Nor-ursane triterpenes are formed by the reduction of one or several methyl groups on the ursane triterpene carbon skeleton. According to the position of vacant methyl, they can be divided into eight types, including 23-nor, 24-nor, 28-nor, 29-nor, 30-nor, 2-nor, 3-nor, and 3,24-nor. Moreover, nor-ursane triterpenes have several pharmacological effects such as anti-cancer, anti-inflammatory, anti-bacterial, inhibition of acyl cholesterol acyl transferase (ACAT) and so on. In this study, more than 30 relevant literatures of nor-ursane triterpenoid compounds at home and abroad were reviewed. The plant distribution, pharmacological activity and structural characteristics of nor-ursane triterpenes were studied. Therefore, this review may provide the basis for further study of this type of compound.

Five new megastigmanes (1-5) were isolated from a decoction of Uncaria rhynchophylla by separation techniques of column chromatography using a combination of multiple stationary phases, including macroporous adsorbent resin, MCI resin, silica gel, Sephadex LH-20, and Toyopearl HW-40F, and reversed phase HPLC. Their structures were characterized by spectroscopic data analysis of HR-ESI-MS, NMR, and CD, in combination with Mosher's mothed as well as ECD and NMR calculations. The new compounds were named uncarphyllonone A (1), uncarphyllonols A (2) and B (3), and uncarphabscisic acids A (4) and B (5). Although the structures of 3 and 4 were previously reported, the reported NMR spectroscopic data were incorrect or do not support the assigned structures in literatures. This is also the first report of discovery of new megastigmane natural products from the Uncaria genus.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

Objective To optimize the preparation of nanoparticles (NP) encapsulating antisense oligodeoxynucleotides (ASODN) and investigate the effects on inhibition of C6 glioma cells. Methods ASODN coated in NT were prepared by interfacial polymerization of butyleyanoacrylate (BCA). Inverted microscope was used to observe the viability of C6 cells transfected by free ASODN, ASODN in NP, ASODN-NP (ASODN sticking to NP) and BCA-NP, respectively. Cell cycle of C6 cells was studied by flow cytometry (FCM), and CCK-8 assay was performed to examine the cytotoxicity and proliferation of C6 cells. Results Compared with the control group, all groups, except BCA-NP group, after transfection with NPs appeared cell morphological changes; C6 cells were detached from the matrix, the cell density was reduced and the cell viability was poor; ASODN in NP group was most significant in a time-dependent manner. The cell cycle in ASODN-in-NP group varied obviously compared with the BCA-NP group, and the number of the cells in the GO/GI phase was increased and the cell number in S phase was decreased significantly (P<0.05). The results of CCK-8 assay showed that all groups, but BCA-NP group, produced the inhibition of the cell proliferation to different degrees, and the inhibitory effect was increased with the final concentration increment, especially remarkably in ASODN-in-NP group (P<0.05). Conclusion ASODN in NP can inhibit the proliferation and cause cell cycle changes of C6 cells effectively after transfected with ASODN in NP, exerting significantly growth inhibitory effect on C6 glioma cells.

OBJECTIVETo study the expression and the location of vascular cell adhesion molecule-1 (VCAM-1) gene and its clinical significance in human oral squamous cell carcinoma (OSCC).

METHODSIn situ hybridization, PV-9000 polymer detection system for immunohistochemical staining was used to detect the expression and the location of VCAM-1 mRNA and VCAM-1 protein in 48 cases of OSCC and 10 cases of normal controls. Statistical analysis was performed using chi-square test in SPSS 13.0.

RESULTSVCAM-1 protein was mainly expressed in tumor cell cytoplasm and membrane, VCAM-1 mRNA was mainly expressed in tumor cell cytoplasm. The expression rate of VCAM-1 mRNA and VCAM-1 protein was significantly higher in OSCC than that in normal oral mucosa (P<0.01). The expression of VCAM-1 mRNA was positively correlated with that of VCAM-1 protein (P<0.01). In the clinicopathologic factors, lymph node metastasis and depth of infiltration were closely correlated with VCAM-1 expression (P<0.01). The expression of VCAM-1 was significantly higher in tumor with lymph node metastasis than in tumor without lymph node metastasis (P<0.01).

CONCLUSIONOverexpression of VCAM-1 gene in OSCC may play a potential role in the development of OSCC. The overexpression of VCAM-1 gene in OSCC may be related to the tumor infiltration and metastasis.

OBJECTIVETo investigate the effects of neuropeptide Y (NPY) Y1 receptor antagonist PD160170 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and accelerating healing of femoral defect in rats.

METHODSThe third generation of rat BMSCs were treated with PBS (control) or 10, 10, or 10 mol/L NPY Y1 receptor antagonist PD160170. After 7 and 14 days of treatment, the cells were examined for osteogenic differentiation with alkaline phosphatase (ALP) and alizarin red staining. At 7 and 21 days of treatment, the mRNA and protein expressions of collagen type I (COLI), osteocalcin (OCN) and Runt-related transcription factor 2 (Runx2) in the cells were detected using q-PCR and Westem Blotting. In a male SD rat model (body weight 300∓20 g) of bilateral femoral condyle defects (2.5 mm in diameter), the effect of daily local injection of 0.2 mL PD160170 (10 and 10 mol/L, for 28 consecutive days) in promoting bone defect repair was evaluated with micro-CT scans.

