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Pioglitazone, an anti-diabetic drug, has been previously shown to ameliorate kidney damage through anti-inflammatory and antioxidant effects. In this study, we employed an integrative bioinformatics approach to study the possible mechanisms involved in the mitigative effect of pioglitazone against colistin-induced nephrotoxicity. Next, we validated the results obtained from the bioinformatics study by pre-treating human kidney-2 (HK-2) cell line with pioglitazone 100 μM for 30 minutes and then treating the cells with colistin sulfate 1200 μM for 24 hours. Inflammatory signaling by cytokines and the nuclear factor erythroid 2 related factor 2 (Nrf2) signaling pathways were predicted to be involved in the ameliorative effect of pioglitazone against colistin-induced nephrotoxicity. The nuclear factor kappa B subunit p65 (NF-κB p65) and Nrf2 were among the predicted transcription factors regulating the hub genes. Moreover, miR-24, miR-16, and miR-21 were identified as potential pathogenic miRNAs regulating the hub genes. In contrast, miR-17, miR-27a, and miR-146a were identified as potential protective miRNAs. The in vitro study indicated that pioglitazone pre-treatment increased cell viability in HK-2 cells exposed to colistin. Pioglitazone pre-treatment reduced the expression of pro-inflammatory cytokine genes (IL6 and TNF). Moreover, pioglitazone reduced the protein expression of NF-κB p65 and increased the protein expression of Nrf2. The protective effect of pioglitazone against colistin-induced toxicity in HK-2 cells is related to its anti-inflammatory and antioxidant activity through modulating NF-κB-mediated inflammatory signaling and Nrf2-mediated antioxidative stress signaling. [ABSTRACT FROM AUTHOR]

Fasciolosis is a zoonotic infection and is considered a developing deserted tropical illness threatening ruminant productivity and causing financial losses. Herein, we applied immunoinformatics and biophysics studies to develop an epitopes vaccine against Fasciola hepatica using glutathione transferase and Cathepsin L-like proteinase as possible vaccine candidates. Using the selected proteins, B- and Tcell epitopes were predicted. After epitopes prediction, the epitopes were clarified over immunoinformatics screening, and only five epitopes, EFGRWQQEKCTIDLD, RRNIWEKNVKHIQEH, FKAKYLTEMSRASDI, TDMTFEEFKAKYLTE, and YTAVEGQCR were selected for vaccine construction; selected epitopes were linked with the help of a GPGPG linker and attached with an adjuvant through another linker, EAAAK linker. Cholera toxin B subunit was used as an adjuvant. The ExPASy ProtParam tool server predicted 234 amino acids, 25.86257 kDa molecular weight, 8.54 theoretical pI, 36.86 instability index, and -0.424 grand average of hydropathicity. Molecular docking analysis predicted that the vaccine could activate the immune system against F. hepatica. We calculated negative binding energy values. A biophysics study, likely molecular docking molecular dynamic simulation, further validated the docking results. In molecular dynamic simulation analysis, the top hit docked compounds with the lowest binding energy values were subjected to MD simulation; the simulation analysis showed that the vaccine and immune cell receptors are stable and can activate the immune system. MMGBSA of -146.27 net energy (kcal/mol) was calculated for the vaccine-TLR2 complex, while vaccine-TLR4 of -148.11 net energy (kcal/mol) was estimated. Furthermore, the C-ImmSim bioinformatics tool predicted that the vaccine construct can activate the immune system against F. hepatica, eradicate the infection caused by F. hepatica, and reduce financial losses that need to be spent while protecting against infections of F. hepatica. The computational immune simulation unveils that the vaccine model can activate the immune system against F. hepatica; hence, the experimental scientist can validate the finding accomplished through computational approaches. [ABSTRACT FROM AUTHOR]

Breast cancer remains a significant global health challenge, demanding innovative therapeutic approaches. Polyphenols, a class of natural compounds widely distributed in fruits, vegetables, and beverages, possess robust antioxidant and anti-inflammatory properties. They exhibit the potential to mitigate cancer cell proliferation and induce apoptosis. Nevertheless, their clinical utility is impeded by limited bioavailability and stability issues. These impediments find a solution through the advent of nanotechnology. Nano-carriers, owing to their diminutive dimensions and distinctive attributes, hold promise in enhancing the delivery of polyphenols to tumor sites, thereby augmenting bioavailability and therapeutic efficacy. Various nano-carriers, including liposomes, polymeric nanoparticles, and solid lipid nanoparticles, have been explored for polyphenol transport. These carriers safeguard polyphenols from degradation and enhance their solubility, facilitating targeted delivery to tumor sites and potentially reducing systemic adverse effects. This comprehensive review provides an in-depth examination of the current state of polyphenol-loaded nano-carriers in breast cancer therapy. It elucidates their potential as an innovative and precision-focused therapeutic modality to improve patient outcomes while mitigating side effects. [ABSTRACT FROM AUTHOR]

