Significant Reduction In Inflammatory Markers Research Articles

Christensenella minuta Alleviates Acetaminophen-Induced Hepatotoxicity by Regulating Phenylalanine Metabolism.

Acetaminophen (APAP)-induced liver injury (AILI), even liver failure, is a significant challenge due to the limited availability of therapeutic medicine. Christensenella minuta (C. minuta), as a probiotic therapy, has shown promising prospects in metabolism and inflammatory diseases. Our research aimed to examine the influence of C. minuta on AILI and explore the molecular pathways underlying it. We found that administration of C. minuta remarkably alleviated AILI in a mouse model, as evidenced by decreased levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and improvements in the histopathological features of liver sections. Additionally, there was a notable decrease in malondialdehyde (MDA), accompanied by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, and superoxide dismutase (SOD) activity. Furthermore, there was a significant reduction in inflammatory markers (IL6, IL1β, TNF-α). C. minuta regulated phenylalanine metabolism. No significant difference in intestinal permeability was observed in either the model group or the treatment group. High levels of phenylalanine aggravated liver damage, which may be linked to phenylalanine-induced dysbiosis and dysregulation in cytochrome P450 metabolism, sphingolipid metabolism, the PI3K-AKT pathway, and the Integrin pathway. Furthermore, C. minuta restored the diversity of the microbiota, modulated metabolic pathways and MAPK pathway. Overall, this research demonstrates that supplementing with C. minuta offers both preventive and remedial benefits against AILI by modulating the gut microbiota, phenylalanine metabolism, oxidative stress, and the MAPK pathway, with high phenylalanine supplementation being identified as a risk factor exacerbating liver injury.

Epigallocatechin-3-Gallate attenuates lipopolysacharide-induced pneumonia via modification of inflammation, oxidative stress, apoptosis, and autophagy

BackgroundPneumonia, the acute inflammation of lung tissue, is multi-factorial in etiology. Hence, continuous studies are conducted to determine the mechanisms involved in the progression of the disease and subsequently suggest effective treatment. The present study attempted to evaluate the effects of Epigallocatechin-3-Gallate (EGCG), an herbal antioxidant, on inflammation, oxidative stress, apoptosis, and autophagy in a rat pneumonia model.MethodsForty male Wistar rats, 5 months old and 250–290 g were divided into four groups including control, EGCG, experimental pneumonia (i/p LPS injection, 1 mg/kg), and experimental pneumonia treated with EGCG (i/p, 15 mg/kg, 1 h before and 3 h after LPS instillation). Total cell number in the bronchoalveolar lavage fluid, inflammation (TNF-a, Il-6, IL-1β, and NO), oxidative stress (Nrf2, HO-1, SOD, CAT, GSH, GPX, MDA, and TAC), apoptosis (BCL-2, BAX, CASP-3 and CASP-9), and autophagy (mTOR, LC3, BECN1) were evaluated.ResultsThe findings demonstrated that EGCG suppresses the LPS-induced activation of inflammatory pathways by a significant reduction of inflammatory markers (p-value < 0.001). In addition, the upregulation of BCL-2 and downregulation of BAX and caspases revealed that EGCG suppressed LPS-induced apoptosis. Furthermore, ECGC suppressed oxidative injury while promoting autophagy in rats with pneumonia (p-value < 0.05).ConclusionThe current study revealed that EGCG could suppress inflammation, oxidative stress, apoptosis, and promote autophagy in experimental pneumonia models of rats suggesting promising therapeutical properties of this compound to be used in pneumonia management.

Effectiveness of Yoga in Modulating Markers of Immunity and Inflammation: A Systematic Review and Meta-Analysis.

Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma,as well as in healthy subjects, compared to usual care or sham interventions.A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha(TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.

Long-term exercise preserves pancreatic islet structure and β-cell mass through attenuation of islet inflammation and fibrosis.

