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Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non‐motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α‐Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long‐term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm² /h and 0.310-3 cm² /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery. [ABSTRACT FROM AUTHOR]

AGRICULTURE productivity is severely hampered by salinity stress in many parts of the world, including the Ararat Plain in Armenia. The need for food security is growing worldwide, and new strategies are essential to meet this challenge. In the context of the Ararat Plain, this paper examines the potential utility and promising role of biogenic nanoparticles (NPs) and biochar in reducing salinity stress, boosting crop resilience, and guaranteeing sustainable food production. This paper involves the mechanisms underlying salinity stress, as well as the properties and synthesis of biogenic nanoparticles and biochar, and their applications in increasing plant salinity tolerance. The potential application of biogenic nanoparticles and biochar to mitigate the adverse effects of salinity on crops, soil, and water resources has been recently illustrated by several case studies and research findings. Additionally, we go over the safety issues, environmental implications, and potential applications of biogenic nanoparticles and biochar in sustainable agriculture on the Ararat Plain and elsewhere. This paper advances our knowledge of innovative strategies for addressing salinity stress and improving food security in areas with comparable problems. [ABSTRACT FROM AUTHOR]

Introduction: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by the presence of glial cytoplasmic inclusions (GCIs) containing aggregated α‐synuclein (α‐Syn). Accurate diagnosis and monitoring of MSA present significant challenges, which can lead to potential misdiagnosis and inappropriate treatment. Biomarkers play a crucial role in improving the accuracy of MSA diagnosis, and phosphorylated α‐synuclein (p‐syn) has emerged as a promising biomarker for aiding in diagnosis and disease monitoring. Methods: A literature search was conducted on PubMed, Scopus, and Google Scholar using specific keywords and MeSH terms without imposing a time limit. Inclusion criteria comprised various study designs including experimental studies, case‐control studies, and cohort studies published only in English, while conference abstracts and unpublished sources were excluded. Results: Increased levels of p‐syn have been observed in various samples from MSA patients, such as red blood cells, cerebrospinal fluid, oral mucosal cells, skin, and colon biopsies, highlighting their diagnostic potential. The α‐Syn RT‐QuIC assay has shown sensitivity in diagnosing MSA and tracking its progression. Meta‐analyses and multicenter investigations have confirmed the diagnostic value of p‐syn in cerebrospinal fluid, demonstrating high specificity and sensitivity in distinguishing MSA from other neurodegenerative diseases. Moreover, combining p‐syn with other biomarkers has further improved the diagnostic accuracy of MSA. Conclusion: The p‐syn stands out as a promising biomarker for MSA. It is found in oligodendrocytes and shows a correlation with disease severity and progression. However, further research and validation studies are necessary to establish p‐syn as a reliable biomarker for MSA. If proven, p‐syn could significantly contribute to early diagnosis, disease monitoring, and assessing treatment response. [ABSTRACT FROM AUTHOR]

Depression is a mood disorder characterized by abnormal thoughts. The pathophysiology of depression is related to the deficiency of serotonin (5HT), which is derived from tryptophan (Trp). Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in the pathogenesis of depression. Notably, the renin–angiotensin system (RAS) is involved in the pathogenesis of depression, and different findings revealed that angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may be effective in depression. However, the underlying mechanism for the role of dysregulated brain RAS‐induced depression remains speculative. Therefore, this review aimed to revise the conceivable role of ACEIs and ARBs and how these agents ameliorate the pathophysiology of depression. Dysregulation of brain RAS triggers the development and progression of depression through the reduction of brain 5HT and expression of brain‐derived neurotrophic factor (BDNF) and the induction of mitochondrial dysfunction, oxidative stress, and neuroinflammation. Therefore, inhibition of central classical RAS by ARBS and ACEIs and activation of non‐classical RAS prevent the development of depression by regulating 5HT, BDNF, mitochondrial dysfunction, oxidative stress, and neuroinflammation. [ABSTRACT FROM AUTHOR]

Three hundred samples, including meat from the slaughtered carcass and water, air samples, and swabs from the floor, wall, and employees' hands, were collected from five municipal abattoirs spread across several Egyptian provinces. The Escherichia coli was isolated from floor swabs, meat, air, wall, hand, and water samples. Serotyping of the recovered isolates clarified the presence of various serotypes, including enterohemorrhagic serotypes (O111: H4, O128: H2, and O127: H6) and enterotoxigenic serotypes (O44: H18 and O125: H21). The isolates were resistant to cefotaxime (100%), amoxiclav (80%), then rifampin (66.7%). The stx1 gene, stx2 gene, eaeA gene, blaCMY2 gene and iss gene were detected in 10-80 % of the isolates. Nanosilver (AgNPs) showed that 12.5 ppm was the lowest concentration that prevented bacterial growth. It was observed that 12% of workers wore a clean white coat, only 24% washed their hands between activities during work, only 14% used soap for hand washing, and 42% utilized the same knife for meat and its offal. [ABSTRACT FROM AUTHOR]

