Hysterosalpingography findings in infertile Sudanese women: a cross-sectional study on tube blockage.

Introduction: infertility is a significant public health concern in Africa and Hysterosalpingography (HSG) is an affordable option for initial treatment. This study aimed to provide information about the incidence of abnormal pathology and tubal findings in HSG of Sudanese women who experienced infertility. Methods: this prospective cross-sectional study included 100 infertile patients who were requested for HSG, including age, duration of infertility, body mass index (BMI), medical history, and HSG findings collected after performing the radiographic test, which was diagnosed by an experienced radiologist. Results: one hundred infertile women (46% and 54%) experienced primary and secondary infertility, respectively. Mean age was (31.1 ± 5.2, 27.5 ± 6.0) years, and BMI was (25.1 ± 3.3, 25.7 ± 2.9) Kg/cm2 for primary and secondary infertility respectively. Abnormal findings prevalence was (29/46, 63%) and (30/54, 56%). The incidence of fallopian tube abnormality was (52/100, 52% (25/46, 54.3%), and (27/56, 50%) for primary and secondary infertility, respectively. Forty-one percent of participants had normal hysterosalpingograms. Pelvic surgery was the highest risk factor in 24% of the participants. Age and medical history were significantly associated with the infertility type (P < 0.05). Conclusion: infertile patients who underwent hysterosalpingography (HSG) were predominantly older, with secondary infertility being slightly more common, underscoring the importance of early diagnostic evaluation and care. Fallopian tube abnormalities were the most common cause of infertility, with tube blockage affecting nearly half of the participants. Additionally, this study revealed that prior pelvic surgery significantly increased the risk of infertility.

Impact of gluten intake on clinical outcomes in patients with chronic inflammatory diseases initiating biologics: Secondary analysis of the prospective multicentre BELIEVE cohort study.

Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten-free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14-16 weeks in patients with CID with high versus low-to-medium gluten intake. Secondary outcomes of interest included changes in disease activity, health-related quality of life and C-reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low-to-medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14-16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium-to-low gluten group (OR = 0.96 [0.51-1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID.

Biologics for eosinophilic otitis media: a retrospective case study in a multidisciplinary center.

PURPOSE: Eosinophilic otitis media (EOM) is a difficult-to-treat otitis media characterized by eosinophilic accumulation in the middle ear mucosa and effusion. It is refractory to conventional treatments and is strongly associated with asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). The diagnostic criteria for EOM were established by IINO in 2011. With the recognition of type 2 inflammatory diseases, the gold standard of treatment is the systemic and topical administration of corticosteroids. Recently, several retrospective studies have demonstrated the efficacy of biologic treatments in EOM. We aimed to share our experience regarding the response of EOM after the use of biologics. METHODS: This is a retrospective observational analysis including patients with refractory EOM treated with different biologics (benralizumab, omalizumab, mepolizumab, dupilumab) for concomitant severe asthma, urticaria and/or severe uncontrolled CRSwNP from 2011 to 2023. Treatment effectiveness in terms of EOM severity was measured using medical Global Evaluation of Treatment Effectiveness (GETE). RESULTS: We illustrated 4 clinical cases of uncontrolled comorbid EOM and demonstrated the complexity of multidisciplinary medical pathway with good response to biologics. We also observed that response to EOM and CRSwNP does not always follow that of asthma. CONCLUSIONS: The results of our small sample were consistent with those found in the literature and showed control of EOM with biologics. We need a larger multicentric sample and methodology to confirm these results and to compare the efficacy of different biologics.

Global burden and cross-country inequalities in six major immune-mediated inflammatory diseases from 1990 to 2021: A systemic analysis of the Global Burden of Disease Study 2021.

