المؤلفون: Bethany Girard, Elisabeth Baum-Jones, Rebecca L. Best, Thomas W. Campbell, Jack Coupart, Kyla Dangerfield, Abhilash Dhal, Michael Jhatro, Brian Martinez, Jack Reifert, John Shon, Minlu Zhang, Rebecca Waitz, Spyros Chalkias, Darin K. Edwards, Maha Maglinao, Robert Paris, Rolando Pajon

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: antibody profile, COVID-19, dosing regimen, mRNA-1273, SARS-CoV-2, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundCharacterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines.MethodsThis study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants.ResultsMultiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster.ConclusionOverall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1285278/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/cc8df3d9850f45bab0fa8123a2fec74eTest

المؤلفون: Tianyou Wang, Xiaofan Zhu, Yumei Chen, Shuhong Shen, Yongmin Tang, Jingying Zhang, Yingyi He, Hui Zhang, Ju Gao, Jianpei Fang, Rong Liu, Xiaoyan Wu, Jinchuan Sun, Minlu Zhang

المصدر: Drugs in R&D, Vol 23, Iss 2, Pp 129-140 (2023)

مصطلحات موضوعية: Therapeutics. Pharmacology, RM1-950

الوصف: Abstract Introduction Despite rasburicase's proven efficiency in Caucasians, Japanese, and Koreans, studies evaluating the safety and effectiveness of rasburicase in Chinese pediatric patients with non-Hodgkin’s lymphoma (NHL) and acute leukemia (AL) in particular are lacking. Objective The aim was to evaluate the safety and effectiveness of rasburicase in Chinese pediatric patients with NHL and AL. Methods In this phase IV, open-label, non-randomized, single-arm, multi-center, interventional study (NCT04349306), children newly diagnosed with NHL or AL who received 0.20 mg/kg/day of rasburicase were included. The primary objective was to assess the safety of rasburicase by the incidence of adverse events (AEs). The secondary objective was to determine the effectiveness of rasburicase in the control of hyperuricemia. Results Out of 50 patients, 25 reported a total of 76 treatment-emergent adverse events (TEAEs), including eight TEAEs of grade ≥ 3 in 12 patients. A drug-related serious AE was reported in one patient, and there was no incidence of death. The response rate in the intent-to-treat population was 100.0% (95% confidence interval 82.4–100.0) in patients (n = 19) with baseline uric acid level of > 8.0 mg/dL. Similarly, the response rate was 86.2% (n = 25) among 29 patients (60.4%) with baseline uric acid levels of ≤ 8.0 mg/dL. The maximum mean percentage decrease of plasma uric acid level in the overall patients was 96.9%. Conclusion Rasburicase was well tolerated and effective in controlling hyperuricemia in Chinese pediatric patients with NHL and AL.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1174-5886Test; https://doaj.org/toc/1179-6901Test

الوصول الحر: https://doaj.org/article/ac04eccf4d1f497e8458b936e1df7fc3Test

المؤلفون: Winston A. Haynes, Kathy Kamath, Joel Bozekowski, Elisabeth Baum-Jones, Melissa Campbell, Arnau Casanovas-Massana, Patrick S. Daugherty, Charles S. Dela Cruz, Abhilash Dhal, Shelli F. Farhadian, Lynn Fitzgibbons, John Fournier, Michael Jhatro, Gregory Jordan, Jon Klein, Carolina Lucas, Debra Kessler, Larry L. Luchsinger, Brian Martinez, M. Catherine Muenker, Lauren Pischel, Jack Reifert, Jaymie R. Sawyer, Rebecca Waitz, Elsio A. Wunder, Minlu Zhang, Yale IMPACT Team, Akiko Iwasaki, Albert Ko, John C. Shon

المصدر: Communications Biology, Vol 4, Iss 1, Pp 1-14 (2021)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Using a high throughput, random bacterial peptide display approach applied to patient serum samples, Haynes, Kamath, Bozekowski et al identify the antigens and epitopes that elicit a SARS-CoV-2 humoral response. They identify differences depending on disease severity and further in silico analysis suggests decreased epitope signal for Q677P but not for D614G mutant SARSCoV-2 strains.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2399-3642Test

