1.Mechanisms of Gut Microbiota Influencing Reproductive Function via The Gut-Gonadal Axis
Ya-Qi ZHAO ; Li-Li QI ; Jin-Bo WANG ; Xu-Qi HU ; Meng-Ting WANG ; Hai-Guang MAO ; Qiu-Zhen SUN
Progress in Biochemistry and Biophysics 2025;52(5):1152-1164
Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.
2.The Role and Mechanism of Circadian Rhythm Regulation in Skin Tissue Regeneration
Ya-Qi ZHAO ; Lin-Lin ZHANG ; Xiao-Meng MA ; Zhen-Kai JIN ; Kun LI ; Min WANG
Progress in Biochemistry and Biophysics 2025;52(5):1165-1178
Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.
3.Association between physical exercise behavior with mobile phone addiction and mental health of college students
LIU Manluo, QI Xin, WU Min, SUN Qin, ZHAO Zhen
Chinese Journal of School Health 2025;46(5):634-637
Objective:
To explore the relationship of physical exercise behavior with mobile phone addiction and mental health of college students, so as to provide evidence for interventions to improve mobile phone addiction and mental health of college students.
Methods:
From October 8 to December 20 in 2024, 896 college students from 4 colleges in Beijing were selected using a combination of convenience sampling and stratified random cluster sampling method. Physical Activity Rating Scale (PARS-3), Mobile Phone Addiction Tendency Scale (MPATS), Adolescence Mental Health Diathesis Questionnaire (AMHDQ) and Symptom Checklist 90 (SCL-90) were used. The correlation of mobile phone addiction and mental health on physical exercise behavior of college students were analyzed by multivariable Logistic regression and linear regression.
Results:
Among the surveyed college students, 504 (56.25%) students had low exercise, 262 (29.24%) had moderate exercise, 130 (14.51%) had high exercise, and 392 (43.75%) had sufficient exercise. The total score of PARS-3 was 18.00 ( 15.00 , 33.00) points. Logistic regression analysis showed that the total score of MPATS ( OR=1.022, 95%CI =1.008-1.036), the total score of SCL-90 ( OR=1.010, 95%CI = 1.005 -1.015), the total AMHDQ score ( OR=0.995, 95%CI =0.992-0.998) were significantly associated with insufficient exercise among college students ( P <0.05). Linear regression analysis showed that the scores of MPATS, AMHDQS and SCL-90 were significantly correlated with physical exercise behavior ( B=-0.20, 0.04, -0.07, P <0.05).
Conclusion
The physical exercise behavior of college students is related to mobile phone addiction and mental health.
7.Theoretical Validation of the Identification of Therapeutic Dominant Stages of Traditional Chinese Medicine Based on Subdivision Model of Disease Course:Taking Premature Ovarian Failure for Example
Rui-Qi ZHANG ; Yuan-Li RAO ; Zhen-Miao PANG ; Zhi-Lai YAN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):625-630
Objective To explore the feasibility and operability in identifying the therapeutic dominant stages of traditional Chinese medicine(TCM)based on subdivision model of disease course.Methods The hierarchical Bayesian model was used to differentiate the disease course of 125 cases of premature ovarian failure(POF),and the disease course of POF were divided into the occult stage,diminished ovarian reserve(DOR)stage,premature ovarian insufficiency(POI)stage,and POF stage.An then the paired sample t-test,Pearson correlation analysis and expert in-depth interview were used for the analysis of the therapeutic effects of TCM for POF at various stages.Results(1)Compared with POF stage,DOR and POI stages were frequently intervened by Chinese patent medicine.(2)In DOR(complicated with POI)stage and POF stage,there was significant difference between the degree of TCM intervention and the therapeutic effect(t =-3.70,P<0.001).(3)The degree of TCM intervention was positively correlated with treatment outcomes in the DOR stage(r = 0.679,P<0.001),so did in the POF stage(r = 0.432,P<0.001),but the correlation in the POF stage was slightly lower than that in the DOR stage.(4)The results of in-depth interviews with experts of TCM gynecology showed that in the concealed phase of POF,the prognosis would be most favorable if TCM regulation and intervention were performed.In the DOR stage and POI stage,treatment with Chinese medicine prescriptions usually brought about better curative effect and prognosis.For the patients at POF stage,the therapeutic effect of TCM depended on the patients'compliance and the treatment course,and the effect was relatively not as good as that of the previous stages.Conclusion In the DOR stage and POF stage,the higher the degree of TCM intervention,the better the prognosis will be achieved for the patients treated with western medicine.In the POF stage,the efficacy of TCM intervention is reduced to a certain extent compared with the DOR stage.The results indicated that it is feasible and operable to identify the TCM therapeutic dominant stages based on the subdivision model of disease course.
