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Engineered exosome hybrid copper nanoscale antibiotics facilitate simultaneous self-assembly imaging and elimination of intracellular multidrug-resistant superbugs

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Chinese Chemical Letters 2024年第7期35卷 319-324页

作者： Zengchao Guo Weiwei Liu Tengfei Liu Jinpeng Wang Hui Jiang Xiaohui Liu Yossi Weizmann Xuemei Wang state Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Department of Chemistry Ben-Gurion University of the NegevBeer-Sheva 8410501Israel

With the increasing emergence of bacterial infections,especially multidrug-resistant(MDR)bacteria,poses an urgent *** study demonstrated a novel multifunctional nanotheranostics platform developed by the strategic integration of both in-situ bio-assembly imaging and target bacteria *** the introduction of copper ions into bacteria,the Cu^(2+)could spontaneously bio-selfassembled into a multifunctional copper nanoclusters(NCs)which efficiently enhanced epigallocatechin gallate(EGCG)uptake into *** visualizing the bacteria,the developed theranostic nanoplatform exhibited highly efficient disinfection activities with negligible side effects as reflected by higher cell viability and insignificant hemolytic ***,the exosomal formulation of EGCG integrated with Cu^(2+)showed an increased intracellular antibacterial activity,which could eliminate most of the methicillin-resistant Staphylococcus aureus(MRSA)phagocytosed by macrophages,guide macrophages toward M2-like phenotype polarization and alleviate inflammation,without exhibiting obvious cytotoxicity on host *** regimen could be viewed as an effective strategy for the sterilization of intractable bacterial infections.

关键词： In situ self-assembled Exosome Antibacterial agents Bioimaging Intracellular infection

N-acetylcysteine and zinc sulphate abate di-2-ethylhexyl phthalate-mediated reproductive dysfunction in rats:Focus on oxidative and sex hormone receptors mechanisms

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Asian pacific Journal of Reproduction 2024年第5期13卷 228-240页

作者： Victor Oghenekparobo Emojevwe Mega Obukohwo Oyovwi Kayode Ezekiel Adewole Peggy Ejiro Ohwin Adeniran Oluwadamilare Akinola Alexander Obidike Naiho Eze Kingsley Nwangwa Victor Omo-Idonije Motunrayo Lade-Ige Benneth Ben-Azu Department of Physiology University of Medical SciencesOndo CityOndo StateNigeria Department of Physiology Delta State UniversityAbrakaDelta StateNigeria Department of Physiology Adeleke UniversityEdeOsun StateNigeria Department of Biochemistry University of Medical SciencesOndo CityOndo StateNigeria Department of Pharmacology Delta State UniversityAbrakaDelta StateNigeria

Objective:To investigate the potential of N-acetylcysteine(NAC)and zinc sulphate(ZnSO_(4))in mitigating reproductive dysfunction caused by di-2-ethylhexyl phthalate(DEHP)in rats and to understand the underlying mechanisms,specifically oxidative stress and sex hormone receptor ***:Thirty-five male Wistar rats were randomly divided into five equal groups(n=7 per group).Group 1 was administered 0.5 mL of distilled water and served as the control *** 2 was given only DEHP(750 mg/kg/day),while group 3,4 and 5 were given DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day),DEHP(750 mg/kg/day)plus ZnSO_(4)(0.5 mg/kg/day),and DEHP(750 mg/kg/day)plus NAC(100 mg/kg/day)as well as ZnSO_(4)(0.5 mg/kg/day),*** treatments lasted for 21 *** were obtained after the rats were sacrificed,and hormones levels in the serum and markers of oxidative stress in the testicles were analyzed using the enzyme-linked immunosorbent *** amount of androgen receptors in the testicles was determined by immunohistochemistry,and the susceptibility of testosterone and DEHP to bind to androgen receptor and 5α-reductase was determined by molecular docking ***:DEHP decreased reproductive hormones,testicular antioxidant enzymes,increased malondialdehyde levels,and negatively impacted histology of the pituitary and *** or ZnSO_(4) treatment showed a marked improvement in testicular antioxidant status and hormone levels,as well as a positive effect on the histology of the pituitary and *** combination of both treatments appeared to be more *** affinity of DEHP to bind to androgen receptors may lead to disruption of androgen receptor signaling,which can further result in dysfunction of hormones related to ***,NAC is more likely to form stronger binding interactions with follicle stimulating hormone and luteinizing hormone receptors,as well as gonadotropin-releasing hormone receptors,when compared to ***:The pos

