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Inhibition of Ehrlich ascites carcinoma growth by melatonin:Studies with micro-CT

Oncology Research 2024年第1期32卷 175-185页

作者： SEHER YILMAZ ZÜLEYHA DOĞANYIĞIT MERT OCAK EVRIM SUNA ARIKAN SÖYLEMEZ ASLI OKAN OFLAMAZ SÜMEYYE UÇAR ŞÜKRÜATEŞ AMMAD AHMAD FAROOQI department of Anatomy Faculty of MedicineYozgat Bozok UniversityYozgatTurkey department of Mechanical and Aerospace Engineering Case Western Reserve UniversityClevelandOhioUSA department of Histology and Embriology Faculty of MedicineYozgat Bozok UniversityYozgatTurkey department of Anatomy Faculty of DentistryAnkara UniversityAnkaraTurkey department of Medical Biology Faculty of MedicineAfyonkarahisar Health Sciences UniversityAfyonTurkey department of Anatomy Faculty of MedicineErciyes UniversityKayseriTurkey department of Molecular Oncology Institute of Biomedical and Genetic Engineering(IBGE)IslamabadPakistan

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling *** has many benefits,such as organizing circadian rhythms and acting as a powerful *** aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin(mTOR)signaling pathway and the Argyrophilic Nucleolar Regulatory Region(AgNOR),using the Microcomputed Tomography(Micro CT).Ehrlich ascites carcinoma(EAC)cells were administered into the mice by subcutaneous *** with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 *** measurements for the taken tumors were made with micro-CT imaging,immunohistochemistry(IHC),real-time polymerase chain reaction(PCR)and ***,the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT *** the IHC analysis,the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8(F8)expression were compared with the control *** was determined that there was a significant decrease(p<0.05).Significant differences were found in the total AgNOR area/nuclear area(TAA/NA)ratio in the treatment groups(p<0.05).Furthermore,there were significant differences between the amount of mTOR mRNA for the phosphatidylinositol 3-kinase(PI3K),AKT Serine/Threonine Kinase(PKB/AKT)genes(p<0.05).Cell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin;It was observed that 100µg/mL melatonin dose caused an increase in the apoptotic cell *** this study,we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice *** characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advanc

关键词： Signaling pathway Apoptosis Real-time PCR AgNOR

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Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1878-1889页

作者： Fouzia Fazal Muhammad Arsalan Khan Sumayya Shawana Rahma Rashid Muhammed Mubarak department of Pathology Jinnah Medical and Dental CollegeKarachi 74800SindhPakistan department of General Surgery Sindh Institute of Urology&Transplantation(SIUT)Karachi 74200SindhPakistan department of Pathology Bahria University of Health SciencesKarachi 74400SindhPakistan department of Pathology SIUTKarachi 74200SindhPakistan

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic ***-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 *** We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological *** A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC *** CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 ***,histopathological,and clinical parameters were *** TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both *** tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological *** Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue *** demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and *** suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

关键词： Colorectal cancer Macrophages Tumor stroma M2 subset Tumor front Tumor stage Lymphovascular invasion Prognosis Tumor-associated macrophages immunohistochemistry

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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao department of Hepatobiliary Surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China department of Cardiothoracic Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c department of Hepatobiliary Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune *** shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein ***:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using ***-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following *** blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular ***:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer *** HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 195-209页

作者： Yan Zhang Zhen-Zhen Wang An-Qi Han Ming-Ya Yang Li-Xin Zhu Fa-Ming Pan Yong Wang department of General Surgery The Second Hospital of Anhui Medical UniversityHefei 230601China department of General Surgery The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefei 230032China The Key Laboratory of Major Autoimmune Diseases Anhui Medical UniversityHefei 230032China

Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant ***,its role in hepatocellular cancer(HCC)is not *** present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC ***:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics *** was used for the *** molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow *** set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western *** tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and *** on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and ***:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western *** silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was ***,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and *** correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall *** constructed immune prognosis model could effectively evaluate the ***:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the oc

关键词： TuBG1 Hepatocellular carcinoma Apoptosis Cell cycling Immunomodulators

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High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 787-797页

作者： Peng-Yang Zhou De-Xiang Zhu Yi-Jiao Chen Qing-Yang Feng Yi-Hao Mao Ao-Bo Zhuang Jian-Min Xu department of General Surgery Zhongshan Hospital Fudan UniversityShanghai 200032China

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer *** studies have focused on its roles as an antioxidant and in lipid ***,the role of PNPLA8 in colorectal cancer(CRC)progression is *** To explore the prognostic effects of PNPLA8 expression in *** A retrospective cohort containing 751 consecutive CRC patients was ***8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive *** patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile *** prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression *** over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank *** PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter *** patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant *** analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

关键词： Biomarker Colorectal cancer Expression level Overall survival Patatin like phospholipase domain containing 8 Prognosis

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WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor *** findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

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Undifferentiated high-grade pleomorphic sarcoma of the common bile duct:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2253-2260页

