Early-stage infective endocarditis (IE) can lead to severe complications, including infarctions and metastatic infections caused by inflammatory embolus shedding. Common embolism sites include the brain, spleen, kidneys, lungs, and intestines. Additionally, acute heart failure (AHF) can occur in up to 40% of cases, and its presence can impact the clinical outcomes of patients with IE. Cardiogenic shock (CGS) is often more likely to occur after AHF has taken place. If bacteria invade the blood, infectious shock can occur. Patients with IE can experience simple CGS, septic shock, or a combination of the two. Extracorporeal membrane oxygenation (ECMO) typically serves as a Bridge for Heart failure and Cardiogenic shock. Previous research indicates that there are limited reports of ECMO support for patients with IE after CGS has occurred. Because CGS may occur at any time during IE treatment, it is important to understand the timing of ECMO auxiliary support and how to carry out comprehensive treatment after support. Timely treatment can help to reduce or avoid the occurrence of serious complications and improve the prognosis of patients with IE. Our work combines a case study to review the ECMO support of IE patients after CGS through a literature review. Overall, we suggest that when patients with IE have large bacterial thrombosis and a greater risk of shedding, it is recommended to carefully evaluate the indications and contraindications for ECMO after discussion by a multidisciplinary team (MDT). Still, active surgical treatment at an early stage is recommended.
To evaluate the efficacy of antioxidants in the treatment of non-alcoholic fatty liver.The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE or PUBMED (1978-2011), EMBASE (1978-2011), ISI, OVID Database (1978-2011), CNKI Net and WANFANG database (1978-2011) were searched for relevant randomized controlled trials, with also manual search of the bibliographies of the retrieved articles. The data were synthesized to assess the histological response of the patients (hepatic steatosis, inflammation and fibrosis) and hepatic biochemical changes after the treatments (alanine aminotransferase responses).Fourteen trials involving 1284 patients were included in the Meta-analysis. The quality of the trials was inconsistent. The data were extracted for meta-analysis or descriptive analysis, which did not yield sufficient evidence that antioxidants could improve hepatic steatosis, inflammation, fibrosis or alanine aminotransferase responses.The current data do not support a positive therapeutic effect of antioxidants on nonalcoholic fatty liver, and antioxidants are therefore not recommended in the clinical treatment of the condition.
Autophagy is a process that degrades endogenous cellular protein aggregates and damaged organelles via the lysosomal pathway to maintain cellular homeostasis and energy production. Baseline autophagy in the kidney, which serves as a quality control system, is essential for cellular metabolism and organelle homeostasis. Renal fibrosis is the ultimate pathological manifestation of progressive chronic kidney disease. In several experimental models of renal fibrosis, different time points, stimulus intensities, factors, and molecular mechanisms mediating the upregulation or downregulation of autophagy may have different effects on renal fibrosis. Autophagy occurring in a single lesion may also exert several distinct biological effects on renal fibrosis. Thus, whether autophagy prevents or facilitates renal fibrosis remains a complex and challenging question. This review explores the different effects of the dual regulatory function of autophagy on renal fibrosis in different renal fibrosis models, providing ideas for future work in related basic and clinical research.
At present, the treatment of intracerebral hemorrhage (ICH)-induced secondary brain injury (ISB) is limited, and the curative effect is not good. Long noncoding RNAs (lncRNAs) have been reported to play a role in ISB after ICH. We preliminarily monitored the induction effect of lncRNA-pseudopodium-enriched atypical kinase 1 (PEAK1) on neuronal cell apoptosis after ICH through our previous study and further experimental verification. However, the specific role and mechanism of lncRNA-PEAK1 in neuronal cell apoptosis after ICH have not been reported.ICH cell models were established with hemin. Pro-inflammatory cytokines, cell proliferation, and apoptosis were evaluated by enzyme-linked immunosorbent assay, Cell Counting Kit-8 assay, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Moreover, lncRNA expression associated with apoptosis was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological functions of lncRNA-PEAK1, miR-466i-5p, and caspase8 were conducted in vitro. Further, we used bioinformatics, a dual-luciferase reporter assay, and rescue experiments to understand the mechanisms of competitive endogenous RNAs.qRT-PCR revealed that lncRNA-PEAK1 was markedly upregulated in ICH cell models. LncRNA-PEAK1 knockdown decreased the interleukin-1β and tumor necrosis factor-alpha levels, promoted cell proliferation, weakened cell apoptosis, and downregulated the key molecular protein levels involved in the cell apoptosis pathway. Bioinformatics analysis and dual-luciferase reporter assay revealed that lncRNA bound to miR-466i-5p, and caspase 8 was a target of miR-466i-5p. The mechanistic analysis demonstrated that lncRNA-PEAK1/miR-466i-5p promoted neuronal cell apoptosis by activating the apoptosis pathway through caspase8 after ICH.Collectively, our investigation identified that the lncRNA-PEAK1/miR-446i-5p/caspase8 axis is closely related to neuronal cell apoptosis after ICH. Additionally, lncRNA-PEAK1 may be a potential target for ICH intervention.
