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1.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063032

RESUMEN

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.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Neoplasias , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Neoplasias/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Animales , Terapia Genética/métodos , Microambiente Tumoral
2.
Int J Mol Sci ; 24(9)2023 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-37175871

RESUMEN

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.


Asunto(s)
Neoplasias del Colon , Humanos , Neoplasias del Colon/patología , Células Madre Neoplásicas/metabolismo , Recurrencia Local de Neoplasia/patología , Inmunoterapia
3.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36077276

RESUMEN

Articular cartilage is a highly organized tissue that provides remarkable load-bearing and low friction properties, allowing for smooth movement of diarthrodial joints; however, due to the avascular, aneural, and non-lymphatic characteristics of cartilage, joint cartilage has self-regeneration and repair limitations. Cartilage tissue engineering is a promising alternative for chondral defect repair. It proposes models that mimic natural tissue structure through the use of cells, scaffolds, and signaling factors to repair, replace, maintain, or improve the specific function of the tissue. In chondral tissue engineering, fibrin is a biocompatible biomaterial suitable for cell growth and differentiation with adequate properties to regenerate damaged cartilage. Additionally, its mechanical, biological, and physical properties can be enhanced by combining it with other materials or biological components. This review addresses the biological, physical, and mechanical properties of fibrin as a biomaterial for cartilage tissue engineering and as an element to enhance the regeneration or repair of chondral lesions.


Asunto(s)
Cartílago Articular , Fibrina , Materiales Biocompatibles/química , Cartílago Articular/patología , Ingeniería de Tejidos , Andamios del Tejido/química
4.
Cancer Cell Int ; 19: 173, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31303863

RESUMEN

Colorectal cancer (CRC) is one type of tumor with the highest frequency and mortality worldwide. Although current treatments increase patient survival, it is important to detect CRC in early stages; however, most CRC, despite responding favorably to treatment, develop resistance and present recurrence, a situation that will inevitably lead to death. In recent years, it has been shown that the main reason for drug resistance is the presence of colon cancer stem cells (CSC). Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME), contributing to the formation of vessels and promoting metastasis; however, they have not been considered very important as a therapeutic target in cancer. In this review, we highlight the contribution of pericytes and cancer stem cells to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss therapies targeting pericytes and cancer stem cells in CRC.

5.
J BUON ; 23(6): 1893-1903, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30610819

RESUMEN

PURPOSE: Advanced cancer is a catastrophic medical condition that is generally treated with surgery and conventional anticancer drugs, which are very toxic and often fail. A promising alternative is using genetically engineered mesenchymal stem cells. A popular method for genetically engineering mesenchymal stem cells (MSCs) is by employing transfection reagents. Nevertheless, a serious limitation of this procedure is its consistently low transfection efficiency. Therefore, the utility of transfection reagents in regenerative medicine - including cancer treatment - might increase strikingly by increasing their transfection efficiency and maintaining, to the greatest extent possible, cell viability and transgene expression levels. The purpose of this study was to analyze various effects on gene expression level, transfection efficiency, and cell viability by increasing the volume of transfection reagents and the plasmid DNA mass. METHODS: Mouse bone marrow MSCs were transfected with trademarked Xfect®, Turbofect® or Lipofectamine 3000® and the plasmid pTracer-EF-His-A® expressing the green fluorescent protein (GFP). Additionally, we tested a protocol modification recommended by the Xfect manufacturer. The GFP expression level, transfection efficiency, and cell viability were evaluated together using a performance index. RESULTS: By doubling the quantities recommended by the manufacturers (reagent volume), plasmid DNA mass or both variables and by following a modified Xfect method, the transfection efficiency improved to 70%, the cell viability did not diminish, and the performance index increased to 47.7% with respect to the values determined using the original Xfect protocol. CONCLUSION: Transgene expression levels, transfection efficiency, and cell viability may be strikingly improved, by increasing the volume of the transfectant agent, the plasmid DNA mass or both, beyond those recommended by transfection kit manufacturers.


