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Association of Congenital Heart Defects (CHD) with Factors Related to Maternal Health and Pregnancy in Newborns in Puerto Rico

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Congenital Heart Disease 2024年第1期19卷 19-31页

作者： Yamixa Delgado Caliani Gaytan Naydi Perez Eric Miranda Bryan Colón Morales Mónica Santos Biochemistry&pharmacology department San Juan Bautista School of MedicineCaguas00726Puerto Rico Hispanic Alliance for Clinical and Translational Research University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico department of Internal medicine University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BMI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(CHD)during neonatal development.Methods:Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with CHD between 2016 and 2020.Our assessment encompassed a range of variables,including maternal age,gestational age,BMI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of preeclampsia.Results:A cohort of 673 patients was included in our study.The average maternal age was 26 years,within a range of 22 to 32 years.The mean gestational age measured 39 weeks,with a median span of 38 to 39 weeks.Of the 673 patients,274(41%)mothers gave birth to neonates diagnosed with CHD.Within this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BMI,whereas 126 displayed a normal BMI.Conclusion:We identiﬁed a statistically signiﬁcant correlation between pre-gestational diabetes mellitus and the occurrence of CHD.However,our analysis did not show a statistically signiﬁcant association between maternal BMI and the likelihood of CHD.These results may aid in developing effective strategies to prevent and manage CHD in neonates.

关键词： Congenital heart defects(CHD) obesisty maternal health diabetes body mass index(BMI)

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Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

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Acta Pharmaceutica Sinica B 2024年第1期14卷 273-291页

作者： Duc-Vinh Pham Thi-Kem Nguyen Bao-Loc Nguyen Jong-Oh Kim Jee-Heon Jeong Inho Choi Pil-Hoon Park department of pharmacology Hanoi University of PharmacyHanoi 100000Viet Nam College of Pharmacy Yeungnam UniversityGyeongsan 38541Republic of Korea department of Medical Biotechnology Yeungnam UniversityGyeongsan 38541Republic of Korea Research Institute of Cell Culture Yeungnam UniversityGyeongsan 38541Republic of Korea department of Precision medicine School of MedicineSungkyunkwan UniversitySuwon 16419Republic of Korea

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese MSC.In this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of MSC.Diet-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese ADSC.Similar effects were also observed in lean ADSC.In addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis.Mechanistically,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a axis.These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

关键词： Adiponectin Adipose-derived stromal cells Colitis Glycolytic induction HIF1a Immunomodulation Mesenchymal stromal cells Obesity

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RNF6 promotes chronic myelogenous leukemia cell proliferation and migration by stabilizing vimentin via multiple atypical ubiquitinations

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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of Clinical pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China department of pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China Division of Hematology&Oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene BCR-ABL.In addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia

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Acupoint Selection Standards of Auricular Therapy in the Treatment of Maintenance Hemodialysis Insomnia Based on Data Mining

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World Journal of Traditional Chinese medicine 2024年第1期10卷 53-64页

作者： Jun-Xin Wang Bing-Qian Zou Yu-Feng Chen Cheng-Long Wang Wei-Hong Li Xue-Ling Ma Xiang-Di Liu department of TCM Nursing School of NursingBeijing University of Chinese MedicineBeijingChina department of Healthcare Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesP.R.China pharmacology of Integrated Chinese and Western medicine School of Traditional Chinese MedicineBeijing University of Chinese MedicineBeijingChina Beijing Key Laboratory of TCM Syndrome and Formula School of Traditional Chinese MedicineBeijing University of Chinese MedicineBeijingChina Key Laboratory of TCM Syndrome and Formula School of Traditional Chinese MedicineBeijing University of Chinese MedicineMinistry of EducationBeijingChina

Background:Insomnia is a high-incidence complication in patients undergoing maintenance hemodialysis(MHD).Auricular therapy can effectively improve sleep with few adverse effects.Acupoint selection affects the impact of auricular therapy.However,there is currently a lack of analysis on the standards of acupoint selection.Our study used data mining technology to investigate the acupoint selection principles and characteristics of auricular therapy for the treatment of MHD-related insomnia.Objective:The objective of the study is to explore the standards of acupoint selection in auricular therapy for the treatment of MHD-related insomnia through data mining technology.Materials and Methods:We searched three English(PubMed,WOS,and Embase)and four Chinese(CNKI,VIP,Wangfang,and CBM)databases for studies on auricular therapy for MHD-related insomnia from self-establishment to November 14,2022.Results:Eighty-one publications were involved,which included 33 acupoints.The most common auricular points in patients with MHD-related insomnia were the Shenmen,heart,and kidney points.More applications involved the visceral,nervous system,and specific acupoints.Five effective clusters and two clusters were obtained through cluster analysis,including specific auricular points for insomnia,such as the multi-dream area,neurasthenia area,deep sleep point,and anterior ear lobe.Complex network analysis showed that the core auricular acupoint combinations for the intervention of MHD-related insomnia were Shenmen with kidney,Shenmen with heart,heart with kidney,heart with Shenmen,and heart and Shenmen with subcortex.Conclusions:The selection of auricular points for the treatment of MHD-related insomnia was guided by the heart theory of traditional Chinese medicine.Clinical treatment attaches importance to the use of the multi-dream area,neurasthenia area,and other acupoints.

