1.Inhibition of HDAC3 Promotes Psoriasis Development in Mice Through Regulating Th17
Fan XU ; Xin-Rui ZHANG ; Yang-Chen XIA ; Wen-Ting LI ; Hao CHEN ; An-Qi QIN ; Ai-Hong ZHANG ; Yi-Ran ZHU ; Feng TIAN ; Quan-Hui ZHENG
Progress in Biochemistry and Biophysics 2025;52(4):1008-1017
ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4+ T lymphocytes, CD8+ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4+ T lymphocytes. Additionally, spleen CD4+ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4+ and CD8+ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4+ and CD8+ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4+ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4+ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.
2.Terms Related to The Study of Biomacromolecular Condensates
Ke RUAN ; Xiao-Feng FANG ; Dan LI ; Pi-Long LI ; Yi LIN ; Zheng WANG ; Yun-Yu SHI ; Ming-Jie ZHANG ; Hong ZHANG ; Cong LIU
Progress in Biochemistry and Biophysics 2025;52(4):1027-1035
Biomolecular condensates are formed through phase separation of biomacromolecules such as proteins and RNAs. These condensates exhibit liquid-like properties that can futher transition into more stable material states. They form complex internal structures via multivalent weak interactions, enabling precise spatiotemporal regulations. However, the use of inconsistent and non-standardized terminology has become increasingly problematic, hindering academic exchange and the dissemination of scientific knowledge. Therefore, it is necessary to discuss the terminology related to biomolecular condensates in order to clarify concepts, promote interdisciplinary cooperation, enhance research efficiency, and support the healthy development of this field.
3.Status Analysis of Acupoint Selection and Stimulation Parameters Application for Acupuncture Treatment of Functional Dyspepsia
Siyi ZHENG ; Han ZHANG ; Yang YU ; Chuanlong ZHOU ; Yan SHI ; Xiaohu YIN ; Shouhai HONG ; Na NIE ; Jianqiao FANG ; Yi LIANG
Journal of Traditional Chinese Medicine 2025;66(12):1293-1299
Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia (FD), this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS, whereas local acupoints alone may be more suitable for EPS. Additionally, the study explores the impact of various factors, such as stimulation techniques, needling order, intensity or stimulation parameters, and depth, on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations, local versus distal, affect the treatment outcomes of FD subtypes, providing new insights for clinical acupuncture prescriptions.
4. Nuclear factor-KB signaling pathway and gender differences in alcoholic liver fibrosis
Xiao-Rain HONG ; San-Qiang LI ; Qin-Yi CUI ; Run-Yue ZHENG ; Meng-Li YANG ; Ren-Li LUO ; Qian-Hui LI ; San-Qiang LI
Acta Anatomica Sinica 2024;55(1):55-61
Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E
5. Association between index finger and ring finger length ratios and polymorphism of homeobox A11 gene locus among Ningxia college students
Meng-Yi YANG ; Shi-Bo NIU ; Jing ZHANG ; Jie DANG ; Zhan-Bing MA ; Hong LU ; Zheng-Hao HUO
Acta Anatomica Sinica 2024;55(1):62-66
Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.
6.Association between index-ring finger length ratio and polymorphisms of 6 phalange-bone development related genes
Meng-Yi YANG ; Shi-Bo NIU ; Jing ZHANG ; Liang PENG ; Jie DANG ; Zhan-Bing MA ; Hong LU ; Zheng-Hao HUO
Acta Anatomica Sinica 2024;55(2):181-187
Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.