BACKGROUND: This study aims to describe the global burden trends of six immune-mediated inflammatory diseases (IMIDs), including asthma, atopic dermatitis (AD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis and rheumatoid arthritis (RA), from 1990 to 2021, and analyze patterns of cross-country inequalities. METHODS: The estimates for the number of disability-adjusted life-years (DALYs) and age-standardized DALYs rates (ASDR), along with the 95 % uncertainty intervals (UI) for asthma, AD, IBD, MS, psoriasis and RA, were obtained from the Global Burden of Diseases Study 2021. The estimated annual percentage change (EAPC) was used to quantify the global burden trends of these six IMIDs from 1990 to 2021. Additionally, slope index of inequality and concentration index were employed to quantify the distributional inequalities in the burden of IMIDs. RESULTS: From 1990 to 2021, the global ASDR of psoriasis (EAPC = 0.23 %, 95 % UI: 0.21 to 0.25) and RA (EAPC = 0.05 %, 95 % UI: 0.01to 0.10) showed an increasing trend, while the global ASDRs of asthma (EAPC = -1.91 %, 95 % UI: -1.98 to -1.84), AD (EAPC = -0.26 %, 95 % UI: -0.27 to -0.26), IBD (EAPC = -0.52 %, 95 % UI: -0.60 to -0.43) and MS (EAPC = -0.39 %, 95 % UI: -0.45 to -0.33) demonstrated declining trends. The cross-country inequality analysis reveals pronounced heterogeneity in the burden of these six IMIDs. CONCLUSIONS: The global distribution of the DALYs burden attributable to IMIDs exhibits significant disparities across regions, underscoring an urgent need for innovative and comprehensive management strategies to address this heterogeneous landscape.

The Risk of Pelvic Inflammatory Disease in Women Infected With Chlamydia (Chlamydia trachomatis): A Literature Review.

A literature review was undertaken to examine the risk of developing pelvic inflammatory disease (PID) in women infected with Chlamydia trachomatis. A search of OVID Medline and Embase databases was conducted for studies published between 1946 and 26 June 2023. This review looked solely at prospective cohort study designs and searched reference lists of studies selected for inclusion. This literature review confirmed that C. trachomatisis a key factor in the development of PID in women through different pathogenic mechanisms. However, to reach more firm conclusions on the subject, further prospective cohort studies with a larger cohort size and a longer follow-up time are needed.

Idiopathic Orbital Inflammatory Disease in a Pediatric Patient: A Case Report Highlighting the Diagnostic Reasoning and Treatment Strategy.

Idiopathic orbital inflammatory disease (IOID) is a rare and poorly understood condition characterized by inflammation of the orbital tissues without an identifiable cause. This disorder can lead to symptoms such as proptosis, pain, and visual disturbances. We present the case of an eight-year-old female diagnosed with IOID who was admitted to the hospital with worsening right eye redness, proptosis, and pain. Her clinical course included significant right eye lagophthalmos, exposure keratopathy, and a corneal ulcer. Management involved a multidisciplinary approach with consultations from ophthalmology and rheumatology, treatment with corticosteroids, and supportive care. This case underscores the importance of early recognition and a comprehensive management strategy to improve outcomes for patients with IOID.

Investigation and Confirmation of PYCARD as a Potential Biomarker for the Management of Psoriasis Disease.

Purpose: Psoriasis is not yet completely curable, and its etiology and pathogenesis are unclear. Necroptosis, also known as programmed necrosis, is a regulated mode of necrotic cell death. The interaction between inflammatory diseases and necrotic apoptosis has recently attracted significant attention. We explored the molecular mechanisms of necrotic apoptosis-related genes in psoriasis using bioinformatics methods to identify potential biomarkers for psoriasis. Patients and Methods: In this study, we screened psoriasis differentially expressed genes from the datasets GSE13355 and GSE14905 and took intersections with necrotic apoptosis-related genes for the next analysis. We used multiple machine learning algorithms to screen key genes and perform enrichment analysis. In addition, we performed an immune infiltration analysis. Transcription factors were predicted by the R package "RcisTarget". We also observed the cellular clustering of key genes in different cell types at the single-cell sequencing level. We used real-time fluorescence-based quantitative-polymerase chain reaction, Western blot, and immunohistochemistry to analyze gene expression in clinical samples. We constructed an imiquimod-induced psoriasis-like dermatitis model in mice for further validation. Results: Seven key genes were screened as follows: AIM2, CARD6, HPSE, MYD88, PYCARD, RAI14, and TNFSF10. Enrichment analysis showed that the key genes were mainly involved in inflammatory pathways. Immune infiltration analysis showed significantly higher levels of CD8 T cells, CD4 initial T cells, and CD4 memory-activated T cells in the disease group's samples than in the normal patients' samples. The key gene expression in single cells analyzed showed that PYCARD was significantly expressed in keratinocytes. PYCARD was selected for gene expression analysis; the results showed that its expression was significantly elevated in the skin lesion tissues of patients with psoriasis. We also verified that PYCARD might play a vital role in the development of psoriasis skin lesions using animal experiments. Conclusion: PYCARD plays a vital role in psoriasis development and is a potential biomarker for psoriasis.

