Applications of Modified Mesenchymal Stem Cells as Targeted Systems against Tumor Cells.

Combined gene and cell therapy are promising strategies for cancer treatment. Given the complexity of cancer, several approaches are actively studied to fight this disease. Using mesenchymal stem cells (MSCs) has demonstrated dual antitumor and protumor effects as they exert massive immune/regulatory effects on the tissue microenvironment. MSCs have been widely investigated to exploit their antitumor target delivery system. They can be genetically modified to overexpress genes and selectively or more efficiently eliminate tumor cells. Current approaches tend to produce more effective and safer therapies using MSCs or derivatives; however, the effect achieved by engineered MSCs in solid tumors is still limited and depends on several factors such as the cell source, transgene, and tumor target. This review describes the progress of gene and cell therapy focused on MSCs as a cornerstone against solid tumors, addressing the different MSC-engineering methods that have been approached over decades of research. Furthermore, we summarize the main objectives of engineered MSCs against the most common cancers and discuss the challenges, limitations, risks, and advantages of targeted treatments combined with conventional ones.

A multicenter study of the efficacy and safety of treatments (endovascular or conservative) in small intracranial aneurysms in Colombia.

BACKGROUND: The registry of cerebral aneurysms <5 mm, known for their low risk of rupture, is significant, given their high incidence globally. Our study aimed to identify, in small aneurysms (<5 mm), the potential morphological characteristics, risk factors that can predict the risk of rupture, and the risk or benefit of treating them with endovascular or conservative treatment in ruptured and unruptured intracranial aneurysms. METHODS: The medical records of patients with cerebral aneurysms <5 mm were retrospectively reviewed between January 2014 and December 2022 at two neurovascular centers in Colombia. We evaluated clinical and angiographic outcomes using statistical tests. RESULTS: Two hundred fifty-six patients (425 intracranial aneurysms) were registered in the database. Two hundred and seventy-five IA were treated with endovascular treatment: 70 ruptured aneurysms and 205 unruptured aneurysms. One hundred fifty intracranial aneurysms underwent conservative treatment (follow-up). Women accounted for 82.1% of cases. Most cases were incidentally diagnosed (83.5%). After a year of follow-up, 87.3% of unruptured and 67.1% of ruptured intracranial aneurysms had an mRS 0-2. In the Raymond-Roy occlusion classification, among 101 unruptured intracranial aneurysms embolized were 53 cases class I, and among 66 ruptured intracranial aneurysms embolized, 67.1% were class I. CONCLUSION: Endovascular therapy for aneurysms <5 mm appears to be a technically feasible treatment, with satisfactory occlusion rates and few re-treatments at the 12-month follow-up. The complication rates were similar to those reported in studies on small aneurysms.

Geographic Relocation in Response to Parents' Health Shocks: Who Moves and How Close?

Objective: This article examines how parent-child geographic proximity changes around the onset of parental health shocks in the United States. Differences in the likelihood of moving closer across social groups are also investigated. Background: Adult children often care for older parents with health problems, but this requires relatively close proximity. As families are becoming smaller and many adult children live away from their parents, it is unclear how responsive families will be to older adults' health problems. Method: We estimate a series of fixed effects and event study models on data from the Health and Retirement Study (2004-2018) to assess changes in parent-child proximity after parents' first onset of cognitive impairment and functional limitations. Results: We find robust evidence that parents and children tend to stay close or move closer to each other in response to parent's health declines. Moves occur immediately and in subsequent waves after the onset of health shocks. Reductions in parent-child distance are consistently larger among mother-daughter dyads, dyads without spouses or multiple children, and non-Hispanic white families. Conclusion: The geographic availability of adult children to provide care is responsive to parents' needs. After the onset of a serious health condition, most older adults have a spouse or child living close enough to provide care. Parents' and children's lives are dynamically linked, and either or both may relocate to facilitate care.

A Study on the Efficacy and Safety of Pipeline Shield Stents and Nonmodified Surface Flow-Diverting Stents in Patients with Intracranial Aneurysms.

