1.Expression of alcohol dehydrogenase 1 A and vascular endothelial growth factor-A in hepatocellular carcinoma
Lele XUE ; Yuying JING ; Kaige YANG ; Liwen QI ; Tong WU ; Yilin REN ; Yichen ZANG ; Lianghai WANG ; Haijun ZHANG ; Weihua LIANG ; Jianming HU
Acta Universitatis Medicinalis Anhui 2024;59(3):499-505
Objective To investigate the expression,synergistic relationship and clinical significance of alcohol de-hydrogenase(ADH1A)and vascular endothelial growth factor-A(VEGFA)in hepatocellular carcinoma(HCC).Methods The expression and correlation of ADH1A and VEGFA in HCC and adjacent normal tissues were ana-lyzed by GEPIA.TCGA and GSEA were used to analyze the pathway of ADH1A in HCC.The clinical and patho-logical data of 84 patients with HCC were collected,and 54 patients with paracancer normal tissue samples were se-lected as controls to analyze the correlation between ADH1A and VEGFA and clinicopathological parameters of HCC.Immunohistochemistry was used to detect the protein expression of ADH1A and VEGFA in cases and con-trols,and the correlation between the expression of ADH1A and VEGFA and the clinical progression and prognosis of patients with HCC was analyzed based on clinical pathological parameters and Kaplan-Meier.Results Bioinfor-matics analysis found that ADH1A was low-expressed in HCC and VEGFA was highly expressed in HCC,and there was a negative correlation between the two(P<0.001);immunohistochemical detection results showed that the expression of ADH1A in HCC tissue was lower than that in normal tissue adjacent to cancer(P<0.01)while the expression rate of VEGFA in HCC tissue was significantly higher than that of normal tissue adjacent to cancer(P<0.01);The recurrence rate of vascular thrombus and HCC patients in HCC group with high expression of ADH1A was lower(P<0.05).The proportion of tumor diameter>5 cm,high TNM stage,microsatellite and G2-G3 dif-ferentiation in HCC tissues in VEGFA high expression group was higher(P<0.05).Kaplan-Meier survival analy-sis showed that patients with high ADH1A expression and low VEGFA expression had a higher five-year survival rate.Conclusion Low expression of ADH1A and high expression of VEGFA in tumor tissues of patients with HCC indicate tumor progression and can be used as one of the prognostic evaluation indicators for patients with HCC.
2.3-Methyladenine alleviates early renal injury in diabetic mice by inhibiting AKT signaling
Benju LIU ; Yelei WANG ; Haiwen REN ; Liwen OU ; Xuan DENG ; Mengxin HUANG ; Xin WU ; Quan GONG
Journal of Southern Medical University 2024;44(7):1236-1242
Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.
3.3-Methyladenine alleviates early renal injury in diabetic mice by inhibiting AKT signaling
Benju LIU ; Yelei WANG ; Haiwen REN ; Liwen OU ; Xuan DENG ; Mengxin HUANG ; Xin WU ; Quan GONG
Journal of Southern Medical University 2024;44(7):1236-1242
Objective To explore the mechanism of 3-methyladenine(3-MA)for alleviating early diabetic renal injury.Methods Mouse models of streptozotocin(STZ)-induced diabetes mellitus were randomized into model group and 3-MA treatment group for daily treatments with normal saline and 10 mg/kg 3-MA by gavage for 6 weeks,respectively.Body weight and fasting blood glucose of the mice were recorded every week.After the treatments,the kidneys of the mice were collected for measurement kidney/body weight ratio,examination of glomerular size with PAS staining,and detection of α-SMA and PCNA expressions using Western blotting and immunohistochemistry.SV40 MES 13 cells cultured in normal glucose(5.6 mmol/L)and high glucose(30 mmol/L)were treated with 24.4 mmol/L mannitol and 5 mmol/L 3-MA for 24 h,respectively,and the changes in cell viability and PCNA expression were examined using CCK8 assay and Western blotting.Bioinformatics analysis of the intersecting gene targets of diabetic kidney disease(DKD)and 3-MA was performed,and the results were verified by Western blotting both in vivo and in vitro.Results In the diabetic mice,treatment with 3-MA produced a short-term hypoglycemic effect,reduced the kidney/body weight ratio and glomerular hypertrophy,and decreased the expressions of α-SMA and PCNA in the renal cortex.In the in vitro study,3-MA significantly lowered the viability and reduced PCNA expression in SV40 MES 13 cells exposed to high glucose.The results of bioinformatic analysis identified AKT1 as the key gene in the therapeutic mechanism of 3-MA for DKD.Western blotting confirmed that 3-MA inhibited the phosphorylation of AKT and S6 in both the renal cortex of diabetic mice and high glucose-treated SV40 MES 13 cells.Conclusion 3-MA suppresses mesangial cell proliferation and alleviates early diabetic renal injury in mice possibly by inhibiting AKT signaling.