作者： Li-Ping Zheng Wen-Yan Shen Chun-Dong Hu Chun-Hua Wang Xu-Jian Chen Jing Wang Yi-Yu Shen department of General Surgery The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina department of Pathology The Second Affiliated Hospital of Jiaxing UniversityJiaxing 314000Zhejiang ProvinceChina

BACKGROUND Undifferentiated pleomorphic sarcoma(UPS)is a rare malignant mesenchymal tumor with a poor *** mainly occurs in the extremities,trunk,head and neck,and retroperitoneum *** to the lack of specific clinical manifestations and imaging features,UPS diagnosis mainly depends on pathological and immunohistochemical examinations for exclusive *** we report an extremely rare case of high-grade UPS in the common bile duct(CBD).There are limited available data on such *** SUMMARY A 70-year-old woman was admitted to our department with yellow eyes and urine accompanied by upper abdominal distending pain for 2 *** laboratory data suggested significantly elevated hepatorenal function *** imaging data revealed calculous cholecystitis,intrahepatic and extrahepatic bile duct dilation with extrahepatic bile duct calculi,and a space-occupying lesion at the distal *** endoscopic biliary stenting and symptomatic support therapy,CBD exploration and biopsy were *** frozen section indicated malignant spindle cell tumor of the CBD mass,and further radical pancreaticoduodenectomy was ***,the neoplasm was diagnosed as a high-grade UPS combined with the light-microscopic morphology and immunohistochemical *** This extremely rare case highlighted the need for increasing physicians'vigilance,reducing the odds of misdiagnosis,and providing appropriate treatment strategies.

关键词： Undifferentiated pleomorphic sarcoma Soft tissue sarcoma Common bile duct Extrahepatic bile duct immunohistochemistry Case report

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Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway

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Chinese Journal of Natural Medicines 2024年第5期22卷 426-440页

作者： SI Jianchao CHEN Xue QI Kerong LI Dongli LIU Bingbing ZHENG Yuying JI Ensheng YANG Shengchang department of Physiology Hebei University of Chinese MedicineShijiazhuang 050000China Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine Shijiazhuang 050000China department of Geriatrics First People’s Hospital of XiaoganXiaogan 432000China

Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive *** evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the *** study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by *** exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH ***,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular *** function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron *** stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western *** further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 *** results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in ***,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling ***,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH *** findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.

关键词： Chronic intermittent hypoxia Cognitive impairment Shengmaisan Liuwei Dihuang Decoction Oxidative stress EPO/EPOR/JAK2 signaling pathway

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Anemarsaponin B mitigates acute pancreatitis damage in mice through apoptosis reduction and MAPK pathway modulation

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BIOCELL 2024年第5期48卷 745-758页

作者： YI HU ZHONGYANG REN ZHENGZHONG ZHAO YONGJIA HUANG WANTING HUANG JIE LIU LING DING Gastroenterology department Chongqing University Jiangjin HospitalJiangjin Central Hosptial of ChongqingChongqingChina Surgical department Chongqing Jiangjin District Hospital of Chinese MedicineChongqingChina Pharmacy department Chongqing University Jiangjin HospitalJiangjin Central Hosptial of ChongqingChongqingChina

Background:Acute pancreatitis(AP),known for its rapid onset and significant incidence and mortality rates,presents a clinical challenge due to the limited availability of effective treatments and preventive *** B(ASB)has emerged as a potential therapeutic agent,demonstrating capabilities in reducing immune inflammation,positioning it as a promising candidate for AP ***:We investigated the effects of ASB on AP in mice,induced by caerulein and lipopolysaccharide(LPS).Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase,amylase,TNF-α,IL-1β,IL-6,SOD,and GSH-Px.A range of techniques such as immunohistochemistry staining,immunofluorescence staining,Western blotting,and quantitative Polymerase Chain Reaction(q-PCR),were employed to measure the expression of critical ***,pancreas samples from the mice were harvested for microbiome and metabolome sequencing,with the data analyzed to understand the impact of ASB on ***:Our study revealed that,compared to the sham group,the AP group exhibited significantly higher serum levels of lipase,amylase,and cytokines,while levels of SOD and GSH Px were notably *** with ASB led to a substantial decrease in the levels of lipase,amylase,and cytokines,and an increase in SOD and GSH-Px levels.q-PCR analysis of pancreatic histiocytes corroborated these serum *** and Eosin(H&E)staining indicated significant alterations in the pathological changes in the pancreas,lungs,and small intestine of the AP model due to *** assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP *** Blot and histological analyses showed that ASB reduced the phosphorylation of TAK,p38,JNK,and ERK proteins,as well as the levels of TRAF6 protein in the AP ***,metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 diffe

关键词： Anemarsaponin B Acute pancreatitis Cytokines MAPK TRAF6 Gut flora

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Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina National Center for Trauma Medicine BeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina department of Orthopedics China-Japan Friendship HospitalBeijingChina department of Central Laboratory and Institute of Clinical Molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

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