Neuro-Behçet Disease Presenting as a Bulbar Lesion: A Case Report.

Behçet's disease (BD), also called neuro-Behçet (NB), is a multisystem inflammatory disease that can affect the nervous system. The authors hereby present the case of a 46-year-old woman with a previous diagnosis of BD with cutaneous, articular, and ocular involvement. The patient was admitted to the emergency room with intense posterior cervical pain, right eyelid ptosis accompanied by anisocoria, left arm hemiparesis, left hemihypoesthesia, right dysmetria, and postural instability. A cerebral MRI revealed a right laterobulbar oval T2 hyperintense lesion, suggesting a diagnosis of NB. Treatment with methylprednisolone pulses and, later, azathioprine was then started. The patient showed progressive improvement in her clinical condition and an imagological resolution of the bulbar lesion. This case highlights the importance of an accurate diagnosis - based on clinical history and imaging studies - for an early initiation of the specific therapy.

Pelvic inflammatory disease and risk of borderline ovarian tumors: A national population-based case-control study in Sweden.

The resemblance between fallopian tube cells and serous borderline ovarian tumors (BOTs) suggests a potential origin link, with salpingitis proposed as a contributing factor in the pathogenesis of BOT. This study aimed to explore the potential association between pelvic inflammatory disease (PID) and the risk of developing BOT. A national population-based case-control study in Sweden included women with BOT between 1999 and 2020 and 10 matched controls. Data from nationwide registers were analyzed using conditional logistic regression, adjusting for age, residential district, educational level and parity. Among 4782 cases and 45,167 controls, 2.0% of cases and 1.3% of controls had a history of PID. Previous PID was associated with an increased risk of BOT overall (aOR, 1.48; 95% CI, 1.19-1.85). Significant association was observed with serous tumors (aOR, 1.76; 95% CI, 1.36-2.29), while not with mucinous tumors (aOR, 0.95; 95% CI, 0.60-1.49). A dose-response relationship between number of PID episodes and serous BOT risk was noted (Ptrend < .001). This study demonstrates that PID is associated with increased risk of serous BOT, with a dose response relationship. The study highlights the potential serious implications of upper reproductive tract infections and inflammation. This underscores the need for further investigation of biological mechanisms and possible impact of PID on serous BOT development.

In-hospital unfavorable outcomes of MIS-C during 2020-2022: a systematic review.