8.CXCL5 participates in carotid plaque formation by inducing vascular calcification
Ming QI ; Lei WANG ; Zhen ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(2):186-192
BACKGROUND:CXC motif chemokine 5(CXCL5)is a neutrophil activating peptide derived from epithelial cells,which may be involved in arterial diseases.However,there is yet no report on the effect of CXCL5 in vascular calcification. OBJECTIVE:To explore the role of CXCL5 in the vascular calcification of carotid atherosclerosis(CAS). METHODS:(1)Cytological experiment:Mouse vascular smooth muscle cells(VSMCs)were divided into five groups:osteogenic medium group,Vector group(vector,blank plasmid transfected into VSMCs),CXCL5 group(CXCL5 plasmid transfected into VSMCs),si-NC group(CXCL5 negative control siRNA transfected into VSMCs),si-CXCL5 group(CXCL5 siRNA transfected into VSMCs),Vector+LY2157299 group and CXCL5+LY2157299 group(LY2157299 transferred into the cells 24 hours after cell transfection).Alizarin red staining,alkaline phosphatase staining,and calcium content determination were performed to evaluate the osteogenic differentiation level of VSMCs.(2)Animal experiment:Forty-eight ApoE-/-mice were randomly divided into four groups(n=12 per group):Con+si-NC group,Con+si-CXCL5 group,CAS+si-NC group and CAS+si-CXCL5 group.Animal models were not prepared in the first two groups,in which si-NC or si-CXCL5 lentivirus was injected into the tail vein;carotid atherosclerosis models were made in the latter two groups,in which si-NC or si-CXCL5 lentivirus was injected into the tail vein.Von Kossa staining and immunohistochemical staining were used to evaluate carotid vascular calcification and the expression of CXCL5 and transforming growth factor-β receptor 1(TGFBR1)in mice. RESULTS AND CONCLUSION:In the CXCL5 group,the protein level of runt-related transcription factor 2(RUNX2)was up-regulated and the level of α-smooth muscle actin was down-regulated,in contrary to the findings in the si-CXCL5 group.In addition,CXCL5 overexpression upregulated the level of TGFBR1,while CXCL5 knockdown inhibited the level of TGFBR1.Compared with the Vector group,the intensity of alizarin red staining,alkaline phosphatase activity and calcium content in the CXCL5 group increased significantly(P<0.05).Compared with the si-NC group,the intensity of alizarin red staining,alkaline phosphatase activity and calcium content in the si-CXCL5 group decreased significantly(P<0.05).When LY2157299 inhibited TGFBR1 expression,the osteogenic differentiation of VSMCs induced by CXCL5 was reduced.Compared with the Con+si-NC group,the expression of CXCL5 protein in the carotid artery and calcification area in the CAS+si-NC group increased significantly(P<0.05).Compared with the CAS+si-NC group,the expression of CXCL5 protein in the carotid artery and vascular calcification area in the CAS+si-CXCL5 group decreased significantly(P<0.05).In addition,compared with the Con+si-NC group,the expression of RUNX2 protein in the carotid artery in the CAS+si-NC group increased significantly(P<0.05),while the expression of α-smooth muscle actin protein decreased significantly(P<0.05).Compared with the CAS+si-NC group,the expression of RUNX2 protein in the carotid artery in CAS+si-CXCL5 group decreased significantly(P<0.05),while the expression of α-smooth muscle actin protein increased significantly(P<0.05).In conclusion,CXCL5 can induce osteogenic transformation of VSMCs by activating the TGFBR1 pathway,and inhibition of CXCL5 expression is effective in improving carotid arterial calcification in CAS mice.
9.Behavior of cartilage-derived microtissue and ability of cartilage formation in three-dimensional dynamic and static culture conditions
Wei LIU ; Hongyu JIANG ; Jiajie CHEN ; Yuyang GAO ; Yanjun GUAN ; Zhibo JIA ; Ying JIAO ; Zhen HUA ; Gehan JIANG ; Ying HE ; Aiyuan WANG ; Jiang PENG ; Jianhong QI
Chinese Journal of Tissue Engineering Research 2024;28(25):4022-4026
BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.
10.Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor.
Ju-Ying JIAO ; Chien-Shan CHENG ; Zhang-Qi CAO ; Lian-Yu CHEN ; Zhen CHEN
Chinese journal of integrative medicine 2024;30(1):85-95
Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.
Animals
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Humans
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Medicine, Chinese Traditional
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Hot Temperature
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Pancreatic Neoplasms/therapy*
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Models, Animal
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Syndrome


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