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Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology Research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI Department of medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan Pharmaceutical Biotechnology Research Center Zanjan University of Medical SciencesZanjanIran Department of Pharmaceutical Biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine Department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer *** decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics *** were loaded on the synthesized Se@BSA@Chi-MTX *** physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis ***,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell *** results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,*** results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of *** results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/*** ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic *** targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the *** results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP *** nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer

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N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 228-238页

作者： Yu-Ze Zhao Xue-Ning Zhang Yi Yin Pei-Lun Xiao Meng Gao Lu-Ming Zhang Shuan-Hu Zhou Shu-Na Yu Xiao-Li Wang Yan-Song Zhao Department of Ophthalmology Affiliated Hospital of Weifang Medical UniversityWeifang 261031Shandong ProvinceChina school of medical Imaging Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of Anatomy Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Departments of Orthopedic Surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

AIM:To observe the effects of N-acetylserotonin(NAS)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling ***:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the *** male Sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAS group(n=28),RIR+FPS-ZM1 group(n=8)and RIR+NAS+FPS-ZM1 group(n=8).The therapeutic effects of NAS were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)*** expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot *** expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELISA).RESULTS:H&E staining results showed that NAS significantly reduced retinal edema and increased the number of RGCs in RIR *** NAS therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein ***,NAS exhibited an anti-inflammatory effect by reducing IL-1β*** inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPS-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR ***:NAS may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

关键词： retinal diseases retinal ischemia—reperfusion injury N-acetylserotonin high mobility group box 1 receptor for advanced glycation end-products nuclear factor-κB rats

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SARS-CoV-2 immunity

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Cellular & Molecular Immunology 2024年第2期21卷 101-102页

作者： Antonio Bertoleti Program in Emerging Infectious Diseases Duke-NUS Medical SchoolSingaporeSingapore

Four years have swiftly passed since the identification of a novel coronavirus from patients with pneumonia that signs the start of the COVID-19 pandemic[1].The world's social and economic landscape has largely reverted to its prepandemic state,and different issues unrelated to the pandemic are currently impacting various regions *** scientific community,which quickly modified its research focus during the initial years of the pandemic to generate a wealth of scientific data that helped in understanding and controlling SARS-CoV-2 infection,is also facing a new phase in the study of virus-host interactions.

关键词： immunity globally landscape

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PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

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Oncology Research 2024年第6期32卷 1063-1078页

作者： KUN FENG HAO PENG QINGPENG LV YEWEI ZHANG Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210000China medical school Southeast UniversityNanjing210000China

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable *** dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment *** elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also ***,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of ***,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT *** findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer *** methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver ***,noteworthy associations were observed between PHLDA2 expression and immune infiltration in *** addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in *** vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy ***,we found that TGF-βinduced the expression of PHLDA2 in *** GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling *** study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

关键词： HCC Immune infiltration Drug resistance TME PHLDA2

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Increased N6-methyladenosine is related to the promotion of the methyltransferase METTL14 in ovarian aging

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Genes & Diseases 2024年第3期11卷 151-154页

作者： Chunfeng Qian Zhenxing Liu Yonghong Qian Jie Ding Rulei Chen Han Su Minghong Shen Hong Li Boxian Huang State Key Laboratory of Reproductive Medicine and Offspring Health Suzhou Affliated Hospital of Nanjing Medicine and Offspring HealthSuzhou Affiliated Hospital of Nanjing Medical UniversitySuzhouMunicipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China Department of Gynecology Affliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China Department of Pathology Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu School of Nanjing Medical UniversitySuzhouJiangsu 215002China

The ovary is a vital female reproductive organ that functions to produce oocyte gametes and cyclically expressed sex hormones to maintain reproductive capacity and hormone *** aging,characterized by declines in follicle quantity and oocyte quality,leads to premature ovarian failure,premature ovarian insufficiency,or diminished ovarian reserve,thus contributing to female *** gene-expression signatures from RNA transcriptional level and post-transcriptional regulation are relative to oocyte quality and reproductive age.

