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Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms

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Bioactive Materials 2023年第8期26卷 52-63页

作者： Nisakorn Yodsanit Takuro Shirasu Yitao Huang Li Yin Zain Husain Islam Alexander Christopher Gregg Alessandra Marie Riccio Runze Tang Eric William Kent Yuyuan Wang Ruosen Xie Yi Zhao Mingzhou Ye Jingcheng Zhu Yi Huang Nicholas Hoyt Mengxue Zhang John A.Hossack Morgan Salmon K.Craig Kent Lian-Wang Guo Shaoqin Gong Bowen Wang Department of Biomedical Engineering Wisconsin Institute for DiscoveryUniversity of Wisconsin-MadisonMadisonWI53715USA Department of Ophthalmology and Visual Sciences University of Wisconsin-MadisonMadisonWI53715USA Department of Surgery School of MedicineUniversity of VirginiaCharlottesvilleVA22908USA The Biomedical Sciences Graduate Program(BIMS) School of MedicineUniversity of VirginiaCharlottesvilleVA22908USA Department of Biomedical Engineering School of EngineeringUniversity of VirginiaCharlottesvilleVA22908USA school of medicine and Health Sciences George Washington UniversityWashingtonDC20052USA Department of Cardiac Surgery Michigan MedicineUniversity of MichiganAnn ArborMI48109USA

Abdominal aortic aneurysm(AAA)is a progressive aortic dilatation,causing~80%mortality upon ***,there is no approved drug therapy for *** repairs are invasive and risky and thus not recommended to patients with small AAAs which,however,account for~90%of the newly diagnosed *** is therefore a compelling unmet clinical need to discover effective non-invasive strategies to prevent or slow down AAA *** contend that the first AAA drug therapy will only arise through discoveries of both effective drug targets and innovative delivery *** is substantial evidence that degenerative smooth muscle cells(SMCs)orchestrate AAA pathogenesis and *** this study,we made an exciting finding that PERK,the endoplasmic reticulum(ER)stress Protein Kinase R-like ER Kinase,is a potent driver of SMC degeneration and hence a potential therapeutic ***,local knockdown of PERK in elastase-challenged aorta significantly attenuated AAA lesions in *** parallel,we also conceived a biomimetic nanocluster(NC)design uniquely tailored to AAA-targeting drug *** NC demonstrated excellent AAA homing via a platelet-derived biomembrane coating;and when loaded with a selective PERK inhibitor(PERKi,GSK2656157),the NC therapy conferred remarkable benefits in both preventing aneurysm development and halting the progression of pre-existing aneurysmal lesions in two distinct rodent models of *** summary,our current study not only establishes a new intervention target for mitigating SMC degeneration and aneurysmal pathogenesis,but also provides a powerful tool to facilitate the development of effective drug therapy of AAA.

关键词： Abdominal aortic aneurysm ER stress PERK Biomimetic nanomedicine Targeted delivery

(Phospho)creatine:the reserve and merry-go-round of brain energetics

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Neural Regeneration Research 2023年第2期18卷 327-328页

作者： Hong-Ru Chen Ton DeGrauw Chia-Yi Kuan Department of Neurosciences University of Virginia School of MedicineCharlottesvilleVAUSA Department of Pediatrics Division of NeurologyEmory UniversityAtlantaGAUSA

Creatine transporter(CrT)-deficiency,the most common form of the cerebral creatine deficiency syndromes,causes cognition impairments and severe reduction of the brain creatine(Cr)and phosphocreatine(PCr)levels,and responds poorly to oral Cr supplement as a treatment *** ca uses of cognitive impairments in CrT-deficient children remain *** recently use gene-targeting to create a mouse model of CrT-deficiency to assess the impacts of Cr/PCr deficiency on brain energetics and stress-adaptation responses(Chen et al.,2021).

