Europinidin Mitigates 3-NPA-Induced Huntington's Disease Symptoms in Rats: A Comprehensive Analysis of Oxidative Stress, Mitochondrial Enzyme Complex Activity, Pro-Inflammatory Markers and Neurotransmitter Alterations.

Huntington's disease (HD) is a neurodegenerative disease that causes progressive motor and cognitive dysfunction. There is no cure for HD, and current therapeutics can only manage the signs and symptoms as well as slowing disease progression. This investigation examines the possible therapeutic advantages of europinidin in 3-nitropropionic acid (3-NPA) injected HD in rats. Wistar rats were randomly assigned to five groups (n = 6): normal control, 3-NPA (10 mg/kg, i.p.), 3-NPA + europinidin-10 (10 mg/kg, p.o.), 3-NPA + europinidin-20 (20 mg/kg, p.o.), and europinidin alone (20 mg/kg, p.o.) for 15-day. Various behavioral and biochemical parameters including antioxidant levels, oxidative stress, pro-inflammatory markers, mitochondrial enzyme complex, and neurotransmitters were assessed. Europinidin restored biochemical, mitochondrial dysfunction, oxidative stress, neurotransmitter, and pro-inflammatory parameters disrupted by 3-NPA. Here we show that europinidin attenuates 3-NPA-induced neurodegeneration in rat models of HD. Europinidin modulates oxidative stress, enhances antioxidants, restores mitochondrial enzyme complex activity, reduces neuroinflammation, and modulates neurotransmitter levels. Our findings reveal the potential of europinidin as a novel therapeutic agent for the treatment of HD. This study also provides new insights into the molecular mechanisms of europinidin-mediated neuroprotection and may have a beneficial role in the management of neurological diseases.

Noncoding RNAs in hepatitis: Unraveling the apoptotic pathways.

Hepatitis is a worldwide health issue that causes inflammation of the liver and is frequently brought on by viral infections, specifically those caused by the hepatitis B and C viruses. Although the pathophysiological causes of hepatitis are complex, recent research indicates that noncoding RNAs (ncRNAs) play a crucial role in regulating apoptosis, an essential process for maintaining liver homeostasis and advancing the illness. Noncoding RNAs have been linked to several biological processes, including apoptosis. These RNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Distinct expression patterns characterising different stages of the disease have been discovered, indicating dysregulation of these non-coding RNAs in liver tissues infected with hepatitis. The complex interplay that exists between these noncoding RNAs and apoptotic effectors, including caspases and members of the Bcl-2 family, plays a role in the precarious equilibrium that regulates cell survival and death during hepatitis. The purpose of this review is to provide an overview of ncRNA-mediated apoptosis in hepatitis, as well as insights into possible therapeutic targets and diagnostic indicators.

The ncRNA-TGF-ß axis: Unveiling new frontiers in colorectal cancer research.

Colorectal cancer (CRC) poses a substantial global challenge, necessitating a deeper understanding of the molecular underpinnings governing its onset and progression. The transforming growth factor beta (TGF-ß) network has been a well-recognized cornerstone in advancing CRC. Nevertheless, a recent study has highlighted the growing importance of non-coding RNAs (ncRNAs) in this context. This comprehensive review aims to present an extensive examination of the interaction between ncRNAs and TGF-signaling. Noncoding RNAs (ncRNAs), encompassing circular RNAs (circRNAs), long-ncRNAs (lncRNAs), and microRNAs (miRNAs), have surfaced as pivotal modulators governing various aspects of TGF-ß signaling. MiRNAs have been discovered to target elements within the TGF-ß signaling, either enhancing or inhibiting signaling, depending on the context. LncRNAs have been associated with CRC progression, functioning as miRNA sponges or directly influencing TGF-ß pathway elements. Even circRNAs, a relatively recent addition to the ncRNA family, have impacted CRC, affecting TGF-ß signaling through diverse mechanisms. This review encompasses recent progress in comprehending specific ncRNAs involved in TGF-ß signaling, their functional roles, and their clinical relevance in CRC. We investigate the possibility of ncRNAs as targets for detection, prognosis, and therapy. Additionally, we explore the interaction of TGF-ß and other pathways in CRC and the role of ncRNAs within this intricate network. As we unveil the intricate regulatory function of ncRNAs in the TGF-ß signaling in CRC, we gain valuable insights into the disease's pathogenesis. Incorporating these discoveries into clinical settings holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of CRC patients. This comprehensive review underscores the ever-evolving landscape of ncRNA research in CRC and the potential for novel interventions in the battle against this formidable disease.

Apoptosis-driven synergistic anti-cancer efficacy of ethyl acetate extract of Memecylon sisparense Gamble leaves and doxorubicin in in-vitro and in-vivo models of triple-negative breast cancer.

