Chronic Systemic Disease Research Articles

Genetic insight into dissecting the immunophenotypes and inflammatory profiles in the pathogenesis of Sjogren syndrome

BackgroundSjogren syndrome (SS) is a chronic systemic autoimmune disease and its pathogenesis often involves the participation of numerous immune cells and inflammatory factors. Despite increased researches and studies recently focusing on this area, it remains to be fully elucidated. We decide to incorporate genetic insight into investigation of the causal link between various immune cells, inflammatory factors and pathogenesis of Sjogren syndrome (SS).MethodsOur study leveraged the genetic variants of multi-omics statistics extracted from genome-wide association study (GWAS), the University of Bristol and the FinnGen study. We performed a bidirectional Mendelian randomization and mediation study based on randomly allocated instrumental variables to infer causality, followed by external validation with UK Biobank data and Bayesian colocalization.ResultsWe demonstrated that an elevated level of CD27 on IgD + CD24 + B cell, a subset of B cells expressing both IgD and CD24, was associated with a higher risk of SS (OR = 1.119, 95% CI: 1.061–1.179, P < 0.001), while CD3 on CD45RA + CD4 + Treg was a protective factor (OR = 0.917, 95%CI: 0.877–0.959, P < 0.001). Results of meta-analysis and colocalization further supported the significant results identified in the primary analysis. A total of 4 inflammatory cytokines and 7 circulating proteins exhibited potential causal relationships with SS despite no significant result achieved after FDR correction. Finally, results of mediation analysis indicated that CD40L receptor levels had significant mediating effects (β = 0.0314, 95% CI: 0.0004–0.0624, P = 0.0471) at a mediation proportion of 28% (95% CI: 0.364%-55.6%) in causal relationship between CD27 on IgD + CD24 + B cell and SS.ConclusionsBy providing a novel genetic insight into unveiling the roles of autoimmunity and inflammation in Sjogren syndrome, our findings may potentially lead to identifying new clinical biomarkers for disease monitoring and therapeutic targets that offer more effective alternatives for treating this condition. Therefore, our study may provide valuable evidence for future clinical intervention and targeted immunotherapy.

Does adopting a healthy diet improve periodontal parameters in patients susceptible to periodontal disease? A systematic review.

The aim of this systematic review is to evaluate evidence relating to whether adopting a diet, associated with improved outcomes for chronic systemic diseases with an inflammatory component, can improve periodontal parameters in patients with periodontal diseases. Electronic databases and one platform were systematically searched; Medline, Embase, Web of Science and the Cochrane Library including references of relevant studies. 1220 studies were identified of which 9 studies were eligible; 4 RCT's, 1 controlled trial and 4 observational cohort studies DATA SYNTHESIS: 8 out of 9 studies found improved periodontal parameters associated with a diet that was low in refined carbohydrates, low in saturated fats, high in fibre and high in nutrition but the studies were low to medium quality of evidence and the diets, method of recording the diets and periodontal parameters varied between the studies as did the study duration and age of participants. Current evidence supports the hypothesis that adopting a healthy diet has the potential to positively impact periodontal parameters in patients with periodontal diseases, particularly in the older population but the effects may be negated by confounding factors such as smoking. 9 studies were included in the review which were rated moderate or low quality of evidence.

Research progress on the pathogenesis of psoriasis and its small molecule inhibitors.

Psoriasis is a prevalent chronic systemic immune disease characterized by T-cellmediated hyperproliferation of keratinized cells. Among its various manifestations, plaque-type psoriasis is the most common. Treatment options for psoriasis encompass topical medications, biological therapies, phototherapy techniques, and others. However, traditional treatments are associated with numerous side effects. In contrast, targeted therapy has garnered increasing attention due to its high selectivity, strong safety profile, and favorable therapeutic outcomes. Patients with psoriasis lesions exhibit elevated levels of proinflammatory cytokines compared with the general population. These proinflammatory cytokines have been implicated in mediating psoriasis pathogenesis by inducing keratinocyte proliferation through multiple signaling pathways within the body. This study will delve into the Janus kinase-signal transducers and activators of transcription, phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB, also known as AKT), and nuclear factor Kappa-light-chain-enhancer of activated B cells signaling pathways to elucidate their roles in mediating psoriasis pathogenesis. In addition, we will summarize potential targets relevant to the treatment of psoriasis and discuss the design and activity assessment of their inhibitors. It also provides new insights for further in-depth study of psoriasis and development of novel molecularly targeted inhibitors.

