1.α-mangostin inhibits LPS/ATP-induced NLRP3 inflammasome activation in microglia via the NF- κB pathway
Min Chen ; Jing Tao ; Huiyan Zhu
Acta Universitatis Medicinalis Anhui 2024;59(4):575-580
Objective :
To investigate the effects and underlying mechanisms of α-mangostin in a spinal cord inj ury model of microglial cell inflammation .
Methods :
Mouse microglial cell line BV-2 was cultured in vitro , and an in- flammation model was established by co-treatment with lipopolysaccharide and adenosine triphosphate (LPS/ATP) . The CCK-8 assay was used to test the influence of different concentrations (0 , 10 , 20 , 40 , 80 μmol/L) of α-man- gostin on cell proliferation vitality under LPS/ATP stimulation to select an appropriate concentration range of α- mangostin; BV-2 cells were divided into Ctrl group , LPS/ATP group , 40 μmol/L α-mangostin group , and inter- vention groups with different concentrations (10 , 20 , 40 μmol/L) of α-mangostin ( designated as LPS/ATP + 10 μmol/L α-mangostin group , LPS/ATP + 20 μmol/L α-mangostin group , and LPS/ATP + 40 μmol/L α-mangostin group , respectively) . ELISA experiments were conducted to detect the levels of pro-inflammatory cytokines inter- leukin -6/1β/18 (IL-6 , IL-1β, IL-18) and tumor necrosis factor (TNF-α) in the supernatants of each group , and Western blot was used to detect the expression of NLRP3 , ASC , cleaved caspase-1 , IL-1β, and the phosphoryla- tion levels of p65 (p-p65/p65) in the NF- κB pathway , as well as the expression of p65 in the nuclei of BV-2 cells .
Results :
Compared with the Ctrl group, cell proliferation vitality in the LPS/ATP group was significantly reduced (P < 0. 05) , but low concentrations (10 , 20 , 40 μmol/L) of α-mangostin significantly improved the inhibi- tory effect of LPS/ATP on microglial cell proliferation vitality (P < 0. 05) , while a high concentration (80 μmol/ L) of α-mangostin exacerbated the damage to microglial cells caused by LPS/ATP (P < 0. 05) . C ompared with the Ctrl group , the levels of inflammatory factors IL-6 , IL-1β, IL-18 , TNF-α, and the expression of NLRP3 , ASC , cleaved caspase-1 , IL-1β, and the p-p65/p65 ratio in the 40 μmol/L α-mangostin group , as well as the expression of p65 protein in the nuclei , showed no significant changes ( P > 0 . 05) , whereas these significantly increased in the LPS/ATP group (P < 0. 05) . Compared with the LPS/ATP group , the levels of IL-6 , IL-1β, IL-18 , TNF-α, and the expression of NLRP3 , ASC , cleaved caspase-1 , IL-1β, and the p-p65/p65 ratio in the intervention groups , as well as the expression of p65 protein in the nuclei , decreased in a concentration-dependent manner with increasing α-mangostin concentration , with the most significant reduction ob served in the LPS/ATP + 40 μmol/L α- mangostin group (P < 0. 01) .
Conclusion
α-mangostin can inhibit the neuroinflammatory response mediated by NLRP3 inflammasome activation in BV-2 cells through the NF- κB pathway .
