1.Optimization of in vitro human follicular helper T cell differentiation condition
Yucong CHEN ; Wei GUO ; Wen LEI ; Yaoyao GE ; Wenyao XUE ; Qianwen LI ; Xiangdong GAO
Journal of China Pharmaceutical University 2017;48(6):733-737
In order to explore the regulation mechanisms of follicular helper T cell (Tfh Cell) differentiation,optimized conditions of in vitro induction from both peripheral blood mononuclear cells and MAC sorted Na(i)ve CD4 + T cells to human Tfh cells were developed.Induction efficiency difference of TCR signal anti-hCD3e stimulation between coated on solid phase and in soluble phase was also determined.Differentiation efficiency of CD4 + CXCR5 + ICOS+PD-1 + Tfh cell was determined by FACS while the expression level of IL-21 in cell supernatant was determined by ELISA tests.An ultimate induction condition that 5 μg/mL coated overnight anti-hCD3e stimulated na(i)ve CD4 + T cells to differentiate into Tfh at an up to 20.4% percentage was finally determined.The optimization of in vitro induction protocol of human Tfh provided an effective examine platform for the studies on Tfh differentiation mechanisms and related pharmacology,toxicity and metabolic experiments.
2.Association between Metabolic Syndrome and Microvascular Complications in Chinese Adults with Type 1 Diabetes Mellitus
Qianwen HUANG ; Daizhi YANG ; Hongrong DENG ; Hua LIANG ; Xueying ZHENG ; Jinhua YAN ; Wen XU ; Xiangwen LIU ; Bin YAO ; Sihui LUO ; Jianping WENG
Diabetes & Metabolism Journal 2022;46(1):93-103
Background:
Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications.
Methods:
We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR).
Results:
Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P<0.05).
Conclusion
Although the prevalence of MetS in adult patients with T1DM in China was relatively low, patients with MetS were more likely to have DKD and DR. A comprehensive management including lifestyle modification might reduce their risk of microvascular complications in adults with T1DM.
3.Reducing language barriers, promoting information absorption, and communication using fanyi
Difei WANG ; Guannan CHEN ; Lin LI ; Shaodi WEN ; Zijing XIE ; Xiao LUO ; Li ZHAN ; Shuangbin XU ; Junrui LI ; Rui WANG ; Qianwen WANG ; Guangchuang YU
Chinese Medical Journal 2024;137(16):1950-1956
Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.
4.Research Progress of Traditional Chinese Medicine Intervention on Intervertebral Disc Degeneration Based on Oxidative Stress
Zhenghan YANG ; Jirong ZHAO ; Junfei MA ; Qianwen CHEN ; Wen CHEN ; Ning ZHAO
Chinese Journal of Modern Applied Pharmacy 2024;41(1):138-144
Intervertebral disc degeneration(IDD) is the pathological basis of spinal diseases. With the development and change of working and living style, IDD gradually presents the trend of younger in recent years. The effective prevention and treatment of IDD has become a hotspot in clinical research. Recent studies have shown that oxidative stress plays an important role in IDD. The disruption of reactive oxygen species balance in cells or the body leads to changes in extracellular matrix and intervertebral disc cell phenotype, which induces oxidative stress of intervertebral disc and leads to IDD. Oxidative stress can affect the development of IDD through apoptosis, autophagy, senescence and extracellular matrix of intervertebral disc. Currently, opioids and drugs for promoting blood circulation and pain relief are commonly used in clinical treatment of IDD, which can alleviate some symptoms to a certain extent, but is easy to induce gastrointestinal and other adverse reactions. Meanwhile, due to the long treatment cycle and poor patient compliance to a certain extent, which brings great difficulties to the treatment. At the same time, traditional Chinese medicine plays an important role in the treatment of IDD due to its advantages of low cost and fewer adverse reactions. With the in-depth research of modern technologies such as molecular biology and network pharmacology, it has been found that traditional Chinese medicine can intervene in the expression of oxidative stress-related functions, namely, slowing down apoptosis, autophagy and degradation of extracellular matrix, etc, to play a role in the treatment of IDD. In this paper, the role of oxidative stress in IDD and the research results on the intervention of traditional Chinese medicine in oxidative stress will be expounded, in order to provide reference for the prevention and treatment of IDD by traditional Chinese medicine.
