Toll-Like Receptor 4 as an Immune Receptor Against Mycobacterium tuberculosis: A Systematic Review.

OBJECTIVE: To review the main Mycobacterium tuberculosis (Mtb) pathogen-associated molecular patterns (PAMPs) and the roles played by toll-like receptor (TLR)4 in determination of Mtb infection outcome. METHODS: Several scientific databases, including Scopus, PubMed, and Google Scholar, were used for searching appropriate research articles from the literature for information on our topic. RESULTS: TLR4 plays positive roles in induction of immune responses against Mtb and participates in eradication of the infection. Some limited investigations approved the roles of TLR4 in induction of apoptosis in macrophages during tuberculosis (TB) and attenuation of immune responses in some situations. CONCLUSIONS: TB outcome appears to be dependent on TLR4/Mtb interaction and several factors, including bacterial load and immune or nonimmune cells, as hosts. Also, other TLR/Mtb interactions can affect TLR4 responses.

Changes in serum level of trace elements in pulmonary tuberculosis patients during anti-tuberculosis treatment.

INTRODUCTIONS: Tuberculosis is spreading throughout the globe, while it is a crucial cause of death in developing countries. In this study, trace elements concentrations and their alterations were determined in TB patients during anti-tuberculosis treatment period. MATERIALS AND METHODS: We have collected blood samples from a total of 180 TB patients with pulmonary Tuberculosis, and 180 healthy controls in Sistan, Iran. The serum iron, copper, lead, calcium, arsenic and selenium concentrations were detected at the beginning of anti-TB chemotherapy, at the end of 2nd, 4th and 6th month after treatment initiation. Data were then analyzed using SPSS version 20. RESULTS AND DISCUSSIONS: Although Ca, Pb, and As levels did not change during the treatment period, serum concentrations of Fe, Zn, Cu, and Se were diminished in TB patients significantly during treatment in comparison with controls (P < 0.001).We also found that there was a significant difference in the Cu/Se and Cu/Zn ratios in tuberculosis patients in comparison with healthy individuals (P < 0.001). CONCLUSIONS: Trace elements serum concentrations are affected by TB infection and anti-TB therapy. Their serum levels were strongly perturbed during infection as well as anti-TB treatment.

Inflammasomes and type 2 diabetes: An updated systematic review.

Type 2 diabetes (T2D) is a metabolic disorder that is accompanied by chronic inflammation. The main mechanisms and molecular signaling of the induction of inflammation in T2D are still unknown. It seems that intracellular sensors that participate in recognition of endogenous damage associated molecular patterns (DAMPs) play key roles in the induction/stimulation of chronic inflammation in T2D. The Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain containing (NLRP) family and accompanying Inflammasomes are important intracellular receptors of inflammatory pathogens and stress signals that elevate caspase-1-mediated release of IL-1ß and IL-18. Studies suggest that disruption of NLRP1 and NLRP3 has a major role for these inflammasomes in internal immunity and inflammation as well as metabolic disorders. Thus, it seems that these mediators may participate in the induction/stimulation of chronic inflammation in patients. This systematic review provides an up-to-date evaluation of our current understanding of the roles of inflammasomes in the pathogenesis of T2D and its complications.

Toll like receptor 4 and hepatocellular carcinoma; A systematic review.

INTRODUCTION: Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC. METHOD: "TLR4", "hepatocellular carcinoma", "liver tumor" and "liver cancer" were used as key words for searching in Scopus, Google Scholar and MEDLINE scientific databases. RESULTS: Most of the investigations documented the roles of TLR4 in induction of HCC via several mechanisms including increased number of T regulatory lymphocytes and liver resident follicular helper like cells, increased production of pro-inflammatory and malignancy related molecules including cytokines, NANOG, Caspase-1, Ephrin-A1, NO and BCL6. TLR4 participates in the proliferation of the cells and also production of the molecules in both chronic infectious and non-infectious inflammatory diseases. DISCUSSION: TLR4 is an innate immunity receptor which plays a pathogenic role during chronic inflammation and can induce HCC in human.

Correction: Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0168312.].

Essential and toxic metals in serum of individuals with active pulmonary tuberculosis in an endemic region.