Fasciolosis is a zoonotic infection and is considered a developing deserted tropical illness threatening ruminant productivity and causing financial losses. Herein, we applied immunoinformatics and biophysics studies to develop an epitopes vaccine against Fasciola hepatica using glutathione transferase and Cathepsin L-like proteinase as possible vaccine candidates. Using the selected proteins, B- and Tcell epitopes were predicted. After epitopes prediction, the epitopes were clarified over immunoinformatics screening, and only five epitopes, EFGRWQQEKCTIDLD, RRNIWEKNVKHIQEH, FKAKYLTEMSRASDI, TDMTFEEFKAKYLTE, and YTAVEGQCR were selected for vaccine construction; selected epitopes were linked with the help of a GPGPG linker and attached with an adjuvant through another linker, EAAAK linker. Cholera toxin B subunit was used as an adjuvant. The ExPASy ProtParam tool server predicted 234 amino acids, 25.86257 kDa molecular weight, 8.54 theoretical pI, 36.86 instability index, and -0.424 grand average of hydropathicity. Molecular docking analysis predicted that the vaccine could activate the immune system against F. hepatica. We calculated negative binding energy values. A biophysics study, likely molecular docking molecular dynamic simulation, further validated the docking results. In molecular dynamic simulation analysis, the top hit docked compounds with the lowest binding energy values were subjected to MD simulation; the simulation analysis showed that the vaccine and immune cell receptors are stable and can activate the immune system. MMGBSA of -146.27 net energy (kcal/mol) was calculated for the vaccine-TLR2 complex, while vaccine-TLR4 of -148.11 net energy (kcal/mol) was estimated. Furthermore, the C-ImmSim bioinformatics tool predicted that the vaccine construct can activate the immune system against F. hepatica, eradicate the infection caused by F. hepatica, and reduce financial losses that need to be spent while protecting against infections of F. hepatica. The computational immune simulation unveils that the vaccine model can activate the immune system against F. hepatica; hence, the experimental scientist can validate the finding accomplished through computational approaches. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a devastating neurodegenerative disease that is manifested by a gradual loss of physical, cognitive, and mental abilities. As the disease advances, age has a major impact on the pathogenic signature of mutant huntingtin (mHTT) protein aggregation. This review aims to explore the intricate relationship between aging, mHTT toxicity, and cellular senescence in HD. Scientific data on the interplay between aging, mHTT, and cellular senescence in HD were collected from several academic databases, including PubMed, Google Scholar, Google, and ScienceDirect. The search terms employed were "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," and "CELLULAR SENESCENCE." Additionally, to gather information on the molecular mechanisms and potential therapeutic targets, the search was extended to include relevant terms such as "DNA DAMAGE," "OXIDATIVE STRESS," and "AUTOPHAGY." According to research, aging leads to worsening HD pathophysiology through some processes. As a result of the mHTT accumulation, cellular senescence is promoted, which causes DNA damage, oxidative stress, decreased autophagy, and increased inflammatory responses. Pro‐inflammatory cytokines and other substances are released by senescent cells, which may worsen the neuronal damage and the course of the disease. It has been shown that treatments directed at these pathways reduce some of the HD symptoms and enhance longevity in experimental animals, pointing to a new possibility of treating the condition. Through their amplification of the harmful effects of mHTT, aging and cellular senescence play crucial roles in the development of HD. Comprehending these interplays creates novel opportunities for therapeutic measures targeted at alleviating cellular aging and enhancing HD patients' quality of life. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, including cancer progression and stress response. Recent studies have demonstrated that copper accumulation induces a unique form of cell death known as cuproptosis, with lncRNAs playing a key role in regulating cuproptosis-associated pathways. These lncRNAs may trigger cell-specific responses to copper stress, presenting new opportunities as prognostic markers and therapeutic targets. This paper delves into the role of lncRNAs in cuproptosis-mediated cancer, underscoring their potential as biomarkers and targets for innovative therapeutic strategies. A thorough review of scientific literature was conducted, utilizing databases such as PubMed, Google Scholar, and ScienceDirect, with search terms like 'lncRNAs,' 'cuproptosis,' and 'cancer.' Studies were selected based on their relevance to lncRNA regulation of cuproptosis pathways and their implications for cancer prognosis and treatment. The review highlights the significant contribution of lncRNAs in regulating cuproptosis-related genes and pathways, impacting copper metabolism, mitochondrial stress responses, and apoptotic signaling. Specific lncRNAs are potential prognostic markers in breast, lung, liver, ovarian, pancreatic, and gastric cancers. The objective of this article is to explore the role of lncRNAs as potential prognostic markers and therapeutic targets in cancers mediated by cuproptosis. [ABSTRACT FROM AUTHOR]

Herbs have been used as medicines since antiquity, and it has been discovered that the human body responds well to herbal remedies. Research on the effect of butin was conducted in the current study in the alloxan-induced diabetic rat paradigm. A total of 30 Wistar rats were randomly assigned into the following groups (n = 6): I-Normal; II-Alloxan-induced (50 mg/kg); III-Alloxan + butin 25 mg/kg; IV-Alloxan + butin 50 mg/kg; V-Butin per se 50 mg/kg. Various diabetic parameters (blood glucose, insulin, HbA1c), lipid profile, inflammatory (TNF-α, IL-1β, IL-6 and NF-κB), antioxidant enzymes (CAT, SOD and GSH), oxidative stress indicators (MDA), apoptosis marker (caspase-3), hepatic markers (ALT and AST), and histopathological changes were assessed. Additionally, molecular docking and dynamics were performed to evaluate the interaction of butin with target proteins. Butin treatment, at both doses, significantly restored biochemical parameters and preserved pancreatic histopathology in diabetic rats. It effectively modulated blood parameters, lipid profiles, inflammatory markers, apoptosis, antioxidant enzyme activity, oxidative stress, and hepatic markers. Molecular docking revealed that butin binds to proteins such as caspase-3 (1NME), NF-κB (1SVC), and serum insulin (4IBM) with binding affinities of − 7.4, − 6.5, and − 8.2 kcal/mol, respectively. Molecular dynamics simulations further suggested that butin induces significant conformational changes in these proteins. Butin exhibits potential effects against alloxan-induced diabetic rats by restoring biochemical balance, reducing inflammation, and protecting pancreatic tissue. Its binding to key proteins involved in apoptosis and inflammation highlights its therapeutic potential in diabetes management. [ABSTRACT FROM AUTHOR]

Cancer is a generic term for a group of disorders defined by uncontrolled cell growth and the potential to invade or spread to other parts of the body. Gene and epigenetic alterations disrupt normal cellular control, leading to abnormal cell proliferation, resistance to cell death, blood vessel development, and metastasis (spread to other organs). One of the several routes that play an important role in the development and progression of cancer is the phosphoinositide 3-kinase (PI3K) signaling pathway. Moreover, the gene PIK3CG encodes the catalytic subunit gamma (p110γ) of phosphoinositide 3-kinase (PI3Kγ), a member of the PI3K family. Therefore, in this study, PIK3CG was targeted to inhibit cancer by identifying a novel inhibitor through computational methods. The study screened 1015 chemical fragments against PIK3CG using machine learning-based binding estimation and docking to select the potential compounds. Later, the analogues were generated from the selected hits, and 414 analogues were selected, which were further screened, and as most potential candidates, three compounds were obtained: (a) 84,332, 190,213, and 885,387. The protein–ligand complex's stability and flexibility were then investigated by dynamic modeling. The 100 ns simulation revealed that 885,387 exhibited the steadiest deviation and constant creation of hydrogen bonds. Compared to the other compounds, 885,387 demonstrated a superior binding free energy (ΔG = −18.80 kcal/mol) with the protein when the MM/GBSA technique was used. The study determined that 885,387 showed significant therapeutic potential and justifies further experimental investigation as a possible inhibitor of the PIK3CG target implicated in cancer. [ABSTRACT FROM AUTHOR]

