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NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway
Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mous...
Source: Frontiers in Pharmacology - May 7, 2021 Category: Drugs & Pharmacology Source Type: research

Preclinical Evaluation of Fingolimod in Rodent Models of Stroke With Age or Atherosclerosis as Comorbidities
This study used a rigorous study design in normal male C57BL/6JOlaHsd mice and in mice with common stroke comorbidities to further evaluate the translational potential of fingolimod. Stroke was induced via middle cerebral artery electrocoagulation in 8–9-week old mice (young mice), 18 month old mice (aged mice), and in high-fat diet-fed 22-week old ApoE−/− mice (hyperlipidaemic mice). Recovery was evaluated using motor behavioural tests 3 and 7 days after stroke. Tissue damage was evaluated at 7 days. A lower dose of fingolimod, 0.5 mg/kg, but not 1 mg/kg, increased lesion size but decreased ipsilateral brain at...
Source: Frontiers in Pharmacology - July 13, 2022 Category: Drugs & Pharmacology Source Type: research

Orally Administered Crocin Protects Against Cerebral Ischemia/Reperfusion Injury Through the Metabolic Transformation of Crocetin by Gut Microbiota
Conclusion Collectively, pharmacokinetic and pharmacodynamic association studies provide evidence that the gut microbiota plays a vital role in the fate of crocin and crocetin in the gastrointestinal tract. In addition, the cross-interaction between gut microbiota and crocin might mediate the activation of the cerebral-protective effect of orally administered crocin. Ethics Statement This study was carried out in accordance with the recommendations of ‘Institutional Animal Research Committee guidelines, Animal Ethics Committee of China Pharmaceutical University.’ The protocol was approved by the ‘An...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

Preventable Cases of Oral Anticoagulant-Induced Bleeding: Data From the Spontaneous Reporting System
Conclusion: Our findings describe the most reported risk factors for preventability of oral anticoagulant-induced bleedings. These factors may be useful for targeting interventions to improve pharmacovigilance activities in our regional territory and to reduce the burden of medication errors and inappropriate prescription. Introduction Oral anticoagulant therapy is widely used for the prevention of stroke and systemic embolism in patients with atrial fibrillation, or for the prevention and treatment of deep vein thrombosis and pulmonary embolism (Raj et al., 1994; Monaco et al., 2017). Oral anticoagulants can be di...
Source: Frontiers in Pharmacology - April 29, 2019 Category: Drugs & Pharmacology Source Type: research

6-Bromoindirubin-3 ′-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver
In this study, we aimed to investigate the anti-aging effect, and molecular mechanism, of the novel anti-aging drug 6BIO on naturally aged mouse liver. Rapamycin, a well-known promising anti-aging drug that delays aging through mTOR-dependent autophagy (Zhou and Ye, 2018), was used as the positive control in the study. To our knowledge, this is the first study to demonstrate the effects of 6BIO treatment in models of natural aging. Our results indicated that 6BIO ameliorates the decline of liver function with age, including lipid metabolism disorder, and attenuates hepatocyte senescence in aged mice, as revealed by altera...
Source: Frontiers in Pharmacology - April 9, 2019 Category: Drugs & Pharmacology Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Nrf2 as a Potential Mediator of Cardiovascular Risk in Metabolic Diseases
Conclusion Activation of the Nrf2-dependent antioxidant system plays an important role in cell defense against oxidative stress damage, whereas the insufficiency of the Nrf2 system is associated with multiple aspects of the genesis and progression of metabolic diseases, posing a great risk to the cardiovascular system (Figure 1). The systemic increase of Nrf2 activity by several activators may be beneficial in the treatment of metabolic diseases. In addition, selective upregulation of Nrf2 genes may represent a potential therapy in obesity, diabetes and atherosclerosis. Looking to the future, experimental research that el...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Apelin-13 Suppresses Neuroinflammation Against Cognitive Deficit in a Streptozotocin-Induced Rat Model of Alzheimer ’s Disease Through Activation of BDNF-TrkB Signaling Pathway
Conclusion The data in this manuscript demonstrates that apelin-13 upregulates BDNF against STZ-induced congnitive impairment by suppressing glial cell activity and inflammatory factors release. This suggests apelin signaling may be a new target in the treatment of AD. Ethics Statement All experimental protocols were carried out according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals approved by the Central South University at XiangYa Animal Care and Use Committee. Author Contributions XqQ and LH conceived the study and contributed to its experimental design. HqL carried out the...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

The Pharmacological Action of Kaempferol in Central Nervous System Diseases: A Review
In conclusion, we suggest that KPF and some glycosylated derivatives (KPF-3-O-rhamnoside, KPF-3-O-glucoside, KPF-7-O-rutinoside, and KPF-4′-methyl ether) have a multipotential neuroprotective action in CNS diseases, and further studies may make the KPF effect mechanisms in those pathologies clearer. Future in vivo studies are needed to clarify the mechanism of KPF action in CNS diseases as well as the impact of glycosylation on KPF bioactivity.
Source: Frontiers in Pharmacology - January 13, 2021 Category: Drugs & Pharmacology Source Type: research

A Novel Creatinine-Based Equation to Estimate Glomerular Filtration Rate in Chinese Population With Chronic Kidney Disease: Implications for DOACs Dosing in Atrial Fibrillation Patients
Conclusion: Xiangya-s equation provides more accurate GFR estimates in Chinese CKD patients who need consecutive monitoring of renal function, which may assist clinicians in choosing appropriate drug dosages.
Source: Frontiers in Pharmacology - February 19, 2021 Category: Drugs & Pharmacology Source Type: research

Low-Dose Piperlongumine Rescues Impaired Function of Endothelial Progenitor Cells and Reduces Cerebral Ischemic Injury in High-Fat Diet-Fed Mice
In conclusion, low-dose piperlongumine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.
Source: Frontiers in Pharmacology - November 15, 2021 Category: Drugs & Pharmacology Source Type: research