BACKGROUND: Few studies have compared the Pipeline Shield stents with previous generations of flow-diverting stents (FDSs) for the treatment of unruptured intracranial aneurysms. This study aimed to evaluate the efficacy and safety of Pipeline Shield stents and FDSs without modified surfaces. METHODS: The present evaluation is a retrospective cohort study of patients endovascularly treated with Pipeline Shield stents or FDSs without modified surfaces for unruptured intracranial aneurysms between January 2014 and June 2022. The data analyzed were obtained from the anonymized database of our institution's interventional radiology service. RESULTS: A total of 147 patients with 155 unruptured intracranial aneurysms were included. Of the 155 aneurysms, 96 were treated with Pipeline Shield stents and 59 with FDSs without modified surfaces. The aneurysms treated with Pipeline Shield stents had higher 6-month (O'Kelly-Marotta [OKM] D; 87.5% vs. 71.4%; P = 0.025) and 1-year (OKM D; 82.5% vs. 63.0%; P = 0.047) occlusion rates than the aneurysms treated using FDSs without modified surfaces. No differences between the devices were found at the 1-year follow-up in the incidence of ischemic stroke (P = 0.939) or hemorrhagic complications (P = 0.559). CONCLUSIONS: Pipeline Shield stents demonstrated superior complete occlusion rates (OKM D) at both the 6-month and the 1-year follow-up assessments compared with nonmodified surface FDSs. No significant differences were found in the safety profiles between the 2 types of stents with regard to thromboembolic complications and ischemic events. Further research with larger study populations is necessary to validate these findings.

Hitting closer to home: State policies' impacts on health by race and legal status.

While the proliferation of inclusionary and exclusionary state policies has led to an increasingly heterogeneous patchwork of state climates, state policy and the climates they create have become increasingly important for health outcomes. We leverage the heterogeneity across state policy climates to test the relationship between state-level policies and health inequality across the US. We include 24 state policies related to public health and safety, immigration enforcement, integration, and healthcare to capture the state climate. Using the Survey of Income and Program Participation (SIPP), a nationally representative study of households in the U.S., we estimate multilevel regression models to assess the relationship between state policy climate and healthcare utilization. We further examine differential effects of the policy climate across various vulnerable groups, by examining differences by citizenship status and race. We find that more exclusionary policies may be detrimental to healthcare utilization for all residents regardless of race and legal status- but ultimately racial minorities and noncitizens see the greatest benefits from inclusive policy climates.

Racial and ethnic diversity in global neuroscience clinical trials.

Background: Despite efforts to increase diversity in neuroscience trials, racial and ethnic minority groups remain underrepresented. Disparities in clinical trial participation could reflect unequal opportunities to participate and may contribute to decreased generalizability of findings and failure to identify important differences in efficacy and safety outcomes. Methods: We retrospectively reviewed the F. Hoffmann-La Roche database for global, multicenter, neuroscience clinical trials from February 2016 to February 2021 and summarized and stratified race and ethnicity distributions by clinical trial therapeutic area and by country. These data were then compared to national population data for each study's targeted age group (available for studies conducted in the US, Canada, and the UK). The underrepresentation or overrepresentation of each racial and ethnic group was summarized. Results: The analysis population included 8015 participants from 47 countries. Globally, 85.6 % of participants were White, 7.1 % were Asian, 1.6 % were Black, 1.3 % were American Indian or Alaska Native, less than 0.1 % were Native Hawaiian or other Pacific Islander, 0.7 % were of multiple races, and 3.6 % were of other/unknown race. White individuals predominated in all but one trial. Black individuals were underrepresented in all trials but one. Asian individuals were overrepresented in approximately 20 % of trials. In the US, 7.3 % of participants were of Hispanic or Latino ethnicity vs 16.4 % of the US population. Conclusion: The findings and learnings from this summary and analysis demonstrate the need for continued awareness and new approaches in designing studies that reflect population diversity.

The Changing Demography of Late-Life Family Caregiving: A Research Agenda to Understand Future Care Networks for an Aging U.S. Population.

Repeated claims that a dwindling supply of potential caregivers is creating a crisis in care for the U.S. aging population have not been well-grounded in empirical research. Concerns about the supply of family care do not adequately recognize factors that may modify the availability and willingness of family and friends to provide care to older persons in need of assistance or the increasing heterogeneity of the older population. In this paper, we set forth a framework that places family caregiving in the context of older adults' care needs, the alternatives available to them, and the outcomes of that care. We focus on care networks, rather than individuals, and discuss the demographic and social changes that may alter the formation of care networks in the future. Last, we identify research areas to prioritize in order to better support planning efforts to care for the aging U.S. population.