Studies on the severity in multisystem inflammatory syndrome in children (MIS-C) show heterogeneous results and may not reflect a global perspective. This systematic review aims to estimate the frequency of in-hospital unfavorable outcomes in patients with MIS-C over the 3 years since the onset of the SARS-CoV-2 pandemic. A systematic search was conducted in Medline, Scopus, Embase, Cochrane, Web of Science, Scielo, and preprint repositories until December 15, 2022. Study selection and data extraction were evaluated independently. The primary outcomes were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death. Additionally, we evaluated cardiovascular-related outcomes. We performed a random-effects model meta-analysis and assessed the certainty of the evidence. Fifty-seven studies (n = 13 254) were included. The frequency of ICU admission was 44.7% (95% CI 38.8-50.7), 11.9% for IMV (95% CI 9.6-14.4), and 2.0% for death (95% CI 1.3-3.0). The requirement of vasoactive/inotropic drugs was 40.1% (95% CI 35.9-44.4), 7.9% for coronary aneurysm (95% CI 4.1-12.7), 30.7% for decreased left ventricle ejection fraction (LVEF) (95% CI 26.3-35.4), and 29.7% for myocarditis (95% CI 18.4-42.4). We assess the included evidence as being of very low certainty. Finally, excess COVID-19 mortality by country and the diagnostic criteria for MIS-C (CDC compared to WHO) were associated with a higher frequency of ICU admissions. The year of study conduction (2022 compared to 2020) was associated with a lower frequency of IMV. CONCLUSION: The frequency of in-hospital unfavorable outcomes in patients with MIS-C was high. Well-designed studies are needed to explore other heterogeneity sources. PROTOCOL REGISTRATION: CRD42021284878. WHAT IS KNOWN: • Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious condition linked to SARS-CoV-2. Studies on the severity of MIS-C show heterogeneous results. These findings may not be representative of the reality in other regions, making it challenging to draw generalizable conclusions. WHAT IS NEW: • Over the 3 years since the onset of the SARS-CoV-2 pandemic, our systematic review has shown that the frequency of in-hospital unfavorable outcomes in patients with MIS-C is high, with a very low certainty of the evidence. Our results reflect the reality from a global perspective, across different countries with varying income levels. • The main sources of heterogeneity in the frequency of severe outcomes could be explained by the excess mortality due to COVID-19 in each country, the type of diagnostic criteria for MIS-C, and the year the study was conducted.

Deconstructing inflammatory memory across tissue setpoints using cell circuit motifs.

Tissue ecosystems are cellular communities that maintain setpoints through a network of intercellular interactions. We position health and chronic inflammatory disease as alternative stable setpoints that are: (1) robust to perturbation, and (2) capable of adaptation and memory. Inflammatory memory-the storage of prior experience to durably influence future responsiveness-is central to how tissue ecosystems may be pushed past tipping points that stabilize disease over health. Here, we develop a reductionist framework of circuit motifs that recur in tissue setpoints. In type 2 immunity, we distinctly find the emergence of two-cell positive feedback motifs. By contrast, directional motif relays and three-cell networks feature more prominently in type 1 and 17 responses. We propose that these differences guide the ecological networks established after surpassing tipping points and associate closely with therapeutic responsiveness. We highlight opportunities to improve our current knowledge of how circuit motifs interact when building towards tissue-level networks across adaptation and memory. By developing new tools for circuit motif nomination and applying them to temporal profiling of tissue ecosystems, we hope to dissect the stability of the chronic inflammatory setpoint and open therapeutic avenues for rewriting memory to restore health.

Methotrexate and Tumor Necrosis Factor Inhibitors Independently Decrease Neutralizing Antibodies after SARS-CoV-2 Vaccination: Updated Results from the SUCCEED Study.

Objective: SARS-CoV-2 remains the third most common cause of death in North America. We studied the effects of methotrexate and tumor necrosis factor inhibitor (TNFi) on neutralization responses after COVID-19 vaccination in immune-mediated inflammatory disease (IMID). Methods: Prospective data and sera of adults with inflammatory bowel disease (IBD), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and systemic lupus (SLE) were collected at six academic centers in Alberta, Manitoba, Ontario, and Quebec between 2022 and 2023. Sera from two time points were evaluated for each subject. Neutralization studies were divided between five laboratories, and each lab's results were analyzed separately using multivariate generalized logit models (ordinal outcomes: absent, low, medium, and high neutralization). Odds ratios (ORs) for the effects of methotrexate and TNFi were adjusted for demographics, IMID, other biologics and immunosuppressives, prednisone, COVID-19 vaccinations (number/type), and infections in the 6 months prior to sampling. The adjusted ORs for methotrexate and TNFi were then pooled in random-effects meta-analyses (separately for the ancestral strains and the Omicron BA1 and BA5 strains). Results: Of 479 individuals (958 samples), 292 (61%) were IBD, 141 (29.4%) were RA, and the remainder were PsA, SpA, and SLE. The mean age was 57 (62.2% female). For both the individual labs and the meta-analyses, the adjusted ORs suggested independent negative effects of TNFi and methotrexate on neutralization. The meta-analysis adjusted ORs for TNFi were 0.56 (95% confidence interval (CI) 0.39, 0.81) for the ancestral strain and 0.56 (95% CI 0.39, 0.81) for BA5. The meta-analysis adjusted OR for methotrexate was 0.39 (95% CI 0.19, 0.76) for BA1. Conclusions: SARS-CoV-2 neutralization in vaccinated IMID was diminished independently by TNFi and methotrexate. As SARS-CoV-2 circulation continues, ongoing vigilance regarding optimized vaccination is required.

