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Electrical signaling plays a crucial role in the cellular response to tissue injury in wound healing and an external electric field (EF) may expedite the healing process. Here, we have developed a standalone, wearable, and programmable electronic device to administer a well-controlled exogenous EF, aiming to accelerate wound healing in an in vivo mouse model to provide pre-clinical evidence. We monitored the healing process by assessing the re-epithelization rate and the ratio of M1/M2 macrophage phenotypes through histology staining. Following three days of treatment, the M1/M2 macrophage ratio decreased by 30.6% and the re-epithelization in the EF-treated wounds trended towards a non-statically significant 24.2% increase compared to the control. These findings provide point towards the effectiveness of the device in shortening the inflammatory phase by promoting reparative macrophages over inflammatory macrophages, and in speeding up re-epithelialization. Our wearable device supports the rationale for the application of programmed EFs for wound management in vivo and provides an exciting basis for further development of our technology based on the modulation of macrophages and inflammation to better wound healing.

Hemorrhagic shock and resuscitation (HSR) enhances the risk of acute lung injury (ALI). This study investigated the protective effect of carbamazepine (CBZ) on HSR-induced ALI in rats. Male Sprague-Dawley rats were allocated into five distinct groups through randomization: control (SHAM), saline + HSR (HSR), CBZ + HSR (CBZ/HSR), dimethyl sulfoxide (DMSO) + HSR (DMSO/HSR), and CBZ + chloroquine (CQ) + HSR (CBZ/CQ/HSR). Subsequently, HSR models were established. To detect tissue damage, we measured lung histological changes, lung injury scores, and wet/dry weight ratios. We measured neutrophil counts as well as assessed the expression of inflammatory factors using RT-PCR to determine the inflammatory response. We detected autophagy-related proteins LC3II/LC3I, P62, Beclin-1, and Atg12-Atg5 using western blotting. Pretreatment with CBZ improved histopathological changes in the lungs and reduced lung injury scores. The CBZ pretreatment group exhibited significantly reduced lung wet/dry weight ratio, neutrophil aggregation and number, and inflammation factor (TNF-α and iNOS) expression. CBZ changed the expression levels of autophagy-related proteins (LC3II/LC3I, beclin-1, Atg12-Atg5, and P62), suggesting autophagy activation. However, after injecting CQ, an autophagy inhibitor, the beneficial effects of CBZ were reversed. Taken together, CBZ pretreatment improved HSR-induced ALI by suppressing inflammation, at least in part, through activating autophagy. Thus, our study offers a novel perspective for treating HSR-induced ALI. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of minocycline on the alveolar bone in experimental periodontitis in rats. Thirty Wistar rats were randomly assigned to three groups: control without periodontitis; experimental periodontitis induced by ligature; experimental periodontitis + intraperitoneal administration minocycline for seven days. Ligatures remained in place in both periodontitis groups for 14 days. At the end of the experiment, the animals were euthanized and one hemimandible underwent micro-computed tomography (micro-CT) analysis to assess vertical bone loss and alveolar bone quality. Histopathological analysis was performed on the other hemimandible. Statistical analysis was performed using ANOVA with Tukey's post-test (p<0.05). The results showed a significant reduction in vertical bone loss in the animals treated with minocycline compared with untreated animals. Minocycline also preserved the alveolar bone thickness, number, spacing, and bone volume to tissue volume ratio. Histopathological analysis indicated that minocycline reduced bone resorption, decreased inflammatory response, and maintained the bone collagen fibers. This study demonstrated the effectiveness of minocycline in reducing vertical bone loss and preserved bone quality in rats with experimental periodontitis. The results of this study indicate that minocycline has the potential to serve as an additional treatment option for periodontitis. However, further research is warranted to assess the efficacy and safety of minocycline use in patients with periodontitis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the efficacy and safety of berberine(BBR) plus 5-aminosalicylic acid (5-ASA) for treating ulcerative colitis (UC). Methods: A comprehensive search was conducted in electronic databases, including Medline/PubMed, Sinomed, Embase, CNKI, Wanfang, and VIP, through January 2024 to identify all randomized controlled trials (RCTs) that administered BBR conjunction in standard therapy(5-ASA) for to support the treatment of UC. The data were synthesized using a meta-analysis approach with RevMan 5.4.1. The primary endpoint was the clinical efficacy rate. In contrast, the secondary endpoints included the Baron score, disease activity index (DAI) score, symptom relief latency, inflammatory markers, immunological indicators, and adverse events. Results: In this analysis, 10 RCTs comprising 952 patients with UC were examined. BBR considerably improved the clinical efficacy rate (RR = 1.22, 95% CI [1.15, 1.30], P < 0.00001), attenuated the Baron score (SMD = -1.72, 95% CI [-2.30, -1.13], P < 0.00001) and reduced the DAI score (SMD = -2.93, 95% CI [-4.42, -1.43], P < 0.00001). Additionally, it ameliorated clinical symptoms (SMD = -2.74, 95% CI [-3.45, 2.02], P < 0.00001), diminished inflammatory responses (SMD = -1.59, 95% CI [-2.14, 1.04], P < 0.00001), and modulated immune reactions (SMD = 1.06,95% CI [0.24,1.87], P <0.00001). Nonetheless, the impact of BBR on reducing adverse reactions was not statistically significant (RR = 0.75, 95% CI [0.42, 1.33], P > 0.05). Conclusion: BBR demonstrates substantial efficacy in treating UC without causing severe adverse reactions and may serve as a viable complementary therapy. However, its clinical application warrants confirmation by additional high-quality, low-bias RCTs. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse" published in the journal PLoS ONE. The correction states that there are errors in Figures 2 to 6, including incorrect labels and axes. The authors have provided the correct versions of the figures and tables. The article explores the effects of paternal arachidonic acid supplementation on offspring behavior and inflammation markers in the hypothalamus. [Extracted from the article]

Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies. [ABSTRACT FROM AUTHOR]

Objectives: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms. Methods: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing. Results: AS-IV decreased the levels of TNF-α, IL-6, and IL-1β in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria. Conclusion: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats. [ABSTRACT FROM AUTHOR]

We investigated the interactions of unopsonized and opsonized Mycoplasma mycoides subsp. mycoides (Mmm) with bovine macrophages in vitro. Mmm survived and proliferated extracellularly on bovine macrophage cell layers in the absence of Mmm-specific antisera. Bovine complement used at non-bactericidal concentrations did neither have opsonizing effect nor promoted intracellular survival, whereas Mmm-specific antisera substantially increased phagocytosis and Mmm killing. A phagocytosis-independent uptake of Mmm by macrophages occurred at a high multiplicity of infection, also found to induce the production of TNF, and both responses were unaffected by non-bactericidal doses of bovine complement. Bovine complement used at higher doses killed Mmm in cell-free cultures and completely abrogated TNF responses by macrophages. These results provide a framework to identify Mmm antigens involved in interactions with macrophages and targeted by potentially protective antibodies and point towards a pivotal role of complement in the control of inflammatory responses in contagious bovine pleuropneumonia. [ABSTRACT FROM AUTHOR]

