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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： Shan Ping Yu Emily Choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

Stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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The Importance of Extensor Mechanism in the Success of Patello-Femoral Arthroplasty

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Open Journal of Orthopedics 2014年第8期4卷 221-225页

作者： Rajkumar Krishnan Ray Randle john flynn medical center Gold Coast Australia

Anterior knee pain is a common symptom in general orthopedic practice and is reported in 8% of women and 2% of men over the age of 55 years. The treatment of isolated patellofemoral arthritis is controversial. Many patients can be effectively managed conservatively. Analysis was done on 14 patients (17 knees) with symptomatic isolated patellofemoral osteoarthritis between 2001 and 2007. 3 patients had additional procedures like tibial tubercle osteotomy and lateral release, tibial tubercle osteotomy with medical plication and iliotibial band lengthening and lateral retinacular release. The operation should be viewed as a soft-tissue procedure involving resurfacing of the femoral trochlea and the articular surface of the patella. Proper balance of the extensor mechanism must be done at the time of surgery to ensure correct tracking of the patella which in turn results in the best outcome for the replacement.

关键词： Patellofemoral Arthroplasty Patellar Maltracking Patello Femoral Pain Lateral Retinacular Release Tibial Tubercle Osteotomy

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Ex vivo 3D osteocyte network construction with primary murine bone cells

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Bone Research 2015年第3期3卷 152-163页

作者： Qiaoling Sun Yexin Gu Wenting Zhang Leah Dziopa Jenny Zilberberg Woo Lee Department of Materials Science and Chemical Engineering Stevens Institute of Technology john Theurer Cancer center Hackensack University Medical Center

Osteocytes reside as three-dimensionally（3D） networked cells in the lacunocanalicular structure of bones and regulate bone and mineral homeostasis. Despite of their important regulatory roles, in vitro studies of osteocytes have been challenging because：（1） current cell lines do not sufficiently represent the phenotypic features of mature osteocytes and（2） primary cells rapidly differentiate to osteoblasts upon isolation. In this study, we used a 3D perfusion culture approach to：（1） construct the 3D cellular network of primary murine osteocytes by biomimetic assembly with microbeads and（2） reproduce ex vivo the phenotype of primary murine osteocytes, for the first time to our best knowledge. In order to enable 3D construction with a sufficient number of viable cells, we used a proliferated osteoblastic population of healthy cells outgrown from digested bone chips. The diameter of microbeads was controlled to：（1） distribute and entrap cells within the interstitial spaces between the microbeads and（2） maintain average cell-to-cell distance to be about 19 mm. The entrapped cells formed a 3D cellular network by extending and connecting their processes through openings between the microbeads. Also, with increasing culture time, the entrapped cells exhibited the characteristic gene expressions（SOST and FGF23） and nonproliferative behavior of mature osteocytes. In contrast, 2D-cultured cells continued their osteoblastic differentiation and proliferation. This 3D biomimetic approach is expected to provide a new means of：（1） studying flow-induced shear stress on the mechanotransduction function of primary osteocytes,（2） studying physiological functions of 3D-networked osteocytes with in vitro convenience,and（3） developing clinically relevant human bone disease models.

关键词： cell Figure Ex vivo 3D osteocyte network construction with primary murine bone cells bone

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Carcinomatous meningitis due to gastric adenocarcinoma:A rare presentation of relapse

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World Journal of Gastrointestinal Oncology 2014年第12期6卷 450-453页

作者： Nibal Saad Ahmad Alsibai Tarik H Hadid Department of Internal Medicine St. John Hospital and Medical Center Department of internal medicine Division of oncology St. John Hospital and Medical Center

While solid tumors are less commonly associated with meningeal involvement; lung, breast and melanoma are the ones most often reported. A few case reports have included gastric carcinoma but these are rare and most often associated with systemic disease at the time of diagnosis. Here we report a unique presentation of gastric carcinoma relapse with leptomeningeal carcinomatosis. An 81-year-old female was diagnosed with gastric cancer approximately one year before presentation. Following neoadjuvant chemotherapy, she had gastrectomy. Her periodic surveillance was stable. Thereafter she presented with a one week history of progressive fatigue lightheadedness, syncope. During hospitalization her mental status deteriorated. A repeat computed axial tomography scan of the head showed no changes to suggest an etiology. A lumbar puncture was performed and cerebral spinal fluid(CSF) cytopathology confirmed gastric signet cell adenocarcinoma. Encephalopathy was likely caused by increased intracranial pressure from communicating *** carcinomatosis is associated with short life expectancy. Therapeutic lumbar punctures and best supportive care or systemic therapy can be applied with guarded prognosis. Survival, however, may improve with cytologic negative conversion of the CSF if patient performance status allows treatment.

