Mitochondrial straightener metabolism and neurodegenerative diseases

This suggests that text messaging programs can facilitate healthy lifestyle and diabetes prevention in this population.
Women with recent GDM increase their step count in the hours following positive and supportive text messages. This suggests that text messaging programs can facilitate healthy lifestyle and diabetes prevention in this population.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may result in a severe pneumonia associated with elevation of blood inflammatory parameters, reminiscent of cytokine storm syndrome. Steroidal anti-inflammatory therapies have shown efficacy in reducing mortality in critically ill patients; however, the mechanisms by which SARS-CoV-2 triggers such an extensive inflammation remain unexplained.
To dissect the mechanisms underlying SARS-CoV-2-associated inflammation in patients with severe coronavirus disease 2019 (COVID-19), we studied the role of IL-1β, a pivotal cytokine driving inflammatory phenotypes, whose maturation and secretion are regulated by inflammasomes.
We analyzed nod-like receptor protein 3 pathway activation by means of confocal microscopy, plasma cytokine measurement, cytokine secretion following invitro stimulation of blood circulating monocytes, and whole-blood RNA sequencing. The role of open reading frame 3a SARS-CoV-2 protein was assessed by confocal microscopy analysis following nucleofection of a monocytic cell line.
We found that circulating monocytes from patients with COVID-19 display ASC (adaptor molecule apoptotic speck like protein-containing a CARD) specks that colocalize with nod-like receptor protein 3 inflammasome and spontaneously secrete IL-1β invitro. This spontaneous activation reverts following patient's treatment with the IL-1 receptor antagonist anakinra. Transfection of a monocytic cell line with cDNA coding for the ORF3a SARS-CoV-2 protein resulted in ASC speck formation.
These results provide further evidence that IL-1β targeting could represent an effective strategy in this disease and suggest a mechanistic explanation for the strong inflammatory manifestations associated with COVID-19.
These results provide further evidence that IL-1β targeting could represent an effective strategy in this disease and suggest a mechanistic explanation for the strong inflammatory manifestations associated with COVID-19.
It has been known that chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammation-dominated disease; however, the reasons causing such type of mucosal inflammation in CRSwNP are not well elucidated.
We sought to investigate the role of microRNA-21-5p (miR-21-5p) in regulating mucosal type 2 inflammation in CRSwNP.
miR-21-5p expression was detected in nasal mucosa of patients with CRSwNP. Correlations between miR-21-5p and indicators of type 2 inflammation were further analyzed. miR-21 knockout mice were used to explore the role of miR-21-5p in a murine model of eosinophilic (E) CRSwNP. Target gene of miR-21-5p related to type 2 inflammation in CRSwNP was identified.
The upregulated miR-21-5p in the nasal mucosa of patients with CRSwNP, compared with control subjects, was expressed higher in patients with ECRSwNP than in patients with nonECRSwNP. miR-21-5p expression was positively correlated with mucosal eosinophil infiltrations and the expression of type 2 inflammatory cytokines. In ttherapeutic target for CRSwNP.
RGPR-p117 was originally discovered as a novel transcription factor, which specifically binds to a nuclear factor I (NFI) consensus motif TTGGC(N)
CC in the promoter region of the regucalcin gene. RGPR-p117 is also called as Lztr2 and SEC16B. The role of RGPR-p117 in cell regulation is poorly understood. This study was undertaken to determine whether the overexpression of RGPR-p117 impacts the proliferation of normal rat kidney proximal tubular epithelial NRK-52E cells in vitro.
The NRK-52E wild-type cells and RGPR-p117-overexpressing NRK-52E cells were cultured in DMEM containing fetal bovine serum.
The overexpression of RGPR-p117 repressed colony formation and proliferation of NRK-52E cells. Interestingly, RGPR-p117 overexpression blocked cell proliferation promoted by culturing with Bay K 8644, a calcium-entry agonist, and phorbol 12-myristate 13-acetate, an activator of protein kinase C. The depressive effects of RGPR-p117 overexpression on cell proliferation were not occurred by culturing with various inhibitors of cell cycle and intracellular signaling processes. RGPR-p117 overexpression increased the translocation of RGPR-p117 into the nucleus of NRK-52E cells. Mechanistically, RGPR-p117 overexpression diminished the levels of Ras, PI3 kinase, Akt, mitogen-activated protein kinase, and mTOR, while it raised the levels of p53, Rb, p21, and regucalcin. Furthermore, RGPR-p117 overexpression protected cell death caused by apoptosis-inducing factors, suggesting that the suppressive effects of RGPR-p117 on cell growth are independent of cell death.
The present study demonstrates that the overexpressed transcription factor RGPR-p117 suppresses cell proliferation via targeting diverse signaling processes, suggesting a role of RGPR-p117 in cell regulation.
The present study demonstrates that the overexpressed transcription factor RGPR-p117 suppresses cell proliferation via targeting diverse signaling processes, suggesting a role of RGPR-p117 in cell regulation.