关键词： Acupoint selection standards auricular therapy data mining insomnia maintenance hemodialysis

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Regulation of sleep by astrocytes in the hypothalamic ventrolateral preoptic nucleus

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Neural Regeneration Research 2025年第4期20卷 1098-1100页

作者： Jae-Hong Kim Ruqayya Afridi Il-Sung Jang Maan Gee Lee Kyoungho Suk Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents School of MedicineKyungpook National UniversityDaeguRepublic of Korea department of pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea department of pharmacology School of DentistryKyungpook National UniversityDaeguRepublic of Korea Brain Science&Engineering Institute Kyungpook National UniversityDaeguRepublic of Korea

Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s lifespan.The astrocytic regulation of neuronal activity has been increasingly recognized in recent years.Astrocytes are now recognized as playing a more complex role than mere bystanders in the central nervous system.However,their role in regulating the sleep neurocircuitry is not well understood.From this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the hypothalamus.We briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.

关键词： sleep ventrolateral astrocytes

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Old-growth mixed dipterocarp forests show variable losses and gains in aboveground biomass and standing carbon over forty years

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Forest Ecosystems 2024年第1期11卷 14-23页

作者： Sisira Ediriweera Champika Bandara Tithira Lakkana Shanika Jayasinghe David Woodbury Arun Dayanandan B.M.P.Singhakumara Xiangcheng Mi I.A.U.N.Gunatilleke C.V.S.Gunatilleke Mark SAshton department of Science and Technology Uva Wellassa UniversityBadullaSri Lanka The Forest school Yale School of the EnvironmentYale UniversityNew HavenCT06511USA department of Forestry and Environmental Science University of Sri JayewardenepuraNugegodaSri Lanka State Key Laboratory of Vegetation and Environmental Change Institute of BotanyChinese Academy of SciencesBeijing100093China Botany department University of PeradeniyaPeradeniyaSri Lanka

Background:No studies have documented long-term trends in aboveground biomass(AGB)for mixed-dipterocarp forests(MDF),the dominant rain forest type in tropical wet equatorial Asia.In our study,we sought to document such trends over forty years across three sites representing lowland to lower montane elevations.Methods:To do this,we established fifty 100 m×25 m plots in 1978 across three sites sampled along an elevation gradient,identified as mature old-growth forest.We measured trees for diameter at breast height that we identified to species and tagged.We took wood samples to calculate species wood-specific gravity.We re-measured plots in 1998 and again in 2018.Results:We show standing AGB for all sites combined to be 517.52 Mg·ha^(-1)in 1978,but this declined by 17%over 40 years to 430.11 Mg·ha^(-1).No differences exist among sites in AGB primarily because of considerable within site variation;but interactions of time with site show declines across sites were not uniform,one remained about the same.Relatively few species represented a high proportion of the AGB with the top five species comprising between 34%and 65%,depending upon site and year sampled.One species,Mesua nagassarium,represented a disproportionately large amount of AGB and decline over time,particularly at the low elevation site.Conclusions:Our results are directly relevant to estimating AGB and standing carbon sequestered in MDF.Our study is the first to demonstrate varying but overall,declining trends in amounts of AGB among forests making predictions of biomass and standing carbon in MDF difficult over wide regions.

关键词： Western ghats Shorea spp. Southeast Asia Sri Lanka Tropical rain forest Wood specific gravity

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Tumor microenvironment of cancer stem cells:Perspectives on cancer stem cell targeting

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Genes & Diseases 2024年第3期11卷 275-302页

作者： Qianqian Guo Yi Zhou Tianyuan Xie Yin Yuan Huilong Li Wanjin Shi Lufeng Zheng Xiaoman Li Wenzhou Zhang department of Pharmacy The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450003China Jiangsu Key Laboratory for pharmacology and Safety Evaluation of Chinese Materia Medica School of PharmacyNanjing University of Chinese MedicineNanjingJiangsu 210023China school of Life Science and Technology Jiangsu Key Laboratory of Carcinogenesis and InterventionChina Pharmaceutical UniversityNanjingJiangsu 211198China