Islet fibrosis is associated with the disruption of islet structure and contributes to β-cell dysfunction, playing an essential role in the pathogenesis of type 2 diabetes. Physical exercise has been shown to attenuate fibrosis in various organs; however, the effect of exercise on islet fibrosis has not been defined. Male Sprague-Dawley rats were divided into four groups: normal diet sedentary [N-Sed], normal diet + exercise [N-Ex], high-fat diet sedentary [H-Sed], and high-fat diet + exercise [H-Ex]. After 60 weeks of exercise, 4452 islets from Masson-stained slides were analyzed. Exercise led to a 68% and 45% reduction in islet fibrosis in the normal and high-fat diet groups and was correlated with a lower serum blood glucose. Fibrotic islets were characterized by irregular shapes and substantial loss of β-cell mass, which were significantly reduced in the exercise groups. Remarkably, the islets from exercised rats at week 60 were morphologically comparable to those of sedentary rats at 26 weeks. In addition, the protein and RNA levels of collagen and fibronectin, and the protein levels of hydroxyproline in the islets were also attenuated by exercise. This was accompanied by a significant reduction in inflammatory markers in the circulation Interleukin-1 beta (IL-1β)] and pancreas [IL-1β, Tumor Necrosis Factor-alpha, Transforming Growth Factor-β, and Phosphorylated Nuclear Factor Kappa-B p65subunit], lower macrophage infiltration, and stellate cell activation in the islets of exercised rats. In conclusion, we have demonstrated that long-term exercise preserves pancreatic islet structure and β-cell mass through anti-inflammatory and anti-fibrotic actions, suggesting additional rationales for the success of exercise training in the prevention and treatment of type 2 diabetes that should be further explored.

Ameliorative effect of Lactobacillus rhamnosus GG on acetaminophen-induced hepatotoxicity via PKC/Nrf2/PGC-1α pathway

BackgroundAcetaminophen (APAP) overdose is a common cause of hepatotoxicity. Antioxidants like N-acetyl cysteine are recommended as a therapeutic option; nevertheless, it has limitations. The search for efficient alternatives is ongoing. Probiotics are live microorganisms that maintain a healthy gut microecology. Lactobacillus rhamnosus GG (LGG) is one of the widely used probiotics. Our study aimed to assess the protective and therapeutic effects of probiotic LGG on APAP-induced hepatotoxicity and evaluate the molecular pathways behind this effect. MethodsWistar Albino male rats were randomly distributed into the following experimental groups: group 1, non-treated rats (vehicle); group 2, rats received oral gavage of suspension of probiotic LGG (5 × 1010 CFU GG/0.5 ml in PBS) daily for 2 weeks (probiotic control); group 3, rats received APAP dose of 2 g/kg body weight (positive control); group 4, rats received oral gavage of suspension of probiotic LGG for 2 weeks followed by a single dose of APAP injection (prophylactic); and group 5, rats received a single dose of APAP and then 24 h later treated with oral gavage of probiotic LGG daily for 2 weeks (treatment). ResultsOur study revealed that administration of probiotic LGG (either as prophylactic or treatment) exhibited a remarkable reduction in APAP-induced liver injury as resembled by the decrease in liver enzymes (ALT and AST) and the histopathological features of liver sections. Moreover, the significant reduction in the oxidative marker malondialdehyde, along with the enhancement in glutathione reductase, and the significant reduction in inflammatory markers (nitric oxide and tumor necrosis factor-α) were all indicators of the efficiency of LGG in ameliorating the alterations accompanied with APAP-induced hepatotoxicity. Our findings also demonstrate that LGG administration boosted the expression of Nrf2 and PGC-1 while decreasing the expression of protein kinase C (PKC). As a result, the nuclear abundance of Nrf2 is increased, and the expression of various antioxidants is eventually upregulated. ConclusionOur study shows that probiotic LGG supplementation exerts a prophylactic and therapeutic effect against APAP-induced hepatotoxicity through modulating the expression of PKC and the Nrf2/PGC-1α signaling pathway and eventually suppressing oxidative damage from APAP overdose.

Role of Itolizumab in the Treatment of COVID-19 Patients, Admitted to ICU at a Tertiary Care Hospital.

Clinical studies have correlated severe deterioration of COVID-19 patients due to excessive and uncontrolled production of cytokines. There is a pressing need to explore therapies, which could prevent the cytokine storm rather than terminating it. The aim of the study is to evaluate the effect of itolizumab on clinical outcomes of patients with moderate-severe COVID-19 disease admitted to ICU. The primary aim of the current study is to find out any mortality benefit in 14 days. The secondary aim is to assess the morbidity outcomes in terms of reduction in inflammatory markers and also the duration of hospital stays to assess the prognostication. It is a retrospective case-control study in which laboratory-confirmed COVID-19 patients admitted to ICU were taken. A total of 62 patients were recruited, 31 patients received itolizumab (cases/treatment group) and 31 patients didn't receive itolizumab (designated as controls). Among the total patients recruited, 68% of the study population was male and 32% were female. A total of 12 patients expired among cases and 13 expired among controls. Overall mortality in both groups was noted to be almost similar. The control group showed mortality at lower computed tomography (CT) scores compared to the cases. There is a significant reduction in inflammatory markers, like interleukins-6 (IL-6) and D-dimer in cases compared to the control group. In conclusion, treating patients with cytokine storms before they require intubation/mechanical ventilation is crucial to preventing deaths. Itolizumab has shown no clinical benefit in critically ill COVID-19 patients, however, timely initiation of itolizumab therapy may serve as a key therapeutic option in preventing the mortality and morbidity outcomes in moderate-severe COVID-19 patients.