The Zika virus (ZIKV) is an emerging virus associated with the Flaviviridae family that mainly causes infection in pregnant women and leads to several abnormalities during pregnancy. This virus has unique properties that may lead to pathological diseases. As the virus has the ability to evade immune response, a crucial effort is required to deal with ZIKV. Vaccines are a safe means to control different pathogenic infectious diseases. In the current research, a multiepitope-based vaccination against ZIKV is being designed using in silico methods. For the epitope prediction and prioritization phase, ZIKV polyprotein (YP_002790881.1) and flavivirus polyprotein (>YP_009428568.1) were targeted. The predicted B-cell epitopes were used for MHC-I and MHC-II epitope prediction. Afterward, several immunoinformatics filters were applied and nine (REDLWCGSL, MQDLWLLRR, YKKSGITEV, TYTDRRWCF, RDAFPDSNS, KPSLGLINR, ELIGRARVS, AITQGKREE, and EARRSRRAV) epitopes were found to be probably antigenic in nature, non-allergenic, non-toxic, and water soluble without any toxins. Selected epitopes were joined using a particular GPGPG linker to create the base vaccination for epitopes, and an extra EAAAK linker was used to link the adjuvant. A total of 312 amino acids with a molecular weight (MW) of 31.62762 and an instability value of 34.06 were computed in the physicochemical characteristic analysis, indicating that the vaccine design is stable. The molecular docking analysis predicted a binding energy of -329.46 (kcal/mol) for TLR-3 and -358.54 (kcal/mol) for TLR-2. Moreover, the molecular dynamics simulation analysis predicted that the vaccine and receptor molecules have stable binding interactions in a dynamic environment. The C-immune simulation analysis predicted that the vaccine has the ability to generate both humoral and cellular immune responses. Based on the design, the vaccine construct has the best efficacy to evoke immune response in theory, but experimental analysis is required to validate the in silico base approach and ensure its safety. [ABSTRACT FROM AUTHOR]

Background: Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. Methods: A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1β (IL-1β), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. Results: The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. Conclusions: The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation. [ABSTRACT FROM AUTHOR]

This comprehensive review aims to provide an overview of the pharmacological properties of erucic acid (EA) and highlight areas that require further research. EA is an omega-9 fatty acid found in certain vegetable oil, such as rapeseed oil has demonstrated favourable effects in rodents, including ameliorating myocardial lipidosis (fat accumulation in the heart muscle), congestive heart disease, hepatic steatosis (fat accumulation in the liver), and memory impairments. These findings have prompted regulatory bodies to establish limits on EA content in food oils. The studies were performed on rodents and led to caution on ingesting the EA at high levels. Moreover, EA is frequently utilized as a nutritional supplement for the treatment of adrenoleukodystrophy, myocardial disease, and memory improvement. The review of the article indicated that EA improves cognitive function, has a part in Huntington's disease, interacts with peroxisome proliferator-activated receptors, inhibits elastase and thrombin, has anti-inflammatory, antioxidant, and anti-tumour properties, and inhibits influenza A virus. This article elucidates the pharmacological effects of EA, an omega-9 fatty acid. [ABSTRACT FROM AUTHOR]

Chronic diseases hold the potential to worsen the overall health of patients by limiting their functional status, productivity, and capacity to live well, affecting their overall health-related quality of life (HRQoL). The purpose of the study was to assess the HRQoL of individuals with chronic diseases residing in the Al-Jouf region of Saudi Arabia. Furthermore, the current study also sought to ascertain the impact of multimorbidity and the duration of illness on HRQoL. Material and Methods: A cross-sectional study was conducted among the residents of Al-Jouf region for a period of 6 months. A self-administered EuroQoL (EQ-5D-5L) study tool was used. Appropriate statistical analysis was conducted to ascertain the relationship between various variables and HRQoL. Results: A total of 500 out of 562 participants completed the study, with a response rate of 88.97%. Participants had a mean age of 46.15 ± 16.79 years, and the majority were female (n = 299; 59.80%). A mean HRQoL score of 0.82 ± 0.20 was reported, poorest in patients with kidney failure (0.65 ± 0.26) and highest in hepatitis. However, nearly half of the participants had diabetes mellitus type II (n = 205, 39.20%). Patients aged < 30 years (OR: 0.109; p = 0.002), male participants (OR: 0.053; p < 0.001), no disability (OR: 0.143; p = 0.002), and < 2 comorbid diseases (0.84 ± 0.18; p < 0.001) reported better QoL. Additionally, comorbid conditions such as DM, prolong the duration of the overall illness (14.19 ± 7.67 years). Overall, imperfect health (n = 390, 78%) was reported by the study participants. Conclusion: The present study provided preliminary data about the current HRQoL status of individuals with imperfect health and lower HRQoL. In the future, large-scale longitudinal studies are required to investigate the most prevalent chronic diseases, their associations, and change in HRQoL, as there is a dearth of information in the Saudi population. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy—a crucial cellular process for maintaining protein and organelle integrity. Methods: This review focuses on the role of non‐coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples. Results: Findings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α‐synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes. Conclusion: ncRNAs hold significant therapeutic potential for addressing autophagy‐related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy‐related ncRNAs and discusses the challenges and prospective directions for developing ncRNA‐based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications. [ABSTRACT FROM AUTHOR]

The immunopathology of herpes simplex virus (HSV)‐associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity. Furthermore, this analysis delves into the delicate equilibrium between immune defence and the potential for immunopathology‐induced neural damage. It meticulously dissects the roles of diverse immune cells, cytokines, and chemokines, unravelling the intricacies of neuroinflammation modulation and its subsequent effects. By exploring HSV's immune manipulation and exploitation mechanisms, this review endeavours to unveil the enigmas surrounding the immunopathology of HSV‐associated neuroinflammation. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of HSV infections. [ABSTRACT FROM AUTHOR]

This study explores the neuroprotective potential of hibiscetin concerning memory deficits induced by lipopolysaccharide (LPS) injection in rats. The aim of this study is to evaluate the effect of hibiscetin against LPS-injected memory deficits in rats. The behavioral paradigms were conducted to access LPS-induced memory deficits. Various biochemical parameters such as acetyl-cholinesterase activity, cholineacetyltransferase, antioxidant (superoxide dismutase, glutathione transferase, catalase), oxidative stress (malonaldehyde), and nitric oxide levels were examined. Furthermore, neuroinflammatory parameters such as tumor necrosis factor-a, interleukin-1β (IL-1β), IL-6, and nuclear factor-kappa B expression and brain-derived neurotrophic factor as well as apoptosis marker i.e., caspase-3 were evaluated. The results demonstrated that the hibiscetin-treated group exhibited significant recovery in LPS-induced memory deficits in rats by using behavioral paradigms, biochemical parameters, antioxidant levels, oxidative stress, neuroinflammatory markers, and apoptosis markers. Recent research suggested that hibiscetin may serve as a promising neuroprotective agent in experimental animals and could offer an alternative in LPS-injected memory deficits in rodent models. [ABSTRACT FROM AUTHOR]

