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ATP6AP2,a regulator of LRP6/β-catenin protein trafficking,promotes Wnt/β-catenin signaling and bone formation in a cell type dependent manner

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Bone Research 2024年第2期12卷 453-468页

作者： Lei Xiong Hao-Han Guo Jin-Xiu Pan Xiao Ren Daehoon Lee Li Chen Lin Mei Wen-Cheng Xiong Department of Neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA Louis Stoke va medical center ClevelandOH 44106USA

Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types,including osteoblast(OB)differentiation and *** how Wnt/β-catenin signaling is regulated in OBs remain ***6AP2,an accessory subunit of V-ATPase,plays important roles in multiple cell types/organs and multiple signaling ***,little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone *** we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone *** knocking out(CKO)ATP6AP2 in the OB-lineage cells(Atp6ap2^(Ocn-Cre))reduced trabecular,but not cortical,bone formation and bone *** and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies revealed impairedβ-catenin signaling in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal and Wnt stimulated conditions,although LRP5 was decreased in ATP6AP2-KO osteocytes,but not *** cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphorylation,but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability,and thus regulatingβ-catenin levels,demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.

关键词： LRP6 impaired organs

Mixed neuroendocrine and adenocarcinoma of gastrointestinal tract:A complex diagnosis and therapeutic challenge

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2295-2299页

作者： Santosh Shenoy Department of General Surgery Kansas City VA Medical CenterUniversity of Missouri-Kansas CityKansas CityMO 64128United States

In this editorial we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal *** neuroendocrine and non-neuroendocrine neoplasms of the gastrointestinal system are rare heterogeneous group of tumors characterized by a high malignant potential,rapid growth,and poor *** to the rarity of these cancers,the standard therapy is poorly *** diagnosis of these tumors is based on combination of morphological features,immunohistochemical and neuroendocrine and epithelial cell *** endocrine and epithelial cell components can act independently of each other and thus,careful grading of each component separately is *** cancers are aggressive in nature and the potential of each component has paramount importance in the choice of treatment and *** of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine *** services and strategies are required for the management of these mixed malignancies to provide the best oncological *** etiopathogenesis of these mixed tumors remains obscure but poses interesting *** briefly discuss a few salient points in this editorial.

关键词： Mixed adenocarcinoma and neuroendocrine carcinoma Mixed neuroendocrine and non-neuroendocrine neoplasm Mixed adeno-neuroendocrine cancer Cell reprograming Tumor plasticity

A simplified noncryogenic strategy to transport mesenchymal stem cells: Potential applications in cell therapy and regenerative medicine

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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing Hao Wei Zeng Rex C.Haydon Hue H.Luu Russell R.Reid Tongchuan He Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

Synchronous gastric and colon cancers:Important to consider hereditary syndromes and chronic inflammatory disease associations

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 571-576页

作者： Santosh Shenoy Department of General Surgery Kansas City VA Medical CenterUniversity of Missouri-Kansas CityKansasMO 64128United States

In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon *** or metachronous primary malignancies at different sites of the gastrointestinal tract pose a unique diagnostic and therapeutic *** services and strategies are required for the management of multiple site primary malignancies,to provide the best oncological *** this study highlights the dual cancers in 76 sporadic cases,the authors excluded 55 patients due to combination of factors which includes;incomplete clinical data,genetic syndrome,gastric stump *** addition,the authors did not elaborate if any patients presented with signet ring cell morphology,E-cadherin mutations or presence of inflammatory bowel *** and mutational errors and epithelial field defects from chronic inflammatory diseases of the gastrointestinal tract are important when considering synchronous gastric and colonic *** will briefly discuss these in this editorial.

关键词： Synchronous gastric Colon cancers Gene mutation Chronic inflammation

Understanding the eff ect of recreational drug use on bone health and musculoskeletal disease in the establishment of pain regimens

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World Journal of Emergency Medicine 2024年第5期15卷 356-364页

作者： Ariella Gartenberg Alexander Petrie Winston Yen Woojn Cho Emergency Medicine Department Montefi ore Medical Center and Jacobi Medical CenterNew York 10461USA Emergency Medicine Department Jacobi Medical Center and North Central BronxNew York 10461USA Touro College of Osteopathic Medicine Touro UniversityNew York 10027USA