Nootkatone Ameliorates Doxorubicin Induced Myocardial Injury through Modulation of NF-κB Signals and Oxidative Stress.

Doxorubicin (DOXO) is a potent chemotherapeutic drug that is used in the treatment of a large number of cancers. Despite its important chemotherapeutic characteristics, its usage is limited because of the serious side effects; the most noticeable is cardiotoxicity which can manifest acutely or years after completion of treatment leading to left ventricular dysfunction, dilated cardiomyopathy and heart failure. Nootkatone (NK) is a recognized bioactive compound isolated from the heartwood of Cupressus nootkatensis and has been reported to have antiseptic, antioxidant, and anti-allergic activities. Male C57B6/J mice were used for mice model of DOXO-cardiac toxicity. Mice were given either DOXO or NK or DOXO+NK or vehicle (normal saline) after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for immunohistochemistry, electron microscopy and enzyme linked immunosorbent assay (ELISA). There were significant reduction in inflammatory markers in hearts of DOXO-NK- treated mice when compared with DOXO-treated mice. Moreover, there were significant increase in antioxidant proteins and reduction of oxidative stress in hearts of DOXO-NK-treated mice when compared with DOXO-treated mice. There was a significant reduction in myocardial damage as shown by significant reduction of troponin I in DOXO-NK- treated mice when compared with DOXO-treated mice. Nootkatone improves DOXO-induced myocardial injury through modulation of NF-κB signals and reduction of oxidative stress.

Mesenchymal Stromal Cell (MSC) Therapy Improve Nonalcoholic Fatty Liver Disease (NAFLD) in Long Term high Fat Diet (HFD) Induced Obesity (DIO) Mouse

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> George Washington University internal Grants. <h3>Background/Synopsis</h3> Elevated oxidative stress by reactive oxygen species and mitochondrial dysfunction have been implicated in diabetes and obesity leading to insulin resistance (IR). Based on our previous studies, we investigated to see the effect of MSCs and SOD2, mitochondrial antioxidant upregulated MSCs therapy delivered intra peritoneally (IP), in DIO mouse model that has been fed 60% HFD over 52 weeks. <h3>Objective/Purpose</h3> To investigate intraperitoneal delivery of MSCs overexpressing antioxidant SOD2 can improve NAFLD in DIO mouse model. <h3>Methods</h3> C57BL/6J male mice (4 to 6weeks old) were obtained from the Jackson Lab. Mice kept in laboratory for one year on HFD. Mouse adipose-derived MSCs transduced with adenovirus constructs containing GFP with Null (termed as Null-MSCs) and Adenoviral SOD2 constructs (termed as SOD2-MSC) were obtained from Vector Biolabs, commercially. They were compared to mice that received only saline IP (control). Glucose tolerance test (GTT), liver and fat depots H& E histology were performed and liver triglycerides (L-TG) using TG kit were quantified. <h3>Results</h3> Liver triglyceride estimated levels were reduced (2-fold) in both SOD2 and Null transduced MSCs compared to control with histology demonstrating better result with SOD2 upregulated group. Next, we looked at different fat depots such as omental, subcutaneous, and liver. The gene expression studies for omental fat from mice that received Null-MSCs and SOD2-MSCs showed significant reduction in inflammatory markers (IL-6 and TNF-<b>α)</b> vs control mice. GTT showed an improvement with total area under the curve (AUC) value less compared to control mice. Moreover, the systemic inflammatory maker plasma TNF- <b>α</b> levels were lowest in mice that received SOD2-MSCs. <h3>Conclusions</h3> Our results indicates that MSC therapy improve NAFLD in aged mice fed HFD over one year (long-term HFD treatment). Antioxidant upregulated MSC therapy appears to be safe and to give even better results and helps in reducing liver fat deposits, systemic inflammation and liver triglycerides.