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis. [ABSTRACT FROM AUTHOR]

HIV can be successfully suppressed to undetectable levels by antiretroviral therapy (ART) in most people with HIV (PWH). However, a small proportion continues to have persistent low-level viremia (LLV) during ART. A presumed source of LLV is production or replication from viral reservoirs, which are maintained in the presence of ART. It is unknown whether the oral cavity can be considered an HIV reservoir. As periodontal inflammation is a common problem in PWH, we hypothesize that periodontal inflammation in the oral cavity activates (latently) infected cells and thus might be associated with LLV. We included 11 individuals with HIV LLV, and compared HIV-RNA levels in saliva and plasma at baseline and at week 24 after switch of ART. We compared the LLV-group at baseline with 11 age-matched controls with suppressed viremia. To investigate the severity of periodontitis we used Periodontal Inflamed Surface Areas (PISA) by measuring probing depth, gingival recession, bleeding on probing and clinical attachment level. Severity of periodontitis was classified according to the CDC-AAP case definition. Additional insights in periodontal inflammation were obtained by comparing immune activation markers and the presence of periodontal pathogens. In four individuals of the LLV group, residual levels of HIV-RNA were detected in saliva at baseline (N = 1) or at week 24 (N = 2) or both (N = 1). Of the four individuals with LLV, three had residual levels of HIV-RNA in saliva. All 22 individuals had moderate to severe periodontitis. PISA was not significantly different between cases with LLV and controls. Similarly, periodontal pathogens were frequently observed in both groups. Total activated HLA-DR+CD38+ CD4+ cells and CD8+ cells were significantly higher in the LLV group than in the control group (p = <0.01). No immune markers were associated with LLV. In conclusion, periodontal inflammation is an unlikely driver of HIV LLV compared to HIV suppressed individuals. [ABSTRACT FROM AUTHOR]

Background and objective: Pulmonary fibrosis caused by lung injury is accompanied by varying degrees of inflammation, and diazepam can reduce the levels of inflammatory factors. Therefore, the purpose of this study was to determine whether diazepam can inhibit inflammation and ameliorate pulmonary fibrosis by regulating the let-7a-5p/myeloid differentiation factor 88 (MYD88) axis. Methods: Lipopolysaccharide (LPS) was used to induce cell pyroptosis in an animal model of pulmonary fibrosis. After treatment with diazepam, changes in cell proliferation and apoptosis were observed, and the occurrence of inflammation and pulmonary fibrosis in the mice was detected. Results: The results showed that LPS can successfully induce cell pyroptosis and inflammatory responses and cause lung fibrosis in mice. Diazepam inhibits the expression of pyroptosis-related factors and inflammatory factors; moreover, it attenuates the occurrence of pulmonary fibrosis in mice. Mechanistically, diazepam can upregulate the expression of let-7a-5p, inhibit the expression of MYD88, and reduce inflammation and inhibit pulmonary fibrosis by regulating the let-7a-5p/MYD88 axis. Conclusion: Our findings indicated that diazepam can inhibit LPS-induced pyroptosis and inflammatory responses and alleviate pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis. [ABSTRACT FROM AUTHOR]

Pro-inflammatory changes contribute to multiple neuropsychiatric illnesses. Understanding how these changes are involved in illnesses and identifying strategies to alter inflammatory responses offer paths to potentially novel treatments. We previously found that acute pro-inflammatory stimulation with high (μg/ml) lipopolysaccharide (LPS) for 10–15 min dampens long-term potentiation (LTP) in the hippocampus and impairs learning. Effects of LPS involved non-canonical inflammasome signaling but were independent of toll-like receptor 4 (TLR4), a known LPS receptor. Low (ng/ml) LPS also inhibits LTP when administered for 2–4 h, and here we report that this LPS exposure requires TLR4. We also found that effects of low LPS on LTP involve the oxysterol, 25-hydroxycholesterol, akin to high LPS. Effects of high LPS on LTP are blocked by inhibiting synthesis of 5α-reduced neurosteroids, indicating that neurosteroids mediate LTP inhibition. 5α-Neurosteroids also have anti-inflammatory effects, and we found that exogenous allopregnanolone (AlloP), a key 5α-reduced steroid, prevented effects of low but not high LPS on LTP. We also found that activation of TLR2, TLR3 and TLR7 inhibited LTP and that AlloP prevented the effects of TLR2 and TLR7, but not TLR3. The enantiomer of AlloP, a steroid that has anti-inflammatory actions but low activity at GABAA receptors, prevented LTP inhibition by TLR2, TLR3 and TLR7. In vivo, both AlloP enantiomers prevented LPS-induced learning defects. These studies indicate that neurosteroids play complex roles in network effects of acute neuroinflammation and have potential importance for development of AlloP analogues as therapeutic agents. [ABSTRACT FROM AUTHOR]

Periprosthetic tissue inflammation is a challenging complication arising in joint replacement surgeries, which is often caused by wear debris from polyethylene (PE) components. In this study, we examined the potential biological effects of grafting a [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) polymer onto the surface of PE through a solvent-evaporation technique. J774A.1 macrophage-like cells and primary cultured mouse osteoblasts were treated with PE powder with or without the MEDSAH coating. MEDSAH grafting on PE substantially reduced the expression of pro-inflammatory cytokines and other mediators in primary cultured mouse osteoblasts, but did not significantly impact macrophage-mediated inflammation. Our findings suggest that a MEDSAH coating on PE-based materials has potential utility in mitigating periprosthetic tissue inflammation and osteolysis and preventing aseptic loosening in total joint replacements. Further research, including large-scale clinical trials and biomechanical analyses, is needed to assess the long-term performance and clinical implications of MEDSAH-coated PE-based materials in total joint arthroplasty. [ABSTRACT FROM AUTHOR]

