Cerebral Hemorrhage ; complications ; Child ; Humans ; Intussusception ; complications ; Male ; Purpura, Schoenlein-Henoch ; complications

The oil content and fatty acid composition of Ganoderma lucidum collected from different producing areas, varieties, tissue types and growth periods were measured and analyzed. The results showed that the oil content was 23. 61%-34.17% in different domestic producing areas of China; the oil content of fruiting bodies from major varieties cultured in Zhejiang province were 0.81%-1.87%, wall-unbroken spores were 0.07%-0.24%, wall-broken spores were 27.54%-34.17%, so the oil content of wall-unbroken spores were much higher than fruiting bodies, and wall-breaking treatment would increase the oil extraction rate 150-340 times. G. lucidum spores oil was mainly composed of unsaturated fatty acid composition. oleic acid and linoleic content were 53.26%-58.16% and 10.69%-16.87% respectively. Fatty acid composition ratio of spores and fruiting bodies were significantly different by PLS-DA. Determining the composition of fatty acid, especially the content of oleic acid, stearic acid and palmitic acid, could identify the tissue types of G. lucidum products' sources. In addition, the study result showed that the spores and fruiting bodies collected in the first year contained richer oil and fatty acid than second year's samples from the same variety of G. lucidum.
Fatty Acids ; analysis ; Oils ; analysis ; Reishi ; chemistry

Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history

Objective To determine the correlation of plasma brain natriuretic peptide(BNP) with severe degree of dilated cardiomyopathy in children.Methods Thirty children with dilated cardiomyopathy and 30 healthy subjects were selected in this degree of study, plasma BNP concentration was measured and compared among groups by using t test.Correlation of BNP levels with left ventricular ejection fraction and heart function was investigated using linear regression analysis.Results Children with dilated cardiomyopathy had significantly higher mean BNP levels compared with healthy children [(429.4?270.2) ng/L vs (67.0?10.2) ng/L].Significantly positive correlations were found between BNP and heart classification(r=0.950 P

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.

Transmembrane serine protease 2 (TMPRSS2) is a cell surface protease widely present in the human body. It is involved in the infection of various viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the cell invasion, tumor growth and metastasis processes of prostate cancer. This study used Boc-Gln-Ala-Arg-AMC as the fluorescent substrate to determine the cleavage activity of TMPRSS2 towards SARS-CoV-2 S protein. Then cell-based screening model for TMPRSS2 inhibitors was established in Vero E6 cells overexpressing TMPRSS2 (Vero E6/TMPRSS2). Seven compounds exhibiting TMPRSS2 inhibitory activities with low toxicity were obtained through high-throughput screening (HTS) from natural and synthetic compound pure product library of National Center for Screening Novel Microbial Drugs. Surface plasmon resonance (SPR) has shown that the obtained inhibitors could bind to TMPRSS2 with moderate affinity in a dose dependent manner. Cell-cell fusion experiments have shown that the obtained inhibitors can inhibit the occurrence of S protein mediated cell-cell fusion by inhibiting TMPRSS2 cleavage of SARS-CoV-2 S protein in a concentration dependent manner. Preliminary pseudovirus experiment showed that the inhibitors may reduce the pseudovirus infection into Opti-HEK-293T-ACE2 cells to varying degrees. In a word, this study successfully established a cell-based HTS model for TMPRSS2 inhibitor and preliminarily confirmed that the seven screened inhibitors possessed in vitro anti-TMPRSS2 activities, providing new structural scaffolds for the development of new drugs against SARS-CoV-2.

OBJECTIVETo examine the efficacy of Muscovite on acetic acid-induced ulcerative colitis in rats, and to research the mechanisms of intestinal mucosal protection.

METHODUlcerative colitis was induced in rats by intracolonic injection of 2 mL of 7% acetic acid. Rats were treated with three different doses of the Muscovite and SASP at random by intracolonic injecion, the normal saline was considered as control group. The rats were sacrificed and the colons were excised and opened longitudinally. Under a dissecting microscope, gross findings were observed and scored. MPO activity was assayed by spectrophotometry in colonic mucosa.

RESULTGross finding showed that multiple ulcer with diameter more than 1 cm, surrounded with erosion, erythematous and edema in the proximal colon in ulcerative coltis. The colon from Muscovite treatment group were histopatholgically normal, with slight erosion, erythematous and edema. The colon in SASP group had small ulceration and severe erosion and edema. The score of gloss change were significant lower in Muscovite groups than that in normal saline group (P < 0.01). There were necrosis and exfoliation of mucosa, multiple cystic dilation of mucosa gland, and large number of and inflammation attenuated in Muscovite groups. There nerutrophils and vessel infiltration in ulcerative colitis. The ulceration disappeared were erosion in mucosa and inflammatory cell infiltrating into submucosa in SASP group. Compared with normal saline group, the pathological scale were significant decreased in Muscovite and SASP groups (P < 0.05). The MPO activity was significant increased in colitis tissue compared with normal group (P < 0.001). After administrating with Muscovite or SASP, the level of MPO were significant decreased (P < 0.01).

