Mechanisms of the Wnt Pathways as a Potential Target Pathway in Atherosclerosis

The proteins of the Wnt family are involved in a variety of physiological processes by means of several canonical and noncanonical signaling pathways. Wnt signaling has been recently identified as a major player in atherogenesis. In this review, we summarize the existing knowledge on the influence of various components of the Wnt signaling pathways on the initiation and progression of atherosclerosis and associated conditions. We used the PubMed database to search for recent papers on the involvement of the Wnt pathways in atherosclerosis. We used the combination of “Wnt” and “atherosclerosis” keywords to find the initial papers, and chose papers published after 2018. In the first section of the paper, we describe the general mechanisms of the Wnt signaling pathways and their components. The next section is dedicated to existing studies assessing the implication of Wnt signaling elements in different atherogenic processes, such as cholesterol retention, endothelial dysfunction, vascular inflammation, and atherosclerotic calcification of the vessels. Lastly, various therapeutic strategies based on interference with the Wnt signaling pathways are considered. We also compare the efficacy and availability of the proposed treatment methods. Wnt signaling can be considered a potential target in the treatment and prevention of atherosclerosis. Therefore, in this review, we reviewed evidences showing that wnt signaling is an important signal for developing appropriate treatment strategies for atherosclerosis.

Therapeutic effects of garlic in cardiovascular atherosclerotic disease / 中国天然药物

Garlic (Allium sativum) is a widely known medicinal plant, potential of which remains to be fully evaluated. Its wide-range beneficial effects appear to be relevant for treatment and prevention of atherosclerosis and related diseases. It is generally believed that garlic-based preparations are able to improve lipid profile in humans, inhibit cholesterol biosynthesis, suppress low density lipoprotein oxidation, modulate blood pressure, suppress platelet aggregation, lower plasma fibrinogen level and increase fibrinolytic activity, thus providing clinically relevant cardioprotective and anti-atherosclerotic effects. It is important to assess the level of evidence available for different protective effects of garlic and to understand the underlying mechanisms. This information will allow adequate integration of garlic-based preparations to clinical practice. In this review, we discuss the mechanisms of anti-atherosclerotic effects of garlic preparations, focusing on antihyperlipidemic, hypotensive, anti-platelet and direct anti-atherosclerotic activities of the medicinal plant. We also provide an overview of available meta-analyses and a number of clinical trials that assess the beneficial effects of garlic.

Treatment of advanced melanoma - A changing landscape / Tratamento de melanoma avançado - Um panorama em transformação

Summary Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.

Resumo Após décadas de ostracismo, os recentes avanços no tratamento do melanoma trouxeram uma nova realidade para pacientes, médicos e pesquisadores. Enquanto anticorpos monoclonais voltados a moléculas envolvidas na modulação da interação entre células do melanoma e do sistema imune consolidaram o uso da "imunoterapia", um melhor conhecimento acerca das aberrações genômicas envolvidas na carcinogênese do melanoma viabilizaram o desenvolvimento de inibidores da via mitogen-activated protein kinase pathway (MAPK), o que também resultou em ganhos significativos em taxas de resposta e sobrevida. Consequentemente, novas modalidades de tratamento foram aprovadas para uso clínico nos Estados Unidos e na Europa, incluindo os bloqueadores de correceptores imunes ipilimumabe, nivolumabe e pembrolizumabe, o herpesvírus oncolítico talimogene laherparepvec (T-VEC), e os agentes-alvo vemurafenibe, dabrafenibe, cobimetinibe e trametinibe. Nesse artigo, revisamos os resultados que trouxeram novas alternativas para a prática clínica e discutimos a incorporação desses avanços ao cuidado de pacientes no Brasil.

Comment on "Long-Term Effects of Diesel Exhaust Particles on Airway Inflammation and Remodeling in a Mouse Model" by Kim et al

No abstract available.

Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy.

Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium‑derived factor [PEDF]) in the vitreous of patients with proliferative diabetic retinopathy (PDR) and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods: Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control) were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein‑1 (MCP‑1), interleukin‑4 (IL‑4), IL‑6, IL‑8, IL‑10, IL‑17A, and secretory immunoglobulin A (sIgA) were simultaneously measured using enzyme‑linked immunoassay. Results: Vitreous levels of VEGF, PEDF, IL‑17A, IL‑6, IL‑8, IL‑4, and sIgA were significantly (Р < 0.05) higher in eyes with PDR compared to control. The concentration of VEGF was more than 17‑times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45‑times) compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Р < 0.05) positive correlations were observed between vitreous concentrations of VEGF and IL‑17А (r = 0.45), VEGF and IL‑8 (r = 0.48), VEGF and IL‑4 (r = 0.51), PEDF and IL‑17А (r = 0.48), PEDF and IL‑8 (r = 0.59), MCP‑1 and PEDF (r = 0.72), MCP‑1 and IL‑8 (r = 0.45), IL‑4 and IL‑17А (r = 0.65), IL‑4 and IL‑8 (r = 0.71), IL‑8 and IL‑17А (r = 0.59). Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

Sleep Forensics: a critical review of the literature and brief comments on the Brazilian legal situation / Medicina do sono Forense: uma revisao critica da literatura e breves comentarios sobre a situacao brasileira

Sleep medicine is a relatively new field among Medical Sciences. Its legal aspects are still obscure, either for lack of knowledge of the biological mechanisms underlying violent behaviour during sleep or the virtual absence of clear legal and uniformly accepted guidelines as to whether to punish or treat those disorders. An updated review of the pertinent literature was performed to determine the most prevalent pathological conditions involving violence and sleep and to identify their most common precipitating factors, attempting to provide some technical support to aid Brazilian medical-experts or assistants in preparing substantial and scientific-based reports in a legal environment.