الوصول الحر: https://doaj.org/article/35fd28046b3d4061a1a0e849a204b9bbTest

المؤلفون: Fuqiang Liu, Yuan Liu, Minzhi Liu, Guangyu Wu, Minlu Zhang, Xia Zhang, Nan Cui, Huiqiu Yin, Li Chen

المصدر: Journal of Diabetes Investigation, Vol 12, Iss 8, Pp 1386-1394 (2021)

مصطلحات موضوعية: Glucagon‐like peptide‐1 receptor agonist, Lixisenatide, Pooled analysis, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Abstract Aims/Introduction The prevalence and pathophysiological background of type 2 diabetes mellitus vary across ethnicities, and can affect treatment responses. Adding lixisenatide to basal insulin (BI) in type 2 diabetes mellitus patients has shown improvements in glycated hemoglobin (HbA1c) and postprandial glycemic (PPG) excursions, without increasing hypoglycemic events. We aim to compare the efficacy of lixisenatide in Asian and white patients inadequately controlled with basal insulin. Materials and Methods An individual‐level pooled analysis of two multi‐national phase III studies, GetGoal‐L and GetGoal‐L‐C, was carried out to assess the efficacy of lixisenatide versus placebo as an add‐on treatment to BI ± metformin in Asian and white patients with type 2 diabetes mellitus. Change in HbA1c, 2‐h PPG and PPG excursion were analyzed, along with possible predictors of glycemic control. Results Pooled data showed that baseline characteristics were similar between Asian and white patients with the exception of bodyweight, body mass index and BI dose being higher in white patients. After 24 weeks, lixisenatide reduced HbA1c in both ethnic groups, with no statistically significant difference between the two groups (Asian patients least squares mean difference −0.49, 95% confidence interval −0.68 to − 0.30 and white patients least squares mean difference −0.45, 95% confidence interval −0.63 to − 0.26; P = 0.6287). Similarly, no significant difference was found in 2‐h PPG reduction between both groups (least squares mean difference for Asian vs white patients: −3.37 vs −3.93; P = 0.3203). Treatment with lixisenatide contributed to HbA1c reduction of −0.56% after adjustment of baseline HbA1c level in Asian patients, and −0.41% in white patients. Conclusions Adding lixisenatide to BI significantly reduced HbA1c and 2‐h PPG levels in both Asian and white participants with type 2 diabetes mellitus. No differences in treatment effect were observed between the two populations.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2040-1116Test; https://doaj.org/toc/2040-1124Test

الوصول الحر: https://doaj.org/article/fffcb0cdaaaa4cfcac5061e371be5ef1Test

المؤلفون: Xia Zhang, Ran Meng, Dalong Zhu, Weimin Wang, Guangyu Wu, Minlu Zhang, Wenhuan Feng, Huiqiu Yin

المصدر: BMJ Open Diabetes Research & Care, Vol 9, Iss 1 (2021)

مصطلحات موضوعية: Diseases of the endocrine glands. Clinical endocrinology, RC648-665

وصف الملف: electronic resource

العلاقة: https://drc.bmj.com/content/9/1/e002290.fullTest; https://doaj.org/toc/2052-4897Test

الوصول الحر: https://doaj.org/article/eff7d78cdce748a5a311359f63092c23Test

المؤلفون: Jeffrey Huang, Sumanta Pal, Tanya Dorff, Owen T M Chan, Hideki Furuya, Ian Pagano, Yosuke Hirasawa, Jared Acoba, David Tamura, Minlu Zhang, Rebecca Waitz, Abhilash Dhal, Winston Haynes, John Shon, Mark Scholz, Charles Rosser

