Background: Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers.Body: IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles of specific M2a proteins in the pathogenesis of asthma. In the current review, we try to illustrate the different functions of M2a macrophages (protective and pathogenic roles) in the pathogenesis of asthma, including explanation of how different M2a proteins and markers act during the pathogenesis of allergic asthma. These include surface markers, enzymes, secreted proteins, chemokines, cytokines, signal transduction proteins and transcription factors.Conclusions: AAM is considered a double-edged sword in allergic asthma. Finally, we recommend further studies that focus on increased selective expression or suppression of protective and pathogenic M2a markers.

β-Defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. β-Defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 μg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select β-defensins, especially human β-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that β-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition ofenv-mediated fusion, and we did not observe any modulation of HIV coreceptors following treatment with hBD1 and hBD2, in both resting and phytohemagglutinin-activated cells. Our data instead suggest that, besides a direct inactivation of HIV virions, hBD2 inhibits HIV replication in the intracellular environment. Therefore, we speculate that β-defensins mediate a novel antiretroviral mechanism that contributes to prevention of oral HIV transmission in the oral cavity. Immunohistochemical data on hBD2 expression in oral mucosal tissue shows that hBD2 is constitutively expressed, forming a barrier layer across the epithelium in healthy subjects, while in HIV-positive subjects levels of hBD2 expression are dramatically diminished. This may predispose HIV-positive subjects to increased incidence of oral complications associated with HIV infection.

We have recently developed a candidate human immunodeficiency virus type 1 (HIV-1) vaccine model based on HIV-1 Pr55 ^gag virus-like particles (HIV-VLPs), produced in a baculovirus expression system and presenting a gp120 molecule from a Ugandan HIV-1 isolate of clade A (HIV-VLP _A s). The HIV-VLP _A s show the induction in BALB/c mice of systemic and mucosal neutralizing antibodies as well as cytotoxic T lymphocytes, by intraperitoneal as well as intranasal administration. In the present article, the effects of the baculovirus-expressed HIV-VLPs on human immature monocyte-derived dendritic cells (MDDCs) have been evaluated. The HIV-VLPs efficiently induce maturation and activation of MDDCs and are incorporated into MDDCs preferentially via an actin-dependent macropinocytosis and endocytosis. The HIV-VLP-activated MDDCs show enhanced Th1- and Th2-specific cytokine production, and the effects of HIV-VLPs on MDDCs are not mediated through Toll-like receptors 2 and 4 (TLR2 and -4) signaling. Finally, HIV-VLP-loaded MDDCs are able to induce a primary and secondary response in autologous human CD4 ⁺ T cells in an ex vivo immunization assay. Our results on the interaction and processing of baculovirus HIV-VLPs by MDDCs give an insight into the mechanisms underlying the immune response induced by HIV-VLP _A s in vivo.

Insulin resistance contributes to several disorders including type 2 diabetes and cardiovascular diseases. Carpachromene is a natural active compound that inhibits α-glucosidase enzyme. The aim of the present study is to investigate the potential activity of carpachromene on glucose consumption, metabolism and insulin signalling in a HepG2 cells insulin resistant model. A HepG2 insulin resistant cell model (HepG2/IRM) was established. Cell viability assay of HepG2/IRM cells was performed after carpachromene/metformin treatment. Glucose concentration and glycogen content were determined. Western blot analysis of insulin receptor, IRS1, IRS2, PI3k, Akt, GSK3, FoxO1 proteins after carpachromene treatment was performed. Phosphoenolpyruvate carboxykinase (PEPCK) and hexokinase (HK) enzymes activity was also estimated. Viability of HepG2/IRM cells was over 90% after carpachromene treatment at concentrations 6.3, 10, and 20 µg/mL. Treatment of HepG2/IRM cells with carpachromene decreased glucose concentration in a concentration- and time-dependant manner. In addition, carpachromene increased glycogen content of HepG2/IRM cells. Moreover, carpachromene treatment of HepG2/IRM cells significantly increased the expression of phosphorylated/total ratios of IR, IRS1, PI3K, Akt, GSK3, and FoxO1 proteins. Furthermore, PEPCK enzyme activity was significantly decreased, and HK enzyme activity was significantly increased after carpachromene treatment. The present study examined, for the first time, the potential antidiabetic activity of carpachromene on a biochemical and molecular basis. It increased the expression ratio of insulin receptor and IRS1 which further phosphorylated/activated PI3K/Akt pathway and phosphorylated/inhibited GSK3 and FoxO1 proteins. Our findings revealed that carpachromene showed central molecular regulation of glucose metabolism and insulin signalling via IR/IRS1/ PI3K/Akt/GSK3/FoxO1 pathway.

Cardiovascular disease is difficult to detect due to several risk factors, including high blood pressure, cholesterol, and an abnormal pulse rate. Accurate decision-making and optimal treatment are required to address cardiac risk. As machine learning technology advances, the healthcare industry’s clinical practice is likely to change. As a result, researchers and clinicians must recognize the importance of machine learning techniques. The main objective of this research is to recommend a machine learning-based cardiovascular disease prediction system that is highly accurate. In contrast, modern machine learning algorithms such as REP Tree, M5P Tree, Random Tree, Linear Regression, Naive Bayes, J48, and JRIP are used to classify popular cardiovascular datasets. The proposed CDPS’s performance was evaluated using a variety of metrics to identify the best suitable machine learning model. When it came to predicting cardiovascular disease patients, the Random Tree model performed admirably, with the highest accuracy of 100%, the lowest MAE of 0.0011, the lowest RMSE of 0.0231, and the fastest prediction time of 0.01 seconds.