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.A preliminary study of mechanosensitive channels Piezo 1 and Piezo 2 promoting neurogenic bladder fibrosis in young rats
Lei LYU ; Yanping ZHANG ; Qi LI ; Junkui WANG ; Shuai YANG ; Zhaokai ZHOU ; Shuai LI ; Yibo WEN ; Yakai LIU ; Guowei SI ; Xingchen LIU ; Jianguo WEN
Journal of Modern Urology 2025;30(4):343-349
Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects,so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method:sham operation group (sham),2-week nerve transection group (NB-2W),6-week nerve transection group (NB-6W),2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W),with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling,while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased,while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group,but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group,but higher than that in the sham group (P<0.05).Compared with the sham group,the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group,NB-P-2W group had lower bladder leakage point pressure (BLPP),but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group,NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that,with the extension of nerve transection time,bladder fibrosis gradually worsened,the bladder wall became rough and thickened,calculi were visible inside,and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups,and no hydronephrosis was observed in the upper urinary tract.In addition,Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos,Collagen Ⅰ and α-SMA than the sham group (P<0.01),while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis,but its mechanism needs further study.
3.Analysis of The Characteristics of Brain Functional Activity in Gross Motor Tasks in Children With Autism Based on Functional Near-infrared Spectroscopy Technology
Wen-Hao ZONG ; Qi LIANG ; Shi-Yu YANG ; Feng-Jiao WANG ; Meng-Zhao WEI ; Hong LEI ; Gui-Jun DONG ; Ke-Feng LI
Progress in Biochemistry and Biophysics 2025;52(8):2146-2162
ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.
4. Exploration of molecular mechanism of Selaginella moelledorffii Hieron. in treatment of laryngeal cancer based on network-based pharmacology, molecular docking techniques and experimental validation
Yuan-Yuan LI ; Xin-Zhou YANG ; Si-Si WANG ; Wen-Qi LIU ; Li KANG ; Xin-Zhou YANG ; Sefidkon FATEMEH
Chinese Pharmacological Bulletin 2024;40(2):352-362
Aim To explore the molecular mechanism of Selaginella moelledorffii Hieron. in the treatment of laryngeal cancer. Methods According to the relevant literature reports, the chemical constituents of S. moellendorffii were obtained, and the active ingredients were screened out through the SwissADME database, and the targets were screened through the PharmMapper database. The laryngeal cancer-related targets were collected by searching OMIM and other databases, and the Venny 2.1.0 online platform was used to obtain the intersection of the two. Protein interaction analysis of the potential targets was performed using the STRNG platform. GO functional analysis and KEGG pathway analysis was carried out using DAVID database. Visual networks were built with Cytoscape 3.8.0 software. Molecular docking was validated by SYBYL-X 2. 0 software. MTT method, Hoechst 33258 staining method and Western blotting were also used for validation. Results At the molecular level, a total of 110 active ingredients of S. moellendorffii and 82 drug targets were screened out, 1,608 targets related to laryngeal cancer, and intersection of 34 targets. GO analysis yielded 135 entries, and KEGG analysis yielded a total of 61 pathways. Molecular docking results showed that the 11 key active ingredients such as 2", 3"-dihydrooch-naflavone wood flavonoids and 4 core target proteins such as MAPK1 had 95. 5% of good docking activity. At the cellular level, SM-BFRE was screened for its strongest inhibitory effect on laryngeal cancer cell proliferation through MTT assay. Furthermore, Hoechst 33258 staining showed that the decrease in Hep-2 cell viability produced by SM-BFRE was related to cell apoptosis. Finally, Western blot verified that SM-BFRE inhibited PI3K/Akt/NF through inhibition- K B/COX-2 pathway to induce apoptosis in laryngeal cancer cells. Conclusions To sum up, it fully reflects the multicomponent, multi-target, and multi-channel synergistic effect of S. moellendorffii in the treatment of laryngeal cancer, and provides a theoretical reference for further elucidation of the mechanism of action of S. moellendorffii in the treatment of laryngeal cancer.
5.A new suberin from roots of Ephedra sinica Stapf
Bo-wen ZHANG ; Meng LI ; Xiao-lan WANG ; Ying YANG ; Shi-qi ZHOU ; Si-qi TAO ; Meng YANG ; Deng-hui ZHU ; Ya-tong XU ; Wei-sheng FENG ; Xiao-ke ZHENG
Acta Pharmaceutica Sinica 2024;59(3):661-666
Six compounds were isolated from the roots of
6.Recent advances in lamellar liquid crystal emulsification methods encapsulating natural active substances for functional cosmetics
Yi ZHANG ; Wei CHEN ; Yan-qi HAN ; Qian-wen SUN ; Yue GAO ; Jun YE ; Hong-liang WANG ; Li-li GAO ; Yu-ling LIU ; Yan-fang YANG
Acta Pharmaceutica Sinica 2024;59(2):350-358
Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.
