Search

Background: Non-motor symptoms (NMS) are important factors when selecting treatments for patients with advanced Parkinson's disease (PD). We sought to elucidate the prescribing practices for advanced PD patients with NMS in Japanese clinical practice. Methods: We examined the prescription rates and doses of anti-PD drugs, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) in post hoc analyses of a 52-week observational study of 996 PD patients with wearing-off on levodopa-containing therapy and ≥1 NMS. Results: Dopamine agonists were the most frequently prescribed drugs combined with levodopa-containing drugs, followed by entacapone, zonisamide, istradefylline, selegiline, and amantadine. The daily dose of levodopa-containing drugs, rotigotine, entacapone, istradefylline, and droxidopa, and the levodopa-equivalent dose increased during the observation period. In a subgroup analysis of patients stratified by NMS status (improved/unchanged/deteriorated), the deteriorated group had higher prescription rates of entacapone and istradefylline, whereas the improved group had higher prescription rates of NSAIDs and zonisamide at Week 52. Prescriptions varied by geographical region for anti-PD drugs and by NMS status for NSAIDs. Conclusions: There were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region. [ABSTRACT FROM AUTHOR]

The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 μM, 95% CI = 7.4 to 10.4 μM) was comparable to that of paracetamol (IC50 = 7.73 μM, 95% CI = 6.14 to 9.73 μM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs. [ABSTRACT FROM AUTHOR]

Background: Wounds significantly affect people's quality of life and the clinical and financial burden of healthcare systems around the world. Many of the current drugs used to treat wounds have problems such as; allergies and drug resistance. Hence, the exploration of new therapeutic agents from natural origin may avert this problem. Clerodendrum myricoides have long been used to treat wounds in Ethiopia. Despite this, nothing has so far been reported about the wound healing and anti-inflammatory activity of C. myricoides. This study aimed to evaluate the wound healing and anti-inflammatory activity of 80% methanol extract and solvent fractions of C. myricoides leaves in mice. Methods: Leaves of C. myricoides were extracted using the maceration technique. The extract was formulated as 5% and 10% w/w ointments. The wound healing activity of the extract was evaluated using excision, incision, and burn wound models whereas the healing activities of solvent fractions were evaluated using the excision wound model. A carrageenan-induced paw edema model was used for the anti-inflammatory test. Results: In the dermal toxicity test, 2000 mg/kg of 10% extract was found to be safe. In excision and burn wound models, treatment with 10% and 5% extract showed a significant (p<0.001) wound contraction. Solvent fractions of the extract significantly reduced wound contraction. A significant reduction in periods of epithelialization and favorable histopathology changes were shown by extract ointments. In incision wounds, 10% (p<0.001) and 5% (p<0.01) extracts significantly increase skin-breaking strength. After one hour of treatment, 400 mg/kg (p<0.001) and 200 mg/kg (p<0.05) showed significant reduction in paw edema. Conclusion: Results of this study indicate that 80% methanol extract and the solvent fraction of the leaves of C. myricoides possess wound-healing and anti-inflammatory activity and support traditional claims. [ABSTRACT FROM AUTHOR]

Inflammation is an immune system response that identifies and eliminates foreign material. However, excessive and persistent inflammation could disrupt the healing process. Plant-derived exosome-like nanoparticles (PDENs) are a promising candidate for therapeutic application because they are safe, biodegradable and biocompatible. In this study, papaya PDENs were isolated by a PEG6000-based method and characterized by dynamic light scattering (DLS), transmission Electron Microscopy (TEM), bicinchoninic acid (BCA) assay method, GC-MS analysis, total phenolic content (TPC) analysis, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. For the in vitro test, we conducted internalization analysis, toxicity assessment, determination of nitrite concentration, and assessed the expression of inflammatory cytokine genes using qRT-PCR in RAW 264.7 cells. For the in vivo test, inflammation was induced by caudal fin amputation followed by analysis of macrophage and neutrophil migration in zebrafish (Danio rerio) larvae. The result showed that papaya PDENs can be well isolated using the optimized differential centrifugation method with the addition of 30 ppm pectolyase, 15% PEG, and 0.2 M NaCl, which exhibited cup-shaped and spherical morphological structure with an average diameter of 168.8±9.62 nm. The papaya PDENs storage is stable in aquabidest and 25 mM trehalose solution at -20˚C until the fourth week. TPC estimation of all papaya PDENs ages did not show a significant change, while the DPPH test exhibited a significant change in the second week. The major compounds contained in Papaya PDENs is 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP). Papaya PDENs can be internalized and is non-cytotoxic to RAW 264.7 cells. Moreover, LPS-induced RAW 264.7 cells treated with papaya PDENs showed a decrease in NO production and downregulation mRNA expression of pro-inflammatory cytokine genes (IL-1B and IL-6) and an upregulation in mRNA expression of anti-inflammatory cytokine gene (IL-10). In addition, in vivo tests conducted on zebrafish treated with PDENs papaya showed inhibition of macrophage and neutrophil cell migration. These findings suggest that PDENs papaya possesses anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Background: Natural propolis has been used since decades owing to its broad-spectrum activities. Burn injuries are a global health problem with negative impacts on communities. Bacterial infections usually accompany burns, which demand implementation of antibiotics. Antibiotics abuse led to emergence of microbial drug resistance resulting in poor treatment outcomes. In such instances, the promising alternative would be natural antimicrobials such as propolis. Objective: Full chemical profiling of propolis and evaluation of in vitro antibacterial, antioxidant and anti-inflammatory activities as well as in vivo burn healing properties. Methods: Chemical profiling of propolis was performed using Liquid chromatography (UHPLC/MS-PDA and HPLC-PDA). In vitro assessment was done using Disc Diffusion susceptibility test against Staphylococcus aureus and infected burn wound mice model was used for in vivo assessment. In vitro antioxidant properties of propolis were assessed using DPPH, ABTS and FRAP techniques. The anti-inflammatory effect of propolis was assessed against lipopolysaccharide/interferon-gamma mediated inflammation. Results: UHPLC/MS-PDA results revealed identification of 71 phytochemicals, mainly flavonoids. Upon flavonoids quantification (HPLC–PDA), Pinocembrin, chrysin and galangin recorded high content 21.58±0.84, 22.73±0.68 and 14.26±0.70 mg/g hydroalcoholic propolis extract, respectively. Propolis showed concentration dependent antibacterial activity in vitro and in vivo burn healing via wound diameter reduction and histopathological analysis without signs of skin irritation in rabbits nor sensitization in guinea pigs. Propolis showed promising antioxidant IC50 values 46.52±1.25 and 11.74±0.26 μg/mL whereas FRAP result was 445.29±29.9 μM TE/mg. Anti-inflammatory experiment results showed significant increase of Toll-like receptor 4 (TLR4), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA levels. Nitric oxide and iNOS were markedly increased in Griess assay and western blot respectively. However, upon testing propolis against LPS/IFN-γ-mediated inflammation, TLR4, IL-6 and TNF-α expression were downregulated at transcriptional and post-transcriptional levels. Conclusion: Propolis proved to be a promising natural burn healing agent through its antibacterial, antioxidant and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Objective: Hand osteoarthritis poses a significant health challenge globally due to its increasing prevalence and the substantial burden on individuals and the society. In current clinical practice, treatment options for hand osteoarthritis encompass a range of approaches, including biological agents, antimetabolic drugs, neuromuscular blockers, anti-inflammatory drugs, hormone medications, pain relievers, new synergistic drugs, and other medications. Despite the diverse array of treatments, determining the optimal regimen remains elusive. This study seeks to conduct a network meta-analysis to assess the effectiveness and safety of various drug intervention measures in the treatment of hand osteoarthritis. The findings aim to provide evidence-based support for the clinical management of hand osteoarthritis. Methods: We performed a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials was conducted until September 15th, 2022, to identify relevant randomized controlled trials. After meticulous screening and data extraction, the Cochrane Handbook's risk of bias assessment tool was applied to evaluate study quality. Data synthesis was carried out using Stata 15.1 software. Results: 21 studies with data for 3965 patients were meta-analyzed, involving 20 distinct Western medicine agents. GCSB-5, a specific herbal complex that mainly regulate pain in hand osteoarthritis, showed the greatest reduction in pain [WMD = -13.00, 95% CI (-26.69, 0.69)]. CRx-102, s specific medication characterized by its significant effect for relieving joint stiffness symptoms, remarkably mitigated stiffness [WMD = -7.50, 95% CI (-8.90, -6.10)]. Chondroitin sulfate displayed the highest incidence of adverse events [RR = 0.26, 95% CI (0.06, 1.22)]. No substantial variation in functional index for hand osteoarthritis score improvement was identified between distinct agents and placebo. Conclusions: In summary, GCSB-5 and CRx-102 exhibit efficacy in alleviating pain and stiffness in HOA, respectively. However, cautious interpretation of the results is advised. Tailored treatment decisions based on individual contexts are imperative. [ABSTRACT FROM AUTHOR]

Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk. [ABSTRACT FROM AUTHOR]

Objective: Describe the trends of exposure to harmful drugs during pregnancy over recent years in France. Design: Nationwide cohort study. Setting: The French National administrative health Data System (SNDS). Population: Pregnancies starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths. Methods: Each pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs. Main outcome measures: Prevalence of pregnancies exposed to at least one harmful drug. Results: Among 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids. Conclusions: In this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern. [ABSTRACT FROM AUTHOR]

Inflammation is a temporary response of the immune system that can be treated using common anti-inflammatory drugs. However, prolonged use of these drugs increases the risk of adverse side effects. Accordingly, there is an increasing need for alternative treatments for inflammation with fewer side effects. Exosomes are extracellular vesicles secreted by most eukaryotic cells and have been studied as a candidate for cell-free therapy for inflammatory diseases due to their immunomodulatory and anti-inflammatory properties. In recent years, the focus of exosome research has shifted from animal cell-derived exosomes to plant-derived exosome-like nanoparticles (PDENs). Plant-derived exosome-like nanoparticles (PDENs) are easier to obtain, have minimal safety concerns, and can be produced in higher quantities and lower cost than exosomes derived from animal cells. In this study, the isolation and analysis of the anti-inflammatory potential of PDENs from black nightshade berries (Solanum nigrum L.) were carried out. The results of isolation and characterization showed that PDENs had a spherical morphology, measuring around 107 nm with zeta potential of -0.6 mV, and had a protein concentration of 275.38 μg/mL. PDENs were also shown to be internalized by RAW264.7 macrophage cell line after 2 hours of incubation and had no cytotoxicity effect up to the concentration of 2.5 μg/mL. Furthermore, exposure to several doses of PDENs to the LPS-stimulated RAW264.7 cell significantly decreased the expression of pro-inflammatory cytokine gene IL-6, as well as the expression of IL-6 protein up to 97,28%. GC-MS analysis showed the presence of neral, a monoterpene compound with known anti-inflammatory properties, which may contribute to the anti-inflammatory activity of PDENs isolated from Solanum nigrum L. berries. Taken together, the present study was the first to isolate and characterize PDENs from Solanum nigrum L. berries. The results of this study also demonstrated the anti-inflammatory activity of PDEN by suppressing the production of IL-6 in LPS-stimulated RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Synthetic corticosteroids, the most well-known anti-inflammatory drugs globally, are effective against inflammatory diseases despite their adverse effects that decrease a patient's quality of life (QOL). One of these effects is sleep disturbance, which causes other health issues and further diminishes the QOL. However, the acute effects of steroid drugs on sleep-wake issues are not fully understood and must be clarified in detail using experimental animals. Therefore, this study examines the dose-dependent effect of dexamethasone (DXM), one of the strongest steroid drugs, on the sleep-wake architecture of mice. We conducted acute DXM administration at multiple doses and 24-hour EEG/EMG recordings. Our results revealed that DXM increased the time spent in arousal and decreased that of NREM sleep, even at very low doses. These results imply that steroid-induced sleep disturbance must be addressed at any dosage. [ABSTRACT FROM AUTHOR]

Bovine respiratory syncytial virus (RSV) has substantial morbidity in young calves, and closely parallels human RSV in infants. We performed a randomized controlled trial in five to six-week-old Holstein calves (Bos taurus). comparing fusion protein inhibitor (FPI) and non-steroidal anti-inflammatory drug (NSAID) singly and in combination at three and five days after experimental BRSV infection. Thirty-six calves received one of six treatments; Ibuprofen started on day 3, Ibuprofen started on day 5, FPI started on day 5, FPI and Ibuprofen started on day 3, FPI and Ibuprofen started on day 5, or placebo. We have previously reported significant clinical benefits when combined FPI and NSAID treatment was started at three and five days after bovine RSV infection. Necropsy was performed on Day 10 following infection and hematoxylin and eosin staining was performed on sections from each lobe. Histology was described using a four-point scale. We performed canonical discrimination analysis (CDA) to determine the structural level where differences between treatments occurred and mixed effects regression to estimate effect sizes. Separation from placebo was maximal for dual therapy at the levels of the alveolus, septum, and bronchus in CDA. We found that the clinical benefits of combined FPI and NSAID treatment of BRSV extend at least partially from histopathological changes in the lung when treatment was started three days after infection. We found decreased lung injury when ibuprofen was started as monotherapy on day 3, but not day 5 following infection. Combined therapy with both an FPI and ibuprofen was always better than ibuprofen alone. We did not prove that the clinical benefits seen starting FPI and ibuprofen five days after infection can be solely explained by histopathological differences as identified on H&E staining.

