The Role of Antioxidants in the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) is a global public health problem that causes liver-related morbidity and mortality. It is also an independent risk factor for non-communicable diseases. In 2020, a proposal was made to refer to it as "metabolic dysfunction-associated fatty liver disease (MAFLD)", with concise diagnostic criteria. Given its widespread occurrence, its treatment is crucial. Increased levels of oxidative stress cause this disease. This review aims to evaluate various studies on antioxidant therapies for patients with MAFLD. A comprehensive search for relevant research was conducted on the PubMed, SCOPUS, and ScienceDirect databases, resulting in the identification of 87 studies that met the inclusion criteria. In total, 31.1% of human studies used natural antioxidants, 53.3% used synthetic antioxidants, and 15.5% used both natural and synthetic antioxidants. In human-based studies, natural antioxidants showed 100% efficacy in the treatment of MAFLD, while synthetic antioxidants showed effective results in only 91% of the investigations. In animal-based research, natural antioxidants were fully effective in the treatment of MAFLD, while synthetic antioxidants demonstrated effectiveness in only 87.8% of the evaluations. In conclusion, antioxidants in their natural form are more helpful for patients with MAFLD, and preserving the correct balance of pro-oxidants and antioxidants is a useful way to monitor antioxidant treatment.

The Influence of Antioxidants on Oxidative Stress-Induced Vascular Aging in Obesity.

Obesity is a worldwide trend that is growing in incidence very fast. Adipose tissue dysfunction caused by obesity is associated with the generation of oxidative stress. Obesity-induced oxidative stress and inflammation play a key role in the pathogenesis of vascular diseases. Vascular aging is one of the main pathogenesis mechanisms. The aim of this study is to review the effect of antioxidants on vascular aging caused by oxidative stress in obesity. In order to achieve this aim, this paper is designed to review obesity-caused adipose tissue remodeling, vascular aging generated by high levels of oxidative stress, and the effects of antioxidants on obesity, redox balance, and vascular aging. It seems that vascular diseases in obese individuals are complex networks of pathological mechanisms. In order to develop a proper therapeutic tool, first, there is a need for a better understanding of interactions between obesity, oxidative stress, and aging. Based on these interactions, this review suggests different lines of strategies that include change in lifestyle to prevent and control obesity, strategies for adipose tissue remodelling, oxidant-antioxidant balance, inflammation suppression, and strategies against vascular aging. Some antioxidants support different lines of these strategies, making them appropriate for complex conditions such as oxidative stress-induced vascular diseases in obese individuals.

Acute phase reactant proteins in Buerger's disease: Is it a systemic disease?

Aim: The aim of this study was evaluating acute phase reactant (APR) proteins including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), fibrinogen, complement C3, hepcidin, and albumin in patients suffering from Buerger's disease (BD) compared to controls.Methods: The APRs were evaluated in 92 cases of BD patients and 90 healthy age and sex matched controls of blood from Iran and Turkey. The diagnosis was done according to Shionoya's criteria. However, patients with age less than 40 were included, instead of those less than 50. The diagnosis was confirmed by angiography or CT angiography. The patients were categorized into active and quiescent phases of the disease according to clinical manifestation. Patients with rest pain, non-healing ulcer, and gangrene were categorized in the active phase of the disease and the patients with unchanged claudication for more than 6 months without trophic lesions or gangrene were categorized in the quiescent phase of the disease.Results: The serum level of PTX3, hsCRP, fibrinogen, C3, and hepcidin in BD was significantly higher than controls (p < 0.004). Also, albumin in the BD group was significantly lower than controls (p < 0.001). In patients that categorized in the active phase, fibrinogen, C3, and hsCRP were significantly higher and albumin was significantly lower compared to patients in the quiescent phase. No significant difference was found between the level of PTX3 and hepcidin in the patients in active and quiescent phases of the disease.Conclusion: The pattern of the level of APRs in BD seems more likely systemic inflammatory disorder than atherosclerosis obliterans. More clinical trials for evaluating the efficacy of anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids as a part of management of BD are required. Also, according to low level of albumin in TAO, a protein rich diet might be beneficial for BD patients in the active phase of their disease.

The Potential Role of Antioxidants in the Treatment of Peripheral Arterial Disease: A Systematic Review.

