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Misfolded proteins in the central nervous system can induce oxidative damage, which can contribute to neurodegenerative diseases in the mitochondria. Neurodegenerative patients face early mitochondrial dysfunction, impacting energy utilization. Amyloid-ß and tau problems both have an effect on mitochondria, which leads to mitochondrial malfunction and, ultimately, the onset of Alzheimer's disease. Cellular oxygen interaction yields reactive oxygen species within mitochondria, initiating oxidative damage to mitochondrial constituents. Parkinson's disease, linked to oxidative stress, α-synuclein aggregation, and inflammation, results from reduced brain mitochondria activity. Mitochondrial dynamics profoundly influence cellular apoptosis via distinct causative mechanisms. The condition known as Huntington's disease is characterized by an expansion of polyglutamine, primarily impactingthe cerebral cortex and striatum. Research has identified mitochondrial failure as an early pathogenic mechanism contributing to HD's selective neurodegeneration. The mitochondria are organelles that exhibit dynamism by undergoing fragmentation and fusion processes to attain optimal bioenergetic efficiency. They can also be transported along microtubules and regulateintracellular calcium homeostasis through their interaction with the endoplasmic reticulum. Additionally, the mitochondria produce free radicals. The functions of eukaryotic cells, particularly in neurons, have significantly deviated from the traditionally assigned role of cellular energy production. Most of them areimpaired in HD, which may lead to neuronal dysfunction before symptoms manifest. This article summarizes the most important changes in mitochondrial dynamics that come from neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Finally, we discussed about novel techniques that can potentially treat mitochondrial malfunction and oxidative stress in four most dominating neuro disorders.
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Enfermedad de Alzheimer , Esclerosis Amiotrófica Lateral , Enfermedad de Huntington , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/patología , Enfermedad de Alzheimer/patología , Enfermedad de Huntington/metabolismo , Esclerosis Amiotrófica Lateral/patología , Estrés Oxidativo/fisiología , Enfermedades Neurodegenerativas/metabolismo , Mitocondrias/metabolismoRESUMEN
Deep sequencing technologies such as RNA sequencing can help unravel mechanisms governing defense or resistance responses in plant-pathogen interactions. Several studies have been carried out to investigate the transcriptomic changes in Musa germplasm against Yellow Sigatoka disease, but the defense response of Musa paradisiaca has not been investigated so far. We carried out transcriptome sequencing of M. paradisiaca var. Kachkal infected with the pathogen Pseudocercospora musae and found that a vast set of genes were upregulated while many genes were downregulated in the resistant cultivar as a result of infection. After transcriptome assembly and differential gene expression analysis, 429 upregulated and 156 downregulated genes were filtered out (considering fold change ± 2, p < 0.01). Functional annotation of the differentially expressed genes (DEGs) enriched the upregulated genes into 49 gene ontology (GO) classes of biological processes (BP), 20 classes of molecular function (MF) and 9 classes of cellular component (CC). Similarly, the downregulated genes were classified into 35 GO classes of BP, 28 classes of MF and 6 classes of CC. The KEGG enrichment analysis revealed that the upregulated genes were most highly represented in 'metabolic' and 'biosynthesis of secondary metabolites' pathways. Additionally, 'plant hormone signal transduction', 'plant-pathogen interaction' and 'phenylpropanoid biosynthesis' pathways were also significantly enriched indicating their involvement in resistance responses against the pathogen. The RNA-seq analysis also depicts that a range of important defense-related genes are modulated as a result of infection, all of which are responsible for either mediating or activating resistance responses in the host. We studied and validated the expression profiles of ten important defense-related genes potentially involved in conferring resistance to the pathogen through qRT-PCR. Almost all the selected defense-related genes were found to be highly and significantly upregulated within 24 h post inoculation (hpi) and for some genes, the expression remained consistently high till the later time point of 72 hpi. These results, thus, indicate that the infection by P. musae leads to a rapid reprogramming of the defense transcriptome of the resistant banana cultivar. The defense-related genes identified to be modulated in response to infection are important not only for pathogen recognition and perception but also for activation and persistence of defense in the host. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03245-9.
