TNF-Alpha Inhibitors and Ustekinumab for the Treatment of Psoriasis: Therapeutic Utility in the Era of IL-17 and IL-23 Inhibitors

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and comorbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10−12) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10−8). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10−5). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1–1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.

Salivary Exosomes: From Waste to Promising Periodontitis Treatment

Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.

Extragenital lichen sclerosus arising in tattooed skin

Lichen sclerosus (LSc) is a chronic inflammatory condition commonly affecting the anogenital area, with extragenital involvement seen in less than 1%–20% of cases. Concomitant extragenital and genital LSc is extremely rare in male patients. The Koebner phenomenon is a recognised feature of LSc; here we present a rare case of extragenital LSc occurring in tattooed skin.

Quality of Life in Cohabitants of Patients Suffering Inflammatory Bowel Disease: A Cross-Sectional Study

(1) Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition with a significant impact on patients’ general health perception. No studies have considered consequences of IBD on cohabitants. (2) Aims: The aims of this study were to address the influence of IBD on cohabitants’ quality of life (QoL) and the factors potentially conditioning this impact. (3) Methods: We conducted a cross-sectional study in which IBD patients and their cohabitants were invited to participate. Validated questionnaires were used to measure QoL in patients and cohabitants. Main clinical and sociodemographic variables were collected. (4) Results: A total of 56 patients and 82 cohabitants with significant QoL impairment were included. A direct association was found between Inflammatory Bowel Disease Questionnaire (IBDQ32) score in patients and the Household Members Quality of Life—Inflammatory Bowel Disease (HHMQoL-IBD). IBDQ32 was related to the number of flares in the last 12 months, number of hospital admissions and Mayo Score. (5) Conclusions: HHMQoL-IBD score was related to patients IBDQ32 score and the presence of extraintestinal disease. We identified CRP, a marker of disease activity, as a factor related to cohabitants’ quality of life, pointing to a direct relationship of patients’ disease activity and their cohabitants’ quality of life.

Link between aging and atheroprotection in Mif-deficient atherosclerotic mice

Atherosclerosis is a lipid-triggered chronic inflammatory condition of our arteries and the main underlying pathology of myocardial infarction and stroke. Pathogenesis is age-dependent, but the mechanistic links between disease progression, age, and atherogenic cytokines and chemokines are incompletely understood. Here, we studied the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) in atherogenic Apoe-/- mice across different stages of aging and cholesterol-rich high-fat diet (HFD). MIF promotes atherosclerosis by mediating atherogenic monocyte and T-cell recruitment, amplifying lesional inflammation, and suppressing atheroprotective B-cell responses. However, age-related links between atherogenesis and MIF and its role in advanced atherosclerosis in aged mice have not been systematically explored. We compared effects of global Mif-gene deficiency in 30-, 42-, and 48-week-old Apoe-/- mice on HFD for 24, 36, or 42 weeks, respectively, and in 52-week-old mice on a 6-week HFD. While a regio-specific atheroprotective phenotype of Mif-deficiency was observed in the 30/24-week-old group, atheroprotection was not detected in the 48/42- and 52/6-week-old groups, suggesting that atheroprotection afforded by global Mif-gene deletion differs across aging stages and atherogenic diet duration. We identify a combination of mechanisms that could explain this phenotype: i) Mif-deficiency promotes lesional Trem2+ macrophage numbers in younger but not aged mice; ii) Mif-deficiency favors formation of lymphocyte-rich stage-I/II ATLOs in younger mice but ATLO numbers equalize with those in Apoe-/- controls in the older mice; and iii) plasma anti-oxLDL-IgM antibody levels are decreased in aged Mif-deficient mice. Of note, these three markers (Trem2+ macrophages, ATLOs, anti-oxLDL-IgM antibodies) have been previously linked to atheroprotection. Together, our study thus suggests that regio-specific atheroprotection due to global Mif-gene deficiency in atherogenic Apoe-/- mice is lost upon advanced aging and identifies mechanisms that could explain this phenotype shift. These observations may have implications for translational MIF-directed strategies.

Association of Oral Lichen Planus with Dyslipidemia in Patients Of Rahim Yar Khan

Introduction: Oral lichen planus (LP) is a chronic inflammatory condition and this inflammation leads to alteration in lipid metabolism and increase the cardiovascular risk factors. Objective: To determine the prevalance of dyslipidemias in patient with oral lichen planus coming in dermatology outdoor of Sheikh Zayed Hoapital Rahim Yar Khan. Methods: It was a case control study that was conducted at Department of Dermatology, Sheikh Zayed Hospital Rahim Yar Khan during October 2016 to April 2017. In this study there were total 50 cases of oral LP and 50 controls of both genders with age range of 15 to 60 years. The cases of both the groups underwent fasting lipid profile in terms to look for serum total cholesterol, triglyceride, LDL cholesterol and HDL cholesterol. Results: In this study there were total 100 cases out of which 50 were cases of oral LP and 50 were controls. In cases groups there were 27 (54%) males and 23 (46%) females while in control group there were same number of males and females were taken with p= 0.85. The mean age in case group was 37.22±8.15 years while in control group was 35.66± 7.78 years while the mean BMI was 24.42±2.21 and 25.11±3.01 respectively. The mean difference in cases and controls in terms of serum total cholesterol, TG, HDL Cholesterol and LDL cholesterol was found statistically significant. Conclusion: Dyslipidemias are common in cases with oral lichen planus and all its parameters have significant association with it especially TG. Keywords; LP, Dyslipidemia, LDL, HDL, TG

