The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization

Marginal zones (MZs) are microdomains in the spleen that contain various types of immune cells, including MZ B cells, MOMA1(+) metallophilic macrophages, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1)(+) endothelial cells. MAdCAM-1(+) and MOMA1(+) cells line the sinus, that separates MZs from splenic follicles. Here we show that a receptor for the lysophospholipid sphingosine-1-phosphate (S1P), S1P(3), is required for normal numbers of splenic immature and MZ B cells, and for S1P-induced chemotaxis of MZ B cells. S1P(3) is also essential for proper alignment of MOMA1(+) macrophages and MAdCAM-1(+) endothelial cells along the marginal sinus. The lack of cohesion of the marginal sinus in S1P(3)(-/-) mice affects MZ B cell functions, as wild-type (WT) MZ B cells migrate more into S1P(3)(-/-) follicles than into WT follicles after treatment with lipopolysaccharide. Additionally, short-term homing experiments demonstrate that WT MZ B cells home to the S1P(3)(-/-) spleen in increased numbers, suggesting a role for the marginal sinus in regulating MZ B cells numbers. Moreover, S1P(3)(-/-) mice are defective in mounting immune responses to thymus-independent antigen type 2 due to defects in radiation-resistant cells in the spleen. These data identify lysophospholipids and the S1P(3) receptor as essential regulators of the MZ sinus and its role as a barrier to the follicle.     

甲状腺癌细胞系方波电脉冲基因转染条件的探讨

目的：探讨方波脉冲基因电转染对人甲状腺癌细胞系的转染条件和效果。方法：选用pEGFP-Cl作为外源基因与方波电脉冲相结合，以人甲状腺癌细胞系TA-K为导入对象，探讨方波脉冲基因电转染对人甲状腺癌细胞系转染的脉冲幅度，脉冲时值，脉冲次数和反应体系大小。结果：当脉冲幅度在60V／mm时，开始出现阳性细胞，脉冲时值20ms时，基因转染效率可高达35％，细胞生存分数55％，脉冲时值20ms、次数1次转染效率高、细胞死亡率低。200μl混合液电转染后观察，对细胞生存影响不大。结论：脉冲幅度在60V／mm，脉冲时值20ms，脉冲次数1次，反应体系200μl，可以为人甲状腺癌细胞系的转染提供良好效果。     

Aberrant TRPC1 expression reflects stromal cervical invasion,lymphovascular invasion,elevated FIGO stage,and poor survival in resectable endometrial carcinoma patients

BackgroundTransient receptor potential channel 1 (TRPC1) promotes tumor growth and metastasis in endometrial carcinoma (EC) cell lines, whereas its clinical role in EC management remains unclear. Therefore, this study aimed to investigate the association of TRPC1 protein expression with the clinical features and survival of EC patients, then was further validated by TRPC1 mRNA measurement and data from The Human Protein Atlas.MethodsTRPC1 protein expression in tumor tissues and normal endometria of 176 resectable EC patients was determined using immunohistochemistry. Besides, TRPC1 mRNA expression of partial patients (n = 80) was detected using RT‐qPCR. Additionally, survival data from The Human Protein Atlas (derived from The Cancer Genome Atlas [TCGA]) was analyzed.ResultsTRPC1 protein expression was up‐regulated in tumor tissue compared with normal endometrium (p < 0.001). Up‐regulated TRPC1 protein expression was associated with stromal cervical invasion (p = 0.044), lymphovascular invasion (p = 0.032), and increased federation of gynecology and obstetrics (FIGO) stage (p = 0.005). Tumor TRPC1 protein high was linked with shortened accumulating disease‐free survival (DFS) (p = 0.009) and overall survival (OS) (p = 0.026), which were also confirmed by multivariate Cox''s regression analysis (both p < 0.050). Further, TRPC1 mRNA validation disclosed that TRPC1 mRNA high was related to shortened accumulating DFS (p = 0.038) and exhibited a correlating trend with declined OS (lacked statistical significance) (p = 0.162). Meanwhile, survival analysis on the data from The Human Protein Atlas (derived from TCGA) also exhibited that TRPC1 mRNA high was correlated with reduced accumulating OS (p < 0.001).ConclusionOur findings support TRPC1 as a prognostic biomarker in resectable EC patients.     

