Cardiovascular Diseases ; Growth Differentiation Factor 15 ; Humans

BACKGROUND: Coffee is commonly consumed among young people in China. However, consumers are rarely aware of physicaly adverse effects as a result of excessive consumption of caffeine. DATA SOURCES: A literature search using multiple databases was performed for articles published with concentration on meta-analyses, systematic reviews, and randomized controlled trials. RESULTS: Excess coffee consumption is also a risk of primary cardiac arrest especially in young people. Treatment modalities include activated charcoals, beta-blockers, vasopressin and hemodialysis when necessary. CONCLUSION: Coffee consumers should be advised not to routinely take more than moderate coffee.

Adult ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; HIV Enteropathy ; complications ; metabolism ; microbiology ; pathology ; Humans ; Male ; Mycobacterium avium Complex ; isolation & purification ; Mycobacterium avium-intracellulare Infection ; complications ; metabolism ; microbiology ; pathology ; Young Adult

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

To detect the effect of PDZ1, domain of postsynaptic density 95 (PSD-95), on apoptosis of hippocampal neurons induced by oxygen-glucose deprivation (OGD), Sprague-Dawley rat hippocampal neurons were infected with PDZ1-viruses after 21 days of plating. Twenty-four hours after infection, cells were treated with OGD for 1.5 h, then were incubated with DAPI and apoptosis-like cells were characterized, or were collected for co-immunoprecipitation and Western blot analyses. The results showed that: (1) PDZ1 overexpression was observed in hippocampal neurons; (2) Apoptosis induced by OGD was obviously decreased in neurons overexpressing PDZ1 (P<0.05); (3) Overexpression of PDZ1 prevented the binding of GluR6 to PSD-95; (4) Overexpression of PDZ1 inhibited MLK3 and JNK1/2 activation induced by OGD. These results indicate that overexpression of PDZ1 may prevent hippocampal neurons from apoptosis induced by OGD.
Animals ; Apoptosis ; Cells, Cultured ; Culture Media ; chemistry ; Disks Large Homolog 4 Protein ; Glucose ; chemistry ; Hippocampus ; cytology ; Intracellular Signaling Peptides and Proteins ; metabolism ; Membrane Proteins ; metabolism ; Neurons ; cytology ; pathology ; Oxygen ; chemistry ; PDZ Domains ; Rats ; Rats, Sprague-Dawley

Abstract: Toxoplasma gondii, an opportunistic pathogenic protozoan, is widely distributed worldwide and can cause zoonoses, which is a serious threat to human health. Nowadays, the relationship between T. gondii infection and neuropsychiatric diseases has attracted researchers' attention increasingly. T. gondii infection is related to the pathogenesis of many neuropsychiatric diseases by affecting the nervous system, such as schizophrenia, depression, Alzheimer's disease, and so on. This review will focus on the relationship between T. gondii infection and neuropsychiatric diseases and summarizes the possible mechanisms of disorders resulting from T. gondii infection． It is expected that the study on the related pathogenic mechanism of T. gondii will lead to new therapeutic directions and feasible solution for the clinical treatment of neuropsychiatric diseases caused by T. gondii infection.

Erectile dysfunction is common complication of diabetes mellitus. The incidence of diabetes mellitus induced erectile dysfunction (DMED) is 20% - 75%. DMED appears to be due to vascular-neuropathic and corpus cavernosum smooth muscular damage. To control blood glucose, blood pressure and blood lipids is the basis of DMED therapy. In 50% of the patients with DMED, the phosphodiesterase 5 inhibitors is effective, while intracavernous pharmacotherapy is effective for more than 90%. Penile prosthesis implantation continues to be the treatment of choice in case of other therapy failure.
Animals ; Diabetes Complications ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; Erectile Dysfunction ; epidemiology ; pathology ; therapy ; Humans ; Male ; Rabbits ; Rats

No abstract available.
Amyotrophic Lateral Sclerosis* ; Charcot-Marie-Tooth Disease* ; China* ; Pedigree*

In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.
Adaptor Proteins, Signal Transducing ; biosynthesis ; chemistry ; genetics ; metabolism ; Cell Aggregation ; genetics ; GPI-Linked Proteins ; metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; HSC70 Heat-Shock Proteins ; genetics ; metabolism ; Heat-Shock Response ; genetics ; Humans ; Interferon Regulatory Factor-3 ; genetics ; metabolism ; Interferon-beta ; genetics ; NF-kappa B ; genetics ; Prions ; metabolism ; Receptors, Retinoic Acid ; metabolism ; Viruses ; drug effects ; metabolism ; pathogenicity

Objective To investigate the accuracy and efficiency of hand-held echocardiography (VSCAN) used by intensivist for the diagnosis and treatment decisions in emergency consultation for patients getting worse at risk of life-threatening setting in non-ICU ward.Methods A prospective study in acutely deteriorated patients needed the intensivist for emergency consultation in general wards was carried out.The consultation process was executed as follows:(1) The intensivist established an initial diagnosis based on medical history,physical examination and laboratory findings,and assessed the hemodynamics and the cause of acute respiratory failure and cardiac arrest according the documented information.The data recorded as control group (Pre-VSCAN) for comparison with the later available data in subsequent analysis.(2) Problem-based ultrasound examination was performed with VSCAN.For patients suffered cardiac arrest,the FEEL protocol was used to find the potential cause of cardiac arrest such as pericardial tamponade and massive pulmonary embolism screened.For the other patients,a simplified eFATE or BLUE-plus protocols were used based on clinical requirement.With the findings of ultrasound examination the intensivist established an final diagnosis and identified the hemodynamics and the lung pathologies.The consultation advice was then provided to the attending doctors of the patient.The intensivist kept the records of echo results,final diagnosis and consultation advice as data of study group data (Post-VSCAN).The response of the treatment and outcome were followed up.Two attending ICU doctors analyzed these data and judged the correctness of Pre-VSCAN and Post-VSCAN based on the response to treatment and the outcome.Results Ninety patients were finally included in statistical analysis.Sixteen (17.8％) cases,40 (44.4％) cases,29 (32.2％) cases and 5 (5.6％) were consulted for acute circulation dysfunction,acute respiratory failure,both reasons and cardiac arrest,respectively.Compared to pre-VSCAN,VSCAN verification can significantly improve the accuracy of the diagnosis (81.1％ vs.58.9％,P =0.001),assessment of hemodynamics (78.3％ vs.52.2％,P =0.009) and can find more accurate judgment of acute respiratory failure (71.0％ vs.43.5％,P =0.001).Conclusion The hand-held echocardiography used by intensivist is valuable for the diagnosis and the assessment of cardiopulmonary status in case of request for emergency consultation in general wards.