We designed and synthesized eighteen lycorine derivatives with five different structural types, and evaluated their antiviral activities on a HCoV-OC43-infected H460 cell model. Structure-activity relationships suggested that the introduction of appropriate substituents on the 6N atom of lycorine was beneficial to activity. Compound 6a gave a good activity with the half effective concentration (EC₅₀) and selectivity index (SI) values of 2.36 μmol·L^-1 and 16.52, respectively. Surface plasmon resonance (SPR) result indicated that 6a might target the non-structural protein 12 (NSP12) subunit in RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 with the dissociation constant (K_D) value of 1.36 μmol·L^-1. Molecular docking indicated that 6a might act on nidovirus RdRp-associated nucleotidyltransferase (NiRAN) catalytic center of NSP12, distinct from the mechanism of nucleoside-like drugs such as remdesivir. This study provides scientific data for the development of lycorine derivatives into a new class of anti-SARS-CoV-2 small molecule inhibitors.

Objective:To determine the expression profile and potential roles of CD24 in oral squamous cell carcinoma and explore the values of CD24 function as a potential target of clinical therapy.Me-thods:Semi-quantitative immunohistochemistry was used to construct the expression profile of CD24 in 78 human oral tissues and 59 Hamster buccal pouch tissues.Real-time RT-PCR and Western blot were used to analyze the CD24 expression levels in oral DOK4 cells,oral cancer CAL-27 and WSU-HN6 cells. Then these two cancer cell lines were selected to evaluate the effect of all-trans retinoic acid (ATRA)and CD24 antibody on CD24 expression,and the proliferation and tumorsphere formation capacity of these two cell lines.Results:CD24 expression was found significantly elevated in both human and animal tissues compared with normal and benign tissues (P<0.05),as well as in oral cancer CAL-27 and WSU-HN6 cells compared with DOK cells (P<0.05).CAL-27 and WSU-HN6 cells possess increased proliferative and specific tumorsphere formation capability compared with DOK cells (P<0.05 ).Both ATRA and CD24 antibody were able to effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells (P<0.05).Among them ATRA at least involved partially in the proliferation by down-regulating the CD24 expression (P<0.05 ),while CD24 antibody blocking had no effect on the CD24 expression.Conclusion:CD24 was upregulated in oral cancer and functioned as a potential factor that promoted the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells.Both ATRA and CD24 antibody might effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells and function as a potential therapy target.

The binding function of EGF1 domain peptide with tissue factor (TF) and its ability of triggering coagulation were explored. The TF expression model in vitro was established by lipopolysaccharide induction. The affinity of EGFP-EGF1 and TF expressing cells was analyzed by fluorescence microscopy and flow cytometry (FCM). The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface plasmon resonance (SPR). The ability of EGFP-EGF1 in triggering coagulation was tested by prothrombin time assay. The FCM results showed recombinant factor VII (rFVII) could definitely depress the integration of EGFP-EGF1 with recombinant TF (rTF) (68.65%+/-3.86% vs 57.98%+/-4.71%, P<0.01). The SPR results indicated the association constant ka of EGFP-EGF1 proteins was higher than rFVII (8.29+/-1.39 vs 3.75+/-0.32, P<0.01). However, the EGFP-EGF1 protein lost the activity of triggering coagulation as compared with blood plasma of normal SD rats (56.8+/-3.2 s vs 17.8+/-3.4 s, P<0.01). It was concluded that the rat EGF1 peptide could specifically bind to TF without the ability of triggering coagulation. EGF1 peptide may be a good target head for delivering drugs to TF in anticoagulation therapy.

This study examined the association of a common polymorphic allele (25G) of the low-density lipoprotein receptor-related protein1 (LRP1) gene with myocardial infarction (MI). The genotypes of LRP1 25CG (rs35282763) were determined in 347 MI patients and 347 age- and sex-frequency-matched controls from an unrelated Chinese Han population. Factor VIII (FVIII) levels were measured in the MI patients and controls by chromogenic assay and enzyme-linked immunosorbent assay (ELISA). The results showed that LRP1 25CG (rs35282763) genotype distribution did not differ significantly between patients (n=206 for 25CC, n=122 for 25CG) and controls (n=191 for 25CC, n=126 for 25CG; P>0.05). The 25G allele was not associated with a reduced risk of MI (P>0.05). Further stratifications for age, sex, and other cardiovascular risk factors did not affect the negative findings. It was concluded that the presence of the G allele at the 25CG (rs35282763) polymorphism of the LRP1 is not associated with a reduced risk of MI, and genotyping for LRP1 25CG (rs35282763) polymorphism is not useful in assessing the individual risk of MI.

