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Type-1 Diabetes Mellitus (T1DM) is regarded as a multifunctional, immune-related disease which causes massive destruction of islet [beta]-cells in pancreas resulting in hyperglycemic, hypoinsulinemia and hyperlipidimic conditions. The aim of the present study, was to investigate the hypothesis that streptozotocin (STZ)-induced T1DM in Balb/c mice when treated with crude polysaccharide from seaweed, Dictyopteris divaricata (CDDP) depicts improvement in diabetes-related symptoms. Treatment with CDDP resulted in decreased body weight loss, improved food consumption and water intake disbalances. The CDDP effectively improved fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, insulin secretion, rejuvenation of [beta]-cells mass, serum lipid profile and pro-inflammatory cytokines levels. Additionally, treatment with CDDP increased the population of beneficial bacteria such as Firmicutes, Bacteroidetes and Lactobacillus at phylum, family and genus levels by 16S rRNA sequencing. Furthermore, immunohistological examination confirmed that CDDP reduces the inflammation and restored the structural morphology of colon and upraised the levels of insulin receptor substrate-1 (IRS-1), Mucin-2 (MUC-2) and tight-junction proteins (TJs) whereby maintaining the gut structures and barrier permeability. Thus, the above presented data, highlights the safe and therapeutic effects of crude polysaccharide (CDDP) from D. divaricata in the treatment and restoration of T1DM disorders and can be used as a food supplement alternative to diabetes medicine. Keywords: Seaweed, Dictyopteris divaricata, Type-1 Diabetes Mellitus (T1DM), Polysaccharide, Streptozotocin, Inflammation, Gut Microbiota, Author(s): Nimra Zafar Siddiqui[sup.1], Ata Ur Rehman[sup.1], Waleed Yousuf[sup.2], Asif Iqbal khan[sup.1], Nabeel Ahmed Farooqui[sup.1], Shizhu Zang[sup.1], Yi Xin[sup.1] and Liang Wang[sup.3] Introduction Diabetes mellitus is a multifaced chronic ailment [...]

Several miRNAs have been recently suggested as potential therapeutic targets for anesthesia-related diseases. This study was carried out to explore the biological roles of miR-24 in isoflurane-treated rat hippocampal neurons. Isoflurane was used to induce neurotoxicity in a rat model. Gain- and loss-of-function of miR-24 was performed, and the size and [Ca.sup.2+] permeability of mitochondria, as well as cell proliferation and apoptosis, and levels of oxidative-stress-related factors were measured both in vivo and in vitro. Dual luciferase reporter gene assays were used to identify the target relationship between miR-24 and [p27.sup.kip1]. In this study, isoflurane treatment decreased miR-24 expression, after which, levels of neuron apoptosis and oxidative-stress-related factors were elevated and neuron viability was reduced. Over-expression of miR-24 inhibited oxidative damage and neuronal apoptosis in hippocampal tissues, and suppressed the size and [Ca.sup.2+] permeability of mitochondria of hippocampal neurons. miR-24 enhanced the viability of rat hippocampal neurons by targeting [p27.sup.kip1]. To conclude, this study demonstrated that miR-24 attenuates isoflurane-induced neurotoxicity in rat hippocampus via its antioxidative properties and inhibiting [p27.sup.kip1] expression. Key words: microRNA-24, isoflurane, oxidative stress, rat hippocampal neurons, [p27.sup.kip1]. Récemment, ona suggéré que plusieurs miARN puissent servir decibles thérapeutiques potentielles dans des maladies associées à l'anesthésie. Cette étude a été réalisée afin d'explorer les rôles biologiques du miR-24 dans les neurones de l'hippocampe de rat traité à l'isoflurane. Le modèle de rat traité à l'isoflurane a été établi pour induire une neurotoxicité. Le gain et la perte de fonction du miR-24 ont été effectués et la taille et la perméabilité des mitochondries au [Ca.sup.2+], la prolifération cellulaire et l'apoptose, et les niveaux de facteurs reliés au stress oxydant ont été mesurés in vivo et in vitro. Un double dosage du gène rapporteur luciférase a été réalisé pour identifier la lien entre le miR-24 et sa cible [p27.syp.kip1]. Dans cette étude, le traitement à l'isoflurane diminuait l'expression du miR-24, à la suite duquel l'apoptose des neurones et les facteurs liés au stress oxydant étaient accrus alors que la viabilité neuronale était réduite. La surexpression du miR-24 inhibait le dommage oxydant et l'apoptose neuronale dans l'hippocampe et diminuait la taille et la perméabilité au [ca.sup.+2] des mitochondries des neurones de l'hippocampe. En conclusion, cette étude a démontré que le miR-24 pouvait atténuer la neurotoxicité induite par l'isoflurane dans l'hippocampe du rat par sa fonction antioxydante et en inhibant l'expression de [p27.sup.kip1]. [Traduit par la Rédaction] Mots-clés : microARN-24, isoflurane, stress oxydant, neurones de l'hippocampe de rat, [p27.sup.kip1]., Introduction Surgeries related to pediatric neurosurgery and neurology require children to be treated with many general anesthetics; however, the majority of those anesthetics have been reported to affect neuronal activity, [...]

Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we showed that an MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in 2 independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock., Introduction In humans, dengue virus (DENV) causes an acute viral infection that manifests as a broad spectrum of disease: from asymptomatic infection to a mild febrile illness, dengue fever (DF), [...]

Byline: Rashmi. Sarkar, Shashank. Bhargava, Vibhu. Mendiratta Severe Acute Respiratory Virus Corona Virus 2 (SARS-CoV-2) has got its name Corona from Latin meaning 'crown.' It has crown-like spikes present on [...]

Author(s): Patricia R. M. Rocco [sup.1], Gary F. Nieman [sup.2] Author Affiliations: (1) grid.8536.8, 000000012294473X, Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Centro de Ciências da Saúde, [...]

Rationale Acute respiratory distress syndrome (ARDS) is frequently associated with hemodynamic instability which appears as the main factor associated with mortality. Shock is driven by pulmonary hypertension, deleterious effects of mechanical ventilation (MV) on right ventricular (RV) function, and associated-sepsis. Hemodynamic effects of ventilation are due to changes in pleural pressure (Ppl) and changes in transpulmonary pressure (TP). TP affects RV afterload, whereas changes in Ppl affect venous return. Tidal forces and positive end-expiratory pressure (PEEP) increase pulmonary vascular resistance (PVR) in direct proportion to their effects on mean airway pressure (mPaw). The acutely injured lung has a reduced capacity to accommodate flowing blood and increases of blood flow accentuate fluid filtration. The dynamics of vascular pressure may contribute to ventilator-induced injury (VILI). In order to optimize perfusion, improve gas exchange, and minimize VILI risk, monitoring hemodynamics is important. Results During passive ventilation pulse pressure variations are a predictor of fluid responsiveness when conditions to ensure its validity are observed, but may also reflect afterload effects of MV. Central venous pressure can be helpful to monitor the response of RV function to treatment. Echocardiography is suitable to visualize the RV and to detect acute cor pulmonale (ACP), which occurs in 20-25 % of cases. Inserting a pulmonary artery catheter may be useful to measure/calculate pulmonary artery pressure, pulmonary and systemic vascular resistance, and cardiac output. These last two indexes may be misleading, however, in cases of West zones 2 or 1 and tricuspid regurgitation associated with RV dilatation. Transpulmonary thermodilution may be useful to evaluate extravascular lung water and the pulmonary vascular permeability index. To ensure adequate intravascular volume is the first goal of hemodynamic support in patients with shock. The benefit and risk balance of fluid expansion has to be carefully evaluated since it may improve systemic perfusion but also may decrease ventilator-free days, increase pulmonary edema, and promote RV failure. ACP can be prevented or treated by applying RV protective MV (low driving pressure, limited hypercapnia, PEEP adapted to lung recruitability) and by prone positioning. In cases of shock that do not respond to intravascular fluid administration, norepinephrine infusion and vasodilators inhalation may improve RV function. Extracorporeal membrane oxygenation (ECMO) has the potential to be the cause of, as well as a remedy for, hemodynamic problems. Continuous thermodilution-based and pulse contour analysis-based cardiac output monitoring are not recommended in patients treated with ECMO, since the results are frequently inaccurate. Extracorporeal CO.sub.2 removal, which could have the capability to reduce hypercapnia/acidosis-induced ACP, cannot currently be recommended because of the lack of sufficient data., Author(s): A. Vieillard-Baron [sup.1] [sup.2] [sup.3], M. Matthay [sup.4], J. L. Teboul [sup.5] [sup.6], T. Bein [sup.7], M. Schultz [sup.8], S. Magder [sup.9], J. J. Marini [sup.10] Author Affiliations: (1) [...]

Multidrug resistance is emerging worldwide at an alarming rate among a variety of bacterial species, causing both community-acquired and nosocomial infections (1). Carbapenems, the last line of therapy, are now [...]

Dengue viruses (DENV) are the most common cause of mosquito-borne viral illness in the world, affecting approximately 400 million people annually. Symptomatic illness ranges from a mild, self-limiting febrile illness to one manifested by plasma leakage that can lead to vascular collapse and death. In this issue of the JCI, Rathore et al. report that DENV can cause mast cell degranulation independently of mast cell infection, resulting in the release of the vasoactive mediators chymase and tryptase. The authors showed that recombinant chymase and tryptase increased endothelial permeability in a dose-dependent manner in human microvascular endothelial cells. They went on to evaluate the tryptase inhibitor nafamostat mesylate in a mouse model for severe DENV viremia. Strikingly, the potential therapeutic prevented and reversed the tryptase-induced vascular permeability. As there are currently no licensed drugs for the treatment of dengue, these findings present a possible treatment modality for severe disease., Mechanism for vascular leakage Nearly two-thirds of the world's population are living in dengue-endemic regions and are at risk of acquiring the disease (1). Twenty-five percent of the estimated 400 [...]