Chronic Inflammatory Conditions Research Articles

Addressing diagnostic delays in inflammatory bowel diseases in Germany

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract that necessitate timely diagnosis to prevent complications and improve patient outcomes. Despite advancements in medical knowledge and diagnostic techniques, significant diagnostic delays persist, particularly in CD. The study by Blüthner et al , published in the World Journal of Gastroenterology , elucidates the diagnostic delays experienced by German patients with IBD and identifies key risk factors contributing to these delays.

Hematopoietic stem cell metabolism within the bone marrow niche - insights and opportunities.

Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo-SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies.

Gender, race, and economic factors influencing screening practices in hidradenitis suppurativa: a cross-sectional analysis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that significantly impacts patients' quality of life. Despite its substantial burden, HS remains underdiagnosed and undertreated, particularly among marginalized populations. This study aimed to elucidate the primary social determinants of health (SDOH) and structural determinants of health (StDOH) influencing rates and patterns of screening for patients diagnosed with HS. Using data from the All of Us Research Program database, participants with HS were identified using ICD-10 codes and stratified based on various sociodemographic factors, including race, gender, and income. The primary outcome variables were participation in viral screening and disease screening among HS patients. Statistical analyses were performed to assess the relationship between sociodemographic factors and screening practices. Income and gender had significant impacts on screening practices. Higher-income patients were more likely to receive necessary disease screening and less likely to receive unnecessary disease screening compared to lower-income patients. Non-male patients had significantly higher rates of unnecessary disease and viral screening than male patients. While differences in screening practices within each income level were significant, there were no significant differences across different income brackets or racial groups. These findings suggest that subjectivity associated with individual physicians' recommendations may contribute to disparities in screening outcomes, especially in lower-income and non-male HS patients. The study highlights the need for more clearly delineated screening guidelines and continued research on the role of SDOH in improving patient health outcomes.

Debate on the relationship between Helicobacter pylori infection and inflammatory bowel disease: a bibliometric analysis

BackgroundInflammatory bowel diseases (IBD) are chronic inflammation conditions affecting the gastrointestinal tract. Studies point out an association between Helicobacter pylori (H. pylori) infection and IBD. This study aims to visually assess the research trends and hotspots in the field of H. pylori infection and IBD, review mainstream perspectives in this field, and provide a foundation for future research and treatment.MethodsWe searched the Web of Science Core Collection Database for literature related to H. pylori and IBD, using VOS viewer to generate visual charts.ResultsA total of 246 publications were included, with articles being the predominant type of document. A significant increase in the number of publications was observed after 2011. China contributed the most of researches. Keyword clusters revealed that the researches primarily focused on immune mechanism, gut microbiome, diagnosis and treatment of IBD. Time trend results indicated that current researches centered on gut microbiota and immune mechanisms.ConclusionH. pylori infection may have a protective effect on IBD. The exact mechanisms remain unclear and may involve immunomodulation and changes of gut microbiota. Further researches are necessary for better understanding this relationship and its implications for clinical practice. Further researches and clinical practice should pay attention to this topic.

Gastric-like (pseudopyloric and pseudofoveolar) metaplasia and Paneth cell hyperplasia-neglected histological features of chronic ileal inflammation.