In the spectrum of breast neoplasms, approximately 15 to 20% of all diagnosed cases are triple-negative breast carcinoma. TNBC grows and spreads faster than other invasive breast cancers and has a worse prognosis. The existing therapies and chemotherapeutic drugs have several limitations, so the development of safe and affordable treatment options is currently in demand. Hence, this research focuses on scientifically evaluating the therapeutic anticancer effect of ethyl acetate extract of MSG and its combined efficacy with doxorubicin against TNBC. MSG has shown an IC50 value of 48.40 ± 1.68 µg/ml on the MDA-MB-231 cell line, and the combination of MSG with Dox demonstrated the synergistic effect. Apoptotic changes such as membrane blebbing chromatin condensation were observed in MSG alone and in combination with doxorubicin treatments. Apoptosis was confirmed with Annexin V-FITC/PI staining and increased apoptotic markers such as Cleaved caspase-3 Bax and decreased anti-apoptotic markers Bcl-2 by western blotting. The tumor burden significantly decreased in MSG and combination treatment groups while restoring their body weights. Meanwhile, the Dox-treated group indicated a decreased tumor burden combined with weight loss. The present investigation revealed that MSG and doxorubicin have a synergistic anticancer effect in TNBC.

Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration.

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.

GAS5: A pivotal lncRNA in diabetes mellitus pathogenesis and management.

The long non-coding RNA (lncRNA), GAS5, has garnered significant attention recently for its multifaceted involvement in cellular processes, particularly within the context of diabetes. This comprehensive review delves into the intricate molecular interactions associated with GAS5 and their profound implications for understanding, diagnosing, and effectively managing diabetes mellitus. The article begins by highlighting the global prevalence of diabetes and the urgent need for innovative insights into its underlying mechanisms and therapeutic approaches. It introduces GAS5 as a crucial regulator of gene expression, with emerging significance in the context of diabetes-related processes. The core of this review unravels the regulatory network of GAS5 in diabetes, elucidating its impact on various aspects of the disease. It explores how GAS5 influences insulin signaling pathways, glucose metabolism, and the function of ß-cells, shedding light on its role in hyperglycemia and insulin resistance. Moreover, the article underscores the clinical relevance of GAS5's interactions by discussing their associations with different diabetes subtypes, predictive value, and potential applications as both diagnostic tools and therapeutic targets. It provides insights into ongoing research endeavours aimed at harnessing the potential of GAS5 for innovative disease management strategies, including the development of RNA-based therapeutics. Concluding with a forward-looking perspective, the abstract highlights the broader implications of GAS5 in the field of diabetes, such as its connection to diabetic complications and its potential for personalized approaches in disease management.

Autologous Stem Cell Transplant in Hodgkin's and Non-Hodgkin's Lymphoma, Multiple Myeloma, and AL Amyloidosis.

Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and self-repair of the cells. Cancer cells multiply uncontrollably and invade healthy tissues, making stem cell transplants a viable option for cancer patients undergoing high-dose chemotherapy (HDC). When chemotherapy is used at very high doses to eradicate all cancer cells from aggressive tumors, blood-forming cells and leukocytes are either completely or partially destroyed. Autologous stem cell transplantation (ASCT) is necessary for patients in those circumstances. The patients who undergo autologous transplants receive their own stem cells (SCs). The transplanted stem cells first come into contact with the bone marrow and then undergo engraftment, before differentiating into blood cells. ASCT is one of the most significant and innovative strategies for treating diseases. Here we focus on the treatment of Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and AL amyloidosis, using ASCT. This review provides a comprehensive picture of the effectiveness and the safety of ASCT as a therapeutic approach for these diseases, based on the currently available evidence.

Exploring GAS5's impact on prostate cancer: Recent discoveries and emerging paradigms.

Novel treatment targets must be discovered to improve the results for patients with prostate cancer, which continues to be a significant worldwide health problem. Growth Arrest-Specific 5 (GAS5) is a long non-coding RNA (lncRNA) that has emerged as a promising target. GAS5 is a non-coding RNA that is a tumour suppressor in many different cancers by reducing cell proliferation and increasing apoptosis. GAS5 influences cell cycle control and apoptosis via interactions with important signalling pathways and microRNAs, as has been shown by recent studies. Furthermore, GAS5 has attracted interest for its diagnostic and prognostic potential in prostate cancer. GAS5 expression is a promising biomarker for disease classification and individualized treatment approaches because of its association with clinicopathological characteristics such as tumour stage, Gleason score, and metastatic potential. Preclinical models have revealed encouraging anticancer benefits from experimental techniques employing GAS5 overexpression or synthetic analogues, indicating the possibility of translational treatments. Whether GAS5 can be used as a diagnostic biomarker and therapeutic target might lead to more effective and individualized ways to fight prostate cancer, improving patient outcomes and quality of life. To utilize its potential for therapy and establish it as a useful addition to the clinical arsenal against this pervasive malignancy, more investigation into the complex molecular pathways of GAS5 in prostate cancer is essential. This review highlights the recent advancements and insights into the role of GAS5 in prostate cancer pathogenesis and progression.