To explore the metabolomics of fatty acids and biological information of related markers in a RAW264.7 cell inflammation model. RAW264.7 macrophage inflammation model was induced by LPS, and RAW264.7 cells were treated with non-steroidal anti-inflammatory drugs (NSAIDs). The fatty acid compositions were identified by GC-MS, combined with standard product spectrum information and NIST (National Institute of Standards and Technology) database. Using chemometrics and Analysis of Variance (ANOVA), the components with VIP > 1 and P < 0.05 were selected as significant difference markers, and combined with biological methods to explore the biological significance of them. GC-MS identified 21 fatty acids in RAW264.7 cells, and screened significant difference biomarkers in each group. Among these biomarkers, C20:5 and C22:6 had significant changes in pairwise comparison among each group. Through ELISA, polymerase chain reaction (PCR) and Western Blot methods, the mRNA and protein expressions of IL-1β, NLRP3, GPR120 and β-Arrestin-2 were up-regulated after RAW264.7 cells induced by LPS and nigericin, and decreased after drug intervention. It indicated that the signal pathway centered on NLRP3 inflammasome was involved in the anti-inflammatory process of ibuprofen. It was the first time to study fatty acid metabolomics in RAW264.7 cell inflammatory model by GC-MS combined with chemometrics. The anti-inflammatory mechanism of ibuprofen was explained from NLRP3 inflammasome perspective without precedent, which enriched the research on the signal pathway of ibuprofen anti-inflammatory mechanism. [ABSTRACT FROM AUTHOR]

IntroductionBovine respiratory syncytial virus (RSV) is a valid model for human RSV and an important bovine pathogen. Very early administration of ibuprofen and GS-561937, a fusion protein inhibitor (FPI), have separately been shown to decrease the severity of bovine RSV. Our aims were to determine how long after RSV inoculation ibuprofen and GS-561937 can be administered with clinical benefit and whether using both was better than monotherapy.Materials and methodsWe conducted a blinded randomized placebo controlled trial of ibuprofen, GS-561937 (FPI), or combinations of the two initiated at 3 or 5 days after artificial infection with bovine RSV in 36 five to six-week-old Holstein calves (Bos taurus). We measured clinical scores, respiratory rate, and viral shedding daily for 10 days following inoculation. We estimated the average effect for each drug and compared treatment arms using mixed effects models.ResultsWe found a significant decrease in clinical scores only in the combined treatment arms. This benefit was greater when treatment was initiated at 3 days rather than 5 days post infection with decreased clinical scores and lower respiratory rates at both time points. Ibuprofen alone started on day 3 increased, and FPI with ibuprofen started on day 3 decreased, viral shedding.ConclusionDual therapy with Ibuprofen and FPI, on average, decrease clinical severity of illness in a bovine model of RSV when started at 3 and 5 days after infection.

The purpose of this study was to extract, identify, and quantify the phenolic compounds in grumixama (Eugenia brasilienses Lam.) and guabiju (Myrcianthes pungens), native fruits from southern region of Brazil, and to explore their antioxidant and anti-inflammatory properties. The phenolic compounds were extracted with acidified water and acidified methanol and evaluated for their bioactive constituents, antioxidant capacity, and anti-inflammatory properties. Spectrophotometric quantification shows tannins to be the most prevalent at 2.3 to 5.8 g/100g fresh fruit with acidified methanol containing higher concentrations of different phenolics than acidified water. HPLC analysis indicates that gallic acid, catechin, vanillic acid, and ellagic acid are the most prevalent phenolics in the two fruits extracts. Scavenging of DPPH and NO radicals showed inhibition by as much as 95% and 80%, respectively, at 2.5 gallic acid equivalent (GAE)/mL of the extract. At 50 μg GAE/mL, the release of pro-inflammatory molecules NO and IL-6 was significantly reduced with acidified methanol extract having higher inhibitory activity. Our results revealed that these native fruits, grown in the south of Brazil, are rich sources of phenolic compounds and have great antioxidant and anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

IL-17 is associated with varied inflammatory and immune-related diseases. However, the biological function of IL-17 and its expression in acute lung damage are not entirely known. Thanks to the powerful antioxidant properties of β-carotene, we presumed that it would show a potent protecting effect against cyclophosphamide (CP) -induced acute lung injury (ALI) in mice. We studied the mechanisms underlying the effect of β-carotene supplementation against CP-induced ALI in mice. We isolated the β-carotene from Scenedesmus obliquus microalgae n-hexane extract and identified it by HPLC and 1H-NMR analysis. Within the experiments, 40 mice were assigned into five groups randomly: Group 1 (Control): Mice received saline. Group 2 (β-carotene control): Mice were administered β-carotene (40 mg/kg; orally) once daily for 10 sequent days without CP injection. Group 3 (CP): One i.p injection of 200 (mg/kg) of CP was given to mice. Group 4 and 5 (CP + β-carotene): Mice were administered β-carotene (20 and 40 mg/kg; orally) once a day for ten days following the CP injection. Lung samples were collected for lab analysis, after scarifying the animals at the experiment end. Administration of β-carotene orally reduced CP-induced ALI and inflammation. β-carotene significantly decreased wet-to-dry weight ratios (W/D), down-regulated IL-17, NF-κB, and IKBKB, decreased the contents of TNF-α, COX-2, and PKC, and increased the contents of SIRT1 and PPARγ in the lung tissues. β-carotene ameliorated the histopathological changes induced by CP and reduced the scoring number of inflammatory cell infiltration and emphysema when compared to CP. Consequently, we conclude natural β-carotene is a promising anti-inflammatory mediator for different inflammatory-related complications. [ABSTRACT FROM AUTHOR]

This paper presents the results of an observational and retrospective study on the therapeutic effects of Jusvinza, an immunomodulatory peptide with anti-inflammatory properties for critically ill COVID-19 patients. This peptide induces regulatory mechanisms on the immune response in experimental systems and in patients with Rheumatoid Arthritis. Exploratory research in COVID-19 patients revealed that Jusvinza promotes clinical and radiological improvement. The aim of this study is to describe the clinical outcome and variations of several inflammatory biomarkers in a cohort of critically ill COVID-19 patients, divided into two groups during the observational research: one group received Jusvinza and the other did not. Research physicians extracted the patients´ data from their hospital's clinical records. The study analyzed 345 medical records, and 249 records from critically ill patients were included. The data covered the demographic characteristics, vital signs, ventilatory parameters and inflammatory biomarkers. Survival outcome was significantly higher in the group receiving Jusvinza (90.4%) compared to the group without Jusvinza (39.5%). Furthermore, in patients treated with Jusvinza there was a significant improvement in ventilatory parameters and a reduction in inflammation and coagulation biomarkers. Our findings show that Jusvinza could control the extent of inflammation in COVID-19 patients. This study indicates that Jusvinza is a helpful drug for the treatment of diseases characterized by hyperinflammation. [ABSTRACT FROM AUTHOR]

Drugs that inhibit cyclooxygenase (COX)-2 and the metabolism of arachidonic acid (ARA) to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins) by cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel) trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90) or placebo (n = 95). We assessed the effect of celecoxib (with and without low dose aspirin) on circulating oxylipins and systolic blood pressure (SBP). Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P