Architectural distortion and basal plasmacytosis are the most widely recognized histologic features of chronic ileal inflammation. However, these features might be difficult to assess in small, poorly oriented, or superficial biopsies. Additional features of chronic mucosal damage, including pseudopyloric or pseudofoveolar metaplasia and Paneth cell hyperplasia, have been less commonly reported, and their broader appreciation could facilitate the diagnosis of chronic ileal inflammatory conditions. The prevalence of gastric-like (pseudopyloric and pseudofoveolar) metaplasia and Paneth cell hyperplasia was evaluated in 102 ileal biopsies obtained from patients with Crohn's disease (n = 47), ulcerative colitis with endoscopically normal ileum (n = 20) or with backwash ileitis (n = 20), and nonsteroidal anti-inflammatory drugs- (NSAIDs-) induced ileitis (n = 15). Gastric-like metaplasia was identified in 23% of CD and 13% of NSAID-induced ileitis cases, whereas it was absent among all ulcerative colitis cases. Pseudopyloric metaplasia, pseudofoveolar metaplasia, or a combination of both was documented in 13%, 2%, and 9% of Crohn's disease cases, respectively. NSAID-associated cases showed only pseudopyloric metaplasia. Paneth cell hyperplasia was detected in 43% of Crohn's disease cases, 13% of NSAID-induced ileitis cases, and 5% of backwash ileitis cases. Accordingly, pseudofoveolar metaplasia, pseudopyloric metaplasia, and Paneth cell hyperplasia are not uncommon in conditions causing chronic ileal inflammation. They are most frequently detected in Crohn's disease, but may also be present in NSAID-induced ileitis, whereas they are significantly less common in backwash ileitis and absent in normal ileum. Given the surface localization of pseudofoveolar metaplasia, its identification can be particularly helpful when dealing with poorly oriented or superficial samples.

Exploring the anti-inflammatory potential of Vitex altissima L.f. bark - An in vitro and in silico approach

Inhibition of the inflammatory response through bark polyphenolics can help to downregulate the effects of chronic inflammation and related conditions. This study mainly investigates the polyphenolic properties and their corresponding bioactivities of Vitex altissima L.f. bark. The extracts assessed for their yield percentage, secondary metabolites, and anti-inflammatory properties of V.altissima were determined using the protein denaturation method. Through in silico modeling, it confirms the binding affinity of compounds from GC-MS analysis to the inflammation protein. The results indicated that Thalavadi-III’s V.altissima recorded the highest phenolic content on 48.23 mg GAE/g extract, while Mundathurai-I exhibited the highest flavonoid content at 25.8 mg RE/g extract. Anti-inflammation properties showed the highest percentage of inhibition in Iggalore’ V.altissima . To add more significance, the compounds from GC-MS analyses were predetermined by in silico docking analyses [benzenamine, 4,4'-[sulfonylbis(4,1-phenyleneoxy)]bis- (-6.73); hematoporphyrin (-6.22)] against inflammation protein, which confirmed

Overexpressed nicotinamide N‑methyltransferase in endometrial stromal cells induced by macrophages and estradiol contributes to cell proliferation in endometriosis

Endometriosis, an estrogen-dependent chronic inflammatory condition, afflicts reproductive-aged women. However, the underlying pathological mechanisms remain to be elucidated. Nicotinamide N-methyltransferase (NNMT) is a critical enzyme involved in cellular metabolism and methylation regulation. This study investigated the role of NNMT in endometriosis. By analyzing datasets GSE5108, GSE7305, GSE141549, GSE23339, and GSE25628, we identified a significant overexpression of NNMT in the eutopic endometrium and ectopic lesions of endometriosis patients compared to normal endometrium. Furthermore, NNMT was upregulated in collected endometrioma specimens and isolated primary endometrial stromal cells (ESCs) compared to their respective controls. Inhibition of NNMT using JBSNF-000088 attenuated the proliferation, migration, and invasion of ESCs. In vivo, treatment of mouse models of endometriosis with JBSNF-000088 resulted in a marked reduction in lesion weight and quantity. NNMT expression in ESCs was dose-dependently upregulated by 17β-estradiol at concentrations of 1 nM, 10 nM, and 100 nM, an effect that was attenuated by 10 nM progesterone. Additionally, treating HESCs with macrophage-conditioned medium elevated NNMT expression at both mRNA and protein levels. Knockdown of NNMT impeded the proliferation, migration, and invasion of ESCs, which was paralleled by decreased phosphorylation levels of Erb-b2 receptor tyrosine kinase 4 (ERBB4), PI3K, and AKT. Conversely, overexpressing ERBB4 mitigated the NNMT knockdown-induced decline in phosphorylated PI3K and AKT and rescued the proliferation of ESCs. Altogether, these results indicate that the overexpression of NNMT induced by estrogen and macrophage interaction modulates ESC proliferation via the NNMT-ERBB4-PI3K/AKT signaling pathway, as well as promotes cellular migration and invasion, contributing to the development of endometriosis.

