Inflammatory Disorders Research Articles

Platelet Indices – Are They Really Biomarkers in Psoriasis? A Cross-sectional Study

Background: Psoriasis is a chronic inflammatory disorder with multiple systemic manifestations in common with other inflammatory disorders. Platelet activation has recently been proposed a major pathogenic factor in psoriasis. Mean platelet volume (MPV) and platelet distribution width (PDW) are considered platelet activation markers. Although there are various inflammatory markers reported to be abnormal in psoriasis, a simple cost-effective and clinically useful marker that could predict the severity of the disease and be used to know about its association with systemic abnormalities and response to treatment is still under study. Aim: The aim of our study was to look at the association of platelet indices with psoriasis and its severity. Methods: This was a single-center cross-sectional study in which 50 patients with psoriasis and 50 apparently healthy age and sex-matched controls who fulfilled the inclusion and exclusion criteria were enrolled after obtaining informed consent. A detailed history was elicited, and a clinical examination was done including anthropometric measurements and calculation of psoriasis area and severity index (PASI). Investigations including hemoglobin, red blood cell (RBC) count, packed cell volume (PCV), mean corpuscular volume, mean corpuscular hemoglobin (MCH), MCH concentration, white blood cell (WBC) and platelet count, plateletcrit, MPV, PDW, and red cell distribution width (RDW) were done. Results: Out of 50 psoriasis patients recruited, 40 (80%) had moderate-to-severe psoriasis, whereas 10 had mild psoriasis (10%) based on PASI scores. In majority of cases, the hemoglobin, PCV, RBC, and WBC counts were within the normal range and were comparable with that of controls. There was no statistically significant difference in the mean values of platelet count, MPV, PDW, plateletcrit, and RDW between cases and controls. There was no significant association between platelet indices and severity of psoriasis. Conclusion: There was no significant association between platelet indices including RDW and the presence or absence of psoriasis in our study. Furthermore, among patients with psoriasis, there was no significant association between platelet indices and severity of the disease.

Diosgenin Alleviates Obesity-Induced Insulin Resistance by Modulating PI3K/Akt Signaling Pathway in Mice Fed a High-Fat Diet.

Obesity is a global medical issue that can be effectively treated by relieving adipose inflammation and subsequent insulin resistance. Diosgenin (DIOS) has various effects as a steroidal saponin in inflammatory disorders. This study explored the effects and mechanism of DIOS on adipose inflammation and insulin sensitivity, both in silico and in vivo. The high-fat diet-induced obesity model in C57BL/6 mice was divided into five groups: normal chow (NC), high-fat diet (HFD), HFD with atorvastatin 10 mg/kg (AT), HFD with DIOS 100 mg/kg (DIOS 100), and HFD with DIOS 200 mg/kg (DIOS 200). Each group underwent an oral intervention for seven weeks. DIOS significantly suppressed weight gain in the body, liver, and epididymal fat pads. Additionally, it significantly improved fasting glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance test results, and reduced the proportion of total and M1 adipose tissue macrophages. Significant changes were shown in mRNA expression of janus kinase 2 (JAK2), insulin receptor (INRS), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), all of which exhibited high binding affinity in the in silico. Safety indices, including aspartate aminotransferase (AST), alanine transaminase (ALT), and creatinine level indicated the preventive effects of DIOS. In conclusion, DIOS improves insulin resistance and obesity-associated inflammation via the PI3K/Akt signaling pathway.

Efficacy and safety of guselkumab in European patients with palmoplantar pustulosis: A multi-center, single-arm clinical trial (GAP study)

BackgroundPalmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder that affects palms and soles. Patients suffer significant pain, itching and daily activity impairment. Guselkumab, an interleukin-23 inhibitor, has been approved for PPP treatment in Japan. However, there is no effective therapy licensed for PPP in Europe and the USA. ObjectiveTo explore the efficacy and safety of guselkumab in patients with moderate-to-severe PPP in the Caucasian population. MethodsA multicenter, single-arm, phase II study involving 50 patients with moderate-to-severe PPP treated with 100 mg guselkumab subcutaneously for 24 weeks was conducted (GAP). Primary endpoint was the reduction of palmoplantar-pustulosis psoriasis area and severity index (PPPASI) at week 24 compared to baseline. Secondary endpoints included physician-assessed and patient-reported measures. Serum samples were taken for exploratory studies. ResultsThe primary endpoint was met with a significant median PPPASI reduction by 59.6% at week 24 compared to baseline (p<0.001). The proportions of patients achieving PPPASI-50 and PPPASI-75 at week 24 were 66.0% and 34.0%, respectively. Median DLQI dropped from 15 at baseline to 5 at week 24 (p<0.001). Week-4 changes in IL-19 serum levels predicted week-24 clinical response. ConclusionGuselkumab may be a promising therapeutic option for PPP in Caucasian patients.