Cancer poses intricate challenges to treatment due to its complexity and diversity. Ferroptosis and circular RNAs (circRNAs) are emerging as innovative therapeutic avenues amid the evolving landscape of cancer therapy. Extensive investigations into circRNAs reveal their diverse roles, ranging from molecular regulators to pivotal influencers of ferroptosis in cancer cell lines. The results underscore the significance of circRNAs in modulating molecular pathways that impact crucial aspects of cancer development, including cell survival, proliferation, and metastasis. A detailed analysis delineates these pathways, shedding light on the molecular mechanisms through which circRNAs influence ferroptosis. Building upon recent experimental findings, the study evaluates the therapeutic potential of targeting circRNAs to induce ferroptosis. By identifying specific circRNAs associated with the etiology of cancer, this analysis paves the way for the development of targeted therapeutics that exploit vulnerabilities in cancer cells. This review consolidates the existing understanding of ferroptosis and circRNAs, emphasizing their role in cancer therapy and providing impetus for ongoing research in this dynamic field. [ABSTRACT FROM AUTHOR]

This review delves into the pivotal role of the long non-coding RNA NEAT1 in cancer biology, particularly in lung cancer (LC). It emphasizes NEAT1's unique subcellular localization and active involvement in gene regulation and chromatin remodeling. The review highlights NEAT1's impact on LC development and progression, including cell processes such as proliferation, migration, invasion, and resistance to therapy, positioning it as a potential diagnostic marker and therapeutic target. The complex web of NEAT1's regulatory interactions with proteins and microRNAs is explored, alongside challenges in targeting it therapeutically. The review concludes optimistically, suggesting future avenues for research and personalized LC therapies, shedding light on NEAT1's crucial role in LC. [ABSTRACT FROM AUTHOR]

Niosomes (NS) are the promising and novel carrier of the drug for effective transdermal delivery. Apigenin (AN) is a natural bioactive compound and has various pharmacological activities. AN is poorly water soluble which directly affects therapeutic efficacy. The aim of this research work was to develop the AN-NS gel to improve transdermal delivery. The thin-film hydration method was used for the development of AN-NS. The optimized AN-NS (AN-NS2) has a vesicle size of 272.56 ± 12.49 nm, PDI is 0.249, zeta potential is -38.7 mV, and entrapment efficiency of 86.19 ± 1.51%. The FTIR spectra of the AN-NS2 depicted that AN encapsulated in the NS matrix. AN-NS2 formulation was successfully incorporated into chitosan gel and evaluated. The optimized AN-NS2 gel (AN-NS2G4) has 2110 ± 14cps of viscosity, 10.40 ± 0.21g.cm/sec of spreadability, and 99.65 ± 0.53% of drug content. AN-NS2G4 displayed significantly (p<0.05) higher AN released (67.64 ± 3.03%) than pure AN-gel (37.31 ± 2.87%). AN-NS2G4 showed the Korsmeyer Peppas release model. AN-NS2G4 displayed significantly (p<0.05) higher antioxidant activity (90.72%) than pure AN (64.53%) at 300 mg/ml. AN-NS2G4 displayed significantly (p<0.05) higher % inhibition of swelling than pane AN-gel in carrageenin-induced paw oedema in rats. The finding concluded that niosomes-laden gel is a good carrier of drugs to improve transdermal delivery and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti‐inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor‐kappa B, mitogen‐activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: We investigated the anti-cancer effect of carnosine-loaded niosomes (Car-NIO) and melittin-loaded niosomes (Mel-NIO) with olaparib in breast cancer cell lines (MCF-7 and MDA-MB-231). Methods: The thin film method was used for preparing the niosomes and characterized in terms of morphology, size, and polydispersity index (PDI). We further evaluated the impact of these peptides on breast cancer cells viability, RTqPCR assays, malondialdehyde (MDA) activity, and cell cycle progression, to determine if these are linked to carnosine and melittin's anti-proliferative properties. Results: Car-NIO and Mel-NIO in vitro study inhibited cancer cell viability. They have also upregulated the expression of protein 53 (P53), BCL2-Associated X Protein (Bax), caspase-9, caspase-3, programmed cell death 4 (PDCD4), and Forkhead box O3 (FOXO3), while downregulated the expression of B-cell lymphoma 2 (Bcl2), poly (ADP-ribose) polymerase (PARP 1), and MicroRNA-183 (miRNA-183). The MCF-7 cells were arrested at the G2/M phase in Car-NIO, on the other hand, the MDA-MB-231 cells were arrested at the S phase. While the Mel- NIO and olaparib arrested the MCF-7 and MDA-MB-231 cells at the G0/1 phase. Conclusion: Our study successfully declared that Mel-NIO had more anti-cancer effects than Car-NIO in both MCF-7 and MDA-MB-231 breast cancer cells. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is the principal cause of premature death. Protecting myocardium from ischemia is the main focus of intense research. 7-hydroxy frullanolide (7-HF) is a potent anti-inflammatory agent, showing its efficacy in different acute and chronic inflammatory disorders such as atherosclerosis, suggesting it can be a potential cardioprotective agent. For the induction of MI, Sprague–Dawley rats (n = 5) were administered isoproterenol (ISO) 85 mg/kg s.c at 24 h intervals for two days. The potential cardioprotective effect of 7-HF and its mechanisms were explored by in vivo and in vitro methods. 7-HF significantly prevented the extent of myocardial injury by decreasing the infarct size, preserving the histology of myocardial tissue, and reducing the release of cardiac biomarkers. Further, 7-HF increased the mRNA expression of cardioprotective gene Nrf2 and reduced the mRNA expression of iNOS. 7-HF also improved cardiac function by decreasing the cardiac workload through its negative chronotropic and negative ionotropic effect, as well as by reducing peripheral vascular resistance due to the inhibition of voltage-dependent calcium channels and the release of calcium from intracellular calcium stores. In conclusion, 7-HF showed cardioprotective effects in the MI model, which might be due to modulating the expression of iNOS and Nrf2 genes as well as improving cardiac functions. [ABSTRACT FROM AUTHOR]

