1.miR-142a-3p Reduces Autophagy in TCMK-1 Cells and Enhances Pyroptosis by Targeting ATG16L1
Xing ZHAO ; Fei YU ; Rui-Yang YUAN ; Ya-Ru YANG ; Jia-Yan LIU ; Hai-Mai DING ; Xue-Ming ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(7):1031-1039
The incidence rate of kidney diseases in China has always remained high.At present,the clinical treat-ment mainly focuses on symptomatic treatment to delay the progression of the disease,and there is a lack of eco-nomical and effective treatment methods.MicroRNA plays an important regulatory role in the occurrence and devel-opment of diseases.This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin(ADR)-induced renal tubular epithelial cell(TCMK-1)injury,with a focus on its potential as a therapeutic target for ADR nephropathy.First,cell viability was assessed using the CCK-8 kit,and a mouse renal tubular epithelial cell model induced by ADR was established.Subsequently,alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR.Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins.Monodansylcadaverin(MDC)staining was performed and the autophagy of cells was detected by flow cytometry.The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased(P<0.0001).Western blotting results showed that the levels of p62(P<0.001)and pyroptosis-related proteins(P<0.001)were increased,while the protein levels of autophagy-related proteins were decreased(P<0.05).The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autoph-agosomes between the ADR group and the autophagosome inhibitor group(3-MA group)(P>0.05),indicating that after ADR induction,cell autophagy was inhibited and pyroptosis was enhanced.When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor,the relative expression level of the target gene ATG16L1 was restored(P<0.001).Western blotting showed that the protein level of p62(P<0.01)and pyropto-sis-related proteins(P<0.01)were decreased,and the protein level of autophagy-related proteins was restored(P<0.001).Flow cytometry results further indicated that cell autophagy was restored(P<0.0001).In conclusion,ADR targets A TG1 6L1 through miR-142a-3p to reduce the autophagy level of TCMK-1,and simultaneously activates GSDMD-mediated pyroptosis.
2.miR-142a-3p Reduces Autophagy in TCMK-1 Cells and Enhances Pyroptosis by Targeting ATG16L1
Xing ZHAO ; Fei YU ; Rui-Yang YUAN ; Ya-Ru YANG ; Jia-Yan LIU ; Hai-Mai DING ; Xue-Ming ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(7):1031-1039
The incidence rate of kidney diseases in China has always remained high.At present,the clinical treat-ment mainly focuses on symptomatic treatment to delay the progression of the disease,and there is a lack of eco-nomical and effective treatment methods.MicroRNA plays an important regulatory role in the occurrence and devel-opment of diseases.This study aims to explore the role and regulatory mechanism of miR-142a-3p in adriamycin(ADR)-induced renal tubular epithelial cell(TCMK-1)injury,with a focus on its potential as a therapeutic target for ADR nephropathy.First,cell viability was assessed using the CCK-8 kit,and a mouse renal tubular epithelial cell model induced by ADR was established.Subsequently,alterations in miR-142a-3p and its target gene ATG16L1 mRNA levels were quantified using RT-qPCR.Western blotting was used to detect the protein levels of autophagy marker proteins and pyroptosis marker proteins.Monodansylcadaverin(MDC)staining was performed and the autophagy of cells was detected by flow cytometry.The results showed that the relative expression of miR-142a-3p in TCMK-1 cells induced by ADR was increased and the relative expression of its target gene ATG16L1 was decreased(P<0.0001).Western blotting results showed that the levels of p62(P<0.001)and pyroptosis-related proteins(P<0.001)were increased,while the protein levels of autophagy-related proteins were decreased(P<0.05).The flow cytometry results showed that there was no difference in the mean fluorescence intensity of autoph-agosomes between the ADR group and the autophagosome inhibitor group(3-MA group)(P>0.05),indicating that after ADR induction,cell autophagy was inhibited and pyroptosis was enhanced.When the expression of miR-142a-3p was inhibited by transfecting miR-142a-3p inhibitor,the relative expression level of the target gene ATG16L1 was restored(P<0.001).Western blotting showed that the protein level of p62(P<0.01)and pyropto-sis-related proteins(P<0.01)were decreased,and the protein level of autophagy-related proteins was restored(P<0.001).Flow cytometry results further indicated that cell autophagy was restored(P<0.0001).In conclusion,ADR targets A TG1 6L1 through miR-142a-3p to reduce the autophagy level of TCMK-1,and simultaneously activates GSDMD-mediated pyroptosis.