Versatile whey acidic protein four-disulfide core domain proteins: biology and role in diseases.

The Whey acidic protein four-disulfide core (WFDC) protein family consists of proteins with one or more WFDC domains which are ubiquitously expressed throughout the body of human and perform a wide range of functions, including antiprotease, antibacterial, and immunomodulatory functions. Aberrant expression of WFDC proteins is associated with human diseases. However, review on the WFDC protein family is limited and insufficient. Furthermore, a systematic summary of the underlying mechanisms of WFDC protein activity is lacking. In this review, we give a summary of the structural basis and molecular function of these proteins and review the immune regulatory mechanisms and signaling pathways of WFDC proteins in the development of certain diseases. Furthermore, we discuss the diagnostic and prognostic potential of multiple WFDC proteins in the aforementioned conditions, as well as their prospective use. At last, we also discuss the progress of WFDC protein in clinical trials and put forward some research difficulties and the directions of follow-up research. Our review highlights the functional diversity and clinical significance of WFDC proteins family, while providing potential targets for drug development and innovative therapeutic strategies, this review lays the foundation and direction for future research on WFDC proteins.

Metabolomics-based profiling of anti-inflammatory compounds from Mentha spicata in shanghe, China.

Mentha spicata is a popular herb used in foods, cosmetics, and medicines. In the present study, liquid chromatography-mass spectrometry-based metabolomics analysis and the zebrafish model were used to investigate the potential biomarkers of M. spicata growing in Shanghe County (Shandong Province, China) and their anti-inflammatory properties. Network pharmacology and molecular docking were performed to screen the main targets of the characteristic compounds to understand their mechanisms of action. Nine potential markers including sugars (1,2), polyphenolic acids (3-5), and flavonoids (6-9) were identified from the species. The inhibitory effects on leukocyte migration confirmed that compounds 1 and 3-9 played a positive role in the protective effect of Shanghe M. spicata (SM) extract against inflammation. Akt (protein kinase B), EGFR (epidermal growth factor receptor), and MMP9 (matrix metalloproteinase 9) were the core target proteins of the identified compounds in the anti-inflammatory process. The most significant Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment terms were response to abiotic stimulus (Biological Process), carbohydrate derivative binding (Molecular Function), and pathways in cancer. In docking simulations, 3-p-coumaroylquinic acid (3-PC, 4) and cirsimaritin (CN, 7) exhibited the highest potential affinity to the active sites of Akt and EGFR proteins, respectively; additionally, 5-demethylsinensetin (5-DS, 9) and luteolin (LN, 6) were considered the most suitable ligands for the MMP9 protein. The present study highlighted the use of SM resources as functional products with health benefits.

Concurrent acute cystitis, pancolitis, and tubo-ovarian abscess following laparoscopic ovarian cystectomy: a case report.

