OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer.Methods A colitis-cancer model was established in C57BL/6 mice using azoxymethane(AOM)combined with dextran sulfate sodium(DSS).Samples were collected at 7,10,and 14 weeks post-modeling and the spleen index,colon length,mass,and colon mass per unit length were measured.Histopathological changes in the colon were observed by hematoxylin and eosin and Masson staining.Expression levels of the cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b,Lrp5,Axin2,and Znrf3 at different pathological stages were detected by reverse transcription quantitative real time PCR.Cancer-associated fibroblasts(FAP),CD44,the proliferation marker Ki67,and goblet cell MUC2 protein were detected by multiple immunofluorescence histochemistry(mIHC)and immunofluorescence.In addition,colon organoids were isolated from model mice at ten and fourteen weeks and cultured in vitro to observe changes in organoid morphology and marker expression.Results AOM/DSS-induced mice showed reduced,distorted,and branched colon crypt structures with a few collagen fibers at 7 weeks,and varying degrees of colon intraepithelial neoplasia,with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining at ten and fourteen weeks.mRNA levels of CD44 and Wnt2b in the colon were significantly increased(P＜0.05)and Axin2 was decreased(P＜0.01)in model mice compared with control mice at fourteen week,and levels of Wnt2b,Lrp5,and Znrf3 were increased compared with seven-week mice(P＜0.01,P＜0.05,P＜0.01),and Axin2 was decreased(P＜0.01).mIHC staining showed increased expression of FAP and CD44 in the colon in model mice at ten and fourteen weeks,with decreased MUC2 expression.Colon organoids showed cystic dilation,especially at fourteen weeks,with more prominent expression of Ki67 and CD44.Conclusions The AOM/DSS-induced mouse model exhibited chronic colonic inflammation,low-grade intraepithelial neoplasia,and high-grade intraepithelial neoplasia at seven,ten,and fourteen weeks,respectively.The pathological microenvironment was characterized by fibroblast activation and abnormal proliferation of epithelial cells.

Objective To investigate the dynamic characteristics of intestinal pathological development at different time points in a mouse model of colitis-associated colon cancer.Methods A colitis-cancer model was established in C57BL/6 mice using azoxymethane(AOM)combined with dextran sulfate sodium(DSS).Samples were collected at 7,10,and 14 weeks post-modeling and the spleen index,colon length,mass,and colon mass per unit length were measured.Histopathological changes in the colon were observed by hematoxylin and eosin and Masson staining.Expression levels of the cancer stem cell marker CD44 and Wnt signaling pathway genes Wnt2b,Lrp5,Axin2,and Znrf3 at different pathological stages were detected by reverse transcription quantitative real time PCR.Cancer-associated fibroblasts(FAP),CD44,the proliferation marker Ki67,and goblet cell MUC2 protein were detected by multiple immunofluorescence histochemistry(mIHC)and immunofluorescence.In addition,colon organoids were isolated from model mice at ten and fourteen weeks and cultured in vitro to observe changes in organoid morphology and marker expression.Results AOM/DSS-induced mice showed reduced,distorted,and branched colon crypt structures with a few collagen fibers at 7 weeks,and varying degrees of colon intraepithelial neoplasia,with an increased proportion of high-grade intraepithelial neoplasia over time and increased collagen fiber staining at ten and fourteen weeks.mRNA levels of CD44 and Wnt2b in the colon were significantly increased(P＜0.05)and Axin2 was decreased(P＜0.01)in model mice compared with control mice at fourteen week,and levels of Wnt2b,Lrp5,and Znrf3 were increased compared with seven-week mice(P＜0.01,P＜0.05,P＜0.01),and Axin2 was decreased(P＜0.01).mIHC staining showed increased expression of FAP and CD44 in the colon in model mice at ten and fourteen weeks,with decreased MUC2 expression.Colon organoids showed cystic dilation,especially at fourteen weeks,with more prominent expression of Ki67 and CD44.Conclusions The AOM/DSS-induced mouse model exhibited chronic colonic inflammation,low-grade intraepithelial neoplasia,and high-grade intraepithelial neoplasia at seven,ten,and fourteen weeks,respectively.The pathological microenvironment was characterized by fibroblast activation and abnormal proliferation of epithelial cells.