关键词： promotion signature maintain

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Protective effect of co-enzyme Q10 on testicular tissue and sperm parameters in adult male rats treated with Sunset Yellow FCF

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Asian pacific Journal of Reproduction 2024年第2期13卷 80-88页

作者： Rohollah Nazari Somayeh Akbari Maryam Naseh Shayan Yousufzai Seyede Fatemeh Hosseini Fatemeh Karimi Histomorphometry and Stereology Research Center Shiraz University of Medical SciencesShirazIran Anatomy Department School of MedicineShiraz University of Medical SciencesShirazIran Student Research Committee Medical SchoolShiraz University of Medical SciencesShirazIran Faculty of Tabas School of NursingBirjand University of Medical SciencesBirjandIran

Objective:To determine the protective effect of co-enzyme Q10(CoQ10)on testicular tissue and sperm parameters in male rats treated with SunsetYellow ***:Sixty male Sprague-Dawley rats were randomly divided into 6 groups of the control,CoQ10(10 mg/kg/day),low dose of Sunset Yellow(2.5 mg/kg),high dose of Sunset Yellow(70 mg/kg),low dose of Sunset Yellow(2.5 mg/kg)plus CoQ10,and high dose of Sunset Yellow(70 mg/kg)plus *** drugs were administered via daily oral gavages for 6 *** the end of the experiment,sperm analysis,stereological and histological assessments of the testis were carried ***:The normal morphology(by 41.1%)and progressive spermatozoa(by 74.8%),testicle volume(by 33.4%),lumen volume(by 38.3%),interstitial tissue volume(by 44.7%),seminiferous tubule volume(by 40.7%),and number of spermatogonia(by 53.9%)and Leydig cells(by 70.7%)reduced in the rats that received high doses of Sunset Yellow in comparison to the control ***,all these alterations were recovered by CoQ10 treatment in the CoQ10 plus high dose of Sunset Yellow ***,low doses of Sunset Yellow did not affect different parameters of the testis and ***:CoQ10 could,to some extent,prevent structural changes of the testis induced by the high dose of SunsetYellow.

关键词： Sunset Yellow FCF Co-enzyme Q10 Testicle Sperm Stereology

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Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 307-323页

作者： Xufeng FU Hang HAN Hong YANG Bo XU Wenjie DAI Ling LIU Tiantian HE Xing DU Xiuying PEI Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education School of Basic Medical SciencesNingxia Medical UniversityYinchuan 750004China Key Laboratory of Reproduction and Genetics in Ningxia Ningxia Medical UniversityYinchuan 750004China

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain *** this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in ***,whole-body imaging found that PS-NPs accumulated in the testes of ***,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were *** oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were *** spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP *** phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by ***,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive *** study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

关键词： Polvstyrene nanoplastics(PS-NPs) Reproductive toxicity Ferroptosis Nuclear factor ervthroid 2-related factor 2(Nrf2)

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3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

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BIOCELL 2024年第5期48卷 861-872页

作者： XIAOQI WU YECHUAN HE YEQIN YUAN XIAN TAN LIN ZHU DANLING WANG BINYUAN JIANG Hengyang medical school University of South ChinaHengyang421001China Institute for Future Sciences University of South ChinaChangsha410008China medical Research Center The Affiliated Changsha Central HospitalHengyang Medical SchoolUniversity of South ChinaChangsha410004China Department of Clinical Laboratory The Affiliated Changsha Central HospitalHengyang Medical SchoolUniversity of South ChinaChangsha410004China

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced ***,drug resistance is typically accompanied by a poor *** the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment ***:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular *** were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation *** observation was performed to identify morphological cell *** cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic *** blotting was conducted to quantify the protein ***:3-MA enhanced PTX-specific inhibition of NPC cell ***,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX *** blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)***:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

关键词： Nasopharyngeal carcinoma Paclitaxel 3-Methyladenine Cell cycle Apoptosis

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Fasn involved in the nephrotoxicity induced by polystyrene nanoplastics and the intervention of melatonin through intestinal microbiota-mediated lipid metabolism disorder

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Nano Research 2024年第8期17卷 7365-7375页

