The development of universal alopecia during therapy with TNF-α inhibitors in patients with ankylosing spondylitis: description of three cases

Alopecia areata (АA) is an autoimmune multifactorial disease characterized by increased hair loss as a result of morphological and functional changes in hair follicles. АA is divided into four main forms, among which the most severe is the universal form (UA), in which complete hair loss is possible throughout the body. Alopecia in the practice of a rheumatologist can occur with some systemic diseases of the connective tissue, with the use of high doses of chemotherapy drugs and, more recently, with the use of inhibitors of tumor necrosis factors alpha (TNF-α). The article presents 3 clinical cases of the development of UA during therapy with TNF-α. Possible mechanisms are discussed, as well as the role of pro-inflammatory cytokines in the development of this condition.

Systemic inflammatory response in infants with craniostenosis sedated with propofol

AIM: This study aimed to investigate the possible effect of intravenous anesthesia (sedation) with propofol on the levels of several cytokines (interleukin [IL]-6, IL-8, IL-10, and tumor necrosis factors-) and S100B protein in the blood plasma of children aged 1 year with craniostenosis. MATERIALS AND METHODS: Twenty patients aged 112 months diagnosed with non-syndromic forms of craniosynostosis, who underwent magnetic resonance imaging (MRI) of the brain under propofol sedation, were classified according to ASA I-II class. Peripheral blood sampling was performed before and after the drug administration, followed by laboratory analysis. RESULTS: A significant increase was found in the serum level of IL-6 (p = 0.004) when intravenous sedation with propofol was used for 29 4.93 min. CONCLUSION: Short exposure of children aged 1 year with craniostenosis to hypnotic propofol during brain MRI significantly increased the level of the pro-inflammatory cytokine IL-6 in the blood plasma.

Wan-Nian-Qing, a Herbal Composite Prescription, Suppresses the Progression of Liver Cancer in Mice by Regulating Immune Response

The Wan-Nian-Qing prescription (WNQP), an herbal composite containing Ornithogalum caudatum, has been used in China for several years for cancer treatment. However, the mechanism of its pharmacological action against liver cancer is not clear. This study aimed to investigate the role of WNQP in inhibiting tumor growth in hepatocellular carcinoma model mice and determine its mechanism of action. We established HepG2- and SMMC-7721-xenografted tumor models in nude mice and BALB/c mice. The mice were administered WNQP for 2 weeks. The bodyweight of each mouse was monitored every day, and the tumor size was measured using vernier caliper before each round of WNQP administration. After the last dose, mice were sacrificed. The tumors were removed, lysed, and subjected to proteome profiling, enzyme-linked immunosorbent assay, and western blotting. The liver, spleen, and kidney were collected for histopathological examination. The effects of WNQP against liver cancer were first systematically confirmed in HepG2- and SMMC-7721-xenografted nude mice and BALB/c mice models. WNQP inhibited tumor growth, but failed to affect bodyweight and organ structures (liver and spleen), confirming that it was safe to use in mice. In BALB/c mice, WNQP regulated immune function, inferred from the modulation of immune-related cytokines such as interleukins, interferon, tumor necrosis factors, and chemokines. Further results confirmed that this regulation occurred via the regulatory effects of WNQP on Nrf2 signaling. WNQP can inhibit the growth of HepG2- and SMMC-7721-xenografted tumors in nude mice and BALB/c mice. This effect manifests at least partially through immunomodulation mediated apoptosis.

Effectiveness of Third-Class Biologic Treatment in Crohn’s Disease: A Multi-Center Retrospective Cohort Study

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.

Ameliorative Effects of Boswellic Acid on Fipronil-Induced Toxicity: Antioxidant State, Apoptotic Markers, and Testicular Steroidogenic Expression in Male Rats

The study investigated the ability of boswellic acid (BA) to alleviate the testicular and oxidative injury FPN insecticide intoxication in the male rat model. Rats were randomly assigned to six equivalent groups (six rats each) as the following: control rats orally administered with 2 mL physiological saline/kg of body weight (bwt); boswellic acid (BA1) rats orally administered 250 mg BA/kg bwt; boswellic acid (BA2) rats orally administered 500 mg BA/kg bwt; fipronil (FPN) rats orally administered 20 mg FPN/kg bwt; (FPN + BA1) rats orally administered 20 mg FPN/kg bwt plus 250 mg BA/kg bwt, and (FPN + BA2) rats orally administered 20 mg FPN/kg bwt plus 500 mg BA/kg bwt. After 60 days, semen viability percentage and live spermatozoa percentage were decreased, and a considerably increased abnormality of the sperm cells in FPN-administered rats improved substantially with the co-administration of BA. BA had refinement of the histological architecture of testes and sexual glands. Quantitative analysis recorded a noticeable decline in the nuclear cell-proliferating antigen (PCNA) percentage area. FPN triggered cell damage, which was suggested by elevated malondialdehyde and interleukin 6, tumor necrosis factors alpha, and decreased glutathione level. Proapoptotic factor overexpression is mediated by FPN administration, while it decreased the antiapoptotic protein expression. Similarly, BA has shown significant upregulation in steroidogenic and fertility-related gene expression concerning the FPN group. Pathophysiological damages induced by FPN could be alleviated by BA’s antioxidant ability and antiapoptotic factor alongside the upregulation of steroidogenic and fertility-related genes and regimented the detrimental effects of FPN on antioxidant and pro-inflammatory biomarkers.

Severe leukocytosis and cytokine storm in a patient with covid-19 pneumonia

Since the emergence of the first cases of COVID-19 that was first reported in Wuhan China, the virus has spread globaly at a fast rate. It has carried a significant increase in the mortality rate. Most of these cases have been secondary to severe pneumonia as well as an increased incidence of thromboembolic complications leading to pulmonary embolism, myocardial infarctions, and strokes. It has been observed that many of these severe COVID-19 pneumonias have been associated with an increased levels of inflammatory markers including Cytokines and Interleukin 3 and 6 which can lead to an exaggereted humoral response with increased immunoglobulin production and tumor necrosis factors that can lead to lung tissue destruction. There is an overwhelming demand to find a mechanism to stop that vicious cycle and minimize tissue destruction. Thus, there is a need for more extensive studies regarding this medical dilemma in order to minimize the number of deaths around the world which so far has almost reached 2.5 million.

Case Report: Refractory Chronic Spontaneous Urticaria Treated With Omalizumab in an Adolescent With Crohn’s Disease

Chronic spontaneous urticaria (CSU) is a mast cell-driven disease that is often associated with autoimmune or autoinflammatory conditions. Omalizumab is recommended in the treatment of refractory CSU in patients over 12 years of age who do not respond to four standard doses of antihistamines. Omalizumab blocks the mast cells’ degranulation, thus interrupting the resulting inflammatory cascade driven by T-helper 2 (Th2) cytokines. The efficacy of omalizumab in controlling CSU and possible associated diseases has been studied in few patients so far. In particular, some case reports describe adults with CSU and concomitant inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) or ulcerative colitis (UC). Although the treatment of CD with anti-tumor necrosis factors-α (TNF-α) seems to be effective in controlling CSU, no cases of the utility of omalizumab in patients with both conditions have been described so far. At the moment, there is no evidence that the pathogenetic mechanisms underlying CD are linked to the same pathways that are inhibited by omalizumab for the treatment of CSU. We present the first pediatric case of refractory CSU and CD in which omalizumab led to CSU remission, even if the follow-up period was limited. In conclusion, our experience shows how CSU could be associated with CD and successfully treated with the monoclonal anti-IgE antibody in a patient on immunosuppressive therapy. However, more data is needed from a larger population.