Type I interferon (IFN) is considered as a bridge between innate and adaptive immunity. Proper activation or inhibition of type I IFN signaling is essential for host defense against pathogen invasion, tumor cell proliferation, and overactive immune responses. Due to intricate and diverse chemical structures, natural products and their derivatives have become an invaluable source inspiring innovative drug discovery. In addition, some natural products have been applied in clinical practice for infection, cancer, and autoimmunity over thousands of years and their promising curative effects and safety have been well-accepted. However, whether these natural products are primarily targeting type I IFN signaling and specific molecular targets involved are not fully elucidated. In the current review, we thoroughly summarize recent advances in the pharmacology researches of natural products for their type I IFN activity, including both agonism/activation and antagonism/inhibition, and their potential application as therapies. Furthermore, the source and chemical nature of natural products with type I IFN activity are highlighted and their specific molecular targets in the type I IFN pathway and mode of action are classified. In conclusion, natural products possessing type I IFN activity represent promising therapeutic strategies and have a bright prospect in the treatment of infection, cancer, and autoimmune diseases.
Biological Products/therapeutic use* ; Immunity, Innate ; Signal Transduction ; Interferon Type I/metabolism*

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD). METHODS: High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism. RESULTS: Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5). CONCLUSION Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.

Objective:To study the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cardia cancer (EGCC) in elderly patients.Methods:A retrospective analysis was performed on data of 499 EGCC patients who underwent ESD from January 2011 to June 2018 in Nanjing Drum Tower Hospital. The patients were divided into two groups by age, the young/middle-aged group (<65 years old) and the elderly group (≥65 years old). The baseline data, lesion features, postoperative complications, short-term efficacy and long-term efficacy of the two groups were compared.Results:The elderly group included 272 patients (283 lesions) and the young/middle-aged group included 227 patients (229 lesions). Except that there were significant differences in the age ( P<0.001) and body mass index ( P=0.002) between the elderly group and the young/middle-aged group, there were no significant differences in the baseline data or pathological features between the two groups. The rate of curative resection in the elderly group was 77.0%, lower than that in the young/middle-aged group (84.3%, P=0.045). No significant differences were found in en bloc resection rate (100.0% VS 99.6%, P=1.000), complete resection rate (94.7% VS 93.9%, P=0.705), postoperative complications incidence (6.4% VS 5.7%, P=0.747), operation time (64.02±39.24 min VS 66.16±44.62 min, P=0.566) or hospitalization time (6.76±2.06 d VS 6.47±1.74 d, P=0.092]. After the median follow-up of 47.9 months, 13.4% patients in the elderly group received additional surgery, which was slightly lower than that in the young/middle-aged group ( P=0.891). There were no significant differences in postoperative recurrence, lymph node metastasis, distant metastasis, overall mortality and disease-related mortality between the two groups. The survival analysis showed that five-year overall survival rates were 94.41% and 96.34% in the elderly group and the young/middle-aged group respectively ( P=0.156), and five-year disease-specific survival rate were 99.18% and 99.03% in the two groups respectively ( P=0.858). Conclusion:ESD is safe and effective for EGCC in elderly patients with satisfactory short-term and long-term efficacy.

Objective To understand the current status of dysphagia among community elderly of Dongcheng District of Beijing Municipality and to explore its related factors.Methods From May 2016 to February 2017, the International Resident Assessment Instrument Home Care (InterRAI HC) was used for data of home care needs assessment of community elderly (≥60 years old) to carry out the focused analysis of dysphagia. The evaluation result of the term "nutrition intake patterns" of InterRAI HC was taken as the standard to determine whether to be with or without dysphagia. The chi-square test and Logistic regression were used to analyze the influencing factors of dysphagia among community elderly.Results Among 229 community elderly, there were 49 cases with dysphagia with 21.4％ for the incidence. The related factors of dysphagia among community elderly included the impaired balanced capacity (OR=4.913, 95％CI: 1.772-13.618, P=0.002), yield of drinking water<1000 ml/d (OR=2.600, 95％CI: 1.253-5.396,P=0.010), ages (OR=1.048, 95％CI: 1.004-1.095,P=0.024), body mass index<18.5 kg/m2 (OR=4.576, 95％CI: 1.220-17.172,P=0.024) and history of Parkinson's disease (OR=2.505, 95％CI: 1.015-6.180,P=0.046).Conclusions The current status of dysphagia in community elderly of Dongcheng District of Beijing Municipality is worth attaching importance to. The dysphagia of the aged should be prevented, discovered and treated early by active measures such as paying close attention to related factors and effective screening.