Objective: To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient synovial cells, aiming to provide new insights for clinical treatment strategies. Materials and methods: Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset. Results: The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression. Conclusion: The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a multi-pathogenic disease characterized by chronic skin inflammation and barrier dysfunction. Therefore, improving the skin's ability to form an epidermal barrier and suppressing the production of cytokines that induce type 2 inflammatory responses are important for controlling atopic dermatitis symptoms. (-)-Blebbistatin, a non-muscle myosin II inhibitor, has been suggested to improve pulmonary endothelial barrier function and control inflammation by suppressing immune cell migration; however, its efficacy in atopic dermatitis is unknown. In this study, we investigated whether (S)-(-)-blebbistatin O-benzoate, a derivative of (-)-blebbistatin, improves dermatitis symptoms in a mite antigen-induced atopic dermatitis model using NC/Nga mice. The efficacy of the compound was confirmed using dermatitis scores, ear thickness measurements, serum IgE levels, histological analysis of lesions, and filaggrin expression analysis, which is important for barrier function. (S)-(-)-Blebbistatin O-benzoate treatment significantly reduced the dermatitis score and serum IgE levels compared to those in the vehicle group (p < 0.05). Furthermore, the histological analysis revealed enhanced filaggrin production and a decreased number of mast cells (p < 0.05), indicating that (S)-(-)-blebbistatin O-benzoate improved atopic dermatitis symptoms in a pathological model. In vitro analysis using cultured keratinocytes revealed increased expression of filaggrin, loricrin, involucrin, and ceramide production pathway-related genes, suggesting that (S)-(-)-blebbistatin O-benzoate promotes epidermal barrier formation. Furthermore, the effect of (S)-(-)-blebbistatin O-benzoate on type 2 alarmin cytokines, which are secreted from epidermal cells upon scratching or allergen stimulation and are involved in the pathogenesis of atopic dermatitis, was evaluated using antigens derived from mite feces. The results showed that (S)-(-)-blebbistatin O-benzoate inhibited the upregulation of these cytokines. Based on the above, (S)-(-)-blebbistatin O-benzoate has the potential to be developed as an atopic dermatitis treatment option that controls dermatitis symptoms by suppressing inflammation and improving barrier function by acting on multiple aspects of the pathogenesis of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Network oscillation in the anterior cingulate cortex (ACC) plays a key role in attention, novelty detection and anxiety; however, its involvement in cognitive impairment caused by acute systemic inflammation is unclear. To investigate the acute effects of systemic inflammation on ACC network oscillation and cognitive function, we analyzed cytokine level and cognitive performance as well as network oscillation in the mouse ACC Cg1 region, within 4 hours after lipopolysaccharide (LPS, 30 μg/kg) administration. While the interleukin-6 concentration in the serum was evidently higher in LPS-treated mice, the increases in the cerebral cortex interleukin-6 did not reach statistical significance. The power of kainic acid (KA)-induced network oscillation in the ACC Cg1 region slice preparation increased in LPS-treated mice. Notably, histamine, which was added in vitro, increased the oscillation power in the brain slices from LPS-untreated mice; for the LPS-treated mice, however, the effect of histamine was suppressive. In the open field test, frequency of entries into the center area showed a negative correlation with the power of network oscillation (0.3 μM of KA, theta band (3–8 Hz); 3.0 μM of KA, high-gamma band (50–80 Hz)). These results suggest that LPS-induced systemic inflammation results in increased network oscillation and a drastic change in histamine sensitivity in the ACC, accompanied by the robust production of systemic pro-inflammatory cytokines in the periphery, and that these alterations in the network oscillation and animal behavior as an acute phase reaction relate with each other. We suggest that our experimental setting has a distinct advantage in obtaining mechanistic insights into inflammatory cognitive impairment through comprehensive analyses of hormonal molecules and neuronal functions. [ABSTRACT FROM AUTHOR]

BACKGROUND: The gut-brain axis involves bidirectional communication between the gut-microbiota and central nervous system. This study aimed to investigate whether probiotics and/or prebiotics, known as Microbiome-targeted Therapies (MTTs), improve cognition and prevent postoperative cognitive dysfunction (POCD). METHODS: Relevant animal and human studies were identified using a systematic database search (PubMed, EMBASE, Cochrane Library, and Web of Science), focusing on the effects of MTTs on inflammation, perioperative and non-perioperative cognitive impairment. Screening and data extraction were conducted by two independent reviewers. The Risk of bias was assessed using the SYRCLEs risk of bias tool for animal studies. The revised Cochrane risk of bias tool (RoB 2) was used for human studies. RESULTS: A total of 24 articles were selected; 16 of these involved animal studies, and 8 described studies in humans. In these papers, the use of MTTs consistently resulted in decreased inflammation in perioperative and non-perioperative settings. Out of 16 animal studies, 5 studies (2 associated with delirium and 3 studies related to POCD) were conducted in a perioperative setting. MTTs improved perioperative cognitive behavior and reduced inflammation in all 5 animal studies. Eleven animal studies were conducted in a non-perioperative setting. In all of these studies, MTTs showed improvement in learning and memory function. MTTs showed a positive effect on levels of pro-inflammatory cytokines and biomarkers related to cognitive function. Among the 8 human studies, only one study examined the effects of perioperative MTTs on cognitive function. This study showed a reduced incidence of POCD along with improved cognitive function. Of the remaining 7 studies, 6 suggested that MTTs improved behavioral test results and cognition in non-perioperative environments. One study failed to show any significant differences in memory, biomarkers of inflammation, or oxidative factors. CONCLUSION: In the studies we examined, most showed that MTTs decrease inflammation by down-regulating inflammatory cytokines and oxidative stress in both perioperative and non-perioperative settings. In general, MTTs also seem to have a positive effect on cognition through neural, immune, endocrine, and metabolic pathways. However, these effects have not yet resulted in a consensus regarding preventative strategies or treatments. Based on these current research results, MTTs could be a potential new preventative strategy for cognitive impairment after surgery.

PURPOSE: Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy. METHOD: Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array. RESULTS: Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at P

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. METHODS: Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-

Clinical illness (CI) scoring using visual observation is the most widely applied method of detecting respiratory disease in cattle but has limited effectiveness in practice. In contrast, body-mounted sensor technology effectively facilitates disease detection. To evaluate whether a combination of movement behavior and CI scoring is effective for disease detection, cattle were vaccinated to induce a temporary inflammatory immune response. Cattle were evaluated before and after vaccination to identify the CI variables that are most indicative of sick cattle. Respiratory rate (H2 = 43.08, P < 0.0001), nasal discharge (H2 = 8.35, P = 0.015), and ocular discharge (H2 = 16.38, P = 0.0003) increased after vaccination, and rumen fill decreased (H2 = 20.10, P < 0.0001). Locomotor activity was measured via leg-mounted sensors for the four days preceding and seven days following vaccination. A statistical model that included temperature, steps, lying time, respiratory rate, rumen fill, head position, and excess saliva was developed to distinguish between scores from before and after vaccination with a sensitivity of 0.898 and specificity of 0.915. Several clinical illness signs were difficult to measure in practice. Binoculars were required for scoring respiratory rate and eye-related metrics, and cattle had to be fitted with colored collars for individual identification. Scoring each animal took up to three minutes in a small research pen; therefore, technologies that can automate both behavior monitoring and identification of clinical illness signs are key to improving capacity for BRD detection and treatment. [ABSTRACT FROM AUTHOR]

