1. MW-9, a chalcones derivative bearing heterocyclic moieties, ameliorates ulcerative colitis via regulating MAPK signaling pathway
Zhao WU ; Nan-Ting ZOU ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ze-Wei MAO ; Chun-Ping WAN ; Ming-Qian JU ; Chun-Ping WAN ; Xing-Cai XU
Chinese Pharmacological Bulletin 2024;40(3):514-520
		                        		
		                        			
		                        			 Aim To investigate the therapeutic effect of the MW-9 on ulcerative colitis(UC)and reveal the underlying mechanism, so as to provide a scientific guidance for the MW-9 treatment of UC. Methods The model of lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cells was established. The effect of MW-9 on RAW264.7 cells viability was detected by MTT assay. The levels of nitric oxide(NO)in RAW264.7 macrophages were measured by Griess assay. Cell supernatants and serum levels of inflammatory cytokines containing IL-6, TNF-α and IL-1β were determined by ELISA kits. Dextran sulfate sodium(DSS)-induced UC model in mice was established and body weight of mice in each group was measured. The histopathological damage degree of colonic tissue was assessed by HE staining. The protein expression of p-p38, p-ERK1/2 and p-JNK was detected by Western blot. Results MW-9 intervention significantly inhibited NO release in RAW264.7 macrophages with IC50 of 20.47 mg·L-1 and decreased the overproduction of inflammatory factors IL-6, IL-1β and TNF-α(P<0.05). MW-9 had no cytotoxicity at the concentrations below 6 mg·L-1. After MW-9 treatment, mouse body weight was gradually reduced, and the serum IL-6, IL-1β and TNF-α levels were significantly down-regulated. Compared with the model group, MW-9 significantly decreased the expression of p-p38 and p-ERK1/2 protein. Conclusions MW-9 has significant anti-inflammatory activities both in vitro and in vivo, and its underlying mechanism for the treatment of UC may be associated with the inhibition of MAPK signaling pathway. 
		                        		
		                        		
		                        		
		                        	
2.Consideration of countermeasures to promote family doctor contracting rate and first-return-visit rate in primary care institutions
Fei SHENG ; Ping LU ; Liqing ZHOU ; Bihua CHEN ; Chuntao YI ; Jiangen CHEN ; Fulai SHEN ; Tiantian DENG ; Dongjian XU ; Liling MAO
Chinese Journal of General Practitioners 2024;23(2):180-184
		                        		
		                        			
		                        			Based on the analysis of the existing problems and implementation dilemmas in family doctor contracting and first-return-visits faced by primary medical institutions in China, the authors propose countermeasures to provide reference for managers of primary health care institutions.
		                        		
		                        		
		                        		
		                        	
3.Practice and thinking of building active learning general practice team based on learning health system
Fei SHENG ; Tiantian DENG ; Dongjian XU ; Liling MAO ; Jing PU ; Yu LIU ; Ping YU ; Weifang LIU ; Fulai SHEN ; Puyang ZHENG
Chinese Journal of General Practitioners 2024;23(4):399-405
		                        		
		                        			
		                        			By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".
		                        		
		                        		
		                        		
		                        	
4.Wnt/β-catenin Signaling Cascades in Cardiovascular Diseases
Yan-Fei QI ; Yan-Ping LIU ; Wen-Qing XU ; Xiao-Xue YAN
Progress in Biochemistry and Biophysics 2024;51(10):2328-2339
		                        		
		                        			
		                        			Cardiovascular diseases are a group of disorders of the heart and blood vessels, primarily including coronary heart disease, stroke, and other diseases. It is the world’s leading cause of death, and its incidence is increasing yearly. Hypertension is a major risk factor for cardiovascular disease. Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes. Wnt signaling pathways include the canonical Wnt pathway (or Wnt/β-catenin pathway), the non-canonical planar cell-polarity pathway, and the non-canonical calcium-dependent pathways. Abnormal Wnt signaling promotes cell proliferation and differentiation, cardiac malformations, various malignancies, so drugs targeting Wnt signaling play a great therapeutic potential. Wnt/β‑catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation, migration, apoptosis, blood-brain barrier permeability, inflammation, oxidative stress, and immune response. Based on the latest research progress, this review summarizes the role of Wnt/β‑catenin signaling in cardiovascular diseases, in order to provide new ideas for the prevention and treatment of cardiovascular diseases. 
		                        		
		                        		
		                        		
		                        	
5.Advances in prophylaxis and treatment of retinal detachment related to Stickler syndrome
Xu GAO ; Yuan YANG ; Ping FEI ; Jie PENG ; Tingyi LIANG ; Mengxiao WU ; Peiquan ZHAO
International Eye Science 2024;24(12):1939-1944
		                        		
		                        			
		                        			 Stickler syndrome is a hereditary connective tissue disorder, characterized in ocular manifestations by high myopia and vitreous abnormalities. The progression of the disease can lead to giant retinal tear and rhegmatogenous retinal detachment, making it the most common cause of inherited pediatric retinal detachment. Surgical intervention is the primary treatment for retinal detachment associated with Stickler syndrome. However, there are currently no evidence-based management strategies. Patients typically require multiple surgeries, with low reattachment rates and high recurrence rates, emphasizing the importance of prophylactic treatment. Current prophylactic measures include scleral bucking, laser photocoagulation and retinal cryotherapy, but their absolute benefits remain insufficiently supported. This review summarizes recent advances in the prophylaxis and treatment of retinal detachment in Stickler syndrome, aiming to provide new insights and essential references for the prevention and treatment for such conditions. 
		                        		