Astragaloside IV Protects Against IL-1β-Induced Chondrocyte Damage via Activating Autophagy.

Osteoarthritis (OA) is a chronic inflammatory condition that affects the articular cartilage. Astragaloside IV (AS-IV) constitutes the primary active component of the Chinese herbal medicine Huangqi (Radix Astragali Mongolici). AS-IV demonstrates anti-inflammatory and anti-apoptotic attributes, exhibiting therapeutic potential across various inflammatory and apoptosis-related disorders. Nevertheless, its pharmaceutical effects in OA are yet to be fully defined. This study aimed to investigate the protective impact of AS-IV on rat chondrocytes treated with IL-1β and ascertain whether autophagy plays a role in this effect. Chondrocytes were isolated and cultivated from the knee joints of neonatal SD mice. The study included the blank control group, the model group, and the AS-IV concentration gradient group (50, 100, 200 μmol/L) to intervene with chondrocytes. The MTT assay was employed to assess cell viability at varying culture periods, enabling the determination of suitable concentration and duration. Subsequently, chondrocytes were treated with the optimal AS-IV concentration and divided into three groups: the model group replicated IL-1β-induced inflammatory chondrocyte injury, the AS-IV group received a co-culture of AS-IV and IL-1β, and a blank control group was established. Changes in cell morphology and structure were observed using ghost pen cyclic peptide staining. ELISA was used to measure TNF-α and GAG levels in cell supernatants. RT-qPCR assessed p62 and LC3 mRNA expression, while Western Blot evaluated p62 and LC3Ⅱ/Ⅰ protein expression. AS-IV promoted chondrocyte proliferation and concurrently inhibited cell apoptosis. An optimal AS-IV dose of 200 μmol/L and a suitable reaction time of 48 h were identified. Ghost pen cyclic peptide staining indicated that the model group's cytoskeleton exhibited fusiform changes with reduced immunofluorescence intensity, as opposed to the blank control group. The AS-IV group displayed more polygonal cytoskeletal morphology with increased immunofluorescence intensity. AS-IV reduced TNF-α levels and elevated GAG levels in the culture supernatant. Additionally, AS-IV lowered p62 mRNA and protein expression while increasing LC3 mRNA expression in cultured chondrocytes. Our findings suggest that AS-IV mitigates inflammatory chondrocyte injury, safeguarding chondrocytes through a potential autophagy suppression mechanism. These results imply that AS-IV could offer preventive advantages for OA.

Increased risk of pulmonary embolism in patients with dermatomyositis/polymyositis, a retrospective cohort study from Israel

BackgroundDespite the well-established association between chronic inflammatory conditions and pulmonary embolism(PE), previous investigations of the relationship between Dermatomyositis(DM) and Polymyositis(PM) with PE were scarce and have been subject to significant limitations, including small sample sizes and failure to account for potential confounders. ObjectivesTo investigate the correlation between DM/PM and PE, as well as assessing the impact of serologic status, myonecrosis, and inflammation markers on this relationship. MethodsIn this large, nationwide population-based study, we used the Clalit Health Services medical database and extracted all DM/PM patients who were first diagnosed between 1 January 2002 to 31 December 2018 and compared them with age and gender matched controls in a ratio of 1:5. Serological and laboratory values were obtained for each patient. Rates of PE were compared between groups using multivariate models. ResultsThe study included 1557 DM patients with 7633 controls, and 528 PM patients with 2560 controls. Compared with matched controls, the rates of PE were significantly higher in the DM/PM group, PM patients(2.8 % vs 0.5 % in controls, OR = 5.73, p < 0.001), DM patients(1.2 % vs 0.3 % in controls, OR = 3.42, p < 0.001). APLA seropositivity was significantly more prevalent in DM/PM patients compared with their matched controls, PM patients(10.8 % vs 2.7 % in controls, p < 0.001), DM patients(7.9 % vs 1.6 % in controls, p < 0.001). APLA seropositivity had a synergistic effect for PE in the DM/PM(OR = 23.18, p < 0.001). ConclusionsDM and PM are associated with higher rates of PE. Furthermore, patients with DM/PM demonstrate a significantly higher prevalence APLA which act as a potentiator of thrombosis in these patients.

