Reduction Of Inflammatory Markers Research Articles

Beneficial Effects of Physical Activity in Rheumatoid Arthritis Patients: Focus on Active Biomolecules

Physical Activity (PA) has a fundamental role in subjects with Rheumatoid Arthritis (RA), in terms of motility, joint function, muscle wasting, BMI (Body Mass Index), Cardiovascular Fitness (CRF), mental health, but also changes in bioactive molecules that might influence the disease activity and patient’s wellbeing. Literature was searched for clinical trials, randomized-controlled trials, and pilot studies published in the last 15 years. Studies using as adjunctive therapy aerobic exercise, High- Intensity Interval Training (HIIT), and moderate training were included. The available papers shown that exercise programs improve joint’s mobility and flexibility and the overall health status, without differences regarding age, gender or disease activity. All these findings are supported by the modulatory role of exercise-induced cytokines as interleukin-6 (IL- 6) and irisin, together with a reduction of inflammatory markers.

Efficacy of Therapeutic Plasma Exchange in Severe Acute Respiratory Distress Syndrome in COVID-19 Patients from the Western Part of Romania.

Background and Objectives: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has surprised the medical world with its devastating effects such as severe acute respiratory distress syndrome (ARDS) and cytokine storm, but also with the scant therapeutic solutions which have proven to be effective against the disease. Therapeutic plasma exchange (TPE) has been proposed from the very beginning as a possible adjuvant treatment in severe cases. Our objective was to analyze the evolution of specific biological markers of the COVID-19 disease before and one day after a therapeutic plasma exchange session, how a change in these parameters influences the patient's respiratory status, as well as the impact of TPE on the survival rate. Materials and Methods: In this retrospective study, we include 65 patients with COVID-19 admitted to the intensive care unit department of our hospital between March 2020 and December 2021, and who received a total of 120 sessions of TPE. Results: TPE significantly reduced the following inflammation markers (p < 0.001): interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, ferritin, and erythrocyte sedimentation rate. This procedure significantly increased the number of lymphocytes and decreased D-dimers levels (p = 0.0024). TPE significantly improved the PaO2/FiO2 ratio (p < 0.001) in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 100). Survival was improved in intubated patients who received TPE. Conclusions: TPE involved the reduction in inflammatory markers in critical patients with COVID-19 disease and the improvement of the PaO2/FiO2 ratio in patients with severe ARDS and had a potential benefit on the survival of patients with extremely severe COVID-19 disease.

Pyridostigmine reduces mortality of patients with severe SARS-CoV-2 infection: A phase 2/3 randomized controlled trial

:Background: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19.Methods:We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described.Results:We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44–64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24–0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively).Conclusion:Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.

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.

Anti-inflammatory potential of SGLT2 inhibitors: a systematic review and meta-analysis of preclinical studies in rodents

Abstract Background Sodium-glucose cotransporter-2 (SGLT2) inhibition is at the forefront of scientific research due to their astonishing effect in ameliorating the prognosis of cardiorenal diseases. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones. Purpose Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibitors on inflammatory markers in experimental rodent models. Methods We conducted a literature search to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP1)] in rodent animal models. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment and the control group as its primary outcome. Studies not reporting in vivo experiments on mice/rats or not measuring inflammatory markers in the plasma or serum were excluded. Moreover, studies not administering SGLT2 inhibitors as treatment or simultaneously utilizing SGLT2 inhibitors with other treatment were further excluded. Effect sizes were pooled via random-effect model and results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). Correction for small-sample bias was also applied with the use of Hedge's g. I2 was chosen as the measure of between-studies heterogeneity. Results The systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): −1.49, 95% CI −2.00 to −0.99, I2: 71%), CRP (SMD: −2.17, 95% CI −2.80 to −1.53, I2: 64%), TNF-α (SMD: −1.68, 95% CI −2.05 to −1.31, I2: 38%), and MCP1 (SMD: −2.04, 95% CI −2.91 to −1.17, I2: 66%) (Figure 1). The effect was of lesser magnitude in cases of empagliflozin use (p for interaction=0.03 to 0.05). Possible publication bias was noted in the case of IL-6 and CRP. The findings remained largely unaffected after the sensitivity analyses and the exclusion of outlying studies. Conclusion The present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in rodents, suggesting an anti-inflammatory mechanism of action Funding Acknowledgement Type of funding sources: None.

