1.Isolation,culture and differentiation of human urine-derived stem cells into smooth muscle cells
Jiahui CHEN ; Xiaoqi DAI ; Yangang XU ; Yuanchao LI ; Mei HUANG ; Yifei ZHAN ; Yuxuan DU ; Liuqiang LI ; Yaochuan GUO ; Jun BIAN ; Dehui LAI
Chinese Journal of Tissue Engineering Research 2025;29(19):4076-4082
BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.
2.Adhesion Mechanisms of Aquatic Fouling Organisms Mediated by Biomacromolecules
Dan HE ; Shi-Guo LI ; Ai-Bin ZHAN
Progress in Biochemistry and Biophysics 2025;52(7):1833-1852
Aquatic organisms can secrete biomacromolecules through specialized organs, tissues, or structures, enabling adhesion to underwater material surfaces and leading to severe biofouling issues. This phenomenon adversely impacts aquatic ecosystem health and human activities. Biofouling has emerged as an emerging global environmental challenge. Adhesion serves as the foundation of biofouling, representing a critical step toward a comprehensive understanding of the adhesion mechanisms of aquatic organisms. Biomacromolecules, including proteins, lipids, and carbohydrates, are the primary functional components in the adhesive substances of aquatic fouling organisms. Research indicates that these biomacromolecules exhibit diversity in types and characteristics across different aquatic organisms, yet their adhesion mechanisms show unifying features. Despite significant progress, there remains a lack of comprehensive reviews on the adhesion mechanisms mediated by biomacromolecules in aquatic fouling organisms, particularly on the roles of lipids and carbohydrates. Through a comprehensive analysis of existing literature, this review systematically summarizes the mechanistic roles of three classes of macromolecules in aquatic biofouling adhesion processes. Proteins demonstrate central functionality in interfacial adhesion and cohesion through specialized functional amino acids, conserved structural domains, and post-translational modifications. Lipids enhance structural stability via hydrophobic barrier formation and antioxidative protection mechanisms. Carbohydrates contribute to adhesion persistence through cohesive reinforcement and enzymatic resistance of adhesive matrices. Building upon these mechanisms, this review proposes four prospective research directions: optimization of protein-mediated adhesion functionality, elucidation of lipid participation in adhesion dynamics, systematic characterization of carbohydrate adhesion modalities, and investigation of macromolecular synergy in composite adhesive systems. The synthesized knowledge provides critical insights into underwater adhesion mechanisms of aquatic fouling organisms and establishes a theoretical foundation for developing mechanism-driven antifouling strategies. This work advances fundamental understanding of bioadhesion phenomena while offering practical guidance for next-generation antifouling technology development.
3.Reviews and Recommendations in Comparative Studies on Quality of Wild and Cultivated Chinese Crude Drugs
Yapeng WANG ; Changsheng YUAN ; Jinxiu QIAN ; Yihan WANG ; Yanmeng LIU ; Yunxiang LIU ; Tiegui NAN ; Liping KANG ; Zhilai ZHAN ; Lanping GUO ; Luqi HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):1-20
By reviewing the research history on quality comparison between wild and cultivated Chinese crude drugs, this paper systematically combed the relevant research reports since the 1950s, and summarized and analyzed the results of existing comparative studies, and found that the existing comparative research on the quality of wild and cultivated Chinese crude drugs were mainly focused on several aspects, including characteristics, microstructures, chemical compositions, pharmacodynamic effects, and genetic diversity. Among these, comparative studies of chemical compositions have been the dominant approach, with a particular emphasis on comparing the contents of index components. However, research on pharmacodynamic effects remained relatively limited. Due to various factors such as sample quantity, sample origin, growth period and cultivation methods, the differences in quality between wild and cultivated Chinese crude drugs vary significantly. In general, most wild Chinese crude drugs exhibited higher quality than cultivated products, with significant differences in their characteristics. The contents and proportions of some chemical components underwent noticeable changes, particularly with a marked increase in the proportion of primary metabolites after cultivation. The quality of cultivated Chinese crude drugs is closely related to the cultivation practices employed. Chinese crude drugs produced through wild nurturing, simulated wild planting, ecological cultivation, and other similar methods demonstrate quality levels comparable to those of wild Chinese crude drugs. Based on the analysis results, it is recommended to explicitly specify the cultivation practices and cultivation period of cultivated Chinese crude drugs in comparative studies of the quality between wild and cultivated Chinese crude drugs. Multiple technical approaches, including characteristics, microscopy, non-targeted metabolomics combined with quantitative analysis of differential components, and bioefficacy evaluation, should be employed to comprehensively assess the quality disparities between wild and cultivated Chinese crude drugs. Moreover, research efforts should be intensified to investigate the changes in pharmacodynamic effects resulting from differences in plant cell wall composition, primary metabolites, and secondary metabolites, in order to guide the production of high-quality Chinese crude drugs.