Asunto(s)
Vectores Genéticos/administración & dosificación , Proteínas Fluorescentes Verdes/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Transfección/métodos , Transgenes/fisiología , Animales , Supervivencia Celular , Células Cultivadas , Ratones , Ratones Endogámicos BALB C
6.
J BUON ; 22(5): 1115-1121, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29135091

RESUMEN

PURPOSE: To determine in vitro, the efficacy and safety window of not-front-line and first-line anti-colorectal (CRC) drug combinations. METHODS: The adenocarcinoma cell line Colo 320DM and normal human mesenchymal stem cells derived from adipose tissue were used respectively to determine the anti-CRC efficacy (% of Colo 320DM cell death [CD]) and safety window [SW] - % Colo 320DM percent cancer death (PCD)/% of mesenchymal stem cell's death) of drug combinations, using the adenosine triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS: First-line anti-CRC drug combinations (5-fluorouracil [5FU]/oxaliplatin [oxa] and 5-FU/Oxa /leucovorin [Leuco]) produced 57.7% and 52.4% CD, and 1.38 and 2.44 SW, respectively. Combinations of 5-FU/Oxa and 1 to 3 non-front line drugs led to 56.3-99.8% CD and to 0.96-2.2 SW. The highest safety window corresponded to 5FU/Oxa/ carboplatin [Carbo] (93% CD and 1.4 SW) and to 5-FU/ Oxa/cisplatin [Cispl] (93.5% CD and 1.4 SW). In contrast, non-front line drugs led to 89.8-97.4% CD and to 1.1-78.2 SW. Outstandingly, those combinations containing Carbo/ Cispl/3,3'-diindolylmethane (DIM), aspirin (Asp), or 3,3'- DIM/ Asp showed a very high CD (91.9-96.9% [39.2-39.5 times higher than first-line-combined drugs]) and very wide SW (57.8-81.56 [66.6-40 times higher than the first-line drug combinations]). CONCLUSIONS: Human mesenchymal stem cells could be an excellent alternative to laboratory animals, when testing the safety profiles of drugs. The most promising combinations of non-frontline drugs to treat CRC are Carbo/Cispl/ Asp and Carbo/Cispl/DIM.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Compuestos Organoplatinos/farmacología
7.
Cancer Cell Int ; 15(1): 2, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25685060

RESUMEN

An area of research that has been recently gaining attention is the relationship between cancer stem cell (CSC) biology and chemo-resistance in colon cancer patients. It is well recognized that tumor initiation, growth, invasion and metastasis are promoted by CSCs. An important reason for the widespread interest in the CSC model is that it can comprehensibly explain essential and poorly understood clinical events, such as therapy resistance, minimal residual disease, and tumor recurrence. This review discusses the recent advances in colon cancer stem cell research, the genes responsible for CSC chemoresistance, and new therapies against CSCs.

8.
Mem Inst Oswaldo Cruz ; 109(6): 814-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25317710

RESUMEN

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman's rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.


Asunto(s)
Técnicas de Genotipaje/métodos , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/transmisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciudades , Comorbilidad , ADN Bacteriano/aislamiento & purificación , Femenino , Genotipo , Humanos , Secuencias Repetitivas Esparcidas/genética , Masculino , México/epidemiología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular/métodos , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/aislamiento & purificación , Polimorfismo de Longitud del Fragmento de Restricción/genética , Factores de Riesgo , Factores Sociológicos , Estadísticas no Paramétricas , Secuencias Repetidas en Tándem/genética , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/genética , Población Urbana , Adulto Joven
9.
IJID Reg ; 12: 100420, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39257852

RESUMEN

Objectives: This research summarizes the impact of the major comorbidities impacting hospitalized women with COVID-19 and their relation to death. Methods: Public data from national databases (2020-2022) for hospitalized women, including identification data, hospitalization time, comorbidities, and intensive care unit (ICU) admissions, were analyzed. Women were stratified by age (split at 50 years). Binary regression models determined the correlation between comorbidities and COVID-19 with mortality, expressed as odds ratios. Results: A total of 46,492 women were hospitalized, with 70.1% aged above 50 years. A total of 17,728 fatalities occurred, with 86.5% in the older age group. A total of 5.82% women required intensive care. The common comorbidities were pneumonia, hypertension, diabetes, obesity, and intubation. A total of 56.6% died within the 1st week; in the ICU, 65.7% died by week 2. In the logistic regression, diabetes and chronic kidney disease (CKD) were initially significant, followed by pneumonia and CKD (days 8-14), intubation and, ICU stay (beyond the 15th day). In the ICU, intubation impact worsened over time. Conclusions: Our study highlights the significant impact of comorbidities on COVID-19 mortality in women in the Valley of Mexico. Pneumonia, diabetes, CKD, and intubation were notably prevalent and correlated strongly with death in older women. Timely intubation improves survival, whereas delayed intubation increases mortality risk, particularly, in the ICU. Urgent targeted interventions are required, especially for older hospitalized women.

