aβ) and tau pathology. Advances in animal models, such as APP-KI mice, and the advancement of anti-Aβ drugs signify progress towards more effective treatments. Therapeutically, the focus has shifted towards intricate approaches targeting multiple pathological pathways simultaneously. Strategies aimed at reducing Aβ plaque accumulation, inhibiting tau hyperphosphorylation, and modulating neuroinflammation are actively being explored, both in preclinical models and clinical trials. While challenges continue in developing validated animal models and translating preclinical findings to clinical success, the continuing efforts in understanding AD at molecular, cellular, and clinical levels offer hope for improved management and eventual prevention of this devastating disease., Competing Interests: Declaration of Competing Interest There is no conflict of interest to be declared. Competing Interests The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The potential for multiorgan toxicities is a significant barrier to the therapeutic use of doxorubicin (DOX) in cancer treatment. With regard to DOX-induced acute cardiotoxicity in rats, the current investigation sought to assess the cardioprotective function of α-bisabolol (BSB) as well as the underlying pharmacological and molecular processes. Acute cardiotoxicity was induced in the rats by the intraperitoneal injection of DOX (12.5 mg/kg, single dosage). Over the course of 5 days, the rats were administered 25 mg/kg of BSB orally twice a day. The DOX administration induced cardiac damage, as evidenced by altered cardiospecific diagnostic markers and macroscopic enzyme mapping assay. The occurrence of mitochondrial oxidative stress was observed by a significant decline in antioxidant defense along with an increase in lipid peroxidation. DOX also perturbed DNA damage, mitochondrial biogenesis, mitochondrial fission and dysfunction, ER stress, Hippo signaling, and caspase-dependent and independent apoptosis including necroptosis and ferroptosis in the myocardium of rats. Conversely, it has been noted that the administration of BSB preserves the myocardium and reverses all cellular, molecular, and structural disruptions in the cardiac tissues of rats exposed to DOX-induced toxicity. The results that are currently available unequivocally show the cardioprotective role of BSB in DOX-induced cardiotoxicity. This effect is attributed to BSB's strong antioxidant, antilipid peroxidative, and antiapoptotic properties, which are mediated by advantageous changes in multiple signaling pathways., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

The interplay between human health and the microbiome has gained extensive attention, with probiotics emerging as pivotal therapeutic agents due to their vast potential in treating various health issues. As significant modulators of the gut microbiota, probiotics are crucial in maintaining intestinal homeostasis and enhancing the synthesis of short-chain fatty acids. Despite extensive research over the past decades, there remains an urgent need for a comprehensive and detailed review that encapsulates probiotics' latest insights and applications. This review focusses on the multifaceted roles of probiotics in promoting health and preventing disease, highlighting the complex mechanisms through which these beneficial bacteria influence both gut flora and the human body at large. This paper also explores probiotics' neurological and gastrointestinal applications, focussing on their significant impact on the gut-brain axis and their therapeutic potential in a broad spectrum of pathological conditions. Current innovations in probiotic formulations, mainly focusing on integrating genomics and biotechnological advancements, have also been comprehensively discussed herein. This paper also critically examines the regulatory landscape that governs probiotic use, ensuring safety and efficacy in clinical and dietary settings. By presenting a comprehensive overview of recent studies and emerging trends, this review aims to illuminate probiotics' extensive therapeutic capabilities, leading to future research and clinical applications. However, besides extensive research, further advanced explorations into probiotic interactions and mechanisms will be essential for developing more targeted and effective therapeutic strategies, potentially revolutionizing health care practices for consumers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Ventricular septal defect (VSD) is the most common congenital cardiac malformation, accounting for approximately 30% of congenital heart defects. Conventional surgical repair using cardiopulmonary bypass is invasive and associated with morbidities and prolonged hospital stay. With the advent of interventional approaches and availability of different occluding devices, the technique of perventricular device closure is evolving and being implemented successfully in larger groups of patients. We present herein, our initial experience of perventricular device closure for the ventricular septal defects in children to assess risks and benefits., Methods: From March, 2023 to February, 2024, we have performed perventricular closure of ventricular septal defects in 13 children, under guidance of transesophageal echocardiography without cardiopulmonary bypass support. The median age at operation was 2 year (range 1.3-10 years) with the median body weight 11 kg (range 8.7-16.6 kg). Sixty-nine percent were males. The ventricular septal defect sizes ranged from 2.7 to 6 mm (mean 4.7 mm). Seven defects were perimembranous, four sub-aortic and two were muscular. One patient also underwent pulmonary artery de-banding with pulmonary artery balloon angioplasty and other one patent ductus arteriosus ligation, concomitantly. For defect closure, we used ventricular septal defect occlusion device (MemoPart™, Lepu Medical Technology Company, China) through a 3-cm skin incision in the lower- third of the sternum. The device sizes ranged from 5 to 8 mm (mean 6.9+-1.8 mm) and all patients except for two required symmetrical devices., Results: All patients underwent device closure successfully. The procedural duration ranged between 32 and 52 min. None of the patients required cardiopulmonary bypass. The mean ventilation time and intensive care unit stay was 3 and 24 h, respectively. None of the patients required inotropic support or blood transfusions. Moreover, no patients developed any arrhythmias including heart block. The average length of hospital stay was 4.4 days. At the latest follow up, there were no residual shunts, conduction disturbances, device dislodgement or major aortic or tricuspid valve complications seen in any patients. There was no mortality., Conclusions: Perventricular device closure of ventricular septal defects is a less invasive, extremely safe and effective method in children. It is associated with very fast recovery, shorter hospitalization time and better cosmetic incision. Moreover, it avoids cardiopulmonary bypass. The modifications and refinements in the design, material and implantation techniques will help in expanding the indications and prevent complications in the long-term., (© 2024. The Author(s).)

