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Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

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Oncology Research 2024年第3期32卷 577-584页

作者： MONA SA BDELLATEIF NAGLAA MHASSAN MAHMOUD MKAMEL YOMNA MEL-MELIGUI department of Cancer Biology Medical Biochemistry and Molecular BiologyNational Cancer InstituteCairo UniversityCairo11976Egypt department of Cinical pathology National Cancer InstituteCairo UniversityCairo11976Egypt

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still unclear.The current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML patients.Methods:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using qRT-PCR.The data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)rates.Results:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].The.median relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML patients.Condusion:miR-34a could be a beneficial diagnostic biomarker for AML patients.In addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

关键词： AML miR 34a microRNA Leukemia

Aspergillus niger prolyl endopeptidase in celiac disease

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World Journal of Gastroenterology 2024年第24期30卷 3044-3047页

作者： Marica Colella Concetta Cafiero Raffaele Palmirotta Interdisciplinary department of Medicine Section of Microbiology and VirologyUniversity of Bari“Aldo Moro”Bari 70124Italy Area of molecular pathology Anatomic Pathology UnitFabrizio Spaziani HospitalFrosinone 03100Italy

We comment here on the article by Stefanolo et al entitled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”,published in the World Journal of Gastroenterology.Celiac disease is a well-recognized systemic autoimmune disorder.In genetically susceptible people,the most evident damage is located in the small intestine,and is caused and worsened by the ingestion of gluten.For that reason,celiac patients adopt a gluten-free diet(GFD),but it has some limitations,and it does not prevent re-exposure to gluten.Research aims to develop adjuvant therapies,and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease(AN-PEP),which is able to degrade gluten in the stomach,reducing its concentration in the small intestine.The study found a high adherence to the GFD,but did not address AN-PEP as a gluten immunogenic peptide reducer,as it was only tested in patients following a GFD and not in gluten-exposing conditions.This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia department of pathology and Municipal Key-Innovative Discipline of molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research Center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina department of Clinical pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

关键词： Alzheimer’s disease caspase-1 GSDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies

Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic,periampullary/ampullary,and choledochal adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 875-882页

作者： Arzu Hazal Aydın Nesrin Turhan department of pathology Aksaray University Aksaray Training and Research HospitalAksaray 68200Turkey department of pathology University of Health Sciences Ankara City HospitalAnkara 06800Turkey

BACKGROUND Pancreatic,periampullary/ampullary,and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis.Immune checkpoint blockade is a promising treatment option for several tumor types.H long terminal repeatassociating 2(HHLA2),which is analogous to programmed death-ligand 1(PDL1),is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.AIM To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.METHODS Ninety-two adenocarcinoma cases located in the pancreas,ampulla,and distal common bile duct were identified.This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021.Immunohistochemistry was conducted to examine the expression of DNA mismatch repair(MMR),PD-L1,and HHLA2 proteins.RESULTS Patients with high HHLA2 expression had a higher mean age than those with low expression.Low HHLA2 expression was associated with high perineural invasion.HHLA2 expression was low in pathological stage T3(pT)3 cases and high in pathological stage T1,T2,and T4 cases.There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.CONCLUSION Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

关键词： H long terminal repeat-associating 2 Programmed death-ligand 1 Adenocarcinoma Pancreas Ampulla of Vater Distal common bile duct

Liver biopsy in the post-hepatitis C virus era in Japan

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World Journal of Gastroenterology 2024年第14期30卷 1949-1957页

作者： Yoshihiro Ikura Takako Okubo Yasuhiro Sakai department of pathology Takatsuki General HospitalTakatsuki 569-1192Osaka PrefectureJapan department of pathology Kansai Medical University Medical CenterMoriguchi 570-8507Japan

In Japan,liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus(HCV)and diagnosing HCV-related hepatocellular carcinoma(HCC).However,due to the development of effective antiviral treatments and advanced imaging,the necessity for biopsies has significantly decreased.This change has resulted in fewer chances for diagnosing liver disease,causing many general pathologists to feel less confident in making liver biopsy diagnoses.This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan.First,it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence.Second,it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions,because clinically diagnosable HCCs are not targets for biopsy.Third,the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs.In conclusion,pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail.

