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OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

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Research 2024年第1期2023卷 455-469页

作者： Yinghong Cui Wei Chen Li Du Zuping He The key laboratory of Model Animals and Stem Cell Biology in hunan province The Research Center of Reproduction and Translational Medicine of Hunan ProvinceHunan Normal University School of MedicineChangsha 410013HunanChina

Spermatogonial stem cells(SSCs)have important applications in both reproduction and regenerative medicine.Nevertheless,specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive.Here,we have demonstrated for the first time that OIP5(Opa interacting protein 5)controlled the self-renewal and apoptosis of human SSCs.RNA sequencing identified that NCK2 was a target for OIP5 in human SSCs,and interestingly,OIP5 could interact with NCK2 as shown by Co-IP(co-immunoprecipitation),IP-MS(mass spectrometry),and GST pulldown assays.NCK2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their apoptosis.Notably,NCK2 knockdown reversed the influence of OIP5 overexpression on human SSCs.Moreover,OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases,while the levels of numerous cell cycle proteins,including cyclins A2,B1,D1,E1 and H,especially cyclin D1,were remarkably reduced.Significantly,whole-exome sequencing of 777 patients with nonobstructive azoospermia(NOA)revealed 54 singlenucleotide polymorphism mutations of the OIP5 gene(6.95%),while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile men.Collectively,these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with azoospermia.As such,this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA,and it provides new targets for treating male infertility.

关键词： OIP5 Apoptosis reversed

Iridoids modulate inflammation in diabetic kidney disease: A review

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Journal of Integrative medicine 2024年第3期22卷 210-222页

作者： Tong-yi Zhou Na Tian Liu Li Rong Yu The First Clinical College of Chinese medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina hunan Provincial key laboratory of translational Research in Traditional Chinese medicine Prescriptions and Zheng Changsha 410208Hunan ProvinceChina

In recent years,preclinical research on diabetic kidney disease (DKD) has surged to the forefront of scientific and clinical attention.DKD has become a pervasive complication of type 2 diabetes.Given the complexity of its etiology and pathological mechanisms,current interventions,including drugs,dietary modifications,exercise,hypoglycemic treatments and lipid-lowering methods,often fall short in achieving desired therapeutic outcomes.Iridoids,primarily derived from the potent components of traditional herbs,have been the subject of long-standing research.Preclinical data suggest that iridoids possess notable renal protective properties;however,there has been no summary of the research on their efficacy in the management and treatment of DKD.This article consolidates findings from in vivo and in vitro research on iridoids in the context of DKD and highlights their shared anti-inflammatory activities in treating this condition.Additionally,it explores how certain iridoid components modify their chemical structures through the regulation of intestinal flora,potentially bolstering their therapeutic effects.This review provides a focused examination of the mechanisms through which iridoids may prevent or treat DKD,offering valuable insights for future research endeavors.

关键词： Diabetic kidney disease Iridoids Gut-kidney axis Traditional Chinese medicine monomer Inflammation

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study

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World Journal of Diabetes 2024年第5期15卷 1021-1044页

作者： Hong Li Liu Li Qiu-Qing Huang Si-Yao Yang Jun-Ju Zou Fan Xiao Qin Xiang Xiu Liu Rong Yu College of Chinese medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina College of International Education Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Science and Technology Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina hunan key laboratory of TCM Prescription and Syndromes translational medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina College of Graduate Hunan University of Chinese MedicineHunan ChangshaHunan ProvinceChina

