Generation of Monoclonal Antibodies against Highly Conserved Antigens

Background: Therapeutic antibody development is one of the fastest growing areas of the pharmaceutical industry. Generating high-quality monoclonal antibodies against a given therapeutic target is very crucial for the success of the drug development. However, due to immune tolerance, some proteins that are highly conserved between mice and humans are not very immunogenic in mice, making it difficult to generate antibodies using a conventional approach. Methodology/Principal Findings: In this report, the impaired immune tolerance of NZB/W mice was exploited to generate monoclonal antibodies against highly conserved or self-antigens. Using two highly conserved human antigens (MIF and HMGB1) and one mouse self-antigen (TNF-alpha) as examples, we demonstrate here that multiple clones of high affinity, highly specific antibodies with desired biological activities can be generated, using the NZB/W mouse as the immunization host and a T cell-specific tag fused to a recombinant antigen to stimulate the immune system. Conclusions/Significance: We developed an efficient and universal method for generating surrogate or therapeuti

Impact of an SMS advice programme on maternal and newborn health in rural China: study protocol for a quasi-randomised controlled trial

Introduction: Expectant mothers in low-income and middle-income countries often lack access to vital information about pregnancy, preparation for birth and best practices when caring for their newborn. Innovative solutions are needed to bridge this knowledge gap and dramatically improve maternal and neonatal health in these settings. This study aims to evaluate the impact of an innovative text messaging intervention on maternal and neonatal health outcomes. Methods and analysis This study offers expectant mothers in rural China a package of free short messages via cell phone regarding pregnancy and childbirth. These messages are tailored to each mother's gestational week. It is hypothesised that delivering these short advice messages to pregnant women can improve maternal and newborn health. The study uses factorial quasi-randomisation to compare psychological, behavioural and health outcomes between 4 groups: 2 groups receiving different sets of short message interventions (ie, good household prenatal practices and healthcare seeking), a group receiving both interventions and a control group. Treatment assignment occurs at the individual level. The primary outcome is newborn health, measured by appropriateness of weight for gestational age. Secondary outcomes include severe neonatal and maternal morbidity as well as psychological and behavioural measures. This study has enrolled pregnant women who attend county maternal and child health centres for their prenatal visits. Discussion This pilot is the first large-scale effort to build a comprehensive evidence base on the impact of prenatal text messages via cell phone on maternal and newborn health outcomes in China. The study has broad implications for public health policy in China and the implementation of mobile health interventions in low-resource settings around the world. Ethics This study was approved by the Ethics Committee of the School of Medicine at Xi'an Jiaotong University on 18 January 2013. Trial registration number NCT02037087; Pre-results

Phenotypic and genotypic characterization of Human Immunodeficiency Virus type 1 CRF07_BC strains circulating in the Xinjiang Province of China

BACKGROUND: HIV-1 CRF07_BC recombinant previously circulated mainly among the intravenous drug users (IDUs) in Xinjiang province of China and is currently spreading in the entire country. The aim of this study is to characterize the genotypic and phenotypic properties of HIV-1 CRF07_BC isolates in comparison with those of the subtype B' (Thailand B) which is prevalent in the former plasma donors (FPDs) in China. RESULTS: Twelve HIV-1 CRF07_BC variants were isolated from the blood of the HIV-1-infected IDUs in Xinjiang province, and 20 subtype B' isolates were obtained from the FPDs in Anhui and Shanxi provinces of China. All the CRF07_BC viruses utilized CCR5 co-receptor, whereas 12 subtype B' viruses were R5-tropic, and the remaining B' isolates were dual (R5X4) tropic. CRF07_BC viruses had lower net charge value in the V3 loop and exhibited slower replication kinetics than subtype B' viruses. The number and location of the potential N-linked glycosylation sites in V1/V2 and the C2 region of the CRF07_BC viruses were significantly different from those of the subtype B' viruses. CONCLUSION: The HIV-1 CRF07_BC recombinant strains with relatively lower net charges in the V3 loop exclusively utilize CCR5 co-receptor for infection and exhibit slow replication kinetics in the primary target cells, suggesting that CRF07_BC may be superior over B' and other HIV-1 subtypes in initiating infection in high-risk population. These findings have molecular implications for the adaptive evolution of HIV-1 circulating in China and the design of tailored therapeutic strategy for treatment of HIV-1 CRF07_BC infection