关键词： impairment cerebral creatine

Autoimmune Hepatitis Induced after Treatment of Syphilitic Hepatitis

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Journal of Clinical and Translational Hepatology 2022年第1期10卷 174-177页

作者： Hasan Ali Taqi Rizvi Mumtaz Niazi Mark Galan Nikolaos Pyrsopoulos Department of Internal medicine Rutgers University New Jersey Medical SchoolNewarkNJUSA Edward Via College of osteopathic medicine SpartanburgSCUSA Division of Gastroenterology and Hepatology Rutgers University New Jersey Medical SchoolNewarkNJUSA Department of Pathology Immunology and Laboratory MedicineRutgers University New Jersey Medical SchoolNewarkNJUSA

We present a unique case of biopsy-proven syphilitic hepa-titis which presented as severe acute liver injury with sig-nificant elevation in aminotransferases and bilirubin,and improved with antibiotic ***,the patient re-turned weeks after initial presentation with new-onset acute liver injury and had developed hypergammaglobulinemia,positive autoantibody titers,and repeat liver biopsy dem-onstrating interface hepatitis,supporting a diagnosis of autoimmune *** had an otherwise unrevealing etiologic workup,and responded to glucocorticoid *** believe that syphilitic hepatitis and its treatment sub-sequently triggered an immunogenic response,leading to autoimmune *** hepatitis is a chronic liver disease thought to manifest as a result of predisposing genetic factors in combination with environmental insults,especially hepatotropic *** is a sexually transmitted disease caused by Treponema pallidum that has been associated with autoimmunity and the develop-ment of *** propose that in the setting of syphilitic hepatitis,a molecular mimicry event resulting from structural similarities between *** and liver antigens,as well as impaired regulatory T-cell function,led to the breakdown of immune tolerance and the onset of au-toimmune *** support this hypothesis,further mo-lecular analyses and case series are necessary to determine if syphilitic hepatitis and its treatment are risk factors for the onset of autoimmune *** hepatitis should be considered early as the cause of acute liver injury in susceptible patients with risk factors for the disease,as prompt recognition and appropriate treatment may prevent progression of liver injury and result in improved outcomes.

关键词： Autoimmune hepatitis Syphilis Molecular mimicry

Risk factors and strategies for prevention of depression, anxiety and eating disorders among adolescents during the coronavirus disease 2019 (COVID-19) pandemic: a review

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Global Health Journal 2023年第2期7卷 78-86页

作者： Rea Pillai Isha Patel Rajesh Balkrishnan Department of Public Health Sciences University of Virginia School of MedicineP.0.Box 800717 CharlottesvilleVirginiaVA 22908USA

The purpose of this review is to identify prevalent trends and risk factors in depression,anxiety,and eating disorders in the adolescent population in the post coronavirus disease 2019(COvID-19)*** examined the literature published on adolescent mental health since the COVID-19 *** chose to summarize studies published from 2019 to 2022,using bibliographic search *** developed criteria for selecting articles for our review using diagnostic indicators and *** health conditions such as depression,anxiety and eating disorders are commonly prevalent in this population and have shown increasing rates in the past three *** risk factors associated with these diagnoses include reduction in social interaction,increased workloads,routine shifts,sleep quality,social media usage and parental ***,sleep cycles,physical activity,and social media should all be considered as a part of prevention in this *** that seem to be successful include maintaining social ties and avoiding negative social media usage with harmful *** global public awareness,as well as parental awareness,through media campaigns,is critical to slowing the spread of mental health challenges in adolescents and teenagers in the post-COvID-19 era.

