inflammatory pathways
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2022 ◽  
Author(s):  
Mona Dastgheib ◽  
Seyed Vahid Shetab-Boushehri ◽  
Maryam Baeeri ◽  
Mahdi Gholami ◽  
Mohammad Yahya Karimi ◽  
...  

Abstract Diabetic neuropathy (DN) is the most challenging microvascular complication of diabetes and there is no suitable treatment for it, so the development of new agents to relieve DN is urgently needed. Since oxidative stress and inflammation play an essential role in the development of DN, clearance of these factors are good strategies for the treatment of this disease. According to key role of cyclic adenosine monophosphate (cAMP) in the regulation of oxidative stress and inflammatory pathways, it seems that phosphodiesterase inhibitors (PDEIs) can be as novel drug targets for improving DN through enhancement of cAMP level. The aim of this study was to evaluate the effects of rolipram, a selective PDE4 inhibitor, and pentoxifylline, a general PDE inhibitor on experimental model of DN and also to determine the possible mechanisms involved in the effectiveness of these agents. We investigated the effects of rolipram (1mg/kg) and pentoxifylline (100 mg/kg) and also combination of rolipram (0.5 mg/kg) and pentoxifylline (50 mg/kg), orally for five weeks in rats that became diabetic by STZ (55 mg/kg, i.p.). After treatments, motor function was evaluated by open-field test, then rats were anesthetized and dorsal root ganglion (DRG) neurons isolated. Next, oxidative stress biomarkers and inflammatory factors were assessed by biochemical and ELISA methods, and RT-PCR analysis in DRG neurons. Rolipram and/or pentoxifylline treatment significantly attenuated DN – induced motor function deficiency by modulating distance moved and velocity. Rolipram and/or pentoxifylline treatment dramatically increased the cAMP level, as well as suppressed DN – induced oxidative stress which was associated with decrease in LPO and ROS and increase in TAC, total thiol, CAT and SOD in DRG neurons. On the other hand, the level of inflammatory factors (TNF-α, NF-kB and COX2) significantly decreased following rolipram and/or pentoxifylline administration.The maximum effectiveness was with rolipram and/or pentoxifylline combination on mentioned factors.These findings provide novel experimental evidence for further clinical investigations on rolipram and pentoxifylline combination for the treatment of DN.


Author(s):  
Habib Zouali ◽  
Juliette Lemasson ◽  
Andreea Calugareanu ◽  
Christophe Battail ◽  
David Michonneau ◽  
...  

Cutaneous involvement of chronic graft-versus-host disease (cGVHD) has a wide range of manifestations including a lichenoid form with a currently assumed mixed Th1/Th17 signature and a sclerotic form with Th1 signature. Despite substantial heterogeneity of innate and adaptive immune cells recruited to the skin and of the different clinical manifestations, treatment depends mainly on the severity of the skin involvement, and relies on systemic, high-dose glucocorticoids alone or in combination with a calcineurin inhibitor. We performed the first study using RNAseq to profile and compare the transcriptome of lichen planus cGVHD (n=8), morphea cGVHD (n=5), and healthy controls (n=6). Our findings revealed shared and unique inflammatory pathways to each cGVHD subtype that are both pathogenic and targetable. In particular, the deregulation of IFN signaling pathway was strongly associated with cutaneous cGVHD, whereas the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway was found to be specific of lichen planus and likely contributes to its pathogenesis. The results were confirmed at a protein level by performing immunohistochemistry staining and at a transcriptomic level using Real-Time quantitative PCR.


Author(s):  
Priya Nijhawan ◽  
Tapan Behl ◽  
Sridevi Chigurupati ◽  
Aayush Sehgal ◽  
Sukhbir Singh ◽  
...  

2022 ◽  
Vol 12 ◽  
Author(s):  
Aritania Sousa Santos ◽  
Edécio Cunha-Neto ◽  
Nelson Vinicius Gonfinetti ◽  
Fernanda Bernardi Bertonha ◽  
Pauline Brochet ◽  
...  