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BACKGROUND: Dementia correlates with Alzheimer's disease, Parkinson's disease, frontotemporal and cerebrovascular diseases. There are supporting shreds of evidence on the pharmacological activity of curcuma caesia (Zingiberaceae family) for its antioxidant, antidepressant, analgesic, anticonvulsant, and anti-acetylcholinesterase effect. OBJECTIVE: This study aims to analyze the fecal microbial profile in Zederone treated demented rat model. METHODS: In our study, isolation and characterization of Zederone were carried out from curcuma caesia rhizomes, followed by estimation of its memory-enhancing effect on Aluminium-induced demented rat, which was evaluated by behavioural study on radial 8 arm maze. Moreover the detection of amyloid plaque formation was carried out using fluorescent microscopy of the congo red-stained rat brain tissues of the cerebral neocortex region. This study included eighteen female Wistar Albino rats that were divided into three groups that consisted of six rats in each group. The study of fecal microbial profile by metagenomic DNA extraction followed by next-generation sequencing was carried out to establish the correlation between gut microbes and amyloid plaques in dementia. RESULTS: Zederone could be characterized as pale yellow colored, needle-shaped crystals with 96.57% purity. This compound at 10 mg/kg body weight showed cognition improving capacity (p ≤ 0.0001) with a reduction of accumulated amyloid plaques that were detected in the demented group in fluorescence microscope and fecal microbiome study divulged an increased shift towards Lactobacillus genera in the treated group from Bacteroides in the demented group. CONCLUSION: This sesquiterpenoid compound would assist in the modulation of gut bacterial dysbiosis and act as a better therapeutic drug for dementia and other neurological disorders.
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Demencia/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Sesquiterpenos/farmacología , Animales , Disbiosis/tratamiento farmacológico , Femenino , Placa Amiloide/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
Cancer is recognized globally as the second-most dominating and leading cause of morbidities. Fighting the global health epidemic threat posed by cancer requires progress and improvements in imaging techniques, surgical techniques, radiotherapy, and chemotherapy. The existence of a small subpopulation of undifferentiated cells known as cancer stem cells has been supported by accumulating evidence and ongoing research. According to clinical data, cancer recurrence, tumor development, and metastasis are thought to be caused by CSCs. Nutritional or dietary supplements can help you to fight against cancer and cope with the treatment side effects. Vitamin D, sometimes known as the sunshine vitamin, is produced in the skin in reaction to sunlight. Vitamin D deficiency is hazardous to any degree, increasing the risk of diseases such as cancer and disorders like osteoporosis. Bioactive vitamin D, or calcitriol, regulates several biological pathways. Many modes of action of Vitamin D might be helpful in protecting somatic stem cells (e.g., DNA damage repair and oxidative stress protection) or restricting cancer stem cell growth (e.g., cell cycle arrest, cell apoptosis). Researchers have recently begun to investigate the inhibitory effects of dietary vitamin D on cancer stem cells. In this review, we investigated the therapeutic impact of vitamin D and its molecular processes to target cancer and cancer stem cells as well.
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Deficiencia de Vitamina D , Vitamina D , Humanos , Vitamina D/uso terapéutico , Vitamina D/metabolismo , Vitamina D/farmacología , Recurrencia Local de Neoplasia/patología , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/prevención & control , Calcitriol/metabolismo , Calcitriol/farmacología , Calcitriol/uso terapéutico , Células Madre Neoplásicas/patologíaRESUMEN
Scientific pieces of evidence support the pharmacological activity of Curcuma caesia for its antidepressant, analgesic, anticonvulsant and antioxidant effect. Here, we evaluate the bioactivity of essential oil and the various polarity-based solvent partitioned fractions obtained from Curcuma caesia for anti-amnesia, anxiolytic and antidepressant activities using Elevated plus maze and Morris water maze models. The cold maceration technique using methanol was adopted for extraction from dried powdered rhizomes and essential oil was extracted by hydrodistillation method. Partitioning of the methanolic extract based on solvent polarity by hexane, ethyl acetate, and methanol was continued, followed by column chromatography of the ethyl acetate fraction. Suspensions were prepared for fractions (dissolved in distilled water) and essential oil (dissolved in tween 20) at 200 mg/kg and 400 mg/kg after acute toxicity study and were orally administered to Wistar albino female rats after the orientation of hypoxia by sodium nitrite (50 mg/kg) and amnesia by scopolamine (1 mg/kg). Behavioural observations, biochemical and histopathological examinations were carried out for all the treated groups. Diazepam (12 mg/kg) and galantamine (3 mg/kg) were used as standard drugs for this study against hypoxia and amnesia. Data acquired from behavioural, biochemical (acetylcholinesterase, myeloperoxidase, superoxide dismutase, reduced glutathione, catalase) and histopathological studies have illustrated that fraction II acquires highly significant memory-enhancing, anxiolytic and antidepressant effects. Rest fractions (I and III) and essential oil showed moderate efficacy. In prospects, identification of active molecules from the most active fraction (fraction II) and further studies on a molecular basis would substantiate its specific mechanism of neuroprotective action.