Utilization and Associated Factors of Community Health Management Services in Hypertensive and Diabetic Patients

BackgroundHypertension and diabetes have been included in the list of China's essential public health services since 2009. During these years, the use and associated factors of community health management services in community-living hypertensive and diabetic patients are not very clear and need to be further studied.ObjectiveTo investigate the use and potential associated factors of community health management services in Shenzhen community-living hypertensive and diabetic residents.MethodsData stemmed from the results of Shenzhen Epidemiological Survey on Chronic Non-communicable Diseases and Risk Factors conducted between September and November 2018. The chi-square test and multinomial Logistic regression were used to examine the association of sex, age, place of hukou registration (Shenzhen or not) , marital status, monthly household income per capita, occupation type, years of living in Shenzhen, prevalence of medical insurance enrollment, and the level of medical institutions making a definite diagnosis with the use of community health management services.ResultsAltogether, 10 042 participants were finally enrolled, including 1 132 with self-reported hypertension, and 402 with self-reported diabetes. Among the hypertensive participants, 530 (46.82%) indicated that they received follow-up management of hypertension from the community health center. Specifically, 436 (82.31%) received blood pressure measurement by the doctor, and 399 (75.25%) received medication guidance from the doctor. Of the diabetic patients, 194 (48.26%) indicated that they received follow-up management of diabetes from the community health center. Specifically, 173 (89.37%) of the 193 cases (one case was excluded due to missed information) received blood glucose measurement by the doctor, and 154 (79.62%) received medication guidance from the doctor. The prevalence of hypertensive participants receiving guidance on smoking cessation or smoking less from the doctor was relatively low (lower than 40%) , and so was that of diabetic participants. The prevalence of hypertensive participants receiving guidance on drinking cessation or drinking less from the doctor was relatively low (lower than 40%) , and so was that of diabetic participants. Multinomial Logistic regression analysis revealed that sex, age, monthly household income per capita, years of living in Shenzhen, and prevalence of medical insurance enrollment were associated with the utilization of community health management services in hypertensive patients (P<0.05) . Age, occupational type, and monthly household income per capita were associated with the utilization of community health management services in diabetic patients (P<0.05) .ConclusionLess than half of the community-living hypertensive and diabetic participants used or were involved in community health management services. Being female, 18-44-year-old, low or moderate monthly household income per capita, and short years of living in Shenzhen were associated with lower rate of utilizing such services. Moreover, hypertensive cases without medical insurance, and diabetics engaging in a manual labor job were far less likely to utilize the services. In view of this, it is suggested to strengthen the publicity of essential public health services in the above-mentioned priority groups. Besides that, the awareness of doctors in community health centers should be strengthened to provide patients with guidance on developing healthy lifestyles, such as stopping smoking and drinking

Bradyrhizobium diazoefficiens USDA 110–glycine max interactome provides candidate proteins associated with symbiosis

Although the legume−rhizobium symbiosis is a most-important biological process, there is a limited knowledge about the protein interaction network between host and symbiont. Using interolog- and domain-based approaches, we constructed an interspecies protein interactome containing 5115 protein−protein interactions between 2291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins. The interactome was further validated by the expression pattern analysis in nodules, gene ontology term semantic similarity, co-expression analysis, and luciferase complementation image assay. In the G. max−B. diazoefficiens interactome, bacterial proteins are mainly ion channel and transporters of carbohydrates and cations, while G. max proteins are mainly involved in the processes of metabolism, signal transduction, and transport. We also identified the top 10 highly interacting proteins (hubs) for each species. Kyoto Encyclopedia of Genes and Genomes pathway analysis for each hub showed that a pair of 14-3-3 proteins (SGF14g and SGF14k) and 5 heat shock proteins in G. max are possibly involved in symbiosis, and 10 hubs in B. diazoefficiens may be important symbiotic effectors. Subnetwork analysis showed that 18 symbiosis-related soluble N-ethylmaleimide sensitive factor attachment protein receptor proteins may play roles in regulating bacterial ion channels, and SGF14g and SGF14k possibly regulate the rhizobium dicarboxylate transport protein DctA. The predicted interactome provide a valuable basis for understanding the molecular mechanism of nodulation in soybean

Novel Genotype-Phenotype Correlations in Five Chinese Families with Von Hippel-Lindau Disease.

