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The effects of single versus combined therapy using LIM-kinase 2 inhibitor and type 5 phosphodiesterase inhibitor on erectile function in a rat model of cavernous nerve injury-induced erectile dysfunction

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Asian Journal of Andrology 2019年第5期21卷 493-500页

作者： Min Chui Cho Junghoon Lee Juhyun Park Sohee Oh Ji Sun Chai Hwancheol Son Jae-Seung Paick Soo Woong Kim Department of Urology Seoul National University College of MedicineSMG-SNU Boramae Medical CenterSeoul 07061Korea Department of Urology Seoul National University College of MedicineSeoul National University HospitalSeoul 03080Korea Department of Biostatistics Seoul National University College of MedicineSMG-SNU Boramae Medical CenterSeoul 07061Korea

We aimed to determine whether combination of LIM-kinase 2 inhibitor(LIMK2i)and phosphodiesterase type-5 inhibitor(PDE5i)could restore erectile function through suppressing cavernous fibrosis and improving caver nous apoptosis in a rat model of cavernous nerve crush injury(CNCI).Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows:(1)sham surgery(Group S),(2)CNCI(Group I),(3)CNCI treated with daily intraperitoneal administration of 10.0 mg kg^-1 LIMK2i(Group I+L),(4)daily oral administration of 20.0 mg kg-1 udenafil,PDE5i(Group I+U),and(5)combined administration of 10.0 mg kg^-1 LIMK2i and 20.0 mg kg^-1 udenafil(Group I+L+U).Rats in Groups I+L,I+U,and I+L+U were treated with respective regimens for 2 weeks after *** 2 weeks after surgery,erectile response was assessed using *** tissues were processed for histological studies and western *** I showed lower intracavernous pressure(ICP)/mean arterial pressure(MAP),lower area under the curve(AUC)/MAP,decreased immunohistochemical staining for alpha-smooth muscle(SM)actin,higher apoptotic index,lower SM/collagen ratio,increased phospho-LIMK2-positive fibroblasts,decreased protein kinase B/endothelial nitric oxide synthase(Akt/eNOS)phosphorylation,increased LIMK2/cofilin phosphorylation,and increased protein expression of fibronectin,compared to Group *** all three treatment groups,erectile responses,protein expression of fibronectin,and SM/collagen ratio were *** I+L+U showed greater improvement in erectile response than Group I+*** content and apoptotic index in Groups I+U and I+L+U were improved compared to those in Group ***,Group I+L did not show a significant improvement in SM content or apoptotic *** number of phospho-LIMK2-positive fibroblasts was normalized in Groups I+L and I+L+U,but not in Group I+***/eNOS phosphorylation was improved in Groups I+U and I+L+U,but not in Group I+***2/cofilin phosphorylation was i

关键词： apoptosis erectile dysfunction fibrosis LIM kinase phosphodiesterase

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Mononeuropathy multiplex associated with systemic vasculitis:A case report

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World Journal of Clinical Cases 2021年第7期9卷 1741-1747页

作者： Hyun Jun Chae Jung Woo Kim Yae Lim Lee Jeong Hwan Park Sang Yoon Lee Department of Rehabilitation Medicine Seoul National University College of MedicineSeoul National University HospitalSeoul 07061South Korea Department of Pathology Seoul National University College of MedicineSMG-SNU Boramae Medical CenterSeoul 07061South Korea Department of Rehabilitation Medicine Seoul National University College of MedicineSMG-SNU Boramae Medical CenterSeoul 07061South Korea

BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis is *** herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex,rectal perforation and antiphospholipid syndrome(APS)presented with pulmonary *** SUMMARY A 61-year-old woman visited hospital with complaints of myalgia and occasional *** was initially diagnosed as proctitis and treated with antibiotics,however,there was no *** addition,she also complained right foot drop with hypesthesia,and left 2^(nd) and 3^(rd) finger tingling *** underwent nerve conduction study for evaluation,and it revealed sensorimotor polyneuropathy in the left arm and bilateral *** sural nerve biopsy strongly suggested vasculitic *** on nerve biopsy and clinical manifestation,she was diagnosed with vasculitis and treated with immunosuppressive *** treatment,sudden rectal perforation and pulmonary thromboembolism occurred,and further laboratory study suggested probable concomitant *** Hartmann operation was performed for rectal perforation,and anti-coagulation therapy was started for *** few cycles of immunosuppressive therapy,tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be *** Vasculitis can be presented with a variety of signs and symptoms,therefore,clinicians should always consider the possibility of diagnosis.