关键词： Liver biopsy Alteration Post-hepatitis C virus era Steatotic liver disease Hepatic tumors Immune checkpoint inhibitors

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 factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The 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 factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This 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

HIV encephalopathy is contributed by macrophages and microglia

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Science China(Life Sciences) 2024年第4期67卷 836-838页

作者： Si-Meng Liu Man Li Chunhui Ma Chunying Liu An Lv Qing Li Yamei Niu Peng Wang Bo Huang Wei-Min Tong department of pathology China Medical UniversityShenyang 110122China department of pathology Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeNeuroscience CenterChinese Academy of Medical SciencesBeijing 100005China department of pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China molecular pathology Research Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Center For Experimental Animal Research Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China department of Immunology and National Key Laboratory of Medical molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100010China department of Biochemistry and molecular Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Dear Editor,Acquired immunodeficiency syndrome(AIDS),characterized by a significant decrease in the number of CD4^(+)T cells,causes a defective T cell immune response,which subsequently leads to various conditional pathogenic infections and tumors(Calmy et al.,2018;Seligmann et al.,1987).Neurological disorders have been reported in 70%–80%of patients with AIDS(Saylor et al.,2016)。

关键词： encephalopathy immunodeficiency

Role of ACLY in the development of gastric cancer under hyperglycemic conditions

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Quantitative Biology 2024年第1期12卷 100-116页

作者： Keran Sun Jingyuan Ning Keqi Jia Xiaoqing Fan Hongru Li Jize Ma Meiqi Meng Cuiqing Ma Lin Wei department of Immunology Immunology Department of Hebei Medical UniversityShijiazhuangChina department of pathology Pathology Department of the Fourth Hospital of Hebei Medical UniversityShijiazhuangChina

To investigate the impact of hyperglycemia on the prognosis of patients with gastric cancer and identify key molecules associated with high glucose levels in gastric cancer development,RNA sequencing data and clinical features of gastric cancer patients were obtained from The Cancer Genome Atlas(TCGA)database.High glucose-related genes strongly associated with gastric cancer were identified using weighted gene co-expression network and differential analyses.A gastric cancer prognosis signature was constructed based on these genes and patients were categorized into high-and low-risk groups.The immune statuses of the two patient groups were compared.ATP citrate lyase(ACLY),a gene significantly related to the prognosis,was found to be upregulated upon high-glucose stimulation.Immunohistochemistry and molecular analyses confirmed high ACLY expression in gastric cancer tissues and cells.Gene Set Enrichment Analysis(GSEA)revealed the involvement of ACLY in cell cycle and DNA replication processes.Inhibition of ACLY affected the proliferation and migration of gastric cancer cells induced by high glucose levels.These findings suggest that ACLY,as a high glucose-related gene,plays a critical role in gastric cancer progression.

关键词： ACLY gastric cancer high glucose immune microenvironment

Blastomas of the digestive system in adults:A review

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1030-1042页

作者： Yu Liu Tony El Jabbour Jonathan Somma Yukihiro Nakanishi Saverio Ligato Hwajeong Lee Zhi-Yan Fu department of pathology LSU Health Sciences Center School of MedicineNew OrleansLA 70112United States department of pathology Hartford HealthCareHartfordCT 06102United States department of pathology Moffitt Cancer CenterTampaFL 33612United States department of pathology and Laboratory Medicine Albany Medical CenterAlbanyNY 12208United States

Blastomas,characterized by a mixture of mesenchymal,epithelial,and undifferentiated blastematous components,are rare malignant neoplasms originating from precursor blast cells.This review focuses on digestive system blastomas in adult patients,including gastroblastoma,hepatoblastoma,and pancreatoblastoma.Gastroblastoma is a biphasic,epitheliomesenchymal tumor,with only sixteen cases reported to date.In addition to the characteristic histology,metastasisassociated lung adenocarcinoma transcript 1-glioma-associated oncogene homolog 1 gene fusion is typical,although recently novel ewing sarcoma breakpoint region 1-c-terminal binding protein 1 and patched 1-glioma-associated oncogene homolog 2 fusions have been described.Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty.Pancreatoblastoma,primarily a pediatric tumor,displays acinar differentiation and squamoid nests with other lines of differentiation also present,especially neuroendocrine.Diagnostic approaches for these blastomas include a combination of imaging modalities,histopathological examination,and molecular profiling.The treatment generally involves surgical resection,which may be supplemented by chemotherapy or radiotherapy in some cases.Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes,particularly in the setting of metastases.This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

关键词： Adult blastomas Gastroblastoma Hepatoblastoma Pancreatoblastoma Digestive system