Background: Emerging epidemiological evidence indicates nature exposure could be associated with greater health benefits among groups in lower versus higher socioeconomic positions. One possible mechanism underpinning this evidence is described by our framework: (susceptibility) adults in low socioeconomic positions face higher exposure to persistent psychosocial stressors in early life, inducing a pro-inflammatory phenotype as a lifelong susceptibility to stress; (differential susceptibility) susceptible adults are more sensitive to the health risks of adverse (stress-promoting) environments, but also to the health benefits of protective (stress-buffering) environments. Objective: Experimental investigation of a pro-inflammatory phenotype as a mechanism facilitating greater stress recovery from nature exposure. Methods: We determined differences in stress recovery (via heart rate variability) caused by exposure to a nature or office virtual reality environment (10 min) after an acute stressor among 64 healthy college-age males with varying levels of susceptibility (socioeconomic status, early life stress, and a pro-inflammatory state [inflammatory reactivity and glucocorticoid resistance to an in vitro bacterial challenge]). Results: Findings for inflammatory reactivity and glucocorticoid resistance were modest but consistently trended towards better recovery in the nature condition. Differences in recovery were not observed for socioeconomic status or early life stress. Discussion: Among healthy college-age males, we observed expected trends according to their differential susceptibility when assessed as inflammatory reactivity and glucocorticoid resistance, suggesting these biological correlates of susceptibility could be more proximal indicators than self-reported assessments of socioeconomic status and early life stress. If future research in more diverse populations aligns with these trends, this could support an alternative conceptualization of susceptibility as increased environmental sensitivity, reflecting heightened responses to adverse, but also protective environments. With this knowledge, future investigators could examine how individual differences in environmental sensitivity could provide an opportunity for those who are the most susceptible to experience the greatest health benefits from nature exposure. [ABSTRACT FROM AUTHOR]

Introduction: Wim Hof, also known as the iceman, developed a method called Wim Hof Method (WHM) which he claims to have several benefits on physical and mental health. The aim of this systematic review is to identify and synthesise the results of the studies conducted on WHM on physiological and psychological health-related outcomes. Materials and methods: This systematic review followed the PRISMA guidelines for systematic reviews. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42022333209. Medline and Web of Science were searched and included studies from January 1, 2014, to July 4, 2022. Studies were included if they met the predetermined inclusion/exclusion criteria. Inclusion criteria included RCTs and cohort studies published in peer-reviewed journals, studies conducted on healthy individuals and people with pre-existing medical conditions (adolescents and adults over the age of 14), studies that included all three pillars (breathing, cold exposure, and commitment) of the WHM, and studies that only focused on Wim Hof breathing method (WHBM). Exclusion criteria included studies that discussed WHM but are not original experimental research or are not peer-reviewed, studies that included children under the age of 14, and studies that used methods similar to WHM, but not actually WHM, such as tummo meditation. The articles were assessed for risk of bias using RoB 2.0 and Scottish Intercollegiate Guidelines Network (SIGN) tools. The effects of WHM were categorised into physiological or psychological related outcomes and narrative synthesis was conducted. Results: Nine papers were included in this review which consisted of eight individual trials. The findings suggest that the WHM may reduce inflammation in healthy and non-healthy participants as it increases epinephrine levels, causing an increase in interleukin-10 and a decrease in pro-inflammatory cytokines. Additionally, effect of WHBM on exercise performance showed mixed findings. Effects on respiratory parameters of minute ventilation, tidal volume, and breathing frequency were mixed following bouts of exercise. Conclusion: Taken together, the findings of this review show promising use of WHM in the inflammatory response category. The focus of future studies should further investigate the benefits of WHM in non-healthy participants with inflammatory disorders and explore the use of Wim Hof breathing method to enhance exercise performance. [ABSTRACT FROM AUTHOR]

Recently, particulate matter (PM) has been shown to exacerbate atopic dermatitis (AD) by inducing an inflammatory response. Meanwhile, several studies revealed that exosomes derived from adipose tissue-derived mesenchymal stem cells promote wound healing and alleviate inflammation via their regenerative and immunomodulatory capacities. Our study aimed to investigate the effects of human adipose tissue-derived mesenchymal stem cell-derived (ASC)-exosomes in PM-induced AD. An AD-like triple-cell model was established by treating human keratinocytes, dermal fibroblasts, and mast cells with polyinosinic:polycytidylic acid (Poly I:C) and interleukin 1 alpha (IL-1α). The effects of PM and ASC-exosomes on the expression of pro-inflammatory cytokines and skin barrier proteins were examined using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. PM increased pro-inflammatory cytokines (IL-6, IL-1β, and IL-1α) and decreased the anti-inflammatory cytokine IL-10, while the mRNA expression of skin barrier proteins (loricrin and filaggrin) decreased. However, when the cells were treated with ASC-exosomes, the PM-induced effects on pro-inflammatory cytokines and skin barrier proteins were reversed. Our results confirmed that PM-induced inflammation and skin barrier damage were alleviated by ASC-exosomes in our AD-like triple-cell model. These data suggest that ASC-exosomes can serve as a therapeutic agent for PM-exacerbated AD. [ABSTRACT FROM AUTHOR]

Introduction: Common cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset. Methods: Out of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11). Results: Comparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p < 0.0001). Earlier and lower symptom severity peak resulted, with shorter time to remission (average 8.9 vs. 10.7 days with latest treatment initiation, p < 0.05), and higher and faster recovering quality of life (p < 0.05). Tolerability was mostly rated as "very good", with adverse events of suspected causal relationship reported in 4.3% of participants. Conclusions: Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole. [ABSTRACT FROM AUTHOR]

Purpose: To establish the effects of anterior chamber inflammation (ACI) on the corneal endothelium parameters and central corneal thickness (CCT). Methods: We conducted a comprehensive literature review using medical databases (PubMed, EMBASE, VHL, and medRxiv) on March 8, 2023, for studies that included patients with ACI who had undergone specular microscopy or pachymetry. Case series with >10 patients, cross-sectional, case-control, and cohort studies were included. The risk of bias was assessed using CLARITY tools and validated scales such as those by Hassan Murad et al. and Hoy et al. A narrative synthesis and a quantitative standardized mean difference meta-analysis, I2 heterogeneity assessment, and publication bias tests were conducted. The study was registered in PROSPERO (CRD42023420148) and approved by the Universidad del Rosario ethical committee (DVO005 2277- CV1712). Results: Thirty-four studies, encompassing 1,388 eyes with ACI, were included. Compared with healthy controls, overall, ACI eyes show significant mean differences in endothelial parameters (endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX)) (P < 0.05). In the subgroup analysis compared with healthy controls, both active and chronic-recurrent ACI demonstrated a reduced ECD. An increased CV was observed in active, inactive, and chronic-recurrent ACI. Lower HEX was evident in inactive, acute, and chronic-recurrent ACI, while both active and acute ACI exhibited high CCT. Conclusion: ACI leads to significant alterations in endothelial parameters and CCT. The primary contributors to these changes are increased IOP, uveitis duration, and intraocular surgeries. Further studies are needed to explore the impact of ACI etiology on the endothelium, potential biases in IOP measurements during acute ACI episodes, and the potential necessity for monitoring the endothelial parameters and CCT in patients with chronic ACI. [ABSTRACT FROM AUTHOR]