Bovine mastitis (BM) is the most common bacterial mediated inflammatory disease in the dairy cattle that causes huge economic loss to the dairy industry due to decreased milk quality and quantity. Milk is the essential food in the human diet, and rich in crucial nutrients that helps in lowering the risk of diseases like hypertension, cardiovascular diseases and type 2 diabetes. The main causative agents of the disease include various gram negative, and positive bacteria, along with other risk factors such as udder shape, age, genetic, and environmental factors also contributes much for the disease. Currently, antibiotics, immunotherapy, probiotics, dry cow, and lactation therapy are commonly recommended for BM. However, these treatments can only decrease the rise of new cases but can't eliminate the causative agents, and they also exhibit several limitations. Hence, there is an urgent need of a potential source that can generate a typical and ideal treatment to overcome the limitations and eliminate the pathogens. Among the various sources, medicinal plants and its derived products always play a significant role in drug discovery against several diseases. In addition, they are also known for its low toxicity and minimum resistance features. Therefore, plants and its compounds that possess anti-inflammatory and anti-bacterial properties can serve better in bovine mastitis. In addition, the plants that are serving as a food source and possessing pharmacological properties can act even better in bovine mastitis. Hence, in this evidence-based study, we particularly review the dietary medicinal plants and derived products that are proven for anti-inflammatory and anti-bacterial effects. Moreover, the role of each dietary plant and its compounds along with possible role in the management of bovine mastitis are delineated. In this way, this article serves as a standalone source for the researchers working in this area to help in the management of BM., Competing Interests: Declaration of Competing interest The authors declare that there are no conflicts of interest. There is no conflict of interest to be declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is a highly prevalent neurodegenerative condition that has devastating effects on individuals, often resulting in dementia. AD is primarily defined by the presence of extracellular plaques containing insoluble β-amyloid peptide (Aβ) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein (P-tau). In addition, individuals afflicted by these age-related illnesses experience a diminished state of health, which places significant financial strain on their loved ones. Several risk factors play a significant role in the development of AD. These factors include genetics, diet, smoking, certain diseases (such as cerebrovascular diseases, obesity, hypertension, and dyslipidemia), age, and alcohol consumption. Age-related factors are key contributors to the development of vascular-based neurodegenerative diseases such as AD. In general, the process of aging can lead to changes in the immune system's responses and can also initiate inflammation in the brain. The chronic inflammation and the inflammatory mediators found in the brain play a crucial role in the dysfunction of the blood-brain barrier (BBB). Furthermore, maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. Therefore, in this review, we discussed the role of age and its related factors in the breakdown of the blood-brain barrier and the development of AD. We also discussed the importance of different compounds, such as those with anti-aging properties, and other compounds that can help maintain the integrity of the blood-brain barrier in the prevention of AD. This review builds a strong correlation between age-related factors, degradation of the BBB, and its impact on AD., Competing Interests: Declaration of Competing Interest There is no conflict of interest to be declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Histamine performs dual roles as an immune regulator and a neurotransmitter in the mammalian brain. The histaminergic system plays a vital role in the regulation of wakefulness, cognition, neuroinflammation, and neurogenesis that are substantially disrupted in various neurodegenerative and neurodevelopmental disorders. Histamine H3 receptor (H3R) antagonists and inverse agonists potentiate the endogenous release of brain histamine and have been shown to enhance cognitive abilities in animal models of several brain disorders. Microglial activation and subsequent neuroinflammation are implicated in impacting embryonic and adult neurogenesis, contributing to the development of Alzheimer's disease (AD), Parkinson's disease (PD), and autism spectrum disorder (ASD). Acknowledging the importance of microglia in both neuroinflammation and neurodevelopment, as well as their regulation by histamine, offers an intriguing therapeutic target for these disorders. The inhibition of brain H3Rs has been found to facilitate a shift from a proinflammatory M1 state to an anti-inflammatory M2 state, leading to a reduction in the activity of microglial cells. Also, pharmacological studies have demonstrated that H3R antagonists showed positive effects by reducing the proinflammatory biomarkers, suggesting their potential role in simultaneously modulating crucial brain neurotransmissions and signaling cascades such as the PI3K/AKT/GSK-3β pathway. In this review, we highlight the potential therapeutic role of the H3R antagonists in addressing the pathology and cognitive decline in brain disorders, e.g., AD, PD, and ASD, with an inflammatory component.