Analysis of the relationships between interferon-stimulated genes and anti-SSA/Ro 60 antibodies in primary Sjögren's syndrome patients via multiomics and machine learning methods.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease characterized by lymphocyte infiltration of the exocrine glands. Interferon-stimulated genes (ISGs) are often upregulated in patients with pSS, and anti-SSA/Ro 60 antibodies are among the main items detected in pSS. However, the relationship between ISGs and anti-SSA/Ro 60 antibodies in pSS remains unclear. Therefore, our study aimed to explore the relationships between ISGs and anti-SSA/Ro 60 antibodies and identify key genes involved in pSS. Transcriptome sequencing and microarray data of PBMC, parotid and labial glands tissues from pSS patients (1341 samples) were downloaded from the GEO database and used in this analysis. A linear model was used to analyze the relationship between ISGs and anti-SSA/Ro 60 antibodies. ELISA was used to measure the levels of anti-SSA/Ro 60 antibodies in the whole blood of pSS patients. Machine learning methods were used to construct a diagnostic model, and further validation was conducted with external datasets and RT-qPCR. After differential analysis of the PBMCs and tissues, 22 and 160 DEGs, respectively, were identified. There was a positive correlation between ISGs and anti-SSA/Ro 60 antibodies in the PBMCs of pSS patients, and there was a significant positive correlation between ISG expression in the PBMCs and tissues of pSS patients. The expression levels of ISGs were increased in the PBMCs and tissues of pSS patients with positive anti-SSA/Ro 60 antibody results, and the ESSDAI, focus scores and CD45 levels were increased. Finally, the expression of EPSTI1, EIF2AK2, IFI44, RSAD2, and OAS2 in PBMCs can be used to diagnose pSS. In patients with pSS, a positive correlation was observed between ISGs and anti-SSA/Ro 60 antibodies. The expression of ISGs reflects the disease severity and pathology scores of pSS patients. Through bioinformatics analysis combined with our clinical data, we identified five key genes with potential diagnostic value for pSS.

Oral Inflammation and Microbiome Dysbiosis Exacerbate Chronic Graft-versus-host Disease.

The oral microbiota, second in abundance to the gut, is implicated in chronic systemic diseases, but its specific role in GVHD pathogenesis has been unclear. Our study finds that mucositis-induced oral dysbiosis in patients post-hematopoietic cell transplantation associated with increased chronic GVHD (cGVHD) even in patients receiving post-transplant cyclophosphamide. In murine HCT models, oral dysbiosis caused by bilateral molar ligatures exacerbated cGVHD and increased bacterial load in the oral cavity and gut with Enterococcaceae significantly increasing in both organs. In this model, the migration of Enterococcaceae to cervical lymph nodes (LNs) both pre- and post-transplantation activated antigen-presenting cells (APCs), thereby promoting the expansion of donor-derived inflammatory T cells. Based on these results, we hypothesize that pathogenic bacteria increased in the oral cavity might not only exacerbate local inflammation but also enhance systemic inflammation throughout the HCT course. Additionally, these bacteria translocated to the gut and formed ectopic colonies, further amplifying systemic inflammation. Furthermore, interventions targeting the oral microbiome mitigated murine cGVHD. Collectively, our findings highlight the importance of oral dysbiosis in cGVHD and suggest that modulation of the oral microbiome during transplantation may be an effective approach for preventing or treating cGVHD.

Estimation of TNF- α and some immunological parameters in patient with systemic lupus erythematosus

Abstract: Abstract— Systemic Lupus Erythematosus (SLE) is a multifactorial chronic systemic autoimmune disease. It is characterized by a lack of immune tolerance to autoantigens such as nuclear antigens. In this study, 25 individuals diagnosed with SLE had their blood samples drawn, while 25 healthy individuals were used as a control group. The results of this investigation show that the patients' TNF-α levels (106.9 ± 10.8) significantly increased more than 52.86 in the control group. Comparing the immunological parameters of the patients to the healthy group, the study revealed a decrease in the eosinophile, basophile, lymphocyte, and monocyte counts (010 ± 0.003, 0.022 ± 0.004, 1.71 ± 0.66, 0.21 ± 0.047 respectively) and a rise in the neutrophile and immature granulocyte counts (7.43 ± 1.66, 2.68 ± 0.46 respectively) in SLE patient. Keywords— SLE,TNF‑α,immunological parameters