关键词： Gastric cancer Gastric adenocarcinoma Leptomenigeal carcinomatosis Signet cell adenocarcinoma Carcinomatous meningitis

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A novel gene——samfR involved in early stage of Streptomyces ansochromogenes differentiation

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Science China(Life Sciences) 1999年第6期42卷 570-576页

作者：田宇清刘钢聂丽平贾君永谭华荣 K.F.Chater john Innes center Norwich England

A 4.6 kb DNA fragment was cloned from the DNA library of Streptomyces ansochromogenes using a partial DNA fragment located in the downstream of promoter-PTH4 as probe. The experiments revealed that this DNA fragment consists of sawD gene and a 1.4 kb Pvu II fragment which can accelerate mycelium formation of S. ansochromogenes. The nucleotide sequence of 1.4 kb DNA fragment was determined and analysed; the result indicated that the fragment contains one complete open reading frame (ORF) which encodes a protein with 213 amino acids, and this gene was designated as samfR. The deduced protein has 36% amino acid identities and 52% amino acid similarities in comparison with that encoded by hppR gene, which is involved in the regulation of catabolism for 3-(3-hydroxyphenyl) propionate (3HPP) in Rhodococcus gtoberulus . The function of samfR gene was studied using strategy of gene disruption, and the resulting samfR mutant failed to form aerial hyphae and spores, its development and differentiation stopped at the stage of substrate mycelium in contrast with wild type strain. The results showed that the samfR gene is closely related to S. ansochromogenes differentiation.

关键词： Streptomyces differentiation samfR gene disruption.

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Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

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Cushing’s syndrome caused by an ACTH-producing large cell neuroendocrine carcinoma of the gallbladder

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World Journal of Gastrointestinal Oncology 2010年第1期2卷 56-58页

作者： Dagmar Lin Nuntra Suwantarat Sandi Kwee Michelle Miyashiro Department of Internal Medicine and john A.Burns School of Medicine University of Hawaii Department of Nuclear Medicine Queens Medical Center Department of Oncology Queens Medical Center

Malignancies of the gallbladder, including neuroendocrine tumors, are uncommon, mostly found incidentally after cholecystectomy and are frequently asymptomatic in the early stages, but highly fatal. Limited data is available on adrenocorticotropic hormone (ACTH) producing neuroendocrine tumors specifically originating from the gallbladder. We report the clinical and radiographic findings, which included positron emission tomography and computed tomography, of a patient with a gallbladder mass who presented with Cushing’s syndrome. Subsequently, a diagnosis of ACTH-producing large cell neuroendocrine carcinoma of the gallbladder was made. Despite being rare and having a poor prognosis, hormone-producing neuroendocrine tumors should be part of the differential diagnosis in the approach of patients with Cushing’s syndrome.

关键词： Adrenocorticotropic hormone Cushing’s syndrome Neuroendocrine Carcinoma Gallbladder

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Management of gastrointestinal bleed in the intensive care setting,an updated literature review

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World Journal of Critical Care Medicine 2025年第1期14卷 20-41页

作者： Vignesh K Nagesh Sai Priyanka Pulipaka Ruchi Bhuju Emelyn Martinez Shruthi Badam Gomathy Aarthy Nageswaran Hadrian Hoang-Vu Tran Daniel Elias Charlene Mansour Jaber Musalli Sanket Bhattarai Lokeash Subramani Shobana Tannishtha Sethi Ritvik Sethi Namrata Nikum Chinmay Trivedi Amer Jarri Colin Westman Nazir Ahmed Shawn Philip Simcha Weissman Jonathan Weinberger Ayrton I Bangolo Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Internal Medicine University of Arkansas for Medical SciencesLittle RockAR 72205United States Department of Internal Medicine Hackensack Palisades Medical CenterNorth BergenNJ 07047United States Department of Gastroenterology Hackensack University Medical CenterHackensackNJ 07061United States Department of Pulmonology and Critical Care HCA Florida Bayonet Point HospitalHudsonFL 34667United States Department of Hematology&Oncology John Theurer Cancer Center at Hackensack University Medical CenterHackensackNJ 07601United States