Efficacy of Madhav Rasayan Plus as adjuvant in moderate COVID-19 patients: Preliminary outcomes of randomized controlled trial

Apart from all the gloominess, the COVID-19 Pandemic has a silver lining of bringing a renaissance as Ayurveda and integrated medicine are becoming a choice for acute as well as infective diseases. Here we report outcomes of a preliminary work, the randomized controlled trial (CTRI/2021/02/031256) of Madhav Rasayan Plus, an Ayurveda formulation as adjuvant in moderate COVID-19 patients. Madhav Rasayan Plus is a herbomineral formulation beneficial for respiratory, coagulative and other systemic complements of COVID-19. Forty patients with moderate COVID-19 disease were included in two parallel groups (n = 20/group). The Intervention group (Treatment) received Madhav Rasayan Plus tablets (250 mg) twice a day for 15 days, along with standard care (SOC), while the control group received SOC alone. The intervention group significantly improved symptoms of COVID-19 like cough, breathlessness, fatigue and gastric disturbances. There was also statistically significant reduction in inflammatory markers like CRP and Ferritin. Tissue level markers like creatinine phosphokinase and NT- Pro BNP were found restored after treatment. The requirement of supplemental oxygen in the control group (6 days) was reduced by 2.5 times compared to the intervention group (2.4 days). There was also reduced hospital stay and reduced requirement of ICU in comparison with the control group. Also, the indices of fatigue severity score, disturbed sleep cycle score and quality of life revealed better and holistic recovery in the intervention group. This study reveals that COVID-19 and such infective diseases with vital complications can be better dealt with integrated management as immunomodulation and protection of tissues and vital organs are strengths of Ayurveda.

The anti-inflammatory effects of inhaled steroids and β2-agonist added to inhaled steroids in the treatment of mild asthma

The use of inhaled corticosteroids (ICS) alone may be sufficient for asthma control in mild asthma. We investigated the effect of inhaled steroid and beta-2 agonist combination on airway function and inflammation in mild asthma.We randomized 20 mild persistent asthma patients treated with the 200μg budesonide (10 patients) or budesonide 200μg -formoterol 12μg (10 patients) twice daily for 4 weeks. We investigated the effects of treatment groups on pulmonary function tests by spirometry and eosinophil percentage and eosinophil cationic protein (ECP) levels in serum and induced sputum. We compared values before and after treatment within budesonide and budesonide-formoterol groups and after treatment between groups. We observed that eosinophil percentage and ECP levels in serum and induced sputum decreased significantly after treatment in both treatment groups. Only the decrease in serum eosinophil percentage level was not significant in the budesonide group. On the other that, there was no significant reduction of inflammatory markers between the two treatment groups. The spirometric measurements (FVC, FEV1, FEF25-75) showed a statistically significant increase within the budesonide-formoterol treatment group, but not in the budesonide group. These measurements were not statistically changed between the two treatment groups. In patients with mild asthma, budesonide and formoterol combination therapy did not add to the improvement of airway obstruction and inflammation more than budesonide therapy.

Effects of Vitamin C and Vitamin E in rheumatoid arthritis - A randomized, open label, and comparative study in a tertiary care hospital

Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of autoimmune origin. It affects many organs and joints symmetrically. The involvement of reactive oxygen species (ROS) in the pathogenesis of RA is significant. Oxidative stress occurs when there is excess production of pro oxidants (ROS) and decrease in the level of antioxidants causing oxidative damage to tissues. Anti-oxidants such as Vitamins C and E are very effective in controlling free-radical induced inflammation. Apart from providing symptomatic relief they also modify the disease. Aims and Objectives: The aim of the study was to study the efficacy of Antioxidants Vitamins C and E as an add-on therapy to standard treatment in the management of RA compared to standard treatment alone. Materials and Methods: This was an open label randomized comparative study. In this study, 96 patients were screened and 60 patients were included. They were randomly divided into 30 each in study and control group. Control group received T. Hydroxy chloroquine 400 mg OD and T. Indomethacin 25 mg BD (standard treatment), study group received standard treatment plus T. Vitamin C 500 mg, and Vitamin E 400 mg for 8 s. They were followed for 4 weeks. Improvement of patients was monitored by, pain by visual analog scale, tender joint score, swollen joint score, disease activity score 28, inflammatory markers (ESR, CRP), and every 4 weeks till 12 weeks. Results: All the 60 patients included in this study completed the study. After 8 weeks of treatment in the study group there is statistically significant improvement in pain score, tender joint score, swollen joint score and DAS score. Similarly, statistically significant reduction in inflammatory markers includes ESR and CRP. In the follow-up period, the improvement in study group was sustained. Conclusion: Adding Vitamins C and E over and above the standard treatment can be a new approach in the treatment of RA.

