Capsaicin Exerts Antitumor Activity in Mesothelioma Cells

Background/Objectives: Mesothelioma is an aggressive cancer with limited treatment options. Mesothelioma therapy often involves a multimodal approach including surgery, radiotherapy and chemotherapy. However, the prognosis for patients remains poor. Difficult diagnosis, late symptoms when the tumor is in an advanced stage and the onset of chemotherapy resistance make mesothelioma difficult to treat. For this reason, it is essential to discover new pharmacological approaches. Capsaicin (CAPS) is the active compound of chili peppers. Based on CAPS’s anticancer properties on various tumor lines and its chemo-sensitizing action on resistant cells, in this study, we evaluated the effects of CAPS on mesothelioma cells to assess its potential use in mesothelioma therapy. Methods: To evaluate antiproliferative effects of CAPS, we performed MTS assays on various mesothelioma cells, representative of all major mesothelioma subtypes. Transwell migration and wound-healing assays were used to examine the effect of CAPS on mesothelioma cell migration. We also determined the effects of CAPS on oncogenic signaling pathways by assessing the levels of AKT and MAPK activation. Results: In this study, we show that CAPS significantly reduces proliferation of both parental and cisplatin-resistant mesothelioma cells. CAPS promotes S-phase cell cycle arrest and inhibits lateral motility and migration of mesothelioma cells. Accordingly, CAPS suppresses AKT and ERK1/2 activation in MSTO-211H and NCI-H2052 cells. Our results support an antitumor effect of CAPS on cisplatin-resistant mesothelioma cells, suggesting that it may reduce resistance to cisplatin. Conclusions: Our results could pave the way for further studies to evaluate the use of CAPS for mesothelioma treatment

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidants, oncolytic virus, engineered exosomes, and natural products obtained from marine organisms that could pave the way for new therapeutic approaches for CML patients

Epicentral disruption of structural connectivity in Alzheimer’s disease.

AIMS:Neurodegenerative changes observed in Alzheimer's disease (AD) have been suggested to begin at the entorhinal cortex and hippocampus and then to propagate in a stereotypical fashion. Using diffusion-weighted imaging, we test whether disruption of structural connectivity in AD is centered on these "epicenters of disease". METHODS: Fifteen healthy controls, 14 amnestic mild cognitive impairment (aMCI), 13 mild, and 15 moderate patients with AD were enrolled. The percentages of affected connections directly linking to the epicenter (named first ring) and to nodes with topological distance 2 from the epicenter (named second ring) were calculated. RESULTS: For the group of aMCI patients, just 5.3% of the first ring (n.s.) and 2.9% of the second ring (n.s.) connections were affected. However, for mild AD there was disruption involving 20% of the first ring (P < 0.0001) and 10.3% of the second ring (P < 0.0001) connections. In the moderate AD group, a stronger effect was observed, with 38.0% of the first ring (P < 0.0001) connections and 17.9% of the second ring (P < 0.0001) connections affected. CONCLUSION: Our results favor an epicentral disruption of structural connectivity in aMCI and AD around entorhinal and hippocampal regions, consistent with the transneuronal spread hypothesis

The Oncolytic Caprine Herpesvirus 1 (CpHV-1) Induces Apoptosis and Synergizes with Cisplatin in Mesothelioma Cell Lines: A New Potential Virotherapy Approach.

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer, against which no curative modalities exist. Oncolytic virotherapy is a promising therapeutic approach, for which MM is an ideal candidate; indeed, the pleural location provides direct access for the intra-tumoral injection of oncolytic viruses (OVs). Some non-human OVs offer advantages over human OVs, including the non-pathogenicity in humans and the absence of pre-existing immunity. We previously showed that caprine herpesvirus 1 (CpHV-1), a non-pathogenic virus for humans, can kill different human cancer cell lines. Here, we assessed CpHV-1 effects on MM (NCI-H28, MSTO, NCI-H2052) and non-tumor mesothelial (MET-5A) cells. We found that CpHV-1 reduced cell viability and clonogenic potential in all MM cell lines without affecting non-tumor cells, in which, indeed, we did not detect intracellular viral DNA after treatment. In particular, CpHV-1 induced MM cell apoptosis and accumulation in G0/G1 or S cell cycle phases. Moreover, CpHV-1 strongly synergized with cisplatin, the drug currently used in MM chemotherapy, and this agent combination did not affect normal mesothelial cells. Although further studies are required to elucidate the mechanisms underlying the selective CpHV-1 action on MM cells, our data suggest that the CpHV-1-cisplatin combination could be a feasible strategy against MM

Hepatitis E and Potential Public Health Implications from a One-Health Perspective: Special Focus on the European Wild Boar (Sus scrofa)

The hepatitis E virus (HEV) has become increasingly important in recent years in terms of risk for public health, as the main causative agent of acute viral hepatitis. It is a foodborne disease transmitted to humans through the consumption of contaminated water or contaminated food. Human-to-human transmission is sporadic and is linked to transfusions or transplants. The main reservoirs of the hepatitis E virus are domestic pigs and wild boars, although, compared to pigs, wild boars represent a lesser source of risk since their population is smaller and the consumption of derived products is more limited. These peculiarities often make the role of the wild boar reservoir in the spread of the disease underestimated. As a public health problem that involves several animal species and humans, the management of the disease requires an interdisciplinary approach, and the concept of “One Health” must be addressed. In this direction, the present review intends to analyze viral hepatitis E, with a particular focus on wild boar. For this purpose, literature data have been collected from different scientific search engines: PubMed, MEDLINE, and Google scholar, and several keywords such as “HEV epidemiology”, “Extrahepatic manifestations of Hepatitis E”, and “HEV infection control measures”, among others, have been used. In the first part, the manuscript provides general information on the disease, such as epidemiology, transmission methods, clinical manifestations and implications on public health. In the second part, it addresses in more detail the role of wild boar as a reservoir and the implications related to the virus epidemiology. The document will be useful to all those who intend to analyze this infectious disease from a “One-Health” perspective

Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells

Introduction: Diffuse pleural mesothelioma (DPM) of the pleura is a highly aggressive and treatment-resistant cancer linked to asbestos exposure. Despite multimodal treatment, the prognosis for DPM patients remains very poor, with an average survival of 2 years from diagnosis. Cisplatin, a platinum-based chemotherapy drug, is commonly used in the treatment of DPM. However, the development of resistance to cisplatin significantly limits its effectiveness, highlighting the urgent need for alternative therapeutic strategies. New selective inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have shown promise in various malignancies by inhibiting cell cycle progression and suppressing tumor growth. Recent studies have indicated the potential of abemaciclib for DPM therapy, and a phase II clinical trial has shown preliminary encouraging results. Methods: Here, we tested abemaciclib, palbociclib, and ribociclib on a panel of DPM cell lines and non-tumor mesothelial(MET-5A) cells. Results: Specifically, we focused on abemaciclib, which was the mosteffective cytotoxic agent on all the DPM cell lines tested. Abemaciclib reduced DPM cell viability, clonogenic potential, and ability to grow as three-dimensional (3D) spheroids. In addition, abemaciclib induced prolonged effects, thereby impairing second-generation sphere formation and inducing G0/G1 arrest and apoptosis/ necrosis. Interestingly, single silencing of RB family members did not impair cell response to abemaciclib, suggesting that they likely complement each other in triggering abemaciclib’s cytostatic effect. Interestingly, abemaciclib reduced the phosphorylation of AKT, which is hyperactive in DPM and synergized with the pharmacological AKT inhibitor (AKTi VIII). Abemaciclib also synergized with cisplatin and reduced the viability of DPM cells with acquired resistance to cisplatin. Discussion: Overall, our results suggest that CDK4/6 inhibitors alone or in combination with standard of care should be further explored for DPM therapy

Teratoma quístico mediastinal. Reporte de dos casos.

Los teratomas extragonadales son más frecuentes en la región sacro coccígea y en el mediastino. En el presente trabajo se reportan dos casos de teratomas mediastinales que simularon procesos infecciosos. Estos casos se presentaron en el primer semestre del año 2000 y representan la casuística del Instituto Autónomo Hospital Universitario de los Andes (IAHULA) en un periodo de diez años (1996-2005). Dos pacientes pediátricos de 10 años y 8 meses de edad respectivamente, ingresaron con los diagnósticos de absceso pulmonar y bronconeumonía con manifestaciones clínicas de tos, disnea, malestar general y fiebre. Se realizó toracotomia posterolateral con resección total de la neoplasia. En ambos casos la pieza quirúrgica correspondió a masa tumoral multiloculada, con espacios ocupados por material sebáceo, pelos y sangre. Histológicamente se demostró la presencia de células neoplásicas parenquimatosas derivadas de más de un estrato germinal. Los teratomas mediastinales son poco frecuente durante la infancia, pero el diagnóstico debe ser considerado en niños con sintomatología respiratoria. El diagnóstico definitivo se realizó después del examen morfológico de la pieza quirúrgica. El diagnóstico microscópico fue sencillo y no requirió de técnicas histológicas adicionales. El tratamiento de elección en estos casos es quirúrgico. La evolución de los pacientes cinco años después es satisfactoria

Health-Promoting and Health-Risk Behaviors: Theory-Driven Analyses of Multiple Health Behavior Change in Three International Samples

Background: Co-occurrence of different behaviors was investigated using the theoretical underpinnings of the Transtheoretical Model, the Theory of Triadic Influence and the concept of Transfer. Purpose: To investigate relationships between different health behaviors' stages of change, how behaviors group, and whether study participants cluster in terms of their behaviors. Method: Relationships across stages for different behaviors were assessed in three studies with N = 3,519, 965, and 310 individuals from the USA and Germany by telephone and internet surveys using correlational analyses, factor analyses, and cluster analyses. Results: Consistently stronger correlations were found between nutrition and physical activity (r = 0.16-0.26, p < 0.01) than between non-smoking and nutrition (r = 0.08-0.16, p < 0.03), or non-smoking and physical activity (r = 0.01-0.21). Principal component analyses of investigated behaviors indicated two factors: a "health-promoting" factor and a "health-risk" factor. Three distinct behavioral patterns were found in the cluster analyses. Conclusion: Our results support the assumption that individuals who are in a higher stage for one behavior are more likely to be in a higher stage for another behavior as well. If the aim is to improve a healthy lifestyle, success in one behavior can be used to facilitate changes in other behaviors--especially if the two behaviors are both health-promoting or health-risky. Moreover, interventions should be targeted towards the different behavioral patterns rather than to single behaviors. This might be achieved by addressing transfer between behaviors