المصدر: Journal for ImmunoTherapy of Cancer, Vol 9, Iss 8 (2021)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background Combining an immune checkpoint inhibitor with a tumor vaccine may modulate the immune system to leverage complementary mechanisms of action that lead to sustained T-cell activation and a potent prolonged immunotherapeutic response in metastatic castration resistant prostate cancer (mCRPC).Methods Subjects with asymptomatic or minimally symptomatic mCRPC were randomly assigned in a 1:1 ratio to receive either atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2). The primary endpoint was safety, while secondary endpoints included preliminary clinical activity such as objective tumor response and systemic immune responses that could identify key molecular and immunological changes associated with sequential administration of atezolizumab and sipuleucel-T.Results A total of 37 subjects were enrolled. The median age was 75.0 years, median prostate specific antigen (PSA) was 21.9 ng/mL, and subjects had a median number of three prior treatments. Most subjects (83.8%) had at least one treatment-related adverse event. There were no grade 4 or 5 toxicities attributed to either study drug. Immune-related adverse events and infusion reactions occurred in 13.5% of subjects, and all of which were grade 1 or 2. Of 23 subjects with Response Evaluation Criteria in Solid Tumors measurable disease, only one subject in Arm 2 had a partial response (PR) and four subjects overall had stable disease (SD) at 6 months reflecting an objective response rate of 4.3% and a disease control rate of 21.7%. T-cell receptor diversity was higher in subjects with a response, including SD. Immune response to three novel putative antigens (SIK3, KDM1A/LSD1, and PIK3R6) appeared to increase with treatment.Conclusions Overall, regardless of the order in which they were administered, the combination of atezolizumab with sipuleucel-T appears to be safe and well tolerated with a comparable safety profile to each agent administered as monotherapy. Correlative immune studies may suggest the combination to be beneficial; however, further studies are needed.Trial registration number NCT03024216.

وصف الملف: electronic resource

العلاقة: https://jitc.bmj.com/content/9/8/e002931.fullTest; https://doaj.org/toc/2051-1426Test

الوصول الحر: https://doaj.org/article/777a359f9d2d4d038339263ff0f9ad51Test

المؤلفون: Minlu Zhang, Hui Cai, Pingping Bao, Wanghong Xu, Guoyou Qin, Xiao Ou Shu, Ying Zheng

المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract Obesity has been well studied in relation to breast cancer survival. However, the associations of post-diagnosis obesity and late outcomes (≥5 years after diagnosis) have been much less studied. A total of 4062 5-year disease-free patients were recruited from the Shanghai Breast Cancer Survival Study, a longitudinal study of patients diagnosed during 2002-2006. Cox proportional hazard model with restricted cubic spline were used to evaluate the potential non-linear associations of post-diagnosis body mass index (BMI) and waist-to-hip ratio (WHR) with late all-cause mortality and late recurrence. While no significant association was observed for post-diagnosis BMI or WHR with late recurrence; a U-shaped association was observed for the two measures with late all-cause death. Women with BMI of 25.0 kg/m2 or WHR of 0.83 were at the lowest risk of late all-cause mortality, whereas those with BMI beyond the range of 22.1–28.7 kg/m2 or WHR beyond the range of 0.81–0.86 had a higher risk. ER, stage or menopausal status did not modify the effect of post-diagnosis BMI or WHR on the outcomes. In conclusion, post-diagnosis BMI and WHR, as indicators of overall and central obesity respectively, were associated with late all-cause mortality in U-shaped pattern among long-term breast cancer survivors.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/d9e9ba4317d8419d8f461c54f4dc55fdTest

المؤلفون: Minlu Zhang, Shengchang Su, Raj K Bhatnagar, Daniel J Hassett, Long J Lu