The global fight against Human Immunodeficiency Virus (HIV) and related viral infections stands at a pivotal juncture, demanding groundbreaking therapeutic strategies. Facing the challenges of existing antiviral treatments, such as viral resistance and nonspecific actions, this paper unveils a transformative approach. We introduce an innovative synergy between proteolysis-targeting chimeras (PROTACs) and exosome-based delivery mechanisms, heralding an innovative era in combating HIV and similar viral diseases. PROTACs emerge as a trailblazing solution, strategically targeting and decomposing crucial viral proteins, and thus, obstructing viral replication and diminishing pathogenesis. Complementing this, the use of exosome-based delivery systemsnature's own nanoscale couriersensures the precise and effective transportation of these dynamic chimeras directly to infected cells and viral reservoirs. This synergistic strategy is not just a leap forward in HIV therapy; it represents a paradigm shift in antiviral interventions at large. The path to realizing the full potential of these avant-garde technologies lies in sustained research investments, cross-disciplinary collaborations, and rigorous safety and efficacy trials. By channeling these efforts toward HIV, a cornerstone in global health research, we are not just envisioning but actively forging path-breaking advancements in antiviral therapeutics. This represents more than scientific progress; it is a beacon of hope, promising to significantly uplift the lives of those battling these formidable diseases. [ABSTRACT FROM AUTHOR]

The epithelial–mesenchymal transition (EMT) represents a pivotal frontier in oncology, playing a central role in the metastatic cascade of cancer—a leading global health challenge. This comprehensive review delves into the complexities of EMT, a process where cancer cells gain exceptional mobility, facilitating their invasion into distant organs and the establishment of secondary malignancies. We thoroughly examine the myriad of factors influencing EMT, encompassing transcription factors, signalling pathways, metabolic alterations, microRNAs, long non‐coding RNAs, epigenetic changes, exosomal interactions and the intricate dynamics of the tumour microenvironment. Particularly, the review emphasises the advanced stages of EMT, crucial for the development of highly aggressive cancer phenotypes. During this phase, cancer cells penetrate the vascular barrier and exploit the bloodstream to propagate life‐threatening metastases through the mesenchymal–epithelial transition. We also explore EMT's significant role in fostering tumour dormancy, senescence, the emergence of cancer stem cells and the formidable challenge of therapeutic resistance. Our review transcends a mere inventory of EMT‐inducing elements; it critically assesses the current state of EMT‐focused clinical trials, revealing both the hurdles and significant breakthroughs. Highlighting the potential of EMT research, we project its transformative impact on the future of cancer therapy. This exploration is aimed at paving the way towards an era of effectively managing this relentless disease, positioning EMT at the forefront of innovative cancer research strategies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aβ). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aβ. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aβ and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aβ. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aβ clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon‐like peptide 1 (GLP‐1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP‐1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic neurological disease characterized by recurrent seizures. Epilepsy is observed as a well‐controlled disease by anti‐epileptic agents (AEAs) in about 69%. However, 30%–40% of epileptic patients fail to respond to conventional AEAs leading to an increase in the risk of brain structural injury and mortality. Therefore, adding some FDA‐approved drugs that have an anti‐seizure activity to the anti‐epileptic regimen is logical. The anti‐diabetic agent metformin has anti‐seizure activity. Nevertheless, the underlying mechanism of the anti‐seizure activity of metformin was not entirely clarified. Henceforward, the objective of this review was to exemplify the mechanistic role of metformin in epilepsy. Metformin has anti‐seizure activity by triggering adenosine monophosphate‐activated protein kinase (AMPK) signalling and inhibiting the mechanistic target of rapamycin (mTOR) pathways which are dysregulated in epilepsy. In addition, metformin improves the expression of brain‐derived neurotrophic factor (BDNF) which has a neuroprotective effect. Hence, metformin via induction of BDNF can reduce seizure progression and severity. Consequently, increasing neuronal progranulin by metformin may explain the anti‐seizure mechanism of metformin. Also, metformin reduces α‐synuclein and increases protein phosphatase 2A (PPA2) with modulation of neuroinflammation. In conclusion, metformin might be an adjuvant with AEAs in the management of refractory epilepsy. Preclinical and clinical studies are warranted in this regard. [ABSTRACT FROM AUTHOR]