Safety and Efficacy of Endovascular Coils and Non-Flow-Diverting Stents for Management of Unruptured Intracranial Aneurysms: A Location-Specific Outcomes Analysis.

INTRODUCTION: The relationship between the anatomical location of an unruptured saccular aneurysm, the efficacy, and the potential complications associated with coil and non-flow-diverting stents remains poorly documented. Therefore, the aim of this study is to evaluate the efficacy and safety of endovascular treatment based on the anatomical position of the unruptured intracranial aneurysm (UIA). METHODS: A retrospective cohort study was conducted using an anonymized database of patients who underwent endovascular therapy for UIAs between 2014 and 2021. RESULTS: A total of 138 patients with 147 UIAs were included. Immediate Raymond-Roy occlusion class I or II was achieved in 99.2% of patients in all anatomical locations, with a 96.2% occlusion rate at the 12-month follow-up. Complications occurred more frequently in the anterior cerebral artery (35%) and internal carotid artery in its ophthalmic segment (25%). However, the difference was not statistically significant. CONCLUSIONS: Our study shows that endovascular treatment with stents and coils is effective and safe for managing UIAs in various anatomical locations. The incidence of thromboembolic complications was significantly higher for UIAs located in the anterior cerebral artery.

Bioactive Compounds of Dietary Origin and Their Influence on Colorectal Cancer as Chemoprevention.

Colorectal cancer (CRC) is one of the most common causes of death and the third most diagnosed cancer worldwide. The tumor microenvironment and cancer stem cells participate in colorectal tumor progression and can dictate malignancy. Nutrition status affects treatment response and the progression or recurrence of the tumor. This review summarizes the main bioactive compounds against the molecular pathways related to colorectal carcinogenesis. Moreover, we focus on the compounds with chemopreventive properties, mainly polyphenols and carotenoids, which are highly studied dietary bioactive compounds present in major types of food, like vegetables, fruits, and seeds. Their proprieties are antioxidant and gut microbiota modulation, important in the intestine because they decrease reactive oxygen species and inflammation, both principal causes of cancer. These compounds can promote apoptosis and inhibit cell growth, proliferation, and migration. Combined with oncologic treatment, a sensitization to first-line colorectal chemotherapy schemes, such as FOLFOX and FOLFIRI, is observed, making them an attractive and natural support in the oncologic treatment of CRC.

Oxaliplatin Enhances the Apoptotic Effect of Mesenchymal Stem Cells, Delivering Soluble TRAIL in Chemoresistant Colorectal Cancer.

A key problem in colorectal cancer (CRC) is the development of resistance to current therapies due to the presence of cancer stem cells (CSC), which leads to poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein that activates apoptosis in cancer cells through union with TRAIL death receptors. Cell therapies as delivery systems can produce soluble TRAIL (sTRAIL) and full-length TRAIL (flTRAIL), showing a high capacity to produce apoptosis in vitro and in vivo assays. However, the apoptotic activity of TRAIL as monotherapy had limitations, so it is important to explore other ways to enhance susceptibility to TRAIL. This study evaluated the cytotoxic and proapoptotic activity of soluble TRAIL overexpressed by mesenchymal stem cells (MSC) in an oxaliplatin-resistant CRC cell line. Bone marrow-MSC were lentiviral transduced for soluble TRAIL expression. DR5 death receptor expression was determined in Caco-2 and CMT-93 CRC cell lines. Sensitivity to first-line chemotherapies and recombinant TRAIL was evaluated by half-maximal inhibitory concentrations. Cytotoxic and proapoptotic activity of soluble TRAIL-MSC alone and combined with chemotherapy pre-treatment was evaluated using co-cultures. Caco-2 and CMT-93 cell lines expressed 59.08 ± 5.071 and 51.65 ± 11.99 of DR5 receptor and had IC50 of 534.15 ng/mL and 581.34 ng/mL for recombinant murine TRAIL (rmTRAIL), respectively. This finding was classified as moderate resistance to TRAIL. The Caco-2 cell line showed resistance to oxaliplatin and irinotecan. MSC successfully overexpressed soluble TRAIL and induced cancer cell death at a 1:6 ratio in co-culture. Oxaliplatin pre-treatment in the Caco-2 cell line increased the cell death percentage (50%) and apoptosis by sTRAIL. This finding was statistically different from the negative control (p < 0.05), and activity was even higher with the oxaliplatin-flTRAIL combination. Thus, oxaliplatin increases apoptotic activity induced by soluble TRAIL in a chemoresistant CRC cell line.