المصدر: PLoS ONE, Vol 7, Iss 7, p e41202 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Pseudomonas aeruginosa (PA) is a ubiquitous opportunistic pathogen that is capable of causing highly problematic, chronic infections in cystic fibrosis and chronic obstructive pulmonary disease patients. With the increased prevalence of multi-drug resistant PA, the conventional "one gene, one drug, one disease" paradigm is losing effectiveness. Network pharmacology, on the other hand, may hold the promise of discovering new drug targets to treat a variety of PA infections. However, given the urgent need for novel drug target discovery, a PA protein-protein interaction (PPI) network of high accuracy and coverage, has not yet been constructed. In this study, we predicted a genome-scale PPI network of PA by integrating various genomic features of PA proteins/genes by a machine learning-based approach. A total of 54,107 interactions covering 4,181 proteins in PA were predicted. A high-confidence network combining predicted high-confidence interactions, a reference set and verified interactions that consist of 3,343 proteins and 19,416 potential interactions was further assembled and analyzed. The predicted interactome network from this study is the first large-scale PPI network in PA with significant coverage and high accuracy. Subsequent analysis, including validations based on existing small-scale PPI data and the network structure comparison with other model organisms, shows the validity of the predicted PPI network. Potential drug targets were identified and prioritized based on their essentiality and topological importance in the high-confidence network. Host-pathogen protein interactions between human and PA were further extracted and analyzed. In addition, case studies were performed on protein interactions regarding anti-sigma factor MucA, negative periplasmic alginate regulator MucB, and the transcriptional regulator RhlR. A web server to access the predicted PPI dataset is available at http://research.cchmc.org/PPIdatabaseTest/.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3404098?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/d294b36f465b4dbea9d78eb718c03fb6Test

المؤلفون: Xizhi Feng, Karthik Krishnan, Daryl L Richie, Vishukumar Aimanianda, Lukas Hartl, Nora Grahl, Margaret V Powers-Fletcher, Minlu Zhang, Kevin K Fuller, William C Nierman, Long Jason Lu, Jean-Paul Latgé, Laura Woollett, Simon L Newman, Robert A Cramer, Judith C Rhodes, David S Askew

المصدر: PLoS Pathogens, Vol 7, Iss 10, p e1002330 (2011)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: Endoplasmic reticulum (ER) stress is a condition in which the protein folding capacity of the ER becomes overwhelmed by an increased demand for secretion or by exposure to compounds that disrupt ER homeostasis. In yeast and other fungi, the accumulation of unfolded proteins is detected by the ER-transmembrane sensor IreA/Ire1, which responds by cleaving an intron from the downstream cytoplasmic mRNA HacA/Hac1, allowing for the translation of a transcription factor that coordinates a series of adaptive responses that are collectively known as the unfolded protein response (UPR). Here, we examined the contribution of IreA to growth and virulence in the human fungal pathogen Aspergillus fumigatus. Gene expression profiling revealed that A. fumigatus IreA signals predominantly through the canonical IreA-HacA pathway under conditions of severe ER stress. However, in the absence of ER stress IreA controls dual signaling circuits that are both HacA-dependent and HacA-independent. We found that a ΔireA mutant was avirulent in a mouse model of invasive aspergillosis, which contrasts the partial virulence of a ΔhacA mutant, suggesting that IreA contributes to pathogenesis independently of HacA. In support of this conclusion, we found that the ΔireA mutant had more severe defects in the expression of multiple virulence-related traits relative to ΔhacA, including reduced thermotolerance, decreased nutritional versatility, impaired growth under hypoxia, altered cell wall and membrane composition, and increased susceptibility to azole antifungals. In addition, full or partial virulence could be restored to the ΔireA mutant by complementation with either the induced form of the hacA mRNA, hacA(i), or an ireA deletion mutant that was incapable of processing the hacA mRNA, ireA(Δ10). Together, these findings demonstrate that IreA has both HacA-dependent and HacA-independent functions that contribute to the expression of traits that are essential for virulence in A. fumigatus.

وصف الملف: electronic resource

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028661/?tool=EBITest; https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test

الوصول الحر: https://doaj.org/article/e8921120d708438bbfb7eba100185cceTest

المؤلفون: Ching Tang, Minlu Zhang, 中尾 聡, 嘉治 寿彦, 平本 昌宏, 横山 和弥, 池滝 何以

المصدر: JSAP Annual Meetings Extended Abstracts. 2011, :2799