REMDESIVIR PLUS DEXAMETHASONE VS TOCILIZUMAB OR BARICITINIB SUPPLEMENTATION INITIATED INSIDE 48 HOURS OF INDEX COVID-19 HOSPITALIZATION IN ICU PATIENTS

REMDESIVIR PLUS DEXAMETHASONE VS TOCILIZUMAB OR BARICITINIB SUPPLEMENTATION INITIATED INSIDE 48 HOURS OF INDEX COVID-19 HOSPITALIZATION IN ICU PATIENTS

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.

S2725 Enteral Nutrition in Crohns Disease With Abscess

Introduction: Enteral nutrition has emerged as a treatment option for patients with active Crohn’s disease. We report a patient achieving remission with enteral nutrition in conjunction with ustekinumab. Case Description/Methods: A 29-year-old Caucasian male with Crohn’s disease not on therapy presented with abdominal pain, nausea and vomiting. In the past 3 years, he had multiple visits to urgent care for symptoms, each treated with systemic steroids. On presentation, he had an elevated CRP of 143.9 mg/L and MR enterography showed inflammation in the small bowel and terminal ileum. The patient completed a 7-day course of piperacillin-tazobactam and was started on ustekinumab. He was readmitted 10 days later with WBC of 16.9 10*3/ul, CRP of 305.6 mg/L, tachycardia, night sweats and worsening abdominal pain. Imaging showed continued inflammation of small bowel and terminal ileum with a mesenteric abscess connected to the D4 portion of duodenum by a fistulous tract. Piperacillin-tazobactam was started for 14 days along with 5 weeks of exclusive enteral nutrition (EEN) with BOOST, ∼2145 kcals daily. Repeat imaging showed interval decrease in abscess size and then complete resolution. Disease remission was obtained with alleviation of abdominal pain and weight gain of 5 lbs. Labs normalized with CRP < 3 mg/L, at the end of the 5 weeks of EEN. Discussion: EEN is the administration of a polymeric formula as the sole source of nutrition for a limited period (4-8 weeks). In Crohn’s disease, EEN has been shown to help reach remission in 85-90% of patients. It has special consideration in achieving remission in CD patients who have steroid intolerance or contraindications to systemic steroids. The mechanism of EEN in treatment of Crohns disease is not completely understood but is hypothesized to be multifactorial and potentially involve alterations in gut microbiota, decreasing gut permeability, and allowing restoration of epithelial barrier. Limited studies have been conducted on concomitant use of EEN with biologic agents. These studies have primarily been done looking at anti-TNF agents, such as infliximab, and sustained remission rates. Induction therapy with such agents as ustekinumab take time to have clinical effect, 56% of patients have response in 6 weeks. In this patient, initiation of ustekinumab along with EEN was successful in achievement of clinical remission and reduction in inflammatory markers.

Millettia ferruginea extract attenuates cisplatin-induced alterations in kidney functioning, DNA damage, oxidative stress, and renal tissue morphology

This study aimed to investigate the beneficial role of Millettia ferruginea extract (MF) in preventing cisplatin (Cisp) induced nephrotoxicity in rats. A total of 55 metabolites were identified using LC-MS analysis. The in vivo results indicated that MF pretreatment for 4 weeks (20 mg/kg b.w.) remarkably attenuated the altered renal biomarkers by decreasing the levels of plasma creatinine, urea, and uric acid when compared to the Cisp-group. The nephroprotective capacity of MF was further strengthened by histopathological observations, where Cisp + MF treated rats showed lower number of inflammatory cells and tubular degenerative changes than the Cisp-group. The harmful effects of cisplatin on renal oxidative stress indicators (MDA, SOD, CAT, and GPx), were restored by the treatment of MF. In addition, the reduction of inflammatory markers (IL-6 and TNF-α), associated with alleviating DNA fragmentation, highlighted the preventive effect of MF in kidney tissue. Additionally, MF components presented lower binding energies when docked into the active site of TNF-α and IL-6. The present findings concluded that M. ferruginea extract exhibited nephroprotective potential, which may be attributed to its antioxidant and anti-inflammatory properties. Further work is recommended to confirm the current results, explore the involved mechanism of action, and determine the therapeutic doses and time.

