Spondyloarthritis (SpA) encompasses a group of chronic inflammatory disorders of the joints frequently associated with uveitis in almost a quarter of cases. SpA-related uveitis typically affects the eye anterior chamber with sudden onset, causing pain, redness, photophobia, and blurred vision. Ophthalmologists will describe an acute anterior unilateral uveitis. Most patients present with episodic acute anterior non-granulomatous uveitis and retain excellent visual acuity. However, systemic treatments are recommended in the event of frequent relapses (2-3/year) or in rare cases of sight-threatening with ocular complications. The improved understanding of the pathogenesis of SpA has led to the management of this disease by biologics. Here, we review the main data regarding the opportunity to target specific components in inflammatory pathways for the treatment of SpA-related uveitis. These therapies are recommended for long-term control when uveitis relapses occur too frequently despite conventional systemic treatments. Significant benefits have been obtained with the tumor necrosis factor-α inhibitors (TNFis), particularly infliximab and adalimumab. Paradoxically, a high number of uveitis occurrences have been shown on etanercept. Mixed results have been demonstrated with interleukin-17 antagonists (secukinumab) and interleukin-12/interleukin-23 antagonists (ustekinumab) in cases of failure of TNFis. JAK inhibitors seem to be a valuable class of medications for these patients in the future. Although SpA-related uveitis is typically managed with conventional local and/or systemic treatments, these biological/targeted therapies may provide avenues to control both the underlying SpA and uveitis manifestations. Thus, a close collaboration between patients, rheumatologists, internists, and ophthalmologists is needed to optimally manage ocular inflammation in SpA.

Recurring episodes of fever characterize tumor necrosis factor receptor-associated periodic syndrome (TRAPS) which is autosomal dominant. The primary symptoms of patients with TRAPS include prolonged fever, abdominal pain, muscle pain, and skin rashes. The prevalence of TRAPS appeared higher in Western countries than in Asian countries. Herein, we present the case of a 13-year-old girl who experienced intermittent fever for 8 years, with episodes that occur every 2 years. The patient demonstrated periodic fever, headache, vomiting, rash, and elevated inflammatory marker levels during the disease course. A heterozygous C55Y mutation was identified via a direct DNA sequencing of her genomic DNA. This mutation is located in exon 4 of TNFRSF1A. Genetic studies of her sister and mother revealed that they possessed the C55Y heterozygous mutation without demonstrating any clinical signs, while the father did not. Further, we conducted a thorough assessment of the literature and compiled the information from the eight TRAPS case series.

Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is considered an essential initiator of PE. Previous studies have compared the levels of various inflammatory biomarkers that indicate the existence of PE; however, the relative levels of pro-inflammatory and anti-inflammatory biomarkers and their dynamic changes during PE progression remain unclear. This knowledge is essential to explain the occurrence and progression of the disease.
We aimed to identify the relationship between inflammatory status and PE using inflammatory biomarkers as indicators. We also discussed the underlying mechanism by which inflammatory imbalance contributes to PE by comparing the relative levels of pro-inflammatory and anti-inflammatory biomarkers. Furthermore, we identified additional risk factors for PE.
We reviewed PubMed, Embase, and the Cochrane Library for articles published until 15th September 2022. Original articles that investigated inflammatory biomarkers in PE and normal pregnancy were included. We selected healthy pregnant women as controls. The inflammatory biomarkers in the case and control groups were expressed as standardized mean differences and 95% confidence intervals using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Publication bias was assessed using Egger\'s test.
Thirteen articles that investigated 2,549 participants were included in this meta-analysis. Patients with PE had significantly higher levels of C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) than the controls. CRP and pro-inflammatory cytokine levels were higher than those of anti-inflammatory cytokines. Patients with gestational age > 34 weeks had significantly higher IL-6 and TNF levels. Patients with higher systolic blood pressure had significantly higher IL-8, IL-10, and CRP levels.
Inflammatory imbalance is an independent risk factor for PE development. Impairment of the anti-inflammatory system is a crucial initiating factor for PE development. Failed autoregulation, manifested as prolonged exposure to pro-inflammatory cytokines, leads to PE progression. Higher levels of inflammatory biomarkers suggest more severe symptoms, and pregnant women after 34 weeks of gestation are more susceptible to PE.