Microbiome characterization of skin biopsies in Spanish patients with hidradenitis suppurativa shows a decrease in D1 and H1 lineages of Cutibacterium acnes.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder, with dysbiosis and loss of Cutibacterium acnes commonly observed in affected skin. This study analyzed the microbiome of lesional, perilesional, and healthy skin samples, finding significant differences, including increased Mycoplasma and Bacillus in lesional skin. The reduction of Cutibacterium variants D1 and H1 in HS-affected skin highlights their potential as therapeutic targets, suggesting a strategy of topical replacement therapy.

Oral Administration of Taurodeoxycholate, A GPCR19 Agonist, Effectively Ameliorates Atopic Dermatitis in A Mouse Model.

Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disorder, characterised by intense pruritus and recurrent eczematous lesions. Recently, the US FDA has approved Janus kinase (JAK) inhibitors for oral treatment in AD patients. However, oral immunomodulatory agents have demonstrated adverse effects. In previous studies, we demonstrated the efficacy of topical taurodeoxycholate (TDCA), a G protein-coupled receptor 19 (GPCR19) agonist, on AD. In this study, we further evaluated the efficacy of orally administered TDCA on MC903- and dinitrochlorobenzene (DNCB)-induced AD mouse models. Oral administration of TDCA significantly ameliorated AD symptoms and reduced both epidermal and dermal thickness. Additionally, oral TDCA treatment inhibited the infiltration of myeloid and lymphoid cells into AD lesions. TDCA also suppressed the expression of thymic stromal lymphopoietin (TSLP), interleukin (IL)-4, IL-13, IL-33, IL-1β, tumour necrosis factor-alpha (TNF-α) and chemokine (C-C motif) ligand 17 in the skin and blood. Given the previously demonstrated safety profiles of TDCA, oral TDCA may offer a beneficial and safer alternative for AD patients.

Neutrophils exhibit flexible migration strategies and trail formation mechanisms on varying adhesive substrates

Substrate anchorage is essential for cell migration and actin polymerization at cell front and myosin contractility at cell rear are known to govern cell forward movement. Yet their differential driving strategies for neutrophil migration on distinct adhesiveness substrates and their contributions to the migration-induced trail formation remain unclear. Here we explore the morphological changes, migration dynamics, and trail formation of neutrophils on ICAM-1 and PLL substrates, with a focus on the relationships among adhesive forces, traction forces, and out-of-plane forces. Results indicate that, on ICAM-1, neutrophil migration and trail formation rely on the coordinated interactions of Arp2/3 and myosin, along with biochemical regulation (via Syk and calpain) of adhesion and de-adhesion. This pattern leads to traction forces being concentrated at relatively fewer adhesive sites, facilitating cell forward migration. On PLL, however, neutrophils primarily depend on Arp2/3-mediated actin polymerization, resulting in a broader distribution of traction forces and weaker adhesions, which allows for higher leading-edge migrating velocities. Elevated membrane tension and out-of-plane forces generated by bleb protrusions on PLL reduce the reliance on myosin-driven contraction at the trailing edge, enabling easier tail detachment through elastic recoil. This work highlights the differential impact of substrate adhesiveness on neutrophil migration and trail formation and dynamics, providing new insights into cell migration mechanisms and potential therapeutic targets for inflammatory and immune-related disorders.

Expanding the frontiers of therapeutic options in hidradenitis suppurativa: The valid contribution of bimekizumab

Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disorder with a significant negative impact on quality of life. Th17 axis has a central role in the pathogenesis of HS. Kimball etal. demonstrated the efficacy and safety of bimekizumab in two double-blind, placebo-controlled phase 3 studies (BE HEARD I-II), adding a new targeting option to the therapeutic armamentarium of HS.1.