关键词： Systemic Vasculitis Peripheral nervous system diseases Mononeuropathies Antiphospholipid syndrome Pulmonary embolism Case report

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno Michael K.E.Schafer Sudena Wang Michael J.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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The Citron homology domain of MAP4Ks improves outcomes of traumatic brain injury

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Neural Regeneration Research 2025年第11期20卷 3233-3244页

作者： Xiaoling Zhong Wenjiao Tai Meng-Lu Liu Shuaipeng Ma Tianjin Shen Yuhua Zou Chun-Li Zhang Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTXUSA Hamon center for Regenerative Science and Medicine University of Texas Southwestern Medical CenterDallasTXUSA Peter O’Donnell Jr.Brain Institute University of Texas Southwestern Medical CenterDallasTXUSA

The mitogen-activated protein kinase kinase kinase kinases(MAP4Ks)signaling pathway plays a pivotal role in axonal regrowth and neuronal degeneration following *** targeting this pathway is beneficial to brain injury remains *** this study,we showed that adeno-associated virus-delivery of the Citron homology domain of MAP4Ks effectively reduces traumatic brain injury-induced reactive gliosis,tauopathy,lesion size,and behavioral *** inhibition of MAP4Ks replicated the ameliorative effects observed with expression of the Citron homology ***,the Citron homology domain acted as a dominant-negative mutant,impeding MAP4K-mediated phosphorylation of the dishevelled proteins and thereby controlling the Wnt/β-catenin *** findings implicate a therapeutic potential of targeting MAP4Ks to alleviate the detrimental effects of traumatic brain injury.

关键词： adeno-associated virus Citron homology Citron homology domain gene therapy mitogen-activated protein kinase kinase kinase kinases traumatic brain injury

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Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 590-595页

作者： Jinwoo Kang Sang Hyub Lee Jin Ho Choi Woo Hyun Paik Dong-Won Ahn Ji Bong Jeong Ji Kon Ryu Yong-Tae Kim Department of Internal Medicine and Liver Research Institute Seoul National University HospitalSeoul National University College of MedicineSeoulKorea Department of Internal Medicine SMG-SNU Boramae Medical CenterSeoulKorea

Background:Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer,and it is important to keep the stent patent as long as ***,few studies have compared stent patency in terms of chemotherapy in patients with pancreatic *** study aimed to evaluate the differences in stent patency in terms of recently evolving ***:Between January 2015 and May 2017,161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively *** relationship between chemotherapy and stent patency was ***,overall survival according to the treatment,risk factors for stent patency,and long-term adverse events were ***:Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy(conventional gemcitabine-based chemotherapy and folfirinox)(P<0.001).Furthermore,the folfirinox group showed the longest median stent patency and overall survival,with 283 days and 466 days,respectively(P<0.001)despite higher adverse events *** who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis(HR=0.26;95%CI:0.12–0.60;P=0.001).Conclusions:Compared with patients who received best supportive care only,patients who underwent chemotherapy after stent insertion had better stent *** prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy.