MiR‑155 promotes an inflammatory response in HaCaT cells via the IRF2BP2/KLF2/NF‑κB pathway in psoriasis.

Psoriasis is a chronic inflammatory skin condition with numerous causes, including genetic, immunological and infectious factors. The course of psoriasis is long and recurrence is common; pathogenesis is not completely understood. However, there is an association between advancement of psoriasis and aberrant microRNA (miR or miRNA)‑155 expression. Through bioinformatics, the present study aimed to analyze the differentially expressed genes and miRNAs in psoriasis and its biological mechanism and function psoriatic inflammation. First of all, differentially expressed genes (DEGs) and miRNAs (DEMs) in patients with psoriasis were identified using GEO2R interactive web application. A psoriasis inflammatory model was established using lipopolysaccharide (LPS)‑treated HaCaT keratinocytes, which were transfected with miR‑155 mimic or inhibitor. Cell Counting Kit‑8 was used for the assessment of cell viability and proliferation, and changes in the cell cycle were examined using flow cytometry. ELISA and reverse transcription‑quantitative PCR (RT‑qPCR) were used to detect the expression levels of the inflammatory factors IL‑1β and IL‑6. The dual‑luciferase reporter assay was used to verify the targeting association between miR‑155‑5p and IFN regulatory factor 2 binding protein 2 (IRF2BP2). To verify the targeting association of miR‑155 and the IRF2BP2/kruppel‑like factor 2 (KLF2)/NF‑κB signaling pathway, expression levels of IRF2BP2, KLF2 and p65 were identified by RT‑qPCR and western blotting. IRF2BP2 levels were also confirmed by immunofluorescence, in conjunction with bioinformatics database analysis. Overexpression of miR‑155 inhibited proliferation of HaCaT cells and increased the number of cells in S phase and decreasing number of cells in G1 and G2 phase. In the LPS‑induced inflammatory state, miR‑155 overexpression heightened the inflammatory response of HaCaT cells while inhibition of miR‑155 lessened it. Suppression of inflammatory cytokine expression by miR‑155‑5p inhibitor was reversed by knockdown of IRF2BP2. miR‑155 was shown to interact with IRF2BP2 to negatively regulate its expression, leading to decreased KLF2 expression and increased p65 expression and secretion of inflammatory factors, intensifying the inflammatory response of HaCaT cells. Therefore, miR‑155 may contribute to development of psoriasis by inducing tissue and cell damage by increasing the inflammatory response of HaCaT cells via the IRF2BP2/KLF2/NF‑κB pathway. In conclusion, the results of the present study offer novel perspectives on the role of miR‑155 in the onset and progression of psoriasis.

Periapical cemento-osseous dysplasia masquerading as asymptomatic chronic apical periodontitis in a Chinese woman: A case report.

Cemento-osseous dysplasia (COD) belongs to a group of fibrous osseous disorders that can masquerade as periapical inflammatory conditions in the jawbones. We present a rare case of COD occurring in a patient who also had periapical periodontitis concurrently. When faced with a patient exhibiting no symptoms, diagnosis may be challenging. COD is a fibrous osseous disorder similar to periapical chronic inflammatory conditions and other cysts in the jaw bones on the radiograph. There is a rare case of COD occurring in a 49-year-old Chinese woman who also had chronic periapical periodontitis concurrently. The lesions were incidentally discovered in the mandibular anterior tooth region during the patient's imaging examination. The patient exhibited no symptoms, and diagnosing the conditions may be challenging due to the confusingly similar radiological features that present as a radiolucent lesion in the periapical region. The final diagnosis was made through pulp vitality tests, cone beam computed tomography (CBCT), and clinical examinations. The COD was recommended for annual follow-up. Root canal therapy has been performed for chronic apical periodontitis. According to the diagnostic process of COD, a thorough history check, multiple clinical examinations, and imaging studies should be emphasized to prevent misdiagnosis and avoid unnecessary or inappropriate therapies. The patient was followed up for 6 years. The recovery of chronic apical periodontitis in tooth #31 and the transformation of osteolytic and osteogenesis of COD had been observed in CBCT.