Currently approved monoamine modulating antidepressant and anxiolytic pharmaceutics fail in over one third of patients due to delayed and variable therapeutic effect, adverse reactions preceding the therapeutic action, and adherence issues. Even with adequate adherence to the regimen and tolerability, one third of the patients do not respond to any class of antidepressants. There is a strong correlation between treatment resistant depression and increase in inflammatory cytokines in plasma and cerebrospinal fluid. Furthermore, epidemiological studies suggest that depression and anxiety are commonly comorbid with pain and inflammation. While a link between pain, inflammation and depression has been suggested it remains unclear which anti-inflammatory treatment may be beneficial to patients with depression and anxiety due to pain. Here, we analyzed 430,783 FDA adverse effect reports of patients treated for pain to identify potential antidepressant and anxiolytic effects of various anti-inflammatory medications. Patients treated for depression or patients taking any known antidepressants were excluded. The odds ratio analysis of 139,072 NSAID reports revealed that ketoprofen was associated with decreased reports of depression by a factor of 2.32 (OR 0.43 and 95% Confidence Interval [0.31, 0.59]) and decreased reports of anxiety by a factor of 2.86 (OR 0.35 [0.22, 0.56]), diclofenac with decreased depression reports by a factor of 2.22 (OR 0.45 [0.40, 0.49]) and anxiety by a factor of 2.13 (OR 0.47 [0.41, 0.54]), while naproxen decreased depression reports by a factor of 1.92 (OR 0.52 [0.49, 0.57]) and anxiety by a factor of 1.23 (OR 0.81 [0.75, 0.88]). Other NSAIDs did not exhibit any noticeable antidepressant and/or anxiolytic effect.

Please see the correct Fig 5 with TLR4 expression showing agarose gel here. In Fig 5, the agarose gel picture for TLR4 expression has been mistakenly replaced by Fig 2 iNOS expression depicting agarose gel. The expression of TLR4 and MyD88 was significantly higher in the LPS-induced macrophage as compared to the control and OWB or CA co-treated group (** P<0.001). [Extracted from the article]

Obesity is characterized by an adipose tissue mass expansion that presents a risk to health, associated with a chronic increase in circulating inflammatory mediators. Anti-inflammatory agents are an obesity alternative treatment. However, the lack of effective agents indicates the need to assess the mechanisms and identify effective therapeutic targets. The present work identified and described the mechanisms of action of anti-inflammatory agents in adipose tissue in experimental studies. The review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO—CRD42020182897). The articles' selection was according to eligibility criteria (PICOS). The research was performed in PubMed, ScienceDirect, Scopus, Web of Science, VHL, and EMBASE. The methodological quality evaluation was assessed using SYRCLE. Initially, 1511 articles were selected, and at the end of the assessment, 41 were eligible. Among the anti-inflammatory agent classes, eight drugs, 28 natural, and five synthetic compounds were identified. Many of these anti-inflammatory agents act in metabolic pathways that culminate in the inflammatory cytokines expression reduction, decreasing the macrophages infiltration in white and adipose tissue and promoting the polarization process of type M1 to M2 macrophages. Thus, the article clarifies and systematizes these anti-inflammatory agents' mechanisms in adipose tissue, presenting targets relevant to future research on these pathways. [ABSTRACT FROM AUTHOR]

Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15–41] vs. 19 [5–30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

A growing body of evidence supports that pentadecanoic acid (C15:0), an odd-chain saturated fat found in butter, is an essential fatty acid that is necessary in the diet to support long-term metabolic and heart health. Here, dose dependent and clinically relevant cell-based activities of pure C15:0 (FA15TM) were compared to eicosapentaenoic acid (EPA), a leading omega-3 fatty acid, as well as to an additional 4,500 compounds. These studies included 148 clinically relevant biomarkers measured across 12 primary human cell systems, mimicking various disease states, that were treated with C15:0 at four different concentrations (1.9 to 50 μM) and compared to non-treated control systems. C15:0 was non-cytotoxic at all concentrations and had dose dependent, broad anti-inflammatory and antiproliferative activities involving 36 biomarkers across 10 systems. In contrast, EPA was cytotoxic to four cell systems at 50 μM. While 12 clinically relevant activities were shared between C15:0 and EPA at 17 μM, C15:0 had an additional 28 clinically relevant activities, especially anti-inflammatory, that were not present in EPA. Further, at 1.9 and 5.6 μM, C15:0 had cell-based properties similar to bupropion (Pearson's scores of 0.78), a compound commonly used to treat depression and other mood disorders. At 5.6 μM, C15:0 mimicked two antimicrobials, climabazole and clarithromycin (Pearson's scores of 0.76 and 0.75, respectively), and at 50 μM, C15:0 activities matched that of two common anti-cancer therapeutics, gemcitabine and paclitaxel (Pearson's scores of 0.77 and 0.74, respectively). In summary, C15:0 had dose-dependent and clinically relevant activities across numerous human cell-based systems that were broader and safer than EPA, and C15:0 activities paralleled common therapeutics for mood disorders, microbial infections, and cancer. These studies further support the emerging role of C15:0 as an essential fatty acid. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are among the most-frequently used medications. Although these medications have different mechanisms of action, they have similar indications and treatment duration has been positively correlated with cardiovascular risk although the degree of risk varies by medication. Our objective was to study treatment effects of chronic use of individual NSAID medications and acetaminophen on all-cause mortality among patients who tested positive for COVID-19 while accounting for adherence. We used the VA national datasets in this retrospective cohort study to differentiate between sporadic and chronic medication use: sporadic users filled an NSAID within the last year, but not recently or regularly. Using established and possible risk factors for severe COVID-19, we used propensity scores analysis to adjust for differences in baseline characteristics between treatment groups. Then, we used multivariate logistic regression incorporating inverse propensity score weighting to assess mortality. The cohort consisted of 28,856 patients. Chronic use of aspirin, ibuprofen, naproxen, meloxicam, celecoxib, diclofenac or acetaminophen was not associated with significant differences in mortality at 30 days (OR = 0.98, 95% CI: 0.95–1.00; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.00, 95% CI: 0.99–1.02, respectively) nor at 60 days (OR = 0.97, 95% CI: 0.95–1.00; OR = 1.00, 95% CI: 0.99–1.01; OR = 0.99, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.00; OR = 0.99, 95% CI: 0.97–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.01, 95% CI: 0.99–1.02, respectively). Although the study design cannot determine causality, the study should assure patients as it finds no association between mortality and chronic use of these medications compared with sporadic NSAID use among those infected with COVID-19. [ABSTRACT FROM AUTHOR]

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.

BackgroundRespiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase.HypothesesWe hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected.MethodsWe performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed.ResultsOne calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (p

Acute kidney injury (AKI) associated with "Triple Whammy" drug therapy consisting of renin-angiotensin system inhibitors, diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported. There have been no reports investigating "Triple Whammy" drug therapy and the time to AKI onset using adverse drug events report databases. The aim of this study was to determine the relationship between the time to AKI onset and treatment with "Triple Whammy" drug therapy. We analyzed AKI cases registered in the Japanese Adverse Drug Event Report database. The data were analyzed using the Kaplan–Meier approach, generalized Wilcoxon tests, and Weibull distribution. AKI was reported in 18,415 cases, of which 7,466 cases used Triple Whammy drugs. All combinations of Triple Whammy drugs were associated with significantly higher odds ratios for reporting AKI. In Weibull analysis, AKI onset was early for most combination patterns of Triple Whammy drugs. The Kaplan–Meier approach showed that the treatment duration to AKI onset was much shorter in cases using NSAIDs; median onsets, 8 days for triple combination, 7 days for NSAIDs added to renin-angiotensin system inhibitors, 9 days for NSAIDs added to diuretics, 6 days for diuretics added to NSAIDs, and 9 days for NSAIDs alone. AKI associated with Triple Whammy drugs is likely to occur in the early stages of treatment, especially with concomitant NSAIDs. Patients should be monitored for the occurrence of AKI within the first 2 weeks. [ABSTRACT FROM AUTHOR]

Objective: To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. Methods: We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval. Results: Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80–1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66–0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57–0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events. Conclusion: Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases. [ABSTRACT FROM AUTHOR]

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States. [ABSTRACT FROM AUTHOR]

Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

Chagas disease is a neglected illness caused by Trypanosoma cruzi and its treatment is done only with two drugs, nifurtimox and benznidazole. However, both drugs are ineffective in the chronic phase, in addition to causing serious side effects. This context of therapeutic limitation justifies the continuous research for alternative drugs. Here, we study the in vitro trypanocidal effects of the non-steroidal anti-inflammatory drug nimesulide, a molecule that has in its chemical structure a toxicophoric nitroaromatic group (NO2). The set of results obtained in this work highlights the potential for repurposing nimesulide in the treatment of this disease that affects millions of people around the world. [ABSTRACT FROM AUTHOR]

Several antibiotics demonstrate both antibacterial and anti-inflammatory/immunomodulatory activities and are used to treat inflammatory pulmonary disorders. Lefamulin is a pleuromutilin antibiotic approved to treat community-acquired bacterial pneumonia (CABP). This study evaluated lefamulin anti-inflammatory effects in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia model in which mouse airways were challenged with intranasal lipopolysaccharide. Lefamulin and comparators azithromycin and dexamethasone were administered 30min before lipopolysaccharide challenge; neutrophil infiltration into BALF and inflammatory mediator induction in lung homogenates were measured 4h postchallenge. Single subcutaneous lefamulin doses (10‒140mg/kg) resulted in dose-dependent reductions of BALF neutrophil cell counts, comparable to or more potent than subcutaneous azithromycin (10‒100mg/kg) and oral/intraperitoneal dexamethasone (0.5/1mg/kg). Lipopolysaccharide-induced pro-inflammatory cytokine (TNF-α, IL-6, IL-1β, and GM-CSF), chemokine (CXCL-1, CXCL-2, and CCL-2), and MMP-9 levels were significantly and dose-dependently reduced in mouse lung tissue with lefamulin; effects were comparable to or more potent than with dexamethasone or azithromycin. Pharmacokinetic analyses confirmed exposure-equivalence of 30mg/kg subcutaneous lefamulin in mice to a single clinical lefamulin dose to treat CABP in humans (150mg intravenous/600mg oral). In vitro, neither lefamulin nor azithromycin had any relevant influence on lipopolysaccharide-induced cytokine/chemokine levels in J774.2 mouse macrophage or human peripheral blood mononuclear cell supernatants, nor were any effects observed on IL-8‒induced human neutrophil chemotaxis. These in vitro results suggest that impediment of neutrophil infiltration by lefamulin in vivo may not occur through direct interaction with macrophages or neutrophilic chemotaxis. This is the first study to demonstrate inhibition of neutrophilic lung infiltration and reduction of pro-inflammatory cytokine/chemokine concentrations by clinically relevant lefamulin doses. This anti-inflammatory activity may be beneficial in patients with acute respiratory distress syndrome, cystic fibrosis, or severe inflammation-mediated lung injury, similar to glucocorticoid (eg, dexamethasone) activity. Future lefamulin anti-inflammatory/immunomodulatory activity studies are warranted to further elucidate mechanism of action and evaluate clinical implications. [ABSTRACT FROM AUTHOR]

Posttraumatic fibrotic scarring is a significant medical problem that alters the proper functioning of injured tissues. Current methods to reduce posttraumatic fibrosis rely on anti-inflammatory and anti-proliferative agents with broad intracellular targets. As a result, their use is not fully effective and may cause unwanted side effects. Our group previously demonstrated that extracellular collagen fibrillogenesis is a valid and specific target to reduce collagen-rich scar buildup. Our previous studies showed that a rationally designed antibody that binds the C-terminal telopeptide of the α2(I) chain involved in the aggregation of collagen molecules limits fibril assembly in vitro and reduces scar formation in vivo. Here, we have utilized a clinically relevant arthrofibrosis model to study the broad mechanisms of the anti-scarring activity of this antibody. Moreover, we analyzed the effects of targeting collagen fibril formation on the quality of healed joint tissues, including the posterior capsule, patellar tendon, and subchondral bone. Our results show that blocking collagen fibrillogenesis not only reduces collagen content in the scar, but also accelerates the remodeling of healing tissues and changes the collagen fibrils' cross-linking. In total, this study demonstrated that targeting collagen fibrillogenesis to limit arthrofibrosis affects neither the quality of healing of the joint tissues nor disturbs vital tissues and organs. [ABSTRACT FROM AUTHOR]

Gastric carcinogenesis is associated with alterations of microRNAs (miRNAs) and reversal of these alterations may be a crucial element in cancer prevention. Here we evaluate the influence of H. pylori eradication, low-dose aspirin (LDA), non-steroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPI) on modification of inflammatory mucosal miRNAs miR-155 and miR-223 in Helicobacter pylori-infected and non-infected subjects. The study was performed in two parts: 1) interventional study in 20 healthy subjects with and without H. pylori infection or following eradication (each n = 10) where LDA (100 mg) was given daily for 7 days; 2) prospective case-control observational study (n = 188). MiR-155 and miR-223 expression was strongly linked to H. pylori-infection and in short-term view showed a trend for reversal after eradication. Daily LDA as well as regular NSAIDs showed no influence on miRNAs expression both in healthy subjects and patients, while regular PPI intake was associated with lower miR-155 expression in antrum of patients with chronic gastritis independent of density of neutrophils and mononuclear infiltrate. In summary, PPI but not LDA or NSAIDs were associated with modification of inflammatory miRNAs miR-155 and miR-223 in an H. pylori dependent manner. The functional role of inflammatory miR-155 and miR-223 in understanding of H. pylori-related diseases needs further evaluation. [ABSTRACT FROM AUTHOR]

Evidence on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticoids for rheumatoid arthritis (RA) is inconclusive and is not up to date. This systematic review assessed the effectiveness and safety of these anti-inflammatories (AI) in the treatment of RA. COCHRANE (CENTRAL), MEDLINE, EMBASE, CINAHL, Web of Science and Virtual Health Library were searched to identify randomized controlled trials (RCT) with adults which used AI (dose represented in mg/day) compared with placebo or active controls and was carried out up to December of 2019. Reviewers, in pairs and independently, selected studies, performed the data extraction and assessed the risk of bias. The quality of the evidence was assessed by GRADE. Network meta-analyses were performed using the Stata v.14.2. Twenty-six articles were selected (NSAIDs = 21 and corticoids = 5). Naproxen 1,000 improved physical function, reduced pain and the number of painful joints compared to placebo. Etoricoxib 90 reduced the number of painful joints compared to placebo. Naproxen 750 reduced the number of swollen joints, except for etoricoxib 90. Naproxen 1,000, etoricoxib 90 and diclofenac 150 were better than placebo regarding patient assessment. Assessment physician showed that NSAIDs were better than placebo. Meta-analyses were not performed for prednisolone and prednisone. Naproxen 1,000 was the most effective drug and celecoxib 200 showed fewer adverse events. However, the low quality of the evidence observed for the outcomes with NSAIDs, the absence of meta-analyses to assess the outcomes with corticoids, as well as the risk of bias observed, indicate that future RCT can confirm such findings. [ABSTRACT FROM AUTHOR]

Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P

Immune checkpoint inhibitors have demonstrated significant efficacy in the treatment of a variety of cancers, however their therapeutic potential is limited by abstruse immune related adverse events. Currently, no robust animal model exists of checkpoint inhibitor-induced adverse events. Establishing such a model will improve our mechanistic understanding of this process, which in turn will inform design of improved therapies. We developed a mouse model to determine inflammatory toxicities in response to dual checkpoint blockade in the presence of syngeneic tumors. Mice from susceptible genetic backgrounds received intraperitoneal injections of anti-mouse PD-1 and CTLA-4 antibodies. The mice were monitored for weight loss and histologic evidence of inflammation. Blood was collected for basic metabolic panels and titers of anti-nuclear antibodies. In parallel, mice were also treated with prednisolone, which is commonly used to treat immune related adverse events among cancer patients. Among all the genetic backgrounds, B6/lpr mice treated with anti-CTLA-4 and anti-PD-1 antibodies developed more substantial hepatitis, pancreatitis, colitis, and pneumonitis characterized by organ infiltration of immune cells. Mice that developed tissue infiltration demonstrated high serum levels of glucose and high titers of anti-nuclear antibodies. Finally, while administration of prednisolone prevented the development of the inflammatory adverse events, it also abrogated the protective anti-tumor effect of the checkout inhibitors. Genetic background and treatment modalities jointly modified the inflammatory adverse events in tumor bearing mice, suggesting a complex mechanism for checkpoint inhibitor-related inflammation. Future studies will assess additional genetic susceptibility factors and will examine possible contributions from the administration of other anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Introduction: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters., Methods and Materials: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity., Results: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013)., Conclusion: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BackgroundMany gram-positive bacteria produce pore-forming exotoxins that contain a highly conserved, 12-residue domain (ECTGLAWEWWRT) that binds cholesterol. This domain is usually flanked N-terminally by arginine and C-terminally by valine. We used this 14-residue sequence as a template to create a small library of peptides that bind cholesterol and other lipids.Methodology/resultsSeveral of these peptides manifested anti-inflammatory properties in a predictive in vitro monocyte chemotactic assay, and some also diminished the pro-inflammatory effects of low-density lipoprotein in apoE-deficient mice. The most potent analog, Oxpholipin-11D (OxP-11D), contained D-amino acids exclusively and was identical to the 14-residue design template except that diphenylalanine replaced cysteine-3. In surface plasmon resonance binding studies, OxP-11D bound oxidized (phospho)lipids and sterols in much the same manner as D-4F, a widely studied cardioprotective apoA-I-mimetic peptide with anti-inflammatory properties. In contrast to D-4F, which adopts a stable alpha-helical structure in solution, the OxP-11D structure was flexible and contained multiple turn-like features.ConclusionGiven the substantial evidence that oxidized phospholipids are pro-inflammatory in vivo, OxP-11D and other Oxpholipins may have therapeutic potential.

Globally, usage of non-steroidal anti-inflammatory drugs (NSAIDs) in elderly with chronic pain has been reported as frequent. Though NSAIDs are fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse effects is of paramount importance as the elderly usually require multiple medications for their co-morbidities. If prescriptions are not appropriately monitored and managed, they are likely to expose patients to serious drug interactions and potentially fatal adverse effects. This study was conducted to assess the appropriateness of NSAIDs use and determine the risk of NSAIDs related potential interactions in elderly. An analytical cross-sectional study was conducted among elderly out-patients (aged 60 and above) who visited three hospitals in Asmara, Eritrea, between August 22 and September 29, 2018. A stratified random sampling design was employed and data was collected using an interview-based questionnaire and by abstracting information from patients' prescriptions and medical cards. Descriptive and analytical statistics including chi-square test and logistic regression were employed using IBM SPSS (version 22). A total of 285 respondents were enrolled in the study with similar male to female ratio. One in four of all respondents were chronic NSAIDs users and NSAIDs risk practice was reported in 24%. Using chronic NSAIDs without prophylactic gastro-protective agents, self-medication, polypharmacy and drug-drug interactions were the main problems identified. A total of 322 potential interactions in 205 patients were identified and of which, 97.2% were classified as moderate, 0.6% severe and the rest were mild. Those who involved in self-medication were more likely to be exposed to drug interactions. Diabetes (AOR = 2.39, 95% CI: 1.14, 5.02) and hypertension (AOR = 9.06, 95% CI: 4.00, 20.51) were associated with chronic NSAIDs use and incidence of potential drug interactions (AOR = 3.5, 95%CI: 1.68, 4.3; AOR = 2.81, 95%CI: 1.61, 4.9 respectively), while diabetes AOR = 4.5, 95% CI: 2.43, 8.35) and cardiac problems (AOR = 4.29, 95% CI: 1.17, 15.73) were more likely to be associated with incidence of polypharmacy. In conclusion, chronic use of NSAIDs without gastro-protective agents and therapeutic duplication of NSAIDs were commonly which requires attention from programmers, health facility managers and healthcare professionals to safeguard elderlies from preventable harm. [ABSTRACT FROM AUTHOR]

Black Americans (BA) have higher incidence and higher mortality rates for colorectal cancers (CRC) as compared to White Americans (WA). While there are several identified risk factors associated with the development of CRC and evidence that high levels of adequate screening can reduce differences in incidence for CRC between BA and WA, there remains little data regarding patient co-morbid contributions towards survival once an individual has CRC. Here we set out to identify patient risk factors that influenced overall survival in a cohort of 293 BA and 348 WA with colon cancer. Amid our cohort, we found that patients' age, tobacco usage, and pre-diagnosed medical conditions such as hypertension and diabetes were associated with shorter overall survival (OS) from colon cancer. We identified pre-diagnosed hypertension and diabetes among BA were responsible for one-third of the colon cancer mortality disparity compared with WA. We also identified long-term regular use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, was associated with shorter OS from colon cancer among WA >65 years of age, but not younger WA patients or any aged BA patients. Our results raise the importance of not only treating the colon cancer itself, but also taking into consideration co-morbid medical conditions and NSAID usage to enhance patient OS. Further evaluation regarding adequate treatment of co-morbidities and timing of NSAID continuance after cancer therapy will need to be studied. [ABSTRACT FROM AUTHOR]

