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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.

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The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-Like Family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which revealed significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~90 potential genes that participate in the regulation of the hypertrophic environment (or CVDs' Environment). Also, the GO analysis showed that genes containing the motif CACCC were enriched for multiple CVDs; in combination with STRING analysis, these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

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Objectives: This work provides an overview of young children's (aged 0-9) infectious diseases epidemiology, by exploring the link between various comorbid conditions, COVID-19, and death rate. Methods: Public data on hospitalized young children was obtained from national databases of the Mexican health care system from 2020-2022. Data included age, year of entry, gender, the time between admission to death (hospitalization time), date of death, comorbidities, and admissions to the intensive care unit. Children were separated into age groups and frequencies were calculated. Binary regression models were developed to determine the correlation of comorbidities and COVID-19 to death as calculated by odds ratios (OR). Results: From 2020-2022, there were 11,815 hospitalizations among young children, of which 15.98% were due to COVID-19, 2.55% of hospitalizations resulted in fatalities from which 32.45% of deaths were COVID-19 related. The highest case-calculated fatality ratio of COVID-19 infected young children was estimated at 7.04% by early 2020, but dropped to 2.11% by the end of the second semester of 2022. The most frequent comorbidities associated with their hospitalization and death for the general population were intubation (OR: 17.967), pneumonia (OR: 2.263), diabetes (OR: 7.301), cardiovascular diseases (OR: 1.528) and COVID-19 (OR: 261). For the COVID-19-positive group, the most impactful comorbidities were intubation (OR: 20.232), pneumonia (OR: 3.057), and diabetes (OR: 12.824). Conclusion: Children's hospitalizations and deaths were common during the pandemic; wherein major comorbidities played an important role. Therefore, effective comorbidity management and vaccination programs are essential to reduce hospitalizations and deaths among young children.

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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.

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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.

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Using cytotoxic reducing and stabilizing agents in the synthesis of gold nanoparticles (AuNPs) limits their use in biomedical applications. One strategy to overcome this problem is using "green" synthesis methodologies using polysaccharides. In the present study, we propose a green methodology for synthetizing AuNPs with mesquite gum (MG) as a reducing agent and steric stabilizer in Gold(III) chloride trihydrate aqueous solutions to obtain biocompatible nanoparticles that can be used for biomedical applications. Through this method, AuNPs can be produced without using elevated temperatures or pressures. For synthetizing gold nanoparticles coated with mesquite gum (AuNPs@MG), Gold(III) chloride trihydrate was used as a precursor, and mesquite gum was used as a stabilizing and reducing agent. The AuNPs obtained were characterized using UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, scanning transmission electron microscopy, and FT-IR spectroscopy. The stability in biological media (phosphate buffer solution), cytotoxicity (MTT assay, hematoxylin, and eosin staining), and hemocompatibility (Hemolysis assay) were measured at different concentrations and exposure times. The results showed the successful synthesis of AuNPs@MG with sizes ranging from 3 to 30 nm and a zeta potential of -31 mV. The AuNPs@MG showed good colloidal stability in PBS (pH 7.4) for up to 24 h. Finally, cytotoxicity assays showed no changes in cell metabolism or cell morphology. These results suggest that these gold nanoparticles have potential biomedical applications because of their low cytotoxicity and hemotoxicity and improved stability at a physiological pH.

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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.

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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.

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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.

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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.