BACKGROUND: Inadequate surgical interventions can lead to serious complications such as tubo-ovarian abscesses in the upper female genital system, often resulting from untreated pelvic inflammatory disease. Pelvic inflammatory disease, caused by infections like Chlamydia trachomatis and Neisseria gonorrhoeae, leads to scarring and adhesions in the reproductive organs, with common risk factors including intrauterine device use and multiple sexual partners. Pelvic inflammatory disease primarily affects sexually active young women and can manifest with varied symptoms, potentially leading to complications like ectopic pregnancy, infertility, and chronic pelvic pain if untreated. CASE PRESENTATION: This case report presents a unique scenario involving a 17-year-old sexually inactive female who experienced concurrent tubo-ovarian abscess, acute cystitis, and pancolitis following laparoscopic ovarian cystectomy. Pelvic inflammatory disease and its complications are well-documented, but the simultaneous occurrence of acute cystitis and pancolitis in this context is unprecedented in the medical literature. The patient's presentation, clinical course, and management are detailed, highlighting the importance of considering diverse and severe complications in individuals with a history of gynecological surgeries. CONCLUSIONS: Our case report highlights the need for healthcare professionals to remain vigilant for atypical presentations of gynecological complications and emphasizes the value of interdisciplinary collaboration for optimal patient care. We encourage further research and awareness to enhance understanding and recognition of complex clinical scenarios associated with gynecological procedures.

Treatment of Idiopathic Inflammatory Orbital Syndrome (IOIS) With Prominent Lacrimal Gland Involvement Using Oral Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).

Idiopathic orbital inflammatory syndrome (IOIS) is a chronic inflammatory process of unknown etiology, which can either be localized or diffuse. In cases where there is isolated inflammation of the lacrimal gland, it is known as dacryoadenitis. This study focuses on the treatment of a patient with IOIS with prominent lacrimal gland involvement. The mainstay of treatment for idiopathic isolated dacryoadenitis is oral corticosteroids, but non-steroidal anti-inflammatory drug (NSAIDs) is known to be effective in treating idiopathic dacryoadenitis as well. There is no formal study yet to evaluate the use of NSAIDs in treating idiopathic dacryoadenitis. Here, we report a case of idiopathic isolated dacryoadenitis which was successfully treated with NSAIDs.

Association between pelvic inflammatory disease and risk of ovarian, uterine, cervical, and vaginal cancers-a meta-analysis.

BACKGROUND AND AIM: The present meta-analysis aims to investigate a potential link between pelvic inflammatory disease (PID) and an increased risk of genitourinary cancers (ovarian, cervical, uterus, and vagina cancers). While previous research has hinted at a possible link, this meta-analysis seeks to delve deeper into the available evidence. Understanding this association is crucial for preventive strategies and improving clinical management practices. METHODOLOGY: A comprehensive literature search was conducted across various databases, covering studies published between 2016 and 2024. We included 13 observational studies meeting stringent criteria, followed by meticulous data extraction and quality assessment. Meta-analytical techniques were then employed to calculate pooled odds ratios (ORs), adjusted hazard ratios (HRs), and 95% confidence intervals (CIs), with heterogeneity assessed using the I2 statistic. RESULTS: Our analysis revealed significant findings, underscoring the association between PID and increased risks of genitourinary cancers. Specifically, individuals with a history of PID demonstrated notably higher odds of developing ovarian cancer (OR = 1.477, 95% CI 1.033-2.207), uterine cancer (OR = 1.263, 95% CI 0.827-2.143), cervical cancer (OR = 1.000, 95% CI 0.900-1.100), and vaginal cancer (OR = 2.500, 95% CI 1.400-4.000) compared to those without such a history. The overall heterogeneity across studies was high (I2 = 82.92%), suggesting varying trends across different populations and study designs. CONCLUSION: This meta-analysis provides updated evidence supporting a significant association between PID and an increased risk of cervical, ovarian, and uterine cancers. Early detection and management of PID are crucial in potentially mitigating the risk of these cancers.

Total tanshinones ameliorates cGAS-STING-mediated inflammatory and autoimmune diseases by affecting STING-IRF3 binding.