Objectives: Chronic immune activation and severe inflammatory states are positively associated with resting metabolic rate (RMR; kcal/day), but the impacts of mild immune stimuli on metabolism are poorly understood. This study investigates the within-individual association between the inflammatory response to influenza vaccination and RMR in young adults. Methods: We evaluated RMRs through indirect calorimetry and circulating c-reactive protein (CRP) concentrations (mg/L)—a direct measure of inflammation—via high-sensitivity immunoassays of dried blood spots (n = 17) at baseline and two- and seven-days post-vaccine. Wilcoxon matched-pairs signed-rank tests were used to evaluate the magnitude of the CRP and RMR responses. Type II Wald chi-square tests of linear mixed-effect models assessed whether those responses were correlated. Results: Baseline CRP was 1.39 ± 1.26 mg/L. On day two post-vaccine, CRP increased by 1.47 ± 1.37 mg/L (p < 0.0001), representing a 106% increase above baseline values. CRP remained higher on day seven post-vaccine, 1.32 ± 2.47 mg/L (p = 0.05) above baseline values. There were no statistically significant changes in RMR from baseline to day two (p = 0.98) or day seven (p = 0.21). Change in CRP from baseline did not predict RMR variation across days (p = 0.46). Conclusions: We find no evidence that adult influenza vaccination results in a corresponding increase in RMR. These results suggest that the energetic cost of an influenza vaccine's mild inflammatory stimulus is either too small to detect or is largely compensated by a temporary downregulation of energy allocated to other metabolic tasks. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea is increasing worldwide, leading to disordered sleep patterns and inflammatory responses in brain and peripheral tissues that predispose individuals to chronic disease. Pro-inflammatory cytokines activate the inflammatory response and are normally regulated by glucocorticoids secreted from adrenal glands. However, the temporal dynamics of inflammatory responses and hypothalamic-pituitary-adrenal (HPA) axis activation in relation to acute sleep fragmentation (ASF) are undescribed. Male C57BL/6J mice were exposed to ASF or control conditions (no ASF) over specified intervals (1, 2, 6, or 24 h) and cytokine gene expression (IL-1β, TNF-α) in brain and peripheral tissues as well as serum glucocorticoid and interleukin-6 (IL-6) concentration were assessed. The HPA axis was rapidly activated, leading to elevated serum corticosterone from 1–24 h of ASF compared with controls. This activation was followed by elevated serum IL-6 concentration from 6–24 h of ASF. The tissue to first exhibit increased pro-inflammatory gene expression from ASF was heart (1 h of ASF). In contrast, pro-inflammatory gene expression was suppressed in hypothalamus from 1 h of ASF, but elevated at 6 h. Because the HPA axis was activated throughout ASF, this suggests that brain, but not peripheral, pro-inflammatory responses were rapidly inhibited by glucocorticoid immunosuppression. [ABSTRACT FROM AUTHOR]

Introduction: Fetal infection during labor with fetal inflammatory response syndrome (FIRS) is associated with neurodevelopmental disabilities, cerebral palsy, neonatal sepsis, and mortality. Current methods to diagnose FIRS are inadequate. Thus, the study aim was to explore whether fetal heart rate variability (HRV) analysis can be used to detect FIRS. Material and methods: In chronically instrumented near-term fetal sheep, lipopolysaccharide (LPS) was injected intravenously to model FIRS. A control group received saline solution injection. Hemodynamic, blood gas analysis, interleukin-6 (IL-6), and 14 HRV indices were recorded for 6 h. In both groups, comparisons were made between the stability phase and the 6 h following injection (H1–H6, respectively) and between LPS and control groups. Results: Fifteen lambs were instrumented. In the LPS group (n = 8), IL-6 increased significantly after LPS injection (p < 0.001), confirming the FIRS model. Fetal heart rate increased significantly after H5 (p < 0.01). In our FIRS model without shock or cardiovascular decompensation, five HRV measures changed significantly after H2 until H4 in comparison to baseline. Moreover, significant differences between LPS and control groups were observed in HRV measures between H2 and H4. These changes appear to be mediated by an increase of global variability and a loss of signal complexity. Conclusion: As significant HRV changes were detected before FHR increase, these indices may be valuable for early detection of acute FIRS. [ABSTRACT FROM AUTHOR]

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3β, 6β, 16β-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention. [ABSTRACT FROM AUTHOR]

Riemerella (R.) anatipestifer poses a significant threat to ducks, resulting in mortality rates ranging from 5–75%. This disease is highly infectious and economically consequential for domestic ducks. Although other avian species, such as chickens, also display susceptibility, the impact is comparatively less severe than in ducks. IL-17A has a pronounced correlation with R. anatipestifer infection in ducks, which is less in chickens. This study performed an in vitro transcriptome analysis using chicken splenic lymphocytes collected at 4-, 8-, and 24-hour intervals following R. anatipestifer stimulation. The primary objective was to discern the differentially expressed genes, with a specific focus on IL-17A and IL-17F expression. Moreover, an association between specific miRNAs with NOS2 and CCL5 was identified. The manifestation of riemerellosis in chickens was linked to heightened expression of Th1- and Th2-associated cells, while Th17 cells exhibited minimal involvement. This study elucidated the mechanism behind the absence of a Th17 immune response, shedding light on its role throughout disease progression. Additionally, through small RNA sequencing, we identified a connection between miRNAs, specifically miR-456-3p and miR-16-5p, and their respective target genes NOS2 and CCL5. These miRNAs are potential regulators of the inflammatory process during riemerellosis in chickens. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a poor prognosis cancer with an aggressive growth profile that is often diagnosed at late stage and that has few curative or therapeutic options. PDAC growth has been linked to alterations in the pancreas microbiome, which could include the presence of the fungus Malassezia. We used RNA-sequencing to compare 14 matched tumor and normal (tumor adjacent) pancreatic cancer samples and found Malassezia RNA in both the PDAC and normal tissues. Although the presence of Malassezia was not correlated with tumor growth, a set of immune- and inflammatory-related genes were up-regulated in the PDAC compared to the normal samples, suggesting that they are involved in tumor progression. Gene set enrichment analysis suggests that activation of the complement cascade pathway and inflammation could be involved in pro PDAC growth. [ABSTRACT FROM AUTHOR]

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26-38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly (p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.

