Activation of Toll-like receptor 2 increases macrophage resistance to HIV-1 infection

Patients infected with HIV-1, the etiological agent of AIDS, have increased intestinal permeability, which allows for the passage of microbial products, including Toll-like receptor (TLR) ligands, into circulation. The exposure of HIV-1-infected cells to certain TLR agonists affects viral replication, but studies associating viral production with the activation of TLR2 in HIV-1-infected cells are rare and controversial. Here, we report that the TLR2 ligands Zymosan and Pam3CSK4 potently inhibit HIV-1 replication in acutely infected monocyte-derived macrophages and the exposure to TLR2 ligands prior to infection renders macrophages refractory to HIV-1 production. Macrophage treatment with Pam3CSK4 did not change the cellular expression of the HIV-1 entry receptors CD4 and CCR5. Both TLR2 ligands increased the macrophage production of β-chemokines and IL-10, and the blockage of these soluble factors prevented the inhibitory effect of TLR2 activation on HIV-1 replication. Our findings show that the direct engagement of TLR2 in HIV-1-infected macrophages increase cellular resistance to HIV-1 infection, and that controlling HIV-1 replication with agonists for TLR2 might have implications for the development of antiretroviral therapies.     

Psychological and relational factors in ESRD hemodialysis treatment in an underserved community

ObjectiveThe researchers investigated the association of depression with treatment adherence, and examined the possible moderating roles of social support and of the physician-patient working alliance (PPWA) on treatment adherence, satisfaction with treatment, and quality of life.MethodsThe current study sampled ninety-five patients with End Stage Renal Disease who were receiving outpatient hemodialysis (HD) treatment.ResultsFindings indicated that higher levels of depression were significantly associated with lower ratings of adherence, quality of life, and social support. In contrast, higher levels of social support and of the PPWA were significantly associated with higher ratings of adherence, satisfaction with treatment, and quality of life. Analyses of moderation showed no effect for PPWA between depression and adherence, satisfaction, or quality of life; however, there was a significant moderation effect for social support.ConclusionThere are mild but significant associations between PPWA and social support. Positive associations between the PPWA and social support on adherence, satisfaction, and quality of life indicate that each one, PPWA and social support, plays its own role on patients’ experiences of and behavior in treatment. Affective social support significantly limits the negative influence of depression on adherence.Practice ImplicationsAssessment of depression and social support is essential in hemodialysis treatment.     

Are there gender differences in left ventricular remodeling after myocardial infarction in rats?

Objective

An unclear issue is whether gender may influence at cardiac remodeling after myocardial infarction (MI). We evaluated left ventricle remodeling in female and male rats post-MI.

Methods

Rats were submitted to anterior descending coronary occlusion. Echocardiographic evaluations were performed on the first and sixth week post-occlusion to determine myocardial infarction size and left ventricle systolic function (FAC, fractional area change). Pulsed Doppler was applied to analyze left ventricle diastolic function using the following parameters: E wave, A wave, E/A ratio. Two-way ANOVA was applied for comparisons, complemented by the Bonferroni test. A P≤=0.05 was considered significant.

Results

There were no significant differences between genders for morphometric parameters on first (MI [Female (FE): 44.0±5.0 vs. Male (MA): 42.0±3.0%]; diastolic [FE: 0.04±0.003 vs. MA: 0.037±0.005, mm/g] and systolic [FE: 0.03±0.0004 vs. MA: 0.028±0.005, mm/g] diameters of left ventricle) and sixth (MI [FE: 44.0±5.0 vs. MA: 42.0±3.0, %]; diastolic [FE: 0.043±0.01 vs. MA: 0.034±0.005, mm/g] and systolic [FE: 0.035±0.01 vs. MA: 0.027±0.005, mm/g] of LV) week. Similar findings were reported for left ventricle functional parameters on first (FAC [FE: 34.0±6.0 vs. MA: 32.0±4.0, %]; wave E [FE: 70.0±18.0 vs. MA: 73.0±14.0, cm/s]; wave A [FE: 20.0±12.0 vs. MA: 28.0±13.0, cm/s]; E/A [FE: 4.9±3.4 vs. MA: 3.3±1.8]) and sixth (FAC [FE: 29.0±7.0 vs. MA: 31.0±7.0, %]; wave E [FE: 85.0±18.0 vs. MA: 87.0±20.0, cm/s]; wave A [FE: 20.0±11.0 vs. MA: 28.0±17.0, cm/s]; E/A [FE: 6.2±4.0 vs. MA: 4.6±3.4]) week.

Conclusion

Gender does not influence left ventricle remodeling post-MI in rats.     