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.

Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19

Anti-SARS-CoV-2 monoclonal antibodies are mainstay COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two dose-cohorts (7000 mg, n = 94; 700 mg, n = 223). No differences in bamlanivimab vs placebo were observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28 (risk ratio = 0.82–1.05 for 7000 mg [p(overall) = 0.88] and 0.81–1.21 for 700 mg [p(overall) = 0.49]), time to symptom improvement (median 21 vs 18.5 days [p = 0.97], 7000 mg; 24 vs 20.5 days [p = 0.08], 700 mg), or grade 3+ adverse events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and faster reductions in inflammatory markers and viral decay by modeling. This study provides evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom durations in non-hospitalized adults with early variants of SARS-CoV-2. Trial Registration: ClinicalTrials.gov Identifier: NCT04518410.

The impact of SGLT2 inhibitors on inflammation: A systematic review and meta-analysis of studies in rodents

BackgroundInhibition of sodium-glucose cotransporter-2 (SGLT2) has received remarkable attention due to the beneficial effects observed in diabetes mellitus, heart failure, and kidney disease. Several mechanisms have been proposed for these pleiotropic effects, including anti-inflammatory ones. Our systematic review and meta-analysis aimed to assess the effect of SGLT2 inhibition on inflammatory markers in experimental models. MethodsA literature search was conducted to detect studies examining the effect of SGLT2 inhibitors on inflammatory markers [interleukin-6 (IL-6), C reactive protein (CRP), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1)]. Consequently, a meta-analysis of the included studies was performed, assessing the differences in the levels of the inflammatory markers between the treatment groups as its primary outcome. Moreover, risk of bias, sensitivity analysis and publication bias were evaluated. ResultsThe systematic literature review yielded 30 studies whose meta-analysis suggested that treatment with an SGLT2 inhibitor resulted in decreases of IL-6 [standardized mean difference (SMD): −1.56, 95% CI −2.06 to −1.05), CRP (SMD: −2.17, 95% CI −2.80 to −1.53), TNF-α (SMD: −1.75, 95% CI −2.14 to −1.37), and MCP-1 (SMD: −2.04, 95% CI −2.91 to −1.17). The effect on CRP and TNF-α was of lesser magnitude in cases of empagliflozin use. Moderate-to-substantial heterogeneity and possible publication bias were noted. The findings remained largely unaffected after the sensitivity analyses, the exclusion of outlying studies, and trim-and-fill analyses. ConclusionThe present meta-analysis suggests that SGLT2 inhibition results in reduction of inflammatory markers in animal models, further validating the suggested anti-inflammatory mechanism of action.

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.

Anti-Inflammatory, Antioxidant, and Anti-Atherosclerotic Effects of Natural Supplements on Patients with FMF-Related AA Amyloidosis: A Non-Randomized 24-Week Open-Label Interventional Study.

We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21–66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis.

Effects of Palmitoylethanolamide on Proinflammatory Markers in Adults Recently Diagnosed With COVID-19