BackgroundPersistent inflammation following vascular injury drives neointimal hyperplasia (NIH). Specialized lipid mediators (SPM) mediate resolution which attenuates inflammation and downstream NIH. We investigated the effects of a synthetic analogue of resolvin D1 (RvD1) on vascular cells and in a model of rat carotid angioplasty.MethodsHuman venous VSMC and endothelial cells (EC) were employed in migration, cell shape, toxicity, proliferation and p65 nuclear translocation assays. Murine RAW 264.7 cells were utilized to test the effect of pro-resolving compounds on phagocytic activity. A model of rat carotid angioplasty was used to evaluate the effects of 17R/S-benzo-RvD1 (benzo-RvD1) and 17R-RvD1 applied to the adventitia via 25% Pluronic gel. Immunostaining was utilized to examine Ki67 expression and leukocyte recruitment. Morphometric analysis was performed on arteries harvested 14 days after injury.ResultsExposure to benzo-RvD1 attenuated PDGF- stimulated VSMC migration across a range of concentrations (0.1-100 nM), similar to that observed with 17R-RvD1. Pre-treatment with either Benzo-RvD1 or 17R-RvD1 (10, 100nM) attenuated PDGF-BB-induced VSMC cytoskeletal changes to nearly baseline dimensions. Benzo-RvD1 demonstrated modest anti-proliferative activity on VSMC and EC at various concentrations, without significant cytotoxicity. Benzo-RvD1 (10nM) inhibited p65 nuclear translocation in cytokine-stimulated EC by 21% (p

BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (

Route of exposure to pathogens can inform divergent disease pathogenesis and mortality rates. However, the features that contribute to these differences are not well established. Host metabolism has emerged as a critical element governing susceptibility and the metabolism of tissue exposure sites are unique. Therefore, specific metabolic niches may contribute to the course and outcome of infection depending on route of infection. In the current study, we utilized a combination of imaging and systems metabolomics to map the spatiotemporal dynamics of the host response to intranasal (i.n.) or intradermal (i.d.) infection of mice using the bacterium Francisella tularensis subsp tularensis (FTT). FTT causes lethal disease through these infection routes with similar inoculation doses and replication kinetics, which allowed for isolation of host outcomes independent of bacterial burden. We observed metabolic modifications that were both route dependent and independent. Specifically, i.d. infection resulted in early metabolic reprogramming at the site of infection and draining lymph nodes, whereas the lungs and associated draining lymph nodes were refractory to metabolic reprogramming following i.n. infection. Irrespective of exposure route, FTT promoted metabolic changes in systemic organs prior to colonization, and caused massive dysregulation of host metabolism in these tissues prior to onset of morbidity. Preconditioning infection sites towards a more glycolytic and pro-inflammatory state prior to infection exacerbated FTT replication within the lungs but not intradermal tissue. This enhancement of replication in the lungs was associated with the ability of FTT to limit redox imbalance and alter the pentose phosphate pathway. Together, these studies identify central metabolic features of the lung and dermal compartments that contribute to disease progression and identify potential tissue specific targets that may be exploited for novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

While inflammation is an important immune response for protection from infections, excessive or prolonged inflammation can lead to a variety of debilitating diseases including skin disease, diabetes, heart disease, stroke, autoimmune diseases and cancer. Inflammation is a graded response that is typically initiated when resident macrophages sense the presence of pathogens or damage in the tissue and produce inflammatory cytokines and chemokines to kill the pathogen, clear debris and dead tissue, and initiate tissue repair. Here we show that copper-infused fabrics can prevent inflammation by blocking the production of inflammatory cytokines from macrophages after being exposed to LPS, a component of bacterial cell wall. Mechanistically, we show that copper-infused fabrics can significantly reduce the NF-κB and IRF3 activation in LPS-stimulated macrophages. Given the importance of excessive inflammation in diabetes, we show that copper can reduce insulin resistance mediated by inflammatory cytokines in muscle cells. Our data show that copper infused fabrics may be useful to reduce excessive inflammation in macrophages and improve insulin sensitivity in skeletal muscles. [ABSTRACT FROM AUTHOR]

BackgroundInsomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated.MethodsWe examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI).ResultsWe observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27).ConclusionWe observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.

ObjectiveTo characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control.MethodsThis is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau.FindingsHIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200-350 blood CD4+ T cells/μL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.

BackgroundOsteoarthritis (OA) is a leading cause of musculoskeletal pain and disability among Americans. Physical therapy (PT) is recommended per the 2019 ACR /Arthritis Foundation Guideline for Treatment of OA of the Hand, Hip, and Knee. During COVID-19, access to healthcare has been altered in a variety of clinical settings, with the pandemic creating delays in healthcare, with an unknown impact on access to PT care for OA.ObjectivesWe sought to determine whether referrals to PT for OA were reduced in 2020 during the COVID-19 pandemic compared to 2019.MethodsA retrospective analysis was done of 3586 PT referrals placed by the University of California, Davis for 206 OA ICD-10 codes from January to November 2019 and from January to November 2020. The numbers of PT referrals per month of each year were compared using both descriptive statistics and Poisson Regression analysis.ResultsA total of 1972 PT referrals for OA were placed from January to November 2019. Only 1614 referrals for OA were placed from January to November 2020, representing a significant decrease (p = 0.001). Month-by-month analysis of 2020 compared to 2019 revealed statistically significant drops in PT referrals for OA in April (p = 0.001), May (p = 0.001), and August (p = 0.001).ConclusionsThese findings reveal a significant reduction in the number of referrals for PT for OA placed in 2020 during the first year of the COVID-19 pandemic. These reductions were particularly evident in the months following state-mandated actions and closures. Factors associated with this outcome may include decreased access to primary care providers, perceptions of PT availability by health care providers, decreased mobility limiting access to both clinic and PT appointments, and/or willingness to engage in PT by patients during the pandemic.

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at

This study is the first to investigate the transcriptomic changes occurring in severe udder cleft dermatitis lesions (UCD) in Holstein-Friesian cows. An examination of the gene expression levels in natural UCD lesions and healthy udder skin through RNA Seq-Technology provided a deeper insight into the inflammatory pathways associated with this disease. A clear distinction between the gene expression patterns of UCD lesions and healthy skin was shown in the principal component analysis. Genes coding for inflammatory molecules were upregulated such as the chemokines C-X-C motif ligand 2 (CXCL2), 5 (CXCL5) and 8 (CXCL8), and C-C motif ligand 11 (CCL11). Moreover, the genes coding for the multifunctional molecules ADAM12 and SLPI were amongst the highest upregulated ones, whereas the most downregulated genes included the ones coding for keratins and keratin-associated molecules. Predominantly inflammatory pathways such as the chemokine signaling, cytokine receptor interaction and IL-17 signaling pathway were significantly upregulated in the pathway analysis. These results point towards a fulminant, dysregulated inflammatory response concomitant with a disruption of the skin barrier integrity and a hampered wound repair mechanism in severe UCD lesions. [ABSTRACT FROM AUTHOR]

Research studies have observed associations of vitamin D with inflammation but data in representative older adult studies is lacking. We aimed to investigate the association of C-reactive protein (CRP) with vitamin D status in a representative sample of the older Irish population. The concentrations of 25-hydroxyvitamin D (25(OH)D) and CRP was measured in 5,381 community dwelling Irish adults aged ≥50 years from the Irish Longitudinal Study on Ageing (TILDA). Demographic, health and lifestyle variables were assessed by questionnaire and categorical proportions of CRP were generated by vitamin D status and age. Multi-nominal logistic regression was used to investigate the association of 25(OH)D and CRP status. The prevalence (mean; 95% confidence interval (95% CI)) of normal CRP status (0–5 mg/dL) was 83.9% (82.6–85.0%), elevated status (5–10 mg/dL) 11.0% (9.9–12.0%) and high status (>10 mg/dL) was 5.1% (4.5–5.8%). Mean (95% CI) CRP concentrations were lower in those with normal vs. deficient 25(OH)D status (2.02 mg/dL (1.95–2.08) vs. 2.60 mg/dL (2.41–2.82); p<0.0001). In a logistic regression analysis, those with insufficient or sufficient 25(OH)D status were less likely to have a high CRP status compared to those with deficient 25(OH)D status (insufficient: coefficient (CE) -0.732, 95% CI -1.12–0.33, p<0.0001; sufficient: CE -0.599, 95% CI -0.95–0.24, p = 0.001). In conclusion older adults with deficient vitamin D status had higher levels of inflammation as measured by CRP. Given that inflammation is an important pathological driver of chronic diseases of ageing, and that emerging evidence suggests that vitamin D therapy can reduce inflammation in some disease settings, optimising vitamin D status could represent an effective low risk/low-cost pathway to modulate inflammation in community dwelling older adults. [ABSTRACT FROM AUTHOR]

