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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

Role of copper in central nervous system physiology and pathology

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Neural Regeneration Research 2025年第4期20卷 1058-1068页

作者： Martina Locatelli Cinthia Farina Institute of Experimental Neurology Division of NeuroscienceIstituto di Ricovero e Cura a Carattere Scientifico(IRCCS)San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly

Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.

关键词： astrocytes central nervous system copper cuprizone multiple sclerosis myelin neurodegenerative disorders

Gouty destruction of a patellar tendon reconstruction and novel revision reconstruction technique: A case report

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World Journal of Orthopedics 2024年第7期15卷 675-682页

作者： Carl C Edge Jonathan Widmeyer Omar Protzuk Maya Johnson Robert O’Connell Department of Orthopaedic Surgery Division of Sports MedicineVirginia Commonwealth University Health SystemRichmondVA 23298-0153United States division of Sports Medicine OrthowestCarroltonGA 30117United States

BACKGROUND Gout is a disease characterized by hyperuricemia,and resultant deposition of uric acid crystals in tissues.While typically manifested as intraarticular crystals or tophi,gout can also cause pathology at entheses.Gouty deposition within ten-dinous structures put them at risk for traumatic and degenerative rupture.Furth-ermore,allografts can also be at risk of rupture in the setting of severe gout.We present the case of a 56-year-old female with severe gouty disease who sustained a re-rupture of a patellar tendon allograft reconstruction.CASE SUMMARY A 56-year-old female presented to clinic after feeling her left knee pop and coll-apse beneath her while descending stairs.She had a history of tophaceous gout and left patellar tendon rupture with reconstruction and multiple revisions over the course of 19 years.This patient presented with pain and extensor lag.A magnetic resonance image demonstrated a ruptured patellar tendon allograft re-construction and avulsion fracture at the tibial tubercle.The patient was treated with a novel intervention of Achilles allograft with bone block in a unique config-uration with a dermal allograft incorporated into the reconstruction.She was made non-weight bearing in the operative extremity in extension for the first four weeks postoperatively and was then progressed to active flexion over the course of eight weeks.At twelve weeks,she was able to fully extend her operative knee and at five months she was resuming her normal activities and exercises.CONCLUSION Failed patellar tendon reconstruction due to gouty infiltration is treated with dermal allograft augmented Achilles tendon reconstruction with bone block.Core Tip:We present a case of a 56-year-old female with severe systemic tophaceous gout who presented with a rupture of her revision patellar tendon reconstruction due to severe gouty infiltration.The major takeaway from this case is that with multiple failed reconstructions of the patellar tendon,both structural and biologic reinforcement were sought to provide th

关键词： sustained injuries revision

A case report of bilateral lateral ventricle calcified pseudoneoplasm of the neuraxins

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Chinese Neurosurgical Journal 2024年第1期10卷 67-72页

作者： Xiaolong Qiao Yinan Chen Ying Ji Chaoshi Niu Chuandong Cheng Anhui University of Science and Technology HuainanAnhui 232001People’s Republic of China Department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China1st Tianehu RoadHefeiAnhui 230031People’s Republic of China

Background Calcifying pseudoneoplasm of the neuraxis(CAPNON)is indeed a rare central nervous system lesion that can occur in central nervous system(CNS).Due to its infrequency and limited literature reports,it is challenging to diagnose and manage CAPNON.Case presentation In this intriguing study,we embarked on a quest to uncover the story of a 16-year-old girl who experienced bothersome headaches.Through advanced imaging techniques like computed tomography(CT)and magnetic resonance imaging(MRI),we glimpsed a delicate calcified growth within the lateral ventricles’posterior horn.Motivated by our unwavering commitment to solving mysteries,we embarked on a surgical journey that not only freed the young patient from her ailment but also shed light on the true nature of her puzzling adversary—a remarkable CAPNON.Conclusions For patients with CAPNON who have multiple or non-respectable lesions,the primary goal is to alleviate symptoms.After alleviating the symptoms with partial resection,close monitoring of any residual lesions is essential.If there is no evidence for disease progression,a strategy of continued close observation is appropriate.