关键词： Di-2-ethylhexyl phthalate Testosterone Androgen receptor 5α-reductase Oestrogen Luteinizing hormone

Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3429-3448页

作者： Hao Peng Meng Yang Kun Feng Qingpeng Lv Yewei Zhang medical School Southeast UniversityNanjing 210009China Department of Ultrasound State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of MedicalSciencesPeking Union Medical CollegeBeijing 100730China Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210009China

More than 90% of hepatocellular carcinoma(HCC)cases develop in the presence of fibrosis or cirrhosis,making the tumor microenvironment(TME)of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts(CAFs)and cancer stem cells(CSCs),which collectively regulate HCC ***,the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain *** study unveils a significant upregulation of Sema3C in fibrotic liver,HCC tissues,peripheral blood of HCC patients,as well as sorafenib-resistant tissues and cells,with its overexpression correlating with the acquisition of stemness properties in *** further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C,activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor ***,HCCcells-derived Sema3Cfacilitated extracellular matrix(ECM)contraction and collagen deposition in vivo,while also promoting the proliferation and activation of hepatic stellate cells(HSCs).Mechanistically,Sema3C interacted with NRP1 and ITGB1 in HSCs,activating downstream NF-kB signaling,thereby stimulating the release of IL-6 and upregulating HMGCR expression,consequently enhancing cholesterol synthesis in ***,CAF-secreted TGF-β1 activates AP1 signaling to augment Sema3C expression in HCC cells,establishing a positive feedback loop that accelerates HCC ***,blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in *** sum,our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CsCs and stroma during hepatocarcinogenesis,thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.

关键词： Sema hepatocellular thereby

Actuality and underlying mechanisms of systemic immuneinflammation index and geriatric nutritional risk index prognostic value in hepatocellular carcinoma

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 260-265页

作者： Konstantin Y Tchilikidi Department of Surgery with Postgraduate Education Altai State Medical UniversityBarnaul 656031Russia

This editorial contains comments on the article“Correlation between preoperative systemic immune inflammation index,nutritional risk index,and prognosis of radical resection of liver cancer”in a recent issue of the World Journal of Gastrointestinal *** pointed out the actuality and importance of the article and focused primarily on the underlying mechanisms making the systemic immuneinflammation index(SII)and geriatric nutritional risk index(GNRI)prediction features *** are few publications on both SII and GNRI together in hepatocellular carcinoma(HCC)and patient prognosis after radical *** release cytokines,chemokines,and enzymes,degrade extracellular matrix,reduce cell adhesion,and create conditions for tumor cell *** promote the adhesion of tumor cells to endothelial cells,through physical *** results in the migration of tumor ***-angiogenic factors from platelets enhance tumor angiogenesis to meet tumor cell supply *** can form a protective film on the surface of tumor *** allows avoiding blood flow damage as well as immune system *** also induces the epithelial-mesenchymal transformation of tumor cells that is critical for *** SII is also associated with macro-and microvascular invasion and increased numbers of circulating tumor cells.A high GNRI was associated with significantly better progression-free and overall *** patients are a very special population that requires increased *** and GNRI have significant survival prediction value in both palliative treatment and radical surgery *** underlying mechanisms of their possible predictive properties lie in the field of essential cancer *** features provide tumor nutrition,growth,and distribution throughout the body,such as vascular *** the other hand,they are tied to the possibility of patients to resist tumor progression and development of complications in bot

关键词： Systemic immune-inflammation index Geriatric nutritional risk index Radical surgery Transarterial chemoembolization Hepatocellular carcinoma Prognosis

