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Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

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Neural Regeneration Research 2024年第2期19卷 350-354页

作者： Jerry Flores Jiping Tang department of Physiology&pharmacology Loma Linda University School of MedicineLoma LindaCAUSA

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical *** clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus *** evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic *** articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after ***2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully *** literature suggests that FPR2 may play a role in the stimulation of scavenger receptor *** receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix ***2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)*** this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

关键词： AnxA1 FPR2 GMH hematoma resolution hemorrhagic stroke M1 M2 microglia polarization microglia phagocytosis

Analysis of the combined effect of rs699 and rs5051 on angiotensinogen expression and hypertension

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Chronic Diseases and Translational medicine 2024年第2期10卷 102-117页

作者： Nicholas R.Powell Tyler Shugg Jacob Leighty Matthew Martin Rolf P.Kreutz Michael T.Eadon Dongbing Lai Tao Lu Todd C.Skaar Division of Clinical pharmacology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA department of pharmacology and Toxicology School of MedicineIndiana UniversityIndianapolisIndianaUSA department of Cardiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nephrology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA department of Medical and Molecular Genetics School of MedicineIndiana UniversityIndianapolisIndianaUSA

Background Hypertension(HTN)involves genetic variability in the renin-angiotensin system and influences antihypertensive *** previously reported that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p and rs699 A>G decreases reporter mRNA in the microRNA functional-assay *** AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT *** independent effect of these variants is understudied due to their LD therefore we aimed to test the hypothesis that increased AGT by rs5051 C>T counterbalances AGT decreased by rs699 A>G,and when these variants occur independently,it translates to HTN-related *** We used in silico,in vitro,in vivo,and retrospective models to test this *** In silico,rs699 A>G is predicted to increase miR-122-5p binding affinity by 3%.Mir-eCLIP results show rs699 is 40–45 nucleotides from the strongest microRNA-binding site in the AGT ***,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression ***-Tissue Expression(GTEx)and UK Biobank analyses demonstrate liver AGT expression and HTN phenotypes are not different when rs699 A>G occurs independently from rs5051 C>***,GTEx and the in vitro experiments suggest rs699 A>G confers cell-type-specific effects on AGT mRNA abundance,and suggest paracrine renal renin-angiotensin-system perturbations could mediate the rs699 A>G associations with *** We found that rs5051 C>T and rs699 A>G significantly associate with systolic blood pressure in Black participants in the UK Biobank,demonstrating a fourfold larger effect than in White *** studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>*** like this will help clinicians move beyond the use of race as a surrogate for genotype.

关键词： angiotensinogen genetic and genomic medicine hypertension rs699

Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

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World Journal of Gastroenterology 2024年第18期30卷 2387-2390页

作者： Aleksandra Boldys Lukasz Buldak department of Internal medicine and Clinical pharmacology School of Medicine in KatowiceMedical University of SilesiaKatowice 40-752Poland

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within *** redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated *** is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic *** challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic ***,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid ***,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic *** is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

关键词： Metabolic dysfunction-associated steatotic liver disease Diagnostics Pathophysiology of metabolic dysfunction-associated steatotic liver disease Therapy of metabolic dysfunction-associated steatotic liver disease Therapeutic innovations

Oleanonic acid inhibits glioma growth by inactivating STAT3 via upregulating SIRT6 in nude mice

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Food Science and Human Wellness 2024年

作者： Jiancun Wang Yuanyuan Wang Hui Gao Qin Sun Wen Li Neurosurgery department of the First Affiliated Hospital of Soochow university department of Neurosurgery， the Third Affiliated Hospital of Naval Medical university department of anesthesiology， General Hospital Of Eastern Theater Command department of pharmacology， school of medicine， shaoxing university

Patients with glioma have a very high mortality rate， thus improving the poor prognosis of glioma has been the goal in the therapeutic field. Searching for more effective drugs for gliomas from natural compounds is a promising strategy. In this study， both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1， but the former has a lower IC50 than the latter. Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5， and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells. Furthermore， knockdown of STAT3 expression inhibited proliferation and migration of glioma cells. Next， the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1， p-ERK1/2， p300 were increased by oleanonic acid. The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells. In addition， the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6. Furthermore， oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts， but not in nude mice bearing intracerebral SIRT6-knockdown U87 xenografts. In conclusion， oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.

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Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

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Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin Jinsong Bian department of pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina department of pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into ***,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell ***^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of *** re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological ***,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell *** recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's *** of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these *** this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell ***,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related *** potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

From the dust:extracellular vesicles as regulators of development and neuroregeneration

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Neural Regeneration Research 2024年第5期19卷 933-934页

作者： Leon G.Coleman Jr The university of North Carolina at Chapel Hill School of MedicineDepartment of PharmacologyBowles Center for Alcohol StudiesChapel HillNCUSA

First impressions can have a lasting *** science,this can be especially problematic,because our lack of understanding often causes us to mislabel and thus ignore important biological *** this vein,extracellular vesicles(EVs)were once considered to be“cellular dust”.Similar to the previous concept of“junk DNA”to describe protein non-coding regions,EVs are far more than just cellular *** fact,EVs are emerging as key mediators of intracellular communication across nearly all biological *** includes peripheral immune responses(e.g.,arthropathies and sepsis),intra-organ communication(Seim et al.,2023),and a host of other physiological and pathological states(Figure 1A and B).

关键词： Figure extracellular

Alzheimer's disease and low-dose radiation therapy:A new hope

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Radiation medicine and Protection 2024年第1期5卷 1-6页

作者： Neal E.Dunlap Robert P.Friedland Lu Cai department of Radiation Oncology University of Louisville School of MedicineLouisvilleKY40202USA department of Neurology The University of Louisville School of MedicineLouisvilleKY40202USA Pediatric Research Institute Departments of PediatricsPharmacology and ToxicologyUniversity of Louisville School of MedicineLouisvilleKY40202USA

The concept of low-dose radiation(LDR)-induced hormetic responses was initially observed approximately 70 years ago and systematically reviewed along with the discovery of LDR-induced adaptive responses in a cytogenetic in vitro study in *** the end of the 1990s,discussions regarding the potential applications of LDRinduced hormesis and adaptive responses for preventing or treating chronic diseases,such as Alzheimer’s disease(AD)had taken *** 2016,reports on radiotherapy for the subjects with AD and for genetic AD model mice were ***,several preclinical studies with animal models of AD and clinical studies in AD subjects were conducted.A significant milestone was achieved with the online availability of a new Systematic Review based on qualified publications from these preclinical and clinical *** mini-review provides a concise historical introduction to LDR-induced hormesis and adaptive responses with discussion of AD radiotherapy with either LDR or relatively high dose *** of this Systematic Review cover promising outcomes,challenges,and new questions,followed by discussion of potential mechanisms.

关键词： Alzheimer’s disease Low-dose radiation Radiation adaptive response Radiation hormesis

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

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World Journal of Clinical Cases 2024年第18期12卷 3555-3560页

作者： Ming-Hui Zhou Min-Feng Ye Zhen-Xing Zhang Feng Tao Yu Zhang department of Gastrointestinal Surgery Shaoxing People’s HospitalShaoxing 312000Zhejiang ProvinceChina school of medicine Shaoxing UniversityShaoxing 312000Zhejiang ProvinceChina

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse ***,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two *** the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse *** SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque *** sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable *** Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

关键词： Cytokine release syndrome Programmed death 1 blockade Sintilimab Psoriasis Gastric cancer Case report

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State Key Laboratory of Natural medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China department of Clinical pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1