关键词： Stent patency Malignant distal biliary obstruction Pancreatic cancer Folfirinox Chemotherapy

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Role of inhibiting LIM-kinase2 in improving erectile function through suppression of corporal fibrosis in a rat model of cavernous nerve injury

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Asian Journal of Andrology 2018年第4期20卷 372-378页

作者： Juhyun Park Sung Yong Cho Kwanjin Park Ji Sun Chai Hwancheol Son Soo Woong Kim Jae-Seung Paick Min Chul Cho Department of Urology Seoul National University College of Medicine SMG-SNU Boramae Medical Center Seoul 03080 Korea Department of Urology Seoul Nationa University College of Medicine Seoul National University Hospital Seoul 07061 Korea

We evaluated whether LIM-kinase 2 inhibitor （LIMK2i） could improve erectile function by suppressing corporal fibrosis through the normalization of the Rho-associated coiled-coil protein kinase 1 （ROCK1）/LIMK2/Cofilin pathway in a rat model of cavernous nerve crush injury （CNCl）. Sixty 11-week-old male Sprague-Dawley rats were divided equally into five groups： sham surgery （S）, CNCl （I）, and CNCl treated with low-dose （L）, medium-dose （M）, and high-dose （H） LIMK2i. The L, M, and H groups were treated with a daily intraperitoneal injection of LIMK2i （2.5, 5.0, and 10.0 mg kg-1 body weight, respectively） for 1 week after surgery. The erectile response was assessed using electrostimulation at 1 week, postoperatively. Penile tissues were processed for Masson＇s trichrome staining, double immunofluorescence, and Western blot assay. Erectile responses in the H group improved compared with the I group, while the M group showed only partial improvement. A significantly decreased smooth muscle/collagen ratio and an increased content of fibroblasts positive for phospho-/IMK2 were noted in the I group. The M and H groups revealed significant improvements in histological alterations and the dysregulated LIMK2/Cofilin pathway, except for LIMK2 phosphorylation in the M group. The inhibition of LIMK2 did not affect the ROCK1 protein expression. The content of fibroblasts positive for phospho-LIMK2 in the H group returned to the level found in the S group, whereas it did not in the M group. However, the L group did not exhibit such improvements. Our data suggest that the inhibition of LIMK2, particularly with administration of 10.0 mg kg^-1 body weight LIMK2i, can improve corporal fibrosis and erectile function by normalizing the LIMK2/Cofilin pathway.

关键词： erectile dysfunction fibrosis LIM kinase penis prostatectomy

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Cellular models of stress resistance may pave ways to fight neurodegenerative diseases

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Neural Regeneration Research 2025年第9期20卷 2579-2580页

作者： Thu Nguyen Minh Pham Christian Behl Institute of Pathobiochemistry University Medical Center of the Johannes Gutenberg UniversityMainzGermany

Alzheimer's disease(AD),the most common form of neurodegeneration,is characterized by selective neuronal vulnerability and brain regionselective neuron *** entorhinal cortex and hippoc,ampal CA1 projection neurons are at greater risk in AD whereas other regions display resistance to ***,the cerebellum,a phylogenetically very old region,is affected only very late in the disease progression.

关键词： cortex resistance Alzheimer

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David J.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Effects of Bifidobacterium lactis BLa80 on fecal and mucosal flora and stem cell factor/c-kit signaling pathway in simulated microgravity rats

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World Journal of Gastroenterology 2025年第1期31卷 93-109页

作者： Ping Zhang Ying Zhu Pu Chen Tong Zhou Zhe-Yi Han Jun Xiao Jian-Feng Ma Wen Ma Peng Zang Ying Chen Graduate School Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Key Laboratory of Aerospace Nutrition and Food Engineering China Astronaut Research and Training CenterBeijing 100094China Department of Gastroenterology The Air Force Medical CenterBeijing 100142China Department of Blood Transfusion Air Force Medical CenterBeijing 100142China

BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility *** pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal ***,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal *** cells are the pacemakers of gastrointestinal *** To investigate the effects of Bifidobacterium lactis(***)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit *** The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 *** tail group was given *** BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/***&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and *** fecal flora and mucosal flora of rats in each group were detected by 16S *** Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic *** microgravity reduced the expressions of SCF and c-kit,and increased the express

关键词： Simulated microgravity Rat Intestinal flora Gastrointestinal motility Stem cell factor/c-kit signaling pathway

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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

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