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The mutation R273H in lipoamide dehydrogenase (Lpd) alters substrate affinities as well as kinetics at physiological substrate concentrations likely favoring a reactional shift towards lipoamide reduction. In addition, genetic reconstructions proved the necessity of all three mutations for formate assimilation by the adapted cells. The largely unpredictable nature of these changes demonstrates the usefulness of the evolutionary approach enabling the selection of adaptive mutations crucial for pathway engineering of biotechnological model organisms.Cancer remains a health-related concern globally. The application of light to be used as therapeuticagent including cancer has been used for several thousand years. Photodynamic therapy (PDT) is a modern, non-invasive therapeutic modality for the treatment of various cancers and infections by bacteria, fungi, and viruses. Mitochondria are subcellular, double-membrane organelles that have a role in cancer and anticancer therapy. Mitochondria play a key role in regulation of apoptosis and these organelles produce most of the cell's energy which enhance its targeting objective. The role of mitochondria in anticancer approach is achieved by targeting its metabolism (glycolysis and TCA cycle) and apoptotic and ROS homeostasis. The role of mitochondria-targeted cancer therapies in photodynamic therapy have proven to be more effective than other similar non-targeting techniques. Particularly in PDT, mitochondria-targeting sensitizers are important as they have a crucial role in overcoming the hypoxia factor, resulting in high efficacy. IR-730 and IR-Pyr are the indocyine derivatives photosensitizers that play a crucial role in targeting mitochondria because of their better photostability during laser irradiation. Clinical and pre-clinical trials are going on this approach to target different solid tumors using mitochondrial targeted photodynamic therapy.Burns are among the most debilitating and devastating forms of trauma. Such injuries are influenced by infections, causing increased morbidity, mortality, and healthcare costs. Due to the emergence of multidrug-resistant infectious agents, efficient treatment of infections in burns is a challenging issue. Antimicrobial photodynamic therapy (aPDT) is a promising approach to inactivate infectious agents, including multidrug-resistant. In this review, studies on PubMed were gathered, aiming to summarize the achievements regarding the applications of antimicrobial photodynamic therapy for the treatment of infected burns. A literature search was carried out for aPDT published reports assessment on bacterial, fungal, and viral infections in burns. The collected data suggest that aPDT could be a promising new approach against multidrug-resistant infectious agents. However, despite important results being obtained against bacteria, experimental and clinical studies are necessary yet on the effectiveness of aPDT against fungal and viral infections in burns, which could reduce morbidity and mortality of burned patients, mainly those infected by multidrug-resistant strains.The oxygenation of polyunsaturated fatty acids such as arachidonic and linoleic acid through enzymes like lipoxygenases (LOXs) are common and often leads to the production of various bioactive lipids that are important both in acute inflammation and its resolution and thus in disease progression. Amongst the several isoforms of LOX that are expressed in mammals, 15-lipoxygenase (15-LOX) has shown to be crucial in the context of inflammation. Moreover, being expressed in cells of the immune system, as well as in epithelial cells; the enzyme has been shown to crosstalk with a number of important signalling pathways. Mounting evidences from recent reports suggest that 15-LOX has anti-cancer activities which are dependent or independent of its metabolites, and is executed through several downstream pathways like cGMP, PPAR, p53, p21 and NAG-1. However, it is still unclear whether the up-regulation of 15-LOX is associated with cancer cell apoptosis. Monoamine oxidase A (MAO-A), on the other hand, is a mitochondrial flavoenzyme which is believed to be involved in the pathogenesis of atherosclerosis and inflammation and in many other neurological disorders. MAO-A has also been reported as a potential therapeutic target in different types of cancers like prostate cancer, lung cancer etc. In this review, we discussed about the role of fatty acids and their lipid mediators in cancer cell apoptosis. Here we particularly focused on the contribution of oxidative enzymes like 15-LOX and MAO-A in mediating apoptosis in lung cancer cell after fatty acid induction.Owing to the serious adverse effects caused by pyrimethamine and sulfadiazine, the drugs commonly used to treat toxoplasmosis, there is a need for treatment alternatives for this disease. Nanotechnology has enabled significant advances toward this goal. This study was conducted to evaluate the activity of biogenic silver nanoparticles (AgNp-Bio) in RAW 264.7 murine macrophages infected with the RH strain of Toxoplasma gondii. The macrophages were infected with T. gondii tachyzoites and then treated with various concentrations of AgNp-Bio. The cells were evaluated by microscopy, and culture supernatants were collected for ELISA determination of their cytokine concentration. Treatment with 6 μM AgNp-Bio reduced the infection and parasite load in infected RAW 264.7 macrophages without being toxic to the cells. The treatment also induced the synthesis of reactive oxygen species and tumor necrosis factor-alpha (both pro-inflammatory mediators), which resulted in ultrastructural changes in the tachyzoites and their intramacrophagic destruction. Our findings suggest that AgNp-Bio affect T. gondii tachyzoites by activating microbicidal and pro-inflammatory mechanisms and may be a potential alternative treatment for toxoplasmosis.Superfluous human airway smooth muscle (HASM) cell proliferation is an important pathological feature of airway remodelling in asthma. This study aimed to determine whether miR-21 is involved in the regulation of HASM cell survival. Overexpressed miR-21 inhibited HASM cell apoptosis and autophagy and promoted proliferation, whereas a miR-21 inhibitor exerted the opposite effects (P less then 0.05). Overexpressed poly (ADP-ribose) polymerase-1 (PARP-1) promoted apoptosis and inhibited proliferation of HASM cells (P less then 0.05). Dual-luciferase assays confirmed that miR-21 directly targeted poly (ADP-ribose) polymerase-1 (PARP-1) mRNA (P less then 0.05). Silencing PARP-1 based on miR-21 downregulation mimicked the role of 3-methyladenine (3-MA), an autophagy inhibitor (P less then 0.05). Overexpressed PARP-1 reversed the effects of miR-21 on HASM cells, somewhat dependently on PARP-1-induced enhanced autophagy, which we elucidated by 3-MA block (P less then 0.05). MicroRNA-21 mimics reduced AMPK and increased mTOR signalling by downregulating PARP-1, and a miR-21 inhibitor exerted the opposite effects (P less then 0.05). Collectively, miR-21 inhibitor could upregulate PARP-1 in HASM cells to promote autophagy and thus inhibit proliferation and promote apoptosis that might be mediated by the AMPK/mTOR signalling pathway.Regulatory T cells (Tregs) comprise a CD4+CD25+Foxp3+ T cell subset for maintaining immune tolerance, and their deficits and/or dysfunction are observed in autoimmune diseases. The lymphocyte activation gene 3 (LAG-3, also known as CD223), which is an immunoglobulin superfamily member expressed on peripheral immune cells, is recognized as an inhibitory regulator of Tregs. selleckchem LAG-3+ T cells represent a novel protective Tregs subset that produces interleukin-10. Alterations in LAG-3+ Tregs have been reported in several autoimmune diseases, suggesting their potential pathogenic role. Recent studies have indicated that LAG-3+ Tregs may be associated not only with immunopathology but also with response to therapy in several autoimmune and autoinflammatory diseases, such as rheumatoid arthritis, psoriasis, psoriatic arthritis and others. We present a review of Tregs phenotypes and functions, with a focus on LAG-3+ Tregs, and discuss their potential role as biomarkers for treatment response in autoimmune diseases.Giant cell arteritis (GCA) is a large-vessel vasculitis that affects cranial and extra-cranial arteries. Extra-cranial GCA presents mainly with non-specific symptoms and the differential diagnosis is very broad, while the cranial form has more typical clinical picture and physicians have a lower threshold for diagnosis and treatment. Although temporal artery biopsy (TAB) has an established role, ultrasound (US) is being increasingly used as the first-line imaging modality in suspected GCA. Vasculitides (especially ANCA-associated), hematological disorders (mainly amyloidosis), neoplasms, infections, atherosclerosis and local disorders can affect the temporal arteries or might mimic the symptoms of cranial GCA and produce US and TAB findings that resemble those of temporal vasculitis. Given that prompt diagnosis is essential and proper treatment varies significantly among these diseases, in this review we aimed to collectively present disorders that can masquerade cranial GCA.