Efficacy and safety of convalescent plasma therapy in patients with moderate-to-severe COVID-19: A non-randomized comparative study with historical control in a referral hospital in Indonesia

BackgroundStudies to confirm the efficacy and safety of convalescent plasma (CP) as an adjunctive treatment for COVID-19 are still required especially for the countries where standard treatments are unevenly distributed. MethodsA non-randomized comparative study was done from June – September 2020 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Plasma with anti-SARS-CoV-2 specific IgG titer of >1:320 were used. Primary end points were clinical and laboratory parameters outcome including BGA, chest X-ray, CT value, CRP, procalcitonin, IL-6, D-Dimer and ALC examined on day 1, 2 and 7 post-transfusion. ResultsThe experimental arm of this study consisted of 15 patients who received CP: 3 (20%) with moderate COVID-19 and 12 (80%) with severe COVID-19. There were 15 historical controls in this study. Ten recipients survived and 5 deceased (survival rate was 66.7%). There were higher rate of pneumonia resolution (OR 1.54, CI95% 0.33–7.23), ARDS resolution (OR 1.20, CI95% 0.25–5.84) and shorter median length of stay (20 vs 22 days, p = 0.41) among recipients compared to controls. Lower mortality rate was observed in recipients vs controls (33.3% vs 46.7% (OR 0.75, CI95% 0.17–3.33)). Median death onset was longer in recipient vs control (7th vs 1st day, p = 0.13). Survival analysis showed protective effect of CP (HR 0.69, CI 95% 0.21–2.27, p = 0.545). Higher CT value improvement (p = 0.51) and negative conversion rate (OR1.20, CI95% 0.25–5.84) were observed in recipients compared to controls. Sub-analysis showed more number of comorbidities, higher procalcitonin and higher D-Dimer among CP recipients who did not survive (p = 0.02 and p = 0.02 respectively). Lower CRP and procalcitonin, and higher ALC were found in survivors compared to non-survivors (p = 0.0437; p = 0.0049; and p = 0.0002 respectively). ConclusionThis study showed promising results for CP marked by improvements in clinical outcome, as well as significant reduction of inflammatory markers among recipients.

Blastocystis Colonization Alters the Gut Microbiome and, in Some Cases, Promotes Faster Recovery From Induced Colitis.

Protists are a normal component of mammalian intestinal ecosystems that live alongside, and interact with, bacterial microbiota. Blastocystis, one of the most common intestinal eukaryotes, is reported as a pathogen that causes inflammation and disease, though health consequences likely vary depending on host health, the gut ecosystem, and genetic diversity. Accumulating evidence suggests that Blastocystis is by and large commensal. Blastocystis is more common in healthy individuals than those with immune mediated diseases such as Inflammatory Bowel Diseases (IBD). Blastocystis presence is also associated with altered composition and higher richness of the bacterial gut microbiota. It is not clear whether Blastocystis directly promotes a healthy gut and microbiome or is more likely to colonize and persist in a healthy gut environment. We test this hypothesis by measuring the effect of Blastocystis ST3 colonization on the health and microbiota in a rat experimental model of intestinal inflammation using the haptenizing agent dinitrobenzene sulfonic acid (DNBS). We experimentally colonized rats with Blastocystis ST3 obtained from a healthy, asymptomatic human donor and then induced colitis after 3 weeks (short term exposure experiment) or after 13 weeks (long term exposure experiment) and compared these colonized rats to a colitis-only control group. Across experiments Blastocystis ST3 colonization alters microbiome composition, but not richness, and induces only mild gut inflammation but no clinical symptoms. Our results showed no effect of short-term exposure to Blastocystis ST3 on gut inflammation following colitis induction. In contrast, long-term Blastocystis exposure appears to promote a faster recovery from colitis. There was a significant reduction in inflammatory markers, pathology 2 days after colitis induction in the colonized group, and clinical scores also improved in this group. Blastocystis colonization resulted in a significant reduction in tumor necrosis factor alpha (TNFα) and IL-1β relative gene expression, while expression of IFNγ and IL17re/17C were elevated. We obtained similar results in a previous pilot study. We further found that bacterial richness rebounded in rats colonized by Blastocystis ST3. These results suggest that Blastocystis sp. may alter the gut ecosystem in a protective manner and promote faster recovery from disturbance.

