Repression of miR-142–3p alleviates psoriasis-like inflammation by repressing proliferation and promoting apoptosis of keratinocytes via targeting Sema3A

Psoriasis is a multifactorial, recurring, and chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. The object of the study was to explore the functions and precise mechanism of miR-142–3p in human keratinocyte HaCaT cells in the presence of M5. Here, the results showed that miR-142–3p expression was heightened in HaCaT cells induced by M5. In addition, inhibition of miR-142–3p dramatically restricted cell proliferation and enhanced apoptosis in HaCaT cells exposed to M5, as exemplified by a decrease in the antiapoptotic Bcl-2 protein, concomitant with an increase in the proapoptotic proteins Bax. Moreover, depleting miR-142–3p effectively ameliorated M5-induced inflammation response, as reflected by the attenuation of multiple inflammatory factors. Importantly, Sema3A was identified as an authentic target of miR-142–3p, and indeed regulated by miR-142–3p. Mechanistically, silencing of Sema3A effectively abolished the anti-proliferative, apoptosis-promoting, and anti-inflammatory effects of miR-142–3p inhibition in keratinocytes. Taken together, these data elucidated that repression of miR-142–3p protect HaCaT cells against M5-induced hyper-proliferation and inflammatory injury by suppressing its target Sema3A, implying that the miR-142–3p/Sema3A axis may be a new target for preventing keratinocyte injury process. These findings provide a new and better understanding of the mediating role of miR-142–3p in psoriasis.     

Effects of baru almond oil (Dipteryx alata Vog.) supplementation on body composition,inflammation, oxidative stress,lipid profile,and plasma fatty acids of hemodialysis patients: A randomized,double-blind,placebo-controlled clinical trial

BackgroundThe consumption of nuts and edible seeds is associated with the improvement of the metabolic profile and reduction of cardiovascular diseases. However, the effects of its subproducts, such as oil, are still poorly studied. This study aimed to evaluate the effect of the baru almond oil supplementation on inflammation, oxidative stress, body composition, lipid profile, and plasma fatty acids of hemodialysis patients.MethodsIn a randomized, double-blind, 12-week placebo-controlled clinical study, hemodialysis patients were supplemented with 5 g of baru oil (BG, n = 17) or 5 g of mineral oil (placebo, BP, n = 12). Body composition, renal function, ultra-sensitive C-reactive protein (us-CRP), oxidative stress, plasma fatty acids, and lipid profile were analysed before and after the intervention.ResultsPatients were aged 50.5 ± 2.2 years and the average time of dialyses was 52,1 ± 42,6 months. The BG decreased us-CRP concentration compared to PG (-1.2 ± 0.2 vs. + 0.8 ± 0.2 mg / L,d = 0.88; p = 0.01). Baru almond oil supplementation was not effective in improving body composition, lipid profile, and oxidative stress.ConclusionBaru almond oil supplementation decreased us-CRP concentration in patients with chronic kidney disease under hemodialysis treatment.     

Effects of sildenafil on inflammatory injury of the lung in sodium taurocholate-induced severe acute pancreatitis rats

BackgroundInflammatory response and acute lung injury (ALI) occur in sodium taurocholate-induced severe acute pancreatitis (SAP). Because sildenafil has anti-inflammatory, anti-oxidant and immune-modulating effects, we investigated its effect on inflammatory and lung injury in sodium taurocholate-induced SAP-associated ALI rat lung.MethodsSodium taurocholate-induced SAP rats received sildenafil (100 mg/kg) or not and were compared to age-matched normal control animals. We evaluated inflammatory response by detecting the expression of inflammatory factors including IL-1β, IL-6 and TNF-α, and detected the level of lung injury through histopathological evaluation. Moreover, we also tested the protein expression of PCNA, P21, Bcl-2 and Bax in the lung.ResultsSildenafil administration rats had a low level of lung injury and inflammation. In addition, sildenafil significantly increased the expression of proliferation-related markers and decreased the expression of apoptosis-related markers in lung tissue.ConclusionsSildenafil administration may attenuate inflammation and lung injury by promoting proliferation and suppressing apoptosis in SAP rats.     

Variability within the human iNOS gene and Achilles tendon injuries: Evidence for a heterozygous advantage effect

ObjectivesThe aim of this case control genetic association study was to explore whether two variants within the inducible nitric oxide synthase (iNOS) gene, rs2779249 (C/A) and rs2248814 (A/G), influenced the risk of Achilles tendinopathy in a British population.DesignCandidate gene, case control association study.MethodWe recruited 145 individuals diagnosed with Achilles tendon pathology and 132 asymptomatic controls. All participants were genotyped for the iNOS variants using qPCR and significant associations were discovered using a combination of Chi squared and ANOVA type analysis.ResultsThe CA genotype of the iNOS rs2779249 variant was protective and conformed to a heterozygous advantage model of inheritance as it was overrepresented in the control participants (p = 0.009). In sex specific analysis the protective association persisted in male participants (p = 0.016) but not in females. Unlike the rs2779249 variant, the rs2248814 variant was not associated with Achilles tendinopathy or Achilles tendon rupture.ConclusionThe rs2779249 CA genotype within the human iNOS gene appears to protect individuals from Achilles tendinopathy. This study further supports a genetic contribution to modifying the risk of Achilles tendon problems. The study also infers an important role for nitric oxide in tendon healing and/or degradation.     