2.Influence of infection frequency and vaccination on virus mutation of SARS-CoV-2
Guo XU ; Huan FAN ; Jianguang FU ; Huiyan YU ; Fei DENG ; Zhuhan DONG ; Shihan ZHANG ; Fengcai ZHU ; Changjun BAO ; Liguo ZHU
Chinese Journal of Experimental and Clinical Virology 2024;38(5):481-488
Objective:To analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.Methods:The whole genome sequencing sequences of 2 659 local SARS-CoV-2 specimens from Jiangsu Province in 2023 were selected for analysis, and relevant information such as demographic and clinical characteristics were collected, and the effects of infection and vaccination on the genome-wide mutation rate and S gene′s selective pressure of the virus were analyzed by univariate and multivariate linear regression models.Results:The average age of these infected patients was 55.0 (31.0, 74.0) years, 1 150 cases (43.2%) in the age group of ≥60 years, 1 367 cases (51.4%) were males, 2 044 cases (76.9%) had a history of COVID-19 vaccination, and 1 629 cases (61.3%) had the first-time infection. The clinical symptoms of the infected patients were mainly mild, with a total of 2434 cases (91.5%), and 29 cases (1.1%) with severe symptoms or more. The average substitution rate of SARS-CoV-2 was 9.69 (9.38, 9.98)×10 -4 subs/site/year, and the dN/dS value of the S gene was 6.08 (5.56, 8.66), which was significantly greater than that of 1 ( P<0.001), indicating positive selection. The result of univariate and multivariate linear regression model analysis showed that the SARS-CoV-2 substitution rate was higher in those with vaccination history and reinfection, aged 20-30 years, ≥60 years, and the SARS-CoV-2 substitution rate was lower in males with moderate clinical symptoms and severe disease and above. Those with a history of vaccination and reinfection, aged 50-60 years old, ≥60 years old have smaller S gene dN/dS. Conclusions:Under the immune pressure exerted by vaccination and infection, the genome-wide mutation of SARS-COV-2 accelerated, but the non-synonymous mutation rate of the S gene decreased. The mechanism causing these phenomena needs further study.
3.Establishing integrated system-based point-of-care testing method for genotyping of respiratory syncytial virus
Fei DENG ; Liguo ZHU ; Ke XU ; Xian QI ; Huiyan YU ; Shenjiao WANG ; Changjun BAO
Chinese Journal of Microbiology and Immunology 2024;44(8):660-664
Objective:To develop an integrated point-of-care testing (POCT) reagent for genotying respiratory syncytial virus (RSV) and evaluate its performance.Methods:Specific primers and probes were designed based on the conserved sequences of the genomes of RSV A and B as well as ON1 and BA9 genotypes. The PCR reaction system and conditions were optimized. The vitrification technology of reagents and multiplex detection platform were integrated to develop the RSV genotyping POCT reagent. The sensitivity, specificity, reproducibility, and clinical performance of the product were then evaluated.Results:The sensitivity of the developed integrated RSV genotyping POCT reagent reached 500 copies/ml. It exhibited good specificity with no cross-reaction with clinically similar pathogens. The coefficient of variation of Ct values for both inter-batch and intra-batch reproducibility was less than 5%, indicating good reproducibility. In testing 53 clinical samples, the detection results showed high consistency and concordance with the reference reagent, with a positive concordance rate of up to 98.11%.Conclusions:The developed integrated RSV genotyping POCT reagent incorporates nucleic acid extraction, purification, and detection into a single process, achieving a "sample in, result out" workflow. It is simple to operate and provides accurate, reliable, and stable detection results. This product can be used for the genotyping of RSV A and B in POCT, offering support for the prevention, control, and diagnosis of RSV.
4.Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching
Xuezhong JIANG ; Weiming GE ; Hui HUANG ; Yating LI ; Xiaojing LIU ; Huiyan PANG ; Rui HE ; Hui WANG ; Zhengqiu ZHU ; Ping HE ; Yinping WANG ; Xuehui MA ; Airong REN ; Bixiao SHEN ; Meijuan WANG
Ultrasonography 2024;43(4):263-271
Purpose:
This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values.
Methods:
This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis.
Results:
PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05).
Conclusion
PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.
5.Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching
Xuezhong JIANG ; Weiming GE ; Hui HUANG ; Yating LI ; Xiaojing LIU ; Huiyan PANG ; Rui HE ; Hui WANG ; Zhengqiu ZHU ; Ping HE ; Yinping WANG ; Xuehui MA ; Airong REN ; Bixiao SHEN ; Meijuan WANG
Ultrasonography 2024;43(4):263-271
Purpose:
This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values.
Methods:
This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis.
Results:
PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05).
Conclusion
PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.
6.Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching
Xuezhong JIANG ; Weiming GE ; Hui HUANG ; Yating LI ; Xiaojing LIU ; Huiyan PANG ; Rui HE ; Hui WANG ; Zhengqiu ZHU ; Ping HE ; Yinping WANG ; Xuehui MA ; Airong REN ; Bixiao SHEN ; Meijuan WANG
Ultrasonography 2024;43(4):263-271
Purpose:
This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values.
Methods:
This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis.
Results:
PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05).
Conclusion
PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.
