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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert j.Thomas M.brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan george jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Hydrogen for a Net-Zero Carbon World

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Engineering 2023年第10期29卷 8-10页

作者： Nigel P.brandon james j.brandon Faculty of Engineering Imperial College LondonSouth Kensington CampusLondon SW72AZUK The First Element Ltd. London N17GUUK

*** hydrogen?The concept of the“hydrogen economy”was first coined by *** Bockris during a talk he gave in 1970 at the General Motors Technical ***’s talk introduced the vision of a world economy in which energy was... 详细信息

关键词： hydrogen Carbon economy

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

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World journal of Gastroenterology 2017年第47期23卷 8263-8276页

作者： brandon j Perumpail Muhammad Ali Khan Eric R Yoo george Cholankeril Donghee Kim Aijaz Ahmed Department of Medicine College of MedicineDrexel University Division of Gastroenterology and Hepatology Health Science CenterUniversity of Tennessee Department of Medicine Santa Clara Valley Medical Center Division of Gastroenterology and Hepatology Stanford University School of Medicine

Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

关键词： Nonalcoholic fatty liver disease Hepatic steatosis Fatty liver Prevalence Incidence Fibrosis Risk factor Epidemiology Outcomes Nonalcoholic steatohepatitis

Use of direct-acting antiviral agents in hepatitis C virusinfected liver transplant candidates

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World journal of Gastroenterology 2018年第3期24卷 315-322页

作者： Chiranjeevi Gadiparthi george Cholankeril brandon j Perumpail Eric R Yoo Sanjaya K Satapathy Satheesh Nair Aijaz Ahmed Division of Gastroenterology and Hepatology University of Tennessee Health Sciences CenterMemphisTN 38104United States Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCA 94304United States Drexel University College of Medicine PhiladelphiaPA 19129United States Department of Medicine Santa Clara Valley Medical CenterSan JoseCA 95128United States

Since the advent of direct acting antiviral(DAA) agents, chronic hepatitis C virus(HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant(LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response(SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

关键词： Hepatitis C virus Direct-acting antiviral therapy Liver transplantation Purgatory Model for End-stage liver disease Sustained virological response

Clinical translation of bioartificial liver support systems with human pluripotent stem cell-derived hepatic cells

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World journal of Gastroenterology 2017年第11期23卷 1974-1979页

作者： Ryoichi Sakiyama brandon j Blau Toshio Miki Department of Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033United States

There is currently a pressing need for alternative the-rapies to liver transplantation. The number of patients waiting for a liver transplant is substantially higher than the number of transplantable donor livers, resulting in a long waiting time and a high waiting list mortality. An extracorporeal liver support system is one possible approach to overcome this problem. However, the ideal cell source for developing bioartificial liver(BAL) support systems has yet to be determined. Recent advancements in stem cell technology allow researchers to generate highly functional hepatocyte-like cells from human pluripotent stem cells(h PSCs). In this mini-review, we summarize previous clinical trials with different BAL systems, and discuss advantages of and potential obstacles to utilizing h PSC-derived hepatic cells in clinical-scale BAL systems.

关键词： Artificial liver Clinical trial Hepatocytes Pluripotent stem cells Bioreactors

The evolution of Hessian fly from the Old World to the New World： Evidence from molecular markers

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Insect Science 2015年第6期22卷 768-784页

作者： brandon j. Schemerhom Yan Ma Crane Charles F. Crane USDA-ARS Department of Entomology Department of Botany and Plant Pathology Purdue University West Lafayette IN 47907USA

Eighteen polymorphic microsatellite loci and 11 single-nucleotide polymor- phisms were genotyped in 1 095 individual Hessian fly specimens representing 23 popula- tions from North America, southern Europe, and southwest Asia. The genotypes were used to assess genetic diversity and interrelationship of Hessian fly populations. While phyloge- netic analysis indicates that the American populations most similar to Eurasian populations come from the east coast of the United States, genetic distance is least between （Alabama and California） and （Kazakhstan and Spain）. Allelic diversity and frequency vary across North America, but they are not correlated with distance from the historically documented point of introduction in New York City or with temperature or precipitation. Instead, the greatest allelic diversity mostly occurs in areas with Mediterranean climates. The mi- crosatellite data indicate a general deficiency for heterozygotes in Hessian fly. The North American population structure is consistent with multiple introductions, isolation by dis- tance, and human-abetted dispersal by bulk transport of puparia in infested straw or on harvesting equipment.

关键词： allele frequency Hessian fly microsatellite population structure SNP SSR

Taxane resistance in castration-resistant prostate cancer: mechanisms and therapeutic strategies

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Acta Pharmaceutica Sinica B 2018年第4期8卷 518-529页

作者： brandon Bumbaca Wei Li Department of Pharmaceutical Sciences College of Pharmacythe University of Tennessee Health Science Center

Despite its good initial response and significant survival benefit in patients with castrationresistant prostate cancer(CRPC), taxane therapy inevitably encounters drug resistance in all *** understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression,and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics,indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.

关键词： Castration-resistant prostate cancer Drug efflux transporters Taxane resistance Androgen receptor PI3K/AKT pathway Microtubules Cancer stem cells Efflux transporter

Evaluation of alum-based water treatment residuals used to adsorb reactive phosphorus

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Water Science and Engineering 2020年第3期13卷 181-192页

作者： george Carleton Teresa j.Cutright Department of Civil Engineering The University of AkronAkronOH 44235-3905USA

Excess reactive phosphorus(PO4)in waterways can lead to eutrophication.A low-cost approach to reducing PO4 levels in surface water was evaluated using the alum-based water treatment residual(Al-WTR)or Al-WTR augmented with powdered activated carbon(PAC-WTR).Batch adsorption-desorption and continuous flow column experiments were performed to assess the specific adsorption capacities under various concentration and flow *** Al-WTR and PAC-WTR exhibited the ability to adsorb *** overall,cumulative sorbed amount after a 28-d desorption step for Al-WTR was 33.93 mg/kg,significantly greater than the PAC-WTR value of 24.95 mg/kg(p<0.05).The continuous flow column experiments showed a theoretical PO4 uptake of 9.00 mg/g for Al-WTR and 7.14 mg/g for PAC-WTR over 720 *** surface water was used,the Al-WTR and PAC-WTR columns removed 67.4%and 62.1%of the PO4,*** results indicated that Al-WTR was more effective for in-field evaluation.

关键词： Phosphorous Alum Water treatment residuals Adsorption Desorption Powered activated carbon