Quality of Dabai Pulp Oil Extracted by Supercritical Carbon Dioxide and Supplementation in Hypercholesterolemic Rat-A New Alternative Fat.

Dabai pulp oil (DPO) is new oil extracted from the pulp of Canarium odontophyllum. The quality and efficacy of DPO are needed to promote its potential as a new alternative fat. Therefore, we investigate the quality of DPO, which includes moisture and volatile content (MVC), free fatty acid content (FFA), iodine value (IV), and peroxide value (PV). Furthermore, we evaluate the efficacy of DPO against hypercholesterolemia elicited by a high-cholesterol diet in rats. The MVC of DPO was <0.001 ± 0.00%. Next, the FFA in DPO was 2.57 ± 0.03%, and the IV of DPO was 53.74 ± 0.08 g iodine/100 g oil. Meanwhile, the PV of DPO was 4.97 ± 0.00 mEq/kg. Supplementation of DPO in hypercholesterolemic rats for 30 days revealed the hypocholesterolemic effect (significant reduction of total cholesterol, triglyceride, and 3-hydroxy-3-methylglutaryl-CoA reductase) accompanied by a significant reduction of inflammatory markers (C-reactive protein, interleukin-6 and tumour necrosis factor-α), and lipid peroxidation (MDA). We also observed a significant improvement of lipoprotein lipase (LPL) and antioxidant capacities (total antioxidant status, superoxide dismutase, glutathione peroxidase, and catalase) of the rats. The results on the quality and efficacy of locally made DPO suggest its potential use as a healthy alternative fat in the future.

Neuropeptide galanin and its effects on metabolic and reproductive disturbances in female rats with estradiol valerate (EV) - Induced polycystic ovary syndrome (PCOS)

A functional role of the neuropeptide galanin, executed through the three G-protein coupled receptor subtypes GAL₁₋₃, has been demonstrated in many biological systems and under pathological circumstances. Galanin is involved in many central and peripheral actions, in particular associated with endocrine mechanisms such as anterior pituitary hormone regulation, reproduction, glucose metabolism and also inflammation. The role of galanin in the pathology of the polycystic ovary syndrome (PCOS) and possible therapeutic effects are unknown. However, based on the well known neuroendocrine changes in PCOS patients, it may be assumed that galanin via effects on gonadotropin-releasing hormone (GnRH) secretory neurons could play a significant role in the development of PCOS. The aim of this study was to examine possible therapeutic effects of galanin on hormonal, metabolic and molecular parameters in PCOS. Accordingly, intraperitoneal injection of galanin in a dose- dependent manner in female PCOS rats induced a significant reduction in inflammatory markers (TNF-α, IL-6), an increase in FSH and a decrease in LH, insulin and testosterone (using ELISA kit) compared to the PCOS groups. Moreover, data from real-time quantitative PCR showed significantly ameliorated changes in the mRNA levels of the steroidogenic acute regulatory protein (StAR) and aromatase cytochrome P450 (CYP19). Taken together, galanin has neuroendocrine, anti- and pro-inflammatory and metabolic effects, and we therefore suggest that treatment with this peptide could represent new therapeutic approach for managing hormonal and metabolic disturbances in the PCOS disease.

Experience with hemoadsorption (CytoSorb®) in the management of septic shock patients

BACKGROUNDCytokines and inflammatory mediators are the hallmarks of sepsis. Extracorporeal cytokine hemoadsorption devices are the newer clinical support system to overcome the cytokine storm during sepsis.AIMTo retrospectively evaluate the clinical outcomes of patients admitted in intensive care unit with septic shock with different etiologies.METHODSThe laboratory parameters including biomarkers such as procalcitonin, serum lactate and C-reactive protein; and the hemodynamic parameters; mean arterial pressure, vasopressor doses, sepsis scores, cytokine levels and other vital parameters were evaluated. We evaluated these outcomes among survivors and non-survivors.RESULTSOf 100 patients evaluated, 40 patients survived. Post treatment, the vasopressors dosage remarkably decreased though it was not statistically different; 34.15% (P = 0.0816) for epinephrine, 20.5 % for norepinephrine (P = 0.3099) and 51% (P = 0.0678) for vasopressin. In the survivor group, a remarkable reduction of biomarkers levels; procalcitonin (65%, P = 0.5859), C-reactive protein (27%, P = 0.659), serum lactate (27%, P = 0.0159) and bilirubin (43.11%; P = 0.0565) were observed from baseline after CytoSorb® therapy. A significant reduction in inflammatory markers; interleukin 6 and interleukin 10; (87% and 92%, P < 0.0001) and in tumour necrosis factor (24%, P = 0.0003) was also seen. Overall, 28 (28%) patients who were given CytoSorb® therapy less than 48 h after onset of septic shock survived and the maximum duration of stay for 70% of these patients in intensive care unit was less than 15 d.CONCLUSIONCytoSorb® is a safe and well tolerated rescue therapy option in patients with septic shock. However, early (preferably within < 48 h after onset of septic shock) initiation could result in better clinical outcomes. Further randomized trials are needed to define the potential benefits of this new treatment modality.