作者： Huiwen Kang Danyang Huang Jiaru Jing Wei Zhang Lei Zhang Jingyu Wang Ziyan Liu Lin Han Ziyan Wang Lefeng Zhang Ai Gao Department of Occupational Health and Environmental Health School of Public HealthCapital Medical UniversityBeijing 100069China Beijing Key Laboratory of Environmental Toxicology Capital Medical UniversityBeijing 100069China

Nanoplastics(NPs)can accumulate in the kidney and cause kidney injury,but the multi-organ interaction mechanism and preventive measures of kidney injury are still *** this study,in vivo(60μg/day,42 days)and in vitro(0.4μg/μL,24 h)exposure models of polystyrene nanoplastics(PS-NPs,80 nm)in mice and human kidney cortex proximal tubule epithelial cells(HK-2 cells)were established,*** study revealed that PS-NPs caused obvious pathological changes and impaired renal function in mice,which were related to lipid metabolism disorders mediated by intestinal ***-fatty acid synthase(Fasn)-docosahexaenoic acid(DHA)pathway may be one of the mechanisms of kidney injury in ***,we also found that melatonin attenuates PS-NPs-induced nephrotoxicity by modulating lipid metabolism disorders(represented by DHA)and affects Fasn *** conclusion,our study revealed the important role of intestinal flora-mediated lipid metabolism in PS-NPs-induced nephrotoxicity and preliminarily provided potential key gene targets and effective preventive measures for PS-NPs-induced nephrotoxicity.

关键词： nanoplastics nephrotoxicity lipid metabolism fatty acid synthase(Fasn) melatonin

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Neuroprotective potential of traditional Ayurvedic Kadha:age-related neurological disorders:a comprehensive literature review

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Traditional Medicine Research 2024年第9期9卷 51-77页

作者： Sarvin Sadreddini Mohammad Javad Emami Kazemabad Sogand Sheikholeslami Kosar Chitzan-Zadeh Mohammad Taha Kouchaki Midia Rashidi Amir Abbas Ghayerin Shahin Sabaghi Ghazal Tavakoli Sepehr Nanbakhsh Tina Mansourian Arefeh Tabashiri Fariba Arbab Mojeni Mohammed Namiq Amin Zahra Taheri Seyed Esmaeil Sedighi Taraneh Tarkashvand Parham Amirazodi Mobina Fathi Shirin Yaghoobpoor Niloofar Deravi school of Medicine Tabriz University of Medical SciencesTabriz ***Iran school of Medicine Qom University of Medical SciencesQom ***Iran school of Medicine Hamadan University of Medical SciencesHamadan ***Iran school of Medicine Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Faculty of Medicine Tabriz University of Medical SciencesTabriz ***Iran school of Medicine Iran University of Medical SciencesTehran ***Iran school of Medicine Shahid Beheshti University of Medical SciencesTehran ***Iran school of Medicine Mazandaran University of Medical SciencesSari ***Iran school of Medicine Kermanshah University of Medical SciencesKermanshah ***Iran Faculty of Pharmacy Pharmaceutical Sciences BranchIslamic Azad UniversityTehran ***Iran Department of Biology Faculty of SciencePayamNoor UniversityTehran ***Iran Faculty of Medicine Islamic Azad University of Medical ScienceTehran 193951495Iran International Campus Shahid Sadoughi University of Medical SciencesYazd ***Iran

Despite modern medicine’s advancements,age-related neurological diseases like Alzheimer’s disease and Parkinson’s disease remain challenging due to high costs,side effects,and limited ***,a traditional Indian medicine system,offers Kadha tea as a potential herbal *** review explores Kadha’s components(basil(Ocimum basilicum L.),black pepper(Piper nigrum L.),Cinnamon(Cinnamomum verum ***),ginger(Zingiber officinale Roscoe),and raisin(Vitis vinifera L.))and their interaction with various neurological *** suggest Kadha exhibits anti-inflammatory,antioxidant,and antiviral properties,potentially impacting Alzheimer’s disease,Parkinson’s disease,neurotoxicity,neuroinflammation,and brain *** focusing on specific disease mechanisms and Kadha’s intergrade effects,this review aims to elucidate its potential role in managing age-related neurological disorders.

关键词： Ayurveda Kadha neuroprotective neurological disorders traditional medicine

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