1.Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation.
Luxun TANG ; Yu SHI ; Qiao LIAO ; Feng WANG ; Hao WU ; Hongmei REN ; Xuemei WANG ; Wenbin FU ; Jialing SHOU ; Wei Eric WANG ; Pedro A JOSE ; Yongjian YANG ; Chunyu ZENG
Acta Pharmaceutica Sinica B 2025;15(1):256-277
The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.
2.Expert consensus on the prevention and treatment of radiochemotherapy-induced oral mucositis.
Juan XIA ; Xiaoan TAO ; Qinchao HU ; Wei LUO ; Xiuzhen TONG ; Gang ZHOU ; Hongmei ZHOU ; Hong HUA ; Guoyao TANG ; Tong WU ; Qianming CHEN ; Yuan FAN ; Xiaobing GUAN ; Hongwei LIU ; Chaosu HU ; Yongmei ZHOU ; Xuemin SHEN ; Lan WU ; Xin ZENG ; Qing LIU ; Renchuan TAO ; Yuan HE ; Yang CAI ; Wenmei WANG ; Ying ZHANG ; Yingfang WU ; Minhai NIE ; Xin JIN ; Xiufeng WEI ; Yongzhan NIE ; Changqing YUAN ; Bin CHENG
International Journal of Oral Science 2025;17(1):54-54
Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans
;
Chemoradiotherapy/adverse effects*
;
Consensus
;
Risk Factors
;
Stomatitis/etiology*
3.Therapeutic Effect of Sargentodoxae Caulis on Ulcerative Colitis and Exploring the Mechanism Based on GEO Chip Combined with Network Pharmacology
Feng XU ; Piao YU ; Linlin DU ; Qian ZENG ; Junyi WANG ; Hongmei WU ; Xiangpei WANG
Chinese Journal of Modern Applied Pharmacy 2024;41(3):332-340
OBJECTIVE
To study the anti-ulcerative colitis(UC) effect of Sargentodoxae Caulis and explore its mechanism.
METHODS
The UC mice model induced by dextran sodium sulfate was used to evaluate the anti-UC effect of Sargentodoxae Caulis. The ingredients of Sargentodoxae Caulis were obtained according to the CNKI and PubMed website, component targets were screened by SwissTargetPrediction database, GEO gene chip was used to extract UC differential genes, then a network of "ingredients-targets-disease" of the Sargentodoxae Caulis was constructed. After screening the core targets, protein interaction and cluster analysis, biological process and pathway enrichment analysis were performed, and the reliability of network analysis was preliminarily verified by molecular docking and literatures.
RESULTS
Sargentodoxae Caulis could significantly improve the disease activity index score, colon shortening and colonic histopathological changes of UC mice, and had a good anti-UC effect. The network analysis found that the core components of the anti-UC of Sargentodoxae Caulis include (+)-Dihydroxyurearetic acid, Isorhaponigenin and Pinosylvin, and 63 core targets, such as EGFR, STAT1 and LCK, regulating PI3K-Akt signal pathway and cancer proteoglycan and other related signal pathways of immune anti-inflammatory and anti-cancer, and it could affect the biological processes such as amino acid modification, kinase activity regulation, cell reaction and oxidative stress to treat UC. Molecular docking and literature showed that the constructed network had high reliability.
CONCLUSION
Sargentodoxae Caulis has a good anti-UC effect, and its mechanism may be closely related to the regulation of intestinal immune inflammation and cell proliferation, differentiation and migration. It has the characteristics of multi-component, multi-target and multi-way.
4.Correlation analysis between coronary artery calcifications and cardiovascular disease in patients with breast cancer after radiotherapy
Buzhi SONG ; Ziyi XIAO ; Zekai ZENG ; Yingshan GAO ; Qingyu WU ; Yingying ZHOU ; Hongmei WANG
Chinese Journal of Radiation Oncology 2024;33(1):85-89
Coronary artery calcifications (CAC) is an independent risk factor for cardiovascular disease (CVD). It has been revealed that this condition can be automatically quantified through computerize tomographic (CT) scan contained in radiotherapy plan for patients with breast cancer, with which, physicians can identify the patients with increased risk of CVD after radiotherapy prematurely and take intervention measures in advance. In this article, the current literature and research progress on the correlation between CAC and cardiotoxicity in patients with breast cancer after radiotherapy were reviewed, expecting to provide a strategy to reduce the CVD risk in patients with breast cancer after radiotherapy.
