The comparison of animal models for premature ovarian failure established by several different source of inducers

The objective of this study was to compare premature ovarian failure animal models established by several different source of inducers. Female ICR mice, KM mice, and SD rats were treated by cyclophosphamide at 120 mg/kg, busulfan at 12 mg/kg, cisplatin at 3 or 4 mg/kg, 4-vinylcyclohexene diepoxide at 160 mg/kg, 35% galactose food pellet, and tripterygium glycosides at 50 mg/kg, respectively. Parameters were analyzed by body weight, serum concentration level of related hormones, ovarian and uterine pathological examination. The results indicated the body weight of mice increased very slowly following single dose of cyclophosphamide (p < 0.05) with damaged ovary; repeated doses of cisplatin could induce body weight significantly decreased (p < 0.01) with a rising trend of serum LH concentration, declining tendency of serum E2 concentration and injured ovary and uterus; 4-vinylcyclohexene diepoxide also hindered the mice growing (p < 0.05) with damaged ovary and uterus; the body weight of mice feed by 35% galactose food pellet increased slowly (p < 0.05) with dramatically higher serum concentration level of galactose, albumin, and total protein (p < 0.001) and injured ovary. Busulfan and tripterygium glycosides did not present obvious evidences. In conclusion, the inducers presented their respective features in such animal models and should be appropriately applied in preventive methods.     

Peroxisome-related genes in hepatocellular carcinoma correlated with tumor metabolism and overall survival

Background and aimA prominent hallmark of tumors is aberrant lipid metabolism, and various peroxisome-related genes (PRGs) are associated with aberrant tumoral metabolic signaling. However, the influence of PRGs on the prognosis of hepatocellular carcinoma (HCC) patients remains debatable. Thus, the current study was designed to evaluate the effect of PRGs on HCC and construct a prognostic model for predicting survival.MethodsWe initially acquired HCC-related gene expression profiles from the Cancer Genome Atlas and International Cancer Genome Consortium databases. We then utilized Cox analysis and Lasso regression to identify suitable PRGs for the risk model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to clarify the functional roles of PRGs. Single-sample gene set enrichment analysis (ssGSEA) was conducted to confirm the relationship between PRGs and immunity.ResultsFour PRGs were correlated with HCC patient survival: 2 risk genes (MPV17, and ABCD1) and 2 protective genes (ACSL1 and ACSL6). We derived risk scores based on PRGs to construct a predictive model that could accurately predict overall survival (OS) among HCC patients. Furthermore, GO and KEGG analyses revealed that these PRGs were potentially involved in lipid metabolism and ferroptosis in HCC. Moreover, ssGSEA results demonstrated that high PRG scores were associated with immune suppressor activation, which caused the suppression of immune effectors (CD8⁺ T-cells, B cells, and NK cells) and the attenuation of the immune-mediated antitumor effect.ConclusionPRGs act as key regulators in tumorigenesis and tumor progression by affecting lipid synthesis and utilization, which we used to predict the outcome of HCC patients. Moreover, PRGs have been shown to promote tumoral immune resistance by serving as a vital bridge between metabolism and immunity. Thus, a personalized treatment approach targeting PRGs would clinically benefit patients by blocking the interaction between tumor metabolism and immunity.     

Lycium Barbarum polysaccharides ameliorates hyperglycemia-exacerbated cerebral ischemia/reperfusion injury via protecting blood-brain barrier

BackgroundHyperglycemia exacerbates brain damage in cerebral ischemia/reperfusion injury. Previous study found that Lycium barbarum polysaccharides (LBP) has a neuroprotective effect on hyperglycemia-aggravated ischemic brain injury, which raising the possibility for treatment of neurodegenerative diseases. However, the underlying mechanism of LBP-induced protection by ameliorating hyperglycemia-aggravated ischemia/reperfusion injury needs to be tested. This study aimed to investigate the effects of LBP on blood–brain barrier (BBB) integrity with a hyperglycemia-aggravated cerebral ischemia/reperfusion injury model.MethodsSprague-Dawley male rats were randomly divided into three groups: normoglycemic (NG), hyperglycemic (HG), and LBP-pretreated hyperglycemic (HG + LBP). Animals underwent middle cerebral artery occlusion (MCAO) for 30 min, followed by 1-, 3-, and 7-day of reperfusion.ResultsOur results showed that the neurological deficit, infarct volume, cell apoptosis, and IgG leakage in the HG group significantly increased separately, compared with that of the NG group, (p < 0.05). Pre-treatment with LBP reversed these injury indicators (p < 0.05). And much more severe degree of swelling endothelium, swollen astrocyte, and decreased tight junctions in the micro-vessel were detected in the HG group comparing to that of the NG group. In addition, increased degree of basement membrane degradation, dissociation between the astrocyte endfeet and basement membrane, and tight junction's protein degradation was found in the HG group compared with the NG group (p < 0.05). However, when exposure to LBP therapy could reverse the above alterations (p < 0.05).ConclusionsThese results demonstrated that LBP could ameliorate hyperglycemia-exacerbated cerebral ischemia/reperfusion injury via protecting the blood-brain barrier.     

Clinically significant portal hypertension (CSPH) on early-stage HCC following hepatectomy: What's the impact?

