This paper examines the intersection of group-based expressions including digital moral outrage, collective guilt, and collective action on Twitter, following the tragic incident of 8 May 2020, in ...which 16 migrant workers were run over by a train after the Indian government imposed a sudden COVID-19-related lockdown. Twitter data were gathered immediately at three different times - May 8–15, May 16- 23, May 24-May 31, and 4598 tweets were manually coded. The analysis revealed that digital moral outrage was the most frequently expressed emotion. It, however, gradually decreased, signaling digital outrage fatigue. Collective guilt and sympathy constituted the second-largest portion of the total tweets, and tweets reflecting collective action by the community progressively increased. The network of relationships among different group-based emotions, the promotion of one-sided narratives and virtue signaling on social media platforms are discussed.
Natural disasters always have a damaging effect on our way of life. Landslides cause serious damage to both human and natural resources around the world. In this paper, the prediction accuracy of ...five hybrid models for landslide occurrence in the Uttarkashi, Uttarakhand (India) was evaluated and compared. In this approach, the Rough Set theory coupled with five different models namely Bayesian Network (HBNRS), Backpropagation Neural Network (HBPNNRS), Bagging (HBRS), XGBoost (HXGBRS), and Random Forest (HRFRS) were taken into account. The database for the models development was prepared using fifteen conditioning factors that had 373 landslide and 181 non-landslide locations that were then randomly divided into training and testing locations with a ratio of 75%:25%. The appropriateness and predictability of these conditioning factors were assessed using the multi-collinearity test and the least absolute shrinkage and selection operator approach. The accuracy, sensitivity, specificity, precision, and F-Measures, and the area under the curve (AUC)-receiver operating characteristics curve, were used to evaluate and compare the performance of the individual and hybrid created models. The findings indicate that the constructed hybrid model HXGBRS (AUC = 0.937, Precision = 0.946, F1-score = 0.926 and Accuracy = 89.92%) is the most accurate model for predicting landslides when compared to other models (HBPNNRS, HBNRS, HBRS, and HRFRS). Importantly, when the fusion is performed with the rough set method, the prediction capability of each model is improved. Simultaneously, the HXGBRS model proposed shows superior stability and can effectively avoid overfitting. After the core modules were developed, the user-friendly platform was designed as an integrated GIS environment using dynamic maps for effective landslide prediction in large prone areas. Users can predict the probability of landslide occurrence for selected region by changing the values of a conditioning factors. The created approach could be beneficial for predicting the impact of landslides on slopes and tracking landslides along national routes.
Cells manage to survive, thrive, and divide with high accuracy despite the constant threat of DNA damage. Cells have evolved with several systems that efficiently repair spontaneous, isolated DNA ...lesions with a high degree of accuracy. Ionizing radiation and a few radiomimetic chemicals can produce clustered DNA damage comprising complex arrangements of single-strand damage and DNA double-strand breaks (DSBs). There is substantial evidence that clustered DNA damage is more mutagenic and cytotoxic than isolated damage. Radiation-induced clustered DNA damage has proven difficult to study because the spectrum of induced lesions is very complex, and lesions are randomly distributed throughout the genome. Nonetheless, it is fairly well-established that radiation-induced clustered DNA damage, including non-DSB and DSB clustered lesions, are poorly repaired or fail to repair, accounting for the greater mutagenic and cytotoxic effects of clustered lesions compared to isolated lesions. High linear energy transfer (LET) charged particle radiation is more cytotoxic per unit dose than low LET radiation because high LET radiation produces more clustered DNA damage. Studies with I-SceI nuclease demonstrate that nuclease-induced DSB clusters are also cytotoxic, indicating that this cytotoxicity is independent of radiogenic lesions, including single-strand lesions and chemically "dirty" DSB ends. The poor repair of clustered DSBs at least in part reflects inhibition of canonical NHEJ by short DNA fragments. This shifts repair toward HR and perhaps alternative NHEJ, and can result in chromothripsis-mediated genome instability or cell death. These principals are important for cancer treatment by low and high LET radiation.
Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a ...somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer’s disease (AD). Activated MAO induces the amyloid-beta (Aβ) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme’s physiology may lead to the future advancement of these drugs.
T cell activation and effector function is characterized by changes in metabolism. Altered metabolism is common to almost all types of activated T cells, but fatty acid synthesis seems to especially ...drive the formation of Th17 cells. Indeed, research has demonstrated that inhibition of early fatty acid synthesis through targeting of acetyl-CoA carboxylase (ACC1) can inhibit Th17 cell formation and instead promote the generation of regulatory T cells. Fatty acid synthase (FASN) is downstream of ACC, and previous studies have shown that FASN activity influences both cancer and inflammation. However, it remains to be determined whether FASN is a viable target for inhibiting Th17 cell function. Here, we demonstrate that FASN is a critical metabolic control for the generation of inflammatory subsets of Th17 cells. Conversely, inhibiting FASN function promotes IFN-γ production by Th1 and Th1-like Th17 cells. In vivo, inhibition of FASN, specifically in Th17 cells, leads to reduction of experimental autoimmune encephalomyelitis disease. These studies demonstrate the necessity of FASN in the autoimmune inflammatory function of Th17 cells.