Trace elements play an important role in tuberculosis infection because their deficiencies can be associated with impaired immunity. Blood samples were collected from a total of 320 active pulmonary tuberculosis patients and healthy individuals. The serum concentrations of Zinc, Iron, Copper, Calcium, lead, Arsenic and Selenium were analyzed by atomic absorption spectrometry. The levels of trace elements were measured after 2, 4 and 6 months of anti-TB treatment initiation in TB infected groups. Compared to the control group, the concentrations of Zinc, Selenium, and Iron were significantly lower (P < 0.001) in tuberculosis patients; however, that of Arsenic, Lead, and copper was significantly higher (P < 0.001) in the serum of patients. Cu/Zn and Cu/Se ratios were also significantly higher (P < 0.001) in TB patients compared to the control group. In addition, serum concentration calcium was similar in both TB patients and healthy controls. Our results indicated that trace elements concentrations in tuberculosis patients are related to each element role in immune system. Wherever the element is essential for the pathogenesis of bacteria, its concentration will remain low; and contrariwise, when the element is toxic for the bacteria, its level will be regulated up to provide a perfect condition for bacterial growth.

Atorvastatin, Losartan and Captopril Lead to Upregulation of TGF-ß, and Downregulation of IL-6 in Coronary Artery Disease and Hypertension.

INTRODUCTION: Coronary artery disease (CAD) and hypertension are the main reasons of ischemic heart diseases (IHDs). Cytokines as the small glycoproteins are the main arm of immune system and manipulate all of the cardiovascular diseases. The aim of the current study was to examine the effects of treatment of hypertension and CAD on serum levels of IL-6, IL-8, TGF-ß and TNF-α. MATERIAL AND METHODS: This interventional study was performed on the patients with hypertension without CAD (group 1), hypertension and CAD (group 2), CAD but not hypertension (group 3) and without hypertension and CAD as controls (group 4). The patients received routine treatment for hypertension and CAD. Serum levels of IL-6, IL-8, TGF-ß and TNF-α were analyzed in the groups treated with various drugs, using ELISA technique. RESULTS: With regard to the medications, Atorvastatin, Losartan and Captopril were administered more in patients (groups 1, 2 and 3) than the patients without hypertension and CAD. The results revealed that serum levels of TGF-ß and IL-6 were significantly increased and decreased, respectively, in the groups 1, 2 and 3 when compared to group 4. Serum levels of TGF-ß were also increased in females in comparison to males in the group 4. DISCUSSION: According to the results it seems that Atorvastatin, Losartan and Captopril have reduced inflammation in in vivo conditions via downregulation of IL-6 and upregulation of TGF-ß.

Evaluation of Outcome and Tolerability of Combination Chemotherapy with Capecitabine and Oxaliplatin as First Line Therapy in Advanced Gastric Cancer.

Background: Combination chemotherapy is accepted as a high efficacy treatment for gastric cancer, whereas choice of standard treatment is unclear. Multiple chemotherapeutic regimens have been used to achieve higher efficacy and lower toxicity. This study was designed to evaluate the treatment results of advanced gastric cancer with Capecitabine and Oxaliplatin regimen. Subjects and Methods: All cases with documented gastric adenocarcinoma and advanced disease were candidates for receiving Xelox regimen (Capecitabine - 750 mg/m2/twice daily/ 1-14 days and Oxaliplatin 125 mg/m2 in 1st day). Results: Twenty five cases with advanced gastric cancer entered in study while 24 cases continued treatment protocol and were evaluated. Mean age was 59.5 ± 12.1 years (range: 20-75), male and female cases were 66.7% and 33.3%, respectively. All cases received at least four cycles of Xelox regimen. Overall response rate was 74.99% with 29.16% complete response. Overall survival rate was 13 ± 0.53 months and DFS (disease-free survival) was 6 ± 1.09 months. Extremities neuropathy (62.5%), headache (45.8%) and muscle cramps (29.2%) were the most common complains. Haematological changes were rare and 16.7% of cases had mild cytopenia. Treatment related death was not observed. Conclusion: Xelox regimen is a safe and highly effective first line treatment for gastric cancer; however, considering it as first line therapy needs larger studies.

The link between TLR7 signaling and hepatitis B virus infection.