MANAGEMENT OF CHRONIC SINUSITIS THROUGH ALTERNATE RECHANA AND SNEHANA NASYA - REPORT FROM A PILOT STUDY

Chronic sinusitis is the chronic inflammatory condition affecting the paranasal sinuses. It may be correlated to Dushta pratisyāya in Ayurveda, which is a Kapha predominant disease affecting jatṟuṛdhva bhāgā which needs teekshna virecana nasya for its management. Vāgbhaṭācārya opines that except for vātika rogas, nasya should be done as ekāhāntara (alternate day) i.e., with a gap of one day in between. But according to Cakṟadatta commentary, ekāhāntara nasya is to be done with virecana nasya and snehana nasya on alternate days. For virecana nasya, Tuḷasi patṟa svarasa (Ocimum sanctum Linn.) and for snehana nasya, Aṇutaila were selected. A patient aged 43 years diagnosed with adult rhinosinusitis diagnostic criteria was taken for the study and was given ekāhāntara nasya with Tuḷasi patṟa svarasa and Aṇutaila for 7 days. During follow up period Pathyākṣadhātṟyādi kaṣāya was given for 15 days. Samyak nasya lakṣaṇa and Event evaluation scales were assessed on each day of nasya and Scale for scoring of symptoms, Rhinosinusitis Disability Index and Visual Analogue Scale were assessed before trial, after trial and after follow up. After the course of treatment 100% improvement was found in the Scale for scoring of symptoms, Rhinosinusitis Disability Index and Visual Analogue Scale. Keywords: Case report, Ekāhāntara (alternate day) nasya, Tuḷasipatṟasvarasa, Aṇutaila, Chronic sinusitis

Role of Platelets in the Pathogenicity of Atherosclerosis and Thrombosis in Coronary Heart Diseases

Atherosclerosis is a chronic inflammatory process that results in coronary artery disease, peripheral artery disease and in many cases of stroke. It is a disease that involves multiple inflammatory cytokine which is regarded as the primary underlying cause of cardiovascular diseases (CVD). CVD is the leading cause of death in the developed and developing countries like Nigeria. From pathological perspective, the chronic inflammatory condition of atherosclerosis occurs due to interplay between platelets, monocytes, macrophages. Physiologically platelets play a significant role in coagulation and repair of endothelial injury. Pathologically, studies have shown that activated platelets release multiple inflammatory cytokines and chemokines that serve as positive mediators of atherosclerosis. This chemokine is (RANTES, P-selectin and PF-4). Activated platelet release p-selectin that mediate platelet adhesion and rolling to injured endothelial cell, RANTES trigger the recruitment of monocytes into the sub- endothelium and PF4 promote the differentiation of monocytes into macrophages in the intimal layer of the endothelium which engulf ox-LDL to form FOAM cells. Thus, the aim of this review is to understand and describe the role of activated platelets in atherosclerosis as well as therapeutic target of these platelet inflammatory chemokines which is the major mediator of atherosclerosis in human.

Curcumin and Mesenchymal Stem Cells Ameliorate Ankle, Testis, and Ovary Deleterious Histological Changes in Arthritic Rats via Suppression of Oxidative Stress and Inflammation

Rheumatoid arthritis (RA) is a chronic inflammatory condition, an autoimmune disease that affects the joints, and a multifactorial disease that results from interactions between environmental, genetic, and personal and lifestyle factors. This study was designed to assess the effects of curcumin, bone marrow-derived mesenchymal stem cells (BM-MSCs), and their coadministration on complete Freund’s adjuvant- (CFA-) induced arthritis in male and female albino rats. Parameters including swelling of the joint, blood indices of pro-/antioxidant status, cytokines and histopathological examination of joints, and testis and ovary were investigated. RA was induced by a single dose of subcutaneous injection of 0.1 mL CFA into a footpad of the right hind leg of rats. Arthritic rats were treated with curcumin (100 mg/kg b.wt./day) by oral gavage for 21 days and/or treated with three weekly intravenous injections of BM-MSCs ( 1 × 10 6 cells/rat/week) in phosphate-buffered saline (PBS). The treatment with curcumin and BM-MSCs singly or together significantly ( P < 0.05 ) improved the bioindicators of oxidative stress and nonenzymatic and enzymatic antioxidants in sera of female rats more than in those of males. Curcumin and BM-MSCs significantly ( P < 0.05 ) improved the elevated TNF-α level and the lowered IL-10 level in the arthritic rats. Furthermore, joint, testis, and ovary histological changes were remarkably amended as a result of treatment with curcumin and BM-MSCs. Thus, it can be concluded that both curcumin and BM-MSCs could have antiarthritic efficacies as well as protective effects to the testes and ovaries which may be mediated via their anti-inflammatory and immunomodulatory potentials as well as oxidative stress modulatory effects.