BACKGROUND Diabetes is a metabolic disease characterized by hyperglycemia,which has increased the global medical burden and is also the main cause of death in most countries.AIM To understand the knowledge structure of global development status,research focus,and future trend of the relationship between diabetes and metabolomics in the past 20 years.METHODS The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23,2023,and the relevant information was analyzed using CiteSpace6.2.2R(CiteSpace),VOSviewer6.1.18(VOSviewer),and Bibliometrix software under R language.RESULTS A total of 3123 publications were included from 2002 to 2022.In the past two decades,the number of publications and citations in this field has continued to increase.The United States,China,Germany,the United Kingdom,and other relevant funds,institutions,and authors have significantly contributed to this field.Scientific Reports and PLoS One are the journals with the most publications and the most citations.Through keyword co-occurrence and cluster analysis,the closely related keywords are"insulin resistance","risk","obesity","oxidative stress","metabolomics","metabolites"and"biomarkers".keyword clustering included cardiovascular disease,gut microbiota,metabonomics,diabetic nephropathy,molecular docking,gestational diabetes mellitus,oxidative stress,and insulin resistance.Burst detection analysis of keyword depicted that"Gene","microbiota","validation","kidney disease","antioxidant activity","untargeted metabolomics","management",and"accumulation"are knowledge frontiers in recent years.CONCLUSION The relationship between metabolomics and diabetes is receiving extensive attention.Diabetic nephropathy,diabetic cardiovascular disease,and kidney disease are key diseases for future research in this field.Gut microbiota,molecular docking,and untargeted metabolomics are key research directions in the future.Antioxidant activity,gene,validation,mass spectrometry,manage

关键词： Diabetes Metabolomics Bibliometric CiteSpace VOSviewer

Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κB-ROS/NLRP3 Pathway

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中国结合医学杂志:英文版 2023年第10期29卷 895-904页

作者： YI Jing LI Li YIN Zhu-jun QUAN Yun-yun TAN Rui-rong CHEN Shi-long LANG Ji-rui LI Jiao ZENG Jin LI Yong SUN Zi-jian ZHAO Jun-ning Department of Pharmacology Southwest Medical UniversityLuzhouSichuan Province646000China Sichuan Institute for translational Chinese medicine Translational Chinese Medicine Key Laboratory of Sichuan ProvinceSichuan Academy of Chinese Medicine SciencesChengdu610000China hunan Provincial key laboratory of the Research and Development of Novel Pharmaceutical Preparations College of PharmacyChangsha Medical UniversityChangsha410219China Sichuan Fengchun Pharmaceutical Co. Ltd.DeyangSichuan Province618100China Sichuan Ant Recommendation Biotechnology Co. Ltd.Chengdu610000China

Objective To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus(PPM)in lipopolysaccharide(LPS)-induced THP-1 macrophages and BALB/c mice.Methods The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE).Subsequently,LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice.In LPS-treated or untreated THP-1 macrophages,cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays;the proinflammatory cytokines and reactive oxygen species(ROS)were measured by enzyme-linked immunosorbent assay and flow cytometry,respectively;and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction(qRT-PCR),respectively.In LPS-induced BALB/c mice,the proinflammatory cytokines were measured,and lung histology and cytokines were observed by hematoxylin and eosin(HE)and immunohistochemical(IHC)staining,respectively.Results The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10–26 kD.In vitro,PPM reduced the production of interleukin 1β(IL-1β),IL-18,tumor necrosis factorα(TNF-α),IL-6 and ROS in LPS-induced THP-1 macrophages(P<0.01).Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factorκB(NF-κB)pathway and thioredoxin interacting protein(TXNIP)/nucleotide-binding oligomerization domain,leucine-rich repeat and pyrin domain containing 3(NLRP3)inflammasome pathway by reducing protein expression of phospho-NF-κB p65,phospho-inhibitors of NF-κB(IκBs)kinaseα/β(IKKα/β),TXNIP,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),and pro-caspase-1(P<0.05 or P<0.01).In addition,qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP,NLRP3,ASC,and caspase-1(P<0.05 or P<0.01).Furthermore,in LPS-induced BALB/c mice,PPM reduced TNF-αand IL-6 levels in serum(P<0.05 or P<0.01),decreased I

关键词： Moschus polypeptide inflammation NLRP3 inflammasome thioredoxin interacting protein nuclear factorκB Chinese medicine

Selection and identification of a novel ssDNA aptamer targeting human skeletal muscle

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生物活性材料(英文) 2023年第2期20卷 166-178页