Ethyl piperate is an effective lipid-lowering drug candidate synthesized from piperine. However, its pharmacokinetic characteristics and oral absorption process remain unclear. A liquid chromatography-tandem mass spectrometry method was applied to determine the oral bioavailability of ethyl piperate. Simulated gastrointestinal pH conditions and intestinal washings were prepared to investigate their contributions to the loss of ethyl piperate. Hydrolysis by carboxylesterase (CES) was evaluated in vitro using microsomes and S9 fractions. In situ intestinal single-pass perfusion experiments were performed to estimate the role of CES in ethyl piperate absorption. The bioavailability of ethyl piperate was extremely low (0.47%) in hamster independent of gastrointestinal environmental effects. Ethyl piperate was a typical substrate of CES with kinetic parameters Km and Vmax of 7.56 ± 1.491 μM and 0.16 ± 0.008 nmol · min−1 · mg protein−1, respectively. CES was responsible for 85.8% of the intestinal hydrolysis of ethyl piperate. Specific inhibition of CES with bis-p-nitrophenyl phosphate (BNPP), decreased degradation clearance to 36% of control with no significant change in absorption clearance. This contrasted with the results of Caco-2 monolayer experiments, which showed a dramatic increase in the apparent permeability coefficient after BNPP treatment. mRNA levels for the CES isozyme, CES2A3, were similar among the three regions of hamster intestine and 60% less than those in liver; CES1B1 mRNA levels were even lower in the intestine and showed a proximal-to-distal decrease. In conclusion, CES markedly contributes to intestinal first-pass hydrolysis of ethyl piperate that is sufficient, but not necessary, to cause the observed extremely low bioavailability.
Co-delivery of a Pt(iv) prodrug and a p53 activator using layered double hydroxide (LDH) nanoparticles results in a significantly improved cell-killing effect.
Emerging research into metabolic dysfunction-associated steatotic liver disease (MASLD) up until January 2024 has highlighted the critical role of cuproptosis, a unique cell death mechanism triggered by copper overload, in the disease's development. This connection offers new insights into MASLD's complex pathogenesis, pointing to copper accumulation as a key factor that disrupts lipid metabolism and insulin sensitivity. The identification of cuproptosis as a significant contributor to MASLD underscores the potential for targeting copper-mediated pathways for novel therapeutic approaches. This promising avenue suggests that managing copper levels could mitigate MASLD progression, offering a fresh perspective on treatment strategies. Further investigations into how cuproptosis influences MASLD are essential for unraveling the detailed mechanisms at play and for identifying effective interventions. The focus on copper's role in liver health opens up the possibility of developing targeted therapies that address the underlying causes of MASLD, moving beyond symptomatic treatment to tackle the root of the problem. The exploration of cuproptosis in the context of MASLD exemplifies the importance of understanding metal homeostasis in metabolic diseases and represents a significant step forward in the quest for more effective treatments. This research direction lights path for innovative MASLD management and reversal.
Objective
To identify Mycobacterium abscessus rapidly with HAIN molecular assay genotype kit、gene chip and hsp65 gene sequencing, and to assess the clinical value of these three methods.
Methods
13 clinical non-tuberculous Mycobacterium (NTM) of in-patient samples were collected from January2014 to January 2015, in the Department of Clinical Laboratory, Yinzhou People′s Hospital, and meanwhile, these strains were identified with HAIN molecular assay genotype Mycobacterium kit and gene chip respectively. The hsp65 gene sequencing was used as the standard method to be compared with HAIN and gene chip.
Results
The results of HAIN kit and hsp65 gene sequencing showed that all the 13 strains were subspecies Mycobacterium abscessus, while that of gene chip showed that these strains were Mycobacteriumchelonae complex strains, and the subtypescould not be identified.
Conclusion
These results obtained from the HAIN molecular assay genotype mycobacterium system are in agreement with those obtained from the hsp65 gene sequencing, whereas the HAIN kit method is easier to use.(Chin J Lab Med, 2015, 38: 861-864)
Key words:
Nontuberculous mycobacteria; Genotype; Reagent kits, diagnostic; Heat-shock proteins; Oligonucleotide array sequence analysis
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