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2022 THESIS questionnaire survey of members of the Latin American Thyroid Society (LATS).

PURPOSE: Inconsistencies in the medical management of hypothyroidism have been reported between endocrinologists in different countries. This study aimed to identify the attitudes of Latin America thyroid specialists towards the use of thyroid hormones. METHODS: Online survey of members of the Latin America Thyroid Society. RESULTS: 81/446 (18.2%) completed the questionnaire. Levothyroxine (LT4) was the initial treatment of choice for all respondents. 56.8% would consider LT4 use in biochemically euthyroid patients: infertile women with elevated anti-thyroid antibodies (46.9%), resistant depression (17.3%) and growing goiter (12%). Most respondents preferred tablets (39.5%) over liquid formulations (21.0%) or soft gel capsules (22.2%) and would not consider switching formulations in patients with persistent symptoms. 39.5% would never use LT4 + liothyronine (LT3) combination therapy in symptomatic euthyroid patients, due to low quality evidence for benefit. 60.5% reported that persistence of symptoms despite normal TSH is rare (below 5% of patients) and its prevalence has been stable over the last five years. Psychosocial factors (84.0%), comorbidities (86.4%) and the patient unrealistic expectation (72.8%) were considered the top three explanations for this phenomenon. CONCLUSION: LT4 tablets is the treatment of choice for hypothyroidism. A significant proportion of respondents would use LT4 in some groups of euthyroid individuals, contrasting the recommendations of the major clinical practice guideline indications. LT4 + LT3 combination treatment in euthyroid symptomatic patients was considered by nearly 50%. Practices based on weak or absent evidence included use of thyroid hormones for euthyroid subjects by 56.8% of respondents and use of LT4 + LT3 treatment by 60.5% of respondents for patients with persistent symptoms. In contrast to many European countries, LATS respondents report a low and unchanged proportion of dissatisfied patients over the last five years.

Comercio ilegal de medicamentos, problemática enfocada en puntos de distribución y destrucción: unidades de eliminación de medicamentos e insumos / Illegal trade in medicines, problems focused on points of distribution and destruction: units for the disposal of medicines and supplies

Introducción: La falsificación y/o adulteración de medicamentos es un problema de salud pública el cual cada día se ve más reflejado en el país; una forma de evitarlo ya sea en mínima escala, es la correcta utilización de las unidades de eliminación de medicamentos e insumos, ayudando así a una eficaz desnaturalización y destrucción de estos.Objetivo General:Reconocer la importancia de la prevención del comercio ilegal de medicamentos mediante la utilización de las unidades de eliminación de medicamentos e insumos, en las etapas de comercialización y destrucción del producto, en los municipios de Santiago de Cali, La Unión y Jamundí en el Departamento del Valle del Cauca.Objetivos Específicos:•Medir el grado de conocimiento de las unidades de eliminación de medicamentos e insumos en cuanto a su funcionalidad e impacto en la población de Santiago Cali y en el municipio de La Unión Valle.•Analizar la incidencia de hallazgos de medicamentos en el material de reciclaje y su nivel de comercialización en Santiago de Cali y Jamundí.Método:Se realizó un estudio descriptivo- comparativo, de corte transversal, con enfoque cuantitativo que incluyó una muestra de 171 personas del municipio de Santiago de Cali y 89 personas en el municipio de La Unión Valle; una muestra de 21 recicladores del municipio de Santiago de Cali y 20 recicladores del municipio de Jamundí. El estudio fue realizado entre octubre y noviembre del 2022. Se utilizaron dos cuestionarios validados, diligenciados uno de forma virtual (grupo A) y otro de forma presencial (grupo B), el cual fue desarrollado de forma voluntaria.Resultados: Respecto al grupo de personas encuestadas en el grupo A, 45 que equivalen al 26.3% del universo de la población encuestada en Cali tienen conocimiento de las unidades de eliminación de medicamentos e insumos, 126 personas que equivalen al 73.7% no tienen conocimiento acerca del mismo.(AU)

