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  • Schneider Udsen posted an update 4 days, 14 hours ago

    Iron, through its participation in oxidation/reduction processes, is essential for the physiological function of biological systems. In the brain, iron is involved in the development of normal cognitive functions, and its lack during development causes irreversible cognitive damage. Yet, deregulation of iron homeostasis provokes neuronal damage and death. Ferroptosis, a newly described iron-dependent cell death pathway, differs at the morphological, biochemical, and genetic levels from other cell death types. Ferroptosis is characterized by iron-mediated lipid peroxidation, depletion of the endogenous antioxidant glutathione and altered mitochondrial morphology. Although iron promotes the emergence of Ca2+ signals via activation of redox-sensitive Ca2+ channels, the role of Ca2+ signaling in ferroptosis has not been established. The early dysregulation of the cellular redox state observed in ferroptosis is likely to disturb Ca2+ homeostasis and signaling, facilitating ferroptotic neuronal death. This review presents an overview of the role of iron and ferroptosis in neuronal function, emphasizing the possible involvement of Ca2+ signaling in these processes. We propose, accordingly, that the iron-ferroptosis-Ca2+ association orchestrates the progression of cognitive dysfunctions and memory loss that occurs in neurodegenerative diseases. Therefore, to prevent iron dyshomeostasis and ferroptosis, we suggest the use of drugs that target the abnormal Ca2+ signaling caused by excessive iron levels as therapy for neurological disorders.Extracellular vesicles are small membrane-derived packages of information that are released from virtually all cell types. These nano-packages contain regulatory material including proteins, lipids, mRNA and microRNA and are a key mechanism of paracellular communication within a given microenvironment. Encompassed with a lipid bilayer, these organelles have been attributed numerous roles in regulating both physiological and pathological functions. Herein, we describe the role of EVs in the context of Rheumatoid and Osteoarthritis and explore how they could be harnessed to treat inflammatory and degenerative joint conditions. These structures offer a promising therapeutic strategy for treating musculoskeletal diseases due to their bioactive content, stability, small size and intrinsic ability to enter the avascular cartilage, a notoriously challenging tissue to target. We also discuss how EVs can be manipulated to load therapeutic cargo or present additional targeting moieties to enhance their beneficial actions and tissue regenerative properties.Eosinophils are granular leukocytes that are evolutionarily preserved in the innate immune system of some invertebrates and vertebrates, and these cells can directly remove invading microorganisms and secrete various cytokines, and are also involved in homeostasis. These eosinophils are made up of specific granular proteins that can be differentiated from other cells, and eosinophil peroxidase (EPX) is a peroxidase released only from eosinophils that plays an important role in maintaining the main function and homeostasis of eosinophils. We obtained the sequence information of EPX for the first time from the starry flounder (Platichthys stellatus), and predicted it by amino acid sequencing to confirm sequence alignment and phylogenetic characteristics with other species. Based on analysis of the expression characteristics of PsEPX mRNA in healthy P. stellatus, it was expressed at the highest level in peripheral blood lymphocytes (PBLs) and was also expressed at a relatively high level in the head kidney and intestine, which are immune-related tissues. After artificial infection with Streptococcus parauberis and viral haemorrhagic septicaemia virus, which are the causes of major pathogenic diseases, the expression level of PsEPX was significantly regulated, which showed specific characteristics of pathogens or tissues. These results suggest that PsEPX is an important component of the immune system of P. stellatus and is considered a basic research case for the study of the immunological function of eosinophils in fish.

    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection-induced inflammatory responses are largely responsible for the death of novel coronavirus disease 2019 (COVID-19) patients. However, the mechanism by which SARS-CoV-2 triggers inflammatory responses remains unclear. Here, we aimed to explore the regulatory role of SARS-CoV-2 spike protein in infected cells and attempted to elucidate the molecular mechanism of SARS-CoV-2-induced inflammation.

    SARS-CoV-2 spike pseudovirions (SCV-2-S) were generated using the spike-expressing virus packaging system. Western blot, mCherry-GFP-LC3 labeling, immunofluorescence, and RNA-seq were performed to examine the regulatory mechanism of SCV-2-S in autophagic response. The effects of SCV-2-S on apoptosis were evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Western blot, and flow cytometry analysis. Enzyme-linked immunosorbent assay (ELISA) was carried out to examine the mechanism of SCV-2-S in inflammatory responses.

    autophagic response. Ultimately, SCV-2-S-induced autophagy triggered inflammatory responses and apoptosis in infected cells. These findings not only improve our understanding of the mechanism underlying SARS-CoV-2 infection-induced pathogenic inflammation but also have important implications for developing anti-inflammatory therapies, such as ROS and autophagy inhibitors, for COVID-19 patients.The COVID-19 pandemic has infected nearly 178 million people and claimed the lives of over 3.8 million in less than 15 months. This has prompted a flurry of research studies into the mechanisms and effects of SARS-CoV-2 viral infection in humans. However, studies examining the effects of COVID-19 in pregnant women, their placentae and their babies remain limited. Furthermore, reports of safety and efficacy of vaccines for SARS-CoV-2 in pregnancy are limited. This review concisely summarises the case studies and research on COVID-19 in pregnancy, to date. check details It also reviews the mechanism of infection with SARS-CoV-2, and its reliance and effects upon the renin-angiotensin-aldosterone system. Overall, the data suggest that infection during pregnancy can be dangerous at any time, but this risk to both the mother and fetus, as well as placental damage, increases during the third trimester. The possibility of vertical transmission, which is explored in this review, remains contentious. However, maternal infection with SARS-CoV-2 can increase risk of miscarriage, preterm birth and stillbirth, which is likely due to damage to the placenta.

