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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

Receptor for advanced glycation end-products axis and coronavirus disease 2019 in inflammatory bowel diseases:A dangerous liaison?

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World Journal of Gastroenterology 2021年第19期27卷 2270-2280页

作者： Armando Rojas Ivan Schneider Cristian Lindner Ileana Gonzalez Miguel Angel Morales medicine Faculty Catholic University of MauleTalca 3634000Chile Department of Molecular and clinical Pharmacology program Institute of Biomedical SciencesUniversity of ChileSantiago 8320000Chile

Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical *** the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of *** the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)*** soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.

关键词： COVID-19 Inflammatory bowel diseases Advanced glycation Angiotensinconverting enzyme 2 Alarmins Receptor for advanced glycation end-products Receptor for advanced glycation end-products axis Inflammation

Pathophysiological significance of increased α-synuclein deposition in sympathetic nerves in Parkinson’s disease: a post-mortem observational study

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Translational Neurodegeneration 2022年第1期11卷 737-746页

作者： Risa Isonaka Patti Sullivan David S.Goldstein Autonomic medicine Section Clinical Neurosciences ProgramDivision of Intramural ResearchNational Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMD 20892USA

Background: Parkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker;however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. Methods: We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innerva-tion) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease. Results: The PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocar-dial TH in the PD group was decreased by 65% compared to the control group (P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG. Conclusions: PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.

关键词： Synuclein Tyrosine hydroxylase Norepinephrine Immunofluorescence Parkinson Post-mortem

clinical curative effect of fuzi-cake-separated moxibustion for preventing dysuria after operation for lower limb fracture

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Journal of Traditional Chinese medicine 2014年第5期34卷 544-549页

作者： Yan Yue Lijun Tao Jianqiao Fang Qi Xie Shaofeng He Chunxia Huang Xueming Yang Acupuncture and Moxibustion Department of Xinchang County Traditional Chinese medicine Hospital Orthopedic Department of Xinchang County Traditional Chinese medicine Hospital Office of The 3rd clinical Medical College of Zhejiang Chinese medicine University academic Section of China Academy of Chinese Medical Sciences Office of Xinchang County Traditional Chinese medicine Hospital Special Laboratory of Xinchang County Traditional Chinese medicine Hospital

OBJECTIVE: To assess the clinical curative effect of fuzi-cake-separated moxibustion at Zhongji(CV 3)and Guanyuan(CV 4) for preventing dysuria after internal fixation of lower limb ***: Sixty patients conforming to the inclusion standards were randomly divided into a treatment group(n=30) and a control group(n=30).Fuzi-cake-separated moxibustion was performed at Guanyuan(CV 4) and Zhongji(CV 3), 20 min at a time, twice a day, for 3 days before operation in the treatment group. No fuzi-cake-separated moxibustion was performed in the control group. After treatment, the score for symptoms of first urination, urinary time, urinary volume, 24 h remaining urinary volume, incidence of uroschesis, and rate of controlling dysuria were compared to evaluate the curative effect of preventing post-operative ***: The score for symptoms of first urination,24 h remaining urinary volume(maximum 120 m L vs 250 m L, and less than 10 m L in 24 cases vs 15 cases), and the rate of controlling dysuria(83.34% vs30%) were significantly better(P0.05) between the two groups in first post-operative urinary time, urinary volume, or incidence of 24 h ***: Fuzi-cake-separated moxibustion at Zhongji(CV 3) and Guanyuan(CV 4) can better prevent post-operative dysuria, effectively promote the functional restoration of the urinary bladder,and control the incidence of post-operative dysuria.

关键词： Moxibustion Point Zhongji (CV 3) Point Guanyuan (CV 4) Lower extremity Fractures,bone Surgery Dysuria

Targeting resolvins in cholestatic liver injury

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 689-691页

作者： Luis AVidela Rodrigo Valenzuela Molecular and clinical Pharmacology program Institute of Biomedical ScienceSantiagoChile Department of Nutrition Faculty of MedicineUniversity of ChileSantiagoChile

In general terms,the acute inflammatory reaction in conditions of infection or tissue damage is a response of the immune system to cope with survival and return to ***,the reaction is initiated by edema followed by the progressive accumulation of polymorphonuclear leukocytes(PMN)and monocytes that differentiate into macrophages,with production of pro-inflammatory mediators such as leukotrienes(e.g.,LTB4)and prostaglandins(e.g.,PGE2,PGI2,PGF2),which in excess may progress to chronic inflammation(1).Considering that the acute inflammatory response is a protective and self-limited phenomenon,its resolution is an active programmed reaction that is set in by specific pro-resolving mediators(SPMs),which are derived from n-3 polyunsaturated fatty acids(n-3 PUFAs).