Peripheral arterial disease (PAD) has a worldwide prevalence and is a significant cause of cardiovascular morbidity and mortality. Due to its high prevalence and higher rates of ischemic cardiovascular and lower-extremity events, its treatment is essential. Increased levels of oxidative stress cause disease. This review aimed to evaluate different studies of antioxidant treatments for PAD patients. A systematic search for relevant studies was performed on the PubMed, SCOPUS, and ScienceDirect databases, and 18 studies fulfilled the inclusion criteria. In total, 16.6% of the studies used natural antioxidants, and 83.3% used synthetic antioxidants. The reviewed studies show that natural antioxidants were completely effective in treating PAD, and synthetic antioxidants showed effective results in only 53% of the studies. A less-than-optimal pro-oxidant-antioxidant balance does not improve the symptoms of PAD. In conclusion, antioxidants in their natural forms are more effective for PAD patients, and ensuring the optimal pro-oxidant-antioxidant balance is an effective method for managing treatment with antioxidants.

The Roles of Exosomal microRNAs in Diffuse Large B-Cell Lymphoma: Diagnosis, Prognosis, Clinical Application, and Biomolecular Mechanisms.

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all patients being cured with R-CHOP therapeutic regimen (Cyclophosphamide, doxorubicin, vincristine, and prednisone, combined with rituximab), remaining patients display aggressive disease. Therefore, there is an urgent need to develop novel diagnostic, prognostic, and predictive biomarkers. Recently, exosomal miRNAs have been approved as novel biomarkers in DLBCL due to their potential involvement in lymphomagenesis. Material and Methods: We conducted an investigation on the potential role of exosomal miRNAs as diagnostic, prognostic, and predictive biomarkers in DLBCL in the PubMed, Scopus, and Web of Science search engines. We searched by using a combination of keywords, such as diffuse large B-cell lymphoma, DLBCL, miRNA, microRNA, miR, exosome, exosomes, exosomal, extracellular vesicles, EVs, and secretome. Then, search results were narrowed based on specific inclusion and exclusion criteria. Results: Twelve articles were eligible for our systematic reviews. Among them, nine discussed diagnostic biomarkers, three considered prognostic significance, four evaluated therapeutic efficacy, two studies were conducted in vitro, and three assessed molecular pathways associated with these exosomal miRNAs in DLBCL. Discussion: According to our systematic review, exosomal miRNAs are not only useful for diagnosis and prognosis in DLBCL but are also promising therapeutic tools and predictors of response to therapy. Although promising results so far, more research is required to develop innovative biomarkers.

The Potential Role of Exosomes in the Treatment of Brain Tumors, Recent Updates and Advances.

Exosomes are small endosomal derived membrane extracellular vesicles that contain cell-specific cargos such as lipid, protein, DNA, RNA, miRNA, long non-coding RNA, and some other cell components that are released into surrounding body fluids upon the fusion of multivesicular bodies (MVB) and the plasma membrane. Exosomes are a one-of-a-kind cell-to-cell communication mechanism that might pave the way for target therapy. The use of exosomes as a therapeutic potential in a variety of cancers has been and is still being investigated. One of the most important of these has been the use of exosomes in brain tumors therapy. Exosome contents play a crucial role in brain tumor progression by providing a favorable niche for tumor cell proliferation. Also, exosomes that are secreted from tumor cells, lead to the protection of tumor cells and their proliferation in the tumor environment by reducing the inflammatory response and suppression of the immune system. Although some treatment protocols such as surgery, chemotherapy, and radiotherapy are common in brain tumors, they do not result in complete remission in the treatment of some malignant and metastatic brain tumors. Identifying, targeting, and blocking exosomes involved in the progression of brain tumors could be a promising way to reduce brain tumor progression. On the other way, brain tumor therapy with effective therapeutic components such as siRNAs, mRNAs, proteins, could be developed. Finally, our research suggested that exosomes of nanoscale sizes might be a useful tool for crossing the blood-brain barrier and delivering effective content. However, further research is needed to fully comprehend the potential involvement of the exosome in brain tumor therapy protocols.

Recent Updates and Advances in Winiwarter-Buerger Disease (Thromboangiitis Obliterans): Biomolecular Mechanisms, Diagnostics and Clinical Consequences.