A new eremophilane derivative, (3aR,4R,5S,7S,7aS)-2-acetyl-7,7a-dihydroxy-3a,4-dimethyl-3a,4,5,6,7,7a-hexahydro-3H-inden-5-yl acetate (1) and three known compounds, 10beta-hydroxy-eremophil-7 (11)-en-12,8alpha-olide(2), beta-sitosterol (3) and beta-daucosterol(4) have been isolated from Ligularia intermedia. The compounds were isolated by column chromatography on silica gel and Sephadex LH-20,and identified on the basis of spectral analyses (MS, 1H-NMR, 13C-NMR).
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Molecular Structure ; Naphthalenes ; chemistry ; isolation & purification ; Sesquiterpenes

Adult ; Benzene ; poisoning ; Chronic Disease ; Female ; Humans ; Occupational Diseases ; diagnosis

A new sesquiterpenoid, 8α-hydroxy-6β-methoxy-1-oxoeremophila-7 (11), 9 (10) -diene-12, 8-olide (1) and five known compounds, petasin (2), caffeic acid (3), hepta-cosanol (4), β-sitosterol (5) and β-daucosterol (6) have been isolated from the roots of Ligularia intermedia. The compounds were isolated by column chromatography on silica gel and Sephadex LH-20, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR).
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Magnetic Resonance Imaging ; Molecular Structure ; Plant Roots ; chemistry ; Spectrometry, Mass, Electrospray Ionization

OBJECTIVETo study the risk factors for capillary leak syndrome (CLS) in neonates.

METHODSThe clinical data of 52 neonates with CLS (case group) were retrospectively reviewed. Fifty hospitalized neonates without CLS were used as the control group. The possible factors for the development of CLS were identified by univariate analysis. The independent risk factors for CLS were determined by multivariate logistic regression analysis.

RESULTSThe univariate analysis showed that the incidences of hyperglycemia, respiratory distress syndrome (RDS), sepsis and cold injury syndrome in the case group were significantly higher than those in the control group (P<0.05). The logistic regression analysis showed that sepsis (OR=5.004, P=0.001), RDS (OR=3.880, P=0.013) and cold injury syndrome (OR=3.207, P=0.023) were the independent risk factors for the development of CLS.

CONCLUSIONSRDS, sepsis and cold injury syndrome are independent risk factors for CLS in neonates. Hyperglycemia may be associated with the development of CLS.

Capillary Leak Syndrome ; etiology ; Female ; Humans ; Infant, Newborn ; Male ; Retrospective Studies ; Risk Factors

OBJECTIVETo compare the efficacy difference on the treatment of supraspinal ligament injury in deficiency syndrome between only-puncturing at Dazhong (KI 4) and routine acupuncture therapy and then explore an optimum process.

METHODSOne hundred and twenty-six cases were randomly divided into a Dazhong group (63 cases) and a routine acupuncture group (63 cases). Based on the same treatment including TDP irradiation, cupping at Shenshu (BL 23), Dachangshu (BL 25), Mingmen (GV 4), Yaoyangguan (GV 3) and Ashi points, the patients in the Dazhong group received only-puncturing Dazhong (KI 4) with respiratory reinforcing method once daily or every other day, three times of which made a course of the treatment, with on interval of one day or without between different courses. For the routine acupuncture group, the same reinforcing method was applied at shenshu (BL 23) pointect, and the other requirements such as courses were also the same.

RESULTSThe cured and markedly effective rate was 88.9% (56/63) in the Dazhong group, which was significantly superior to that of 54.0% (34/63) in the routine acupuncture group (P < 0.01). Compared before and after the treatment, the score of Numerical Rating Scale (NRS) and the clinical symptom score of the two groups were significantly decreased (all PF < 0.01). Compared between the two groups, there were significant differences in NRS and clinical symptom score the Dazhong group was better than the routine acupuncture group (both P < 0.01).

CONCLUSIONThe only-puncturing Dazhong (KI 4) method combined with cupping and TDP irradiation are simple and effective for supraspinal ligament injury in deficiency syndrome.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Humans ; Ligaments ; injuries ; Male ; Middle Aged ; Treatment Outcome ; Young Adult