关键词： protective acute homeostasis

^(68)Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy

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Cancer Biology & medicine 2019年第1期16卷 157-165页

作者： Janice S.H.Tan Charles X.Y.Goh Yen Sin Koh Youquan Li Jeffrey K.L.Tuan Eu Tiong Chua Terence W.K.Tan Michael L.C.Wang Lui Shiong Lee Kae Jack Tay Ravindran Kanesvaran Chee Keong Toh Aaron K.T.Tong Winnie W.C.Lam Melvin L.K.Chua Division of Radiation Oncology National Cancer Centre Singapore Department of Nuclear medicine and Molecular Imaging Singapore General Hospital Radiological Sciences academic clinical programme Duke-NUS Medical School Oncology academic clinical programme Duke-NUS Medical School Department of Urology Singapore General Hospital Department of Surgery Sengkang General Hospital Division of Medical Oncology National Cancer Centre Singapore Division of Medical Sciences National Cancer Centre Singapore

Objective: Prostate cancers(PCa) in Asian individuals are molecularly distinct from those found in their Caucasian *** is no risk stratification tool for Asian men with rapid biochemical recurrence(BCR) following radical prostatectomy(Rad P). This study aims to assess the detection rate of ^(68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography(PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-Rad ***: ^(68)Ga PSMA-PET and CT body with/without bone scan [conventional workup(CWU)] were performed in 55 Asian patients with BCR within 36 months post-Rad P. Two blinded reviewers assessed the images. Detection rates of ^(68)Ga PSMAPET/CT were evaluated, and impact on management was reviewed by comparison with ***: Median time to BCR post-Rad P was 8.1 months. Detection rate for ^(68)Ga PSMA-PET/CT was 80%(44/55). A positive scan was significantly associated with increasing prostate-specific antigen(PSA) level [odds ratio(OR) = 1.13(95% CI 1.05–1.30), P =0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, ^(68)Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44(56.8%) patients: 10 to hormonal therapy(HT) and whole pelvis radiotherapy(RT) in addition to bed RT, and 15 to palliative HT ***: In the present report, we demonstrated the diagnostic and treatment decision utility of ^(68)Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels(< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

关键词： ^68Ga PSMA PET/CT prostate cancer Asian diagnostic recurrence prostatectomy salvage radiotherapy

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

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Neural Regeneration Research 2022年第10期17卷 2172-2178页

作者： Wei Zheng So Natalie Shi Qi Wong Hong Chang Tan Molly Tzu Yu Lin Isabelle Xin Yu Lee Jodhbir S.Mehta Yu-Chi Liu Yong Loo Lin School of medicine National University of SingaporeSingaporeSingapore Singapore Eye Research Institute SingaporeSingapore Department of Endocrinology Singapore General HospitalSingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CentreSingaporeSingapore Ophthalmology and Visual Sciences academic clinical program Duke-NUS Medical SchoolSingaporeSingapore

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,*** peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin ***,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic *** recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral *** this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and *** will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

关键词： corneal nerve quantification corneal nerves diabetic cornea diabetic corneal neuropathy diabetic microvascular complications diabetic peripheral neuropathy in vivo confocal microscopy neurotrophic keratopathy ocular surface

Recent advances in liver preconditioning: Thyroid hormone, n-3 long-chain polyunsaturated fatty acids and iron

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World Journal of Hepatology 2012年第4期4卷 119-128页

作者： Virginia Fernández Gladys Tapia Luis A Videla Molecular and clinical Pharmacology program Institute of Biomedical Sciences Faculty of Medicine University of Chile Casilla 70000 Santiago-7 Chile

Liver preconditioning (PC), defined as an enhanced tolerance to injuring stimuli induced by previous specific maneuvers triggering beneficial functional and molecular changes, is of crucial importance in human liver transplantation and major hepatic resection. For these reasons, numerous PC strategies have been evaluated in experimental models of ischemia-reperfusion liver injury, which have not been transferred to clinical application due to side effects, toxicity and difficulties in implementation, with the exception of the controversial ischemic PC. In recent years, our group has undertaken the assessment of alternate experimental liver PC protocols that might have application in the clinical setting. These include thyroid hormone (T3), n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA), or iron, which suppressed liver damage due to the 1 h ischemia-20 h reperfusion protocol. T3, n-3 LCPUFA and iron are hormetic agents that trigger biologically beneficial effects in the low-dose range, whose multifactorial mechanisms of action are discussed in the work.

关键词： Liver preconditioning Thyroid hormone n-3 polyunsaturated fatty acids Iron

PCSK9 and triglyceride-rich lipoprotein metabolism

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The Journal of Biomedical Research 2015年第6期29卷 429-436页

作者： Irena Druce Hussein Abujrad Teik Chye Ooi clinical Research Laboratory Division of Endocrinology and MetabolismDepartment of MedicineUniversity of Ottawa Chronic Disease program Ottawa Hospital Research InstituteThe Ottawa Hospital

Pro-protein convertase subtilisin-kexin 9 （PCSK9） is known to affect low-density lipoprotein （LDL） metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipopro- teins, especially triglyceride-rich lipoproteins （TRL）. This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of （1） a correlation between plasma PCSK9 and triglyceride （TG） levels in health and disease, （2） a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, （3） an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, （4） an effect of PCSK9 on postprandial lipemia, （5） an effect of PCSK9 on adipose tissue biology, （6） an effect of PCSK9 on apolipoprotein B production from the liver and intestines, （7） an effect of PCSK9 on receptors other than low density lipoprotein receptor （LDLR） that are involved in TRL metabolism, and （8） an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge.

关键词： hyperlipidemia hypercholesterolemia molecular biology