[Advances in the study of programmed cell death protein 1 and its ligand inhibitors in the treatment of late stage HCC].

The treatment of late stage hepatocellular carcinoma (HCC) presently remains a great challenge. A very few drugs have been recently approved for clinical use except sorafenib and lenvatinib. After decades of failure and experience with molecular targeted and immunosuppressive therapy, immune checkpoint inhibitors are becoming one of the potentially effective therapies for patients with HCC, whose tumor is in the middle and late stages. Moreover, immune checkpoint is one of the main mechanisms of tumor immune evasion; of which programmed cell death protein 1 and its ligand (PD1/PD-L1) are important immune checkpoint targets, and its related pathway has shown to have an antitumor effect in a variety of solid or hematologic tumors and its inhibitors can effectively exert antitumor immunosuppressive effects. This review summarizes the current role of PD1/PD-L1 inhibitors in the treatment of late stage HCC, and explores the forecasting value of combined therapy strategy for HCC.

Complete genome sequence of a tobacco isolate of the tobacco vein banding mosaic virus strain prevailing in China.

Tobacco vein banding mosaic virus (TVBMV) is a species of the largest plant virus genus Potyvirus. Its incidence has been increasing in Chinese tobacco-growing area. TVBMV isolates can be clustered into three genetic groups that are corresponding with their geographical origin. We have reported the complete genomic sequence of TVBMV isolate YND with unique NIb/CP cleavage site. Here, we determined and analyzed the complete genomic sequence of isolate HN39, which was collected from tobacco in Henan Province and represented Chinese prevalent strain of TVBMV. HN39 has similar host range with YND, but induce mild vein banding symptom in Nicotiana tabacum cv. Samsun. The genome of TVBMV-HN39 is composed of 9,570 nucleotides, excluding the poly(A) tail. It contains a large ORF of 9,240 nucleotides and encode a polyprotein of 3,079 amino acids. The putative NIa-Pro cleavage site for NIb/CP is Q/G. The identities between the complete genomes of isolates HN39 and YND were 90.0% at nucleotide level and 95.4% at amino acid level. As for other potyviruses, HN39 shared the highest identity with wild tomato mosaic virus (WTMV) at complete genomic level, while different genes shared the highest identities with different potyviruses. This is the second complete genomic sequence of TVBMV reported.

Molecular diversity of tobacco vein banding mosaic virus.

Tobacco vein banding mosaic virus (TVBMV) is of increasing importance in tobacco production on the Chinese mainland. The 3'-terminal genomic sequences (1624 nucleotides) of 12 TVBMV isolates from China were determined and compared to the sequences of only four TVBMV isolates available in databanks. The results revealed that TVBMV consists of several phylogenetically distinguishable strains that show a degree of correlation with the geographical origin. Two isolates from Yunnan had a unique putative NIb/CP proteolytic cleavage site of Q/N that is uncommon for potyviruses, whereas other TVBMV isolates had the more typical Q/G amino acids at that site. One isolate (ZB6) from Zibo, Shandong Province, was predicted to have experienced recombination within the characterized genomic region.

Differential eudismic ratios in the antagonism of human platelet function by phenoxy- and thiophenoxyacetic acids.

The antilipidemic drug clofibric acid (CPIB) exhibits antiplatelet effects. In order to examine the role of enantioselectivity and hydrophobicity, the mono(desmethyl) enantiomers of 2-(4-chlorophenoxy)propanoic acid (CPPA), related butanoate homologs, 2-(4-chlorophenoxy)butanoic acid (CPBA), thioether relatives, 2-(4-chlorothiophenoxy)propanoic acid (CTPA) and corresponding butanoate homologs, 2-(4-chlorothiophenoxy)butanoic acid (CTBA) were studied. All compounds inhibit prostaglandin-dependent human platelet aggregation and serotonin secretion induced by ADP. For the phenoxy acid series, (+)-(R)-CPPA is 5-fold more potent than either (-)-(S)-CPPA or CPIB giving a rank order potency of (+)-(R)-CPPA > (+)-(R)-CPBA > (-)-(S)-CPPA > (-)-(S)-CPBA. With the exception of (-)-(S)-CTPA, all thiophenoxy acid enantiomers are less potent than their respective phenoxy acid isomers [(+)-(R)-CTPA > (-)-(S)-CTPA > (+)-(R)-CTBA > (-)-(S)-CTBA]. The same rank order of potencies are observed against responses induced by arachidonic acid (AA) with the exception of CPIB which is inactive. However, inhibition of thrombin-induced [3H]-AA release by phenoxyacetic acids is not stereoselective but correlates with hydrophobicity.