Mycobacterium tuberculosis and host interactions in the manifestation of tuberculosis.

The final step of epigenetic processes is changing the gene expression in a new microenvironment in the body, such as neuroendocrine changes, active infections, oncogenes, or chemical agents. The case of tuberculosis (TB) is an outcome of Mycobacterium tuberculosis (M.tb) and host interaction in the manifestation of active and latent TB or clearance. This comprehensive review explains and interprets the epigenetics findings regarding gene expressions on the host-pathogen interactions in the development and progression of tuberculosis. This review introduces novel insights into the complicated host-pathogen interactions, discusses the challengeable results, and shows the gaps in the clear understanding of M.tb behavior. Focusing on the biological phenomena of host-pathogen interactions, the epigenetic changes, and their outcomes provides a promising future for developing effective TB immunotherapies when converting gene expression toward appropriate host immune responses gradually becomes attainable. Overall, this review may shed light on the dark sides of TB pathogenesis as a life-threatening disease. Therefore, it may support effective planning and implementation of epigenetics approaches for introducing proper therapies or effective vaccines.

The Effects of Antioxidant Supplementation on the Pathologic Mechanisms of Metabolic Syndrome and Cardiovascular Disease Development.

In people with obesity, diabetes, and hypertension, lipid and glucose metabolism and oxidative stress generation interact. This condition, known as a "metabolic syndrome" (MetS), presents a global challenge and appears to be the underlying mechanism for the development of cardiovascular diseases (CVDs). This review is designed based on evidence indicating the pathogenic mechanisms of MetS. In detail, we will look at the mechanisms of oxidative stress induction in MetS, the effects of elevated oxidative stress levels on the condition's pathophysiology, and matters related to endothelial function. According to different components of the MetS pathophysiological network, the effects of antioxidants and endothelial dysfunction are reviewed. After considering the strategic role of oxidative stress in the pathophysiology of MetS and its associated CVDs, oxidative stress management by antioxidant supplementation seems an appropriate therapeutic approach.

Diagnostic criteria for Buerger's disease: International Consensus of VAS - European Independent Foundation in Angiology/Vascular Medicine.

Buerger's disease (BD) remains a debilitating condition and early diagnosis is paramount for its effective management. Despite many published diagnostic criteria for BD, selective criteria have been utilized in different vascular centers to manage patients with BD worldwide. A recent international Delphi Consensus Study on the diagnostic criteria of BD showed that none of these published diagnostic criteria have been universally accepted as a gold standard. Apart from the presence of smoking, these published diagnostic criteria have distinct differences between them, rendering the direct comparison of patient outcomes difficult. Hence, the expert committees from the Working Group of the VAS-European Independent Foundation in Angiology/Vascular Medicine critically reviewed the findings from the Delphi study and provided practical recommendations on the diagnostic criteria for BD, facilitating its universal use. We recommend that the 'definitive' diagnosis of BD must require the presence of three features (history of smoking, typical angiographic features and typical histopathological features) and the use of a combination of major and minor criteria for the 'suspected' diagnosis of BD. The major criterion is the history of active tobacco smoking. The five minor criteria are disease onset at age less than 45 years, ischemic involvement of the lower limbs, ischemic involvement of one or both of the upper limbs, thrombophlebitis migrans and red-blue shade of purple discoloration on edematous toes or fingers. We recommend that a 'suspected' diagnosis of BD is confirmed in the presence of a major criterion plus four or more minor criteria. In the absence of the major criterion or in cases of fewer than four minor criteria, imaging and laboratory data could facilitate the diagnosis. Validation studies on the use of these major and minor criteria are underway.

An International Delphi Consensus on Diagnostic Criteria for Buerger's Disease.