Patients with primary Sjögren's syndrome(pSS) have increased risk of non-Hodgkin lymphoma (NHL). However, whether pSS patients have increased risk of other malignancies is unclear. The aim of this study is to investigate the association between pSS and the risk of malignancy, with a focus on hematological malignancies besides lymphoma and solid tumors through a systematic review and meta-analysis.

We searched PubMed and EMBASE by March 21st 2021. Inclusion criteria were as follows (1) pSS was the exposure of interest; (2) newly developed malignancies were the outcome of interest; (3) standardized incidence ratio or relative risk with 95% confidence interval or essential data to calculate them were reported. (4) Study design was cohort study. Patient with other connective diseases were excluded. Quality assessment was conducted according to Newcastle-Ottawa Scale for cohort study. Random or fixed effect models were used to calculate the pooled SIR according to heterogeneity measured by I

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A total of 1002; 1.81), liver cancer(pooled SIR 1.70, 95%CI 1.13-2.57) and prostate cancer(pooled SIR 1.50, 95%CI 1.02-2.22).

This meta-analysis showed that pSS patients had increased risk of overall cancer, which not only contributed by NHL, but also by other hematological malignancies and solid tumors.

This meta-analysis showed that pSS patients had increased risk of overall cancer, which not only contributed by NHL, but also by other hematological malignancies and solid tumors.Renal artery stenosis (RAS) may cause secondary hypertension, progressive decline in renal function, and cardiac destabilization syndromes including "flash" pulmonary edema, recurrent congestive heart failure, and cerebro-cardiovascular disease. Atherosclerotic lesions, fibromuscular dysplasia, and vasculitides are the pathophysiological basis of the disease. Common therapeutic pathways for RAS include medical therapy and revascularization with or without stenting. Randomized controlled trials evaluating renal revascularization have not reported any advantages of revascularization over medical therapy alone in terms of renal function improvement or prevention of cardiovascular events. However, mounting clinical experience suggests that the best strategy in RAS management is to identify which patients are most likely to benefit from renal artery stenting and to optimize the safety and durability of the procedure. This review presents 3 cases of patients who have undergone renal revascularization and discusses the available clinical evidence for the identification of RAS patients who will potentially respond well to revascularization.