7.Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching
Xuezhong JIANG ; Weiming GE ; Hui HUANG ; Yating LI ; Xiaojing LIU ; Huiyan PANG ; Rui HE ; Hui WANG ; Zhengqiu ZHU ; Ping HE ; Yinping WANG ; Xuehui MA ; Airong REN ; Bixiao SHEN ; Meijuan WANG
Ultrasonography 2024;43(4):263-271
Purpose:
This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values.
Methods:
This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis.
Results:
PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05).
Conclusion
PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.
8.Arterial stiffness in subclinical atherosclerosis quantified with ultrafast pulse wave velocity measurements: a comparison with a healthy population using propensity score matching
Xuezhong JIANG ; Weiming GE ; Hui HUANG ; Yating LI ; Xiaojing LIU ; Huiyan PANG ; Rui HE ; Hui WANG ; Zhengqiu ZHU ; Ping HE ; Yinping WANG ; Xuehui MA ; Airong REN ; Bixiao SHEN ; Meijuan WANG
Ultrasonography 2024;43(4):263-271
Purpose:
This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values.
Methods:
This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis.
Results:
PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05).
Conclusion
PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.
9.Photohardening therapy for idiopathic actinic dermatoses
Huiyan DENG ; Jiaoquan CHEN ; Huaping LI ; Quan CHEN ; Sanquan ZHANG ; Huilan ZHU
Chinese Journal of Dermatology 2023;56(12):1091-1095
Photohardening therapy, also known as photodesensitization therapy, refers to the phototherapy and photochemotherapy of idiopathic actinic dermatoses, and its goal is to improve the patients′ tolerance to sunlight and prevent disease flares. Its mechanisms of action involve a variety of cellular and inflammatory factors. This therapy is suitable for all idiopathic actinic dermatoses, with definite efficacy and good safety. However, the treatment specificity usually leads to poor compliance. The development of UVA1 rush hardening and home phototherapy is expected to solve this problem.
10.Characterisation of serum lipidomic profiles in patients with chronic actinic dermatitis based on liquid chromatography-mass spectrometry
Quan CHEN ; Yi TANG ; Huaping LI ; Weihong WU ; Huiyan DENG ; Jiaoquan CHEN ; Lezi CHEN ; Zhenjie LI ; Huilan ZHU
Chinese Journal of Dermatology 2023;56(12):1107-1114
Objective:To investigate serum lipidomic profiles in patients with chronic actinic dermatitis (CAD), and to search for biomarkers of CAD.Methods:A retrospective analysis was conducted. Serum samples were collected from 46 patients with CAD and 16 age- and gender-matched healthy controls in the Guangzhou Institute of Dermatology from April 2011 to December 2021. Changes in serum lipid composition and expression were assessed by liquid chromatography-mass spectrometry. Principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis were performed to screen differential biomarkers, and receiver operating characteristic (ROC) curve analysis was conducted to screen diagnostic markers. Comparisons of the age and gender distribution between groups were performed using t test and chi-square test, respectively. Results:The 46 CAD patients were aged from 30 to 84 (60.39 ± 10.52) years, including 41 males and 5 females; the 16 healthy controls were aged from 50 to 89 (59.81 ± 10.72) years, including 14 males and 2 females; there were no significant differences in the age or gender distribution between the two groups (age: t = 0.19, P = 0.853; gender: χ2 = 0.03, P = 0.859). Totally, 4 136 lipid molecules belonging to 40 subclasses were identified in the serum samples from CAD patients as well as healthy controls. Twenty-two differential lipid molecules were identified between the CAD patients and healthy controls, belonging to 9 subclasses (triglycerides, sphingomyelin, phosphatidylserine, phosphatidylethanolamine, monofatty acid glycerides, lysophosphatidylcholine, hexose ceramide, diglycerides, and cardiolipin). When the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, or those of phosphatidylserine (18.0_18.1) and H served as diagnostic markers separately, the areas under the ROC curve (AUCs) were all > 0.8, and the AUCs of 16 differential lipid molecules were all > 0.7. Conclusion:The serum lipid composition differed between healthy controls and CAD patients, and the combinations of triglycerides (37.7e) and Na, those of monoglycerides (22.3) and NH 4, and those of phosphatidylserine (18.0_18.1) and H may be promising biomarkers for the diagnosis of CAD.


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