No studies of the current status of treatment options are available for ankylosing spondylitis (AS) patients in South Korea. This study assesses the current status of AS treatment trends using a nationwide database. This study was conducted using a Korean National Health Insurance System (KNHIS) dataset from 2006 to 2016. We randomly extracted 50% of the total number of patients registered as As patients in the KNHIS. The distribution of the number of patients according to age and gender was analyzed each year. The types and combination methods of drugs used during the study period were estimated yearly. Between 2006 and 2016, the number of AS patients increased linearly by an average of 9% annually, 6372 in 2006 to 15188 in 2016. The study found that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was the most commonly prescribed pharmacological treatment option, followed by disease-modifying anti-rheumatic drugs (DMARDs) and then biologics. Biologics such as tumor necrosis factor alpha (TNF-α) inhibitors increased from 10% to 35% consistently for 10 years. In terms of combination therapy, DMARDs + NSAIDs accounted for almost 90% of treatments in 2006, but decreased by 65% in 2016. The use of biologics and NSAIDs increased from 3% to 28%. Prescriptions for dual therapies and mono therapies largely dominated prescription habits, accounted for up to approximately 80% of treatments. Among 10- to 14-year-old patients, there was no triple therapy, dual and triple therapies decreased gradually for those 60 and older, and the ratio of conservative treatments has increased. This study shows how South Korea reflects changes in AS treatment trends, along with the emergence of TNF-α inhibitors that are effective in treating AS. Research on clinical outcomes for AS treatments will be needed on following these drug changes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in glaucoma patients who were treated with prostaglandin analogues (PGs). Method: The presenting study was designed as a meta-analysis of previous research. Databases include PubMed, Web of science, Cochrane library, and Embase were searched with keywords of "intraocular pressure, prostaglandin analogues, NSAIDs, latanoprost, travoprost, bimatoprost, tafluprost, unoprostone, latanoprostene bunod, ketorolac, diclofenac, nepafenac, bromfenac, flurbiprofen". Inclusion criteria were: 1. Study population were glaucoma patients; 2. Comparison between PGs monotherapy and PGs in combination with topical NSAIDs; 3. Changes of IOP as final outcomes. Studies with non-randomized design, treatments combining other anti-glaucomatous drugs, or unavailable absolute IOP were excluded from the analysis. Estimated difference in IOP were calculated using STATA 14.0. Result: Seven studies were retrieved for this meta-analysis. Since there is a significant heterogeneity (I2 = 94%) in these studies, random-effect model was used to calculate pooled standardized mean differences (SMD). Our results showed a significantly favorable IOP lowering effect in glaucoma patients treated with combination of topical NSAIDs and PGEs (SMD: 1.3 and -0.03, 95% CI: 0.29 to 2.38 and -0.32 to 0.26, Z = 2.50 and 0.23, p = 0.013 and 0.820, respectively). Conclusion: Results of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of photobiomodulation therapy (PBMT) and pharmacological therapy (glucocorticoids and non-steroidal anti-inflammatory drugs) applied alone and in different combinations in mdx mice. Methods: The animals were randomized and divided into seven experimental groups treated with placebo, PBMT, prednisone, non-steroidal anti-inflammatory drug (NSAIDs), PBMT plus prednisone and PBMT plus NSAID. Wild type animals were used as control. All treatments were performed during 14 consecutive weeks. Muscular morphology, protein expression of dystrophin and functional performance were assessed at the end of the last treatment. Results: Both treatments with prednisone and PBMT applied alone or combined, were effective in preserving muscular morphology. In addition, the treatments with PBMT (p = 0.0005), PBMT plus prednisone (p = 0.0048) and PBMT plus NSAID (p = 0.0021) increased dystrophin gene expression compared to placebo-control group. However, in the functional performance the PBMT presented better results compared to glucocorticoids (p<0.0001). In contrast, the use of NSAIDs did not appear to add benefits to skeletal muscle tissue in mdx mice. Conclusion: We believe that the promising and optimistic results about the PBMT in skeletal muscle of mdx mice may in the future contribute to this therapy to be considered a safe alternative for patients with Duchenne Muscular Dystrophy (DMD) in a washout period (between treatment periods with glucocorticoids), allowing them to remain receiving effective and safe treatment in this period, avoiding at this way periods without administration of any treatment. [ABSTRACT FROM AUTHOR]

Background: The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. Objective: To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. Methods: All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. Results: Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). Conclusion: Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population. [ABSTRACT FROM AUTHOR]

Background: Quantifying dose-dependent ultra-early edema and ultrastructural changes in the myocyte after drug delivery is important for the development of new mixed calcium channel blockers (CCBs). Materials and methods: Arterial cannulation was used to measure mean arterial pressure in real time; simultaneously, magnetic resonance imaging proton density mapping was used to quantify edema 5–55 min after the delivery of L-type CCBs, T- and L-type CCBs, and solvent to a spontaneously hypertensive rat model. Transmission electron microscopy was used to show ultrastructural changes in the myocyte. Results: Analysis of variance showed significant differences among the three groups in mean arterial pressure reduction (F = 246.36, P = 5.75E-25), ultra-early level of edema (ULE) (F = 175.49, P = 5.62E-22), and dose-dependent level of edema (DLE) (F = 199.48, P = 4.28E-23). Compared with the solvent's mean arterial pressure reduction (2.65±6.56±1.64), ULE (1.16±0.09±0.02), and DLE (0.0010±0.0001±0.0000), post hoc tests showed that T- and L-type CCBs had better mean arterial pressure reduction (90.67±11.58±2.90, P = 1.06E-24 vs. 68.34±15.19±3.80, P = 1.76E-12), lower ULE (1.53±0.14±0.04, P = 4.74E-9 vs. 2.08±0.18±0.04, P = 2.68E-22), and lower DLE (0.0025±0.0004±0.0001, P = 1.14E-11 vs. 0.0047±0.0008±0.0002, P = 2.10E-11) than L- type CCBs. Transmission electron microscopy showed that T- and L-type CCBs caused fewer ultrastructural changes in the myocytes after drug delivery than L-type CCBs. Conclusion: T- and L-type CCBs produced less ultra-early and dose-dependent edema, fewer ultrastructural changes in the myocyte, and a greater antihypertensive effect. Proton density mapping combined with arterial cannulation and transmission electron microscopy allowed for quantification of ultra-early and dose-dependent edema, antihypertensive efficacy, and ultrastructural changes in the myocyte. This is important for the evaluation of induced vasodilatory edema. [ABSTRACT FROM AUTHOR]