Inflammatory Myopathies and Autoimmune Gluten-related Disorders: A Scoping Review of Pathophysiological Interconnections and Hypothesis

Introduction: Anecdotal reports describe patients with concurrent idiopathic inflammatory myopathy (IIM) and celiac disease (CeD) in whom the introduction of a gluten-free diet led to dramatic improvement of myositis. We first systematically reviewed all peer-reviewed publications on concomitant IIM and duodenal biopsy-verified CeD. The collected evidence was suggestive of associations between myositis disease activity and gluten exposure in some patients with IIM-CeD. Objective/Methods: To investigate possible explanations for the observations, an exploratory review of basic pathophysiological relationships between IIM and gluten-related disorders was performed using a combined strategy of systematic and non-systematic literature searches and forward and backward citation tracking. Results: The investigations revealed close pathophysiological associations between IIM and the autoimmune gluten-related disorders CeD, dermatitis herpetiformis, and gluten ataxia. Common traits include shared genetic predisposition through HLA-DQ2.5/-DQ8, disease activity-associated autoantibodies, histopathological parallels with inflammatory cell infiltrates, and similarly distributed structural homologous transglutaminases (TGs). HLA-DQ2.5-restricted gluten-specific CD4+ T cells of a rare, uniform phenotype are reported in CeD and connective tissue disease. Expanded T-cell clones with identical phenotypes and CDR3β motifs indicate the presence of a continuous, antigen-driven T-cell response. Conclusion: The investigations revealed that the main components involved in the adaptive immune response in the CeD gut may be present in HLA-DQ2.5+/-DQ8+ IIM muscle. The collected evidence supports the notion that in some genetically predisposed patients with IIM, gluten may act as an exogenous antigen driving myositis. Further Research/Clinical Implications: To test the above hypothesis, clinical trials combined with immunological studies are needed. Meanwhile, the inclusion of HLA-DQ typing may be justified, and subsequent small-intestinal biopsies in HLA-DQ2.5/8+ individuals with IIM.

Integrating multiomics and Single-Cell communication analysis to uncover Ankylosing spondylitis mechanisms

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory joint disorder, necessitating early diagnosis and effective treatment. The specific mechanism of action of Cassia twigs in the treatment of AS is not fully understood. MethodsBlood samples and clinical data from 28,458 individuals (6,101 with AS, 22,357 without AS) were collected. To construct a predictive model, we utilized logistic regressions and machine learning techniques to create a dynamic nomogram. Immune cell infiltration was evaluated using the GSE73754 dataset. Subsequently, we obtained vertebral bone marrow blood from AS patients for 10X single-cell sequencing. We also extracted and purified total RNA from hip joint ligament tissue samples from six AS patients and six non-AS patients. The genes related to the expression of AS and Cassia twigs were analyzed comprehensively, and the specific drug targets were identified by molecular docking. The interactions between immune cells through cell communication analysis were elucidated. ResultsWe developed a dynamic nomogram incorporating the neutrophil count (NEUT) and other variables. Neutrophil immune responses were confirmed through immune infiltration analysis utilizing GSE73754. We observed the early involvement of neutrophils in the pathology of AS. The CAT-expressing Cassia twigs gene could be used as a drug target for the treatment of AS. Moreover, comprehensive RNA analysis revealed notable CAT expression in neutrophils and various other immune cells. ConclusionsNeutrophils play dual roles in AS, regulating inflammation and initiating differentiation signals to other cells. The CAT gene, which is expressed in Cassia twigs, has emerged as a potential therapeutic target for AS treatment.

Lutein improves remyelination by reducing of neuroinflammation in C57BL/6 mouse models of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory neurodegenerative disorder characterized by demyelination. Lutein, a xanthophyll carotenoid, has well-known antioxidant and anti-inflammatory properties. In this experiment, we aimed to investigate the neuroprotective and remyelination potential of lutein in comparison with dimethyl fumarate (DMF) as a reference drug in post-cuprizone-intoxicated C57BL/6 mice. Lutein (50, 100, and 200 mg/kg/day; p.o.) and DMF (15 mg/kg/day, i.p.) were administered either alone or in combination for three weeks at the end of the six-week cuprizone (0.2 % w/w) feeding period. At the end of the study, behavioral tests, histopathological staining, immunohistochemistry (olig2), ELISA, and real-time PCR were performed to evaluate the target parameters. Lutein treatment significantly enhanced motor functions, reversed cuprizone-induced demyelination and increased serum TAC. In addition, treatment with lutein increased the number of Olig2+ cells in the corpus callosum, reduced the IL-1β and TNF-α and increased BDNF. Lutein administration significantly increased the expression levels of genes involved in myelin production (MBP, PLP, MOG, MAG, and OLIG-1) and notably reduced GFAP expression levels. In the present study, our results showed that lutein treatment could promote remyelination and neuroprotective effects by reducing neuroinflammation and upregulating the expression of the genes involved in myelin formation These findings suggest that lutein could serve as a potential adjuvant therapy for patients with multiple sclerosis. Further clinical trials are necessary to confirm its efficacy.