关键词： CAPNON Imaging pathology Operation

Expression of Osteopontin and caudal-related homeobox gene 2:indications of phenotypes and prognosis in advanced gastric cancer

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福州总医院学报 2010年第4期17卷 212-217页

作者： Xia Zhang Tetsuya Tsukamoto Tsutomu Mizoshita Ban Hisayo Toyoda Takeshi Masae Tatematsu division of Oncological pathology Aichi Cancer Center Research Institute 1 - 1Kanokoden Chikusa-ku Nagoya Aichi 464-8681 Japan. Oncology department of Nanjing Command Fuzhou general hospital xi＇ er huan - lu156 Fuzhou 86-350025 China

Objective:To investigate the expression of osteopontin(OPN)and caudal-related homeobox gene 2(CDX2)in advanced gastric cancer,and to correlate them with clinicopathological features.Method:One-hundred and nine patients suffered from gastric cancer recruited.Expression of OPN and CDX2 and other molecular markers were determined using immunohistochemistry method.Results:Total positive rate of OPN expression was 46.79%,and related with depth of cancer invasion and different phenotype(P<0.001),no association with the patient's age,gender,tumor histological type and lymph node metastasis.In different phenotypes of gastric cancers,OPN frequently expressed in CDX2-negative-expressed G and N type(16/109 and 21/109,respectively),and in CDX2-positive-expressed GI and I types expression level were lower.OPN expression reversely correlated with cdx-2 expression(P<0.001).Patients with OPN positive expression had worse 5-year survival,and patients with OPN negative,5-year survival time better(P<0.001).Further analysis revealed patients with OPN-/CDX2+ had better 5-year survival than other three groups including OPN+/CDX2-,OPN-/CDX2-and OPN+/CDX2+.With multivariate analysis for 5-year survival,it suggested that OPN was the most significant predictor of poor prognosis in gastric cancer(P =0.0043),with lymph node metastasis and tumor depth of invasion were also independent indicators(P =0.0359 and P =0.0315,respectively).Conclusion:Osteopontin is a useful prognostic marker in gastric cancer,and combined with CDX2,it may be much more useful for predicting the survival time in advanced gastric cancer patients.Furthermore it also gave us a clue that in gastric cancer,CDX2 may be a transcription factor modulating the expression of osteopontin.

关键词：胃癌肿瘤症状临床分析

The role of gut microbiota associated metabolites in digestive disorders

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Engineered Regeneration

Engineered Regeneration 2024年第2期5卷 228-246页

作者： Na Li Cheng Zhao Pingnan Zhang Songting Wu Xiaotan Dou Saifei Xu Xiaoqi Zhang Chunyan Peng Ying Xie Shuling Huang Lin Zhou Yonghua Shen Lei Wang Jinglin Wang Chenggong Yu Department of Gastroenterology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China division of Hepatobiliary and Transplantation Surgery Department of Gernal SurgeryNanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China

The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and pathology.Besides,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a challenge.However,research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases.By modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease.Currently,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying mech-anisms.In this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system disorders.It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

关键词： Gut microbial metabolites Digestive disorders Inflammatory bowel disease(IBD) Non-alcoholic fatty liver disease(NAFLD)

Assessment of risks, implications, and opportunities of waterborne neurotoxic pesticides

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Journal of Environmental Sciences 2023年第3期125卷 735-741页

作者： Delaram Dara Andrei P.Drabovich division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaAlberta T6G 2G3Canada

Pesticides are a well-known family of chemicals that have contaminated water systems globally. Four common subfamilies of pesticides include organochlorines, organophosphates, pyrethroids, and carbamate insecticides which have been shown to adversely affect the human nervous system. Studies have shown a link between pesticide exposure and decreased viability, proliferation, migration, and differentiation of murine neural stem cells. Besides human exposure directly through water systems, additional factors such as pesticide bioaccumulation, biomagnification and potential synergism due to co-exposure to other environmental contaminants must be considered. A possible avenue to investigate the molecular mechanisms and biomolecules impacted by the various classes of pesticides includes the field of-omics. Discovery of the precise molecular mechanisms behind pesticidemediated neurodegenerative disorders may facilitate development of targeted therapeutics.Likewise, discovery of pesticide biodegradation pathways may enable novel approaches for water system bioremediation using genetically engineered microorganisms. In this minireview, we discuss recently established harmful impacts of various categories of pesticides on the nervous system and the application of-omics field for discovery, validation, and mitigation of pesticide neurotoxicity.

关键词： Neurotoxic pesticides Water pollution Neural stem cells Omics approaches Drug discovery

Appropriate leucine-richα-2 glycoprotein cut-off value for Japanese patients with ulcerative colitis

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World Journal of Clinical Cases 2023年第32期11卷 7753-7760页

作者： Masanao Yamazato Shunichi Yanai Tomofumi Oizumi Makoto Eizuka Shun Yamada Yosuke Toya Noriyuki Uesugi Tamotsu Sugai Takayuki Matsumoto division of Gastroenterology and Hepatology Department of Internal MedicineIwate Medical UniversityYahaba 028-3695Japan division of Molecular Diagnostic pathology Iwate Medical UniversityYahaba 028-3695Japan