Aim: Our study developed a prednisolone acetate polymeric micelles (PM) system for ocular inflammation related to allergic uveitis. Methods: For PM development, a thin-film hydration procedure was used. Irritation, in vitro, ex vivo transcorneal permeation, micelle size, entrapment efficiency and histology within the eye were all calculated for PM. Results: The optimized in situ gel (A4) showed superior ex vivo transcorneal permeation with zero-order kinetics. Conclusion: The developed formulation could be a promising candidate for treating anterior uveitis via topical application to the anterior segment of the eye. [ABSTRACT FROM AUTHOR]

Background: Diversifying the conventional role of community pharmacists from dispensing to involvement in public health services could help in optimized patient care and ultimately good health practices. The current study aimed to ascertain the involvement of community pharmacists, barriers to involvement, their preparedness towards the provision of public health services in the future, and effective strategies to improve their existing role, especially in remote areas of the Kingdom of Saudi Arabia. Methods: A cross-sectional study was conducted in the Al-Jouf region of Saudi Arabia (KSA), between January to April 2023. A convenient sampling technique was used to recruit community pharmacists (CPs). A self-designed and validated questionnaire was used for data collection. The relative importance index (RII) was utilized to rank the barriers to participation in public health services. Data were subjected to statistical analysis using SPSS. Results: This study recruited 119 participants (mean age: 32.2 ± 7.9; male gender: 67.2%). Of these, 91.6% were involved in the provision of public health services at community pharmacies. Majority of CPs (n = 114/119, 95.8%) provided drug use-related written information to the patients, and the least practiced service was screening of dyslipidemia (n = 81; 68.1%). According to RII, the major barrier was the lack of time given by patients (RII: 0.812). Overall, the majority of the pharmacists (n = 94/119; 79%) were willing to provide public health services. Most of the CPs reported that empowerment through education and awareness (n = 100/119; 84%) is most effective strategy to enhance the involvement of pharmacists in public health services. Conclusions: Findings of the present study underscored the adequate participation of community pharmacists in public health activities. Further studies are required in other remote regions of KSA to get a clear insight into the overall participation of community pharmacists in public health services and generalize the findings. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women and is typically managed through surgery, radiation therapy, and chemotherapy. However, chemotherapy drugs often lack specificity, leading to various adverse effects. To address this challenge, mesoporous silica nanoparticles (MSNPs) have emerged as a potential solution to enhance drug delivery in cancer treatment. MSNPs possess advantageous properties such as high porosity, a large surface area, versatile pore sizes, and compatibility with biological systems. In preclinical studies, MSNPs have shown promise for loading with chemotherapeutic agents like paclitaxel, doxorubicin, and docetaxel. These drugs can be loaded onto the surface of MSNPs or encapsulated within their pores, allowing for controlled release profiles and accommodating different drug properties. To enhance specificity towards cancer cells, targeting ligands such as folic acid, HER2/neu antibodies, and aptamers can be attached to the MSNPs. MSNPs have demonstrated the ability to improve drug uptake and release, resulting in enhanced anticancer activity. Furthermore, MSNP-based drug delivery has improved pharmacodynamic and pharmacokinetic characteristics, ultimately improving therapeutic outcomes. In conclusion, the experimental data presented in the review underscores the significance of utilizing mesoporous silica nanoparticles in designing targeted drug formulations for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Chemists found Imidazole as a multipurpose nucleus, primarily notable for its biological role in drug discovery. This compilation of the reports gives information regarding the development and the previous background of the synthesis of the nucleus. However, the synthesis through multicomponent is taken to narrow the report. The importance of the multicomponent reactions with many nucleus has been part of the heavy literature; however, the synthesis of the bioactive scaffold as imidazole has been highlighted here with the essential points. The emphasis of the review is to show the multicomponent approach where the multicomponent reaction plays a vital role in the formation of the ring. The MCR approaches align with modern‐day drug discovery, where the library of the molecules is needed for drug development within a limited time frame. The multicomponent also comes under the green chemistry, where the reaction time and fewer reactions step plays a crucial role. [ABSTRACT FROM AUTHOR]

The analytical quality by design (AQbD) approach is utilized for developing and validating the simple, sensitive, cost-effective reverse-phase high performance liquid chromatographic method for the estimation of xanthohumol (XH) in bulk and nanoformulations. The Box–Behnken design (BBD) is applied for method optimization. The mobile phase ratio, pH and flow rate were selected as independent variables, whereas retention time, peak area, peak height, tailing factor, and theoretical plates were selected as dependent variables. The chromatogram of XH obtained under optimized conditions has given optimum conditions such as retention time (5.392 min), peak area (1,226,737 mAU), peak height (90,121 AU), tailing factor (0.991) and theoretical plates (4446.667), which are contoured in the predicted values shown by BBD. Validation of the method has been performed according to ICH Q2(R1) recommendations, using optimized conditions for linearity, limit of detection (LOD) and limit of quantification (LOQ), accuracy, precision, robustness and system suitability. All the values of validation parameters lie within the acceptable limits prescribed by ICH. Therefore, the developed and validated method of XH by the AQbD approach can be applied for the estimation of XH in bulk and various nanoformulations. [ABSTRACT FROM AUTHOR]