Successful Microablative Fractional Carbon Dioxide Laser Therapy for Vulvar Lichen Sclerosus: A Case Report and Mini-review

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disorder affecting the vulvar region. VLS predominantly affects women, and most cases occur after menopause. Common symptoms include itching, skin-whitening, pain, discomfort, fissures, and scarring. Treatment options include topical steroids, emollients, lifestyle modifications, regular follow-up, and surgical interventions. Carbon dioxide (CO2) laser treatment is a therapeutic option for managing lichen sclerosus. We report a case of VLS successfully treated with a fractional microablative CO2 laser. A 72-year-old female presented with a dry vagina and vulvar itching for 6 months. She visited a local medical clinic, and oral anti-itching medication and topical anti-itching ointment were administered. However, the condition did not improve, and she felt itching. She visited our outpatient department, and a pelvic examination showed bilateral labia minor, revealing a white skin color change and a hardening sensation. The patient was diagnosed with VLS. Microablative fractional CO2 laser therapy was subsequently administered. The treatment course comprised three laser therapy sessions (treatment day, 1 month, and 2 months after the first therapy). The vulvovaginal symptoms questionnaire-21 scores were 14, 6, and 2 for the first, second, and third courses of treatment, respectively. Vulvar itching improved significantly after laser treatment – no more steroid treatment needed. After 10 months of follow-up, the condition of the vulva was maintained well. Although the treatment protocol requires further exploration, CO2 laser treatment could be considered for VLS if topical steroids are ineffective.

Recent Insight into Herbal Bioactives-based Novel Approaches for Chronic Intestinal Inflammatory Disorders Therapy.

Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.

A Study of Onychoscopic Findings in Various Dermatological Disorders

Context: About 10% of all the dermatological conditions are comprised nail disorders. It is challenging for the dermatologists to diagnose nail disorders quickly without the help of invasive procedures. Aims: The aim of the study was to evaluate onychoscopic patterns associated with various nail disorders. Settings and Designs: Hospital-based cross-sectional observational study was conducted at a tertiary care teaching institute in Maharashtra, India from November 2019 to May 2021. Materials and Methods: One hundred and fifty patients, with a history and clinical presentation suggestive of nail disorders, were recruited in the study after confirming the clinical diagnosis. Patients having secondarily modified lesions were excluded. Dry as well as wet onychoscopy using polarized and nonpolarized modes was performed with the help of DermLite 4 dermoscope with an attached OnePlus 8T mobile phone camera to capture and save the dermoscopic images. Data were compiled and statistically analyzed using SPSS version 21.0. Statistical Analysis Used: Categorical variables were expressed in frequency and percentages. Data were entered in Microsoft Excel and analyzed using SPSS version 20. P value (using Z-test for proportions) was calculated wherever needed. Results: The majority of the patients were in the age group of 21–50 years with slight male preponderance. Overall most common onychoscopic findings studied in all the disorders were the nail plate alterations followed by chromonychia. The most common nail changes associated with connective tissue disorders were changes in the proximal nail fold capillaries along with changes in the curvature. The most common change observed in onychomycosis was chromonychia. Aurora borealis, spikes, and jagged edges of onycholytic plate with ruin pattern of hyperkeratosis were specific to onychomycosis. Inflammatory disorders of the nail unit (e.g., lichen planus and nail psoriasis) showed nail plate alterations with increased nail plate fragility. Conclusions: Some onychoscopic patterns are observed consistently with certain diseases, and these can be used for their diagnosis, hence, avoiding unnecessary biopsies, thus improving the patient outcome.

Immortalized mesenchymal stromal cells overexpressing alpha-1 antitrypsin protect acinar cells from apoptotic and ferroptotic cell death.

