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Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin jiangsu Key Laboratory of New drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China Department of Pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China Department of Pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New drug screening center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom Department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China Department of Pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological ***,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains ***,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH *** the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH *** of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)***’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 *** findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

Commentary:brain endothelial GSDMD as a novel target for brain disorders associated with BBB damage

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Chinese Journal of Natural Medicines 2024年第7期22卷 580-581页

作者： LIU Kui PANG Tao State Key Laboratory of Natural Medicines New Drug Screening and Pharmacodynamics Evaluation CenterChina Pharmaceutical UniversityNanjing 210009China

The blood-brain barrier(BBB)is a highly selective and critical interface between the blood and the central nervous system(CNS),essential for maintaining the microenvironment necessary for normal brain function and homeostasis[1].The BBB is primarily formed by brain endothelial cells(bECs),pericytes,and astrocytes,and it operates in concert with microglia/macrophages and neurons[2,3]to constitute the neurovascular unit(Fig.1).Disruption of the BBB or the presence of systemic inflammation can precipitate or exacerbate various CNS pathologies,including Alzheimer’s disease[4],amyotrophic lateral sclerosis[5],Huntington’s disease[6]and multiple sclerosis.

关键词： Brain endothelial cells GSDMD Blood-brain barrier Natural products Neuroinflammation Brain disorders

A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou Guangdong Provincial Key Laboratory of New drug screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for Research and Evaluation of drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin Pharmaceutical Research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug druggability

LncRNA HOTTIP facilitated tumor growth via stimulating the hnRNPA2B1/DKK1/Wnt/β-catenin regulatory axis in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 53-56页

作者： Weiqiang Zeng Chuanjian Shi Liqiang Deng Weiming Fu Jinfang Zhang Cancer center Shenzhen Hospital(Futian)of Guangzhou University of Chinese MedicineShenzhenGuangdong 518000China Guangdong Provincial Key Laboratory of New drug screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China

Hepatocellular carcinoma(HcC)has become the fifth leading cause of cancer mortality worldwide in the past decade.1 Dysregulated long noncoding RNAs(lncRNAs)are closely associated with its occurrence and *** identified IncRNA named"HOXA transcript at the distal tip"(HOTTIP)has been considered as an oncogene in multiple ***,the mechanism underlying HOTTiP-mediated hepatocarcinogenesis remains mostly unknown.

关键词： DKK1 mortality stimulating

Evaluation of Latent Tuberculosis Infection Using the ESAT6-CFP10 Skin Test Among International Freshmen With Diverse Skin Tones at a University—Nanjing City,jiangsu Province,China,September 2023

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China CDC weekly 2024年第35期6卷 896-900,I0001页

作者： Peng Lu Rong Wang Jingjing Xu Jianming Wang Fangfang Du Guozhi Wang Shiming Cheng Limei Zhu Department of Chronic Communicable Disease Jiangsu Provincial Center for Disease Control and PreventionNanjing CityJiangsu ProvinceChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjing CityJiangsu ProvinceChina Nanjing City center for Disease Control and Prevention Nanjing CityJiangsu ProvinceChina Chinese Antituberculosis Association BeijingChina National Institutes for Food and drug Control BeijingChina

Introduction:Newer skin tests,including the ESAT6-CFP10(EC)skin test,were recommended for diagnosing Mycobacterium tuberculosis(***)***,no data exist assessing the diagnostic performance of the EC skin test among foreign students with different skin ***:A cohort study at Nanjing Medical University screened incoming foreign *** EC skin test was used to assess for *** infection,and results were read at 24,48,72,and 96-hours ***:Among 96 participants,*** infection rates at 24,48,72,and 96-hours post-injection were 3.13%,7.29%,13.54%,and 9.38%,*** infection rates were lower among individuals with darker skin tones,the difference was not statistically significant(P=0.186),and variations were consistent across different measurement *** analysis revealed 5.3%in the continuousincreasing group,86.5%in the low-stable group,and 5.2%in the elevated-decreasing ***,participants in the elevated-decreasing group had lighter skin tones,with trajectory patterns consistent across different skin ***:The EC skin test is safe,and redness diameter is a more reliable indicator than *** should be collected within 48 to 72 hours,with verification at 72 hours crucial if initial results are ***,skin color does not affect EC skin test outcomes.

关键词： CFP10 Skin Nanjing

Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility

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Journal of Biomedical Research 2024年第5期38卷 473-484,I0003-I0008页

作者： Liping Cheng He Jin Tianheng Xiao Xiaoyu Yang Tingting Zhao Eugene Yujun Xu State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjingJiangsu 211166China center for Clinical Reproduction the First Affiliated Hospital with Nanjing Medical University&Jiangsu Province HospitalNanjingJiangsu 210029China Cellular screening center the University of ChicagoChicagoIL 60637USA

Reliable molecular biomarkers to predict fertility remain *** current study investigated the potential of testis-specific circBOULE RNAs as biomarkers for male infertility and sperm *** reverse transcription-PCR and real-time reverse transcription-PCR assays,we identified seven circular RNAs from the human BOULE gene in human *** observed that the expression level of circEx3-6 was significantly reduced in asthenozoospermia,while the expression levels of both circEx2-6 and circEx2-7 were decreased in terato-zoospermia,compared with the ***,we demonstrated that the expression level of circEx2-6 was negatively correlated with the sperm DNA fragmentation index,and the expression level of circEx2-7 was correlated with both fertilization and cleavage rates in those treated with the assisted reproductive *** functional analyses in a transgenic fly model supported the roles of circBOULE RNAs in sperm development and human male ***,our findings support that sperm circBOULE RNAs may serve as diagnostic biomarkers for assessing sperm motility and DNA ***,clinical application and significance of sperm circBOULE RNAs in the assisted reproductive technologies warrant further investigation.