CONTEXT: Von Hippel-Lindau (VHL) disease manifests as a variety of benign and malignant neoplasms. Previous studies of VHL disease have documented several genotype-phenotype correlations; however, many such correlations are still unknown. Increased identification of new mutations and patients with previously described mutations will allow us to better understand how VHL mutations influence disease phenotypes. PATIENTS AND DESIGN: A total of 45 individuals from five unrelated families were evaluated, of which 21 patients were either diagnosed with VHL disease or showed strong evidence related to this disease. We compared the patients\u27 gene sequencing results with their medical records including computed tomography or magnetic resonance imaging scans, eye examinations, and laboratory/pathological examinations. Patients were also interviewed to obtain information regarding their family history. RESULTS: We identified four missense mutations: c. 239G\u3eT (p.Ser80Ile), linked with VHL Type 2B, was associated with renal cell carcinoma (RCC), pheochromocytoma (Pheo), and hemangioma (HB) in the cerebellum; c. 232A\u3eT (p.Asn78Tyr) manifested as RCC alone and likely caused VHL Type 1; c.500G\u3eA (p.Arg167Gln) mutation was more likely to cause VHL Type 2 than Type 1 as it preferentially induced Pheo and HB in the retina, cerebellum, and spinal cord; c.293A\u3eG (p.Try98Cys) was associated with Pheo and thus likely induced VHL Type 2. CONCLUSIONS: Characterizing VHL disease genotype-phenotype correlations can enhance the ability to predict the risk of individual patients developing different VHL-related phenotypes. Ultimately, such insight will improve the diagnostics, surveillance, and treatment of VHL patients

Association between systemic inflammatory indicators with the survival of chronic kidney disease: a prospective study based on NHANES

Backgroundsystemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the systemic inflammatory indicators could be optimal predictors for the survival of CKD remains less studied.MethodsIn this study, participants were selected from the datasets of the National Health and Nutrition Examination Survey (NHANES) between 1999 to 2018 years. Four systemic inflammatory indicators were evaluated by the peripheral blood tests including systemic immune-inflammation index (SII, platelet*neutrophil/lymphocyte), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). Kaplan-Meier curves, restricted cubic spline (RCS), and Cox regression analysis were used to evaluate the association between the inflammatory index with the all-cause mortality of CKD. Receiver operating characteristic (ROC) and concordance index (C-index) were used to determine the predictive accuracy of varied systemic inflammatory indicators. Sensitive analyses were conducted to validate the robustness of the main findings.ResultsA total of 6,880 participants were included in this study. The mean age was 67.03 years old. Among the study population, the mean levels of systemic inflammatory indicators were 588.35 in SII, 2.45 in NLR, 133.85 in PLR, and 3.76 in LMR, respectively. The systemic inflammatory indicators of SII, NLR, and PLR were all significantly positively associated with the all-cause mortality of CKD patients, whereas the high value of LMR played a protectable role in CKD patients. NLR and LMR were the leading predictors in the survival of CKD patients [Hazard ratio (HR) =1.21, 95% confidence interval (CI): 1.07-1.36, p = 0.003 (3rd quartile), HR = 1.52, 95%CI: 1.35-1.72, p<0.001 (4th quartile) in NLR, and HR = 0.83, 95%CI: 0.75-0.92, p<0.001 (2nd quartile), HR = 0.73, 95%CI: 0.65-0.82, p<0.001 (3rd quartile), and = 0.74, 95%CI: 0.65-0.83, p<0.001 (4th quartile) in LMR], with a C-index of 0.612 and 0.624, respectively. The RCS curves showed non-linearity between systemic inflammatory indicators and all-cause mortality risk of the CKD population.ConclusionOur study highlights that systemic inflammatory indicators are important for predicting the survival of the U.S. population with CKD. The systemic inflammatory indicators would add additional clinical value to the health care of the CKD population