Thromboangiitis obliterans (TAO) or Buerger's disease is a segmental inflammatory, thrombotic occlusive peripheral vascular disease with unknown aetiology that usually involves the medium and small-sized vessels of young male smokers. Due to its unknown aetiology and similarities with atherosclerosis and vasculitis, TAO diagnosis is still challenging. We aimed to review the status of biomolecular and laboratory para-clinical markers in TAO compared to atherosclerosis and vasculitis. We reported that, although some biomarkers might be common in TAO, atherosclerosis, and vasculitis, each disease occurs through a different pathway and, to our knowledge, there is no specific and definitive marker for differentiating TAO from atherosclerosis or vasculitis. Our review highlighted that pro-inflammatory and cell-mediated immunity cytokines, IL-33, HMGB1, neopterin, MMPs, ICAM1, complement components, fibrinogen, oxidative stress, NO levels, eNOS polymorphism, adrenalin and noradrenalin, lead, cadmium, and homocysteine are common markers. Nitric oxide, MPV, TLRs, MDA, ox-LDL, sST2, antioxidant system, autoantibodies, and type of infection are differential markers, whereas platelet and leukocyte count, haemoglobin, lipid profile, CRP, ESR, FBS, creatinine, d-dimer, hypercoagulation activity, as well as protein C and S are controversial markers. Finally, our study proposed diagnostic panels for laboratory differential diagnosis to be considered at first and in more advanced stages.

Assessment of T helper 17-associated cytokines in thromboangiitis obliterans.

BACKGROUND: The management of thromboangiitis obliterans (TAO) remains a medical challenge because of its unknown etiology. It is also not known whether it is a systemic or localized disease or a type of autoimmune vasculitis. METHODS: In this study, we evaluated the serum level of IL-17 and IL-23 which increase in both systemic inflammation and autoimmunity, in 60 TAO patients and 30 age- and smoking habit-matched controls. Also, IL-22, which has reported high level during infection but not in autoimmunity, was evaluated. RESULTS: The serum levels of IL-17, IL-22 and IL-23 were significantly higher in the TAO patients in comparison with the controls (P<0.001). Notably, the serum levels of IL-17, IL-22 and IL-23 were highest in the patients with the chief complaint of chronic ulcer and lowest in the patients with gangrene (P<0.05). Also, the serum level of IL-22 was significantly higher in the anemic patients in comparison with the non-anemic patients (P=0.03). CONCLUSION: Owing to our findings, TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. Also, according to our findings regarding the high level of IL-22, the trigger of TAO development may be an infectious pathogen. However, additional research is highly recommended to investigate whether TAO is an infectious disease or an infectious-induced autoimmunity.

Angiogenesis induction in Buerger's disease: a disease management double-edged sword?

Due to unknown aetiology of Thromboangiitis obliterans (TAO), its effectively treating is challenging. However, angiogenesis induction is one of the acceptable treatments for TAO patients. Recently, we have noticed that TAO patients who were under long-term treatment with angiogenesis-inducing medication showed considerable improvement in terms of healing chronic ulcers over the course of one to 2 years of treatment. However, some of them developed dermal gangrene despite the warming of their feet, with or without palpable pulses in the extremities, and with hair growth on the affected skin. Unfortunately, following the progression of dermal gangrene, some of these patients had to undergo amputation and limb loss.During histopathological evaluation, we detected some changes in the amputee TAO patients under long-term angiogenic medical treatment that were not present in amputee TAO patients who had not received any treatment for many years. The greatest pathological changes were observed in the microvascular of the skin, appearing as a proliferation of endothelial cells, NETosis and thrombus formation inside the vessels with proliferation of endothelial cells. The immunohistochemistry for CD31 and Ki67 as markers of vascular endothelium differentiation and cell mitosis confirmed the proliferation of endothelial cells. However, in the patients who had not received any treatment for years the typical pathology view of BD, including preserved vascular architecture with infiltration of inflammatory cells and inflammatory cells inside the thrombus, organised thrombus with recanalisation and intimal thickening was observed. Further longitudinal cohort studies regarding long-term treatment with angiogenic medications for TAO in different geographic areas are highly recommended.