P65 Clinical characteristics of pruritus in Bangladeshi psoriasis patients

Abstract Background Psoriasis is a chronic systemic autoimmune disease associated with pruritus and seriously affects the quality of life of patients, but published data on its frequency and characteristics are limited. Objectives The purpose of this study is to find out the characteristics of pruritus in patients with different types of psoriasis and its impacts on the quality of life in Bangladesh. Materials and Methods This descriptive cross-sectional study was carried out in the Department of Dermatology and Venereology of Chittagong Medical College Hospital, Bangladesh for the period between March 2021 and August 2022 by using various validated tools like Visual Analog Scale, body surface area (BSA), psoriasis area and severity index (PASI), palmoplantar pustulosis severity index, severity of generalized pustular psoriasis, Static Physician Global Assessment Scale, Dermatology Life Quality Index (DLQI) and Family Reported Outcome Measure (FROM). After developing a questionnaire assessing various aspects of pruritus, we have surveyed 270 patients of psoriasis with different varieties regarding the presence and intensity of pruritus and life quality assessment. Results The mean age of the patients was 38.86 (±14.32) years, and males 182 (67.4%) outnumber females 88 (32.6%). A total of 210 (77.8%) patients reported having pruritus, 110 (40.74%) had moderate pruritus, 82 (30.37%) had mild pruritus, and 18 (6.7%) had severe pruritus. Pruritus was more common in the 21–40 years age group (35%), male sex (53%), low-income group (51%), outside field workers (23%), winter and spring exacerbation (31%), BSA &amp;lt;9% group (45%), palmoplantar psoriasis types (19%) and mild PASI (38%) group. In regards to DLQI, the majority 91 (33.7%) patients had a small effect, 68 (25.2%) had a large effect, 54 (20%) had a moderate effect, 53 (19.6%) had extremely large effect, and 4 (1.5%) had no effect. Conclusion Though pruritus is not specific to psoriasis, this study conveys the severity of pruritus in psoriasis patients in which a physician may encounter in clinical practice to monitor disease severity and optimization of treatment as well as take proper steps to improve the quality of life of patients.

P57 Cross-sectional application of the dermatologist-centred screening tool, looking for axial psoriatic arthritis in patients with severe plaque psoriasis

Abstract Psoriasis is a chronic, inflammatory and immune-mediated systemic disease that primarily affects the skin and joints. In ∼70% of cases, the skin disease precedes joint involvement, and it is estimated that approximately one-third of patients with psoriatic disease will develop psoriatic arthritis (PsA) over the course of their disease. Researchers often seek to establish good screening tools or even biomarkers that can help the clinical dermatologist in this assessment, improving the window of opportunity for action. Most of the validated tools, such as PEST and PASE, despite their excellent performance, do not consider the axial domain of PsA. We conducted a cross-sectional study on our cohort of severe psoriasis patients from our outpatient clinic, applying the dermatologist-centred screening (DCS) questionnaire. PsA was defined by CASPAR criteria. Statistical analysis was performed in SPSS 20.0. The study underwent ethical review and was approved: average age of 50.84 years, with a slight predominance of females (53.2%). The average duration of the disease was 15.89 years. Mean PASI and body surface area (BSA) were, respectively, 16.65 and 20.88%. Hundred and fifty-eight patients were studied: average age of 50.84 years, with a slight predominance of females (53.2%). The average duration of the disease was 15.89 years. Mean PASI and BSA were, respectively, 16.65 and 20.88%. Fifty of the 158 patients were diagnosed with PsA (31.6%). In the sample, 35 patients had positive DCS. Of these 35, in fact, 25 (71.4%) had PsA. Having positive DCS implies a prevalence at least three times higher than having PsA (prevalence ratio: 3.254, P &amp;lt; 0.0001, 95% confidence interval = 2.195–4.824). Among the 25 with positive DCS, 10 patients had low back pain at the end of the night, sometimes even being woken up by the pain; maintaining it during the morning, associated with stiffness for at least 30 min; in addition to relief with movement and stretching. Of these 10, 7 (14% of patients with PsA and 28% of all with positive DCS) had a confirmed diagnosis of axial PsA, supported by evaluation by a board-certified rheumatologist, in addition to complementary exams (all with positive magnetic resonance imaging showing sacroiliitis). The ATTRACT study studied 365 patients; selecting through DCS 124. Of these, 36 (29%) confirmed a diagnosis of Axial PsA and 21 (16.9%) had peripheral PsA, without axial involvement. DCS appears to be a practical, quick and easy tool to perform in clinical practice, correctly selecting patients for better evaluation by a rheumatologist, probably contributing to a better diagnosis. The limitations of this work are the cross-sectional design and small sample.