关键词： Coronavirus disease 2019(COVID-19) Mental health Teenagers Impact of mental health

Decellularized extracellular matrix mediates tissue construction and regeneration

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Frontiers of medicine 2022年第1期16卷 56-82页

作者： Chuanqi Liu Ming Pei Qingfeng Li Yuanyuan Zhang Department of Plastic and Burn Surgery West China HospitalSichuan UniversityChengdu 610041China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Stem Cell and Tissue Engineering Laboratory Department of OrthopaedicsWest Virginia UniversityMorgantownWV 26506USA Wake Forest Institute for Regenerative medicine Wake Forest University Health SciencesWinston-SalemNC 27109USA

Contributing to organ formation and tissue regeneration,extracellular matrix(ECM)constituents provide tissue with three-dimensional(3D)structural integrity and cellular-function *** the crucial traits of the cellular microenvironment,ECM substitutes mediate cell–matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in ***,these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D *** cells also produce rich ECM,particularly stromal *** ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as *** better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select,produce,and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo ***,the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are ***,current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

关键词： decellularized extracellular matrix 3D culture organoids tissue repair

Hepatic Adenoma Secondary to Long-Term Oral Contraception Use in a Young Female

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Open Journal of Internal medicine 2023年第2期13卷 104-113页

作者： Kelsey M. Lamb Jessica E. Darden Suresh G. Jayatilaka Edward Via College of osteopathic medicine in virginia Blacksburg USA Department of Gastroenterology Southern Gastroenterology Associates St. Georges University School of Medicine St. Georges Grenada

Hepatic adenomas are a rare byproduct of oral contraceptive pill (OCP) use. Laboratory workup is often inconclusive. Diagnosis can be made via MRI;however, select cases may require further testing such as fine needle aspiration or core needle biopsy. We report a case of a 36-year-old female who was referred to gastroenterology for further evaluation of several liver lesions found incidentally on imaging. Due to risk factors, such as age, long-term oral contraceptive use and obesity, adenoma was high on the differential. Although infrequent, this case emphasizes the importance of a detailed history, including medication review, and physical examination.

关键词： Hepatic Adenoma Oral Contraceptives Liver Lesion

Clinical characteristics and outcomes of COVID-19 in patients with autoimmune hepatitis:A population-based matched cohort study

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World Journal of Hepatology 2023年第1期15卷 68-78页

作者： Arunkumar Krishnan Ruhee A Patel Yousaf Bashir Hadi Diptasree Mukherjee Sarah Shabih Shyam Thakkar Shailendra Singh Tinsay A Woreta Saleh A Alqahtani Section of Gastroenterology and Hepatology West Virginia University School of MedicineMorgantownWV 26505United States Division of Gastroenterology and Hepatology Johns Hopkins University School of MedicineBaltimoreMD 21287United States Department of medicine Apex Institute of Medical ScienceKolkata 700075West BengalIndia Liver Transplant Center King Faisal Specialist Hospital and Research CenterRiyadh 12713Saudi Arabia

BACKGROUND Patients with autoimmune hepatitis(AIH)require life-long immunosuppressive agents that may increase the risk of poor coronavirus disease 2019(COVID-19)*** is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe *** To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with *** We conducted a population-based,multicenter,propensity score-matched cohort study with consecutive adult patients(≥18 years)diagnosed with COVID-19 using the TriNeTx research network *** outcomes of patients with AIH(main group)were compared to a propensity score-matched cohort of patients:(1)Without chronic liver disease(CLD);and(2)Patients with CLD except AIH(non-AIH CLD)control *** patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding *** primary outcome was all-cause mortality,and secondary outcomes were hospitalization rate,need for critical care,severe disease,mechanical ventilation,and acute kidney injury(AKI).For each outcome,the risk ratio(RR)and confidence intervals(CI)were calculated to compare the association of AIH with the *** We identified 375 patients with AIH,1647915 patients with non-CLD,and 15790 patients with non-AIH CLD with COVID-19 *** to non-CLD patients,the AIH cohort had an increased risk of all-cause mortality(RR=2.22;95%CI:1.07-4.61),hospitalization rate(RR=1.78;95%CI:1.17-2.69),and severe disease(RR=1.98;95%CI:1.19-3.26).The AIH cohort had a lower risk of hospitalization rate(RR=0.72;95%CI:0.56-0.92),critical care(RR=0.50;95%CI:0.32-0.79),and AKI(RR=0.56;95%CI:0.35-0.88)compared to the non-AIH CLD *** Patients with AIH are associated with increased hospitalization risk,severe disease,and all-cause mortality compared to patients without pre-existing CLD from the diagnosis of ***,p