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BACKGROUND: Alternaria brassicae, the causal organism of Alternaria blight, is a necrotroph infecting crops of the Brassicaceae family at all growth stages. To circumvent this problem, several disease management strategies are being used in the field, and disease-resistant varieties have also been developed. However, no strategy has proven completely successful, owing to the high variability in virulence among A. brassicae isolates, which causes a diverse spectrum of symptoms. Nonhost resistance (NHR) is a robust and broad-spectrum defense mechanism available in plants, and the exploitation of gene pools from plant species that are nonhost to A. brassicae could serve as novel sources of resistance. METHODOLOGY: We searched the literature using key words relevant to this study in various search engines, such as PubMed, Web of Science, and Google Scholar, as well as certain journal websites. The literature was retrieved, sorted, and mined to extract data pertinent to the present review. RESULTS: In this review, we have comprehensively covered the recent progress made in developing Alternaria blight resistance in Brassica crops by exploiting host germplasm. We also enumerate the potential NHR sources available for A. brassicae and the NHR layers possibly operating against this pathogen. In addition, we propose different strategies for identifying NHR-related genes from nonhost plants and testing their relevance in imparting broad-spectrum resistance when transferred to host plants. CONCLUSION: This review will help broaden the current knowledge base pertaining to the resistance sources available in host germplasm, the exploitation of NHR mechanisms, and their applications in protecting Brassica crops from Alternaria blight. The insights might also be applicable to a wider repertoire of plant pathogens.
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OBJECTIVE: To evaluate the antihyperglycemic property of Cinnamomum bejolghota (Buch.-Ham.) on streptozotocin induced type-2 diabetic rats. METHODS: Oral glucose tolerance test level was measured at 0, 30, 60, 90 and 120 min after the administration of extract. The extract was orally administered once daily at two dose levels of 250 and 500 mg/kg for 15 d. The effect of methanolic extract of Cinnamomum bejolghota (MECB) on the divergence of body weights, blood glucose levels and the biochemical parameters viz., total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, aspartate transaminase, alanine transaminase, alkaline phosphatase were measured in an autoanalyzer. Histopathology of pancreas and in vivo antioxidative status was studied. RESULTS: A significant increase in bodyweights and rapid decrease in hyperglycemic peak was experiential in animals treated with MECB. After 15 d treatment the total cholesterol, TG, low density lipoprotein level decreased and high density cholesterol level increased significantly. MECB reduced the levels of the elevated marker enzymes aspartate transaminase, alanine transaminase and alkaline phosphatase. MECB reduced the lipid peroxidation and improved the level of catalase and glutathione in liver. Histopathological studies of pancreas in diabetic and treated groups substantiate the cytoprotective action of extract. CONCLUSIONS: It can be evident from the research work that Cinnamomum bejolghota (Buch.-Ham.) has potent antihyperglycemic activity and supports the in vivo antioxidative status.
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Stem bark of Nyctanthes arbor-tristis Linn. was extracted in methanol to evaluate their analgesic and anti-inflammatory activities. The analgesic activity was determined on Wistar albino rats by hot plate method, tail flick assay, and tail immersion method using Morphine sulphate as standard drug at a dose of 5 mg/kg of body weight and the results were expressed as mean increase in latency after drug administration ± SEM. The anti-inflammatory activity was assessed by Carrageenan-induced rat paw oedema using diclofenac sodium as standard drug at a dose of 100 mg/kg of body weight and expressed in terms of mean increase in paw volume ± SEM. Stem bark extract was given at a dose of 250 mg/kg and 500 mg/kg of body weight. Both standard drugs and extract were administered orally to the animals. Control received distilled water orally. Results showed that Nyctanthes arbor-tristis Linn. had potent analgesic and anti-inflammatory activities.