7.Application of the OmniLogTM microbial identification system in the detection of the host spectrum for wild-type plague phage in Qinghai Plateau
Cun-Xiang LI ; Zhi-Zhen QI ; Qing-Wen ZHANG ; Hai-Hong ZHAO ; Long MA ; Pei-Song YOU ; Jian-Guo YANG ; Hai-Sheng WU ; Jian-Ping FENG
Chinese Journal of Zoonoses 2024;40(1):21-25
The growth of three plague phages from Qinghai Plateau in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,PTB5,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were detected through a micromethod based on the OmniLogTM microbial identification system and by the drop method,to provide a scientific basis for future ecological studies and classification based on the host range.For plague vaccine strains EV76 and 614F,successful phage infection and subsequent phage growth were observed in the host bacte-rium.Diminished bacterial growth and respiration and a concomitant decrease in color were observed with the OmniLogTM mi-crobial identification system at 33 ℃ for 48 h.Yersinia pseudotuberculosis PTB5 was sensitive to Yersinia pestis phage 476,but Yersinia pseudotuberculosis PST5 was insensitive to phage 087 and 072204.Three strains of non-Yersinia pestis(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersinia enterocolitica 52302-2)were insensitive to Yersinia pestis pha-ges 087,072204,and 476 showed similar growth curves.The growth of phages 476 and 087,as determined with the drop method,in two Yersinia pestis strains(plague vaccine strains EV76 and 614F)and four non-Yersinia pestis strains(Yersinia pseudotuberculosis PTB3,Escherichia coli V517,and Yersin-ia enterocolitica 52302-2)showed the same results at 37 ℃,on the basis of comparisons with the OmniLogTM microbial i-dentification system;in contrast,phages 072204 did not show plaques on solid medium at 37 ℃ with plague vaccine strains EV76 and 614F.Determination based on the OmniLogTM detection system can be used as an alternative to the traditional determination of the host range,thus providing favorable application val-ue for determining the interaction between the phage and host bacteria.
8.Research Status of Irisin in Improving Hepatic Lipid Metabolism Disorder and Reducing NAFLD
Kai-Ling HUANG ; Xin-Cheng YANG ; Liang-Ming LI ; Wen-Qi YANG
Progress in Biochemistry and Biophysics 2024;51(8):1873-1882
Nonalcoholic fatty liver disease (NAFLD) does great harm to human health, and the incidence is increasing year by year. The liver serves an important role in lipid metabolism. Hepatic steatosis develops as a consequence of lipid metabolic dysregulation, namely the imbalance among fatty acid uptake, de novo lipogenesis (DNL), fatty acid oxidation (FAO) and very low density lipoprotein-mediated lipid export. With diverse health-promoting effects, exercise is a cheap and effective intervention for the prevention and treatment of NAFLD. Amelioration of impaired lipid metabolism acts as an important mechanism by which exercise protects against NAFLD. However, how exercise ameliorates lipid metabolic dysregulation is still unclear. Skeletal muscle is not only a vital organ of motion, but also has an endocrine function, it secretes numerous myokines which mediates exercise-induced benefits on our body. Irisin is a small peptide derived from proteolytic cleavage of fibronectin type III domain containing protein 5 (FNDC5). As a myokine, its production is regulated by exercise and it play an important role in exercise-induced protection against obesity-related chronic diseases, such as NAFLD. A growing body of research has demonstrated that Irisin ameliorates lipid metabolic dysregulation in NAFLD. Irisin mediated inhibition of hepatic DNL and FAO has been reported. However, the effect of Irisin on fatty acid uptake and lipid export is still unknown. In the present review, we summarized the researches focusing on how exercise regulated Irisin production and the effect of Irisin on lipid metabolism on NAFLD. To clarify the above problems will help us to better understand the role of Irisin on exercise-mediated protection against NAFLD.
9.A new iridoid from Eucommia ulmoides
Shi-qi ZHOU ; Zhi-you HAO ; Meng YANG ; Chao-yuan XIAO ; Jun-yang ZHANG ; Bo-wen ZHANG ; Si-qi TAO ; Xiao-ke ZHENG ; Wei-sheng FENG
Acta Pharmaceutica Sinica 2024;59(7):2062-2068
Eleven compounds were isolated from
10.Research Progress on Animal Models of Sepsis-Related Organ Injury
Jiahao YANG ; Chunlei DING ; Fenghua QIAN ; Qi SUN ; Xusheng JIANG ; Wen CHEN ; Mengwen SHEN
Laboratory Animal and Comparative Medicine 2024;44(6):636-644
Sepsis is a multi-organ dysfunction syndrome caused by infection and immune dysfunction, with a high mortality rate. It affects multiple important organs such as the heart, lungs, kidneys, liver, and brain. Establishing corresponding animal models of organ dysfunction syndrome is an essential step in clarifying its pathogenesis, researching potential effective drugs, and evaluating the effectiveness and safety of treatment plans. This article first summarizes classic modeling methods for sepsis related organ injury, including the destruction of intestinal barrier tissue integrity and the implantation of pathogens or toxic drugs. The former mainly includes cecal ligation and puncture, ascending colon stent implantation, and cecal ligation incision. The latter is divided into intraperitoneal injection, intravenous injection, and intratracheal administration based on the clinical infection route being simulated. Cecal ligation and puncture and lipopolysaccharide intraperitoneal injection are the most commonly used methods. Secondly, this article summarizes the common modeling methods and evaluation methods for animal models of sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction. It points out that almost all organ injuries use classic modeling methods, and different organ injury models have additional modifications according to their different pathogenesis. For example, in addition to the classic modeling methods, lipopolysaccharide instillation in the trachea is more effective in modeling acute lung injury as it better simulates lung barrier dysfunction. Cecal ligation and puncture followed by Pseudomonas instillation in the trachea in a secondary challenge model better represents sepsis-induced acute kidney injury. Intraperitoneal injection of galactosamine is a mature modeling method of sepsis-induced acute liver injury. Intracerebral injection of lipopolysaccharide is a feasible model of sepsis-associated encephalopathy. In addition to the different modeling methods, there are differences in the administration time, dosage and experimental time points according to the different experimental purposes. This article reviews the research progress of animal experimental models for sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction, aiming to provide a reference for the selection of animal experimental models and optimization of experimental design.

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