Introduction: Counterfeiting and/or adulteration of medicines is a public health problem which is increasingly reflected in the country; One way to avoid it, whether on a small scale, is the correct use of the blue dot, thus helping to effectively denature and destroy them.General Objective: Recognize the importance of preventing the illegal trade of medicines using the blue point, in the stages of commercialization and destruction of the product, in the municipalities of Santiago de Cali, La Unión and Jamundí in the Department of Valle del Cauca.Specific Objectives: Measure the degree of knowledge of the blue dot in terms of its functionality and impact on the population of Santiago Cali and the municipality of La Uniòn Valle.Analyze the incidence of drug display in recycling material and its level of commercialization in Santiago de Cali and Jamundi.Method: A descriptive-comparative, cross-sectional study was conducted, with a quantitative approach that included a sample of 171 people from the municipality of Santiago de Cali and eighty-nine people from the municipality of La Union Valle, a sample of twenty-one recyclers from the municipality of Santiago de Cali and twenty recyclers from the municipality of Jamundí. The study was conducted between October and November 2022. Two validated questionnaires were used, one completed online (group A) and the other in person (group B), which was developed voluntarily.Results: Regarding the group of people surveyed in group A, 45, equivalent to 26.3% of the universe of the population surveyed in Cali, are aware of the blue dot, while 126 people, equivalent to 73.7%, are unaware of it. In Unión Valle, 14 people, equivalent to 15.7%, know about the blue dot, while 75 people, equivalent to 84.3%, are unaware of it.(AU)

Disease severity and mortality in Alzheimer's disease: an analysis using the U.S. National Alzheimer's Coordinating Center Uniform Data Set.

BACKGROUND: Evidence on the relative risk of death across all stages of Alzheimer's disease (AD) is lacking but greatly needed for the evaluation of new interventions. We used data from the Uniform Data Set (UDS) of the National Alzheimer's Coordinating Center (NACC) to assess the expected survival of a person progressing to a particular stage of AD and the relative risk of death for a person in a particular stage of AD compared with cognitively normal (CN) people. METHODS: This was a retrospective observational cohort study of mortality and its determinants in participants with incident mild cognitive impairment (MCI) due to AD or AD dementia compared with CN participants. Overall survival and hazard ratios of all-cause mortality in participants ≥ 50 years of age with clinically assessed or diagnosed MCI due to AD, or mild, moderate, or severe AD dementia, confirmed by Clinical Dementia Rating scores, versus CN participants were estimated, using NACC UDS data. Participants were followed until death, censoring, or until information to determine disease stage was missing. RESULTS: Aged between 50 and 104 years, 12,414 participants met the eligibility criteria for the study. Participants progressing to MCI due to AD or AD dementia survived a median of 3-12 years, with higher mortality observed in more severe stages. Risk of death increased with the severity of AD dementia, with the increase significantly higher at younger ages. Participants with MCI due to AD and CN participants had a similar risk of death after controlling for confounding factors. CONCLUSIONS: Relative all-cause mortality risk increases with AD severity, more so at younger ages. Mortality does not seem to be higher for those remaining in MCI due to AD. Findings might imply potential benefit of lower mortality if preventing or delaying the progression of AD is successful, and importantly, this potential benefit might be greater in relatively younger people. Future research should replicate our study in other samples more representative of the general US population as well as other populations around the world.

Comparison of Clopidogrel and Ticagrelor for Dual Antiplatelet Therapy of Patients with Unruptured Cerebral Aneurysms Undergoing Endovascular Treatment.