4.Herbal Textual Research on Pharbitidis Semen in Famous Classical Formulas
Liping YANG ; Xudong GUO ; Shaoyang XI ; Xiaohui MA ; Zhilai ZHAN ; Ling JIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):179-189
By consulting the ancient and modern literature, the textual research of Pharbitidis Semen has been conducted to clarify the name, origin, distribution of production areas, quality specification, harvesting, processing and so on, so as to provide reference for the development and utilization of the relevant famous classical formulas. Through textual research, it can be seen that Pharbitidis Semen was first published in Mingyi Bielu(《名医别录》), and all dynasties have taken Qianniuzi as the correct name. Based on the original research, the main source of Pharbitidis Semen used in previous dynasties is the dried mature seeds of Pharbitis nil, which is consistent in ancient and modern times. The white Pharbitidis Semen appearing in Compendium of Materia Medica(《本草纲目》) from Ming dynasty is similar to the present P. purpurea. It is produced all over the country, and the quality is better if the particles are full and free of impurities. In ancient times, the harvesting time was mostly in the September. Now it is autumn. The fruits are ripe and harvested, dried to remove impurities for standby. In ancient times, the processing methods of Pharbitidis Semen were mainly wine steaming, steaming and frying until half cooked and grinding the head and end. In modern times, they have been simplified to stir-frying method. The nature, taste, meridian tropism and their effects also change supplements with the deepening of practice. Before the Ming dynasty, they were all bitter, cold and toxic. In the Ming dynasty, there appeared the characteristics of pungent, hot and small poisonous. The efficacy has evolved from controlling low Qi, curing foot edema, removing wind toxin, and facilitating urination to facilitating water and defecation, eliminating phlegm and drinking, and eliminating accumulated insects. The main clinical contraindications are those with weak spleen and kidney, those with weak spleen and stomach, pregnant women, and should not be used with croton and croton cream. Based on the textual research, it is suggested that when developing the classic famous formula with Pharbitidis Semen as the main raw material in the future, it is clear that the source should be the dried mature seeds of Pharbitis nil(black product is its black-brown seeds, white product is its beige seeds). The processing requirements indicated in the original formula are all processed according to the requirements, and the raw product is recommended to be used as medicine if not specified.
5.Effect of high fat diet intake on pharmacokinetics of metronidazole tablets in healthy Chinese volunteers
Na ZHAO ; Cai-Hui GUO ; Ya-Li LIU ; Hao-Jing SONG ; Ben SHI ; Yi-Ting HU ; Cai-Yun JIA ; Zhan-Jun DONG
The Chinese Journal of Clinical Pharmacology 2024;40(1):102-106
Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P<0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P>0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.
6.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
7.Bioequivalence test of metronidazole tablets in healthy human in China
Xiu-Qing PENG ; Cai-Hui GUO ; Ya-Li LIU ; Na ZHAO ; Hao-Jing SONG ; Wan-Jun BAI ; Zhan-Jun DONG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1943-1947
Objective To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90%confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00%-125.00%.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90%CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00%-125.00%.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.
8.mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion.
Huan WANG ; Zhuxuan JIANG ; Zhiwei GUO ; Gan LUO ; Tianhao DING ; Changyou ZHAN
Acta Pharmaceutica Sinica B 2024;14(2):808-820
Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.
9.Herbal Textual Research on Euryales Semen in Famous Classical Formulas
Zixuan GAO ; Cheng QU ; Hui YAN ; Ling XIA ; Sheng GUO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):210-217
This paper systematically combed and verified the name, origin, producing area, quality evaluation, harvesting, processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica, medical books, prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi, and since the Ming dynasty, Qianshi has been used as a proper name and continues to this day, with other aliases such as Yanhuishi. Euryale ferox, a plant of the Nymphaeaceae family, is the same as that used in the past dynasties. However, due to long-term artificial domestication, the varieties vary with the origin, including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel, its origin of ancient records mainly includes Shandong, Jiangsu, Henan and other places, since the Ming and Qing dynasties, Euryales Semen produced in Suzhou has been highly praised. Since modern times, it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains, white cross-section, powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder, pounding powder after steaming, drying and frying. Up to now, two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results, it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula, it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.
10.Visualization Analysis of Artificial Intelligence Literature in Forensic Research
Yi-Ming DONG ; Chun-Mei ZHAO ; Nian-Nian CHEN ; Li LUO ; Zhan-Peng LI ; Li-Kai WANG ; Xiao-Qian LI ; Ting-Gan REN ; Cai-Rong GAO ; Xiang-Jie GUO
Journal of Forensic Medicine 2024;40(1):1-14
Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.

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