RESULTSALP and alizarin red staining showed that the BMSCs treated with PD160170, at the optimal concentration of 10 mol/L, contained more intracellular cytoplasmic brown particles and mineralized nodules in extracellular matrix than PBS-treated cells. PD160170 (10 mol/L) significantly up-regulated the mRNA and protein expressions of COLI at day 7 and those of OCN and Runx2 at day 21 (P<0.05). In the rat models of femoral bone defect, the volume/tissue volume ratio, bone mineral density and the number of bone trabeculae were significantly greater in 10 mol/L PD160170 group than in the control group (P<0.05), but the bone trabecular thickness (P=0.07) and bone volume (P=0.35) were similar between the two groups.

CONCLUSIONNPY Y1 receptor antagonist PD160170 can promote osteogenic differentiation of BMSCs and healing of femoral defects in rats, suggesting the potential of therapeutic strategies targeting NPY Y1 receptor signaling in the prevention and treatment of bone fracture and osteoporosis.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most important swine diseases worldwide. In the present study, a new virulent strain of PRRS virus (PRRSV), GDsg, was isolated in Guangdong province, China, and caused high fever, high morbidity, and high mortality in sows and piglets. The genome of this new strain was 15,413 nucleotides (nt) long, and comparative analysis revealed that GDsg shared 82.4% to 94% identity with type 2 PRRSV strains, but only 61.5% identity with type 1 PRRSV Lelystad virus strain. Phylogenetic analysis indicated that type 2 PRRSV isolates include five subgenotypes (I, II, III, IV, and V), which are represented by NADC30, VR-2332, GM2, CH-1a, and HuN4, respectively. Moreover, GDsg belongs to a newly emerging type 2 PRRSV subgenotype III. More interestingly, the newly isolated GDsg strain has multiple discontinuous nt deletions, 131 (19 + 18 + 94) at position 1404–1540 and a 107 nt insertion in the NSP2 region. Most importantly, the GDsg strain was identified as a virus recombined between low pathogenic field strain QYYZ and vaccine strain JXA1-P80. In conclusion, a new independent subgenotype and recombinant PRRSV strain has emerged in China and could be a new threat to the swine industry of China.
China ; Fever ; Genome ; Mortality ; Nucleotides ; Porcine Reproductive and Respiratory Syndrome ; Porcine respiratory and reproductive syndrome virus ; Swine ; Swine Diseases

Objective To establish a suitable exponential smoothing prediction model for school absentees due to illness, to discuss its application value for predicting school absences due to illness, and to provide a basis for early warning of absence due to illness. Methods Numbers of schools absences by year and month due to illness in 30 primary schools from November 2015 to June 2017 were collected from symptom monitoring system of border county, southern Yunnan and Simple seasonal model, Winters addition model and Winters multiplication model were used to build simulation. The data of July 2017 to December 2017 were used for model validation. The three models were overall compared and evaluated through indicator analysis, statistical analysis and residual diagram analysis. The best model was selected to predict school absences due to illness from January 2018 to March 2018. Results Simple seasonal model, Winters addition model and Winters multiplication model were used to fit the variation trend of number of school absences due to illness in time series. The root mean square error (RMSE) of three models were 445.11, 420.99 and 258.75; R2adj were 0.72, 0.72 and 0.77; R2 were 0.92, 0.93 and 0.98; P values of Ljung-Box Q were 0.54, 0.43 and 0.21. As for prediction method linear trend, Alpha were 0.999, 1.000 and 0.298. The average relative error between predicted value and actual value was 9.62%, 21.90% and 7.52%. Conclusion Winters multiplication model has practical value to predict school absence due to illness and provide scientific basis for early identification of abnormal signals.

AIM: To investigate the effect of the expression of miR-375 on the proliferation and invasion of choroidal melanoma(CM)MUM-2B cells.METHODS: MUM-2B cells were cultured and were transfected with miR-375 mimic sequence(mimic group), miR-375 inhibitor sequence(inhibitor group), negative control group and no treatment(blank group). The qRT-PCR, CCK-8, apoptosis and Transwell experiments were used respectively to detect the expression of miR-375, cell proliferation activity, apoptosis, cell migration and invasion.RESULTS: Compared with the negative control group(1.01±0.10)and the blank group(1.03±0.07), the expression level of miR-375 in the cells of the mimic group(2.65±0.15)was increased, while the expression level of miR-375 in the cells of the inhibitor group(0.28±0.06)was decreased(P<0.05). Compared with the blank group and negative control group, the OD values of the cells in the mimic group at 24, 48, 72, and 96h were decreased(P<0.05), while the OD values of the cells in the inhibitor group at 24, 48, 72, and 96h were increased(P<0.05). Compared with the apoptosis rates in the blank group and negative control group, which were(20.54±4.01)% and(22.80±4.28)%, the apoptosis rate in the mimic group(39.11±3.37)% was increased(P<0.05), while it was decreased in the inhibitor group(10.13±2.17)%(P<0.05). Compared with the blank group and negative control group, the number of migration cell and the number of invasion cell in the mimic group were decreased(P<0.05), while the number of migration cell and the number of invasion cell in the inhibitor group were increased(P<0.05). CONCLUSIONS: Up-regulating the expression of miR-375 in MUM-2B cells can reduce cell proliferation activity, accelerate cell apoptosis, and inhibit cell migration and invasion, while down-regulating the expression of miR-375 has the opposite effect. It indicates that miR-375 may play the function of tumor suppressor in the course of CM.