5.Role of Nrf2/HO-1 Signaling Pathway in Osteoporosis and Chinese Medicine Intervention: A Review
Jirong ZHAO ; Peng JIANG ; Wen CHEN ; Xiaping XIAO ; Xingsheng WANG ; Qianwen CHEN ; Junfei MA ; Zhenghan YANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(20):241-249
Osteoporosis is a chronic skeletal disease characterized by low bone mass, destruction of bone tissue microarchitecture, and imbalance of bone homeostasis, leading to increased bone fragility and increased risk of fractures. Oxidative stress caused by the disruption of the balance between excess reactive oxygen species (ROS) and the anti-oxidative system is an important factor in the occurrence and progression of osteoporosis. Nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) is an important anti-oxidative stress pathway. Nrf2 is a primary factor in regulating cellular oxidative stress. Activating Nrf2 can stimulate the expression of HO-1. HO-1 is a key enzyme whose metabolites are bile green Oxygen, carbon monoxide, and free iron. The metabolites can scavenge ROS, thereby exerting an antioxidant effect in cells. At present, domestic and foreign scholars have reported that the Nrf2/HO-1 signaling pathway is closely related to the occurrence and development of osteoporosis and the mechanism of drugs. Chinese medicine can effectively solve the insufficiency of western medicine with multi-target, multi-channel, and multi-level advantages. Chinese medicine can resist oxidative stress, inflammatory response, and apoptosis by regulating the Nrf2/HO-1 signaling pathway, thus treating osteoporosis. This article reviewed the relationship between Nrf2/HO-1 signaling pathway and its key target protein factors and osteoporosis, to clarify the important role of the Nrf2/HO-1 signaling pathway in osteoporosis. At the same time, a systematic summary of Chinese medicines targeting and regulating the Nrf2/HO-1 signaling pathway for the treatment of osteoporosis was conducted, to provide a theoretical basis for further precise treatment of osteoporosis.
6.Study on the Metabolic Characteristics of Piperitylmagnolol in Different Species of Liver Microsomes by UPLC-MS/MS
Xing DENG ; Liya LUO ; Liping GOU ; Qianwen WEN ; Minghai TANG ; Li WAN
China Pharmacy 2019;30(2):170-175
OBJECTIVE: To establish a method for the determination of piperitylmagnolol in the incubation system of liver microsomes, and to investigate the metabolic characteristics of it in different species of liver microsomes. METHODS: The piperitylmagnolol were respectively dissolved in NADPH activated liver microsome incubation systems of human, rat, mouse, monkey and dog, and then incubated in water at 37 ℃. The reaction was terminated with methanol at 0, 2, 5, 10, 15, 20, 30, 45 and 60 minutes of incubation, respectively. Using magnolol as internal standard, UPLC-MS/MS method was used to determine the concentration of piperitylmagnolol in the incubation system. The determination was performed on Acquity UPLCTM CSH C18 column with mobile phase consisted of 0.1% formic acid-methanol (gradient elution) at the flow rate of 0.3 mL/min. The column temperature was set at 30 ℃, and the sample size was 2 μL. The ion source was electrospray ion source, and the positive ion scanning was carried out in the multiple reaction monitoring mode. The ion pairs used for quantitative analysis were m/z 401.2→331.1 (piperitylmagnolol) and m/z 265.1→247.0 (internal standard), respectively. Using the concentration of piperitylmagnolol at 0 min of incubation as a reference, the residual percentage, metabolism half-life in vitro (t1/2) and intrinsic clearance (CLint) were calculated for different incubation systems. The metabolic pathway of piperitylmagnolol was studied by chemical inhibitor method. Under the above chromatographic conditions, the metabolites in vitro were preliminarily analyzed by first-order full scanning and positive ion detection. RESULTS: The linear range of piperitylmagnolol was 3.91-500.00 ng/mL. The limit of quantitation was 3.91 ng/mL. RSDs of intra-day and inter-day were less than 10%. The accuracy ranged 87.40%-103.75%. Matrix effect didn’t affect the determination of the substance to be measured. The piperitylmagnolol was metabolized significantly in human, rat, mouse and dog liver microsomes, but not in monkey liver microsomes. After incubating for 30 min, residual percentage of piperitylmagnolol kept stable in different species of liver microsomes. The t1/2 of piperitylmagnolol were 12.07, 17.68, 17.59, 216.56 and 61.88 min in human, rat, mouse, monkey and dog liver microsomes; CLint were 0.115, 0.078, 0.079, 0.006, 0.022 mL/(min·mg), respectively. Inhibitory rates of CYP2A6, CYP2D6, CYP2C19, CYP3A4, CYP2C9, CYP2E1 and CYP1A2 to compound metabolism were 55.76%, 93.94%, 96.01%, 93.69%, 71.81%, 23.25%, 28.04%, respectively. Quasi-molecular ion peaks of the two main metabolites of piperitylmagnolol in human liver microsomes were m/z 441.2([M+Na]+) and m/z 337.2([M+H]+), respectively. CONCLUSIONS: Established UPLC-MS/MS method is simple, rapid and specific, and can be used for the determination of piperitylmagnolol concentration in the incubation system of liver microsomes and pharmacokinetic study. The metabolic characteristics of the compound are different among liver microsomes of human, rat, mouse, monkey and dog. Its metabolism process may be associated with CYP2D6, CYP2C19, CYP3A4, CYP2C9, etc.