Clinical observations of skin Kaposi’s sarcoma

Kaposi's sarcoma is an angioproliferative disease of endothelial origin associated with human herpes virus-8 (HHV-8), or Kaposi's sarcoma herpesvirus. The disease was first described in 1872 by Moritz Kaposi as a pigmented cutaneous sarcoma localized on the lower extremities. The disease is considered quite rare, but at present there is an increase in the incidence worldwide, due to which there is a growing interest in this problem. Today, it remains the leading skin pathology among HIV-positive patients, occurring in 20%. However, the assessment of the pathological process can be difficult, and the diagnosis may not be made at all, due to atypical clinical manifestations (especially in HIV-negative patients), so the problem of Kaposi's sarcoma diagnostics remains relevant for doctors of any specialty, especially dermatovenerologists and oncologists. Kaposi's sarcoma can affect almost any organ, including the skin. The most common localization is on the skin of the extremities and face. Clinical manifestations are rashes in the form of spots, nodules, plaques, nodes. Kaposi's sarcoma is classified according to clinical and epidemiological forms: classical, endemic, epidemic and iatrogenic. Recently, a fifth form has been described, called non-epidemic Kaposi's sarcoma, which is observed in HIV-negative men who have sex with other men. The persistence of HHV-8 alone in the human body is not sufficient for Kaposi's sarcoma to occur, as the development of the disease is dependent on immunosuppressive conditions such as HIV infection, cytostatic drugs, and chronic systemic inflammatory diseases (e.g., rheumatoid arthritis). The interaction between human immune dysfunction and the local inflammatory response to herpesvirus creates a favourable environment for the onset and progression of the disease. These clinical cases demonstrate an atypical clinical course of Kaposi's sarcoma of the skin with the absence of HIV-1, HIV-2 and HHV-8 in the blood of the presented patients.

Dentin hypersensitivity and quality of life in patients with chronic systemic disease.

To assess the potential impact of dentin hypersensitivity on the quality of life in people with chronic systemic diseases. We included 252 volunteers, 18 years or older, with ≥ 6 teeth, and under outpatient medical follow-up for systemic chronic diseases. Short Form Health Survey 36 (SF-36) was used to assess quality of life (QoL); Oral Health Impact Profile-14 (OHIP-14) and Dentine Hypersensitivity Experience Questionnaire (DHEQ-15) were used for oral health-related quality of life (OHRQoL). Dentin hypersensitivity pain was assessed using an evaporative and tactile test, and pain assessment was performed using a numerical rating scale and a verbal rating scale. Medical information was obtained from anamnesis forms and the hospital digital medical records. Of 252 participants, 60% had dentin hypersensitivity. There was a negative impact on the QoL/OHRQoL of individuals with dentin hypersensitivity regarding the vitality, mental health, physical functioning, and bodily pain dimensions of SF-36, and the functional limitation, physical pain, physical disability, and psychological disability dimensions of OHIP-14. Dentin hypersensitivity appeared to exert an indirect influence on QoL. Dentin hypersensitivity negatively impacts the quality of life in patients with chronic systemic diseases.

Anti-inflammatory potential of Curcuma heyneana: An in vitro and in silico investigation

Rheumatoid arthritis (RA) is a progressive and chronic systemic autoimmune disease. However, currently treatment is often carried out using NSAIDs and corticosteroids. Although it reduces symptoms, this treatment has a high rate of side effects. This study aims to determine the anti-inflammatory property of Curcuma heyneana so that it can be used as an alternative treatment for RA. Based on author knowledge, this study on C. heyneana from the Indonesian region for the treatment of RA is still limited. C. heyneana’s rhizome was extracted by maceration with ethanol followed by fractionation process using n-hexane, ethyl acetate, and n-butanol. The anti-inflammatory invitro activities were determined by heat-induced hemolysis, effect on protein denaturation, and cyclooxygenases (COX) inhibition assay. Molecular docking of major predictive compounds was performed by AutoDock Vina. The results showed that some fractions of C. heyneana contained terpenoids, flavonoids, and alkaloids. The ethyl acetate fraction exhibited the highest anti-inflammatory activity, which was attributed to the presence of curcuminoids. Molecular docking studies further confirmed the potential of demethoxycurcumin, a curcuminoid identified in the ethyl acetate fraction, to inhibit COX-2. These findings suggest that C. heyneana, particularly its previously unreported curcuminoid-rich fractions, holds promise as a natural anti-inflammatory agent. Further research is warranted to explore the therapeutic potential of this plant in the management of RA and other inflammatory disorders.