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Headache is one of the most prevalent, although often underreported, symptoms of coronavirus disease 2019 (COVID-19). It is generally accepted that this symptom is a form of secondary headache due to systemic viral infection. There are several hypotheses that try to explain its aetiopathogenesis. One of the most compelling is related to innate immune response to viral infection. This rationale is supported by similarities to other viral infections and the temporal overlap between immunological reactions and headache. Moreover, several key factors in innate immunity have been shown to facilitate headache e.g. interferons, interleukin (IL) -1-β, IL-6, and tumour necrosis factor. There is also a possibility that the virus causes headache by the direct activation of afferents through pattern recognition receptors (i.e. Toll-like receptor 7). Moreover, some data on post-COVID-19 headache and after vaccination against SARS-CoV-2 infection suggests a similar cytokine-mediated pathomechanism in these clinical situations. Future research should look for evidence of causality between particular immune response factors and headache. Identifying key molecules responsible for headache during acute viral infection would be an important step towards managing one of the most prevalent secondary headache disorders.

BACKGROUND: The anti-inflammatory properties of statins have been suggested by several researches. However, clinical trials have reported incongruous findings regarding the effect of statins on the levels of inflammatory markers other than high-sensitive C-reactive protein. Therefore, a systematic review and meta-analysis of randomized clinical trials were conducted to illuminate the effect of statins on serum levels of TNF-α, MCP-1, VCAM1, and IL-6 in patients with cardiovascular diseases (CVDs).
METHODS: To find eligible studies, a systematic literature search of the main databases were conducted up to July 2021. The calculation of the effect sizes was conducted by standardized mean difference (SMD) and 95% confidence intervals (CI).
RESULTS: The pooled analyses revealed that statins significantly reduced the TNF-α concentration (SMD = - 0.99 pg/mL; 95% CI - 1.43 to - 0.55 pg/mL; P < 0.001). Regarding dosage, high intensity (SMD = - 0.65 pg/mL; 95% CI - 1.19 to - 0.10, P = 0.02) and moderate/low (SMD = - 1.16 pg/mL; 95% CI - 1.84 to - 0.47, P = 0.001) intensity statins significantly decreased TNF-α levels. Moderate/low intensity statins administration in < 10 weeks treatment duration decreased serum level of TNF-α (SMD =  - 0.91 pg/mL; 95% CI  - 1.38 to - 0.44, P < 0.001). Lipophilic statins with high intensity dosage significantly decreased level of TNF-α (SMD =  - 0.73 pg/mL; 95% CI - 1.43 to - 0.03, P = 0.04). Statins did not change serum levels of MCP-1, VCAM1, and IL-6 in CVD patients.
CONCLUSIONS: The analyses indicated that statins have beneficial effects in decreasing serum levels of TNF-α in patients with CVDs.

Tumor necrosis factor-alpha (TNF-α) inhibitors are frequently used for the management of type 1 helper T-cell (Th1) immune-mediated chronic inflammatory conditions such as psoriasis and Crohn\'s disease. Although TNF-α inhibitors are usually well-tolerated, various cutaneous side effects are frequently observed, including eczematous or atopic dermatitis-like eruptions. It is postulated that the attenuation of the Th1 immune pathway with TNF-α inhibition causes a shift towards a type 2 helper T-cell (Th2) immune response, leading to the development of skin lesions grossly and histologically consistent with the Th2 mediated disease atopic dermatitis. Herein, we describe the development of an eczematous eruption in two patients with a history of Th1-mediated disease after months of therapy with a TNF-α inhibitor.