Gastrointestinal(GI)bleeding is a critical and potentially life-threatening condition frequently observed in the intensive care unit(ICU).This literature review consolidates current insights on the epidemiology,etiology,management,and outcomes of GI bleeding in critically ill *** bleeding remains a significant concern,especially among patients with underlying risk factors such as coagulopathy,mechanical ventilation,and renal *** GI bleeding in the ICU requires a multidisciplinary approach,including resuscitation,endoscopic intervention,pharmacologic therapy,and sometimes surgical *** with enhanced management strategies,GI bleeding in the ICU is associated with considerable morbidity and mortality,particularly when complicated by multi-organ *** review reiterates the need for adequate resuscitation and interventions in managing GI bleeding in critically ill patients,aiming to enhance survival rates and improve the quality of care within the ICU setting.

关键词： Gastrointestinal bleed Varices Variceal bleeding Diverticular bleed Angiodysplasia Ulcer Hemorrhoids Endoscopy Enteroscopy Embolization

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Impact of gut microbiome in the development and treatment of pancreatic cancer:Newer insights

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World Journal of Gastroenterology 2023年第25期29卷 3984-3998页

作者： Ayrton I Bangolo Chinmay Trivedi Ishan Jani Silvanna Pender Hirra Khalid Budoor Alqinai Alina Intisar Karamvir Randhawa Joseph Moore Nicoleta De Deugd Shaji Faisal SuchithBoodgere Suresh Parva Gopani Vignesh K Nagesh Tracy Proverbs-Singh Simcha Weissman Department of Internal Medicine Palisades Medical CenterNorth BergenNJ 07047United States Department of Gastrointestinal Malignancies John Theurer Cancer CenterHackensackNJ 07601United States

The gut microbiome plays an important role in the variation of pharmacologic *** aspect is especially important in the era of precision medicine,where understanding how and to what extent the gut microbiome interacts with drugs and their actions will be key to individualizing *** impact of the composition of the gut microbiome on the efficacy of newer cancer therapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell treatment has become an active area of *** adenocarcinoma(PAC)has a poor prognosis even in those with potentially resectable disease,and treatment options are very *** studies have concluded that there is a synergistic effect for immunotherapy in combination with cytotoxic drugs,in the treatment of PAC.A variety of commensal microbiota can affect the efficacy of conventional chemotherapy and immunotherapy by modulating the tumor microenvironment in the treatment of *** review will provide newer insights on the impact that alterations made in the gut microbial system have in the development and treatment of PAC.

关键词： Pancreatic cancer Gut microbiome Chemotherapy Dysbiosis Intratumoral microbiome Gut flora

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Autologous tissue patch rich in stem cells created in the subcutaneous tissue

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World Journal of Stem Cells 2015年第8期7卷 1127-1136页

作者： Ignacio Garcia-Gomez Krishnamurthy P Gudehithlu Jose A L Arruda Ashok K Singh Division of Nephrology Hektoen Institute of Medicine john H.Stroger Jr.Hospital of Cook County Division of Nephrology Department of MedicineUniversity of Illinois Medical Center at Chicago and the Chicago VA Medical Center

AIM:To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair. METHODS: We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries:(1) a large-sized polyvinyl tube(L = 25 mm,internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair;(2) a fine polyvinyl tubing(L = 25 mm,internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and(3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted(1 or 2 per rat). The incisions were closed with silk sutures,and the animals were allowed to recover. In case of the polydextran gel slurry 5 m L of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination,histology,and histochemistry for organization,vascularity,and presence of mesenchymal stem cells(MSCs)(CD271+CD34+ cells). RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension gave rise to a b

关键词： Autologous tissue patch Foreign body Subcutaneous

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