检索结果-南通市图书馆

The bumpy road of purinergic inhibitors to clinical application in immune-mediated diseases

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第6期19卷 1206-1211页

作者： Matihias T.Wyss Christine Heuer Marina Herwerth Institute of pharmacology and toxicology University of Zurich Neuroscience Center Zurich (ZNZ) University of Zurich and ETH Zurich 3. Neurology Department University Hospital of Zurich

Purinergic signaling plays important roles throughout the body in the regulation of organ functions during and following the disruption of homeostasis. This is also reflected by the widespread expression of two families of purinergic receptors(P1 and P2) with numerous subtypes. In the last few decades, there has been increasing evidence that purinergic signaling plays an important role in the regulation of immune functions. Mainly, signals mediated by P2 receptors have been shown to contribute to immune system-mediated pathologies. Thus, interference with P2 receptors may be a promising strategy for the modulation of immune responses. Although only a few clinical studies have been conducted in isolated entities with limited success, preclinical work suggests that the use of P2 receptor inhibitors may bear some promise in various autoimmune diseases. Despite the association of P2 receptors with several disorders from this field, the use of P2 receptor antagonists in clinical therapy is still very scarce. In this narrative review, we briefly review the involvement of the purinergic system in immunological responses and clinical studies on the effect of purinergic inhibition on autoimmune processes. We then open the aperture a bit and show some preclinical studies demonstrating a potential effect of purinergic blockade on autoimmune events. Using suramin, a non-specific purinergic inhibitor, as an example, we further show that off-target effects could be responsible for observed effects in immunological settings, which may have interesting implications. Overall, we believe that it is worthwhile to further investigate this hitherto underexplored area.

关键词： autoimmune diseases neurological disorders P2 receptor inhibitors purinergic system suramin

Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第3期19卷 629-635页

作者： Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao State Key Laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina Academy of Medical Engineering and Translational Medicine Medical CollegeTianjin UniversityTianjinChina

Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

关键词： AAV9P1 astrocytes astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury

A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

在线全文

学校读者我要写书评

暂无评论

Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang State Key Laboratory of toxicology and Medical Countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China Tianjin University of Science and Technology Tianjin 300222China Hebei University of Science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa department of Critical Care Medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan department of Clinical toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural Institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan Division of toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular arrhythmias.We describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and vasopressors.Nine hours after arrival,an electrocardiogram revealed a return to sinus rhythm.The patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,respectively.On hospital day 15,he was transferred to a psychiatric hospital.The other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the root.Serum on admission contained 1.50 ng/mL of aconitine.Beyond hospital day 2,neither were detected.Urine on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day 3.CONCLUSION The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

Targeting NRP1 axis as a strategy for treating energy metabolism impairment induced by SARS-CoV-2 spike

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science China Life Sciences 2024年

作者： Lihui Zhang Wanting Hu Jingxuan Li Yuehan Li Feng Liu Wenyi Xiao Ning Jiang Zhiyong Xiao Lu Han Wenxia Zhou Beijing Institute of pharmacology & toxicology State Key Laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology & Toxicology School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine

Dear Editor,Free spike protein of SARS-CoV-2 alone can cause abnormal energy metabolism(Table S1 in Supporting Information), and limited research suggested a potential correlation between spike-induced mitochondrial damage and the ACE2 receptor(Lei et al., 2021; Yang et al., 2023). In order to further explore the mechanisms involved, we observed that the wild-type S1 protein of SARS-CoV-2 exerts a more potent inhibitory effect on host cell ATP compared to the wild-type S protein, S2protein, the Omicron variant S1 protein and HCoV-NL63 S1protein in HLMVEC and 293T cell lines(Figure 1A and B),indicating the importance of exploring the mechanism by which the S1 protein causes ATP decrease. Meanwhile, the S1protein did not lead to significant changes in cellular lactate levels, indicating that its primary mechanism involves impairing oxidative phosphorylation and mitochondrial damage(Figure 1C and D).

关键词：

Investigating epithelial-neuronal signaling contribution in visceral pain through colon organoid-dorsal root ganglion neuron co-cultures

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第6期19卷 1199-1200页

作者： Francesco Margiotia Lorenzo Di Cesare Mannelli Antonino Morabito Carla Ghelardini Elena Lucarini department of Neuroscience Psychology Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section University of Florence department of Neuroscience Psychology Drug Research and Child Health-NEUROFARBA University of Florence 3. Meyer Children's Hospital IRCCS

Abdominal pain is a common symptom associated with irritable bowel syndrome and inflammatory bowel diseases(IBDs), affecting about 20% of the global population(Grundy et al., 2019). Current pain therapies are poorly effective on visceral pain of intestinal origin and present several side effects, hence the need to identify novel molecular and cellular targets for drug development. The pathophysiology of visceral-abdominal pain,

关键词：

CRABP1-mediated non-canonical retinoic acid signaling in motor neurons and neural stem cells

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Neural Regeneration Research 2024年第6期19卷 1169-1170页

作者： Li-Na Wei department of pharmacology University of Minnesota Medical School

Retinoic acid(RA), the active metabolite of vitamin A(the retinoids), elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems(Corcoran et al., 2002). The effects of RA are mediated by two very distinct pathways; the first is manifested in the nucleus by binding to a large family of nuclear RA receptors(RARs) to regulate proper expression of RAtargeted genes,

关键词：

Sodium intake:a double-edged sword wielded by the brain

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2024年第7期67卷 1545-1547页

作者： Lingyu Xu Xiaolong Ma Yi Wang Zhong Chen Key Laboratory of Neuropharmacology and Pharmaceutical Sciences Zheiiang Chinese Medical UniversityHangzhou 310053China Institute of pharmacology&toxicology College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China

Taste receptors on the tongue discriminate between five fundamental tastes:sour,sweet,bitter,salty,and umami(Chandrashekar et al.,2006).Typically,stimuli that evoke bitterness and acidity prompt aversive responses by animals,whereas sweet and umami flavors are appetitive and enjoyable.Saltiness is unique in that it transitions from an appetitive to an aversive stimulus with increasing concentrations.

关键词： prompt sweet sword

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

在线全文

学校读者我要写书评

暂无评论

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 response.We 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 PASSPORT-seq.The AGT promoter variant rs5051 C>T is in linkage disequilibrium(LD)with rs699 A>G and increases AGT transcription.The 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 phenotypes.Methods We used in silico,in vitro,in vivo,and retrospective models to test this hypothesis.Results 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 mRNA.Unexpectedly,rs699 A>G increases AGT mRNA in an AGT-plasmid-cDNA HepG2 expression model.Genotype-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>T.However,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 HTN.Conclusions 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 participants.Further studies are warranted to determine if altered antihypertensive response in Black individuals might be due to rs5051 C>T or rs699 A>G.Studies 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