Headaches in Sjogren's disease: A narrative review.

To review the most common types of primary and secondary headaches that are associated with Sjogren's disease (SjD). Sjogren's disease is a chronic systemic autoimmune disease that typically presents with xerophthalmia, xerostomia, and arthralgias. Sensory and motor neuropathies are commonly reported neurological complications with SjD. Primary and secondary headaches are also frequent neurological complications associated with SjD, which may be under-recognized. In this study, researchers conducted a literature review through the platforms of PubMed and Google Scholar with the keywords: (1) Sjogren's syndrome, (2) Sjogren's disease, (3) headache, (4) migraine, (5) tension-type headache, (6) aseptic meningitis, (7) cerebral venous sinus thrombosis, and (8) idiopathic intracranial hypertension. Included articles involved a study population of patients with both SjD and headache. There were no exclusion criteria. A total of 54 articles were identified, and 31 articles were utilized for study analysis. In patients with SjD, headaches were a frequently reported neurological complaint. The most common types of primary headaches associated with SjD were found to be migraine and tension-type headache. Patients with SjD were more likely to report severe, debilitating headaches compared to the general population. Furthermore, patients with SjD have been found to experience dangerous types of secondary headaches, including aseptic meningitis and cerebral venous sinus thrombosis. Headaches are a common neurological complication in patients with SjD. Current literature suggests that there is an increased risk of both primary and secondary headaches in individuals with SjD compared to the general population and that headaches may occur throughout the clinical course of the disease. There are also reports of patients who experience the onset of primary and secondary headaches prior to the diagnosis of SjD. SjD has been linked to dangerous, life-threatening conditions that cause headaches, which require urgent recognition and treatment. Therefore, it is important to have a higher index of suspicion for patients who present with headaches and clinical symptoms of SjD, such as xerophthalmia and xerostomia. Utilizing a detailed history, physical examination, and neuroimaging can assist clinicians to recognize and diagnose types of headaches in patients with SjD to prevent dangerous complications.

Ferroptosis of select skin epithelial cells initiates and maintains chronic systemic immune-mediated psoriatic disease.

Dysregulations of epithelial-immune interactions frequently culminate in chronic inflammatory diseases of the skin, lungs, kidneys, and gastrointestinal tract. Yet, the intraepithelial processes which initiate and perpetuate inflammation in these organs are poorly understood. Here, by utilizing redox lipidomics we identified ferroptosis-associated peroxidation of polyunsaturated phosphatidylethanolamines in the epithelia of patients with asthma, cystic fibrosis, psoriasis and renal failure. Focusing on psoriasis as a disease model, we used high-resolution mass spectrometry imaging and identified keratin 14 (K14)-expressing keratinocytes executing a ferroptotic death program in human psoriatic skin. Psoriatic phenotype with characteristic Th1/Th17 skin and extracutaneous immune responses was initiated and maintained in a murine model designed to actuate ferroptosis in a fraction of K14+ glutathione peroxidase 4 (Gpx4)-deficient epidermal keratinocytes. Importantly, an anti-ferroptotic agent, Liproxstatin-1, was as effective as clinically relevant biologic IL-12/IL-23/TNFα-targeting therapies or the depletion of T cells in completely abrogating molecular, biochemical and morphologic features of psoriasis. As ferroptosis in select epidermal keratinocytes triggers and sustains a pathologic psoriatic multi-organ inflammatory circuit, we suggest that strategies targeting ferroptosis, or its causes, may be effective in preventing or ameliorating a variety of chronic inflammatory diseases.

Prognostic nutritional index and albuminuria in adults aged 20 years and above: a cross-sectional analysis in the United States.

Albuminuria is an important early marker of kidney damage and progression of chronic kidney disease and is also linked to several chronic systemic diseases. The Prognostic Nutritional Index (PNI) is widely used in the assessment of multiple diseases. However, research dealing with the relationship between PNI and albuminuria remains scarce. This research project aims to examine this association. The present study employed data from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020, including 7,737 adult participants who met the study criteria. PNI was analyzed as a quartile-categorized variable. Multivariable regression models and smoothing curve fitting were adopted to examine the relationship between PNI and albuminuria. In order to ascertain the stability of the association across different populations, subgroup analyses were performed. The study found a statistically significant inverse relationship between higher PNI levels and the prevalence of albuminuria. The fully adjusted model indicates that a one-unit increase in PNI is associated with a 4% reduced odds of albuminuria prevalence [0.96 (0.93, 0.98)]. Quartile analysis showed a stable inverse relationship, with the highest PNI quartile having the significantly lower odds of albuminuria prevalence [0.76 (0.62, 0.94), p for trend = 0.0004]. Smooth curve fitting and two-piecewise linear regression models indicated a nonlinear relationship between PNI and albuminuria, with a turning point at 42. Subgroup analysis confirmed the reliability of the inverse relationship between PNI and albuminuria across all groups. The findings of this study indicated that higher PNI levels are significantly inversely related to the odds prevalence of albuminuria. PNI could serve as an important predictor for the occurrence of albuminuria. Further prospective studies are needed to validate this association.

