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TPOL triggers apoptosis with mitochondrial injury through activating a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signaling

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中国病理生理杂志 2024年第8期40卷 1488-1496页

作者： CHENG Zongwei ZENG Boning XING Feiyue Department of Immunobiology Institute of Tissue Transplantation and ImmunologyJinan UniversityGuangzhou 510632China

AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential ***:HEK293T cells sensitive to TPOL were treated with different concentrations of TPOL with or without exposure to light radiation,before treatment with various inhibitors,N-acetyl-Lcysteine(NAC),pifithrin-αand *** viability was measured by CCK-8 *** V/propidium iodide staining was used to count the number of apoptotic ***-DA staining was used to detect reactive oxygen species(ROS)levels,and JC-1 staining was used to assess mitochondrial membrane potential by flow *** expression of apoptosis-related proteins and cell cycle-regulated molecules was measured by Western ***:TPOL enhanced the apoptosis of HEK293T cells in a dose-dependent manner(P<0.05),with a decrease in Bcl-2 and increases in Bax and cytochrome C(Cyto C),followed by up-regulation of activated caspase-9 and caspase-3,and the cleavage of PARP(P<0.05).The TPOL-enhanced cleavage of caspase-3 and PARP was rescued by Z-DVED-FMK(P<0.01).TPOL also led to a rapid increase in ROS,a reduction in mitochondrial membrane potential,and the release of Cyto C(P<0.01),all of which could be reversed by the ROS scavenger ***,the TPOL-caused alterations in p21,p27,Rb,and CDK2 were also recovered by the p53 inhibitor pifithrin-α(P<0.05).The TPOL-induced changes in Bax,Bcl-2,cleaved caspase-9,activated caspase-3,and cleaved PARP were subsequently rescued by pretreatment with pifithrin-α(P<0.05).CONCLUSION:TPOL can induce cellular apoptosis with ROS-mediated mitochondrial membrane damage through the activation of a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signal axis.

关键词： ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate reactive oxygen species mitochondria apoptosis

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Standardization is needed in reporting risk and outcomes of machine perfusion in liver transplantation

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 709-714页

作者： Chase J.Wehrle Charles Miller Koji Hashimoto Andrea Schlegel transplantation Center Department of SurgeryDigestive Disease InstituteCleveland ClinicClevelandOHUSA Department of immunology Lerner Research InstituteCleveland ClinicClevelandOHUSA

We congratulate Yamamoto et *** their study“Impact of Portable Normothermic Machine Perfusion for Liver transplantation from Adult Deceased Donors”(1).The surge of interest in normothermic machine perfusion(NMP)in the United States(US)has generated considerable *** authors present generally exciting results from their single-center analysis of 541 liver *** these,469 were from donors after brain dead(DBD);58(12.4%)received NMP and 411 static cold storage(SCS,87.6%).Seventy-two transplants were from donors after circulatory death(DCD);52(72.2%)received NMP(device-to-donor)vs.20 SCS(27.8%).

关键词： Liver transplantation machine perfusion normothermic machine perfusion(NMP) transplantation viability assessment

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PD-1^(+)and TIM-3^(+)T cells widely express commonγ-chain cytokine receptors in multiple myeloma patients,and IL-2,IL-7,IL-15 stimulation up-regulates PD-1 and TIM-3 on T cells

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Oncology Research 2024年第10期32卷 1575-1587页

作者： EGOR V.BATOROV ALISA D.INESHINA TATIANA A.ARISTOVA VERA V.DENISOVA SVETLANA A.SIZIKOVA DARIA S.BATOROVA GALINA Y.USHAKOVA EKATERINA Y.SHEVELA ELENA R.CHERNYKH Laboratory of Cellular Immunotherapy Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia V.Zelman institute of Medicine and Psychology Novosibirsk National Research State UniversityNovosibirsk630090Russia Department of Hematology and Bone Marrow transplantation Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia

Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)***,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic *** aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint ***:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM ***:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and *** of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−*** proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription ***,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 *** stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in ***:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine *** in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell *** blockade appears to alleviate lymphopenia-induced prolif

关键词： Autologous hematopoietic stem cell transplantation(AHSCT) CD25 CD122 Eomesodermin(EOMES) Homeostatic proliferation

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The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & Molecular immunology 2024年第2期21卷 197-200页

作者： Valeria Fumagalli Matteo Iannacone Division of immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly Experimental Imaging Centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative *** vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be *** review delves into the potential influence of nirmatrelvir on enduring *** parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory *** importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

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Comparison of resistive index and shear-wave elastography in the evaluation of chronic kidney allograft dysfunction

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World Journal of transplantation 2024年第1期14卷 154-163页

作者： Ameet Kumar Jesrani Syed M Faiq Rahma Rashid Tariq Ali Kalwar Rehan Mohsin Tahir Aziz Nida Amin Khan Muhammed Mubarak Department of Radiology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan Department of Pathology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan Department of transplantation Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan Department of Urology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan

BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term *** and novel ultrasound-based investigations are being increasingly used for this purpose with variable *** To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological *** This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of transplantation and Radiology,Sindh institute of Urology and transplantation,Karachi,Pakistan,from August 2022 to February *** consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this *** and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic *** The mean age of all patients was 35.32±11.08 *** these,126(81.8%)were males and 28(18.2%)were *** mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 *** allograft biopsy results showed chronic changes in 55(37.66%)*** sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft *** can be of great help during the routine follow-up of kidney transplant recipients for screening a

关键词： Shear wave Sonoelastography Resistive index Chronic allograft changes Biopsy Histopathology

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Reinforcing the management of type 1 gastric esophageal varices

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World Journal of Gastroenterology 2024年第19期30卷 2615-2617页

作者： Zain Majid Ghazi Abrar Department of Gastroenterology Sindh Institute of Urology and TransplantationKarachi 75500Pakistan

Variceal bleed represents an important complication of cirrhosis,with its presence reflecting the severity of liver *** varices,though less frequently seen than esophageal varices,present a distinct clinical challenge due to its higher intensity of bleeding and associated *** upon the Sarin classification,GOV1 is the most common subtype of gastric varices seen in clinical practice.

关键词： Gastric varices Sarin classification Gastroesophageal varices Cyanoacrylate Endoscopic variceal ligation Trans jugular intrahepatic portosystemic shunt

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Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 123-128页

作者： Prashant Bhangui institute of Liver transplantation and Regenerative Medicine Medanta–The MedicitySector 38GurgaonDelhi NCR 122001India

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for *** recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in *** review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic *** therapies have helped make curative resection or LT a reality in selected *** review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy *** patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

关键词： Hepatocellular carcinoma Portal vein tumour thrombosis Downstaging therapies Living donor liver transplantation and resection Outcomes

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Tumor deposits in axillary adipose tissue in patients with breast cancer:Do they matter?

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World Journal of Clinical Cases 2024年第6期12卷 1045-1049页

作者： Muhammed Mubarak Rahma Rashid Shaheera Shakeel Department of Histopathology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan

Tumor deposits(TDs)are defined as discrete,irregular clusters of tumor cells lying in the soft tissue adjacent to but separate from the primary tumor,and are usually found in the lymphatic drainage area of the primary *** definition,no residual lymph node structure should be identified in these tumor *** present,TDs are mainly reported in colorectal cancer,with a few reports in gastric *** are very few reports on breast cancer(BC).For TDs,current dominant theories suggest that these are the result of lymph node metastasis of the tumor with complete destruction of the lymph nodes by the tumor *** some pathologists classify a TD as two lymph node metastases for *** pathologists also believe that TDs belong to the category of disseminated ***,regardless of the origin,TDs are an indicator of poor ***,for BC,sentinel lymph node biopsy is generally used at *** radical axillary lymph node dissection should be adopted for BC with TDs in axillary lymph nodes is still *** present commentary of this clinical issue has certain guiding *** is aimed to increase the awareness of the scientific community towards this under-recognized problem in BC pathology.

关键词： Breast cancer Tumor deposits Lymph node metastasis Staging

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Combined hepatocellular cholangiocarcinoma: A clinicopathological update

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World Journal of Hepatology 2024年第5期16卷 766-775页

作者： Mukul Vij Fadl H Veerankutty Ashwin Rammohan Mohamed Rela Department of Pathology Institute of Liver Disease and TransplantationChennai 600044India Comprehensive Liver Care institute VPS LakeshoreCochin 682040India institute of Liver Disease and transplantation Dr.Rela Institute and Medical CentreChennai 600044India

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling *** diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists *** diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored *** a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare *** this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

关键词： Combined hepatocellular-cholangiocarcinoma Immunotherapy Nestin Hepatocellular carcinoma Cholangiocarcinoma Liver cancer Biomarker Immune checkpoint inhibitors Pathology Genomic landscape

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In search of a pan-coronavirus vaccine:next-generation vaccine design and immune mechanisms

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Cellular & Molecular immunology 2024年第2期21卷 103-118页

作者： S.Cankat M.U.Demael L.Swadling Division of Infection and Immunity Institute of Immunity and TransplantationUniversity College LondonPears BuildingLondon NW32PPUK

Members of the coronaviridae family are endemic to human populations and have caused several epidemics and pandemics in recent *** this review,we will discuss the feasibility of and progress toward the ultimate goal of creating a pan-coronavirus vaccine that can protect against infection and disease by all members of the coronavirus *** will detail the unmet clinical need associated with the continued transmission of SARS-CoV-2,MERS-CoV and the four seasonal coronaviruses(HCoV-OC43,NL63,HKU1 and 229E)in humans and the potential for future zoonotic *** will highlight how first-generation SARS-CoV-2 vaccines and natural history studies have greatly increased our understanding of effective antiviral immunity to coronaviruses and have informed next-generation vaccine *** will then consider the ideal properties of a pan-coronavirus vaccine and propose a blueprint for the type of immunity that may offer ***,we will describe a subset of the diverse technologies and novel approaches being pursued with the goal of developing broadly or universally protective vaccines for coronaviruses.

关键词： Vaccine Coronavirus Cross-reactive immunity Cross-protection Universal

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