ObjectivesInflammation is at the core of many chronic conditions and exacerbates infectious conditions, including the severity of COVID-19 infections. The aim of this study was to examine the effects of a novel food supplement, palmitoylethanolamide, specifically Levagen+™ (LEV), versus placebo (CON) on proinflammatory biomarkers in an adult population recently diagnosed with COVID-19 who were non-hospitalized. MethodsThis study was a double-blind randomized placebo-controlled trial conducted October 2020-March 2021. Participants (n = 30/group) were unvaccinated and recently infected with COVID-19 as indicated by a positive test per RT-PCR or antigen test (antigen tests accepted upon symptomatic infection consistent with COVID-19 symptoms per the CDC) and reported to the test site following diagnosis as allowed by the CDC’s return to work policy. Participants were stratified by age, sex, and BMI and randomized by coin toss to receive LEV (600 mg BID) or CON tablets twice daily for four weeks. Participants completed health histories, 24-hour dietary recalls, anthropometrics, and non-fasting blood sampling at baseline and week four. Blood samples were analyzed for inflammatory biomarkers. ResultsThere were no baseline differences by group for age, sex, weight, BMI, type or total number of COVID symptoms reported, nutritional profiles, or interval between date of COVID-19 diagnosis and study enrollment. Following the 4-week trial, change in serum concentration did not differ between groups for IL-6, TNFα, or CRP. However, IL-1β, IL-2, and P-selectin showed reductions in the LEV group after four weeks compared to the CON group which saw increases in these markers (p < .05), though only P-selectin remained significant after Bonferroni correction for multiple comparisons (p < .05). ConclusionsThough inflammatory mechanisms are crucial to an optimal immune response, unchecked secretion of cytokines and thrombo-inflammatory markers can promote the development of the inflammatory response in unresolved disease states and are implicated in COVID-19 complications. Therefore, the reduction in inflammatory markers noted herein suggests that PEA may exert anti-inflammatory actions, and possibly reduce the severity of COVID-19 disease. Funding SourcesThis research was funded by Gencor Lifestage Solutions.

Cytoprotective Effects of Pancreatic Cells of Interleukin 1 Inhibitors (DIACEREIN) on Glucose Homeostasis and Beta Cell in Diabetic Rat Model

Objective: This study was conducted to evaluate the pancreatic cells regeneration with interleukin 1 inhibitor drugs (diacerein) of natural source. Material &amp; Methods: This experimental study was conducted at the Isra University animal house in which 60 albino rats were divided into 4 subgroups of 10 in each. Experimental group of them given alloxan and induced diabetes. interleukin 1 inhibitor (diacerein) was given to 2 experimental groups, diabetic experimental C and D respectively, in dosages of 30 mg/kg and 50 mg/kg for 21 days. After the completion of the experiment, rats were sacrificed by cervical dislocation. The pancreas of rats was removed and set in 10% formalin for fixation after being washed with normal saline. For appropriate fixation, the slides were placed on a hot plate. Hematoxylin and eosin were used to stain the slides, and under the light microscope, stained slides were examined. The study proforma was used to document all of the data. Results: Diabetic rats showed sustained hyperglycemia, total destruction of beta cells histologically. However, diabetic group rats showed degenerative changes of the pancreatic characterized by ultra-structural changes, shrinkage of beta islet cells, and showing RBCs and fibrosis of regions of endocrine glandular epithelial cells. Beta cells were showing mild regeneration with proliferative changes in the beta cells of islets as well as dilatation of ducts seen in treated groups with interleukin 1 inhibitor with lab findings of improving to euglycemic levels. Conclusions: Pancreatic tissue of diabetic rats showed ultra-structural changes and regeneration, as well as reduction in inflammatory markers as well as obvious effects on D.M., hence would be used as a cheap, safe drug to control and reduce the oxidative injury of pancreatic cells and its regenerative effects. Keywords: Diacerein, interleukin 1 inhibitor, regeneration of pancreas hyperglycemia, diabetes mellitus

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 effect of TCF7L2 polymorphisms on inflammatory markers after 16 weeks of legume-based dietary approach to stop hypertension (DASH) diet versus a standard DASH diet: a randomised controlled trial