The efficacy of the novel interleukin (IL)-23p19 inhibitor guselkumab for psoriatic arthritis (PsA) has recently been demonstrated in two phase 3 trials (DISCOVER-1 & -2) but has not been evaluated vs other targeted therapies for PsA. The objective was to compare guselkumab to targeted therapies for PsA for safety and joint and skin efficacy through network meta-analysis (NMA).
A systematic literature review was conducted in January 2020 to identify randomized controlled trials. Bayesian NMAs were performed to compare treatments on American College of Rheumatology (ACR) 20/50/70 response, mean change from baseline in van der Heijde-Sharp (vdH-S) score, Psoriasis Area Severity Index (PASI) 75/90/100 response, adverse events (AEs) and serious adverse events (SAEs).
Twenty-six phase 3 studies evaluating 13 targeted therapies for PsA were included. For ACR 20 response, guselkumab 100 mg every 8 weeks (Q8W) was comparable to IL-17A inhibitors and subcutaneous tumor necrosis factor (TNF) inhibitors. Similar findings were observed for ACR 50 and 70. For vdH-S score, guselkumab Q8W was comparable to other agents except intravenous TNF therapies. Results for PASI 75 and PASI 90 response suggested guselkumab Q8W was better than most other agents. For PASI 100, guselkumab Q8W was comparable to other active agents. For AEs and SAEs, guselkumab Q8W ranked highly but comparative conclusions were uncertain. Similar results were observed for all outcomes for guselkumab 100 mg every four weeks.
In this NMA, guselkumab demonstrated favorable arthritis efficacy comparable to IL-17A and subcutaneous TNF inhibitors while offering better PASI response relative to many other treatments.

Tumor necrosis factor inhibitors (TNFi) are indicated to treat ankylosing spondylitis (AS), also termed radiographic axial spondyloarthritis (axSpA). The main indication for TNFi is symptom relief, and whether they retard spinal structural damage as assessed by radiography is debated. Hips are the most common \"non-spinal\" joints involved in AS patients leading to major incapacitation. No major treatment guidelines mention measures to prevent peripheral joint damage, especially hips, in individuals with AS. We present our experience of prevention of structural damage in hips by TNFi in 4 AS patients from our practice. We conducted a literature review looking for articles describing prevention of structural damage progression in hips by TNFi. Over a 10-year period, three out of four patients were treated with TNFi and had no progression in hip damage as assessed by imaging. Only one patient that withdrew the TNFi due to infectious complications developed rapid worsening and required hip arthroplasty. Our literature review showed multiple case series with similar results suggesting that use of TNFi in patients with AS may prevent structural damage and at least postpone a hip replacement at a young age. Based on our experience, as well as from the literature review, we believe that treatment guidelines in axSpA should recommend prompt institution of TNFi following identification of hip involvement in patients to prevent a major source of disability. Whether interleukin (IL)-17 inhibitors or targeted synthetic anti-rheumatic drugs have hip sparing effects in patients with AS should also be investigated. Key Points • Hip involvement in ankylosing spondylitis is a major source of disability. • TNFi prevent hip damage in ankylosing spondylitis. • Prompt institution of TNFi should follow suspicion of hip involvement in ankylosing spondylitis.

Myricetin, one of the most extensively studied polyphenols, is present abundantly in various fruits and vegetables and exhibits diverse pharmacological properties. The multifaceted biological action of myricetin against tumor heterogeneity makes it an impressive anticancer agent whose efficacy has been confirmed by an overwhelming number of studies. Myricetin shows its therapeutic potential by targeting and modulating the expression of various molecular target which are involved in inflammation, cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Myricetin deters tumor progression by inducing apoptosis via both intrinsic and extrinsic pathway, activating/inactivating several signaling pathways, and reactivating various tumor suppressor genes. This comprehensive review represents the effect of myricetin on various hallmarks of cancer with insight into the molecular mechanism employed by myricetin to mitigate cell proliferation, angiogenesis, metastasis, and induce apoptosis. In addition, enhanced bioavailability of myricetin through conjugation and its increased efficacy as an anticancer agent when used in combination are also highlighted.