BACKGROUND: An important signaling pathway connecting illness and natural immunity is the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, but aberrant activation of this pathway is associated with the development of autoimmune and inflammatory diseases. Hence, targeted inhibition of the activation of the cGAS-STING pathway is potentially valuable in the treatment of disease. The primary active component of Salvia miltiorrhiza is total tanshinone (TTN). Research has indicated that TTN possesses noteworthy anti-inflammatory properties. However, the protective mechanism of TTN against acute liver injury (ALI) and autoimmune diseases is unknown. METHODS: A model of aberrant activation of the cGAS-STING pathway was established in various cells and treated with TTN, and the expression of cGAS-STING pathway-related proteins, type I interferon, interferon stimulated genes and inflammatory factors was assessed by western blotting, real-time qPCR. Immunofluorescence analysis of the effect of TTN on the entry of associated proteins into the nucleus following aberrant activation of the cGAS-STING pathway. The effect of TTN on STING oligomerisation was investigated using 2'-3'-cyclic GMP-AMP (2',3'-cGAMP) to induce STING oligomerisation. Western blotting was used to examine the impact of TTN on the interactions of STING, tank-binding kinase 1 (TBK1), and interferon regulatory factor 3 (IRF3) after HA or Flag-labelled plasmids were transfected into HEK-293 T cells. A dimethylxanthenone-4-acetic acid (DMXAA) -induced activation model of the cGAS-STING pathway in mice was established to study the effect of TTN on aberrant activation of the cGAS-STING pathway in vivo. On the other hand, an animal model of lipopolysaccharide/D-galactosamine (LPS/D-GaIN)-induced ALI and an autoimmune disease model induced by trex1 knockout were established to study the effects of TTN on inflammatory and autoimmune diseases mediated by the cGAS-STING pathway in vivo. RESULTS: In several models of aberrant activation of the cGAS-STING pathway, TTN significantly inhibited the phosphorylation of STING and IRF3, thereby suppressing the expression of type I interferon, interferon-stimulated genes and inflammatory factors. Additionally, TTN prevented P65 and IRF3 from entering the nucleus after the cGAS-STING signalling pathway was abnormally activated. Subsequent research indicated that TTN was not involved in the oligomerization of STING or the integration of STING-TBK1 and TBK1-IRF3. However, TTN was found to have a substantial effect on the binding process between STING and IRF3. On the other hand, DMXAA-induced STING activation and activation of downstream signalling in vivo are inhibited by TTN. Furthermore, TTN exhibits positive treatment effects on autoimmune diseases caused by deficiency of trex1 and LPS/D-GaIN-induced ALI. CONCLUSION: Our research indicates that TTN effectively treats ALI and autoimmune illnesses mediated by the cGAS-STING pathway by inhibiting the abnormal activation of this pathway.

[Autoinflammatory diseases associated with IL-18]. / Maladies auto-inflammatoires associées à l'IL-18.

Autoinflammatory diseases (AIDs) are conditions characterized by dysfunction of innate immunity, causing systemic inflammation and various clinical symptoms. The field of AIDs has expanded due to improved comprehension of pathophysiological mechanisms and advancements in genomics techniques. A new emerging category of AIDs is characterized by a significant increase in interleukin 18 (IL-18), a pro-inflammatory cytokine synthesized in macrophages and activated by caspase 1 via various inflammasomes. IL-18 plays a role in the regulation of innate and adaptive immunity. IL-18 is involved in various functions, such as the proliferation, survival, and differentiation of immune cells, tissue infiltration of immune cells, polarization of immune responses, and production of other pro-inflammatory cytokines. This review analyzes the literature on IL-18 regarding its functions and its implications in the diagnosis and treatment of AIDs. IL-18-associated AIDs comprise Still's disease and diseases associated with mutations in NLRC4, XIAP, CDC42, and PSTPIP1, as well as IL-18BP deficiencies. With the exception of PSTPIP1-associated diseases, these conditions all carry a risk of macrophagic activation syndrome. Measuring IL-18 levels in serum can aid in the diagnosis, prognosis, and monitoring of these diseases. Therapies targeting IL-18 and its signaling pathways are currently under investigation.