CONCLUSIONMuscovite has the effect of mucosal protection by attenuating the inflammation of colonic mucosa and decreasing the activity of MPO.

Acetic Acid ; Aluminum Silicates ; pharmacology ; Animals ; Colitis, Ulcerative ; chemically induced ; enzymology ; pathology ; Colon ; enzymology ; pathology ; Intestinal Mucosa ; enzymology ; pathology ; Male ; Materia Medica ; pharmacology ; Peroxidase ; metabolism ; Protective Agents ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Drug Screening Assays, Antitumor ; methods ; G1 Phase ; High-Throughput Screening Assays ; methods ; Humans ; Mice ; NIMA-Interacting Peptidylprolyl Isomerase ; Neoplasms ; pathology ; Peptidylprolyl Isomerase ; antagonists & inhibitors ; Temperature ; Xenograft Model Antitumor Assays ; Yeasts

OBJECTIVETo evaluate the efficacy and safety of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules in treatment of irritable bowel syndrome.

METHODSEighty-five patients [male 32, female 53; age (45.31+/-11.72) years] were given live combined Bifidobacterium, Lactobacillus and Enterococcus capsules 1260 mg/d t.i.d.x4 weeks. Syndrome scales were used to evaluate the efficacy in gastrointestinal syndrome. Fecal flora was also measured before and after the treatment. Six bacteria were cultured and the colony forming units were counted in stool. SPSS was used for data analysis.

RESULTSSeventy-four patients finished the follow-up. No side-effect was found. For treatment of irritable bowel syndrome, the effective rate of live combined Bifidobacterium, Lactobacillus and Enterococcus capsules was 56.8% in the second week, 74.3% in the fourth week and 73.0% in the sixth week. Single symptom was improved, especially in abdominal pain and stool character. The probiotica containing live combined Bifidobacterium, Lactobacillus and Enterococcus could increase bifidobacterium count (P<0.01) and lactobacillus count (P<0.05); decrease bacteroides count (P<0.05) and enterococci count (P<0.01); No obvious changes were observed in clostridium difficile colonitis and enterobacteriaceae (P>0.05).

CONCLUSIONThe result of the study indicated that the administration of live combined Bifidobacterium, Lactobacillus and Enterococcus improved the symptom of irritable bowel syndrome and that there was a gradual increase of this effect. Thereafter conditions remained stable for 2 weeks. That improvement may be associated with alterations in gastrointestinal flora.

Adult ; Bifidobacterium ; Enterococcus ; Female ; Humans ; Intestines ; microbiology ; Irritable Bowel Syndrome ; drug therapy ; Lactobacillus ; Male ; Middle Aged ; Probiotics ; therapeutic use

The purpose of this study was to investigate the influence of electrical stimulation of anterior cingulate cortex (ACC) on spontaneous activity of neurons in thalamic ventrobasal nucleus (VB). Experiments were performed on 12 male Sprague-Dawley rats weighing 250-310 g (4-5 months old). According to Paxinos and Watson's coordinate atlas of the rat, the frontal and parietal cortical areas were exposed by craniotomy, the recording electrodes were then inserted into the VB (P 2.4-4.1 mm, R 2.0-3.5 mm, H 5.2-6.8 mm) and the stimulating electrodes into the ACC (A 1.1-3.0 mm, R 0.0-1.0 mm, H 1.5-2.4 mm). Single-unit activities were recorded extracellularly in the VB by glass micropipettes (impedance 3-8 MOmega) filled with 0.5 mol/L sodium acetate solution containing saturated Fast Green. To study the effects of ACC activation on the spontaneous activities of VB cells, single electrical pulse (0.2 ms duration) was delivered to the ACC by a concentric bipolar stainless steel electrode (0.32 mm outer diameter). An effective ACC stimulation was determined for each VB neuron by gradually increasing the current intensity from 0.1 mA until either a significant change in the spontaneous activity of the VB neuron was observed, or the current intensity reached 0.4 mA. The results showed that ACC stimulation significantly suppressed the spontaneous activities in 12 out of 53 VB neurons (22.6%). (1) After the stimulation was delivered to ACC, the spontaneous activities of different VB neurons were totally suppressed for different time span. (2) There was obvious dose-effect relevance between ACC stimulation intensity and their inhibitory effect. The duration of complete inhibition was prolonged with the increases in the intensity and number of stimulation impulses in ACC. (3) The stimulation in the ACC depressed the spontaneous activities of VB neurons in different forms and this inhibition exhibited an accumulative effect. All these results indicate that the stimulation of ACC exerts an inhibitory influence on the spontaneous activities of VB neurons.
Animals ; Electric Stimulation ; Gyrus Cinguli ; physiology ; Male ; Neurons ; cytology ; Rats ; Rats, Sprague-Dawley ; Thalamic Nuclei ; cytology