Objective: Post-COVID 19 depression has gained much attention due to the increasing percentage of depressive symptoms reported by COVID-19 survivors. Among many factors postulated to be responsible for this depression, neuroinflammation gained the most attention. Therefore, in current work, we selected an anandamide reuptake inhibitor, VDM11, as a possible candidate for managing post-COVID depression. Methods: The role of VDM11 in attenuating neuroinflammation was established by using network pharmacology, molecular docking, and an in vivo LPS-induced depression model. Results: The results of network pharmacology revealed that among all the genes that can be targeted by VDM11, 47 genes were directly linked to the pathophysiology of depression. Additionally, on the basis of protein–protein interaction (PPI) analysis, the top 10 hub genes probably responsible for VDM11 antidepressant attribute were screened. These genes include MAPK3, TNF-α, IL-1β, IL-6, PPARG, MAPK1, CNR1, MTOR, NR3C1, and IGF1R. These genes were also enriched in GO and KEGG analysis. Molecular docking was carried out with top five hub genes screened by PPI network and KEGG analysis which showed that VDM11 interacts well with these targets. The antidepressant potential of VDM11 was also assessed by employing a LPS-induced depression model. Animals provided with VDM11 demonstrated increased exploration time and spontaneous alterations in elevated plus and Y maze models. Additionally, the level of astrocyte marker GFAP, microglia marker CD11b, and proinflammatory cytokines, including TNFα, IL-1β, and IL-6, in the hippocampus were significantly reduced by VDM11, further strengthening its role in neuroinflammation. Conclusion: VDM11, an anandamide reuptake inhibitor, might serve as a possible candidate for post-COVID depression, probably by modulating neuroinflammation. However, detailed pharmacological studies are required to validate these outcomes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is an incurable metabolic disease characterized by a change in blood glucose level. Luteolin (LT) is a bioactive flavonoid and reported for potential antidiabetic activity. LT loaded chitosan (CH)—polylactic co-glycolic acid (PLGA) nanoparticles (NPs) were prepared by emulsification—evaporation process and further optimized by Box-Behnken design using CH (A), PLGA (B), and polyvinyl alcohol (C) as formulation variables and their effect evaluated on particle size (Y1), drug loading (Y2), and entrapment efficiency (Y3). CH-PLGA-LT-NPs showed a particle size of 273.43 ± 5.24 nm, DL of 15.25 ± 2.43%, and EE of 65.28 ± 1.76%. The zeta potential was found to be positive with spherical surface morphology. CH-PLGA-LT-NPs exhibited sustained drug release (68.23 ± 6.17%) than LT-dispersion (29.66 ± 4.2%). The permeation study and pharmacokinetic study results revealed 3.19 fold as well as 2.63 fold (AUC0-t) enhancement in pure LT. CH-PLGA-LT-NPs also exhibited a significant (P < 0.05) reduction in blood glucose level in streptozotocin-induced diabetic rats than LT-dispersion. CH-PLGA-LT-NPs also showed notable improvement in biochemical parameters as compared to diabetic control and LT-dispersion group. The results concluded that LT-CH-PLGA-NPs is a good alternative to the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Current research into the role of engineered nanoparticles in drug delivery systems (DDSs) for medical purposes has developed numerous fascinating nanocarriers. This paper reviews the various conventionally used and current used carriage system to deliver drugs. Due to numerous drawbacks of conventional DDSs, nanocarriers have gained immense interest. Nanocarriers like polymeric nanoparticles, mesoporous nanoparticles, nanomaterials, carbon nanotubes, dendrimers, liposomes, metallic nanoparticles, nanomedicine, and engineered nanomaterials are used as carriage systems for targeted delivery at specific sites of affected areas in the body. Nanomedicine has rapidly grown to treat certain diseases like brain cancer, lung cancer, breast cancer, cardiovascular diseases, and many others. These nanomedicines can improve drug bioavailability and drug absorption time, reduce release time, eliminate drug aggregation, and enhance drug solubility in the blood. Nanomedicine has introduced a new era for drug carriage by refining the therapeutic directories of the energetic pharmaceutical elements engineered within nanoparticles. In this context, the vital information on engineered nanoparticles was reviewed and conferred towards the role in drug carriage systems to treat many ailments. All these nanocarriers were tested in vitro and in vivo. In the coming years, nanomedicines can improve human health more effectively by adding more advanced techniques into the drug delivery system. [ABSTRACT FROM AUTHOR]

A primary illness that accounts for a significant portion of fatalities worldwide is cancer. Among the main malignancies, lung cancer is recognised as the most chronic kind of cancer around the globe. Radiation treatment, surgery, and chemotherapy are some medical procedures used in the traditional care of lung cancer. However, these methods lack selectivity and damage nearby healthy cells. Several polysaccharide-based nanomaterials have been created to transport chemotherapeutics to reduce harmful and adverse side effects and improve response during anti-tumour reactions. To address these drawbacks, a class of naturally occurring polymers called polysaccharides have special physical, chemical, and biological characteristics. They can interact with the immune system to induce a better immunological response. Furthermore, because of the flexibility of their structures, it is possible to create multifunctional nanocomposites with excellent stability and bioavailability for the delivery of medicines to tumour tissues. This study seeks to present new views on the use of polysaccharide-based chemotherapeutics and to highlight current developments in polysaccharide-based nanomedicines for lung cancer. [ABSTRACT FROM AUTHOR]

Hyperglycemia is seen in approximately 68 percent of patients admitted to a medical intensive care unit (ICU). In many acute circumstances, such as myocardial infarction, brain, injury and stroke, it is an independent predictor of mortality. Hyperglycemia is induced by a mix of genetic, environmental, and immunologic variables in people with type 1 diabetes. These factors cause pancreatic beta cell death and insulin insufficiency. Insulin resistance and irregular insulin production cause hyperglycemia in type 2 diabetes patients. Hyperglycemia activates a number of complicated interconnected metabolic processes. Hyperglycemia is a major contributor to the onset and progression of diabetes' secondary complications such as neuropathy, nephropathy, retinopathy, cataracts, periodontitis, and bone and joint issues. Studies on the health benefits of ginger and its constituent's impact on hyperglycemia and related disorders have been conducted and gingerol proved to be a potential pharmaceutically active constituent of ginger (Zingiber officinale) that has been shown to lower blood sugar levels, because it possesses antioxidant properties and it functions as an antioxidant in the complicated biochemical process that causes hyperglycemia to be activated. Gingerol not only helps in treating hyperglycemia but also shows effectivity against diseases related to it, such as cardiopathy, kidney failure, vision impairments, bone and joint problems, and teeth and gum infections. Moreover, fresh ginger has various gingerol analogues, with 6-gingerol being the most abundant. However, it is necessary to investigate the efficacy of its other analogues against hyperglycemia and associated disorders at various concentrations in order to determine the appropriate dose for treating these conditions. [ABSTRACT FROM AUTHOR]