4.Comparison of emotional and behavioral problems of only and non only child in the kindergartens in Chengdu
REN Yan, ZHU Diling, YE Liwen, LI Chunrong, CHEN Yue, YANG Liu, QIN Chengjie, LUO Tongyong
Chinese Journal of School Health 2023;44(5):733-737
Objective:
To analyze the emotional and behavioral problems and associated factors of the only and non only child, and to provide some clues for further monitoring and intervention of psychological and behavioral development among preschool children.
Methods:
Using a convenience sampling method, a total of 45 065 children enrolled in 153 kindergartens in 23 districts and counties of Chengdu were selected from May to June 2021 to investigate demographic characteristics and children s psycho behavioral development through online questionnaires filled out by their guardians. The Chi square tests were used to analyze whether the differences in abnormality rates of each dimension were statistically significant between the only and non only children. The emotional and behavioral problems of only children and non only children were analyzed by propensity score measurement.
Results:
The detection rate of abnormal emotional behavior problems in children was 6.10%, including 6.34% in the only child group and 5.84 % in the non only child group. After matching, total difficulty score, and scores of emotional symptoms, conduct problems, hyperactive attention deficit, peer interaction, and social behavior differed between the only child group and the non only child group ( t =9.91, 8.97, 3.91, 15.57, -5.46, 4.08, P <0.01).
Conclusion
In terms of the total score of difficulties, emotional symptoms, moral problems, and hyperactivity attention defects, the non only child is better than the only child,but the opposite is true in terms of peer interaction and social behavior. Mental health conditions among the only child should be paid more attention. Whether or not the only child should be taken as an important consideration for preschool children s mental health care.
5.Two cases of acute methyl acetate poisoning
Xianhan ZHU ; E REN ; Meijuan YU ; Yinji ZHOU ; Liwen SHEN ; Zuying HU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(11):856-858
This article analyzed the clinical data and on-site occupational health survey results of a patient with occupational acute methyl acetate poisoning in Zhejiang. Based on the pathways of methyl acetate poisoning and the characteristics of target organ damage, diagnosis and treatment experience were summarized, providing reference for the diagnosis and treatment of occupational acute methyl acetate poisoning and occupational health monitoring of methyl acetate.
6.Two cases of acute methyl acetate poisoning
Xianhan ZHU ; E REN ; Meijuan YU ; Yinji ZHOU ; Liwen SHEN ; Zuying HU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(11):856-858
This article analyzed the clinical data and on-site occupational health survey results of a patient with occupational acute methyl acetate poisoning in Zhejiang. Based on the pathways of methyl acetate poisoning and the characteristics of target organ damage, diagnosis and treatment experience were summarized, providing reference for the diagnosis and treatment of occupational acute methyl acetate poisoning and occupational health monitoring of methyl acetate.
7.The biology, function, and applications of exosomes in cancer.