Chronic pancreatitis (CP) is a progressive inflammatory disorder that impairs endocrine and exocrine function. Our previous work showed that mesenchymal stem/stromal cells (MSCs) and MSCs overexpressing alpha-1 antitrypsin (AAT-MSCs) could be therapeutic tools for CP. However, primary MSCs are predisposed to undergo senescence during culture expansion, which limits their therapeutic applications. We generated and characterized immortalized human MSCs (iMSCs) and AAT-MSCs (iAAT-MSCs) and tested their protective effect on 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced acinar cell death in an invitro cell culture system. Primary MSCs were immortalized by transduction with simian virus 40 large T antigen (SV40LT), and the resulting iMSC and iAAT-MSC lines were analysed for proliferation, senescence, phenotype and multi-differentiation potential. Subsequently, apoptosis and ferroptosis pathways were investigated by assessing changes before and after TNBS treatment. Coculture of iMSCs and iAAT-MSCs with acinar cell lines inhibited early cell death induced by TNBS, reduced ER stress and reversed TNBS-induced protein reduction at tight junctions. Additionally, iMSCs and iAAT-MSCs exerted such protection by regulating mitochondrial respiration, ATP content and ROS production in TNBS-induced acinar cells. Furthermore, iMSCs and iAAT-MSCs ameliorated TNBS-induced ferroptosis by modulating iron generation and ROS production and regulating the ferritin heavy chain 1 (FTH1)/protein disulfide isomerase (PDI)/glutathione peroxide 4 (GPX4) signalling pathways in acinar cells. These findings identify ferroptosis as an unrecognized mechanism that leads to TNBS-induced cell death and offer mechanistic insights relevant to using stem cell therapy to treat acinar cell death associated with CP.

Identification of SUMOylation-related signature genes associated with immune infiltration in ulcerative colitis through bioinformatics analysis and experimental validation

ObjectiveUlcerative colitis (UC) is a chronic inflammatory disorder challenging to diagnose clinically. We focused on identifying and validating SUMOylation-related signature genes in UC and their association with immune infiltration. MethodsFive eligible gene expression profiles were selected from the Gene Expression Omnibus (GEO) database and merged into a single dataset comprising 260 UC patients and 76 healthy controls (HC). Differentially expressed genes (DEGs) were identified, and these were intersected with SUMOylation-related genes to obtain differentially expressed SUMOylation-related genes (DESRGs). Next, we identify the signature genes and validate them through comprehensive analyses employing GO, KEGG, GSVA, Lasso-cox regression, ROC curves, and clustering analysis. The infiltrating immune cells were analyzed using the CIBERSORT algorithm and Pearson correlation analysis. Finally, in vitro and in vivo experiments validated the identified signature genes. ResultsPALMD, THRB, MAGED1, PARP1, and SLC16A1 were identified. Next, an excellent predictive model for UC was established and distinct subgroups of patients associated with SUMOylation were identified. Moreover, the NF-κB signaling pathway likely plays a pivotal role in the regulation of SUMOylation in UC. Additionally, we validated that the alterations in PALMD, THRB, and MAGED1 expression in LPSinduced Caco-2 cells concurred with our bioinformatics findings, particularly demonstrating statistically significant differences in PALMD and THRB expression. Finally, in a DSS-induced mouse colitis model, we observed a significant upregulation of PALMD expression. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation. ConclusionThis study comprehensively elucidates the biological roles of SUMOylation-related genes in UC, identifying PALMD, MAGED1, THRB, PARP1, and SLC16A1 as signature genes that represent promising biomarkers for UC diagnosis and prognosis.

Ethanolic extract of Parkia speciosa pods exhibits antioxidant and anti-inflammatory properties in lipopolysaccharide-induced murine macrophages by inhibiting the p38 MAPK pathway