There are few tumor cell subpopulations with stem cell characteristics in tumor tis-sue,defined as cancer stem cells(CSCs)or cancer stem-like cells(CSLCs),which can recon-struct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited generation.The microenvironment that CsCs depend on consists of various cellular components and corresponding medium components.Among these factors existing at a variety of levels and forms,cytokine networks and numerous signal pathways play an important role in signaling transduction.These factors promote or maintain cancer cell stem-ness,and participate in cancer recurrence,metastasis,and resistance.This review aims to summarize the recent molecular data concerning the multilayered relationship between CsCs and CsC-favorable microenvironments.We also discuss the therapeutic implications of target-ing this synergistic interplay,hoping to give an insight into targeting cancer cell stemness for tumortherapyandprognosis.

关键词： Cancer stem cells Cancerstem-like cells Cellular factors Non-cellularfactors Tumor microenvironment

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Efficacy of Yisui granule(益髓颗粒)on myelodysplastic syndromes in SKM-1 mouse xenograft model through suppressing Wnt/β-catenin signaling pathway

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Journal of Traditional Chinese medicine 2024年第1期44卷 78-87页

作者： WU Jieya HOU Li ZHANG Xiaoyuan Elizabeth Gullen GAO Chong WANG Jing department of Oncology and Hematology Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100700China department of pharmacology Yale Medical SchoolNew HavenCT 06510USA department of Oncology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China

OBJECTIVE:To unmask the underlying mechanisms of Yisui granule(益髓颗粒,YSG)for the treatment of Myelodysplastic syndromes(MDS).METHODS:Our study used an SKM-1 mouse xenograft model of MDS to explore the anti-tumor potential of YSG and its safety,assess its effect on overall survival(OS),and evaluate whether its mechanism is associated with the demethylation of the secreted frizzled related protein 5(s FRP5)gene and suppressing Wnt/β-catenin pathway.Bisulfite amplicon sequencing was applied to detect the level of methylation of the s FRP5 gene;western blotting,immunofluorescence staining,and real-time Polymerase Chain Reaction were performed to detect DNA methyltransferase 1(DNMT1),s FRP5,and other Wnt/β-catenin pathway-related m RNA and protein expression.RESULTS:The results showed that high-dosage YSG exerted an anti-tumor effect similar to that of decitabine,improved OS,and reduced long-term adverse effects in the long term.Mechanically,YSG reduced the expression of DNMT1 methyltransferase,decreased the methylation,and increased the expression of the Wnt/β-catenin pathway antagonist-s FRP5.Furthermore,components of the Wnt/β-catenin pathway,including Wnt3a,β-catenin,c-Myc,and cyclin D1,were down-regulated in response to YSG,suggesting that YSG could treat MDS by demethylating the s FRP5 gene and suppressing the Wnt/β-catenin pathway.CONCLUSIONS:Our findings demonstrated that YSG could be used alone or in combination with decitabine to improve outcomes in the MDS animal model,providing an alternative solution for treating MDS.

关键词： myelodysplastic syndromes Wnt signaling pathway beta catenin decitabine survival adverse effects sFRP5 gene methylation Yisui granule

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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling

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Chinese Journal of Integrative medicine 2024年第6期30卷 525-533页

作者： Lucas dos Santos Zamarioli Michele Rosana Maia Santos Adolfo Garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto department of pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research Group on Phytocomplexes and Cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 fibroblasts.Methods Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)spectrometry.Viability and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,respectively.Ferrostatin-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this event.Cytosolic calcium measurements were made using Fura-2-AM.Results HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling

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Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK-STAT pathway

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2554-2566页

作者： Jingyi Tan Jiayu Zhang Cheng Hu Gongwei Wang Qianyao Ren Chaoqun Wang Jia Dan Zexin Zeng Jun Hu Wenbo Zhu Jiankai Liang Jing Cai Ying Liu Guangmei Yan Yuan Lin department of pharmacology Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China The Sixth Affiliated Hospital Sun Yat-sen UniversityGuangzhou 510655China department of Urology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Advanced Medical Technology Center the First Affiliated Hospital-Zhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Human Microbiome and Elderly Chronic Diseases Ministry of EducationGuangzhou 510655China department of Infectious Diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China

Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer agents.Unlike traditional drugs composed of non-replicating compounds or biomolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further studies.Despite some pharmacokinetics studies of OVs,mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague.Here,we characterized the pharmacokinetic profile of oncolytic virus M1(OVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of OVM pharmacokinetics.By suppressing the JAK-STAT pathway,early OVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor efficacy.Rather than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade,such as anti-PD-L1.Taken together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

关键词： Pharmacokinetics Oncolytic virus JAK-STAT Anticancer

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