Toll-Like Receptors (TLRs) play crucial roles in recognition and induction of appropriate immune responses against viral infections, including hepatitis B. TLR7 detects intracellular viral single strand RNA which leads to the activation of several pro-inflammatory transcription factors via the MYD88 dependent pathway. Patients with prolonged infectious forms of hepatitis B, including active and inactive chronic forms, are unable to clear HBV from hepatocytes completely. It is believed that the differences in genetic and immunological parameters of the patients and clearance subjects, who successfully clear HBV infections, are the main factors responsible for allowing the long term infections to persist. It appears that defective expression of TLR7 may result in impaired immune responses against HBV. The aim of this review is to address the recent information regarding the crucial roles played by TLR7 in hepatitis B infection and also the main mechanisms used by HBV to escape from recognition by TLR7 in prolonged HBV infected patients. Considering that chronic hepatitis B infection is not yet curable, it could be possible to activate TLR7-related immunological pathways as a therapy directed towards persistent HBV infection. Hence, another aim of this study is to present recent developments of TLR7 agonists as a therapeutic strategy for chronic hepatitis B.

Economic Burden of Road Traffic Accidents; Report from a Single Center from South Eastern Iran.

OBJECTIVE: To determine the economic burden of road traffic accidents (RTAs) in patients admitted to a single center in south eastern Iran. METHODS: This cross-sectional study was conducted in Amir-Al-Momenin hospital of Zabol affiliated with Zabol University of Medical Sciences during a 12-month period from April 2012 to April 2013. All the RTAs patients who were admitted to our emergency department were included. The direct expenses of hospital care were recorded according to their medical charts and the accountant registration information. Data are presented according to different RTAs characteristics. RESULTS: Overall 1155 patients were included in the current study with mean age of 36.7 ± 5.14 years among whom there were 673(58.3%) men and 482 (41.7%) women. The annual incidence of RTAs were calculated to be 288 per 100,000 population. The RTAs economic burden in our center was 589,448.49 USD which accounted for 10.4% of total hospital expenses during the study period. The money spend on RTAs in our center was 130 times more than gross national income per capita. Cost of each patient in road traffic was 15 times more than cost of an average patient of the hospital in other sections. CONCLUSION: With considerable high ratio of accidents in Zabol, proper intervention is needed for controlling and preventing RTAs in order to decrease its injuries, impact and the associated economic burden.

Toll-like receptor 2 and type 2 diabetes.

Innate immunity plays a crucial role in the pathogenesis of type 2 diabetes and related complications. Since the toll-like receptors (TLRs) are central to innate immunity, it appears that they are important participants in the development and pathogenesis of the disease. Previous investigations demonstrated that TLR2 homodimers and TLR2 heterodimers with TLR1 or TLR6 activate innate immunity upon recognition of damage-associated molecular patterns (DAMPs). Several DAMPs are released during type 2 diabetes, so it may be hypothesized that TLR2 is significantly involved in its progression. Here, we review recent data on the important roles and status of TLR2 in type 2 diabetes and related complications.

The prevalence of zinc deficiency in patients with thalassemia in South East of iran, sistan and baluchistan province.

BACKGROUND: There are different and controversial reports about zinc deficiency in patients with major thalassemia. OBJECTIVES: The aim of this study was to evaluate zinc status in patients with major thalassemia in Sistan and Baluchistan province, southeastern Iran. PATIENTS AND METHODS: The study was performed in Ali Asghar Hospital, a specialized governmental hospital located in Zahedan, Iran. In this cross-sectional study, 369 patients with a history of major thalassemia for more than 5 years entered the study using convenience sampling method. Thirty-six subjects were excluded from the study based on our exclusion criteria. Zinc level was measured in all patients after 12 hours fasting using atomic absorption spectrometry method in 2012. RESULTS: Of 369 cases, 333 patients were eligible and evaluated. The mean age was 15.63 ± 7.4 years. One hundred ninety two cases were male and others were female (141 cases). About 27% (90) of the cases were 5-10 years-old, 24% (80) were 10-15 years-old and 49% were older than 15 years old. Iron chelator in 65.46% was Desferrioxamine, in 28.2% was Deferasirox and in 19.5% was combination of Desferrioxamine and Deferiprone. All cases had zinc deficiency, and 98.5% had severe zinc deficiency. Others (1.5%) had mild deficiency. CONCLUSIONS: Our study on 333 patients with major thalassemia documented severe zinc deficiency in all cases. We had no cases with normal or increased zinc levels. It was different with other reports in the world.