BackgroundParkia speciosa (PS) is commonly used in Southeast Asian cuisine and traditional medicine to treat diabetes, hypertension, dermatitis, and kidney diseases. PS has emerged as a subject of interest because of its potential antioxidation and anti-inflammatory properties. However, despite its historically long and wide usage, a comprehensive investigation of these properties in PS pods (PSp) have not been conducted. Aims of this studyThis study aimed to identify the phytochemical compounds in the ethanolic extract of PSp collected from Southern Thailand and assess whether PSp exhibit antioxidant properties and mitigate inflammation in a lipopolysaccharide (LPS)-induced RAW264.7 model. Materials and methodsThe ethanolic extract of PSp was comprehensively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC/MS) to identify its phytochemical constituents. To assess the antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) assays were performed, and cytotoxicity was evaluated using the MTT assay. The effect of PSp on reactive nitrogen and oxygen species (RNS and ROS) was determined using a nitric oxide (NO) assay, and its effect on pro-inflammatory cytokines was assessed using enzyme-linked immunosorbent assay (ELISA) and real-time quatitvative polymerase chain reaction (qPCR). Morphological changes following treatment were observed using a microscope. Western blot analysis was performed to quantify MAPK pathway expression. ResultsPSp contain polyphenols, phytosterols, triterpenes, oxaloacetic acid, and unsaturated fatty acids. PSp demonstrated high antioxidant potential in scavenging free radicals and exhibited no cytotoxic effects on macrophages. Moreover, PSp effectively reduced NO release and inhibited pro-inflammatory cytokines such as IL1-β, TNF-α, and IL-6. PSp treatment induced notable morphological changes in macrophages, characterized by an increase in cell size and the presence of intracellular vacuoles. In addition, Western blot analysis showed the selective suppressive effect of PSp on the p38-MAPK pathway. ConclusionPSp possess strong antioxidant and anti-inflammatory properties, making it a potential therapeutic agent for the treatment of inflammatory disorders.

Evaluation of Albumin Denaturation, and Phospholipase A2 (Pla2) Inhibition, and Phytochemical Composition of Methanol Leaf Extract of Psychotria Vogeliana, Benth (Rubiaceae)

Inflammation is a protective response elicited by physical, chemical, biochemical, and/or microbial assault on the body, which serves to prevent progression/escalation of injury. If the response is sufficient the body continues to operate normally, if the reaction is excessive a disease condition (inflammation) occurs which predisposes to various health disorders. Current treatment of inflammation includes immunosuppressant, steroidal, and nonsteroidal agents. Most of these are known to have sometimes serious side/adverse effects. Natural compounds from plants known to have pharmacological activities, including anti-inflammatory and are being used as alternatives. This study aimed to investigate the phytochemical composition and anti-inflammatory properties of the methanol leaf extract of Psychotria vogeliana. Acute toxicity study was conducted following the OECD guidelines 423 Annex 2C. Anti-inflammatory activity was evaluated using albumin denaturation, and phospholipase A2 (PLA2) inhibition assay. Phytochemical analysis was conducted using spectrophotometric methods, and GC-FID. The LD50 of the extract is more than 5000 mg/kg. The extract contained bioactive compounds such as catechin, epicateechin, resvesterol, rutin, narigenin, kaempferol, flavonones, tannins, steroids and anthocynins. Anti-inflammatory evaluation showed activity comparable to that of diclofenac. Possible mechanism of action was identified as Phospholipase A2 (PLA2) inhibition. The use of Psychotria vogeliana in traditional medicine for the management and treatment of inflammatory disorders is therefore justified.

Physiology and immunology of the adrenergic anti-inflammatory pathway

The adrenergic anti-inflammatory pathway represents a critical intersection between the nervous and immune systems, modulating the body's response to inflammation through the action of catecholamines on adrenergic receptors. This review explored the physiology underlying this pathway, focusing on the mechanisms by which the sympathetic nervous system influences immune function. We delved into the roles of specific adrenergic receptors, primarily the beta-adrenergic receptors, in mediating anti-inflammatory effects, highlighting the involved molecular signaling pathways. Additionally, we examined the immunological implications of adrenergic modulation, discussing how these pathways contributed to the resolution of inflammation and the potential for dysregulation in various disease states. Emerging evidence on the therapeutic potential of targeting the adrenergic anti-inflammatory pathway in conditions such as sepsis, autoimmune diseases, and chronic inflammatory disorders was also reviewed. By integrating current knowledge on the physiology and immunology of this pathway, this review aimed to provide a comprehensive understanding of its role in health and disease, offering insights into future research directions and clinical applications.

Differential expression of cardiometabolic and inflammation markers and signaling pathways between overweight/obese Qatari adults with high and low plasma salivary α-amylase activity.