7.Effect and mechanism of dandelion flavonoids in alleviating lipopolysaccharide-induced colon epithelial cell injury
Jia-Qi ZHANG ; Dong-Xue MEI ; Sha LI ; Sheng-Gai GAO ; Jia ZHENG ; Hong-Xia LIANG ; Yi WANG
The Chinese Journal of Clinical Pharmacology 2024;40(4):549-553
Objective To investigate the protective effect of dandelion flavone(DF)on lipopolysaccharide(LPS)-induced colon epithelial cell injury by intervening oxidative stress and inflammation with AT-specific binding protein 2(SATB2).Methods Colon epithelial cells FHC were cultured.FHC cells were randomly divided into control group(normal cultured),LPS group(10 μg·mL-1 LPS),experimental-L group(10 μg·mL-1 LPS+1 μmol·L-1 DF),experimental-H group(10 μg·mL-1 LPS+5 μmol·L-1 DF),experimental-H+sh-NC group(transfected with sh-NC+10 μg·mL-1 LPS+5 μmol·mL-1 DF),experimental-H+sh-SATB2 group(transfected with sh-SATB2+10 μg·mL-1 LPS+5μmol·L-1 DF).The relative expression level of SATB2 protein in FHC cells was detected by Western blotting.The survival rate of FHC cells in each group was determined by tetramethylazolium blue(MTT).The apoptosis rate of FHC cells in each group was detected by flow cytometry.The levels of malondialdehyde(MDA)and interleukin-6(IL-6)in FHC cells were detected by the kit.Results The relative expression levels of SATB2 protein in control group,LPS group,experimental-H group,experimental-H+sh-NC group and experimental-H+sh-SATB2 group were 0.83±0.09,0.19±0.03,0.66±0.05,0.62±0.07 and 0.23±0.03,respectively;cell viability rates were(100.00±1.00)%,(48.16±4.31)%,(85.31±5.83)%,(81.39±6.47)%and(58.75±5.24)%,respectively;cell apoptosis rates were(3.27±0.81)%,(41.26±2.09)%,(11.35±1.04)%,(10.29±1.26)%and(35.87±2.15)%,respectively;MDA levels were(13.16±1.73),(52.87±3.49),(23.19±2.05),(20.98±3.17)and(44.87±3.05)μmol·L-1,respectively;IL-6 levels were(507.18±103.26),(2 132.09±198.15),(883.16±136.92),(801.69±119.85)and(1 736.29±206.91)pg·mL-1,respectively.The above indicators in the LPS group showed significant differences compared to the control group(all P<0.05);the above indicators in the experimental-H group showed significant differences compared to the LPS group(all P<0.05);the above indicators in the experimental-H+sh-SATB2 group showed significant differences compared to the experimental-H+sh-NC group(all P<0.05).Conclusion DF has a protective effect on LPS-induced colon epithelial cell injury by intervening oxidative stress and inflammation through SATB2.
8.Determination of L-synephrine in rat plasma by UHPLC-MS/MS method in pharmacokinetic study
Wei-Kang CHEN ; De-Hong LIU ; Yang-Bin ZHENG ; Qian-Ying WU ; Yi-Sheng YANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2256-2260
Objective To establish an ultra-high performance liquid phase tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma and to study its pharmacokinetics.Methods The plasma samples were precipitated by acetonitrile vortex,centrifuged,dried by nitrogen,dissolved by mobile phase,and then analyzed.Chromatographic column:Shiseido CAPCELL PAK CR(1∶4)column(2.0 mm × 150.0 mm,5 μm),temperature:25 ℃.Mobile phase:Acetonitrile:0.1%formic acid solution(containing 10 mmoL·L-1 ammonium formate)(73∶27)with flow rate:0.3 mL·min-1 and injection volume was 2 μL.The electrospray ion source ionization and positive ion multiple reaction monitoring mode were used for mass spectrometry detection,and biological sample methodology verification was carried out according to requirements.After intragastric administration with 5 mg·kg-1 dose of L-synephrine,blood samples were collected at different time points to investigate the pharmacokinetic characteristics of L-synephrine in rats.Results L-synephrine showed a good linear relationship in the range of 2-800 ng·mL-1,the lowest limit of quantification of L-synephrine was 2 ng·mL-1.Precision,extraction recovery,matrix effect,accuracy,dilution effect and residual effect all meet the requirements all met the requirements.The main pharmacokinetic parameters:Cmax were(464.83±76.68)ng·L-1,tmax were(0.67±0.26)h,t1/2z were(1.89±0.48)h,AUC0-t were(602.26±42.25)ng·mL-1·h-1,AUC0-∞ were(612.28±41.18)ng·mL-1·h-1.Conclusion The established ultra high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the determination of L-synephrine in rat plasma is simple and rapid,and can be used for the determination of L-synephrine in plasma.
9.Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study
Qing Zi KONG ; Qun Li LIU ; Qin De HUANG ; Tong Yu WANG ; Jie Jing LI ; Zheng ZHANG ; Xi Xi WANG ; Ling Chuan LIU ; Di Ya ZHANG ; Kang Jia SHAO ; Min Yi ZHU ; Meng Yi CHEN ; Mei LIU ; Hong Wei ZHAO
Biomedical and Environmental Sciences 2024;37(5):457-470
Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.
10.Schisandrin A ameliorates DSS-induced acute ulcerative colitis in mice via regulating the FXR signaling pathway
Jia-rui JIANG ; Kua DONG ; Yu-chun JIN ; Xin-ru YANG ; Yi-xuan LUO ; Shu-yang XU ; Xun-jiang WANG ; Li-hua GU ; Yan-hong SHI ; Li YANG ; Zheng-tao WANG ; Xu WANG ; Li-li DING
Acta Pharmaceutica Sinica 2024;59(5):1261-1270
Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects

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