作者： Shuming Sun Han Liu Yan Hu Yanpeng Wang Mingri Zhao Yijun Yuan Yafei Han Yingying Jing Jin Cui Xiaoxiang Ren Xiao Chen Jiacan Su Molecular Biology Research Center Center for Medical GeneticsHunan Province Key Laboratory of Basic and Applied HematologySchool of Life SciencesCentral South UniversityChangsha410078China Institute of translational medicine Shanghai UniversityShanghai200444China Center for Medical Genetics&hunan key laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangsh1Hunan410013China Molecular Science and Biomedicine laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of BiologyCollege of Chemistry and Chemical EngineeringAptamer Engineering Center of Hunan ProvinceHunan UniversityChangshaHunan410082China Department of Orthopedics Traum1 Shanghai Changhai HospitalNaval Medical UniversityShanghai200433China

Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.

关键词： Aptamer SELEX Human skeletal muscle Target delivery Nanoliposomes

High-throughput quantitative detection of triple-negative breast cancer-associated expressed miRNAs by rolling circle amplification on fluorescence-encoded microspheres

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中国化学快报:英文版 2023年第9期34卷 199-203页

作者： Jieyu Liu Liming Zhang Wentao Zeng Lihua Zhang Nongyue He Zhuoxuan Lu key laboratory of Tropical translational medicine of Ministry of Education NHC Key Laboratory of Control of Tropical DiseasesSchool of Tropical MedicineMicronano Technology Research InstituteSchool of Basic Medicine and Life SciencesHainan Medical UniversityHaikou 571199China Beadstar Biotechnology Hainan province Co. Ltd.Haikou 570110China State key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in hunan province Hunan Key Laboratory of Biomedical Nanomaterials and DevicesHunan University of TechnologyZhuzhou 412007China

Compared with other types of breast cancer,triple-negative breast cancer(TNBC)has the characteristics of a high degree of malignancy and poor prognosis.Early diagnosis of TNBC through biological markers and timely development of effective treatment methods can reduce its mortality.Many Research experiments have confirmed that some specific mi RNA expression profiles in TNBC can used as markers for early diagnosis.However,detecting the expression profiles of multiple groups of miRNAs according to traditional detection methods is complicated and consumes many samples.To address this issue,we developed a method for high-throughput,high-sensitivity quantitative detection of multiple sets of miRNAs(including mi R-16,mi R-21,mi R-92,mi R-199,and mi R-342)specifically expressed in TNBC by rolling circle amplification(RCA)on fluorescence-encoded microspheres.Through the optimization of reaction system conditions,the developed method showed an extensive linear dynamic range and high sensitivity for all five miRNAs with the lowest limit of detection of 2 fmol/L.Meanwhile,this high-throughput detection method also appeared reasonable specificity.Only in the presence of a specific target miRNA,the fluorescence signal on the correspondingly encoded microspheres is significantly increased,while the fluorescence signal on other non-correspondingly encoded microspheres is almost negligible.Furthermore,this process exhibited good recovery and reproducibility in serum.The advantages of this method allow us to more conveniently obtain the expression profiles of multiple groups of TNBC-associated mi RNAs,which is beneficial for the early detection of TNBC.

关键词： MicroRNAs Rolling circle amplification Fluorescence-encoded microspheres High-throughput Triple-negative breast cancer

The role of homozygous LOF variant of the PNLDC1 gene in oligo-astheno-teratozoospermia(OAT)and male infertility

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Asian Journal of Andrology 2023年第6期25卷 754-755页

作者： Zi-Xin Cheng Li Du Zuping He The key laboratory of Model Animals and Stem Cell Biology in hunan province School of MedicineHunan Normal UniversityThe Research Center of Reproduction and Translational Medicine of Hunan ProvinceThe Manufacture-Based Learning and Research Demonstration Center for Human Reproductive Health New Technology of Hunan Normal UniversityChangsha 410013China

Dear Editor,An interesting article from Zhao et al.recently published in Asian Journal of Andrology,has shown the association of a novel loss-of function(LOF)variant in PARN-like ribonuclease domain-containing exonucl... 详细信息

