1.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.
2.Screening and evaluation of the biocontrol efficacy of a Trichoderma brevicompactum strain and its metabolite trichodermin against banana Fusarium wilt.
Xiajun YAO ; Jin XIE ; Yanhua QI ; Bin WANG ; Wenxia FANG ; Gang TAO ; Xiliang JIANG
Chinese Journal of Biotechnology 2024;40(1):211-225
The banana Fusarium wilt (BFW) caused by Fusarium oxysporum f. sp. cubense tropical race4 (FocTR4) is difficult to control worldwide, which causes a huge economic losse to banana industry. The purpose of this study was to screen Trichoderma strains with antagonistic activity against FocTR4, to isolate and purify the active compound from the fermentation broth, so as to provide important biocontrol strains and active compound resources. In this work, Trichoderma strains were isolated and screened from the rhizosphere soil of crops, and the strains capable of efficiently inhibiting FocTR4 were screened by plate confrontation, and further confirmed by testing inhibition for the conidial germination and mycelial growth of FocTR4. The phylogenetic tree clarified the taxonomic status of the biocontrol strains. Moreover, the active components in the fermentation broth of the strains were separated and purified by column chromatography, the structure of the most active component was analyzed by nuclear magnetic resonance spectroscopy (NMR), the BFW control effect was tested by pot experiments. We obtained a strain JSHA-CD-1003 with antagonistic activity against FocTR4, and the inhibition rate from plate confrontation was 60.6%. The fermentation broth of JSHA-CD-1003 completely inhibited the germination of FocTR4 conidia within 24 hours. The inhibition rate of FocTR4 hyphae growth was 52.6% within 7 d. A phylogenetic tree was constructed based on the ITS and tef1-α gene tandem sequences, and JSHA-CD-1003 was identified as Trichoderma brevicompactum. Purification and NMR identification showed that the single active compound was trichodermin, and the minimum inhibitory concentration (MIC) was 25 μg/mL. Pot experiments showed that the fermentation broth of strain JSHA-CD-1003 was effective against BFW. The control rate of leaf yellowing was 47.4%, and the rate of bulb browning was 52.0%. Therefore, JSHA-CD-1003 effectively inhibited FocTR4 conidial germination and mycelium growth through producing trichodermin, and showed biocontrol effect on banana wilt caused by FocTR4, thus is a potential biocontrol strain.
Fusarium
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Musa
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Phylogeny
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Trichodermin
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Hypocreales
3.Effect of deep muscle stimulation on muscle structure and function in children with spastic cerebral palsy
Yanhua LIANG ; Qi ZHANG ; Xiaoshi HU ; Xiaosong LI ; Qing YUE ; Tiantian ZHOU ; Sijia LI ; Amei FENG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(12):1452-1460
ObjectiveTo observe the effect of deep muscle stimulation on muscle structure and function in children with spastic cerebral palsy. MethodsFrom January, 2023 to March, 2024, 30 children with spastic cerebral palsy in Beijing Bo'ai Hospital were randomly divided into control group (n = 15) and intervention group (n = 15). Both groups received conventional rehabilitation therapy, while the intervention group added deep muscle stimulation, for four weeks. Before and after training, the gastrocnemius muscle was examined by ultrasound diagnosis system in two aspects: transverse incision and longitudinal incision. Indicators included fascicle length, muscular thickness, cross sectional area and pennation angle. The modified Ashworth Scale (MAS) was used to assess the muscle tension of the lower extremity of the affected side. The standing, walking, running and jumping function were evaluated by Gross Motor Function Measure (GMFM) D and E areas. ResultsAfter training, the fascicule length and pennation angle improved significantly in both groups (|t| > 6.329, P < 0.001), and they were better in the intervention group than in the control group (|t| > 2.347, P < 0.05); the scores of MAS decreased in both groups (t > 2.432, P < 0.05), and were better in the intervention group than in the control group (t = 2.140, P < 0.05); the scores of GMFM D and E areas significantly decreased in both groups (|t| > 8.473, P < 0.001), and were better in the intervention group than in the control group (|t| > 2.191, P < 0.05). ConclusionDeep muscle stimulation could improve the fascicule length and pennation angle, and improve the spasticity and motor function of lower extremities in children with spastic cerebral palsy.