Depression is one of the most debilitating psychiatric disorders affecting people of all ages worldwide. Despite significant heterogeneity between studies, increased inflammation and oxidative stress ...have been found in depression. Oxidative stress and inflammation are involved in the pathogenesis of depression. In the current review, we discussed the markers of oxidative stress and inflammation in depressive disorder and the association between these markers and the antidepressant treatment. The role of natural polyphenols in regulating various cell signaling pathways related to oxidative stress and inflammation has also been reviewed. The inhibitory effect of polyphenols on several cell signaling pathways reveals the vital role of polyphenols in the prevention and treatment of depressive disorder. Understanding the mechanism of polyphenols implicated in the regulation of cell signaling pathways is essential for the identification of lead compounds and the development of novel effective compounds for the prevention and treatment of depressive disorder.
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•Oxidative stress and inflammation are involved in the pathogenesis of depression.•Reactive oxygen species activate various cell signaling pathways.•Polyphenols inhibit the activation of oxidative stress-induced signaling pathways.•Polyphenols suppress oxidative stress and inflammation in depressive disorder.•Polyphenols exhibit antioxidative and anti-inflammatory effects.
Diabetes is a condition that affects a large percentage of the population and it is the leading cause of a wide range of costly complications. Diabetes is linked to a multi-fold increase in mortality ...and when compared to non-diabetics, the intensity and prevalence of COVID-19 ailment among diabetic individuals are more. Since its discovery in Wuhan, COVID-19 has grown rapidly and shown a wide range of severity. Temperature, lymphopenia, non-productive cough, dyspnoea, and tiredness are recognized as the characteristic of individuals infected with COVID-19 disease. In COVID-19 patients, diabetes and other related comorbidities are substantial predictors of disease and mortality. According to a recent study, SARS-CoV-2 (the virus responsible for covid-19 disease) may also lead to direct pancreatic harm, which could aggravate hyperglycemia and potentially cause the establishment of diabetes in formerly non-diabetic individuals. This bidirectional association of COVID-19 and diabetes load the burden on health care professionals throughout the world. It is recommended that gliptin medications be taken moderately, blood glucose levels must be kept under control, ACE inhibitors should be used in moderation, decrease the number of avoidable hospitalizations, nutritional considerations, and some other prevention measures, such as immunization, are highly recommended. SARS-CoV-2 may cause pleiotropic changes in glucose homeostasis, which could exacerbate the pathophysiology of pre-existing diabetes or result in new disease processes.
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•Diabetes and additional associated comorbidities are strong determinants of illness and death in COVID-19 individuals.•· SARS-CoV-2 may also lead to direct pancreatic harm.•· Diabetes mellitus is associated to decreased expression ACE2.•Patients with unmanaged DM have a weaker body's mechanism of defence.•Patients with unmamaged DM have weaker body.s mechanism of defense•·Diabetes mellitus and uncontrolled glycemia are significant indicators of morbidity and fatality.
Biodegradable polymeric nanoparticles have garnered pharmaceutical industry attention throughout the past decade. PLGA Poly(lactic-co-glycolic acid) is an excellent biodegradable polymer explored for ...the preparation of nanoparticles that are administered through various routes like intravenous and transdermal. PLGA's versatility makes it a good choice for the preparation of nanoparticles.
The main objective of this review paper was to summarize methods of preparation and characterization of PLGA nanoparticles along with their role in the transdermal delivery of various therapeutic agents.
A literature survey for the present review paper was done using various search engines like Pubmed, Google Scholar, and Science Direct.
In comparison to traditional transdermal administration systems, PLGA nanoparticles have demonstrated several benefits in preclinical investigations, including fewer side effects, low dosage frequency, high skin permeability, and simplicity of application.
PLGA nanoparticles can be considered efficient nanocarriers for the transdermal delivery of drugs. Nevertheless, the clinical investigation of PLGA nanoparticles for the transdermal administration of therapeutic agents remains a formidable obstacle.
Depression is one of the most prevalent forms of mental disorders and is the most common cause of disability in the Western world. Besides, the harmful effects of stress-related mood disorders on the ...patients themselves, they challenge the health care system with enormous social and economic impacts. Due to the high proportion of patients not responding to existing drugs, finding new treatment strategies has become an important topic in neurobiology, and there is much evidence that neuropeptides are not only involved in the physiology of stress but may also be clinically important. Based on preclinical trial data, new neuropharmaceutical candidates may target neuropeptides and their receptors and are expected to be essential and valuable tools in the treatment of psychiatric disorders. In the current article, we have summarized data obtained from animal models of depressive disorder and transgenic mouse models. We also focus on previously published research data of clinical studies on corticotropin-releasing hormone (CRH), galanin (GAL), neuropeptide Y (NPY), neuropeptide S (NPS), Oxytocin (OXT), vasopressin (VP), cholecystokinin (CCK), and melanin-concentrating hormone (MCH) stress research fields.
•Overactivation of the hypothalamic-pituitary-adrenal (HPA)-axis in depression•Increased cerebrospinal fluid level of Corticotropin-releasing hormone in depression•Increased hypothalamic Vasopressin activity in depression sustains HPA-axis overactivity.•Modulation of serotonin and noradrenergic systems by Galanin and Substance P•Neuropeptide Y modulates monoaminergic neurotransmitters involved in depression.
Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an ...isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.
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