BACKGROUND: Thromboembolic events are critical complications in neuroendovascular procedures, and dual antiplatelet therapy (DAPT) can reduce them. The effects of using aspirin and clopidogrel in DAPT are well characterized, but use of aspirin and ticagrelor has been less studied. METHODS: This retrospective cohort study, conducted between April 1, 2015, and December 30, 2020, included patients with endovascular treatment with flow-diverting and non-flow-diverting stents for unruptured cerebral aneurysms who received DAPT with aspirin and clopidogrel or with aspirin and ticagrelor. RESULTS: Of 148 patients with unruptured intracranial aneurysms with flow-diverting and non-flow-diverting stents started on DAPT with aspirin (100 mg/day) and clopidogrel (75 mg/day), 24 had a poor response to clopidogrel according to the VerifyNow test and had DAPT changed to aspirin (100 mg/day) and ticagrelor (90 mg every 12 hours). One thrombotic complication (0.81%) and 1 bleeding complication (0.81%) occurred in patients receiving DAPT with clopidogrel and aspirin during the procedure. These complications did not occur (0.00%) in patients receiving DAPT with ticagrelor and aspirin. At the 6-month follow-up, 4 patients (3.15%) in the clopidogrel group presented with thrombotic complications, whereas no patients (0.00%) in the ticagrelor group experienced this complication. At 6-month follow-up, 4 patients (3.23%) in the clopidogrel group presented with hemorrhagic complications, whereas only 1 patient (4.17%) in the ticagrelor group experienced this complication. CONCLUSIONS: Our study showed that DAPT with ticagrelor (90 mg every 12 hours) and aspirin (100 mg/day) is a safe and effective alternative to DAPT with clopidogrel (75 mg/day) and aspirin (100 mg/day) for patients with an inadequate response to clopidogrel.

Cell Therapy as Target Therapy against Colon Cancer Stem Cells.

Cancer stem cells (CSCs) are a small subpopulation of cells within tumors with properties, such as self-renewal, differentiation, and tumorigenicity. CSCs have been proposed as a plausible therapeutic target as they are responsible for tumor recurrence, metastasis, and conventional therapy resistance. Selectively targeting CSCs is a promising strategy to eliminate the propagation of tumor cells and impair overall tumor development. Recent research shows that several immune cells play a crucial role in regulating tumor cell proliferation by regulating different CSC maintenance or proliferation pathways. There have been great advances in cellular immunotherapy using T cells, natural killer (NK) cells, macrophages, or stem cells for the selective targeting of tumor cells or CSCs in colorectal cancer (CRC). This review summarizes the CRC molecular profiles that may benefit from said therapy and the main vehicles used in cell therapy against CSCs. We also discuss the challenges, limitations, and advantages of combining conventional and/or current targeted treatments in the late stages of CRC.

Angiographic outcomes of embolization in patients with intracranial aneurysms with coil- assisted Laser cut stent versus braided stents.

INTRODUCTION: Intracranial aneurysms (IA) are a focal dilatation of the vessel wall, the rupture of these, causes subarachnoid hemorrhage. Until now, endovascular management is the ideal treatment, providing the interventionist a range of options among which the stent and coils embolization stands out because of its occlusion rate. This study presents the results of a retrospective cohort comparing the effectiveness, morbidity, and mortality of IA treatment with laser-cut stent-assisted coils versus braided stents. METHODOLOGY: Retrospective cohort of patients diagnosed with unruptured intracranial aneurysms treated with coil-assisted laser-cut stents or braided stents between January 2014 and December 2021. RESULTS: In total, 138 patients with 147 intracranial aneurysms were analyzed, 91 of them were treated with laser-cut stent and 56 with braided stents. The main antecedent was arterial hypertension (48.55%). In the immediate angiographic control, a Raymond Roy scale (RRO) I was obtained in 86.81% of the patients with laser-cut stents and 87.50% of the patients with braided stents. In the angiographic follow-up at 12 months, an RRO I occlusion rate of 85.19% was reported in both groups. Perioperative complications occur in 16 patients treated with laser-cut stents and 12 patients treated with braided stents. Three patients presented bleeding complications during the 12-month follow-up, of which two correspond to patients treated with braided stents and one with a laser-cut stent. CONCLUSION: Treatment of patients with intracranial aneurysms with laser-cut stents or braided stents and coils is just as safe and effective.

Cancer Stem Cell and Hepatic Stellate Cells in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common liver cancer. It is highly lethal and has high recurrence. Death among HCC patients occur mainly due to tumor progression, recurrence, metastasis, and chemoresistance. Cancer stem cells (CSCs) are cell subpopulations within the tumor that promote invasion, recurrence, metastasis, and drug resistance. Hepatic stellate cells (HSCs) are important components of the tumor microenvironment (TME) responsible for primary secretory ECM proteins during liver injury and inflammation. These cells promote fibrogenesis, infiltrate the tumor stroma, and contribute to HCC development. Interactions between HSC and CSC and their microenvironment help promote carcinogenesis through different mechanisms. This review summarizes the roles of CSCs and HSCs in establishing the TME in primary liver tumors and describes their involvement in HCC chemoresistance.