Background and aimThe impact of currently clinically significant portal hypertension (CSPH) for patients with early-stage HCC after surgery remains controversial. The purpose of this study is to understand the specific effect of CSPH on patients with early-stage (BCLC A stage) HCC after surgery.MethodsWe collected data from 386 HCC patients treated at two centers from December 2009 to January 2017.224 patients (all treated by hepatectomy) were in BCLC stage A, of which, 122 had no CSPH, and 102 had CSPH. There were 162 patients in BCLC stage B (who underwent surgery, TACE, and conservative treatment). The prognosis of the CSPH and non-CSPH groups in BCLC stage A was compared using the Kaplan-Meier method. We used multivariate Cox regression to analyze prognostic factors in patients in BCLC stage A and compared the prognosis of the two groups with the BCLC stage B group.ResultsAmong the 224 BCLC stage A patients after surgery, the overall survival (OS) and recurrence-free survival (RFS) of the CSPH group were worse than those of the non-CSPH group (P < 0.001, HR = 2.340[1.554–3.523]; P < 0.001, HR = 2.577[1.676–3.812]) The multivariate Cox proportional hazards model indicated that CSPH was an independent prognostic factor for OS and RFS in BCLC stage A patients. BCLC stage A patients with CSPH treated by hepatectomy had a comparable prognosis to BCLC B stage patients (P = 0.378), and the OS and RFS (P = 0.229; P = 0.077) in the CSPH (BCLC A) group were also comparable to BCLC stage B patients treated with surgery alone.ConclusionsCSPH can affect the surgical prognosis of early-stage (BCLC stage A) HCC. BCLC stage A patients with CSPH have a prognosis comparable to patients with BCLC stage B. An additional stage, such as the BCLC stage A-B, can be considered.     

Inverted U-Shaped Associations between Glycemic Indices and Serum Uric Acid Levels in the General Chinese Population: Findings from the China Cardiometabolic Disease and Cancer Cohort (4C) Study

Objective The relationship between serum uric acid(SUA)levels and glycemic indices,including plasma glucose(FPG),2-hour postload glucose(2 h-PG),and glycated hemoglobin(HbA1 c),remains inconclusive.We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population.Methods The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study.A total of 105,922 community-dwelling adults aged≥40 years underwent the oral glucose tolerance test and uric acid assessment.The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models.Results A total of 30,941 men and 62,361 women were eligible for the current analysis.Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels,but with different inflection points in men and women.The thresholds for FPG,2 h-PG,and HbA1 c for men and women were 6.5/8.0 mmol/L,11.0/14.0 mmol/L,and 6.1/6.5,respectively(SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices).Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes,while the inflection points were reached earlier in men than in women.     

Inhibition of hsa_circ_0001313 (circCCDC66) induction enhances the radio-sensitivity of colon cancer cells via tumor suppressor miR-338-3p: Effects of cicr_0001313 on colon cancer radio-sensitivity

Circular RNA_0001313 (circ_0001313), also known as circCCDC66, is a novel circRNA that recently found to be upregulated in colon cancer tissues and promote colon cancer progression. However, the role of circ_0001313 in regulating radio-sensitivity of colon cancer and its molecular mechanism remain undetermined. Here we found circ_0001313 was significantly upregulated and miR-338-3p was downregulated in radio-resistant colon cancer tissues compared to radio-sensitive tissues. Radiation treatment in colon cells triggered a remarkable upregulation of circ_0001313 and a downregulation of miR-338-3p. Knockdown of circ_0001313 reduced cell viability, colony formation rate and increased caspase-3 activity in colon cancer cells under irradiation. Moreover, circ_0001313 act as a sponge for miR-338-3p in colon cancer cells. Furthermore, miR-338-3p could reverse the effects of circ_0001313 knockdown on cell viability, colony formation, and caspase-3 activity. These findings revealed that knockdown of circ_0001313 could induce radio-sensitivity of colon cancer cells by negatively regulating miR-338-3p.     

西罗莫司自微乳化释药系统的制备及体内外评价

 目的 制备西罗莫司（sirolimus,雷幅霉素,rapamycin,RAPA）自微乳化释药系统（RAPA-SMEDDS）以提高低水溶性药物-RAPA的生物利用度。 方法 用HPLC-UV测定RAPA含量;通过溶解度实验和伪三元相图筛选SMEDDS 组分;采用星点设计和效应面法优化处方以获得自乳化后粒径小于50 nm的自微乳化制剂;考察并比较优化处方与市售口服液在大鼠体内的药动学行为。结果 优化后RAPA-SMEDDS的处方为30%MCT、50%Cremopher EL和20% Labrasol,每1 g SMEDDS中载药2.0 mg;自乳化后形成乳滴的粒径和PDI分别为41.10 nm和0.247;不同稀释介质及不同稀释倍数对微乳粒径大小及其分布影响较小;单剂量灌胃给药后大鼠体内SMEDDS和Rapamune口服液的主要药动学参数：ρ_max分别为（13.37±2.78）和（4.15±1.48）μg·L-1,t_max分别为（2.60±1.29）和（5.40±1.34）h,AUC_{0-48 h}分别为（157.75±70.77）和（73.36±34.12）μg·h·L-1。结论 优化所得处方自乳化后粒径小于50 nm,大鼠体内相对生物利用度为215.04％,RAPA-SMEDDS可明显提高药物的口服吸收。