5.Incidence, mortality, and disability-adjusted life years of female breast cancer in China, 2022
Kexin SUN ; Bailin ZHANG ; Shaoyuan LEI ; Rongshou ZHENG ; Xin LIANG ; Li LI ; Xiaolong FENG ; Siwei ZHANG ; Hongmei ZENG ; Yifei YAO ; Peiqing MA ; Shaoming WANG ; Ru CHEN ; Bingfeng HAN ; Wenqiang WEI ; Jie HE
Chinese Medical Journal 2024;137(20):2429-2436
Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.
6.Effect of Aspergillus fumigatus on DNA damage and IL-33 expression in human bronchial epithelial cells and its mechanism
Qiao WANG ; Ziling ZENG ; Xing WANG ; Ning MA ; Zhibin WANG ; Guofeng XU ; Xiefang YUAN ; Xiaoyun WANG ; Yuejiao LI ; Hongmei TANG ; Yun ZHANG
Journal of Jilin University(Medicine Edition) 2024;50(5):1205-1216
Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P>0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P<0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P<0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P<0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P<0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P<0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P<0.01),the expression level of γH2AX(P<0.05),and the ROS level(P<0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P<0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P<0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P<0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P<0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P<0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P<0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P<0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.
7.Cancer incidence and mortality in China, 2022
Rongshou ZHENG ; Ru CHEN ; Bingfeng HAN ; Shaoming WANG ; Li LI ; Kexin SUN ; Hongmei ZENG ; Wenqiang WEI ; Jie HE
Chinese Journal of Oncology 2024;46(3):221-231
Objective:The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center.Methods:According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022.Results:The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas.Conclusions:The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.
8.Cancer incidence and mortality in China, 2022
Rongshou ZHENG ; Ru CHEN ; Bingfeng HAN ; Shaoming WANG ; Li LI ; Kexin SUN ; Hongmei ZENG ; Wenqiang WEI ; Jie HE
Chinese Journal of Oncology 2024;46(3):221-231
Objective:The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center.Methods:According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022.Results:The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas.Conclusions:The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.
9.Prenatal diagnosis and genetic analysis of a special case with complex structural rearrangements of chromosome 8.
Yan ZENG ; Tingting LUO ; Feiyan QIAN ; Dehua CHENG ; Caiping CHEN ; Jiaming FAN ; Lifang ZHANG ; Tao ZHANG ; Hongmei LI ; Zhiqiang WU
Chinese Journal of Medical Genetics 2023;40(9):1181-1184
OBJECTIVE:
To present on a prenatally diagnosed case with complex structural rearrangements of chromosome 8.
METHODS:
Chromosome karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a fetus with increased nuchal thickness.
RESULTS:
The karyotype of the amniotic fluid sample showed extra materials on 8p. FISH revealed a centromeric signal at the terminal of 8p with absence of telomeric signal. CMA revealed partial deletion of 8p23.3 [(208049_2256732)×1], partial duplication of 8p23.3p23.2 [(2259519_3016818)×3], and partial duplication of 8q [8q11.1q12.2(45951900_60989083)×3].
CONCLUSION
The complex structural rearrangements of chromosome 8 in this case has differed from the commonly seen inv dup del(8p).
Female
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Pregnancy
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Humans
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Chromosomes, Human, Pair 8/genetics*
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In Situ Hybridization, Fluorescence
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Gene Rearrangement
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Prenatal Diagnosis
;
Centromere
10.Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.
Dandong FANG ; Yu LI ; Bo HE ; Daqian GU ; Mingming ZHANG ; Jingwen GUO ; Hongmei REN ; Xinyue LI ; Ziyue ZHANG ; Ming TANG ; Xingbing LI ; Donghai YANG ; Chunmei XU ; Yijie HU ; Hongyong WANG ; Pedro A JOSE ; Yu HAN ; Chunyu ZENG
Acta Pharmaceutica Sinica B 2023;13(9):3756-3769
Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.


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