关键词： human circBOULE RNAs sperm DNA fragmentation index fertilization rate cleavage rate semen parameters assisted reproductive technology

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

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Zoological Research 2024年第5期45卷 1037-1047页

作者： Chun-Xue Niu Jia-Wei Li Xiao-Li Li Lin-Lin Zhang Yan Lang Zhen-Bo Song Chun-Lei Yu Xiao-Guang Yang Hai-Feng Zhao Jia-Ling Sun Li-Hua Zheng Xue Wang Ying Sun Xiao-Hong Han Guan-Nan Wang Yong-Li Bao National Engineering Laboratory for druggable Gene and Protein screening Northeast Normal UniversityChangchunJilin 130117China China International Joint Research center for Human Stem Cell Bank Northeast Normal UniversityChangchunJilin 130117China Jilin Institute for drug Control ChangchunJilin 130022China

Serine protease 50(PRSS50/TSP50)is highly expressed in *** study investigated its role in testicular development and ***,PRSS50 knockdown was observed to impair DNA synthesis in *** further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male ***,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic *** analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−*** together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

关键词： PRSS50(TSP50) Meiotic progression Sperm quality MKP3 ERK

Cancer profiles in China and comparisons with the USA:a comprehensive analysis in the incidence,mortality,survival,staging,and attribution to risk factors

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Science China(Life Sciences) 2024年第1期67卷 122-131页

作者： Siyi He Changfa Xia He Li Maomao Cao Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Wanqing Chen Office of Cancer screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

China faces a disproportionate cancer burden to the population size and is undergoing a transition in the cancer *** extracted data in five aspects of cancer incidence,mortality,survival,staging distributions,and attribution to risk factors in China,the USA and worldwide from open-source *** conducted a comprehensive secondary analysis of cancer profiles in China in the above aspects,and compared cancer statistics between China and the USA.A total of 4,546,400 new cancer cases and 2,992,600 deaths occurred in China in 2020,accounting for 25.1%and 30.2%of global cases,***-related cancers including lung cancer,colorectal cancer,and breast cancer showed an upward trend and have been the leading cancer types in China.41.6%of new cancer cases and 49.3%of cancer deaths occurred in digestive-system cancers in China,and the cancers of esophagus,nasopharynx,liver,and stomach in China accounted for over 40%of global ***-related cancers showed the highest population-attributable fractions among Chinese adults,and most cancers could be attributed to behavioral and metabolic *** proportions of stage I for most cancer types were much higher in the USA than in China,except for esophageal cancer(78.2%vs.41.1%).The 5-year relative survival rates in China have improved substantially during 2000–2014,whereas survival for most cancer types in the USA was significantly higher than in China,except for upper gastrointestinal *** findings suggest that although substantial progress has been made in cancer control,especially in digestive system cancers in China,there was still a considerable disparity in cancer burden between China and the *** robust policies on risk factors and standardized screening practices are urgently warranted to curb the cancer growth and improve the prognosis for cancer patients.

关键词： cancer burden survival rate neoplasm staging risk factors China

Cancer statistics for young adults aged 20 to 49 years in China from 2000 to 2017:a population-based registry study

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Science China(Life Sciences) 2024年第4期67卷 711-719页

作者： Yi Teng Changfa Xia He Li Maomao Cao Fan Yang Xinxin Yan Siyi He Mengdi Cao Shaoli Zhang Qianru Li Wanqing Chen Office of Cancer screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

An increasing cancer incidence among adults younger than 50 years has been reported for several types of cancer in multiple *** aimed to report cancer profiles and trends among young adults in *** from the China Cancer Registry Annual Report were used to estimate incidence and mortality among young adults(ages 20–49 years)in China in 2017,and an age-period-cohort model was employed to estimate the average annual percent change(AAPC)in incidence and mortality from 2000 to *** 25 cancer types were grouped into obesity-or overweight-associated cancers(12 cancer types)and additional cancers(13 cancer types).In 2017,there were 681,178new cases and 214,591 cancer deaths among young adults in *** young adults,the most common cancers were thyroid,breast,cervical,liver,lung,and colorectal cancer,and the leading causes of cancer deaths were liver,lung,cervical,stomach,breast,and colorectal *** 2000 to 2017,the cancer incidence increased for all cancers combined among young adults,with the highest AAPC(1.46%)for adults aged 20–24 years,while cancer mortality decreased,with the highest AAPC(-1.63%)for those aged 35–39 *** conclusion,the cancer incidence in China has increased among young adults,while cancer mortality has decreased for nearly all *** control measures,such as obesity control and appropriate screening,may contribute to reducing the increasing cancer burden among young adults.

关键词： young adults incidence mortality trends China