Mesenchymal Stem Cells Genetically Modified by Lentivirus-Express Soluble TRAIL and Interleukin-12 Inhibit Growth and Reduced Metastasis-Relate Changes in Lymphoma Mice Model.

BACKGROUND: Cancer treatment has many side effects; therefore, more efficient treatments are needed. Mesenchymal stem cells (MSC) have immunoregulatory properties, tumor site migration and can be genetically modified. Some proteins, such as soluble TRAIL (sTRAIL) and interleukin-12 (IL-12), have shown antitumoral potential, thus its combination in solid tumors could increase their activity. MATERIALS AND METHODS: Lentiviral transduction of bone marrow MSC with green fluorescent protein (GFP) and transgenes (sTRAIL and IL-12) was confirmed by fluorescence microscopy and Western blot. Soluble TRAIL levels were quantified by ELISA. Lymphoma L5178Y cells express a reporter gene (GFP/mCherry), and TRAIL receptor (DR5). RESULTS: An in vivo model showed that combined treatment with MSC expressing sTRAIL+IL-12 or IL-12 alone significantly reduced tumor volume and increased survival in BALB/c mice (p < 0.05) with only one application. However, at the histological level, only MSC expressing IL-12 reduced tumor cell infiltration significantly in the right gastrocnemius compared with the control group (p < 0.05). It presented less tissue dysplasia confirmed by fluorescence and hematoxylin-eosin dye; nevertheless, treatment not inhibited hepatic metastasis. CONCLUSIONS: MSC expressing IL-12, is or combination with BM-MSC expressing sTRAIL represents an antitumor strategy for lymphoma tumors since they increase survival and reduce tumor development. However, the combination did not show significative additive effect. The localized application did not inhibit metastasis but reduced morphological alterations of tissue associated with liver metastasis.

The Involvement of Krüppel-like Factors in Cardiovascular Diseases.

Krüppel-like factors (KLFs) are a set of DNA-binding proteins belonging to a family of zinc-finger transcription factors, which have been associated with many biological processes related to the activation or repression of genes, inducing cell growth, differentiation, and death, and the development and maintenance of tissues. In response to metabolic alterations caused by disease and stress, the heart will undergo cardiac remodeling, leading to cardiovascular diseases (CVDs). KLFs are among the transcriptional factors that take control of many physiological and, in this case, pathophysiological processes of CVD. KLFs seem to be associated with congenital heart disease-linked syndromes, malformations because of autosomal diseases, mutations that relate to protein instability, and/or loss of functions such as atheroprotective activities. Ischemic damage also relates to KLF dysregulation because of the differentiation of cardiac myofibroblasts or a modified fatty acid oxidation related to the formation of a dilated cardiomyopathy, myocardial infarctions, left ventricular hypertrophy, and diabetic cardiomyopathies. In this review, we describe the importance of KLFs in cardiovascular diseases such as atherosclerosis, myocardial infarction, left ventricle hypertrophy, stroke, diabetic cardiomyopathy, and congenital heart diseases. We further discuss microRNAs that have been involved in certain regulatory loops of KLFs as they may act as critical in CVDs.

Intergenerational support and retirement timing among older men and women by race/ethnicity.

Retirement timing is associated with health and economic outcomes for older adults. However, it is unclear how the pressures of supporting older parents and young adult children are associated with retirement. This study uses a life course perspective to consider how the linked lives of working older adults and their support of adult children and parents are associated with retirement. Cox proportional hazard models are estimated using the Health and Retirement Study (1992-2014) to assess the relationship between intergenerational support exchanges and retirement timing by gender and race/ethnicity. Providing most types of intergenerational support and especially providing time support are associated with an increased risk of retirement. Unlike all other respondents, Hispanic women providing intergenerational time support have similar retirement risks as those not providing any intergenerational support. These differing patterns by race/ethnicity suggest that earlier life course trajectories may shape older adults' ability to respond to family needs.