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is a highly contagious respiratory disease with widespread societal impact. The symptoms range from cough, fever, and pneumonia to complications affecting various organs, including the heart, kidneys, and nervous system. Despite various ongoing efforts, no effective drug has been developed to stop the spread of the virus. Although various types of medications used to treat bacterial and viral diseases have previously been employed to treat COVID-19 patients, their side effects have also been observed. The way SARS-CoV-2 infects the human body is very specific, as its spike protein plays an important role. The S subunit of virus spike protein cleaved by human proteases, such as furin protein, is an initial and important step for its internalization into a human host. Keeping this context, we attempted to inhibit the furin using phytochemicals that could produce minimal side effects. For this, we screened 408 natural phytochemicals from various plants having antiviral properties, against furin protein, and molecular docking and dynamics simulations were performed. Based on the binding score, the top three compounds (robustaflavone, withanolide, and amentoflavone) were selected for further validation. MM/GBSA energy calculations revealed that withanolide has the lowest binding energy of -57.2 kcal/mol followed by robustaflavone and amentoflavone with a binding energy of -45.2 kcal/mol and -39.68 kcal/mol, respectively. Additionally, ADME analysis showed drug-like properties for these three lead compounds. Hence, these natural compounds robustaflavone, withanolide, and amentoflavone, may have therapeutic potential for the management of SARS-CoV-2 by targeting furin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kumar Tiwari, Chouhan, Mishra, Gupta, Chaudhary, Al-Zharani, Ahmed Qurtam, Nasr, Jha, Pant, Kumar and Kumar.)

Pancreatic cancer is a prevalent lethal gastrointestinal cancer that generally does not show any symptoms until it reaches advanced stages, resulting in a high mortality rate. People at high risk, such as those with a family history or chronic pancreatitis, do not have a universally accepted screening protocol. Chemotherapy and radiotherapy demonstrate limited effectiveness in the management of pancreatic cancer, emphasizing the urgent need for innovative therapeutic strategies. Recent studies indicated that the complex interaction among pancreatic cancer cells within the dynamic microenvironment, comprising the extracellular matrix, cancer-associated cells, and diverse immune cells, intricately regulates the biological characteristics of the disease. Additionally, mounting evidence suggests that EVs play a crucial role as mediators in intercellular communication by the transportation of different biomolecules, such as miRNA, proteins, DNA, mRNA, and lipids, between heterogeneous cell subpopulations. This communication mediated by EVs significantly impacts multiple aspects of pancreatic cancer pathogenesis, including proliferation, angiogenesis, metastasis, and resistance to therapy. In this review, we delve into the pivotal role of EV-associated miRNAs in the progression, metastasis, and development of drug resistance in pancreatic cancer as well as their therapeutic potential as biomarkers and drug-delivery mechanisms for the management of pancreatic cancer.

Biofilms are an intricate community of microbes that colonize solid surfaces, communicating via a quorum-sensing mechanism. These microbial aggregates secrete exopolysaccharides facilitating adhesion and conferring resistance to drugs and antimicrobial agents. The escalating global concern over biofilm-related infections on medical devices underscores the severe threat to human health. Carbon dots (CDs) have emerged as a promising substrate to combat microbes and disrupt biofilm matrices. Their numerous advantages such as facile surface functionalization and specific antimicrobial properties, position them as innovative anti-biofilm agents. Due to their minuscule size, CDs can penetrate microbial cells, inhibiting growth via cytoplasmic leakage, reactive oxygen species (ROS) generation, and genetic material fragmentation. Research has demonstrated the efficacy of CDs in inhibiting biofilms formed by key pathogenic bacteria such as Escherichia coli , Staphylococcus aureus , and Pseudomonas aeruginosa. Consequently, the development of CD-based coatings and hydrogels holds promise for eradicating biofilm formation, thereby enhancing treatment efficacy, reducing clinical expenses, and minimizing the need for implant revision surgeries. This review provides insights into the mechanisms of biofilm formation on implants, surveys major biofilm-forming pathogens and associated infections, and specifically highlights the anti-biofilm properties of CDs emphasizing their potential as coatings on medical implants.