The relationship between salivary α-amylase activity (sAAa) and susceptibility to cardiovascular disorders lacks a definitive consensus in available studies. To fill this knowledge gap, the present study endeavors to investigate this association among overweight/obese otherwise healthy Qatari adults. The study specifically categorizes participants based on their sAAa into high and low subgroups, aiming to provide a more comprehensive understanding of the potential link between sAAa levels and cardiovascular and inflammation markers in this population. Plasma samples of 264 Qatari overweight/obese (Ow/Ob) participants were used to quantify the sAAa and to profile the proteins germane to cardiovascular, cardiometabolic, metabolism, and organ damage in low sAAa (LsAAa) and high sAAa (HsAAa) subjects using the Olink technology. Comprehensive statistical tools as well as chemometric and enrichments analyses were used to identify differentially expressed proteins (DEPs) and their associated signaling pathways and cellular functions. A total of ten DEPs were detected, among them five were upregulated (QPCT, LCN2, PON2, DPP7, CRKL) while five were down regulated in the LsAAa subgroup compared to the HsAAa subgroup (ARG1, CTSH, SERPINB6, OSMR, ALDH3A). Functional enrichment analysis highlighted several relevant signaling pathways and cellular functions enriched in the DEPs, including myocardial dysfunction, disorder of blood pressure, myocardial infraction, apoptosis of cardiomyocytes, hypertension, chronic inflammatory disorder, immunes-mediated inflammatory disease, inflammatory response, activation of leukocytes and activation of phagocytes. Our study unveils substantial alterations within numerous canonical pathways and cellular or molecular functions that bear relevance to cardiometabolic disorders among Ow/Ob Qatari adults exhibiting LsAAa and HsAAa in the plasma. A more comprehensive exploration of these proteins and their associated pathways and functions offers the prospect of elucidating the mechanistic underpinnings inherent in the documented relationship between sAAa and metabolic disorders.

BML-111 Modulates and Alleviates p38/MAPK Signaling Pathway and Th1/Th2/Th17 Cytokine Response in Murine Psoriasis-Like Dermatitis.

Psoriasis is a prevalent cutaneous inflammatory disorder characterized by elevated keratinocyte inflammation. 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), an established analogue of lipoxin A4, is known for its potent anti-inflammatory properties. However, the precise role of BML-111 within a murine psoriasis-like dermatitis model requires further clarification. This research aims to investigate the modulatory effects of BML-111 on inflammatory responses, the p38/mitogen-activated protein kinase (MAPK) signaling cascade, and T helper type 1 (Th1), Th2, and Th17 cell responses within the context of a murine psoriasis-like dermatitis model. A psoriasis-like dermatitis model was established by applying 5% imiquimod (IMQ) cream to the backs of C57BL/6 mice, which were pretreated intraperitoneally with or without BML-111 prior to IMQ application. Hematoxylin-eosin staining was utilized to detect the pathological alterations of the murine dorsal skin tissue. Furthermore, the psoriasis area and severity index (PASI) scoring system was used to assess the dynamic cutaneous alterations in the mice. The levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6, IL-4, and IL-17A in the murine serum samples were quantified by means of enzyme-linked immunosorbent assays (ELISA). Western blotting was conducted to detect the proteins of TNF-α, IL-1β, IL-6, phospho-p38 (p-p38), and p38 in murine skin tissues. Lastly, a flow cytometry analysis was executed to evaluate the expression of peripheral blood Th1/Th2/Th17 cell subsets. BML-111 attenuated IMQ-induced pathological changes in skin tissue of psoriasis-like dermatitis mice. BML-111 treatment substantially reduced TNF-α, IL-1β, IL-6, IFN-γ and IL-17A levels and elevated IL-4 levels in serum and skin lesion tissues of IMQ-induced mice (p < 0.01, p < 0.01, p < 0.01, p < 0.05, p < 0.05, p < 0.05, respectively). The ratio of Th1/Th17 cells in the peripheral blood of BML-111-treated mice was substantially diminished and the ratio of Th2 cells was substantially augmented (p < 0.05, p < 0.01, p < 0.001, respectively). Mechanistically, p-p38 protein level was substantially reduced in the skin tissues of BML-111-treated mice (p < 0.05). While, dehydrocorydaline (DHC, a p38/MAPK pathway agonists) reversed the reduction of p-p38 protein level induced by BML-111 treatment in psoriasis-like mice (p < 0.05). BML-111 modulates the p38/MAPK signaling pathway and Th1/Th2/Th17 cytokine response, and alleviates psoriasis-like dermatitis in mice.