Evaluation of anti-cancer effects of carnosine and melittin-loaded niosomes in MCF-7 and MDA-MB-231 breast cancer cells.

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, RT-qPCR 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.

Detection of Circulating Tumor Cells and Epithelial Progenitor Cells: A Comprehensive Study.

Technological advancement to enhance tumor cells (TC) has allowed discovery of various cellular bio-markers: cancer stem cells (CSC), circulating tumor cells (CTC), and endothelial progenitor cells (EPC). These are responsible for resistance, metastasis, and premetastatic conditions of cancer. Detection of CSC, CTC, and EPC assists in early diagnosis, recurrence prediction, and treatment efficacy. This review describes various methods to detect TC subpopulations such as in vivo assays (sphere-forming, serial dilution, and serial transplantation), in vitro assays (colony-forming cells, microsphere, side-population, surface antigen staining, aldehyde dehydrogenase activity, and Paul Karl Horan label-retaining cells, surface markers, nonenriched and enriched detection), reporter systems, and other analytical methods (flow cytometry, fluorescence microscopy/spectroscopy, etc.). The detailed information on methods to detect CSC, CTC, and EPC in this review will assist investigators in successful prognosis, diagnosis, and cancer treatment with greater ease.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro, and in silico mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1H NMR, 13C NMR, 13C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.Communicated by Ramaswamy H. Sarma.

Revealing genetic links of Type 2 diabetes that lead to the development of Alzheimer's disease.

Background: A factor leading to Alzheimer's Disease (AD), portrayed by peripheral insulin resistance, is Type 2 diabetes mellitus (T2D). The likelihood of T2D cases would be at boosted danger in alternating AD cases has severe social consequences. Several genes have been detected via gene expression profiling or different techniques; despite the consideration of the utility of numerous of these genes stays insufficient. Methods: This project is designed to uncover the mutual genomics motifs between AD and T2D via non-negative matrix factorization (NMF) of differentially expressed genes (DEGs) of T2D Mellitus of human cortical neurons of the neurovascular unit gene expression data. A rank factorization value is calculated by employing the combination of the NMF model with the unit invariant knee (UIK) point method. The metagenes are further determined by remarking the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment tools. In this study, the most highly expressed genes of metagenes are subjected to protein-protein interaction (PPI) network study to discover the most significant biomarkers of T2D Mellitus in the ageing brain. Results: We screened the most important shared genes (CDKN1A, COL22A1, EIF4A, GFAP, SLC1A1, and VIM) and essential human molecular pathways that motivate these diseases. The study aimed to validate the most significant hub genes using network-based methods which detected the corresponding relationship between AD and T2D. Conclusions: Using in silico tools, the computational pipeline has broadly examined transformed pathways and discovered promising biomarkers and drug targets. We validated the most significant hub genes using network-based methods which detected the corresponding relationship between AD and T2D. These consequences on brain cells hypothetically reserve to diabetic Alzheimer's so-called type 3 diabetes (T3D) and may offer promising methodologies for curative intrusion.

Synergism of CD28 Immune Molecule in Late Immunosuppressive Phase of COVID-19: Effectiveness in Vaccinated Individuals.

Context: Lymphopenia has been frequently documented and linked to coronavirus disease 2019 (COVID-19) in a severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) attack. A decrease in the T-lymphocyte count has shown promise as a clinical indicator and predictor of COVID-19 severity. Objective: The review intended to examine the relationship of COVID-19 infections in individuals to lost expression of CD28 on naive CD4+/CD8+-mediated, vaccine-specific, neutralizing antibody responses. Design: The research team performed a narrative review by searching eight databases: Medline, Elsevier, Cochrane, PubMed, Google Scholar, Mendeley, and Springer Nature. The search used the following key terms: SARS CoV-2, clinical aspects and pathology of SARS CoV-2, involvement of viral spike (S) protein in SARS CoV-2, immunological changes in COVID-19 infection, basic overview of CD28 immuno-molecule ligand, reduction of vaccine therapeutic efficacy in COVID-19 infection, and immunomodulatory response of lost CD28 ligand. Setting: This study was done in a Maharishi Arvind College of Pharmacy, Jaipur, India. Results: In COVID-19 patients, particularly those with severe disease, had increased levels of IL-2 or IL-2R. Given IL-2's supportive role in the expansion and differentiation of T cells, the authors exhibiting that lymphopenia, particularly in severe COVID-19, could be attributed to nonfunctional and dysfunctional differentiation of CD4+ and CD8+ T cells as a result of low CD28 immuno-molecule expression on naive T cells. Conclusions: The literature review found that independent, early immunological prognostic markers for a poor prognosis, in addition to higher levels of IL-6, include a substantial proportion of large inflammatory monocytes and a small proportion of chronic CD28+ CD4+T cells. The current findings suggest that a combination of COVID-19 vaccination with SARS CoV-2-reactive naive T cells with the CD28 immune-molecule may be a viable method for establishing T-cell-based, adaptive cellular immunotherapy against COVID-19 infection. Further research is needed, especially larger studies to confirm the current findings, to improve early clinical treatment.