4.GNMT inhibits intrauterine adhesion fibrosis through TGF-β1/Smad3 signaling pathway and its mechanism
Hong GU ; Jia WANG ; Wenwen ZHANG ; Xiao YANG ; Xiyue HUANG ; Yingfeng ZHANG ; Yanhua MAO ; Changjiang LI ; Qiuhong CHEN ; Jinglin HUANG ; Qi LIU ; Ling WEI ; Congcong SUN
Journal of Army Medical University 2024;46(18):2110-2120
Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6~8 weeks old and weighing from 180~220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.
5.Diagnostic value of serum ferritin in Mycoplasma pneumoniae pneumonia was analyzed based on the decision curve
Dachen BIAN ; Jungu WANG ; Yuqing QI ; Zhuqi YANG ; Yanhua CHEN ; Hui GAO
International Journal of Laboratory Medicine 2024;45(19):2403-2407
Objective To analyze the value of serum ferritin(SF)in the early diagnosis of Mycoplasma pneumoniae pneumonia(MPP)based on decision curve analysis(DCA)and dose-response relationship.Meth-ods A total of 104 MPP patients in Taizhou People's Hospital from October 2016 to October 2021 were se-lected as the MPP group,and 90 healthy adults who underwent physical examination in Taizhou People's Hos-pital during the same period were selected as the healthy group.The clinical data of the two groups were com-pared.The influencing factors of MPP in patients were screened.The diagnostic value of SF for MPP was analyzed,the best cut-off value was sought,and the clinical predictive value of SF for MPP was evaluated.Results White blood cell count,C-reactive protein,tumor necrosis factor-α,lactate dehydrogenase,SF were independent risk factors for MPP,and 25-hydroxyvitamin D was its protective factor(P<0.05).The dose-response relationship analysis showed that there was a nonlinear dose-response relationship between the continuous change of SF and MPP(P<0.05).When SF>127.68 ng/mL,the risk of MPP increased with the increase of SF level.DCA analysis showed that SF had important clinical value in the early prediction of MPP.Conclusion SF has a high value in the early diagnosis of MPP,and there is a nonlinear dose-response relationship between SF and MPP.When SF>127.68 ng/mL,the risk of MPP increases with the increase of SF level.
6.Effect of orthopedic elastic bandages on gait symmetry and walking ability in children with spastic hemiplegic cerebral palsy
Xiaoshi HU ; Qi ZHANG ; Qing YUE ; Yanhua LIANG ; Xiaosong LI ; Amei FENG ; Yanqing ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2023;29(9):1083-1089
ObjectiveTo investigate the short-term efficacy of orthopedic elastic bandages on gait symmetry and walking ability in children with spastic hemiplegic cerebral palsy. MethodsFrom June, 2020 to June, 2023, 31 children with spastic hemiplegic cerebral palsy from Beijing Bo'ai Hospital were randomly divided into control group (n = 15) and experimental group (n = 16). Both groups received routine rehabilitation, while the control group received routine walking training, and the experimental group wore an orthopedic elastic bandage for walking training, for four weeks. The indexes of gait symmetry of foot deviation angle ratio (affected/healthy), step length ratio (affected/healthy), gait line ratio (affected/healthy) and standing stage ratio (affected percentage/healthy percentage) were calculated before and after training, and they were measured step width and the optional and maximum walking speed of 10-meter walk test (10MWT). ResultsOne case dropped off in the experimental group. After training, the foot deviation ratio, step length ratio, gait line ratio, and standing stage ratio improved in both groups (|t| > 2.434, P < 0.05), and they were better in the experimental group than in the control group (|t| > 2.230, P < 0.05); while the optional and maximum walking speed of 10MWT improved in both groups (|t| > 9.186, P < 0.001), and they were better in the experimental group than in the control group (|t| > 2.278, P < 0.05). ConclusionWearing orthopedic elastic bandages during rehabilitation can promote the gait symmetry and walking ability of children with spastic hemiplegic cerebral palsy.