BACKGROUND:The widespread use of recreational drugs has raised concerns regarding their eff ects on various organ *** use of cannabis and opioids in chronic pain management increases their prevalence among patients with musculoskeletal conditions whose bone health may already be *** article aims to review the pathophysiology and toxic eff ects of recreational drug use on musculoskeletal health to establish appropriate pain regimens for patients with substance ***:medical literature published from 1970 until 2022 was identifi ed utilizing MEDLINE/PubMed and the Cochrane *** addition to the databases,references were obtained through the use of reference lists of published articles identifi ed by the aforementioned *** initial search terms included opioids,inhalants,hallucinogens,cannabis,stimulants,and bone *** were no methodological limitations in relation to the initial acquisition and analysis of ***:A total of 55 research articles were included in this ***,stimulants,opioids,and inhalants impact bone maintenance,specifically osteoblast and osteoclast activity,as well as impede hormone *** substances inhibit bone remodeling and development,manifesting as lower bone mineral density and increased fracture risk in chronic ***:Although the current literature suggests a deleterious effect of recreational drugs on bone health and musculoskeletal disease,further research is warranted to evaluate the clinical effects of long-term substance *** evaluation of such effects will aid in establishing appropriate pain regimens,as well as appropriate screening and treatment plans for recreational drug users.

关键词： Musculoskeletal disorders Bone health Cannabis Opioids Stimulants

Closing the Experiment-Modeling-Perturbation Loop in Whole-Brain Neuroscience

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Neuroscience Bulletin 2024年第8期40卷 1212-1214页

作者： Misha B.Ahrens Janelia Research Campus Howard Hughes Medical InstituteAshburnVAUSA

Understanding the mechanisms by which the central nervous system processes information,forms memories,makes decisions,and executes actions is a challenging *** is an interdisciplinary field in which cell biology,anatomy,network theory,and other scientific disciplines come together to jointly push our knowledge of brain function forward.

关键词： execute knowledge jointly

Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

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Asian Journal of Urology 2024年第2期11卷 316-323页

作者： Ryan A.Dornbier Chirag P.Doshi Shalin C.Desai Petar Bajic Michelle van Kuiken Mark Khemmani Ahmer V.Farooq Larissa Bresler Thomas M.T.Turk Alan J.Wolfe Kristin G.Baldea Loyola University medical center Department of UrologyMaywoodILUSA Loyola University chicago Department of Microbiology and ImmunologyMaywoodILUSA

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains *** evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis ***:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without *** sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene ***:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS *** controls had uric acid stone *** EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to *** validate our EQUC results,we performed 16 S ribosomal RNA gene *** 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced *** were detected in both“infectious”and“non-infectious”stone ***:Bacteria are more common and more abundant in MetS stones than control *** findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

关键词： Nephrolithiasis Urolithiasis Metabolic syndrome Urinary microbiome Percutaneous nephrolithotomy

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

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World Journal of Hepatology 2024年第7期16卷 1009-1017页

作者： Tung Huynh Delana MyAn Bui Tina Xiwen Zhou Ke-Qin Hu Department of Pharmacy University of California Irvine Medical CenterOrangeCA 92868United States University of Houston HoustonTX 77204United States chicago medical School at Rosalind Franklin University North ChicagoIL 60064United States Division of Gastroenterology and Hepatology University of California IrvineSchool of MedicineOrangeCA 92868United States

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic *** To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with *** A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated *** The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,*** 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,*** baseline to switching week 144,the rates of ALT and AST60 mL/min was increased from 86.5%at baseline to 88.2%at switching week *** Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

关键词： Tenofovir alafenamide Tenofovir disoproxil fumarate Switching Hepatic fibrosis improvement Aspartate aminotransferase to platelet ratio index Fibrosis-4 Shear wave elastography

Parasites of the liver:A global problem?

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World Journal of Gastroenterology 2024年第30期30卷 3554-3559页

作者： Vladislav V Tsukanov Alexander V vasyutin Julia L Tonkikh Clinical Department of the Digestive System Pathology of Adults and Children Federal Research Center“Krasnoyarsk Science Center”of the Siberian Branch of the Russian Academy of SciencesScientific Research Institute of Medical Problems of the NorthKrasnoyarsk 660022Russia

Parasitic liver diseases can be caused by trematodes,cestodes,nematodes,and *** pathology is significant because millions of people in different parts of the world have liver parasites,which can manifest themselves in the development of inflammation,liver cysts,cholecystitis,cholelithiasis,pancreatitis and liver cirrhosis that are often threatening their *** International Agency for Research on Cancer considers three species of trematodes,Schistosoma haematobium,Opisthorchis viverrini and Clonorchis sinensis,to be *** modern examination methods,in some cases including extensive screening of large populations,are required for diagnosing liver *** of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic *** is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.

关键词： Liver Parasites Epidemiology Diagnosis Clinics Treatment Echinococcosis Opisthorchiasis Fascioliasis Schistosomiasis