AIMP2 restricts EV71 replication by recruiting SMURF2 to promote the degradation of 3D polymerase

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Virologica Sinica 2024年第4期39卷 632-644页

作者： Junrui Ren Lei Yu Qiuhan Zhang Pengyu Ren Yumeng Cai Xueyun Wang Ke Lan Shuwen Wu state Key Laboratory of Virology College of Life SciencesWuhan UniversityWuhan430072China medical Research Institute Wuhan UniversityWuhan430072China Taikang Center for Life and medical Sciences Wuhan UniversityWuhan430072China

Hand,foot and mouth disease(HFMD),mainly caused by enterovirus 71(EV71),has frequently occurred in the Asia-Pacific region,posing a significant threat to the health of infants and young ***,research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming *** 3D polymerase,as the most critical RNA-dependent RNA polymerase(RdRp)for EV71 replication,is widely targeted to inhibit EV71 *** this study,we identified a novel host protein,AIMP2,capable of binding to 3D polymerase and inhibiting EV71 *** investigations revealed that AIMP2 recruits the E3 ligase SMURF2,which mediates the polyubiquitination and degradation of 3D ***,the antiviral effect of AIMP2 extended to the CVA16 and CVB1 *** research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection,revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.

关键词： AIMP2 Enterovirus 71(EV71) 3D polymerase E3 ligase SMURF2 Ubiquitination

Ex vivo liver resection and auto-transplantation and special systemic therapy in perihilar cholangiocarcinoma treatment

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 635-640页

作者： Konstantin Y Tchilikidi Department of Surgery with Postgraduate Education Altai State Medical UniversityBarnaul 656031Russia

This editorial contains comments on the article“Systematic sequential therapy for ex vivo liver resection and autotransplantation:A case report and review of li-terature”in the recent issue of World Journal of Gastrointestinal *** points out the actuality and importance of the article and focuses primarily on the role and place of ex vivo liver resection and autotransplantation(ELRAT)and systemic therapy,underlying molecular mechanisms for targeted therapy in perihilar cho-langiocarcinoma(pCCA)*** is a tough malignancy with a high proportion of advanced disease at the time of *** only curative option is radical *** excision and reconstruction become extremely com-plicated and not always could be performed even in localized *** the other hand,ELRAT takes its place among surgical options for carefully selected pCCA *** advanced disease,systemic therapy becomes a viable option to prolong *** editorial describes current possibilities in chemotherapy and reveals underlying mechanisms and projections in targeted therapy with ki-nase inhibitors and immunotherapy in both palliative and adjuvant ***-broblast grow factor and fibroblast grow factor receptor,human epidermal grow-th factor receptor 2,isocitrate dehydrogenase,and protein kinase cAMP activated catalytic subunit alpha(PRKACA)and beta(PRKACB)pathways have been ac-tively investigated in CCA in last *** agents were introduced and approved by the Food and Drug *** all demonstrated mean-ingful activity in CCA patients with no global change in *** is why every successfully treated patient counts,especially those with advanced *** conclusion,pCCA is still hard to treat due to late diagnosis and extremely complicated surgical *** also brings some hope,but it could be performed in very carefully selected *** disease requires systemic anticancer treatment,which is supposed to be indivi

关键词： Perihilar cholangiocarcinoma Klatskin’tumor Ex vivo liver resection and autotransplantation Chemotherapy Immunotherapy Targeted therapy

Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia

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Virologica Sinica 2024年第1期39卷 31-43页

作者： Dongyan Zhang Xiulin Wu Xing Xue Wenshi Li Ping Zhou Zhao Lv Kexin Zhao Fan Zhu state Key Laboratory of Virology and Department of medical Microbiology School of Basic Medical SciencesWuhan UniversityWuhan430071China Hubei Province Key Laboratory of Allergy&Immunology Wuhan UniversityWuhan430071China

