scholarly journals The protective effects of Olmesartan against interleukin-29 (IL-29)-induced type 2 collagen degradation in human chondrocytes

Bioengineered ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 1802-1813
Author(s):  
Yunlong Liu ◽  
Junyi Liu ◽  
Yan Ma ◽  
Yongyong Zhang ◽  
Qiong Chen ◽  
...  
2019 ◽  
Vol 15 (5) ◽  
pp. 349-356 ◽  
Author(s):  
Angus Gill ◽  
Stephen P. Gray ◽  
Karin A. Jandeleit-Dahm ◽  
Anna M.D. Watson

Background: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. Conclusion: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds.


2002 ◽  
Vol 70 (12) ◽  
pp. 6715-6725 ◽  
Author(s):  
D. F. Hoft ◽  
C. S. Eickhoff

ABSTRACT Chagas' disease results from infection with Trypanosoma cruzi, a protozoan parasite that establishes systemic intracellular infection after mucosal invasion. We hypothesized that ideal vaccines for mucosally invasive, intracellular pathogens like T. cruzi should induce mucosal type 2 immunity for optimal induction of protective secretory immunoglobulin A (IgA) and systemic type 1 immunity protective against intracellular replication. However, differential mucosal and systemic immune memory could be difficult to induce because of reciprocal inhibitory actions between type 1 and type 2 responses. To test our hypotheses, we investigated the protective effects of type 1 and type 2 biased vaccines against mucosal and systemic T. cruzi challenges. Intranasal vaccinations were given with recombinant interleukin-12 (IL-12)- and IL-4-neutralizing antibody (Ab) for type 1 immune bias, or recombinant IL-4 and gamma interferon-neutralizing Ab for type 2 immune bias. Cytokine RNA and protein studies confirmed that highly polarized memory immune responses were induced by our vaccination protocols. Survival after virulent subcutaneous T. cruzi challenge was used to assess systemic protection. Mucosal protection was assessed by measuring the relative inhibition of parasite replication in mucosal tissues early after oral T. cruzi challenge, using both PCR and quantitative culture techniques. As expected, only type 1 responses protected against systemic challenges (P < 0.01). However, contrary to our original hypothesis, type 1 responses optimally protected against mucosal challenges as well (P < 0.05). Type 1 and type 2 biased vaccines induced similar secretory IgA responses. We conclude that future vaccines for T. cruzi and possibly other mucosally invasive, intracellular pathogens should induce both mucosal and systemic type 1 immunity.


Author(s):  
Manouchehr Nakhjavani ◽  
Mehrnaz Imani ◽  
Mehrdad Larry ◽  
Arash Aghajani-Nargesi ◽  
Afsaneh Morteza ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V.O Baris ◽  
B Dincsoy ◽  
E Gedikli ◽  
A Erdem

Abstract Introduction Sotalol (SOT) is a Class 3 antiarrhythmic drug and commonly used for various arrhythmia treatments. However; it can prolong QT interval and lead to malignant arrhythmias. Empagliflozin is a selective SGLT-2 inhibitor used in the treatment of Type 2 diabetes and has been shown to have positive effects on cardiovascular outcomes. Since the effect of empagliflozin (EMPA) on potassium channel activation is not yet known, there is no recommendation for the concomitant use of these drugs. Purpose In this study, we aimed to evaluate possible protective effects of empagliflozin in sotalol induced QT prolongation. Materials and methods Twenty-four male Wistar Alba rats were randomized into four groups. The first (control) group (n: 6) received only serum physiologic (1ml) via orogastric gavage (OG). The second (EMPA) group (n: 6) received EMPA (10 mg/kg) via OG. The third (SOT) group (n: 6) received SOT (80 mg/kg) via OG. The fourth (EMPA+SOT) group (n: 6) received EMPA (10 mg/kg) and SOT (80 mg/kg) via OG. Under anesthesia; PR, QT intervals and heart rate (HR) were measured and QTc value was also calculated at second hour on lead II using electrocardiogram (ECG). Results In the SOT group; QT intervals, T wave durations and QTc values were found to be statistically longer than the control group, whereas HR was found to be lower than the control group (p&lt;0.01). In the EMPA+SOT group; QT intervals, T wave durations and QTc values were significantly lower and HR was significantly higher compared to the SOT group (p&lt;0.001, p&lt;0.01, p&lt;0.001, p&lt;0.001 respectively) (Table) Conclusion In the present study, we detected that EMPA significantly ameliorates SOT induced QT prolongation. In addition to this, we have also shown that EMPA can be used safely with SOT in clinical practice. With more clinical trials, the routine use of EMPA may be suggested to prevent QTc prolongation in diabetic patients receiving SOT. Finally; our study indicates that EMPA can effect on potassium channels. Funding Acknowledgement Type of funding source: None


2018 ◽  
Vol 132 (5) ◽  
pp. 581-593 ◽  
Author(s):  
Douglas M. Bennion ◽  
Chad H. Jones ◽  
Alex N. Dang ◽  
Jacob Isenberg ◽  
Justin T. Graham ◽  
...  

Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor (AT2 receptor) agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular (ICV) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2 receptor agonists are blood–brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1 (ET-1)-induced ischemic stroke. The results obtained from the present study indicated that C21 applied N2B entered the cerebral cortex and striatum within 30 min in amounts that are therapeutically relevant (8.4–9 nM), regardless of whether BBB was intact or disintegrated. C21 was first applied N2B at 1.5 h after stroke indeed provided neuroprotection, as evidenced by a highly significant, 57% reduction in cerebral infarct size and significant improvements in Bederson and Garcia neurological scores. N2B-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2 receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective in certain human central nervous system diseases, the N2B application of AT2 receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.


2014 ◽  
Vol 33 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Ying-Ju Chen ◽  
Ding-Cheng Chan ◽  
Kuo-Cheng Lan ◽  
Ching-Chia Wang ◽  
Chang-Mu Chen ◽  
...  

2022 ◽  
Vol 8 ◽  
Author(s):  
Fangyu Yan ◽  
Ehab S. Eshak ◽  
Kokoro Shirai ◽  
Jia-Yi Dong ◽  
Isao Muraki ◽  
...  

The evidence on the protective effects of soy foods against type 2 diabetes has been inconsistent. We thought to examine the association between the dietary intakes of soy and the risk of diabetes in a prospective study encompassing 21,925 healthy Japanese men and women aged 40–79 years. A validated self-administered food frequency questionnaire determined the intakes of soy, and their associations with risk of type 2 diabetes were evaluated by the logistic regression analysis. During the 5-year follow-up period, we observed 593 new cases of type 2 diabetes (302 in men and 291 in women). There was no association between dietary intakes of soy foods and the risk of type 2 diabetes among men. Whereas among women, higher tofu intake was inversely associated with risk of type 2 diabetes; the multivariable odds ratios (ORs) of type 2 diabetes were 0.92 (95% CI: 0.69–1.21) for 3–4 times per week and 0.67 (95% CI: 0.49–0.94) for almost daily (p-trend = 0.03) in reference to those consuming tofu less than 3 times per week. Intakes of boiled beans and miso soup were not associated with the risk in both genders. The inverse association tended to be more evident among overweight women and postmenopaused women. In conclusion, the frequency of tofu intake was inversely associated with the risk of type 2 diabetes among women.


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