Objective To explore the effects of case nursing combined with cognitive nursing intervention on general status and cognitive function in stroke patients with depression.Methods From October 2016 to April 2018, we selected 96 stroke patients with depression in Department of Neurology of He'nan Provincial People's Hospital. All of the patients were divided into observation group and control group with the random number table, 48 cases in each group. Control group received routine nursing. On the basis of that in control group, observation group applied case nursing combined with cognitive nursing intervention. The investigation was carried out with the Mini-mental State Examination (MMSE), Nurses' Observation Scale for Inpatient Evaluation (NOSIE), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) before and after intervention. We also observed patients' abnormal body condition and hospital days.Results The incidence of abnormal body condition of patients in observation group was lower than that in control group with a statistical difference (P<0.05). After intervention, the scores of NOSIE of patients in observation group, the scores of personal neatness, interest and social competence were higher than those in control group; the scores of depression, irritability and slowness were lower than those in control group; the differences were all statistical (P<0.01). The incidence of cognitive disorder and the scores of HAMA as well as HAMD all decreased after intervention, and the improvements of observation group were statistically better than those of control group (P<0.05). There was statistical differences in the hospital days between two groups (P<0.05). Conclusions Case nursing combined with cognitive nursing intervention can improve depression, anxiety and cognitive function, and shorten hospital days among stroke patients with depression which is worth further promotion in clinical application.

Objectives To investigate the clinical and imaging features discriminating mass forming chronic pancreatitis (CP) from pancreatic carcinoma. Methods The clinical, radiologic, laboratory and pathologic profiles of eleven patients with mass forming CP were reviewed retrospectively. Results The patients with mass forming CP were predominantly older, male, and presented with obstructive jaundice or abdominal symptoms. Serum level of CA19-9 was slightly elevated, generally below 100 U/ml, which was lower than that of pancreatic carcinoma. The diagnostic accuracy of B-ultrasound for mass forming CP was only 18.2% and it could only be the screening method; the diagnostic accuracy of CT was 45.5%, and the main CT features included dilation of main pancreatic duct and the branches, as well as pancreatic pseudocysts or calcification. The findings of MRCP and EUS were irregular dilation of main pancreatic duct and common bile duct, which were similar to pancreatic carcinoma. ERCP could provide imaging characteristics of biliary and pancreatic duct, and the nature of obstruction, the stricture and dilation of biliary and pancreatic duct. When combined with CT scan, ERCP was useful for differentiation from pancreatic head cancer. According to histopathology, a few mass forming CP was autoimmune pancreatitis. Conclusions Mass forming CP is associated with clinical and radiologic features that are similar to those of pancreatic carcinoma. It is necessary to carefully evaluating clinical and imaging findings, laboratory findings and histopathological examinations.

To get specific scFv (Single-chain fragment variable) antibody against soluble Abeta1-42(Amyloid-beta) oligomers, we constructed a human single-chain Fv (scFv) antibody library by phage display technology. Using RT-PCR, we amplified the variable heavy (VH) and variable light (VL) genes from peripheral blood lymphocytes (PBL). Then we obtained the scFv fragments through SOE-PCR, and the scFv fragments were cloned into the vector pCANTAB5E and electroporated into competent Escherichia coli TG1 cells. Consequently, a scFv phage display library containing 2.5 x 10(9) clones was constructed. The recombinant phagemids were rescued by reinfection of helper phage M13K07. Recombinant phages specific for Abeta1-42 oligomers were enriched after four rounds of biopanning and the antigen-positive clones were selected from the enriched clones by phage ELISA. Positive clone B19 was used to infect E. coli HB2151 to express soluble scFv antibody. SDS-PAGE and Western blotting analysis showed that the soluble scFv B19 antibody was expressed successfully and could bind specifically to Abeta1-42 trimer and protofiber. The specific scFv against Abeta1-42 oligomers can be used in the therapeutic research on Alzheimer's disease.
Amyloid beta-Peptides ; genetics ; immunology ; Antibody Specificity ; immunology ; Humans ; Peptide Fragments ; genetics ; immunology ; Peptide Library ; Single-Chain Antibodies ; genetics ; immunology ; isolation & purification