Knowledge, attitude, and practice of asthma among the adults in Shendi locality, Sudan: A cross-sectional study.

Asthma is a chronic inflammatory condition leading to intermittent airway narrowing and obstruction. Although millions suffer from asthma globally, there is limited data from African countries, particularly Sudan. This study addresses the gap in research on asthma knowledge, attitudes, and practices among the adults in Shendi locality, Northern Sudan. This cross-sectional, community-based study was conducted in Kabushiya village, Shendi, Sudan, involving 148 participants selected through multistage random sampling. Data were collected via face-to-face interviews using a validated, structured questionnaire. Statistical analyses included Mann-Whitney, Kruskal-Wallis, Chi-square, Fisher exact tests, and multiple linear regression. Participants demonstrated high levels of knowledge, positive attitudes, and good practices regarding asthma. Knowledge scores were significantly associated with marital status, education, occupation, and income (P values: .040, .003, .000, and .006, respectively), with the highest medians among divorced individuals, those with higher education, professional workers, and people earning <50,000 SDGs (medians: 17, 16, 17, and 16, respectively). Attitude scores varied significantly by marital status, education, occupation, and family asthma history (P values: .001, .000, .003, and .016, respectively), with highest scores among divorced individuals, those with high school or higher education, professionals, and those with a first-degree relative with asthma (medians: 6, 5, 5, and 5, respectively). Patient practice scores differed by marital status and income (P values: .026 and .006, respectively), with higher scores among singles and those earning <50,000 SDGs. Co-patient practice scores were significantly influenced by occupation, personal or familial asthma experience, and family asthma status (P values: .026, .003, and .000, respectively). No significant differences were observed in co-patient practice scores between groups. The study highlights a generally good level of asthma knowledge and positive attitudes among participants, with some variability in practices based on socio-demographic factors. These findings emphasize the need for targeted education and intervention programs to improve asthma management in rural Sudan.

Perianal Pulse Granuloma Induced by Plant-Derived Baby Wipes.

Pulse granulomas are unusual foreign body reactions to exogenous plant material, featuring the presence of hyaline ring structures and granulomatous inflammation. Pulse granulomas have been reported to occur in the oral cavity, gastrointestinal tract, and respiratory tract. Cutaneous pulse granulomas are exceedingly rare. All reported cases have been closely associated with underlying pathology such as chronic inflammatory conditions, trauma, or surgical procedures which likely facilitated implantation of exogenous plant material. We report a novel case of a cutaneous pulse granuloma presenting in the perianal region of an otherwise healthy man. The authors propose that the source of the exogenous plant material is plant-derived baby wipes, which the patient had been using daily to the perianal region.

Efficacy of Treatments in Reducing Facial Erythema in Rosacea: A Systematic Review.

Rosacea is a chronic inflammatory skin condition that affects over 5% of individuals worldwide. Its clinical presentation is characterized by an array of features, including erythema, papules and pustules, phymatous changes, telangiectasia, and ocular manifestations. Specifically, the multifaceted manifestation of erythema varies widely in intensity and distribution. Factors contributing to pathogenesis include neurovascular dysregulation, increased levels of pro-inflammatory mediators, and aberrant vasodilation. Erythema management plays an important role in reducing the psychosocial burden associated with rosacea and improving overall quality of life. Cochrane CENTRAL, Medline, and Embase databases were searched from inception to September 2023 and included 33 clinical trials reporting on a total of 7411 rosacea patients (74.1% female) and 21 different topical or systemic treatments. The mean age was 48.8 years (range, 18-83 years), and the mean time to outcome assessment was 8.1 weeks (standard deviation, 4.1 weeks). Treatment efficacy was assessed by outcome measures including percent improvement from baseline on 4- and 5-point scales, clinician erythema assessment (CEA) success (improvement ≥1 point), and CEA and patient self-assessment success (improvement ≥1 point). Pooled effect sizes for each treatment were calculated as a weighted average based on the number of patients in each study. The most effective topical treatments for reducing erythema include sodium sulphacetamide and sulphur, praziquantel, metronidazole, and B244 spray (Nitrosomonas eutropha). The most effective systemic treatment was paroxetine. Our findings highlight the varying efficacy of treatments in addressing the erythema in rosacea, recognizing the nuances of clinical presentations.