Role of Flavonoids in Management of Various Biological Targets in Alzheimer's Disease: Evidence from Preclinical to Clinical Studies.

More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aß42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis.

Promises of Molecular Pharmaceutics in the Development of Novel Drug Delivery Formulations.

Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics.

Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice / Efeitos anticonvulsivantes da desvenlafaxina na modulação da monoamina cerebral e do estresse oxidativo em camundongos

Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P<0.01) increased and LPO reduced significantly (P<0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P < 0,01) e o LPO reduziu significativamente (P < 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.

Anticonvulsant effects of desvenlafaxine on modulating brain monoamine and oxidative stress in mice

Abstract Desvenlafaxine succinate (DVS) inhibits serotonin reuptake selectively and is approved for major depressive disorders. This research investigated influence of DVS on modulating brain monoamine and oxidative stress in mice. The antiepileptic potential of DVS (10, 20, or 30 mg/kg/i.p.) in pentylenetetrazole (PTZ; 85 mg/kg) with i.p. route of administration, strychnine (STR; 75 mg/kg) with i.p. route, pilocarpine (400 mg/kg) with s.c. route and maximal electroshock MES-induced convulsion in mouse models. The activities of oxidative stress, i.e. superoxide dismutase (SOD), glutathione (GSH) and lipid peroxidation (LPO) as well as gamma-aminobutyric acid (GABA) in the brains of PTZ-induced convulsive mice. Treatment with DVS increased the latency to develop siezures and declined mortalities in rodents against PTZ, STR and pilocarpine-induced convulsions. Results of MES-leaded siezures revealed that DVS reduced tonic hind limb extension duration and mortalities significantly. Brain, SOD, GSH and GABA level were significantly (P 0.01) increased and LPO reduced significantly (P 0.01) after DVS treatment. Furthermore, the DVS did not show any motor coordination signs in the rotarod test. We demonstrated that the role of DVS in convulsion genesis in mice under control condition and attenuate the PTZ-induced oxidative damage.

Resumo O succinato de desvenlafaxina (DVS) inibe seletivamente a recaptação da serotonina e é aprovado para transtornos depressivos maiores. Esta pesquisa investigou a influência do DVS na modulação da monoamina cerebral e do estresse oxidativo em camundongos. O potencial antiepiléptico de DVS (10, 20 ou 30 mg / kg / i.p.) Em pentilenotetrazole (PTZ; 85 mg / kg) com i.p. via de administração, estricnina (STR; 75 mg / kg) com i.p. via, pilocarpina (400 mg / kg) com s.c. rota e convulsão induzida por MES de eletrochoque máximo em modelos de camundongos. As atividades de estresse oxidativo, ou seja, superóxido dismutase (SOD), glutationa (GSH) e peroxidação lipídica (LPO), bem como ácido gama-aminobutírico (GABA) nos cérebros de camundongos convulsivos induzidos por PTZ. O tratamento com DVS aumentou a latência para desenvolver crises e diminuiu a mortalidade em roedores contra convulsões induzidas por PTZ, STR e pilocarpina. Os resultados de siezures conduzidos por MES revelaram que o DVS reduziu significativamente a duração e a mortalidade da extensão tônica dos membros posteriores. Os níveis de cérebro, SOD, GSH e GABA aumentaram significativamente (P 0,01) e o LPO reduziu significativamente (P 0,01) após o tratamento com DVS. Além disso, o DVS não apresentou sinais de coordenação motora no teste do rotarod. Demonstramos o papel do DVS na gênese da convulsão em camundongos sob condição de controle e atenua o dano oxidativo induzido por PTZ.

Gingerol, a Natural Antioxidant, Attenuates Hyperglycemia and Downstream Complications.

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.

Polysaccharide-Based Nanomedicines Targeting Lung Cancer.

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.

Barriers and facilitators of childhood COVID-19 vaccination among parents: A systematic review.

Background: The acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program. Method: A systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS). Results: The results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (>85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%). Conclusion: This review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.