关键词： infertility LOF terat

Antihepatoma peptide,scolopentide,derived from the centipede scolopendra subspinipes mutilans

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World Journal of Gastroenterology 2023年第12期29卷 1875-1898页

作者： Yu-Xing Hu Zhuo Liu Zhen Zhang Zhe Deng Zhen Huang Ting Feng Qing-Hong Zhou Si Mei Chun Yi Qing Zhou Pu-Hua Zeng Gang Pei Sha Tian Xue-Fei Tian College of Integrated Chinese and Western medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina hunan key laboratory of translational Research in Formulas and Zheng of Traditional Chinese medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Scientific Research Hunan Academy of Traditional Chinese Medicine Affiliated HospitalChangsha 410208Hunan ProvinceChina hunan province University key laboratory of Oncology of Traditional Chinese medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Pediatric Shenzhen Hospital of Beijing University of Chinese MedicineShenzhen 518000Guangdong ProvinceChina Department of Physiology Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Pathology Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Andrology First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina Department of Oncology Hunan Academy of Traditional Chinese Medicine Affiliated HospitalChangsha 410208Hunan ProvinceChina College of Pharmacy Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Dr Neher’s Biophysics laboratory for Innovative Drug Discovery Macao University of Science and TechnologyMacao 999078China

BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines.AIM To purify,characterize,and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism.METHODS An antihepatoma peptide(scolopentide)was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis,a Sephadex G-25 column,and two steps of high-performance liquid chromatography(HPLC).Additionally,the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity.The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry(QTOF MS),and the sequence was matched by using the Mascot search engine.Based on the sequence and molecular weight,scolopentide was synthesized using solid-phase peptide synthesis methods.The synthetic scolopentide was confirmed by MS and HPLC.The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro.The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo.In the tumor xenograft experiments,qualified model mice(male 5-week-old BALB/c nude mice)were randomly divided into 2 groups(n=6):The scolopentide group(0.15 mL/d,via intraperitoneal injection of synthetic scolopentide,500 mg/kg/d)and the vehicle group(0.15 mL/d,via intraperitoneal injection of normal saline).The mice were euthanized by cervical dislocation after 14 d of continuous treatment.Mechanistically,flow cytometry

关键词： Scolopendra Centipede Antihepatom peptide Hepatocellular carcinoma Death receptor 4 Death receptor 5

Xihuang pills induce apoptosis in hepatocellular carcinoma by suppressing phosphoinositide 3-kinase/protein kinase- B/mechanistic target of rapamycin pathway

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World Journal of Gastrointestinal Oncology 2022年第4期14卷 872-886页

作者： Yong-Jie Teng Zhe Deng Zhao-Guang Ouyang Qing Zhou Si Mei Xing-Xing Fan Yong-Rong Wu Hong-Ping Long Le-Yao Fang Dong-Liang Yin Bo-Yu Zhang Yin-Mei Guo Wen-Hao Zhu Zhen Huang Piao Zheng Di-Min Ning Xue-Fei Tian The First Hospital of hunan University of Chinese medicine Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina College of Integrated Chinese and Western medicine Hunan Key Laboratory of Translational Research in Formulas and Zheng of Traditional Chinese MedicineHunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina Department of Preventive Dentistry Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative MedicineGuangzhou Medical UniversityGuangzhou 510132Guangdong ProvinceChina Department of Physiology Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina State key laboratory of Quality Research in Chinese medicine Macao Institute For Applied Research in Medicine and HealthMacao University of Science and TechnologyMacaoChina School of Pharmacy Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina College of Acupuncture and Massage Hunan University of Chinese MedicineChangsha 410208Hunan ProvinceChina

BACKGROUND The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin(PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills(XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma(HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHPassociated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway.AIM To confirm the effect of XHP on HCC and the possible mechanisms involved.METHODS The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS). Cellbased experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP(0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay.Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction(RT-qPCR), respectively.Third, Western blotting and RT–qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of

关键词： Hepatocellular carcinoma Xihuang pills Apoptosis Antitumour Phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin pathway