Human endogenous retroviruses(HERVs)are remnants of retroviral infections in human germline cells from millions of years *** these,ERVW-1(also known as HERV-W-ENV,ERVWE1,or ENVW)encodes the envelope protein of the HERV-W family,which contributes to the pathophysiology of ***,neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with ***,our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset(GSE53987)were mainly related to ferroptosis and its associated *** data demonstrated significantly lower expression levels of ferroptosis-related genes,particularly Glutathione peroxidase 4(GPX4)and solute carrier family 3 member 2(SLC3A2),in schizophrenia patients compared to normal *** in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in *** indicated that ERVW-1 increased iron levels,malondialdehyde(MDA),and transferrin receptor protein 1(TFR1)expression while decreasing glutathione(GSH)levels and triggering the loss of mitochondrial membrane potential,suggesting that ERVW-1 can induce *** research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter ***,Ferrostatin-1(Fer-1),the ferroptosis inhibitor,reversed the iron accumulation and mitochondrial membrane potential loss,as well as restored the expressions of ferroptosis markers GSH,MDA,and TFR1 induced by *** conclusion,ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2,revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.

关键词： ERVW-1 Glutathione peroxidase 4(GPX4) Solute carrier family 3 member 2(SLC3A2) Ferroptosis Schizophrenia

Evaluation of sodium borocaptate(BSH)and boronophenylalanine(BPA)as boron delivery agents for neutron capture therapy(NCT)of cancer:an update and a guide for the future clinical evaluation of new boron delivery agents for NCT

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Cancer Communications 2024年第8期44卷 893-909页

作者： Rolf F.Barth Nilendu Gupta Shinji Kawabata Department of Pathology The Ohio State UniversityColumbusOhioUSA Department of Radiation Oncology The Ohio State UniversityColumbusOhioUSA Department of Neurosurgery Osaka Medical and Pharmaceutical UniversityTakatsukiOsakaJapan

Boron neutron capture therapy(BNCT)is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10,a stable isotope,is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form,which undergoes instantaneous nuclear fission to produce high-energy,tumoricidal alpha *** primary purpose of this review is to provide an update on the first drug used clinically,sodium borocaptate(BSH),by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug,boronophenylalanine(BPA),which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous ***,BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers,specifically brain tumors and recurrent tumors of the head and neck *** focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with highgrade ***,wewill summarize the studies thatwere carried out in Japan with BSH and subsequently at our own institution,The Ohio state university,and those of several other ***,we will describe studies carried out in Japan with BPA and then in the United states that have led to its use as the primary drug that is being used clinically for ***,although there have been intense efforts to develop new and better boron delivery agents for BNCT,none of these have yet been evaluated *** present reportwill provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

关键词： Boron neutron capture therapy(BNCT) boronophenylalanine(BPA) brain tumors head and neck cancer sodium borocaptate(BSH)

Improving lung allograft function in the early post-operative period through the inhibition of pyroptosis

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medical Review 2024年第5期4卷 384-394页

作者： Doug A.Gouchoe Zhentao Zhang Jung-Lye Kim Yong Gyu Lee Bryan A.Whitson Hua Zhu Department of Surgery Division of Cardiac SurgeryThe Ohio State University Wexner Medical CenterColumbusOHUSA COPPER Laboratory The Ohio State University Wexner Medical CenterColumbusOHUSA Cardiac Surgery The Ohio State University Wexner Medical CenterColumbusOH 43210USA

Lung transplantation is the only deﬁnitive ther-apy for end-stage pulmonary *** than 20%of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality man-ifested by pulmonary edema,hypoxia,or ***,poor donor organ recovery and utilization are signiﬁcant barriers to wider implementation of the life-saving therapy of *** ischemia reperfusion injury(IRI)is often identiﬁed as the underlying molecular insult leading to immediate poor lung function in the post-operative period,this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory *** is a central molecular inflammatory pathway that is the most signiﬁcant contributor to injury in this early post-operative *** is another form of pro-grammed cell death and is often associated with *** mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all *** we detail the pyroptotic pathway,its importance in lung transplantation,and several therapeutic modalities that can mitigate this harmful inflammatory pathway.

关键词： lung transplantation pyroptosis ischemia reperfusion injury IRI ex vivo lung perfusion EVLP