关键词： Autoimmune hepatitis SARS-CoV-2 COVID-19 Mortality Outcomes Liver disease Severe

CCL17 exerts neuroprotection through activation of CCR4/mTORC2 axis in microglia after subarachnoid haemorrhage in rats

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Stroke & Vascular Neurology 2023年第1期8卷 4-16页

作者： Anke Zhang Yibo Liu Houshi Xu Zeyu Zhang Xiaoyu Wang Ling Yuan Cameron Lenahan Chuan Zhang Junkun Jiang Chaoyou Fang Yuanjian Fang Jianmin Zhang Sheng Chen Department of Neurosurgery Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina Clinical Research Center for Neurological Diseases of Zhejiang Province HangzhouZhejiangChina Department of Neurosurgery Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Biomedical Sciences Burrell College of Osteopathic MedicineLas CrucesNew MexicoUSA Department of Biology Tongji UniversityShanghaiChina

Background and purpose C-C motif chemokine ligand 17(CCL17)presents an important role in immune regulation,which is critical in the pathophysiology of brain injury after subarachnoid haemorrhage(SAH).There is rare evidence to illustrate the function of CCL17 towards *** this study,we try to reveal the therapeutic effects of CCL17 and its underlying mechanism in rat SAH *** SAH rat models were assigned to receive recombinant CCL17(rCCL17)or phosphate buffer saline(PBS).AZD2098 and JR-AB2-011 were applied to investigate the C-C motif chemokine receptor 4(CCR4)/mammalian target of rapamycin complex 2(mTORC2)axis in CCL17-mediated *** elucidate the underlying mechanism,the in vitro kinase assay was performed in primary ***-specific Rictor knockdown was administered via intracerebroventricular injection of adenovirus-associated *** water content,short-term neurobehavioural evaluation,western blot analysis,quantitative RT-PCR and histological staining were *** The expression of CCL17 was increased and secreted from neurons after oxyhaemoglobin *** rCCL17 significantly alleviated neuronal apoptosis,and alleviated short-term neurofunction after SAH in *** addition,rCCL17 increased M2-like polarisation of microglia in rats post-SAH and in primary microglia *** neuroprotection of rCCL17 was abolished via inhibition of either CCR4 or *** CCL17 activated the CCR4/mTORC2 axis in microglia,which can alleviate SAH-induced neurological deficits by promoting M2-like polarisation of microglia.

关键词： CCL17 CCR4 mTORC2

Antitangling and manufacturable Fog Harps for high‐efficiency water harvesting

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Droplet 2023年第4期2卷 38-44页

作者： Jimmy K.Kaindu Kevin R.Murphy Nicholas G.Kowalski Alexandra N.Jones Matthew Davis Fleming Brook S.Kennedy Jonathan B.Boreyko Department of Mechanical Engineering Virginia TechBlacksburgVirginiaUSA Department of Biomedical Engineering and Mechanics Virginia TechBlacksburgVirginiaUSA school of Architecture and Design Virginia TechBlacksburgVirginiaUSA Samscreen Inc. ConklinNew YorkUSA

Fog Harps harvest substantially more water than conventional mesh‐based ***,to date,all large‐scale Fog Harps have been impractically hand‐wound at low wire tensions and suffer from elastocapillary wire ***,we develop large‐scale and high‐tension Fog Harps that are manufacturable and *** Fog Harps retain the record‐setting fog harvesting efficiency(η≈17%)of their optimized scale‐model counterparts,while uniquely enabling practical real‐life *** was achieved by adapting the industrial process for making harp screens,a pre‐existing technology used for screening solid *** critical tension required to minimize wire tangling was rationalized by an improved elastocapillary tangling model.

关键词： harvesting capillary rational