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A systematic review of salivary biomarkers in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2613-2625页

作者： Maria Ilenia De Bartolo Daniele Belvisi Romina Mancinelli Matteo Costanzo Claudia Caturano Giorgio Leodori Alfredo Berardelli Giovanni Fabbrini Giorgio Vivacqua IRCCS Neuromed PozzilliItaly department of Human Neurosciences Sapienza University of RomeRomeItaly department of anatomical HistologicalForensic Medicine and Orthopedics SciencesSapienza University of RomeRomeItaly department of Experimental Morphology and Microscopy-Integrated Research Center(PRAAB)-Campus Biomedico University of Rome RomeItaly

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,a

关键词： alpha-synuclein amyloid-beta autophagy DJ-1 neurodegeneration neuroinflammation Parkinson's disease salivary biomarkers tau

Intraductal Prostatic Carcinoma: Epidemiological and Anatomopathological Aspects in Dakar

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Open Journal of Pathology 2024年第2期14卷 54-63页

作者： Ibou Thiam Fabrice Senghor Omar Sow Kor Ndiaye Mohamed Moustapha Chérif Dial anatomical Pathology department Aristide Le Dantec University Hospital Dakar Senegal anatomical Pathology department Peace Hospital Ziguinchor Senegal General Surgery department Peace Hospital Ziguinchor Senegal anatomical Pathology department Idrissa Pouye University Hospital Dakar Senegal

Introduction: Intraductal carcinoma is often associated with high-grade, high-stage adenocarcinoma. Its frequency is variable and it is considered a poor prognostic factor. In our context, when prostatic carcinoma is diagnosed, pathologists do not always report the presence of this anatomopathological entity. We therefore conducted a study to determine the epidemiological and anatomopathological profile of patients with this lesion in Dakar. Materials and Methods: This is a retrospective descriptive study covering a 1-year period from January to December 2022. It focused on cases of intraductal carcinoma diagnosed among prostatic carcinomas collected in the anatomopathology laboratories of Hôpital Général Idrissa Pouye (HOGIP) and Hôpital Militaire de Ouakam (HMO). It was based on archives of anatomopathological reports, blocks and slides. A total of 200 cases of prostatic carcinoma were collated and reviewed to identify those presenting with intraductal carcinoma according to the diagnostic criteria of Guo and Epstein. Results: 87 cases of intraductal carcinoma were found, representing 43.5% of prostatic carcinomas. The mean age was 71 years. Patients in their seventh decade were the most represented, i.e. 42.5%. The majority of samples examined were biopsies (72.4%). The mean PSA level was 965.91 ng/ml, with extremes ranging from 0.03 to 10,000 ng/ml. Histologically, 96.5% of cases (N = 84) were invasive prostatic carcinoma. Gleason score 8 (4 + 4) was the most common, accounting for 42.53% (N = 37). On average, the study found four (04) foci of intraductal carcinoma per specimen, with extremes ranging from 1 to 30. Dense cribriform architecture accounted for 78.16%, loose cribriform for 11.5%, solid for 8.04% and micropapillary for 2.3%. Six cases (6.9%) showed foci of comedonecrosis. The vast majority of radical prostatectomies (87.5%) were classified as pT3. Node invasion and perineural sheathing were observed in 12.5% and 52.32% of cases respectively. Conclusion: Intraductal carcinoma is a poor prognostic f

关键词： Intraductal Carcinoma Prostate Pathological Anatomy Senegal

Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna Jennifer Aguilar Emily Lee William J.Mack department of Integrative anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1248-1255页

作者： Waiian Leong Jia-Qi Guo Chun Ning Fei-Fei Luo Rui Jiao Dong-Ye Yang Division of Gastroenterology&Hepatology The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina department of Accident&Emergency The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina department of anatomical Pathology The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Endoscopy Center The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChin

BACKGROUND The strategy for preventing colorectal cancer is screening by colonoscopy,which offers a direct way for detection and removal of adenomatous polyps(APs).American College of Gastroenterology guidelines recommend that people aged≥45 years should undergo colonoscopy;however,how to deal with people aged≤45 years is still unknown.AIM To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients≤45 years.METHODS A retrospective observational study was conducted at a single tertiary III hospital in China.This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021.The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated.RESULTS A total of 3053 cases were included.The prevalence of APs in the left and right colon was 55.0%and 41.6%,respectively(OR 1.7,95%CI 1.6-2.4;P3 polyps(14.1%;OR 0.3,95%CI 0.1-0.6;P<0.05).CONCLUSION This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged≤45 years and would be a more cost-effective and safe strategy.

关键词： Adenomatous polyps High-grade neoplasia Colonoscopy Flexible sigmoidoscopy

Assessment and Visualization of Ki67 Heterogeneity in Breast Cancers through Digital Image Analysis

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Advances in Breast Cancer Research 2024年第2期13卷 11-26页

作者： Chien-Hui Wu Min-Hsiang Chang Hsin-Hsiu Tsai Yi-Ting Peng department of anatomical Pathology Far Eastern Memorial Hospital New Taipei AI Lab Quanta Computer Inc. Taoyuan