BackgroundsThis randomized controlled trial aimed to investigate the effects of replacing red meat with legumes in the dietary approach to stop hypertension (DASH) diet on inflammatory markers over 16 weeks in overweight and obese individuals with type 2 diabetes. Also, the modulatory effects of TCF7L2 rs7903146 variant on this effect were assessed.MethodsIn this trial, 300 participants with type 2 diabetes, aged 30–65 years with an identified TCF7L2 rs7903146 genotype, were studied. The participants were randomly assigned to the DASH diet or the legume-based DASH diet over 16 weeks. In the DASH diet group, the participants were instructed to follow the standard DASH diet. The legume-based DASH diet was similar to the standard DASH diet, with the exception that one serving of red meat was replaced with one serving of legumes at least five days a week. At the beginning of the study and 16-week follow-up, venous blood samples were collected from all participants who fasted for 12–14 h overnight. The serum concentration of High-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the serum malondialdehyde (MDA) concentration was assessed based on a colorimetric method using a commercial kit. The primary outcome was the difference in hs-CRP changes between the diets. A secondary outcomes was the difference in IL-6, TNF-α, and MDA between the groups among total population and based on TCF7L2 rs7903146 risk allele (CT + TT) and non-risk allele (CC) separately.ResultsThe hs-CRP level reduced in the legume-based DASH diet group as compared to the DASH diet group in the 16-week follow-up group. The levels of TNF-α, IL-6, and MDA reduced after the legume-based DASH diet relative to the DASH diet. Reduction of inflammatory markers was observed in both carriers of rs7903146 risk allele and non-risk allele.ConclusionsSubstituting one serving of red meat with one serving of legumes in DASH diet, at least five days a week, could improve the hs-CRP, TNF-α, IL-6, and MDA in participants with type 2 diabetes regardless of having rs7903146 risk or non-risk allele.Trial registration IRCT, IRCT20090203001640N17.

MO670: Angiotensin Converting Enzyme Blockers, Angiotensin Receptor Blockers and Statins are Associated with a Reduction of Inflammation Markers Without Modification of the Peritoneal Membrane Transport Status in Peritoneal Dialysis

Abstract BACKGROUND AND AIMS Therapy with angiotensin converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) as well as statins might protect the peritoneal membrane and vessels in peritoneal dialysis. The aim of this study was to analyse the effect of treatment on peritoneal transport and inflammation markers. METHOD The first two peritoneal equilibration tests in adult peritoneal dialysis patients, respectively, 6 and 12 months after dialysis start, were analysed for this retrospective study. Use of ACE, ARB and statins was registered. Serum C reactive protein (sCRP), blood leukocyte and platelet count were used as inflammation markers. Data sets of 220 examinations were acquired. Mann–Whitney U-test was performed for the comparison of therapy groups. Median patient age was 67 years. RESULTS A total of 84 measurements (38.2%) were without ACE and ARB, whereas 93 measurements (423%) without statins. Dialysate to plasma (D/P) creatinine in patients without ACE, ARB and statins was 0.64 (all median values, n = 41), respectively, in patients under therapy with ACE, ARB and statins 0.66 (n = 52). Use of ACE and ARB without statins resulted in D/P creatinine 0.64 (n = 54), whereas use of statins alone in D/P creatinine 0.63 (n = 48). The difference between groups was statistically not significant. There was a tendency of higher values of D/P creatinine (median 0.68) in patients under therapy with ACE and statins (Fig. A). sCRP was higher in patients without ACE, ARB and statins compared to patients with ACE, ARB or statins (0.60 versus 0.30 mg/dL, P &amp;lt; 0.05) (Fig. B). Furthermore platelet count was slightly higher in patients without ACE, ARB and statins (25 8000 versus 22 6000/mm3). Blood leukocyte count did not present significant differences (median values 6930 to 6855/mm3). CONCLUSION Our data suppose the absence of a protective effect of ACE, ARB and statins on peritoneal transport expressed by P/D creatinine despite reduced signs of systemic inflammation.

Effect of daily tiotropium on allergen-induced early asthmatic responses and airway inflammation

Long-acting muscarinic antagonists (LAMAs) have been approved as an add-on treatment for moderate-to-severe asthma—tiotropium as an individual inhaler and umeclidinium as a combination inhaler. Data from ovalbumin-sensitized and challenged animals treated with muscarinic antagonists, including tiotropium, reveal reductions in inflammatory markers and allergen-associated changes.1,2 Inhaled muscarinic antagonists may, therefore, protect the airways of patients with allergic asthma through both bronchodilators (ie, decrease the early asthmatic response [EAR]) and anti-inflammatory action (ie, decrease type 2 [T2] eosinophilic airway inflammation).