Aging is a significant risk factor for the majority of prevalent human illnesses. The chance of having severe chronic conditions grows dramatically with advancing age. Indeed, more than 90% of people over 65 get at least one chronic disease, including diabetes, heart disease, malignancy, memory loss, and kidney disease, whereas more than 70% have two or more of these ailments. Mouse and human aging lead to increased senescent cells and decreased klotho concentrations. Mice lacking the protein α‐klotho show faster aging, similar to human aging. α‐Klotho upregulation extends life and slows or suppresses the onset of many age‐related illnesses and kidney diseases. Like the consequences of α‐klotho deficiency, senescent cell accumulation is linked to tissue dysfunction in various organs and multiple age‐related kidney diseases. In addition, α‐klotho and cell senescence are negatively and presumably mechanistically linked. Earlier research has demonstrated that klotho exerts its protective effects in age‐related and kidney disease by interacting with Wnt ligands, serving as an endogenous antagonist of Wnt/β‐catenin signaling. In addition, decreasing senescent cell burden with senolytics, a class of drugs that remove senescent cells selectively and extend the life span of mice. In this work, we are studying the molecular mechanism of the combination of quercetin and dasatinib as senolytic in easing age‐related chronic renal illness by altering the level of klotho/Wnt/β‐catenin. Practical applications: There is an inverse relationship between the onset and the development of age‐related disorders and cellular senescence and Klotho. Earlier attempts to suppress transforming growth factor‐beta 1 (TGF‐β1) in kidney disease with anti‐TGF‐β1 antibodies were ineffective, and this should be kept in mind. Senolytic medications may benefit from targeting senescent cells, which enhances the protective factor α‐klotho. In addition, our study provides a unique, translationally feasible route for creating orally active small compounds to enhance α‐klotho, which may also be a valuable biomarker for age‐related kidney disease. Additionally, other aspects of aging can be affected by senolytics, such as limiting age‐related mitochondrial dysfunction, lowering inflammation and fibrosis, blunting reactive oxygen species (ROS) generation, decreasing deoxyribonucleic acid (DNA) damage, and reinforcing insulin sensitivity. Senolytic agents have been shown to increase adipose progenitor and cardiac progenitor cell activity in aging animals and animals with cellular senescence‐related diseases, such as heart, brain, and kidney disease. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a disease due to the aging of the articular cartilage, a post‐mitotic tissue that stays functioning until primary homeostatic processes fail. Because of pain and disability, OA significantly influences national healthcare expenses and patient quality of life. It is a whole‐joint illness characterized by inflammatory and oxidative signaling pathways and significant epigenetic alterations that cause cartilage extracellular matrix degradation. The canonical Wnt pathway (Wnt/β‐catenin pathway) and nuclear factor kappa B (NF‐κB) signaling pathways may function in joint tissues by modulating the activity of synovial cells, osteoblasts, and chondrocytes. However, finding innovative ways to treat osteoarthritis and get the joint back to average balance is still a struggle. Nutraceuticals are dietary supplements that promote joint health by balancing anabolic and catabolic signals. New therapeutic methods for OA treatment have been developed based on many research findings that show nutraceuticals have strong anti‐inflammation, antioxidant, anti–bone resorption, and anabolic properties. For the treatment of osteoarthritis, we explore the possible involvement of nutraceuticals that target the Wnt/β‐catenin and NF‐κB pathways. Practical applications: In keeping with the aging population, osteoarthritis is becoming more widespread. In this extensive research, we studied the role of the Wnt/β‐catenin and NF‐κB pathway in OA formation and progression. Nutraceuticals that target these OA‐related signaling pathways are a viable therapy option. Wnt/β‐catenin and NF‐κB signaling pathway are inhibited by polyphenols, flavonoids, alkaloids, and vitamins from the nutraceutical category, making them possible therapeutic drugs for OA therapy. [ABSTRACT FROM AUTHOR]

Emotional stress is believed to be associated with increased tumor progression. Stress-induced epigenetic modifications can contribute to the severity of disease and poor prognosis in cancer patients. The current study aimed to investigate the expression profiles along with the prognostic significance of psychological stress-related genes in metastatic breast cancer patients, to rationalize the molecular link between emotional stress and cancer progression. We profiled the expression of selected stress-associated genes (5-HTT, NR3C1, OXTR, and FKBP5) in breast cancer including the stress evaluation of all participants using the Questionnaire on Distress in Cancer Patients–short form (QSC-R10). A survival database, the Kaplan–Meier Plotter, was used to explore the prognostic significance of these genes in breast cancer. Our results showed relatively low expressions of 5-HTT (p = 0.02) and OXTR (p = 0.0387) in metastatic breast cancer patients as compared to the non-metastatic group of patients. The expression of NR3C1 was low in tumor grade III as compared to grade II (p = 0.04). Additionally, the expression of NR3C1 was significantly higher in patients with positive estrogen receptor status. However, no significant difference was found regarding FKBP5 expression in breast cancer. The results suggest a potential implication of these genes in breast cancer pathology and prognosis. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world's most popular beverages. The same plant, Camellia Sinensis (L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines' excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins' neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer's, Parkinson's, multiple sclerosis, and cognitive deficit. [ABSTRACT FROM AUTHOR]

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson's disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson's paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats. [ABSTRACT FROM AUTHOR]

Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90–95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box–Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of −34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer–Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm2) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (p < 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP. [ABSTRACT FROM AUTHOR]

It has been reported from the previous literature that butin restores mitochondrial dysfunction by modulation of oxidative stress and glutamate-induced neurotoxicity in mouse hippocampus HT22 cells. Butin also possesses an anti-Huntington's effect in rats. Considering the current background, this study was designed to evaluate the neuroprotective effect of butin against memory loss caused by streptozotocin (STZ). STZ (40 mg/kg) was intraperitoneally injected into rats. Three days later, diabetic rats were identified and included in the study. A total of 30 rats (12 nondiabetic and 18 diabetics) were grouped as Group A (control-non-diabetic rats) and Group B (STZ diabetic control) were treated with 1 mL of sodium CMC (0.5% w/v). Group C (STZ+ butin 25) were treated with butin 25 mg/kg. Group D (STZ+ butin 50) and Group E (butin per se) were administered with butin 50 mg/kg. Each therapy was administered orally once each day for 15-day. The Morris water maze and the Y-maze behavioural tests were run throughout the experimental programme. Animals were put to death on day 15 and their brains were removed for biochemical assays (CAT, SOD, GSH, MDA, nitrite, acetylcholinesterase (AchE), IL-1, and mitochondrial enzyme complexes). Rats with neurobehavioral impairments brought on by STZ have less spontaneous movement, learning capacity, and memory. Additionally, STZ decreased endogenous antioxidants and increased pro-inflammatory cytokines, nitrite, MDA, and AchE. Neurobehavioral deficits and metabolic markers were dramatically improved by butin. [ABSTRACT FROM AUTHOR]

The symptoms of ageing are somewhat different and can lead to the altered role of the cardiovascular system at the levels of genetic, biochemical, tissue, organ, and systems. Ageing is an autonomous cardiovascular risk factor. In the ageing rat heart, oxidative and inflammatory stress, immune cell infiltration, increasing myeloperoxidase function, elevated caspase-3 activity, and protein fibronectins were detected and associated with ageing and cardiovascular disease. The intracellular Ca2 + homeostasis disturbed in an older heart dramatically increases cardiomyopathy, atherosclerosis, stroke, ischemia, myocardial infarction, hypertrophy, remodelling, and hypertension. Evidence shows that suppression of Wnt/β signals prevents cardiovascular dysfunction, such as remodelling, high blood pressure, and excessive overload stress. However, one study has shown that the pharmacological disruption of Wnt-β-catenin by decreasing expression of α-smooth muscle actin, fibronectin and collagen I proteins attenuates angiotensin II mediated hypertension cardiac fibrosis. Thus, this review examined the impacts of calcium overload and age-related diseases, including cardiovascular. Energy dysregulation, calcium overloading, and mitochondrial dysfunction are the main activities causing cardiovascular disease linked with age. Therefore, the current study explores that age-associated cardiovascular disease has triggered the WNT/β-catenin pathway, and pharmacological inhibition can delay pathological changes by attenuating calcium dyshomeostasis. [ABSTRACT FROM AUTHOR]