The Ki67 index (KI) is a standard clinical marker for tumor proliferation;however, its application is hindered by intratumoral heterogeneity. In this study, we used digital image analysis to comprehensively analyze Ki67 heterogeneity and distribution patterns in breast carcinoma. Using Smart Pathology software, we digitized and analyzed 42 excised breast carcinoma Ki67 slides. Boxplots, histograms, and heat maps were generated to illustrate the KI distribution. We found that 30% of cases (13/42) exhibited discrepancies between global and hotspot KI when using a 14% KI threshold for classification. Patients with higher global or hotspot KI values displayed greater heterogenicity. Ki67 distribution patterns were categorized as randomly distributed (52%, 22/42), peripheral (43%, 18/42), and centered (5%, 2/42). Our sampling simulator indicated analyzing more than 10 high-power fields was typically required to accurately estimate global KI, with sampling size being correlated with heterogeneity. In conclusion, using digital image analysis in whole-slide images allows for comprehensive Ki67 profile assessment, shedding light on heterogeneity and distribution patterns. This spatial information can facilitate KI surveys of breast cancer and other malignancies.

关键词： Ki67 Heterogeneity Breast Cancer Digital Image Analysis

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)expression.This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of pneumonia.Remarkably,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G.The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient.Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan Fuda Xie Yigan Zhang Li Liang Kam Tong Leung Kwok Wai Lo Jun Yu Gary M.K.Tse Wei Kang Ka Fai To department of anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State Key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHK-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina department of Pediatrics The Chinese University of Hong KongHong KongChina department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease progression.As an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease development.Extensive research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue concentration.This has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer progression.Zinc transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc intake.Additionally,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on cancer.We also compile a summary of clinical trials involving zinc ions.Given the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

Enhancing sensitivity of triple-negative breast cancer to DNA-damaging therapy through chemical inhibition of the m6A methyltransferase METTL3

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Cancer Communications 2024年第2期44卷 282-286页

作者： Bianca Cesaro Alessia Iaiza Fabio Piscopo Marco Tarullo Eleonora Cesari Dante Rotili Antonello Mai Alberto Diana Michela Londero Luca Del Giacco Riccardo Masetti Alba Di Leone Chiara Naro Silvia Masciarelli Giulia Fontemaggi Claudio Sette Francesco Fazi Alessandro Fatica department of anatomical HistologicalForensic&Orthopedic SciencesSection of Histology&Medical EmbryologySapienza University of RomeRomeItaly department of Biology and Biotechnologies“Charles Darwin” Sapienza University of RomeRomeItaly GSTeP Organoids Research Core Facility Fondazione Policlinico A.Gemelli Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)RomeItaly department of Drug Chemistry and Technologies Sapienza University of RomeRomeItaly Pasteur Institute Cenci-Bolognetti FoundationSapienza University of RomeRomeItaly department of BioSciences University of MilanMilanItaly Multidisciplinary Breast Center Dipartimento Scienze della Salute della Donna e del Bambino e di SanitàPubblicaCatholic University of the Sacred HeartRomeItaly department of Neuroscience Section of Human AnatomyCatholic University of the Sacred HeartRomeItaly Oncogenomic and Epigenetic Unit IRCCS Regina Elena National Cancer InstituteRomeItaly

Dear Editor,N 6-methyladenosine(m^(6)A)is a critical mRNA modi-fication catalyzed by the enzyme methyltransferase-like 3(METTL3),with implications in RNA metabolism.METTL3 upregulation is associated with cancer progre... 详细信息

关键词： cancer methyltransferase metastasis

A novel saliva-based miRNA profile to diagnose and predict oral cancer

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International Journal of Oral Science 2024年第1期16卷 97-109页

作者： Jaikrishna Balakittnen Chameera Ekanayake Weeramange Daniel F.Wallace Pascal H.G.Duijf Alexandre S.Cristino Gunter Hartel Roberto A.Barrero Touraj Taheri Liz Kenny Sarju Vasani Martin Batstone Omar Breik Chamindie Punyadeera Saliva&Liquid Biopsy Translational Laboratory Griffith Institute for Drug DiscoveryGriffith UniversityNathanQLDAustralia department of Medical Laboratory Sciences Faculty of Allied Health SciencesUniversity of JaffnaJaffnaSri Lanka Menzies Health Institute Griffith UniversityGold CoastQLDAustralia School of Biomedical Sciences Faculty of HealthQueensland University of TechnologyBrisbaneQLDAustralia Centre for Cancer Biology Clinical and Health SciencesUniversity of South Australia&SA PathologyAdelaideSAAustralia Institute of Clinical Medicine Faculty of MedicineUniversity of OsloOsloNorway department of Medical Genetics Oslo University HospitalOsloNorway Griffith Institute for Drug Discovery Griffith UniversityNathanQLDAustralia QIMR Berghofer Medical Research Institute Statistics UnitBrisbaneQLDAustralia School of Public Health The University of QueenslandBrisbaneQLDAustralia School of Nursing Queensland University of TechnologyBrisbaneQLDAustralia eResearch Research InfrastructureAcademic DivisionQueensland University of TechnologyBrisbaneQLDAustralia department of anatomical Pathology Royal Brisbane and Women’s HospitalHerstonQLDAustralia Faculty of Medicine The University of QueenslandBrisbaneQLDAustralia Royal Brisbane and Women’s Hospital Cancer Care ServicesHerstonQLDAustralia department of Otolaryngology Royal Brisbane and Women’s HospitalHerstonQLDAustralia department of Oral and Maxillofacial Surgery Royal Brisbane and Women’s HospitalHerstonQLDAustralia

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

关键词： specificity salivary diagnosis