Exome Profiling Suggests Combined Effect of Myeloperoxidase, Toll-Like Receptors, and Metallopeptidase in Hidradenitis Suppurativa

Background: Hidradenitis suppurativa, also called acne inversa, is a chronic skin inflammatory condition involving hair follicles, sebaceous glands, and apocrine glands. Symptoms can be variable in intensity, ranging from mild to severe. The exact causes of hidradenitis suppurativa are not fully understood, but the etiology is presumed to be multifactorial, encompassing genetics and environmental factors. Methods: Two families presented with hidradenitis suppurativa with an autosomal dominant pattern. We performed whole-exome sequencing in two unrelated patients from the two families. Results: We identified two and three variants in the two families, respectively. Variants involved the TLR2 and MPO genes in the first family and the MMP2, GJB2, and TLR4 genes, some of which have already been previously reported as possible candidates for hidradenitis suppurativa. Conclusion: It is very likely that variants in a single gene only rarely cause the condition and that most cases, especially familial hidradenitis suppurativa cases, may more probably take the form of polygenic disorders.

Cellular and Molecular Pathophysiology of Gestational Diabetes

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD’s cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD’s impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD’s complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.

Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.

Obesity represents a low-grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low-dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT). An adipose tissue-resident bacterium Sphingomonas paucimobilis is identified as a potential inhibitor on the activation of brown fat and browning of inguinal WAT, resulting in defective adaptive thermogenesis. Mechanically, LPS and S. paucimobilis inhibit the production and release of 15-HETE by suppressing its main metabolic enzyme 12 lipoxygenase (12-LOX) and 15- Hydroxyeicosatetraenoic acid (15-HETE) rescues the impaired thermogenesis. Interestingly, 15-HETE directly binds to AMP-activated protein kinase α (AMPKα) and elevates the phosphorylation of AMPK, leading to the activation of uncoupling protein 1 (UCP1) and mitochondrial oxidative phosphorylation (OXPHOS) complexes. Further analysis with human obesity subjects reveals that individuals with high body mass index displayed lower 15-HETE levels. Taken together, this work improves the understanding of how chronic inflammation impairs adaptive thermogenesis and provides novel targets for alleviating obesity.

Transcriptome analysis of rheumatoid arthritis uncovers genes linked to inflammation-induced pain

Autoimmune diseases such as rheumatoid arthritis (RA) can promote states of chronic inflammation with accompanying tissue destruction and pain. RA can cause inflammatory synovitis in peripheral joints, particularly within the hands and feet, but can also sometimes trigger temporomandibular joint (TMJ) arthralgia. To better understand the effects of ongoing inflammation-induced pain signaling, dorsal root ganglia (DRGs) were acquired from individuals with RA for transcriptomic study. We conducted RNA sequencing from the L5 DRGs because it contains the soma of the sensory neurons that innervate the affected joints in the foot. DRGs from 5 RA patients were compared with 9 non-arthritic controls. RNA-seq of L5 DRGs identified 128 differentially expressed genes (DEGs) that were dysregulated in the RA subjects as compared to the non-arthritic controls. The DRG resides outside the blood brain barrier and, as such, our initial transcriptome analysis detected signs of an autoimmune disorder including the upregulated expression of immunoglobulins and other immunologically related genes within the DRGs of the RA donors. Additionally, we saw the upregulation in genes implicated in neurogenesis that could promote pain hypersensitivity. Overall, our DRG analysis suggests that there are upregulated inflammatory and pain signaling pathways that can contribute to chronic pain in RA.