Xanthohumol (XH) a prenylated chalcone has diverse therapeutic effects against various diseases. In the present study, a bioanalytical method was developed for XH in rat plasma using reverse phase high performance liquid chromatography. The validation of the method was performed as per ICH M10 guidelines using curcumin as an internal standard. The Isocratic elution method was used with a run time of 10 min, wherein the mobile phase ratio 0.1% v/v OPA (A): Methanol (B) was 15:85 v/v at flow rate 0.8 mL/min and injection volume of 20 µL. The chromatograms of XH and curcumin was recorded at a wavelength of 370 nm. The retention time for XH and curcumin was 7.4 and 5.8 min, respectively. The spiked XH from plasma was extracted by the protein precipitation method. The developed method was linear with R2 value of 0.9996 over a concentration range of 50–250 ng/mL along with LLOQ. The results of all the validation parameters are found to be within the accepted limits with %RSD value less than 2 and the percentage recovery was found to be greater than 95%. Based on the %RSD and percentage recovery results it was confirmed that the method was precise and accurate among the study replicates. LOD and LOQ values in plasma samples were found to be 8.49 ng/mL and 25.73 ng/mL, respectively. The stability studies like freeze thaw, short term and long-term stability studies were also performed, %RSD and percentage recovery of the XH from plasma samples were within the acceptable limits. Therefore, the developed bioanalytical method can be used effectively for estimation of XH in plasma samples. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer. [ABSTRACT FROM AUTHOR]

Aim: A monoterpene and bioactive component of the plant Rhodiola rosea (R. rosea), rosiridin has beneficial effects on the human central nervous system and enhances brain function. The goal of this scientific study was to determine if rosiridin might shield rats from neurocognitive problems induced by scopolamine. Methods: To track the potential toxicities in rats, the acute toxicity in rats was clarified. Rosiridin at a dose of 10 mg/kg was tested in rats for 14 days. At the conclusion of the investigation, behavioral parameters that were used to identify the rats' cognitive and motor abilities were evaluated. Several biochemical parameters were estimated using the prepared homogenate, including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), radical scavengers produced by the body (Catalase-CAT, superoxide dismutase-SOD, and reduced glutathione-GSH), indicators of oxidative and nitrative burnout, pro-inflammatory (Interleukins- IL-1β, IL-6, interferon gamma IFN-ꝩ, and tumor necrosis factor-TNF-α), and cell apoptosis caspases 3 and 9. Results and Conclusion: A significant behavioral parameter restoration was seen in the rosiridin-treated group, including reduction in latency time during acquisition and retention trial in the Morris water maze test, and percentage of spontaneous alterations in the y-maze test, when compared to the disease control group that received scopolamine; rosiridin also altered the oxidative stress and neuroinflammatory markers, as well as restoring Ach and ChAT activities and normalizing GSH, SOD, MDA, TNF-α, nitrate, IL-1β, IL-6, IFN-ꝩ, caspases 3 and 9 levels. The results imply that rosiridin limits the effect of scopolamine on rat cognitive function. [ABSTRACT FROM AUTHOR]

A rapid rise in antibiotic resistance by bacterial pathogens is due to these pathogens adaptation to the changing environmental conditions. Antibiotic resistance infections can be reduced by a number of ways such as development of safe and effective vaccine. Klebsiella aerogene is a gram-negative, rod-shaped bacterium resistant to a variety of antibiotics and no commercial vaccine is available against the pathogen. Identifying antigens that can be easily evaluated experimentally would be crucial to successfully vaccine development. Reverse vaccinology (RV) was used to identify vaccine candidates based on complete pathogen proteomic information. The fully sequenced proteomes include 44,115 total proteins of which 43,316 are redundant and 799 are non-redundant. Subcellular localization showed that only 1 protein in extracellular matrix, 7 were found in outer-membrane proteins, and 27 in the periplasm space. A total of 3 proteins were found virulent. Next in the B-cell-derived T-cell epitopes mapping phase, the 3 proteins (Fe2+− enterobactin, ABC transporter substrate-binding protein, and fimbriae biogenesis outer membrane usher protein) were tested positive for antigenicity, toxicity, and solubility. GPGPG linkers were used to prepare a vaccine construct composed of 7 epitopes and an adjuvant of toxin B subunit (CTBS). Molecular docking of vaccine construct with major histocompatibility-I (MHC-I), major histocompatibility-II (MHC-II), and Toll-like receptor 4 (TLR4) revealed vaccine robust interactions and stable binding pose to the receptors. By using molecular dynamics simulations, the vaccine-receptors complexes unveiled stable dynamics and uniform root mean square deviation (rmsd). Further, binding energies of complex were computed that again depicted strong intermolecular bindings and formation of stable conformation. [ABSTRACT FROM AUTHOR]

Background and Objectives: To assess the antioxidant and neuroprotective role of rosinidin on rat memory impairment that is induced by streptozotocin. Materials and Methods: Wistar rats were given an intraperitoneal (i.p) injection of streptozotocin (60 mg/kg) followed by treatment with rosinidin at selective doses (10 and 20 mg/kg) for 30 days. The behavioral parameters were estimated by Y-maze test and Morris water test. Biochemical parameters such as acetylcholinesterase (AChE), choline aacetyltransferase (ChAT), and nitric oxide, and antioxidants such as glutathione transferase (GSH), superoxide dismutase (SOD) IL-6, IL-10, Nrf2, and BDNF, were determined. Results: The study results revealed that rosinidin improved cognition by reverting the behavioral parameters. The treatment with rosinidin restored the antioxidant enzymes and inflammatory cytokines. Conclusions: From the results, it has been proven that rosinidin possesses antioxidant, anti-amnesic, and anti-inflammatory activity. Rosinidin improved the cognitive and behavioral deficits that were induced by streptozotocin. Furthermore, 20 mg/kg rosinidin was found to have strong protective action against streptozotocin-induced toxicity. [ABSTRACT FROM AUTHOR]