    Few controlled trials have assessed the impact of Mindfulness Based Cognitive Therapy (MBCT) on symptoms and functioning in bipolar disorder (BD). This study aims to evaluate the effectiveness of MBCT adjunctive group treatment.

    Randomized, prospective, multicenter, single-blinded trial that included BP-outpatients with subthreshold depressive symptoms. Participants were randomly assigned to three arms treatment as usual (TAU); TAU plus psychoeducation; and TAU plus MBCT. Primary outcome was change in Hamilton-D score; secondary endpoints were change in anxiety, hypo/mania symptoms and functional improvement. Patients were assessed at baseline (V1), 8 weeks (V2) and 6 months (V3). Main hypothesis was that adjunctive MBCT would improve depressive symptoms more than psychoeducation.

    Eighty-four participants were recruited (MBCT=40, Psychoeducation=34, TAU=10). Depressive symptoms improved in the three arms between V1 and V2 (p<0.0001), and between V1 and V3 (p<0.0001), and did not change between V2 and V3. At V3 no significant differences between groups were found. There were no significant differences in other measures either.

    In our BD population we did not find superiority of adjunctive MBCT over adjunctive Psychoeducation or TAU on subsyndromal depressive symptoms; neither on anxiety, hypo/mania, relapses, or functioning.

    In our BD population we did not find superiority of adjunctive MBCT over adjunctive Psychoeducation or TAU on subsyndromal depressive symptoms; neither on anxiety, hypo/mania, relapses, or functioning.

    Thromboinflammation, resulting from a complex interaction between thrombocytopathy, coagulopathy, and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system disruption, leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients.

    A prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival in the emergency department. The primary endpoint was 90-day mortality. The area under the curve (AUC) and Cox regression analyses were used to assess discriminatory ability and association with the endpoint.

    A total of 359 patients were enrolled, and the 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cutoff of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%,ans with risk stratification.

    Trichinellosis is a globally distributed food-borne parasitic disease. Initially, diagnosis is usually made based on clinical signs, symptoms, and history of eating raw or undercooked meat. In the present study, an immunochromatographic test (ICT) kit was developed to diagnose trichinellosis by detecting IgG antibodies in sera of infected humans.

    Somatic extract from Trichinella spiralis larvae was used as the antigen for the ICT kit development. Diagnostic efficacy was evaluated using human serum samples from proven trichinellosis patients, healthy persons, and those with other parasitic infections.

    The diagnostic sensitivity, specificity, positive and negative predictive values and accuracy of the ICT kit were 100.0% (95%; CI 88.8 to 100.0%), 92.5% (95% CI; 86.9 to 96.2%), 73.8% (95% CI; 58.0 to 86.1%), 100.0% (95% CI; 97.3 to 100.0%) and 93.8% (95% CI; 89.2 to 96.9%), respectively.

    This ICT diagnostic kit can be used as a testing tool for human trichinellosis. This test should permit rapid detection of infection to enable prompt anthelminthic treatment. It can also be used for retrospective diagnoses and field surveys based at laboratories where sophisticated equipment is lacking.

    This ICT diagnostic kit can be used as a testing tool for human trichinellosis. This test should permit rapid detection of infection to enable prompt anthelminthic treatment. It can also be used for retrospective diagnoses and field surveys based at laboratories where sophisticated equipment is lacking.

    The authors assessed the performance of pocket-sized transthoracic echocardiography (pTTE) compared with standard transthoracic echocardiography (sTTE) and auscultation for early screening of valvular heart disease (VHD). Early diagnosis of significant VHD is a challenge, but it enables appropriate follow-up and implementation of the best therapeutic strategy.

    sTTE, pTTE, and auscultation were performed by three different experienced physicians on 284 unselected patients. All cases of VHD detected by each of these three techniques were noted. sTTE was the gold standard. Each physician performed one examination and was blinded to the results of other examinations.

    We diagnosed a total of 301 cases of VHD, with a large predominance of regurgitant lesions 269 cases (89.3%) of regurgitant VHD and 32 (10.7%) of stenotic VHD. pTTE was highly sensitive (85.7%) and specific (97.9%) for screening for VHD, while auscultation detected only 54.1%. All significant cases of VHD (at least mild severity) were detected on pTTE.