ENaC contributes to macrophage dysfunction in cystic fibrosis.

Cystic fibrosis (CF) is a chronic systemic disease caused by dysfunctional or absent cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is expressed in human immune cells and plays a role in regulating innate immunity both directly and indirectly. Besides CFTR, research indicates that the epithelial sodium channel (ENaC) also contributes to dysfunction in CF airway epithelial cells. However, the impact of non-CFTR ion channel dysfunction on CF immune responses is not yet fully understood. A precise understanding of how CF immune function is regulated by ion channels may allow antibiotic-and mutation-agnostic treatment approaches to chronic bacterial infection and inflammation. Therefore, we hypothesized that ENaC is aberrantly expressed in CF macrophages and directly contributes to impaired phagocytic and inflammatory functions. ENaC expression was characterized in human immune cells isolated from CF and non-CF blood donors. Monocyte-derived macrophage (MDM) function and bacterial killing was tested in the setting of ENaC modulation. Baseline expression of ENaC in human CF MDMs, lymphocytes, and granulocytes was increased at both the transcript and protein level relative to non-CF controls and persisted after exposure to bacteria. Inhibition of CFTR in non-CF MDMs resulted in ENaC overexpression.CFTR modulator treatment reduced but did not eliminate ENaC overexpression in CF MDMs. Interestingly, ENaC inhibition with Amiloride increased CFTR expression. Amiloride-treated CF MDMs also showed normalized ROS production, improved autophagy, and decreased pro-inflammatory cytokine production. Finally, results from an ion channel microarray indicated that sodium channel expression in CF MDMs normalized after Amiloride treatment with minimal effect on other ion channels. ENaC is overexpressed in CF immune cells and is associated with abnormal macrophage function. ENaC modulation in immune cells is a novel potential therapeutic target for infection control in CF, either in combination with CFTR modulators, or as a sole agent for patients not currently eligible for CFTR modulators.

Myosteatosis: diagnostic significance and assessment by imaging approaches.

Myosteatosis has emerged as an important concept in muscle health as it is associated with an increased risk of adverse health outcomes, a higher rate of complications, and increased mortality associated with ageing, chronic systemic and neuromuscular diseases, cancer, metabolic syndromes, degenerative events, and trauma. Myosteatosis involves ectopic infiltration of fat into skeletal muscle, and it exhibits a negative correlation with muscle mass, strength, and mobility representing a contributing factor to decreased muscle quality. While myosteatosis serves as an additional biomarker for sarcopenia, cachexia, and metabolic syndromes, it is not synonymous with sarcopenia. Myosteatosis induces proinflammatory changes that contribute to decreased muscle function, compromise mitochondrial function, and increase inflammatory response in muscles. Imaging techniques such as computed tomography (CT), particularly opportunistic abdominal CT scans, and magnetic resonance imaging (MRI) or magnetic resonance spectroscopy (MRS), have been used in both clinical practice and research. And in recent years, ultrasound has emerged as a promising bedside tool for measuring changes in muscle tissue. Various techniques, including CT-based muscle attenuation (MA) and intermuscular adipose tissue (IMAT) quantification, MRI-based proton density fat fraction (PDFF) and T1-T2 mapping, and musculoskeletal ultrasound (MSUS)-based echo intensity (EI) and shear wave elastography (SWE), are accessible in clinical practice and can be used as adjunct biomarkers of myosteatosis to assess various debilitating muscle health conditions. However, a stan¬dard definition of myosteatosis with a thorough understanding of the pathophysiological mechanisms, and a consensus in assessment methods and clinical outcomes has not yet been established. Recent developments in image acquisition and quantification have attempted to develop an appropriate muscle quality index for the assessment of myosteatosis. Additionally, emerging studies on artificial intelligence (AI) may provide further insights into quantification and automated assessment, including MRS analysis. In this review, we discuss the pathophysiological aspects of myosteatosis, all the current imaging techniques and recent advances in imaging assessment as potential biomarkers of myosteatosis, and the most common clinical conditions involved.