BACKGROUND It has been suggested that serum leucine-richα-2 glycoprotein(LRG)could be a novel monitoring biomarker for the assessment of disease activity in inflammatory bowel disease.In particular,the relationship between LRG levels and the endoscopically assessed activity of ulcerative colitis(UC)has become a matter of interest.AIM To clarify appropriate LRG cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with UC.METHODS This was a cross-sectional,single-center,observational study of Japanese patients with UC.Among 213 patients with UC,in whom LRG was measured from September 2020 to February 2022,we recruited 30 patients for whom a total colonoscopy and measurements of LRG and C-reactive protein(CRP)were performed on the same day.We retrospectively analyzed correlations between the LRG and CRP levels and endoscopic indices,including the Mayo endoscopic subscore and UC endoscopic index of severity.RESULTS Correlations between the LRG values and the Mayo endoscopic subscore or UC endoscopic index of severity were significant(r=0.754,P<0.0001;r=0.778,P<0.0001,respectively).There were also significant correlations between CRP levels and Mayo endoscopic subscore or UC endoscopic index of severity(r=0.599,P=0.0005;r=0.563,P=0.0012,respectively),although the correlation coefficients were higher for LRG.The LRG cutoff value for predicting endoscopic remission was 13.4μg/mL for a Mayo endoscopic subscore of 0[area under the curve(AUC):0.871;95%confidence interval(CI):0.744-0.998],and 13.4μg/mL for an UC endoscopic index of severity of 0 or 1(AUC:0.904;95%CI:0.792-1.000).CONCLUSION LRG may be a surrogate marker for endoscopic activity in UC,with a cut-off value of around 13.4μg/mL for endoscopically inactive disease.

关键词： Ulcerative colitis Leucine-rich alpha-2 glycoprotein C-reactive protein Japanese patients

Anoctamin 5 regulates the cell cycle and affects prognosis in gastric cancer

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World Journal of Gastroenterology 2022年第32期28卷 4649-4667页

作者： Tomoyuki Fukami Atsushi Shiozaki Toshiyuki Kosuga Michihiro Kudou Hiroki Shimizu Takuma Ohashi Tomohiro Arita Hirotaka Konishi Shuhei Komatsu Takeshi Kubota Hitoshi Fujiwara Kazuma Okamoto Mitsuo Kishimoto Yukiko Morinaga Eiichi Konishi Eigo Otsuji division of Digestive Surgery Department of SurgeryKyoto Prefectural University of MedicineKyoto 602-8566Japan Department of pathology Kyoto City HospitalKyoto 604-8845Japan Department of pathology Kyoto Prefectural University of MedicineKyoto 602-8566Japan

BACKGROUND Anoctamin 5(ANO5)/transmembrane protein 16E belongs to the ANO/transmembrane protein 16 anion channel family.ANOs comprise a family of plasma membrane proteins that mediate ion transport and phospholipid scrambling and regulate other membrane proteins in numerous cell types.Previous studies have elucidated the roles and mechanisms of ANO5 activation in various cancer types.However,it remains unclear whether ANO5 acts as a plasma membrane chloride channel,and its expression and functions in gastric cancer(GC)have not been investigated.AIM To examine the role of ANO5 in the regulation of tumor progression and clinicopathological significance of its expression in GC.METHODS Knockdown experiments using ANO5 small interfering RNA were conducted in human GC cell lines,and changes in cell proliferation,cell cycle progression,apoptosis,and cellular movement were assessed.The gene expression profiles of GC cells were investigated following ANO5 silencing by microarray analysis.Immunohistochemical staining of ANO5 was performed on 195 primary tumor samples obtained from patients with GC who underwent curative gastrectomy between 2011 and 2013 at our department.RESULTS Reverse transcription-quantitative polymerase chain reaction(PCR)and western blotting demonstrated high ANO5 mRNA and protein expression,respectively,in NUGC4 and MKN45 cells.In these cells,ANO5 silencing inhibited cell proliferation and induced apoptosis.In addition,the knockdown of ANO5 inhibited G1-S phase progression,invasion,and migration.The results of the microarray analysis revealed changes in the expression levels of several cyclin-associated genes,such as CDKN1A,CDK2/4/6,CCNE2,and E2F1,in ANO5-depleted NUGC4 cells.The expression of these genes was verified using reverse transcription-quantitative PCR.Immunohistochemical staining revealed that high ANO5 expression levels were associated with a poor prognosis.Multivariate analysis identified high ANO5 expression as an independent prognostic factor for 5-year survival in patients with GC(P=0

关键词： Anoctamin 5 Gastric cancer Cell cycle G1/S checkpoint Cell proliferation