3.Application value of intestinal stent placement assisted by disposable subscope for acute malignant colorectal obstruction (with video)
Yuanzhi WANG ; Bengang ZHOU ; Bangjie LIU ; Guanghuai YAO ; Guiqing LI ; Yaoyao LI ; Feng XUE ; Ming ZHOU ; Yanbing DING
Chinese Journal of Digestive Endoscopy 2025;42(9):722-726
To investigate the application value of disposable subscope-assisted intestinal metal stent placement in the treatment for acute malignant colorectal obstruction, a retrospective analysis was conducted on the patients who underwent intestinal metal stent placement assisted by disposable subscope for acute malignant colorectal obstruction at the Digestive Endoscopy Center, Affiliated Hospital of Yangzhou University from June 2023 to July 2024. The technical success rate, clinical success rate, operation time, postoperative complications and first-stage surgical resection anastomosis rate of intestinal metal stent placement assisted by subscope were analyzed. Among the 16 included patients, there were 10 males and 6 females, with the age of 72.19±9.40 years. Obstruction occurred at the descending colon in 8 cases (50.00%), at the sigmoid colon in 6 cases (37.50%), at the rectosigmoid junction in 1 case (6.25%), and at the splenic flexure of the transverse colon in 1 case (6.25%). All 16 patients successfully underwent stent placement, with a technical success rate of 100.00% (16/16). Obstruction symptoms did not relieve in one patient (6.25%) after stent placement, resulting in a clinical success rate of 93.75% (15/16). The endoscopic operation time for the 16 patients was 37.8±13.9 minutes. No bleeding, perforation, stent displacement, or detachment occurred after the operation. Fourteen patients underwent subsequent surgical treatment, the first-stage surgical resection anastomosis rate was 71.43% (10/14). This preliminary study suggests that the disposable subscope-assisted intestinal metal stent placement for the treatment of acute malignant colorectal obstruction is safe and effective, with no radiation exposure.
4.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
5.Acupuncture regulates dynamic flux of Ca2+, Na+, and H2O2 in skeletal muscle injury induced by eccentric exercise in rats.
Xue-Lin ZHANG ; Qian ZHAO ; Ai-Shan LIU ; Ming-Liang DUAN ; Jing-Jing DING ; Hua WANG
Acta Physiologica Sinica 2025;77(1):47-61
This study aimed to investigate the effects of acupuncture on dynamic changes in Ca2+, Na+, and H2O2 flux following eccentric exercise-induced muscle injury. The total of 324 healthy male Wistar rats were randomly divided into 6 groups: control group (C), eccentric exercise group (E), eccentric exercise with acupuncture group (EA), EA with TRP channel blocker group (EAT), EA with NOX2 blocker group (EAN) and EA with placebo group (EAP). Gastrocnemius muscles were subject to lengthening contractions with percutaneous electrical stimulation, followed by immediate pretreatment with blocking agents. After 30 min, acupuncture needling was administered to the gastrocnemius muscle, and real-time dynamic changes of Ca2+, Na+ and H2O2 flux were measured with non-invasive micro-test technique during the needle retention period, immediately, 3 h, 6 h, and 24 h post-extraction respectively. Results showed that compared with the E group, acupuncture significantly increased net Ca2+ efflux (P < 0.05), extended the period of net Na+ influx, and significantly decreased net H2O2 efflux (P < 0.05). However, these effects were significantly attenuated in the EAT and EAN groups, where excessive net H2O2 efflux was observed (P < 0.001). These findings indicate that acupuncture regulates the dynamic changes of Ca2+, Na+ and H2O2 flux by activating the TRP channels and interacting with NOX2 activity following eccentric exercise-induced skeletal muscle injury.
Animals
;
Muscle, Skeletal/metabolism*
;
Rats, Wistar
;
Rats
;
Male
;
Calcium/metabolism*
;
Hydrogen Peroxide/metabolism*
;
Physical Conditioning, Animal
;
Sodium/metabolism*
;
Acupuncture Therapy
;
NADPH Oxidase 2
6.Research progress on molecular mechanisms of ginsenosides in alleviating acute lung injury.
Han-Yang ZHAO ; Xun-Jiang WANG ; Qiong-Wen XUE ; Bao-Lian XU ; Xu WANG ; Shu-Sheng LAI ; Ming CHEN ; Li YANG ; Zheng-Tao WANG ; Li-Li DING
China Journal of Chinese Materia Medica 2025;50(16):4451-4470
Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology*
;
Humans
;
Acute Lung Injury/immunology*
;
Animals
;
Panax/chemistry*
;
Drugs, Chinese Herbal
7.Curative Efficacy Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with ASXL1 Mutation.
Ya-Jie SHI ; Xin-Sheng XIE ; Zhong-Xing JIANG ; Ding-Ming WAN ; Rong GUO ; Tao LI ; Xia ZHANG ; Xue LI ; Yu-Pei ZHANG ; Yue SU
Journal of Experimental Hematology 2025;33(3):720-725
OBJECTIVE:
To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation.
METHODS:
The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed.
RESULTS:
Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients.
CONCLUSION
Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans
;
Leukemia, Myeloid, Acute/therapy*
;
Hematopoietic Stem Cell Transplantation
;
Female
;
Male
;
Middle Aged
;
Mutation
;
Adult
;
Repressor Proteins/genetics*
;
Adolescent
;
Retrospective Studies
;
Aged
;
Nucleophosmin
;
Young Adult
;
Transplantation, Homologous
;
Prognosis
;
Survival Rate
8.Short-term Effects of Fine Particulate Matter and its Constituents on Acute Exacerbations of Chronic Bronchitis: A Time-stratified Case-crossover Study.