Association between vulvar lichen sclerosus and celiac disease in woman.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory condition involving mainly the genital area with an undetermined aetiology. Recent studies show that in up to 34% of cases in adult women, VLS coexists with allergies or autoimmune diseases like celiac disease (CD), among others. However, literature data relating strictly to the co-occurrence of celiac disease and Duhring's disease (DH) in patients with VLS are very limited. In our study, we sought to clarify the possible relationship between vulvar lichen sclerosus in adult women and celiac disease in its cutaneous form. The aim of the study was to demonstrate the presence of celiac disease-specific antibodies in women with VLS. The control group consisted of 41 healthy women, and the study group consisted of 50 women aged 24-83 years with diagnosed vulvar lichen sclerosus who were hospitalized in the Department of Gynaecology, Obstetrics and Gynaecologic Oncology of the Bonifraters Medical Centre in Katowice. There were no significant differences in blood serum levels of CD-specific antibodies between both groups. The study conducted did not confirm the association between vulvar lichen sclerosus and celiac disease or Duhring's disease. The main limitation of the research was the small size of the study and control groups. Further studies on a larger group of patients are needed. They could clarify the possible mechanisms behind the co-occurrence of these two conditions. Earlier diagnostic will help prevent the development of severe and irreversible complications.

Advanced biologic therapies are associated with fewer adverse cardiovascular events in patients with inflammatory bowel diseases

Abstract Background Chronic inflammation is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD) and associated events. Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions, and meta-analyses of cohort studies demonstrate an increased risk of ASCVD events in IBD patients. Advanced biologic therapies (ABT) targeting the immune system revolutionized treatment of IBD patients but the impact of these therapies on ASCVD events is not known. Purpose To investigate the impact of ABT on ASVCD events in IBD patients. Methods A retrospective cohort study was performed using the TriNetX Diamond Network, a multi-institutional database providing real-time access to de-identified electronic health records, with data updated on 02/14/2024. ABT were defined as one or more the following: infliximab, adalimumab, golimumab, certolizumab pegol, ustekinumab, risankizumab, vedolizumab, or natalizumab. ASCVD events were based on ICD codes for ischemic heart, cerebrovascular, and peripheral vascular diseases. Individuals &amp;gt;40 years with IBD were included. ASCVD events in (1) patients on ABT and (2) patients not on ABT (NABT) were compared. Propensity score matching was performed on sex, aspirin use, and the following ASCVD risk factors: age, hypertension, hyperlipidemia, tobacco use, and type 2 diabetes mellitus. Results This study includes 72,650 individuals in each of the two matched cohorts. There were no differences in baseline characteristics between the two propensity-score matched cohorts (Table). The probabilities of experiencing any ASCVD event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (8.3% vs. 12.4%, OR 0.64; 13% vs. 18.6%, OR 0.66; and 15% vs. 21.2%, OR 0.65; respectively, all p&amp;lt;0.01). Similarly, the probability of experiencing an ischemic heart disease event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (5.2% vs. 7.9%, OR 0.64; 8% vs. 11.7%, OR 0.66; and 9.2% vs. 13.4% OR 0.66; respectively, all p&amp;lt;0.01). The probability of cerebrovascular disease events at one, three, and five years in the ABT group were all significantly lower than in the NABT group (2% vs. 3.3%, OR 0.59; 3.5% vs. 5.7%, OR 0.59; and 4.2% vs. 6.8% OR 0.60; respectively, all p&amp;lt;0.01) and the probability of a peripheral artery disease event at one, three, and five years in the ABT group were also all significantly lower than in the NABT group event (2.8% vs. 4.5%, OR 0.62; 5.1% vs. 7.6%, OR 0.65; and 6.2% vs. 9.3% OR 0.65; respectively, all p&amp;lt;0.01). Conclusions ABT are associated with significantly fewer ASCVD events in the IBD patient population. Future studies examining the differential benefit of drug subclasses on ASCVD outcomes and mechanisms responsible for the ABT benefit, as well as prospective study designs have the potential to identify new therapeutic targets in IBD patients and with applicability beyond IBD patients.Table