7.RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway.
Chaochao WANG ; Hao XUE ; Rongrong ZHAO ; Zhongzheng SUN ; Xiao GAO ; Yanhua QI ; Huizhi WANG ; Jianye XU ; Lin DENG ; Gang LI
Frontiers of Medicine 2023;17(1):143-155
Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.
Humans
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Phosphatidylinositol 3-Kinases/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
MicroRNAs/metabolism*
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Glioma/genetics*
;
Genes, Tumor Suppressor
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Cell Proliferation
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Gene Expression Regulation, Neoplastic
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Cell Line, Tumor
8.Surveillance of environmental avian influenza virus in Fujian province, 2017-2021
Jingjing WU ; Qi LIN ; Yanhua ZHANG ; Jinzhang WANG ; Hongbin CHEN ; Yuqing YAN ; Yuwei WENG
Chinese Journal of Experimental and Clinical Virology 2023;37(1):61-66
Objective:To analyze the epidemiologic characteristics of environmental samples of avian influenza virus in Fujian province from 2017 to 2021, and provide a reference for the prevention and control of avian influenza.Methods:Six types of specimens were collected from four types of environments in six cities in Fujian province. And the specimens were subjected to nucleic acid detection for influenza A, subtypes H5, H7 and H9 by fluorescence quantitative PCR, and the results were analyzed statistically with descriptive epidemiological methods.Results:From 2017 to 2021, a total of 4 214 samples were collected from 6 cities, of which the positive rate of avian influenza virus was 41.53%, and the positive rates of H5, H7 and H9 subtypes were 2.33%, 1.16% and 23.16%, respectively. The positive rate for mixed subtypes of H5 and H7 was 0.05%, the positive rate for mixed subtypes of H5 and H9 was 1.83%, the positive rate for mixed subtypes of H7 and H9 was 0.83%, the positive rate for mixed subtypes of H5, H7 and H9 was 0.09%, and the positive rate of A-type unclassified was 12.08%. The difference in avian influenza virus detection among different monitoring places ( χ2=517.57, P<0.001), different types of specimens( χ2= 51.58, P<0.001), and different cities ( χ2=458.34, P<0.001) was statistically significant. Among different monitoring places, the positive rate of avian influenza virus in urban and rural live poultry markets was the highest. The highest rate of positive detection was found in specimens from the cage surface, cleaning poultry sewage and poultry chopping board surface, with 48.09%, 47.34% and 45.66%, respectively. In terms of different cities, Sanming city had the highest positivity rate (56.00%), while Zhangzhou city had the lowest positivity rate(3.34%). And the positive rate was higher from November to February of the next year and June to August each year. Conclusions:The overall positive rate of avian influenza viruses in Fujian province was relatively high, with H9 subtype accounting for the main proportion. The monitoring of avian influenza viruses in winter, spring and summer should be strengthened. And effective measures should be taken to deal with avian influenza especially in urban and rural live poultry markets.