		                        		
		                        		
		                        	
6.PRMT7 Regulates Adipogenic Differentiation of hBMSCs by Modulating IGF-1 Signaling
Qian GUO ; Jia QING ; Da-Zhuang LU ; Xu WANG ; Yang LI ; Hui ZHANG ; Ying-Fei ZHANG ; Yun-Song LIU ; Yong-Sheng ZHOU ; Ping ZHANG
Progress in Biochemistry and Biophysics 2024;51(6):1406-1417
		                        		
		                        			
		                        			ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases. 
		                        		
		                        		
		                        		
		                        	
7.Application of Mitochondrial Targeting Strategy of Nano-delivery System in Tumor Diagnosis and Treatment
Jun QU ; Shuang YAN ; Long-Tian-Yang LEI ; Fei-Jun OUYANG ; Hai-Tao ZHANG ; Xu-Ping QIN
Progress in Biochemistry and Biophysics 2024;51(1):70-81
		                        		
		                        			
		                        			Tumor is one of the major diseases that endanger people’s health. At present, the treatments used for tumor include surgery, chemotherapy, radiotherapy and so on. Nonetheless, the traditional treatments have some disadvantages, such as insufficient treatment effect, liable to cause multidrug resistance, toxicity and side effect. Further research and exploration of tumor treatment schemes are still necessary. As the energy converter of cells, mitochondria are currently considered to be one of the most important targets for the design of new drugs for tumor, cardiovascular and neurological diseases. Nano-drug delivery carriers have the characteristics of being easily modified with active targeting groups, and it can achieve accurate targeted drug delivery to cells and organelles. This paper reviews the application of mitochondrial targeted nanoparticles in tumor diagnosis and treatment from the aspects of inhibiting tumor cell proliferation, promoting tumor cell apoptosis, inhibiting tumor recurrence and metastasis, and inducing cell autophagy. 
		                        		
		                        		
		                        		
		                        	
8.Mechanism of Kechuanting granules in suppressing IL-33/ILC2s and pathogenic T cells to intervene in allergic airway inflammation
Nan-Ting ZOU ; Zhao WU ; Xiao-Dong YAN ; Chun-Fei ZHANG ; Hao-Hong ZHANG ; Qing-Yan MO ; Ming-Qian JU ; Jin-Zhu XU ; Chun-Ping WAN
Chinese Pharmacological Bulletin 2024;40(7):1350-1357
		                        		
		                        			
		                        			Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.
		                        		
		                        		
		                        		
		                        	
9.Investigation on the effect of decocting gypsum into medicine on calcium content of Xiao'er Magan granules
Yiqin FEI ; Tao JIANG ; Pan LÜ ; Ping YANG ; Fangling ZHAN ; Ling XU
Drug Standards of China 2024;25(2):187-194
		                        		
		                        			
		                        			Objective:To establish a microwave digestion and inductively coupled plasma mass spectrometry(ICP-MS)for determination on calcium content of Xiao'er Magan granules and discuss the effect of decocting gypsum into medicine on calcium content.Methods:ICP-MS was adopted to determine the calcium content in the preparation,and the difference of calcium content in the small preparation and Xiao'er Magan granules prepared by different pul-verization degree gypsum and different alcohol precipitation processes were compared.Results:The consistency of calcium content between different enterprises and batches of the same enterprise was poor.The results showed that the larger the particles,the lower the calcium transfer rate.The smaller the particles,the higher the calcium trans-fer rate.Conclusion:The transfer rate of gypsum decocted calcium is related to its degree of comminution to ensure consistency of preparation quality.It is suggested to unify the comminution degree of gypsum.The method can pro-vide guidance for the optimization on preparation technology of Xiao'er Magan granules.
		                        		
		                        		
		                        		
		                        	
10.Quality analysis of Xiao'er Magan granules based on chemometrics combined with quantitative analysis of different components
Yiqin FEI ; Pan LYU ; Ping YANG ; Fangling ZHAN ; Ling XU
China Pharmacist 2024;27(6):937-950
		                        		
		                        			
		                        			Objective To analyse the quality of Xiao'er Magan granules by the combination of chemometrics and difference analysis of component content.Methods The ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry(UPLC-Q-TOF/MS)method was used to study the characteristic spectrum of basic components.The partial least squares discriminant analysis was used to quantify and screen the markers of quality difference,the methods of muti-component quantification for differential components and fingerprint were established,and the principal component analysis was used to calculate the comprehensive scores of principal components.Results The 12 common peaks were identified by the characteristic spectrum,which were attributed to 6 medicinal herbs,namely Rhizome,Mulberry bark,Bitter almond,Licorice,Perilla seed and Scutellaria.Taking the variable importance projection value>1 as the criterion,4 characteristic components of quality differences(mulberry A,amygdalin,rosmarinic acid and baicalin)were screened out.The fingerprints similarity of 45 batches of samples were 0.867-0.997.14 components were calibrated,and 8 components were identified,which were mulberroside A,L-amygdalin,amygdalin,rosmarinic acid,baicalin,oroxindin,baicalein and wogonin.The scores of principal component 1 of each enterprise were as follows:G>H>A>C>E>D>F>I>B.The scores of principal component 2 were as follows:F>G>H>B>E>D>C>A>I.The ranking of the comprehensive scores was as follows:G>H>C>A>E>F>D>I>B.Conclusion The preparation quality of enterprise G and H is the best.The established fingerprint and quantitative method of quality differential components are accurate and reliable,which can provide reference for the quality analysis of Xiaoer Magan granules.
		                        		
		                        		
		                        		
		                        	
            
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