Colonization of a localized area of human skin by Borrelia burgdorferi after a bite from an infected tick is the first step in the development of Lyme disease. The initial interaction between the pathogen and the human host cells is suggested to impact later outcomes of the infection. MicroRNAs (miRNAs) are well known to be important regulators of host inflammatory and immune responses. While miRNAs have been shown to play a role in the inflammatory response to B. burgdorferi at late stages of infection in the joints, the contributions of miRNAs to early B. burgdorferi infection have yet to be explored. To address this knowledge gap, we used the published host transcriptional responses to B. burgdorferi in erythema migrans skin lesions of early Lyme disease patients and a human dermal fibroblasts (HDFs)/B. burgdorferi co-culture model to predict putative upstream regulator miRNAs. This analysis predicted a role for miR146a-5p in both, B. burgdorferi-infected skin and -stimulated HDFs. miR146a-5p was confirmed to be significantly upregulated in HDF stimulated with B. burgdorferi for 24 hours compared to uninfected control cells. Furthermore, manipulation of miR146a-5p expression (overexpression or inhibition) altered the B. burgdorferi driven inflammatory profile of HDF cells. Our results suggest that miR146a-5p is an important upstream regulator of the transcriptional and immune early response to early B. burgdorferi infection. [ABSTRACT FROM AUTHOR]

Context: Periodontitis is a chronic multifactorial inflammatory disease linked to oral microbiota dysbiosis. This disease progresses to infection that stimulates a host immune/inflammatory response, with progressive destruction of the tooth-supporting structures. Objective: This systematic review aims to present a robust critical evaluation of the evidence of salivary protein profiles for identifying oral diseases using proteomic approaches and summarize the use of these approaches to diagnose chronic periodontitis. Data sources: A systematic literature search was conducted from January 1st, 2010, to December 1st, 2022, based on PICO criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and by searching the three databases Science Direct, Scopus, and Springer Link. Study selection: According to the inclusion criteria, eight studies were identified to analyze the proteins identified by proteomics. Results: The protein family S100 was identified as the most abundant in patients with chronic periodontitis. In this family, an increased abundance of S100A8 and S100A9 from individuals with the active disease was observed, which strongly relates to the inflammatory response. Moreover, the ratio S100A8/S100A9 and the metalloproteinase-8 in saliva could differentiate distinct periodontitis groups. The changes in protein profile after non-surgical periodontal therapy improved the health of the buccal area. The results of this systematic review identified a set of proteins that could be used as a complementary tool for periodontitis diagnosis using salivary proteins. Conclusion: Biomarkers in saliva can be used to monitor an early stage of periodontitis and the progression of the disease following therapy. [ABSTRACT FROM AUTHOR]

Canine Chronic Ulcerative Stomatitis is a spontaneously occurring inflammatory disease of the oral mucosa. An immune-mediated pathogenesis is suspected though not yet proven. We have recently reported on the clinical and histologic features, and identification of select leukocyte cell populations within the lesion. A clinical and histologic similarity to oral lichen planus of people was proposed. In the present study, these initial observations are extended by examining lesions from 24 dogs with clinical evidence of chronic ulcerative stomatitis. Because dogs with chronic ulcerative stomatitis often have concurrent periodontal disease, we wondered if dental plaque/biofilm may be a common instigator of inflammation in both lesions. We hypothesized that dogs with chronic ulcerative stomatitis would exhibit a spectrum of pathologic changes and phenotype of infiltrating leukocytes that would inform lesion pathogenesis and that these changes would differ from inflammatory phenotypes in periodontitis. Previously we identified chronic ulcerative stomatitis lesions to be rich in FoxP3+ and IL17+ cells. As such, we suspect that these leukocytes play an important role in lesion pathogenesis. The current study confirms the presence of moderate to large numbers of FoxP3+ T cells and IL17+ cells in all ulcerative stomatitis lesions using confocal immunofluorescence. Interestingly, the majority of IL17+ cells were determined to be non-T cells and IL17+ cell frequencies were negatively correlated with severity on the clinical scoring system. Three histologic subtypes of ulcerative stomatitis were determined; lichenoid, deep stomatitis and granulomatous. Periodontitis lesions, like stomatitis lesions, were B cell and plasma cell rich, but otherwise differed from the stomatitis lesions. Direct immunofluorescence results did not support an autoantibody-mediated autoimmune disease process. This investigation contributes to the body of literature regarding leukocyte involvement in canine idiopathic inflammatory disease pathogenesis.

Spontaneous preterm birth (sPTB) is a major cause of infant morbidity and mortality. While metabolic changes leading to preterm birth are unknown, several factors including dyslipidemia and inflammation have been implicated and paradoxically both low (30 kg/m2) body mass indices (BMIs) are risk factors for this condition. The objective of the study was to identify BMI-associated metabolic perturbations and potential mid-gestation serum biomarkers of preterm birth in a cohort of underweight, normal weight and obese women experiencing either sPTB or full-term deliveries (n = 102; n = 17/group). For this purpose, we combined untargeted metabolomics and lipidomics with targeted metabolic profiling of major regulators of inflammation and metabolism, including oxylipins, endocannabinoids, bile acids and ceramides. Women who were obese and had sPTB showed elevated oxidative stress and dyslipidemia characterized by elevated serum free fatty acids. Women who were underweight-associated sPTB also showed evidence of dyslipidemia characterized by elevated phospholipids, unsaturated triglycerides, sphingomyelins, cholesteryl esters and long-chain acylcarnitines. In normal weight women experiencing sPTB, the relative abundance of 14(15)-epoxyeicosatrienoic acid and 14,15-dihydroxyeicosatrienoic acids to other regioisomers were altered at mid-pregnancy. This phenomenon is not yet associated with any biological process, but may be linked to estrogen metabolism. These changes were differentially modulated across BMI groups. In conclusion, using metabolomics we observed distinct BMI-dependent metabolic manifestations among women who had sPTB. These observations suggest the potential to predict sPTB mid-gestation using a new set of metabolomic markers and BMI stratification. This study opens the door to further investigate the role of cytochrome P450/epoxide hydrolase metabolism in sPTB.