Modulation of Reactive Oxygen Species to Overcome 5-Fluorouracil Resistance

5-Fluorouracil (5-FU) remains to be an important chemotherapeutic drug for treating several cancers when targeted therapy is unavailable. Chemoresistance limits the clinical utility of 5-FU, and new strategies are required to overcome the resistance. Reactive oxygen species (ROS) and antioxidants are balanced differently in both normal and cancer cells. Modulating ROS can be one method of overcoming 5-FU resistance. This review summarizes selected compounds and endogenous cellular targets modulating ROS generation to overcome 5-FU resistance.     

Biofunctional Layered Double Hydroxide Nanohybrids for Cancer Therapy

Layered double hydroxides (LDHs) with two-dimensional nanostructure are inorganic materials that have attractive advantages such as biocompatibility, facile preparation, and high drug loading capacity for therapeutic bioapplications. Since the intercalation chemistry of DNA molecules into the LDH materials were reported, various LDH nanohybrids have been developed for biomedical drug delivery system. For these reasons, LDHs hybridized with numerous therapeutic agents have a significant role in cancer imaging and therapy with targeting functions. In this review, we summarized the recent advances in the preparation of LDH nanohybrids for cancer therapeutic strategies including gene therapy, chemotherapy, immunotherapy, and combination therapy.     

Epidemiology and Transmission Dynamics of Infectious Diseases and Control Measures

The epidemiology and transmission dynamics of infectious diseases must be understood at the individual and community levels to improve public health decision-making for real-time and integrated community-based control strategies. Herein, we explore the epidemiological characteristics for assessing the impact of public health interventions in the community setting and their applications. Computational statistical methods could advance research on infectious disease epidemiology and accumulate scientific evidence of the potential impacts of pharmaceutical/nonpharmaceutical measures to mitigate or control infectious diseases in the community. Novel public health threats from emerging zoonotic infectious diseases are urgent issues. Given these direct and indirect mitigating impacts at various levels to different infectious diseases and their burdens, we must consider an integrated assessment approach, ‘One Health’, to understand the dynamics and control of infectious diseases.     

Prevalence of obstructive sleep apnea syndrome in hospitalized patients with type 2 diabetes in Beijing,China

Aims/IntroductionTo estimate the prevalence, and patient clinical and demographic profile, as well as risk factors associated with obstructive sleep apnea syndrome (OSAS) in hospitalized patients with type 2 diabetes mellitus in Beijing, China.Materials and MethodsHospitalized adult patients with type 2 diabetes mellitus were consecutively screened and invited for an overnight polysomnography from four hospitals in Beijing, China, from May 2016 to February 2017. We used the American Academy of Sleep Medicine 2012 polysomnography recording techniques and scoring criteria to identify the type of apnea and the severity of OSAS. The χ²‐test was used to evaluate differences between groups regarding the prevalence, and demographic and other clinical parameters.ResultsA total of 735 patients were found eligible for the study, of whom 309 patients completed the overnight polysomnography. The mean age of the patients was 58.2 ± 10.9 years, and most (67.3%) were men. The prevalence of overall (apnea hypopnea index ≥5/h), moderate‐to‐severe (apnea hypopnea index ≥15/h) and severe (apnea hypopnea index ≥30/h) OSAS was 66.3% (95% confidence interval 60.8–71.6%), 35.6% (95% confidence interval 30.3–41.2%) and 16.5% (95% confidence interval 12.5–21.1%), respectively. Central and mixed apnea contributed 12% to all sleep‐disordered breathing. With the aggravation of OSAS, the combined prevalence for central, mixed and obstructive apnea increased from 57% to 70%. We found OSAS to be associated with older age, obesity, self‐reported snoring and apnea, and diabetes complications.ConclusionsGuidelines on screening and treatment of OSAS among hospitalized patients with diabetes are needed to direct the routine practice for diabetes endocrinologists for optimal clinical care of such patients.     

Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity,Insulin Resistance,and New Onset Diabetes after Peritoneal Dialysis

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57–3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08–2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80–13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13–12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006–0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02–0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35–50.5, p = 0.02). Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.