Entamoeba moshkovskii perspectives of a new agent to be considered in the diagnosis of amebiasis

During the last decade Entamoeba moshkovskii has become relevant given its capacity to infect humans, especially when considering that it is morphologically indistinguishable from E. histolytica. For a long time, E. moshkovskii was considered as a free living amoeba, but in the last decade it has been demonstrated that E. moshkovskii can infect humans and can be found more frequently in regions where amebiasis shows high prevalence values, becoming a challenge to differentiate it from the E. histolytica/E. dispar complex. Recently there have been studies that raise the possibility that E. moshkovskii could be a pathogenic species, as there are reports in different countries that associated this infection with gastrointestinal symptoms even though others have described it as a non pathogenic species. For this reasons, both clinical and epidemiological studies are required.     

Ankle-brachial index as a predictor of coronary disease events in elderly patients submitted to coronary angiography

OBJECTIVES:

To correlate the importance of the ankle-brachial index in terms of cardiovascular morbimortality and the extent of coronary arterial disease amongst elderly patients without clinical manifestations of lower limb peripheral arterial disease.

METHODS:

We analyzed prospective data from 100 patients over 65 years of age with coronary arterial disease, as confirmed by coronary angiography, and with over 70% stenosis of at least one sub-epicardial coronary artery. We measured the ankle-brachial index immediately after coronary angiography, and a value of <0.9 was used to diagnose peripheral arterial disease.

RESULTS:

The patients'' average age was 77.4 years. The most prevalent risk factor was hypertension (96%), and the median late follow-up appointment was 28.9 months. The ankle-brachial index was <0.9 in 47% of the patients, and a low index was more prevalent in patients with multiarterial coronary disease compared to patients with uniarterial disease in the same group. Using a bivariate analysis, only an ankle-brachial index of <0.9 was a strong predictive factor for cardiovascular events, thereby increasing all-cause deaths and fatal and non-fatal acute myocardial infarctions two- to three-fold.

CONCLUSION:

In elderly patients with documented coronary disease, a low ankle-brachial index (<0.9) was associated with the severity and extent of coronary arterial disease, and in late follow-up appointments, a low index was correlated with an increase in the occurrence of major cardiovascular events.     

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis,DNA binding and molecular docking

Multidrug resistance to chemotherapy is a critical health problem associated with mutation of the therapeutic target. Therefore, the development of anticancer agents remains a challenge to overcome cancer cell resistance. Herein, a new series of quinazoline-based pyrimidodiazepines 16a–g were synthesized by the cyclocondensation reaction of 2-chloro-4-anilinoquinazoline-chalcones 14a–g with 2,4,5,6-tetraaminopyrimidine. All quinazoline derivatives 14a–g and 16a–g were selected by the U.S. National Cancer Institute (NCI) for testing their anticancer activity against 60 cancer cell lines of different panels of human tumors. Among the tested compounds, quinazoline-chalcone 14g displayed high antiproliferative activity with GI₅₀ values between 0.622–1.81 μM against K-562 (leukemia), RPMI-8226 (leukemia), HCT-116 (colon cancer) LOX IMVI (melanoma), and MCF7 (breast cancer) cancer cell lines. Additionally, the pyrimidodiazepines 16a and 16c exhibited high cytostatic (TGI) and cytotoxic activity (LC₅₀), where 16c showed high cytotoxic activity, which was 10.0-fold higher than the standard anticancer agent adriamycin/doxorubicin against ten cancer cell lines. COMPARE analysis revealed that 16c may possess a mechanism of action through DNA binding that is similar to that of CCNU (lomustine). DNA binding studies indicated that 14g and 16c interact with the calf thymus DNA by intercalation and groove binding, respectively. Compounds 14g, 16c and 16a displayed strong binding affinities to DNA, EGFR and VEGFR-2 receptors. None of the active compounds showed cytotoxicity against human red blood cells.

A new series of quinazoline-based chalcones and pyrimidodiazepines were tested against 60 human tumor cell lines.     

World Workshop on Oral Medicine VII: Targeting the microbiome for oral medicine specialists—Part 1. A methodological guide

Advances in high‐throughput sequencing technologies have allowed for a rapid increase in knowledge about the human microbiome in both healthy and diseased states, which is expected to increase our understanding of multifactorial diseases. The World Workshop on Oral Medicine VII chose the microbiome as one of its topics of focus. Part 1 of this review provides updated knowledge in the field of microbiome research, describes the advantages and disadvantages of currently available sequencing technologies, and proposes a seven‐step “recipe” for designing and performing studies that is supported by contemporary evidence. Part 2 of this review in a companion paper discusses the results of high‐throughput sequencing studies published to date on the microbiota associated with oral mucosal diseases. The goal of this collective enterprise is to encourage more oral medicine specialists to become engaged in multidisciplinary collaborations to investigate the role of the microbiome in relation to oral diseases, which could potentially lead to enhanced diagnosis, risk assessment and treatment of these patients.