Objective: Selective cyclooxygenase-2 inhibitors (celecoxib) can minimize the gastrointestinal complications related to non-steroidal anti-inflammatory drug (NSAID) use. NAXOZOL is a new combination formulation designed to provide sequential delivery of a non-enteric-coated, immediate-release esomeprazole strontium tetrahydrate 20 mg mantle followed by an enteric-coated naproxen 500 mg core. However, there have been no studies comparing NAXOZOL to celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. This study was undertaken to compare the effects of NAXOZOL and celecoxib with respect to gastrointestinal tract protection and pain relief in patients with osteoarthritis. Methods: The randomized enrolled patients were divided into two treatment groups: a NAXOZOL group and a celecoxib group. All participants received treatments (NAXOZOL, 500/20 mg (naproxen 500 mg, esomeprazole strontium tetrahydrate 20 mg) twice per day versus celecoxib, 200 mg daily) on a 1:1 allocation basis for 12 weeks. The primary outcome was the Leeds Dyspepsia Questionnaire (LDQ) score used for non-inferiority testing. Secondary outcome measures included the Gastrointestinal Symptom Rating Scale (GSRS) score, Visual Analogue Scale (VAS) score, European Quality of Life-5 dimensions (EQ-5D) scale and the EQ-5D Visual Analogue Scale (EQ VAS). Other outcome measures included the use of supplementary or rescue drugs, and the incidence of adverse events. Results: The baseline-adjusted LDQ scores immediately after 12 weeks of treatment in NAXOZOL group were not inferior to those in celecoxib group. The overall change in the baseline-adjusted GSRS score, VAS score, EQ-5D, and EQ VAS was not different between the two groups. The usage of supplementary drugs and the drug-related incidence of adverse events were not different. However, the days to use rescue drug were longer in celecoxib group than in NAXOZOL group. Conclusion: NAXOZOL was not inferior to celecoxib in protecting the gastrointestinal tract and providing pain relief in patients with osteoarthritis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to demonstrate the non-inferiority of a single intra-articular injection of 2.0% non-chemically modified sodium hyaluronate (SH) vs 0.8% hylan G-F 20 (control) in symptomatic knee osteoarthritis. Design: This was a double-blind, randomized, controlled trial conducted in patients with painful tibiofemoral osteoarthritis (American College of Rheumatology criteria) with insufficient response or intolerance to first-line analgesics and regular non-steroidal anti-inflammatory drugs. Subjects received a single intra-articular injection of either SH or hylan G-F 20. The primary outcome was the 6-month change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale (WOMAC A), with a pre-specified lower margin for non-inferiority of 8 mm. Results: Of the 292 patients randomized (SH: 144), 288 received an injection (SH: 142), 266 completed the study (SH: 134). In the Per Protocol dataset (SH: 113, control: 112), the WOMAC A change at 6 months was -34.3 mm (95% confidence interval (CI): -37.8, -30.8) and -36.2 mm (95% CI: -40.3, -32.1) for the SH and hylan G-F 20 patients, respectively (P = 0.5). The intergroup difference was -1.9 mm (95% CI: -7.3, 3.5). Results were similar in the Full Analysis Set (SH: 139, control: 141) with a difference between the groups of -2.9 mm (95% CI: -7.9, 2.2). A total of 31.3% of the injected patients reported a treatment-emergent adverse event, including injection site reactions (pain, inflammation or effusion) which occurred in 8.5% of the SH patients vs 13.0% of the hylan G-F 20 patients. No serious reactions were reported. Conclusions: This clinical trial demonstrated the non-inferiority of a single intra-articular injection of SH vs hylan G-F 20 on the WOMAC A change from baseline at 6 months. [ABSTRACT FROM AUTHOR]

Enhancement of oral absorption of food allergens by non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, is considered an exacerbating factor in the development of food allergies. In this study, we examined the effect of aspirin on oral sensitization to and absorption of the egg-white allergen ovalbumin (OVA) in rats. The absorption of OVA was evaluated by measuring the plasma concentration of OVA after oral administration by gavage. To evaluate oral sensitization to OVA, plasma levels of immunoglobulin (Ig) E and IgG1 antibodies (Abs) specific to OVA were determined by enzyme-linked immunosorbent assay after initiation of sensitization. High-dose aspirin (30 mg/kg) increased oral OVA absorption and plasma levels of OVA-specific IgE and IgG1 Abs compared with those observed in vehicle-treated rats. In contrast, low-dose aspirin (3 mg/kg) exerted no changes in either absorption or sensitization. Spermine, an absorption enhancer, increased the oral absorption of OVA to nearly the same extent as high-dose aspirin, whereas the plasma levels of OVA-specific IgE and IgG1 Abs exhibited no significant differences between spermine- and vehicle-treated rats. Among the NSAIDs, diclofenac and indomethacin increased sensitization to OVA, similar to high-dose aspirin, but meloxicam exerted no effects on Ab levels. In conclusion, we showed that high-dose aspirin enhanced oral sensitization to OVA. Our study suggests that enhanced oral sensitization to OVA cannot be ascribed to increased absorption of OVA from the intestinal tract. Although the mechanisms underlying this enhancement of sensitization are still controversial, our study suggests that modification of cytokine production due to impairment of the intestinal barrier function and inhibition of cyclooxygenase-1 activity by aspirin may be involved. [ABSTRACT FROM AUTHOR]

Background: Studies investigating the effectiveness of acupuncture therapies in alleviating pain in pelvic inflammatory disease (PID) have gained increasing attention. However, to date, there have been no systematic reviews and meta-analyses providing high-quality evidence regarding the efficacy and safety of acupuncture therapies in this context., Objective: The objective of this review was to assess the efficacy and safety of acupuncture therapies as complementary or alternative treatments for pain relief in patients with PID., Method: A comprehensive search was conducted in eight databases from inception to February 20, 2023: PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database. Randomized controlled trials (RCTs) investigating acupuncture therapies as complementary or additional treatments to routine care were identified. Primary outcomes were pain intensity scores for abdominal or lumbosacral pain. The Cochrane risk of bias criteria was applied to assess the methodological quality of the included trials. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence. Data processing was performed using RevMan 5.4., Result: This systematic review included twelve trials comprising a total of 1,165 patients. Among these, nine trials examined acupuncture therapies as adjunctive therapy, while the remaining three did not. Meta-analyses demonstrated that acupuncture therapies, whether used alone or in combination with routine treatment, exhibited greater efficacy in relieving abdominal pain compared to routine treatment alone immediately after the intervention (MD: -1.32; 95% CI: -1.60 to -1.05; P < 0.00001). The advantage of acupuncture therapies alone persisted for up to one month after the treatment (MD: -1.44; 95% CI: -2.15 to -0.72; P < 0.0001). Additionally, acupuncture therapies combined with routine treatment had a more pronounced effect in relieving lumbosacral pain after the intervention (MD: -1.14; 95% CI: -2.12 to -0.17; P < 0.00001) in patients with PID. The incidence of adverse events did not increase with the addition of acupuncture therapies (OR: 0.56; 95% CI: 0.21 to 1.51; P = 0.25). The findings also indicated that acupuncture therapies, as a complementary treatment, could induce anti-inflammatory cytokines, reduce pro-inflammatory cytokines, alleviate anxiety, and improve the quality of life in patients with PID., Conclusion: Our findings suggest that acupuncture therapies may effectively reduce pain intensity in the abdomen and lumbosacral region as complementary or alternative treatments, induce anti-inflammatory cytokines, decrease pro-inflammatory cytokines, alleviate anxiety, and enhance the quality of life in patients with PID, without increasing the occurrence of adverse events. However, due to the low quality of the included trials, the conclusion should be interpreted with caution, highlighting the need for further high-quality trials to establish more reliable conclusions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P < 0.001 for each), but it was not significantly different from the sham group (6.2 ± 4.0 pg/mL, P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1β and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Iwata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)