Lysine-Specific Demethylase 1 Promises to Be a Novel Target in Cancer Drug Resistance: Therapeutic Implications.

Chemotherapy, targeted therapy, and immunotherapy are effective against most tumors, but drug resistance remains a barrier to successful treatment. Lysine-specific demethylase 1 (LSD1), a member of histone demethylation modifications, can regulate invasion, metastasis, apoptosis, and immune escape of tumor cells, which are associated with tumorigenesis and tumor progression. Recent studies suggest that LSD1 ablation regulates resensitivity of tumor cells to anticarcinogens containing immune checkpoint inhibitors (ICIs) via multiple upstream and downstream pathways. In this review, we describe the recent findings about LSD1 biology and its role in the development and progression of cancer drug resistance. Further, we summarize LSD1 inhibitors that have a reversal or resensitive effect on drug resistance and discuss the possibility of targeting LSD1 in combination with other agents to surmount resistance.

Discovery of 1,3,4-oxadiazole derivatives containing a bisamide moiety as a novel class of potential cardioprotective agents.

Myocardial injury is a nonnegligible problem in cardiovascular diseases and cancer therapy. The functional feature of N-containing heterocycles in the cardiovascular field has attracted much attention in recent years. Herein, we discovered a lead compound 12a containing 1,3,4-oxadiazole by extensive screening of anticancer derivatives containing nitrogen-heterocycle, which exhibited potential protective activity against oxidative stress in cardiomyocytes. Follow-up structure-activity relationship (SAR) studies also highlighted the role of substitution sites and bisamide moiety in enhancing the protective activity against oxidative stress. Specifically, compound 12d exhibited low cytotoxicity under high concentration and potent myocardial protection against oxidative stress in H9c2 cells. Preliminary mechanistic studies showed compound 12d could decrease the expression of cardiac hypertrophy and oxidative stress-related proteins/genes and reduce mitochondria-mediated cell apoptosis, thereby enhancing the cell vitality of injured cardiomyocytes. In this study, 1,3,4-oxadiazole may represent a novel pharmacophore that possesses potential myocardial protection and provides more choices for future optimization of cardiovascular drugs, especially for the treatment of onco-cardiology.

[Correlation analysis between degenerative spondylolisthesis and T2WI hyperintensity on MRI of interspinous ligament].

OBJECTIVE: To explore the relationship between lumbar degenerative spondylolisthesis and T2WI high signal in the interspinous ligament in MRI in order to improve the understanding of the signal changes of the interspinous ligament. METHODS: The clinical data of 43 patients with clinically diagnosed lumbar degenerative spondylolisthesis were collected from March 2018 to March 2020, there were 19 males and 24 females, aged 50 to 92 years with an average of 69 years old. Using picture archiving and communication systems (PACS) to access images and record the distribution and incidence of T2WI high signal in the interspinous ligament between the slipped and non-slipped segments. Using Spearman correlation analysis to explore the relationshipbetween the T2WI high signal of the interspinous ligament and the degree of lumbar spondylolisthesis. RESULTS: Except for 8 ligaments that were not included in the statistical results due to poor image quality, 43 patients with a total of 207 lumbar vertebrae and interspinous ligaments were included in the study. According to the Meyerding classification method, 43 patients had a total of 48 segments with spondylolisthesis, 41 segments in grade Ⅰ and 7 segments in grade Ⅱ. There were 30 cases of MRI T2WI high signal in the interspinous ligament corresponding to spondylolisthesis segment, including 3 cases on L2,3 segment, 3 cases on L3,4 segment, 20 cases on L4,5 segment, and 4 cases on L5S1 segment. And there were 53 cases of MRI T2WI hyperintensity in 159 non slipped interspinous ligaments, of which 6 cases were at L1,2, 6 were at L2,3, 13 were on L3,4, 7 were on L4,5, and 21 were on L5S1. Compared with the non slipped segment, the incidence of high signal on the T2WI of the interspinous ligament was 62.5% and 33.3%, respectively, and the difference was statistically significant (χ2= 13.06, P<0.05). Spearman correlation analysis showed that the presence of T2WI hyperintensity of interspinous ligament was positively correlated with the degree of lumbar spondylolisthesis (r=0.264, P<0.05). CONCLUSION: In patients with degenerative lumbar spondylolisthesis, the MRI T2WI hyperintensity is more common in the interspinous ligament. The occurrence of T2WI high signal is positively correlated with the degree of spondylolisthesis, which should be payed enough attention in imaging diagnosis.

A study on the effect of repeated -dose toxicity on rats exposed to dichloromethane by dermal route for 28 days / 预防医学

Objective To learn the toxic effects on rats repeatedly exposed to dichloromethane by dermal route at the same dose for 28 days.Methods Seventy two Sprague Dawley rats were divided into six groups:a solvent control group (oliver oil),four exposure groups (0.75,1.5,3.0 and 6.0 g/kg·BW)and a recovery group.Each group included six female and six male rats.The exposure groups were dermal exposed to DCM at 1.5,3.0 and 6.0 g/kg·BW,6 hours/day,5 days/week for four weeks.The recovery group was dermal exposed to 6.0 g/kg BW of DCMduring the same period then recovered for 2 weeks.Clinical signs including body weight and food consumption of each group were observed.After rats were sacrificed,the hematological and serum biochemical parameters were determined.Histopathological examination was performed on selected tissues for all animals.Results The male rats in test groups including four exposure groups and a recovery group,showed decreased body weight gain.Neutrophilia and lymphocytopenia were determined in females of 3.0 and 6.0 g/kg BW groups and males of 1.5,3.0 and 6.0 g/kg BW groups by blood routine test (P <0.05).The mean levels of serum ALT and AST significantly increased in males of 3.0 and 6.0 g/kg BW groups (P <0.05).Only the mean level of serum TG in males of 6.0 g/kg BW group decreased (P <0.05).No significant differences of these indexes were shown in female rats of all exposure groups compared to control group.The exposure -related significant increases on the incidences of epidermis and dermis lesion,hepatocellular degeneration and necrosis were observed in test groups compared to the control group.The rats of recovery group were exhibited normal percentages of lymphocytes and neutrophils,levels of ALT,AST and TG. The skin and hepatocellular lesion were improved to some extent, but not recovered exactly.Conclusion In a 4 -week repeated -dose toxic study,DCM induce dose -related effects in rats involving skin lesion and liver injury with adverse changes in body weight gain of male rats,part parameters of hematology and serum biochemistry .

[Characterization of rabies virus phosphoprotein in high prevalence provinces of China].

OBJECTIVE: Characterization of rabies virus phosphoprotein through analyzation of genetic variations about rabies virus phosphoproteins in high-incidence regions in China. METHODS: The nucleotide sequence of the P gene of Guangxi, Guizhou and Hunan provinces positive sample's were sequenced, and the P region's similarity and phylogenetic analyses were completed by using softer wares. RESULTS: The similarity of P region's nucleotide sequence is 82.1%-100%, while, the similarity of amino acid sequence is 87.5%-100%. A little variation in phosphoprotein cannot influence its biological functions. CONCLUSION: All rabies viruses isolated from Guangxi, Guizhou and Hunan provinces belong to genotype 1 and share same phylogenesis and same genome characteristic; Virus distribution presents unique Characterization; Some virus isolates from Hunan province and Thailand may come from the same virus.