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

OBJECTIVETo observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.

METHODSThe UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.

RESULTSCompared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).

CONCLUSIONTreatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.

Animals ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Intestinal Mucosa ; metabolism ; Intestines ; Lung ; Male ; Rabbits ; Rats ; Vasoactive Intestinal Peptide