9.DHX37 gene heterozygous variant—a frequent cause of embryonic testicular regression syndrome
Lili PAN ; Zhe SU ; Yanhua JIAO ; Junjie SUN ; Jianchun YIN ; Hao WANG ; Xianping JIANG ; Shumin FAN ; Hongtao QI ; Rongfei ZHENG ; Yue SHANG
Chinese Journal of Endocrinology and Metabolism 2022;38(4):306-312
Objective:To report embryonic testicular regression syndrome(ETRS) caused by DHX37 heterozygous variant for the first time in China and summarize the clinical manifestations of ETRS as to improve the understanding of doctors for this disease.Methods:The clinical data and whole exome sequencing results of five cases of ETRS from Shenzhen Children′s Hospital were collected. The reported cases of DHX37 heterozygous variant were reviewed.Results:Five patients with ETRS visited the doctors at the age of 2 months to 5 years and 5 months. Three patients raised as males came to hospital due to virilition and 2 female patients visited a doctor due to clitoral hypertrophy. No uterus was detected by ultrasound in all patients. The gonadal pathologies from 4 cases displayed no testicular tissue or gonadal dysgenesis, complicated with gonadoblastoma in one case. The genetic testing revealed that the heterozygous variant(c.923G>A, p. R308Q) in DHX37 was found in 2 cases, without variant in other 3 cases. According to the review, ETRS and 46, XY gonadal dysgenesis due to DHX37 herozygous variant was firstly reported in 2019. A total of 40 cases, including 21 cases of ETRS, presented with the virilition or female phenotype, with the disappearance of testicular tissue as the main pathologies. There is no report in China.Conclusion:The article summarized the clinical manifestations and whole exome sequencing results of 5 patients with ETRS, among which two cases were caused by DHX37 variants and one was complicated with gonadoblastoma.
10.Clinical features and prognosis of newborns with congenital fissure of larynx presented with choking
Yanhua SHEN ; Fei JIN ; Yujie QI ; Hailan WU ; Lu CHEN ; Xu ZHENG ; Jie ZHANG ; Mingyan HEI
Chinese Pediatric Emergency Medicine 2022;29(8):626-630
Objective:To summarize the clinical features and prognosis of neonates with congenital fissure of larynx due to choking, and improve the diagnosis and treatment of congenital fissure of larynx by neonatal medical professionals.Methods:This study was a single-center retrospective case series report.With "choking" as the key word, combined with the information from the first page of the medical record, we searched in the electronic medical record system, and summarized the clinical characteristics and prognosis of neonates diagnosed as congenital fissure of larynx.The study period was from January 2017 to February 2021.Results:A total of seven cases were diagnosed as congenital fissure of larynx, accounting for 2.2% of the total number of hospitalized children due to choking during the same period.Among them, six cases were male, gestational age was 38 (36, 39) weeks, birth weight was 2 820 (2 255, 3 420) g, admission age was 18(5, 20) days and hospitalization duration was 26 (6, 45) days.The common clinical symptoms were choking (7/7) and cyanosis (5/7). Six of the seven children with fissure of larynx were clearly classified as type Ⅰ(two cases), type Ⅲ(three cases), and type Ⅳ(one case). All the seven cases were accompanied by other site/tracheal malformations or congenital abnormalities, among which four (4/7) cases had VACTERL syndrome.A total of three children (two cases of type Ⅲ and one case of type Ⅳ) underwent laryngeal cleft repair operation, and all died shortly after surgery.Four cases didn′t receive laryngeal cleft repair operation (two cases of type Ⅰ, one case of type Ⅲ, one case of parting was unknown), one case with type Ⅰ fissure of larynx accepted the tracheoesophageal fistula repair operation only, who was followed up until the age of two years and six months, and he could have normal diet, one case of typeⅠfissure of larynx with gastric tube discharge, who was followed up to one year and eight months old, could be normal diet too, the two cases of children with no difference between the growth with their peers; one case with type Ⅲ fissure of larynx was lost to follow-up; One case, whose classification was unknown, was followed up until he was 40 days old, and still could be fed orally.The physical development of the child was significantly behind that of the same age.Conclusion:Congenital fissure of larynx is rare, with choking as its main symptom and other malformations.Diagnosis and classification require fiberlaryngoscope and bolting laryngoscope under general anesthesia combined with bronchoscopy, which is difficult to treat.Type Ⅰ has a good prognosis, while type Ⅲ and Ⅳ have poor prognosis.

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