Obesity-induced testicular oxidative stress,inflammation and apoptosis: Protective and therapeutic effects of orlistat

Obesity has been reported to induce oxidative stress, inflammation and apoptosis in the testis. The objective of this study was to determine the effects of the anti-obesity drug orlistat, on testicular oxidative stress, inflammation and apoptosis in high-fat diet (HFD)-fed rats. Twenty-four adult male Sprague Dawley rats weighing 250−300 g were randomized into four groups (n = 6/group), namely; normal control (NC), high-fat diet (HFD), HFD plus orlistat (10 mg/kg body weight/day administered concurrently for 12 weeks) (HFD + Opr) and HFD plus orlistat (10 mg/kg body weight/day administered 6 weeks after induction of obesity) (HFD + Ot) groups. Antioxidant enzymes activities were significantly decreased, while mRNA levels of pro-apoptotic markers (p53, Bax/BCl-2, caspase-9, caspase-8 and caspase-3) were significantly increased in the testis of HFD group relative to NC group. Furthermore, the mRNA levels of pro-inflammatory markers (nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis factor alpha and interleukin (IL)-1β increased significantly, while anti-inflammatory marker (IL-10) decreased significantly in the testis of the HFD group relative to NC group. However, in both models of orlistat intervention (protective and treatment models) up-regulated antioxidant enzymes, down-regulated inflammation and apoptosis were observed in the testis of HFD-fed rats. Orlistat ameliorated testicular dysfunction by attenuating oxidative stress, inflammation and apoptosis in HFD-fed rats, suggesting its potential protective and therapeutic effects in the testis compromised by obesity.     

Ex vivo culture of lesional psoriasis skin for pharmacological testing

BackgroundPsoriasis is a chronic, inflammatory skin disorder resulting from a complex interplay between immune and skin cells via release of soluble mediators. While a lot is known about the molecular mechanisms behind psoriasis pathogenesis, there is still a need for preclinical research models that accuratelyreplicate the disease.ObjectiveThis study aimed to develop and characterize ex vivo culture of psoriasis skin as a model for pharmacological testing, where the immunological events of psoriasis can be followed.MethodsFull thickness punch biopsies of lesional psoriasis skin were cultured in submerged conditions up to 144 h followingin situ T cell stimulation with rhIL-23 and anti-CD3 and anti-CD28 antibodies. The T cell mediated skin inflammation was assessed by gene and protein l analysis for a panel of inflammatory mediators. Tissue integrity and morphology were evaluated by histological analysis.ResultsT cell stimulation resulted in functional and psoriasis specificin situ activation of T cells. The expression levels of most of the proinflammatory mediators related to both immune and skin cells were comparable to these in freshly isolated tissue at 48 and 96 h of culture. Tissue integrity and morphology were sustained up to 96 h. Treatment with a corticosteroid reduced the expression of several pro-inflammatory cytokines and chemokines, whereas anti-IL-17A antibody treatment reduced the expression of the IL-17A downstream markers IL-8 and DEFB4.ConclusionBy preserving keyimmunopathological mechanisms of psoriasis, ex vivo culture of psoriasis skin can be used for the investigation of inflammatory processes of psoriasis and for preclinical drug discovery research.     

Inflammatory and infectious complications of laser therapy in treatment of hypertrophic burn scars: Correlations in literature review & case reports

IntroductionHypertrophic burn scars contribute to morbidity through secondary symptoms of pain, pruritus, and scar contracture. Traditional treatment methods are now augmented by the use of monochromatic light therapies, which are generally accepted as safe and effective. However, little literature is available regarding the complications of laser treatments of hypertrophic burn scars and even less regarding inflammatory and infectious complications.MethodsA literature search using PubMed was performed to identify literature pertaining to infectious and inflammatory complications of cutaneous laser treatments. Additionally, we reviewed cases of inflammatory and infectious complications occurring at our institution after laser treatment of hypertrophic burn scars.ResultsWe identified 1 publication related to complications of laser therapy in the treatment of burn scars. In this series of 163 laser sessions, the reported incidence of adverse events was 25.1%, of which 6 cases 3.7% were related to inflammatory and infectious processes. In the 391 laser sessions performed at our institution (December, 2015 and July, 2016) 9 cases of inflammatory and infectious complications were noted yielding an incidence of 2.3%. Cases included 3 each of cellulitis, Systemic Inflammatory Response Syndrome (SIRS), and complicated SIRS.ConclusionWe found the most common inflammatory complication was SIRS with MSSA positive wound cultures. Three cases underwent hospitalization along with fluids and vasopressors, despite negative blood cultures. In light of the high prevalence of MSSA in the natural skin flora and negative blood cultures, the inability to establish a true source of infection lead to declaring these cases “complicated SIRS” and not sepsis. Correlative factors that may have led to complications reported in our cases were: preoperative evidence of infection, no preoperative antibiotics administered, no postoperative antibiotic dressings, combined procedures, and large treatment areas. The true mechanism of inflammatory and infectious complication is yet to be determined, but we postulate that these factors place a greater challenge on an already burdened immune system. Determining whether this is a true causal mechanism, leading to an aggravated inflammatory response, benefits from further investigation.Applicability of research to practiceWe urge institutions preforming such procedures to advise patients on preoperative wound preparation. We recommend that each individual with a preexisting history of infection and/or preoperative culture evidence of infection receive antibiotics, particularly when undergoing combined procedures or procedures involving higher surface areas. Although complications are rare, the benefits of these precautionary measures outweigh the risks when it comes to prevention and management.