Prolonged Endoplasmic Reticulum Stress (ERS) is involved in the pathogenesis of metabolic syndrome, including type-2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. There have been significant efforts to discover molecules to treat ERS and/or to ameliorate associate symptoms. In this study, we investigated the effect of 7,8-Dihydroxyflavone (7,8-DHF) on ERS in liver and pancreas tissues in a cafeteria (CAF) diet induced metabolic syndrome model.
Male C57BL/6 mice were fed CAF diet for 16weeks and 7,8-DHF was administered intraperitoneally (5mg/kg/day) for last four weeks. 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) in liver and pancreas tissues, insulin and interleukin-1β (IL-1β) in serum were analyzed by ELISA method and serum biochemistry parameters were analyzed with autoanalyzer. GRP78 and CHOP gene expression levels were determined by qRT-PCR. In addition, histopathological analyzes were performed on liver and pancreas tipound to ameliorate ERS and related metabolic symptoms.
Colonisation with non-typeable Haemophilus influenzae (NTHi) is common in COPD. Iron is required by bacteria for nutrition. Gallium is imported into bacteria using iron import proteins. AG-221 Gallium cannot fulfill key metabolic functions, causing bactericidal effects. We tested the efficacy of gallium compounds as antimicrobials against NTHi in hemin rich conditions, and their ability to reduce NTHi induced pro-inflammatory responses in macrophages.
NTHi was cultured with the free iron analogue gallium nitrate (GaN) and heme iron analogue gallium protoporphyrin (GaPP) (0.5-4μM; 24h). Growth of NTHi reference strain (NCTC 12699) and 6 clinical isolates from COPD patients (including antibiotic resistant isolates) was assessed by optical density, and viability by Miles Misra. Monocyte derived macrophages (MDMs) were treated with GaPP before/after NTHi exposure. Viable intracellular NTHi was assessed by gentamicin protection assay. GaN or GaPP was added to NTHi cultures prior to culture with MDMs. Cytokine gene expression (qPCR) and protein secretion (ELISA) were measured.
NTHi growth and viability were reduced by GaPP but not GaN. GaPP inhibited growth of COPD isolates (4μM 87% reduction). GaPP reduced intracellular viability of NTHi in macrophage infection models. MDM cytokine gene expression and protein secretion (TNF-α, IL-6 and CXCL8) in response to NTHi was reduced (82, 66 and 86% for gene expression) when cultured with GaPP 4μM.
GaPP is an effective antimicrobial for NTHi while GaN showed no effect on growth or viability. Culture of NTHi with GaPP also reduced the pro-inflammatory cytokine response in MDMs.
GaPP is an effective antimicrobial for NTHi while GaN showed no effect on growth or viability. Culture of NTHi with GaPP also reduced the pro-inflammatory cytokine response in MDMs.
Characterise how changes in chest compression depth and rate affect variations in end-tidal CO
(ETCO
) during manual cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA).
Retrospective analysis of adult OHCA monitor-defibrillator recordings having concurrent capnogram, compression depth, transthoracic impedance and ECG, and with atleast 1,000 compressions. Within each patient, during no spontaneous circulation, nearby segments with changes in chest compression depth and rate were identified. Average ETCO
within each segment was standardised to compensate for ventilation rate variability. Contributions of relative variations in depth and rate to relative variations in standardised ETCO
were characterised using linear and non-linear models. Normalisation between paired segments removed intra and inter-patient variation and made coefficients of the model independent of the scale of measurement and therefore directly comparable.
A total of 394 pairs of segments from 221 patienndardised, variation in chest compression depth explained variations in ETCO2 better than variation in chest compression rate.
The use of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrests (OHCA) has increased dramatically over the past decade. ECPR is resource intensive and costly, presenting challenges for policymakers. We sought to review the cost-effectiveness of ECPR compared with conventional cardiopulmonary resuscitation (CCPR) in OHCA.
We searched Medline, Embase, Tufts CEA registry and NHS EED databases from database inception to 2021 or 2015 for NHS EED. Cochrane Covidence was used to screen and assess studies. Data on costs, effects and cost-effectiveness of included studies were extracted by two independent reviewers. Costs were converted to USD using purchasing power parities (OECD, 2022).
The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist (Husereau et al., 2022)
was used for reporting quality and completeness of cost-effectiveness studies; the review was registered on PROSPERO, and reported according to the Preferred Reporting Items for Systemary models.A large part of the world's agricultural production, despite its adverse effects on human health and water resources, depends on the use of pesticides. Despite strict regulations, the use of pesticides continues around the world. This study aimed to determine the residual concentrations of malathion and diazinon in samples of drinking water resources. To achieve this goal, 384 samples from 8 various sites from January to December 2020 were analyzed using gas chromatography (GC) with an electron capture detector (ECD) and liquid-liquid extraction technique. Besides, statistical analysis and a risk-modeling approach supported by an automatic Monte-Carlo procedure were applied. The results showed that there is a high carcinogenic risk regarding malathion and that the low age population is at the most non-carcinogenic risk regarding diazinon.