Abdominal Pain ; etiology ; Acute Disease ; Adult ; Atropine ; therapeutic use ; Chemical and Drug Induced Liver Injury ; etiology ; therapy ; Diarrhea ; etiology ; Fatal Outcome ; Female ; Humans ; Male ; Middle Aged ; Multiple Organ Failure ; etiology ; Muscarinic Antagonists ; therapeutic use ; Mushroom Poisoning ; complications ; therapy

OBJECTIVETo quantitatively evaluate mutual relations of 4 component drugs in anti-HIV action.

METHODSThe effect of TCM four components on cell growth was detected using MTT assay. The antiviral effects of 4 components were observed at the maximal nonvenomous dose. The combination index (CI) value of combined two or four components were calculated using median-effect principle. The mutual relations of two or four components for antiviral actions were assessed using CI.

RESULTSSynergism was dominant in combination of A and B, and the effect was dose-dependent. Antagonism was dominant in combination of C and D, and the effect was dose-dependent. But the combination of A, B, C, and D was synergistic when the inhibition rate was over 10%.

CONCLUSIONMedian-effect principle can be used to quantitatively assess the anti-HIV effect of four components.

Antiviral Agents ; administration & dosage ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Drug Antagonism ; Drug Synergism ; HIV-1 ; drug effects ; Humans

BACKGROUNDNurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.

METHODSThe mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.

RESULTSThe relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).

CONCLUSIONSDA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

Adult ; Aged ; Aged, 80 and over ; Dopamine Agonists ; therapeutic use ; Female ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Middle Aged ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; genetics ; Parkinson Disease ; drug therapy ; genetics ; RNA, Messenger ; genetics ; Young Adult

HIV/AIDS patients in high prevalence areas with different routes of infection (sexually transmitted 878 cases, 527 cases of intravenous drug user, paid blood donor 652 cases) were choosen for traditional Chinese medicine (TCM) syndrome investigation for one-year clinical follow-up. This paper primarily concluded the nature, location and pathogenesis of AIDS diseases. Deficiency of Yang and Yin, combining deficiency of Qi are the basic deficiency syndromes, while stagnation of dampness, toxic fire are the excess syndromes; the disease location of HIV infector is spleen, main syndrome is deficiency of spleen Qi; the disease location of AIDS patient is kidney, main syndrome is deficiency of spleen and kidney Yang. The pathogenic development tendency is from deficiency of Qi to combining stagnation of dampness and toxic fire, finally to deficiency of Qi and Yin, deficiency of Yang.
Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; HIV Infections ; diagnosis ; etiology ; transmission ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Young Adult

Chemical constituents were isolated and purified from fruiting bodies of Ganoderma calidophilum by various column chromatographic techniques, and their chemical structures were identified through combined analysis of physicochemical properties and spectral data. As a result, 11 compounds were isolated and identified as(24E)-lanosta-8,24-dien-3,11-dione-26-al(1), ganoderone A(2), 3-oxo-15α-acetoxy-lanosta-7,9(11), 24-trien-26-oleic acid(3),(23E)-27-nor-lanosta-8,23-diene-3,7,25-trione(4), ganodecanone B(5), ganoderic aldehyde A(6), 11β-hydroxy-lucidadiol(7), 3,4-dihydroxyacetophenone(8), methyl gentiate(9), ganoleucin C(10), ganotheaecolumol H(11). Among them, compound 1 is a new triterpenoid. The cytotoxic activities of all of the compounds against tumor cell lines were evaluated. The results showed that compounds 1, 3, 4 and 6 showed cytotoxic activity against BEL-7402, with IC_(50) values of 26.55, 11.35, 23.23, 18.66 μmol·L~(-1); compounds 1 and 3-6 showed cytotoxic activity against K562, with IC_(50) values of 5.79, 22.16, 12.16, 35.32, and 5.59 μmol·L~(-1), and compound 4 showed cytotoxic activity against A549, with IC_(50) value of 42.50 μmol·L~(-1).
Cell Line, Tumor ; Fruiting Bodies, Fungal ; Ganoderma ; Molecular Structure ; Triterpenes/pharmacology*

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become one major threat to human population health. The RNA-dependent RNA polymerase (RdRp) presents an ideal target of antivirals, whereas nucleoside analogs inhibitor is hindered by the proofreading activity of coronavirus. Herein, we report that corilagin (RAI-S-37) as a non-nucleoside inhibitor of SARS-CoV-2 RdRp, binds directly to RdRp, effectively inhibits the polymerase activity in both cell-free and cell-based assays, fully resists the proofreading activity and potently inhibits SARS-CoV-2 infection with a low 50% effective concentration (EC