Maternal nutritional status influences fetal development and long-term risk for adult non-communicable diseases. However, the underlying mechanisms remain poorly understood. We examined whether biomarkers for metabolism and inflammation during pregnancy were associated with maternal health and with child biomarkers and health at 9-12 years of age in 44 maternal-child dyads from the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT, ISRCTN34151616) in Lombok, Indonesia. Archived blood for each dyad from maternal enrollment, later in pregnancy, postpartum, and from children at 9-12 years comprised 132 specimens. Multiplex microbead immunoassays were used to quantify vitamin D-binding protein (D), adiponectin (A), retinol-binding protein 4 (R), C-reactive protein (C), and leptin (L). Principal component analysis (PCA) revealed distinct variance patterns, i.e. principal components (PC), for baseline pregnancy, bp.pc1.D↓A↓R↓ and bp.pc2.C↓L↑; combined follow-up during pregnancy and postpartum, dp-pp.pc1.D↑↓A↑R↑↓L↓ and dp-pp.pc2.A↑C↑L↑; and children, ch.pc1.D↑R↑C↑ and ch.pc2.D↓A↑L↑. Maternal multiple micronutrient (MMN) supplementation led to an association of baseline maternal bp.pc2.C↓L↑ with decreased post-supplementation maternal dp-pp.pc2.A↑C↑L↑ (p = 0.022), which was in turn associated with both increased child ch.pc1.D↑R↑C↑ (p = 0.036) and decreased child BMI z-score (BMIZ) (p = 0.022). Further analyses revealed an association between maternal dp-pp.pc1.D↑↓A↑R↑↓L↓ and increased child BMIZ (p = 0.036). Child ch.pc1.D↑R↑C↑ was associated with decreased birth weight (p = 0.036) and increased child BMIZ (p = 0.002). Child ch.pc2.D↓A↑L↑ was associated with increased child BMIZ (p = 0.005), decreased maternal height (p = 0.030) and girls (p = 0.002). A pattern of elevated maternal adiponectin and leptin in pregnancy was associated with increased C-reactive protein, vitamin A, and D binding proteins pattern in children, suggesting biomarkers acting in concert may have qualitative as well as quantitative influence beyond single biomarker effects. Patterns in pregnancy proximal to birth were more associated with child status. In addition, child patterns were more associated with child status, particularly child BMI. MMN supplementation affects maternal biomarker patterns of metabolism and inflammation in pregnancy, and potentially in the child. However, child nutrition conditions after birth may have a greater impact on metabolism and inflammation.

Extracellular adenosine triphosphate (eATP) released by damaged cells, and its purinergic receptors, comprise a crucial signaling network after injury. Purinergic receptor P2X7 (P2RX7), a major driver of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and IL-1β processing, has been shown to play a role in liver injury in murine diet- and chemically-induced liver injury models. It is unclear, however, whether P2RX7 plays a role in non-alcoholic steatohepatitis (NASH) and which cell type is the main target of P2RX7 pharmacological inhibition. Here, we report that P2RX7 is expressed by infiltrating monocytes and resident Kupffer cells in livers from NASH-affected individuals. Using primary isolated human cells, we demonstrate that P2RX7 expression in CD14+ monocytes and Kupffer cells primarily mediates IL-1β release. In addition, we show that pharmacological inhibition of P2RX7 in monocytes and Kupffer cells, blocks IL-1β release, reducing hepatocyte caspase 3/7 activity, IL-1β-mediated CCL2 and CCL5 chemokine gene expression and secretion, and hepatic stellate cell (HSC) procollagen secretion. Consequently, in a chemically-induced nonhuman primate model of liver fibrosis, treatment with a P2RX7 inhibitor improved histological characteristics of NASH, protecting from liver inflammation and fibrosis. Taken together, these findings underscore the critical role of P2RX7 in the pathogenesis of NASH and implicate P2RX7 as a promising therapeutic target for the management of this disease.

Endothelial cells synthesize biochemical signals to coordinate a response to insults, resolve inflammation and restore barrier integrity. Vascular cells release a variety of vasoactive bioactive lipid metabolites during the inflammatory response and produce pro-resolving mediators (e.g., Lipoxin A4, LXA4) in cooperation with leukocytes and platelets to bring a halt to inflammation. Aspirin, used in a variety of cardiovascular and pro-thrombotic disorders (e.g., atherosclerosis, angina, preeclampsia), potently inhibits proinflammatory eicosanoid formation. Moreover, aspirin stimulates the synthesis of pro-resolving lipid mediators (SPM), so-called Aspirin-Triggered Lipoxins (ATL). We demonstrate that cytokines stimulated a time- and dose-dependent increase in PGI2 (6-ketoPGF1α) and PGE2 formation that is blocked by aspirin. Eicosanoid production was caused by cytokine-induced expression of cyclooxygenase-2 (COX-2). We also detected increased production of pro-resolving LXA4 in cytokine-stimulated endothelial cells. The R-enantiomer of LXA4, 15-epi-LXA4, was enhanced by aspirin, but only in the presence of cytokine challenge, indicating dependence on COX-2 expression. In contrast to previous reports, we detected arachidonate 5-lipoxygenase (ALOX5) mRNA expression and its cognate protein (5-lipoxygenase, 5-LOX), suggesting that endothelial cells possess the enzymatic machinery necessary to synthesize both pro-inflammatory and pro-resolving lipid mediators independent of added leukocytes or platelets. Finally, we observed that, endothelial cells produced LTB4 in the absence of leukocytes. These results indicate that endothelial cells produce both pro-inflammatory and pro-resolving lipid mediators in the absence of other cell types and aspirin exerts pleiotropic actions influencing both COX and LOX pathways. [ABSTRACT FROM AUTHOR]

Palmitic acid (PA) is considered a major contributor to the inflammation in many metabolic diseases; however, this role has been questioned recently for the complicated procedures in preparing PA-bovine serum albumin (BSA) complex. This study is aimed to evaluate the effect of PA-BSA complexing methods on cell viability and inflammatory responses of BV-2 cells. Three commercially available BSA brands and two types of solvents were compared for their effects on the expression of inflammatory cytokines. Three commonly used proportions of PA-BSA were tested for cell viability and inflammatory responses. We found that all the three types of BSA were proinflammatory. Both ethanol and isopropanol dampened inflammation except that 1% isopropanol treatment increased the IL-1β level by 26%. When reducing the BSA content in PA-BSA solutions from 3:1 to 5:1, a marked increase in cell viability (11%) was seen. To our surprise, reducing BSA content in PA-BSA solutions from 5:1 to 10:1 decreased cell viability by 11%. The 5:1 group exhibited the lowest inflammatory profile. Either PA-BSA or BSA alone increased the entry of LPS to the cytosol, which further caused pyroptosis. In summary, we found 5:1 (PA:BSA) to be the best binding ratio for studying inflammation in BV-2 microglia. The presence of LPS in the cytosol in the context of BSA might be the reason for confounding results from palmitate studies. [ABSTRACT FROM AUTHOR]