BackgroundChanges in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms.MethodsWe assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls.ResultsWe identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (LFT, DEFA4, DEFA1, CTSG, KCNMA1) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (AREG) and immune tolerance (SMAD6). SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these dataConclusionsOur analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Yang Tan ◽  
Hao-Yue Jing ◽  
Yue-Rong Ma

Chronic kidney disease (CKD) is a major public health problem that affects more than 10% of the population worldwide and has a high mortality rate. Therefore, it is necessary to identify novel treatment strategies for CKD. Incidentally, renal fibrosis plays a central role in the progression of CKD to end-stage renal disease (ESRD). The activation of inflammatory pathways leads to the development of renal fibrosis. In fact, interleukin-33 (IL-33), a newly discovered member of the interleukin 1 (IL-1) cytokine family, is a crucial regulator of the inflammatory process. It exerts pro-inflammatory and pro-fibrotic effects via the suppression of tumorigenicity 2 (ST2) receptor, which, in turn, activates other inflammatory pathways. Although the role of this pathway in cardiac, pulmonary, and hepatic fibrotic diseases has been extensively studied, its precise role in renal fibrosis has not yet been completely elucidated. Recent studies have shown that a sustained activation of IL-33/ST2 pathway promotes the development of renal fibrosis. However, with prolonged research in this field, it is expected that the IL-33/ST2 pathway will be used as a diagnostic and prognostic tool for renal diseases. In addition, the IL-33/ST2 pathway seems to be a new target for the future treatment of CKD. Here, we review the mechanisms and potential applications of the IL-33/ST2 pathway in renal fibrosis; such that it can help clinicians and researchers to explore effective treatment options and develop novel medicines for CKD patients.


Author(s):  
Juan Wang ◽  
Jianmin Chai ◽  
Linlin Zhang ◽  
Lijiao Zhang ◽  
Wei Yan ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Pandji I. Fianza ◽  
Anita Rahmawati ◽  
Shofura Afifah ◽  
Suhendra Praptama ◽  
Mohammad Ghozali ◽  
...  

Background. Patients with thalassemia major may suffer from complications due to iron overload. It has been suggested that several adipokines may play a potential role in the development of complications in thalassemia. Fatty acid-binding protein 4 (FABP4) is one of the adipokines, bridging several aspects of metabolic and inflammatory pathways. Little is known about the relationship between this adipokine and cardiac and liver function, especially in patients with thalassemia major. Aims. This study is aimed at determining serum FABP4 levels in patients with thalassemia major and whether its concentration correlated with serum ferritin levels, as well as cardiac and liver function. Methods. Thalassemia major outpatients ( n = 48 ) completed laboratory examination, echocardiography, and electrocardiography. Results. The mean age was 21.9 ± 8.0 years. A negative and weak correlation between serum ferritin and FABP4 was observed ( r = − 0.291 , p < 0.05 ). In addition, there was moderate and positive correlation between left atrial volume index (LAVI) and FABP4 ( r = 0.316 , p < 0.05 ). Conclusions. Serum FABP4 correlated with serum ferritin and cardiac function in patients with thalassemia major. FABP4 may be a potential clinical biomarker for cardiac dysfunction via metabolic and inflammatory pathways due to iron accumulation and toxicity in patients with thalassemia major.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jianqing Xu ◽  
Zhihong Ren ◽  
Kangli Cao ◽  
Xianping Li ◽  
Jing Yang ◽  
...  

Boosting and prolonging SARS-CoV-2 vaccine-elicited immunity is paramount for containing the COVID-19 pandemic, which wanes substantially within months after vaccination. Here we demonstrate that the unique strain of probiotic Lactobacillus plantarum GUANKE (LPG) could promote SARS-CoV-2-specific immune responses in both effective and memory phases through enhancing interferon signaling and suppressing apoptotic and inflammatory pathways. Interestingly, oral LPG administration promoted SARS-CoV-2 neutralization antibodies even 6 months after immunization. Furthermore, when LPG was given immediately after SARS-CoV-2 vaccine inoculation, specific neutralization antibodies could be boosted &gt;8-fold in bronchoalveolar lavage (BAL) and &gt;2-fold in sera, T-cell responses were persistent and stable for a prolonged period both in BAL and the spleen. Transcriptional analyses showed that oral application of LPG mobilized immune responses in the mucosal and systemic compartments; in particular, gut-spleen and gut-lung immune axes were observed. These results suggest that LPG could be applied in combination with SARS-CoV-2 vaccines to boost and prolong both the effective and memory immune responses in mucosal and systemic compartments, thereby improving the efficacy of SARS-CoV-2 vaccination.


Cytokine ◽  
2021 ◽  
Vol 148 ◽  
pp. 155710
Author(s):  
Mohammed M.H. Al-Gayyar ◽  
Abdullah Alattar ◽  
Reem Alshaman ◽  
Ahmed M. Hamdan

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