BACKGROUND: Buerger's disease (BD) remains a debilitating condition. Despite multiple published diagnostic criteria for BD, none is universally accepted as a gold standard. METHODS: We conducted a 2-round modified Delphi consensus study to establish a consensus on the diagnostic. The questionnaire included statements from several commonly used diagnostic criteria for BD. Qualitative and quantitative analysis methods were performed. An agreement level of 70% was applied. RESULTS: Twenty nine experts from 18 countries participated in this study. Overall, 75 statements were circulated in Round 1. Of these, 28% of statements were accepted. Following comments, 21 statements were recirculated in Round 2 and 90% were accepted. Although more than 90% of the experts did not agree that the diagnosis of BD can be based only on clinical manifestation, none of the nonclinical manifestations of BD were agreed as a part of the diagnostic criteria. There was an agreement that a history of tobacco consumption in any form, not necessarily confined to the current use, should be a part of the diagnostic criteria of BD. The history of thrombophlebitis migrans, even if not present at presentation, was accepted as a clue for BD diagnosis. It was also agreed that discoloration of the toes or fingers could be included in the diagnostic criteria of BD. Experts agreed that histology results could differentiate BD from atherosclerosis obliterans and other types of vasculitis. The presence of corkscrew collaterals on imaging and burning pain reached the agreement at the first round but not at the second. There was no consensus regarding age cut-off, the requirement of normal lipid profile, and normal blood glucose for BD diagnosis. CONCLUSIONS: The present study demonstrated discrepancies in the various published diagnostic criteria for BD and their selective utilization in routine clinical practice worldwide. We propose that all published diagnostic criteria for BD be re-evaluated for harmonization and universal use.

The IL-33/sST2 Axis in Thromboangiitis Obliterans.

BACKGROUND: Until recently, it remains unknown whether thromboangiitis obliterans (TAO) is a type of systemic vasculitis. A high level of IL-33 and its soluble decoy receptor sST2 in the acute phase of systemic vasculitis has been demonstrated. METHODS: The serum level of IL-33 and sST2 in 50 TAO patients, 20 age- and smoking habit-matched controls and 19 age-matched non-smoker controls was evaluated. RESULTS: The mean level of IL-33 in TAO, smokers and non-smokers was 370.2±61.7ng/mL,132.14±2.6ng/mL and 11.3±0.38ng/mL, respectively. The IL-33 was significantly higher in the TAO than in either control groups (p < 0.001). The IL-33 in the acute phase of TAO was significantly higher than in the patients in the quiescent phase of the disease (p = 0.019). Also, IL-33 in the patients with gangrene was significantly higher than in the patients with non-healing ulcers (p = 0.021). The sST2 in the TAO patients was 49.3±5.58ng/mL, and in smoker and non-smoker controls, it was 45.3±6.3ng/mL and 4.11±0.17ng/mL, respectively. No significant difference was found between the patients and smoker control groups (p = 0.87). The mean ratio of IL-33/sST2 was 27.89±10.44 in the TAO group and, in smokers and non-smokers, it was 2.85±0.48 and 2.84±0.14, respectively. A significantly high level of IL-33/sST2 ratio was observed in TAO patients in both the active and quiescent phases of the disease in comparison to both control groups (p<0.001). CONCLUSION: The regulation pattern of IL-33/sST2 was different in TAO in comparison to autoimmune vasculitis.

The Imbalance among Oxidative Biomarkers and Antioxidant Defense Systems in Thromboangiitis Obliterans (Winiwarter-Buerger Disease).

(1) Background: Thromboangiitis obliterans or Winiwarter-Buerger disease (WBD), is an inflammatory, thrombotic occlusive, peripheral vascular disease, usually occurring in young smokers. The pathophysiological mechanisms underlying the disease are not clearly understood. The aim of this study is to investigate the imbalance between oxidants and antioxidants occurring in these patients. (2) Patients and Methods: In this cross-sectional study, 22 male patients with WBD and 20 healthy male smoking habit matched control group were included. To evaluate the possible sources of oxidative stress, the antioxidant biomarkers, and the markers of lipid peroxidation and protein oxidation, serum samples were analyzed for total oxidative status (TOS), total antioxidant capacity (TAC), myeloperoxidase (MPO), coenzyme Q10 (CoQ10), superoxide dismutase (SOD), glutathione reductase (GR), malondialdehyde (MDA), and protein carbonyl (PC) activity and/or content. (3) Results: The circulating levels of TOS, TAC, and CoQ10 were significantly higher in WBD patients, with respect to healthy smokers as controls. No significant difference was found among the serum level of PC, total cholesterol, MPO, and GR activity in WBD patients and healthy smoker controls. The activity of SOD and the mean serum level of MDA were significantly lower in WBD patients, with respect to healthy smoker controls. (4) Conclusion: Considerably high levels of oxidative stress were detected in WBD patients, which were greater than the antioxidant capacity. The low level of MDA may be associated with the enzymatic degradation of lipid peroxidation products. High levels of CoQ10 and low levels of SOD may be related to a harmful oxidative cooperation, leading to the vasoconstriction of WBD, representing a promising tool to discern possible different clinical risks of this poorly understood peripheral occlusive disease.