Jing Wei ZHANG ; Jian ZHANG ; Peng Fei LI ; Yan Dan XU ; Xue Song ZHOU ; Xiu Li TANG ; Jia QIU ; Zhong Ao DING ; Ming Jia XU ; Chong Jian WANG
Biomedical and Environmental Sciences 2025;38(3):389-393
9.Audiological characterization of the GJB2 gene c.109G>A (p.V37I) hotspot variant during childhood and comparison between family members.
Zhoushu ZHENG ; Jiangyang XUE ; Lu DING ; Jiewen PAN ; Meihong WANG ; Yinghui ZHANG ; Danyan ZHUANG ; Yihui YANG ; Ming TANG ; Haibo LI
Chinese Journal of Medical Genetics 2025;42(9):1061-1068
OBJECTIVE:
To determine the prevalence of GJB2 gene c.109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families.
METHODS:
One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c.109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c.109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children's Hospital of Ningbo University (Ethics No.: EC2023-009).
RESULTS:
For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c.109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c.109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined (n = 53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined (n = 24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls (P = 0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1 ± 12.0 dB nHL, P = 0.005).
CONCLUSION
Infants harboring the GJB2 c.109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c.109G>A variant can confer a more severe hearing loss.
Humans
;
Connexin 26/genetics*
;
Female
;
Male
;
Infant, Newborn
;
Infant
;
Hearing Loss/genetics*
;
Retrospective Studies
;
Child, Preschool
;
Child
;
Genotype
;
Connexins/genetics*
;
Mutation
10.Audiological characterization of the GJB2 gene c. 109G>A (p.V37I) hotspot variant during childhood and comparison between family members
Zhoushu ZHENG ; Jiangyang XUE ; Lu DING ; Jiewen PAN ; Meihong WANG ; Yinghui ZHANG ; Danyan ZHUANG ; Yihui YANG ; Ming TANG ; Haibo LI
Chinese Journal of Medical Genetics 2025;42(9):1061-1068
Objective:To determine the prevalence of GJB2 gene c. 109G>A (p.V37I) variant among infants with congenital hearing loss and analyze the initial audiological characteristics of children harboring the variant, compare the audiometric difference among individuals with various genotypes, and explore genetic and audiological manifestations of the affected families. Methods:One hundred twenty six infants diagnosed with congenital hearing loss at the Neonate Screening Center of Ningbo City from June 2021 to December 2024 were selected as the study subjects. The neonates, in addition with members from 16 of their families, had undergone genetic screening for variants of 208 hotspot sites within 24 deafness-associated genes. For cases identified with monoallelic variants and concurrent hearing loss, the full GJB2 gene was sequenced. Meanwhile, a retrospective analysis was carried out on 23 children whom were confirmed to have hearing loss and the c. 109G>A variant by whole exome sequencing from March 2022 to December 2024. And 102 children who were excluded to have hearing loss and pathogenic variants by whole exome sequencing were selected as normal controls. Audiological features of individuals harboring the c. 109G>A variant were compared. This study has been approved by the Medical Ethics Committee of The Affiliated Women and Children′s Hospital of Ningbo University (Ethics No.: EC2023-009). Results:For the 126 infants with congenital hearing loss, prospective screening has identified 58 (46.03%) to harbor the c. 109G>A variant. These included 38 homozygotes and 16 compound heterozygotes. Retrospective review of the 23 c. 109G>A positive children has identified 15 as homozygotes and 8 as compound heterozygotes. Genetic testing of the 16 pedigrees has identified 7 homozygotes and 1 compound heterozygote. For the homozygotes combined ( n=53), 96.2% exhibited bilateral symmetric hearing loss, with 78.3% showing high-frequency sloping patterns, and 98.1% having a hearing threshold ranging from 20 to 65 dB. For the compound heterozygotes combined ( n=24), 95.8% showed symmetric loss, with 59.4% having high-frequency sloping, and 97.9% had a hearing threshold ranging from 20 to 65 dB. Both groups showed significantly elevated ABR/PTA thresholds compared with the normal controls ( P=0.000). The compound heterozygous group had higher ABR thresholds (43.3 ± 15.0 dB nHL) compared with the homozygous group (39.1±12.0 dB nHL, P=0.005). Conclusion:Infants harboring the GJB2 c. 109G>A variant primarily manifest as mild-to-moderate, symmetric, high-frequency sloping hearing loss. Nearly one-third of affected children have thresholds between 20 to 35 dB nHL, suggesting that ABR > 35 dB nHL alone may underestimate the hearing impairment in this population. Compared with homozygotes, compound heterozygotes with the the GJB2 c. 109G>A variant can confer a more severe hearing loss.

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