Whole Body Vibration Therapy after Ischemia Reduces Brain Damage in Reproductively Senescent Female Rats.

A risk of ischemic stroke increases exponentially after menopause. Even a mild-ischemic stroke can result in increased frailty. Frailty is a state of increased vulnerability to adverse outcomes, which subsequently increases risk of cerebrovascular events and severe cognitive decline, particularly after menopause. Several interventions to reduce frailty and subsequent risk of stroke and cognitive decline have been proposed in laboratory animals and patients. One of them is whole body vibration (WBV). WBV improves cerebral function and cognitive ability that deteriorates with increased frailty. The goal of the current study is to test the efficacy of WBV in reducing post-ischemic stroke frailty and brain damage in reproductively senescent female rats. Reproductively senescent Sprague-Dawley female rats were exposed to transient middle cerebral artery occlusion (tMCAO) and were randomly assigned to either WBV or no-WBV groups. Animals placed in the WBV group underwent 30 days of WBV (40 Hz) treatment performed twice daily for 15 min each session, 5 days each week. The motor functions of animals belonging to both groups were tested intermittently and at the end of the treatment period. Brains were then harvested for inflammatory markers and histopathological analysis. The results demonstrate a significant reduction in inflammatory markers and infarct volume with significant increases in brain-derived neurotrophic factor and improvement in functional activity after tMCAO in middle-aged female rats that were treated with WBV as compared to the no-WBV group. Our results may facilitate a faster translation of the WBV intervention for improved outcome after stroke, particularly among frail women.

Inflammatory Cytokines and SIRT1 Levels in Subcutaneous Abdominal Fat: Relationship With Cardiac Performance in Overweight Pre-diabetics Patients.

Objectives: In obese patients the superficial adipose tissue expresses cytokines, and sirtuins, that may affect myocardial function. In this study, we investigated the effect of metformin therapy added to a hypocaloric diet on the inflammatory pattern and cardiac performance (MPI) in obese patients with pre-diabetic condition.Materials and Methods: Fifty-eight obese patients that were enrolled for abdominoplastic surgery were divided into patients with pre-diabetic condition (n 40) and normo-glycemic patients (n18). Patients with pre-diabetic condition were randomly assigned to metformin therapy added to a hypocaloric diet (group 1, n 20) or to a hypocaloric diet therapy alone (group 2, n20). Patients with normo-glycemic condition were assigned to a hypocaloric diet therapy.Results: During enrollment, obese patients with a pre-diabetic condition (group 1 and 2) presented higher glucose values, lower values of insulin, and higher values of the homeostasis model for the assessment of insulin resistance (HOMA-IR) than obese patients with normo-glycemic condition(group 3). In addition, they had higher values of C Reactive protein (CRP), interleukin 6 (IL6), and lower values of sirtuin 1(SIRT1). In the 12th month of the follow-up, metformin therapy induced in patients with pre-diabetic condition (group 1) a significant reduction of glucose values, HOMA-IR, and inflammatory markers such as CRP (1.04 ± 0.48 vs. 0.49 ± 0.02 mmol/L, p < 0.05), IL6 (4.22 ± 0.45 vs. 3.33 ± 0.34 pg/ml, p < 0.05), TNFα (6.95 ± 0.59 vs. 5.15 ± 0.44 pg/ml, p < 0.05), and Nitrotyrosine (5,214 ± 0,702 vs. 2,151 ± 0,351 nmol/l, p < 0.05). This was associated with a significant reduction of Intima-media thickness (1.01 ± 0.15 vs. 0.86 ± 0.15 mm, p < 0.05), Septum (14 ± 2.5 vs. 10.5 ± 2 mm, p < 0.05), Posterior wall (11 ± 1.5 vs. 8 ± 1 mm, p < 0.05), LV mass (192.5 ± 49.5 vs. 133.2 ± 37.6 g, p < 0.05) and of MPI (0.58 ± 0.03 vs. 0.38 ± 0.02, p < 0.05). At 12 months of follow-up, group 2 experienced only a reduction of cholesterol (4.15 ± 0.94 vs. 4.51 ± 0.88 mmol/L, p < 0.05) and triglycerides (1.71 ± 1.18 vs. 1.83 ± 0.54 mmol/L, p < 0.05). At 12 months of follow-up, group 3 experienced a significant reduction of inflammatory markers, and also of echographic parameters, associated with amelioration of myocardial performance. To date, IL6 expression was related to higher values of left ventricle mass (R-value 0.272, p-value 0.039), and to higher IMT (R-value 0.272, p-value 0.039), such as those observed for CRP (R-value 0.308, p-value 0.021), for glucose blood values (R-value 0.449, p-value 0.001), and for HOMA-IR (R-value 0.366, p-value 0.005). An inverse correlation was found between subcutaneous fat expression of SIRT1 and myocardial performance index (R-value−0.236, p-value 0.002).Conclusion: In obese patients with pre-diabetic condition a metformin therapy may reduce inflammation and oxidative stress, and this may be associated with the amelioration of the cardiac performance.Clinical research trial number: NCT03439592.

Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats: Effects of Laser Photobiomodulation

Unusual and exhaustive physical exercise can lead to muscle lesions depending on the type of contraction, intensity, duration, age, and level of conditioning. Different therapies have been proposed to prevent or reduce exercise-induced muscle damage. In this study, we investigate the effects of low-level laser therapy on skeletal muscle strain in an experimental model in rats. Male Wistar rats (200 g) were used. The animals were randomized into groups of six animals. We performed tibialis muscle elongation using a previously described protocol. The animals were anesthetized and submitted to passive stretching of the anterior tibial muscle attached to a weight corresponding to 150% of the body mass of the animal for 20 min, rested for 3 min, and received a second traction for 20 min. The cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, edema, and C-reactive protein (CRP) levels were determined in the tibialis anterior muscle. Plasma extravasation of groups treated with different doses of laser energy, lesion +1 J (2.61 ± 0.46), lesion +3 J (2.33 ± 0.13), lesion +6 J (2.92 ± 0.91), and lesion +9 J (2.80 ± 0.55), shows a significant reduction of extravasation when compared with the injury group (5.46 ± 1.09). Laser therapy was able to significantly reduce CRP and cytokine levels (TNF-α, IL-1β, IL-6, and IL-10). Laser photobiomodulation reduced skeletal muscle edema as well as cytokines and CRP, leading to a significant reduction in inflammatory markers.

Omega3 Fatty Acids Intake Versus Diclofenac in Osteoarthritis Induced in Experimental rats

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by abnormal remodeling pattern of joints driven by inflammatory mediators within the affected joints. Its symptoms are many like pain, stiffness, and decreased function.Objective: The present study mainly focused on the anti-inflammatory effect of omega 3 fatty acids (F.As) versus diclofenac, non-steroidal anti-inflammatory drug in OA induced in ratsDesign: Intraarticular injection of monosodiumiodoacetate (MIA) 24.6 mg/kg in 0.6 ml saline was used to induce OA. Diclofenacand omega-3 F. These were administered orally, daily for 21 days and after 24 hours of OA induction.Results: Osteoarthritis induction resulted in an increase in serum levels of IL-6 (479.5%), TNF-a(545.5%), and CRP (754.2%) along with IL-10 level decrease (70.3%) as compared to normal group. Diclofenac intake demonstrated significant increase of IL-6 (24.9%), CRP (88.6%), and TNF-a (25.2%) compared to the OA control group. Omega 3 FAs intake showed significant reduction in inflammatory markers along with IL-10 increase, in comparison to OA group. Both treatment demonstrated a significant increase in TIMP2 along with decreased MMP2 and MPO in comparison with OA control. Positive correlation of IL-6 with MPO (r = 0.7, P=0.002), and negative one with IL-10 (r = 0.9, p&lt;0.0001) and TIMP2 (r = -0.5, p&lt;0.008) was observed. Interleukin-10 was negatively correlated with MMP2 (r = - 0.5, p&lt;0.007) and MPO (r = -0.8, p&lt;0.0001).Conclusion: Data derived from biochemical and histopathological results, indicated that omega3 FAs may be expressed as a natural anti-inflammatory agent of a significant potential in OA with evident remarkable effect.Keywords: OA; omega3FAs; diclofenac; MMP2; TIMP2; MPO