Jinyi LIU ; Liwen REN ; Sha LI ; Wan LI ; Xiangjin ZHENG ; Yihui YANG ; Weiqi FU ; Jie YI ; Jinhua WANG ; Guanhua DU
Acta Pharmaceutica Sinica B 2021;11(9):2783-2797
Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial-mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.
8.Effects of miR-497 on cytobiology behaviors of papillary thyroid carcinoma by targetingly regulating YAP1 expression
Jiuzhou LIU ; Shasha REN ; Lijun FU ; Hongting LI ; Liwen LI ; Xinguang QIU
Chinese Journal of Endocrine Surgery 2021;15(1):21-26
Objective:To investigate the effects of miR-497 on cytobiology behaviors of papillary thyroid carcinoma (PTC) by targetingly regulating the expression of Yes-associated protein 1 (YAP1) .Methods:Human TPC-1 cells were divided into control group, miR-497 group, si-YAP1 group and miR-497+si-YAP1 group. The liposome transfection was conducted by LipofectamineTM3000. The targeted relationship between miR-497 and YAP1 was validated by Luciferase Reporter Assay. The cell proliferation activity in each group was detected by MTT method. The apoptosis rates were analyzed by flow cytometry. The number of invasion cells was detected by Transwell. The cell migration rates were detected by scratch assay. The expression of Cyclin D1, matrix metalloproteinase 2 (MMP-2) , MMP-9, matrix metalloproteinase inhibitor-1 (TIMP-1) and activated caspase 3 (cleaved Caspase-3) was detected by Western blot. SPSS 22.0 was used to analyze data, and normally distributed measurement data were expressed as ( ± s) . One-way ANOVA was analyzed for the difference between multiple groups, and SNK-q were analyzed for the difference between two groups. Results:Compared with the control group, the expression of YAP1 mRNA and protein was decreased in miR-497 group and si-YAP1 group ( q=14.682, 14.597; 23.743, 23.571; P<0.05) , cell proliferation activity, number of invasion cells and migration rate were decreased ( q=4.724, 4.568, 3.841; 4.216, 3.952, 3.274; P<0.05) , apoptosis rate was increased ( q=3.783; 4.336; P<0.05) , expression of CyclinD1, MMP-2, MMP-9 and cleared Caspase-3 proteins was decreased ( q=5.823, 5.981, 6.036, 6.485; 5.934, 6.110, 6.573, 6.614; P<0.05) , and expression of TIMP-1 protein was increased ( q=6.071; 6.148; P<0.05) . Compared with si-YAP1 group, miR-497 level was increased in miR-497+si-YAP1 group ( q=14.726, P<0.05) , the expression of YAP1 mRNA and protein was decreased ( q=3.089, 3.126; P<0.05) , cell proliferation activity, number of invasion cells and migration rate were decreased ( q=2.654, 2.537, 2.246; P<0.05) , apoptosis rate was increased ( q=2.875, P<0.05) , expression of CyclinD1, MMP-2, MMP-9 and cleared Caspase-3 proteins was decreased ( q=4.371, 4.365, 4.383, 4.368; P<0.05) , and expression of TIMP-1 protein was increased ( q=4.275, P<0.05) . Conclusion:MiR-497 can negatively targetingly regulate the expression of YAP1, inhibit proliferation, invasion and migration of TPC-1 cells.
9.Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway.
Xiangjin ZHENG ; Wan LI ; Huanli XU ; Jinyi LIU ; Liwen REN ; Yihui YANG ; Sha LI ; Jinhua WANG ; Tengfei JI ; Guanhua DU
Acta Pharmaceutica Sinica B 2021;11(11):3465-3480
Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant,
10.3--Acetyl-11-keto- -boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma.
Wan LI ; Liwen REN ; Xiangjin ZHENG ; Jinyi LIU ; Jinhua WANG ; Tengfei JI ; Guanhua DU
Acta Pharmaceutica Sinica B 2020;10(2):301-312
Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3--Acetyl-11-keto--boswellic acid (AKBA), one of the most active ingredients of gum resin from Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDI-MSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.


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