Endometriosis, a prevalent disease, is associated with significant cardiac disease

Abstract Background Endometriosis, a chronic systemic gynecological disease affecting 10% of women in the reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiac outcomes are scarce. Further research is needed to address this gap in knowledge as highlighted by recent calls from the European Heart Journal. Purpose To examine the incidence of the following outcomes both as a composite and individually: 1) ischemic events, 2) arrhythmias, and 3) heart failure among women with endometriosis compared with the background population. Methods Using Danish nationwide registries, all women with a diagnosis of endometriosis (1977-2021) were identified and matched with women from the background population in a 1:4 ratio based on year of birth. The incidence of 1) ischemic heart disease and ischemic stroke, 2) arrhythmias (including atrial flutter/fibrillation), and 3) heart failure were examined and compared between women with and without endometriosis. Results After exclusion of women with ischemic events/arrhythmias/heart failure prior to index, 59,194 women with endometriosis and 238,352 matched controls were included (median age 37.1 years [IQR 29.8-44.4 years]). The women were followed for a median of 17 years and a maximum of 45 years. Overall, women with endometriosis were more comorbid and used more medications than their matched controls. The 40-year cumulative incidences of the composite outcome were 36.2% (95%CI 35.4-37.1%) and 30.2% (95%CI 29.8-30.7%) among women with and without endometriosis, whereas it were 23.8% (95%CI 23.0%-24.5%) and 18.8% (95%CI 18.5%-19.1%) for ischemic events, 20.1% (95%CI 19.4%-20.9%) and 17.2% (95%CI 16.8%-17.5%) for arrhythmias, and 7.5% (95%CI 7.0-8.0%) and 6.6% (95%CI 6.3-6.8%) for heart failure, respectively (Figure 1). The most common arrhythmia was atrial fibrillation/flutter constituting more than half of the events in both groups. In both unadjusted and adjusted analyses, women with endometriosis compared with controls had a significantly higher associated risks of the composite outcome (unadjusted HR 1.30 [95%CI 1.27-1.34], adjusted HR 1.29 [95%CI 1.25-1.32]), ischemic events (unadjusted HR 1.32 [95%CI 1.28-1.37], adjusted HR 1.31 [95%CI 1.26-1.35]), arrhythmias (unadjusted HR 1.25 [95%CI 1.20-1.30], adjusted HR 1.24 [95%CI 1.19-1.29]), and heart failure (unadjusted HR 1.07 [95%CI 1.01-1.14]), adjusted analysis (HR 1.05 [95%CI 0.98-1.12]). Conclusions Women with endometriosis have a higher associated long-term risk of significant cardiac outcomes compared with the background population. Despite the small relative differences, the high prevalence of endometriosis underscores the importance of these findings and emphasizes the need for enhanced understanding and prevention of its long-term cardiac outcomes.

Associations between Gut Microbiota and Microbial Metabolites in Adjuvant- induced Arthritis Rats with Moist Heat Arthralgia Spasm Syndrome.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease. According to Traditional Chinese Medicine (TCM) syndromes theory, moist heat arthralgia spasm syndrome is the most prevalent syndrome of RA patients in the active period. However, the mechanism of alteration of gut microbiota in RA with moist heat arthralgia spasm syndrome has not been reported until now. This study focused on the alteration of gut microbiota in adjuvant-induced arthritis rats with moist heat arthralgia spasm syndrome, elaborated its regulation mechanism, and analyzed the associations between gut microbiota and microbial metabolites. The disease-syndrome combination rat model of RA with moist heat arthralgia spasm syndrome was constructed with Adjuvant-Induced Arthritis (AIA) under damp-heat stimulating. Enzyme-Linked Immunosorbent Assay (ELISA) was used to measure serum biochemical indicators. Damages of ankle joints were observed using hematoxylin and eosin (H&E). 16 small ribosomal subunit RNA (16S rRNA) gene sequencing was conducted to assess the gut microbiota composition and function on feces from rats. Alterations in fecal metabolites profiling were evaluated by fecal metabolomics through Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectrometry (GC-MS). Pearson correlation analysis was performed to explore the associations of altered gut microbiota and microbial metabolites in Model rats. The imbalance of gut microbiota in Model rats was accompanied by metabolic disorders. Lactobacillus, Prevotellaceae_NK3B31_group, Allobaculum, Prevotellaceae_UCG_001, Alloprevotella, and Dubosiella were found to be dominant genera in Model rats. In total, 357 metabolites were significantly altered in Model rats and predominantly enriched into fatty acid degradation and glycerophospholipid metabolism. Pearson correlation analysis showed that TNF-α and IL-1β were associated with Prevotellaceae_Ga6A1_group and 3R-hydroxy-docosan-5S-olide, alpha-N-(3-hydroxy-14-methyl-pentadecanoyl)-ornithine, 17-methyl-trans-4,5- methylenenona-decanoic acid, Semiplenamide F. The key differential microbiota genera and differential microbial metabolites may become important targets for the treatment of RA and provide the theoretical basis for exploring the pathogenesis of RA.