A medicina do sono é um campo relativamente novo dentro das Ciências Médicas. Seus aspectos legais encontram-se ainda na obscuridade, seja por falta de conhecimento dos mecanismos biológicos do desenvolvimento dos transtornos de comportamento e da violência praticada em estados alterados de sono, seja por virtual ausência de previsão legal do binômio tratamento/punição. Realizamos revisão atualizada da literatura para determinar as condições patológicas mais prevalentes envolvendo violência e sono, identificar seus fatores precipitantes mais comuns e os critérios médico-legais que podem auxiliar eventuais médicos-peritos ou assistentes na elaboração de pareceres abalizados em âmbito legal.

Oplopanax elatus (Nakai) Nakai: chemistry, traditional use and pharmacology / 中国天然药物

Oplopanax elatus (Nakai) Nakai, a member of the ancient angiosperm plant family Araliaceae, is used for the treatment of different disorders in the medicine systems of China, Russia, and Korea, and was designated in Russia as a classical adaptogen. Despite extensive studies of classical adaptogens, there are comparatively few reports concerning the chemical composition and pharmacological effects of O. elatus in English. The plant is a potential source of saponins, flavonoids, anthraquinones, terpenes, and other active compounds. Experimental studies and clinical applications have indicated that O. elatus possesses a number of pharmacological activities, including adaptogenic, anti-convulsant, anti-diabetic, anti-fungal, anti-inflammatory, anti-oxidant, blood pressure modulating, and reproductive function effects. In this review, the chemistry, safety, and therapeutic potential of O. elatus are summarized and highlighted to encourage the further development of this plant.

Systematic review and meta-analysis of the interaction between Plasmodium falciparum and Plasmodium vivax in humans.

OBJECTIVES: This study aimed to quantify the interaction between Plasmodium falciparum and R vivax and the sources of heterogeneity between studies. METHODS: We systematically reviewed three databases: Medline (1966-2001), Embase (1980-2001) and CAB-health (1976-2001). Random effects meta-analysis was applied to the data of 62 selected populations. Meta-regression was used to assess the following potential sources of heterogeneity: age-group, presence of fever, continent, temporal and spatial span of studies, and endemicity level. RESULTS: The summary odds ratio (OR) between P. falciparum and P. vivax was 0.6 (95% CI: 0.49-0.79). The minimum and maximum observed ORs were 0.01 and 10.9, respectively, and the heterogeneity test was highly significant (tau2 = 0.92, p < 0.0001)--the ORs varied over a very wide range. The ORs in longer studies and in those from areas with higher prevalence yielded smaller, more strongly negative association. This is consistent with the idea that any difference in the species' temporal patterns should decrease the OR, and more so over longer periods of time. INTERPRETATION & CONCLUSION: Although such odds ratios between Plasmodium species may be partly due to missed mixed infections when reading blood slides, the negative association between the OR and prevalence supports the existence of biological interactions such as suppression or cross-immunity between species.

A survey on surgical site infection among cancer patients at Chong Hua Hospital

A retrospective descriptive study on the relative frequency of surgical site infection (SSI) among 235 operated cancer patients at Chong Hua Hospital was done covering the period from January 1991 up to May 1993. SSI occurred in 9.4 percent (22/235). There was a significant increase in SSI as the population became older (p=0.01). Dirty operations had a significantly higher infection rate of 50 percent (2/4) compared to 8.7 percent (20/211) for the rest (p=0.45). Clean operations had a significantly lower infection rate of 2.5 percent (3/121) compared to 16.7 percent (19/114) for the rest. There was no difference in SSI between early and late stage cancer cases. Operations in the alimentary tract had a significantly higher infection rate of 19.3 percent (11/57) compared to 6.4 percent (11/172) for operations on the other sites (p=0.004). Operations on solf tissues, breast and thyroid had a signifanctly lower rate of 4.6 percent (4/87) compared to 12.7 percent (18/142) for operations on other sites (p=0.045).(Author)

Characteristics of monoclonal antibodies reactive with human sperm and seminal plasma.

The characteristics of monoclonal antibodies developed against human spermatozoa are described. Out of 10 monoclonal antibodies 9 did not react in ELISA with human RBC, WBC, platelets, Raji cells nor mouse sperm. Four monoclonal antibodies reacted with monkey sperm and all 10 reacted with human seminal plasma. Monoclonal antibodies showed differential reactivity with pre- and post-capacitated sperm. Four monoclonal antibodies were able to agglutinate sperm whereas none of these were positive in sperm-immobilization assay. Interestingly, two monoclonal antibodies (MA-46 and MA-50) were able to block the attachment of pre-capacitated sperm to zona denuded hamster oocytes. MA-46 and MA-50 recognized in immunoblot spermatozoa antigens having apparent molecular weights of 14 and 20 K Da and greater than 200 K Da respectively. The monoclonal antibodies reported in this study will be useful in further delineating the spermatozoa antigens involved in regulation of fertility.

En busca de una vacuna para el control de la fertilidad / In search of a vaccine for fertility control

Se revisan diferentes procedimientos de investigación en relación a una vacuna contra la fertilidad. Se necesita mayor investigación al respecto. Una vacuna para el control de la fertilidad debe ser sometida a diversos juicios, desde los puntos de vista moral, político y religioso. Siempre se valorá la sobrepoblación, falta de recursos económicos, y el futuro de los países en desarrollo con alto índice de natalidad