Mechanism of Xue-Jie-San treating Crohn's disease complicated by atherosclerosis: Network pharmacology, molecular docking and experimental validation

BackgroundCrohn's disease (CD), as a chronic systemic inflammatory disease, is strongly associated with the development of premature atherosclerosis (AS). Atherosclerotic cardiovascular disease, including coronary heart disease, myocardial infarction and stroke, is a lethal complication of CD. Nowadays, there is a lack of effective monotherapy for CD complicated by AS. PurposeTo explore the underlying effects and mechanisms of Xue-Jie-San (XJS) on treating CD complicated by AS via network pharmacology and experimental validation. MethodsThe targets of XJS components were obtained from TCMSP, ETCM and PubChem databases as well as the disease genes of CD and AS from GeneCards, DisGeNET and OMIM databases. The core targets were screened out from the drug-disease common targets identified by protein–protein interaction (PPI) network analysis and then analyzed with GO and KEGG enrichment. The interaction between core target and XJS component was detected by molecular docking and molecular dynamics simulation. Subsequently, the core targets were validated via GEO datasets and their biological functions were confirmed in vitro. Nile red staining was used to evaluated lipid accumulation in human umbilical vein endothelial cells (HUVECs) challenged by lipopolysaccharide (LPS) combined with oxidized low-density lipoprotein (ox-LDL). Levels of pro-inflammatory cytokines were examined by enzyme-linked immunosorbent assay. Chemokine CCL2 and CXCL8 were detected by immunofluorescence staining. The activity of the TLR4/Myd88/NF-κB signaling pathway was assessed using Western blot. ResultsIn total, 26 common target genes of XJS, CD and AS were found. Among them, 11 core genes were identified by PPI network analysis. The effects of XJS treating CD complicated by AS were mainly mediated by the lipid and atherosclerosis pathway, inflammatory bowel disease pathway and toll-like receptor signaling pathway. Molecular docking and molecular dynamics simulation displayed strong binding affinity between XJS component and the core target. Six core genes including TLR4, IL-1β, TNF, ICAM1, CCL2 and CXCL8 were validated by GEO datasets. In vitro, the effects of XJS on reducing lipid accumulation, secretion of IL-1β, IL6, TNF-α, CCL2 and CXCL8, and the protein expressions of TLR4, Myd88, p-p65 and ICAM1 were verified. ConclusionXJS is a potential candidate drug for the treatment of CD complicated by AS. The underlying mechanisms involve mitigation of lipid accumulation-mediated endothelial dysfunction and blockage of immune inflammatory response by targeting TLR4.

Endometriosis specific vaginal microbiota links to urine and serum N-glycome

Endometriosis is a chronic systemic disease, which results in endometrial-type tissue growing outside the uterus, and affects approximately 10% of reproductive-aged women worldwide. Its aetiology is poorly understood, and there is currently no long-term cure. Development and persistence of the disease depend on several coexisting factors including the vaginal microbiome. However, the role played by this important entity in endometriosis and its systemic involvement is not fully understood. Here, we investigated the vaginal microbiota, the serum and urine glycome, and antibody glycosylation in endometriosis patients. We reveal an endometriosis-specific vaginal microbiota in patients, being distinct from that present in a control group. Endometriosis patients were typified by a loss of the dominant Lactobacillus species, i.e. Lactobacillus iners, increased bacterial diversity and the presence of species such as Anaerococcus senegalensis, Prevotella jejuni, Porphyromonas bennonis and Anaerococcus octavius. The presence of trigalactosylated and triantennary serum glycans and urine core fucosylated mono-antennary glycans from IgG correlated with the vaginal presence of the bacterium A. senegalensis in endometriosis patients. Urine glycans did not differ in endometriosis, but urine IgG identified four novel sulfated glycans differing from serum IgG indicating functional relevance. Our findings contribute to understanding the relationships between the vaginal microbiota and the serum and urine glycome on the one hand, and endometriosis on the other. Further functional studies are warranted.