10.
Life (Basel) ; 14(4)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38672763

RESUMEN

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.

11.
Mem Inst Oswaldo Cruz ; 108(2): 160-6, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23579794

RESUMEN

The resistance of 139 Mycobacterium tuberculosis (MTB) isolates from the city of Monterrey, Northeast Mexico, to first and second-line anti-TB drugs was analysed. A total of 73 isolates were susceptible and 66 were resistant to anti-TB drugs. Monoresistance to streptomycin, isoniazid (INH) and ethambutol was observed in 29 cases. Resistance to INH was found in 52 cases and in 29 cases INH resistance was combined with resistance to two or three drugs. A total of 24 isolates were multidrug-resistant (MDR) resistant to at least INH and rifampicin and 11 MDR cases were resistant to five drugs. The proportion of MDR-TB among new TB cases in our target population was 0.72% (1/139 cases). The proportion of MDR-TB among previously treated cases was 25.18% (35/139 cases). The 13 polyresistant and 24 MDR isolates were assayed against the following seven second-line drugs: amikacin (AMK), kanamycin (KAN), capreomycin (CAP), clofazimine (CLF), ethionamide (ETH), ofloxacin (OFL) and cycloserine (CLS). Resistance to CLF, OFL or CLS was not observed. Resistance was detected to ETH (10.80%) and to AMK (2.70%), KAN (2.70%) and CAP (2.70%). One isolate of MDR with primary resistance was also resistant to three second-line drugs. Monterrey has a high prevalence of MDR-TB among previously treated cases and extensively drug-resistant-MTB strains may soon appear.


Asunto(s)
Antituberculosos/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/microbiología , Adolescente , Adulto , Femenino , Geografía Médica , Humanos , Masculino , México/epidemiología , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Factores de Riesgo , Factores Socioeconómicos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Pulmonar/epidemiología , Adulto Joven
12.
Life (Basel) ; 13(10)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37895359

RESUMEN

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.

13.
Polymers (Basel) ; 15(17)2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37688159

RESUMEN

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.

14.
Technol Cancer Res Treat ; 22: 15330338231163677, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36938618

RESUMEN

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.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/patología , Línea Celular Tumoral , Movimiento Celular , Células Madre Neoplásicas/metabolismo , Microambiente Tumoral
15.
IJID Reg ; 9: 72-79, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37928801

RESUMEN

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.

16.
Pharmaceuticals (Basel) ; 16(10)2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37895919

RESUMEN

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.

17.
Life (Basel) ; 13(2)2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36836777

RESUMEN

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.

18.
Biomedicines ; 11(2)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36831131

RESUMEN

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.

19.
Cancers (Basel) ; 14(16)2022 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-36010940

RESUMEN

Gastrointestinal adenocarcinomas are one of the world's deadliest cancers. Cancer stem cells and the tissue microenvironment are highly regulated by cell and molecular mechanisms. Cancer stem cells are essential for maintenance and progression and are associated with resistance to conventional treatments. This article reviews the current knowledge of the role of the microenvironment during the primary establishment of gastrointestinal adenocarcinomas in the stomach, colon, and rectum and its relationship with cancer stem cells. We also describe novel developments in cancer therapeutics, such as targeted therapy, and discuss the advantages and disadvantages of different treatments for improving gastrointestinal cancer prognosis.

20.
Life (Basel) ; 12(8)2022 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-35892919

RESUMEN

Cardiovascular diseases are a leading cause of death worldwide. Current treatments directed at heart repair have several disadvantages, such as a lack of donors for heart transplantation or non-bioactive inert materials for replacing damaged tissue. Because of the natural lack of regeneration of cardiomyocytes, new treatment strategies involve stimulating heart tissue regeneration. The basic three elements of cardiac tissue engineering (cells, growth factors, and scaffolds) are described in this review, with a highlight on the role of artificial scaffolds. Scaffolds for cardiac tissue engineering are tridimensional porous structures that imitate the extracellular heart matrix, with the ability to promote cell adhesion, migration, differentiation, and proliferation. In the heart, there is an important requirement to provide scaffold cellular attachment, but scaffolds also need to permit mechanical contractility and electrical conductivity. For researchers working in cardiac tissue engineering, there is an important need to choose an adequate artificial scaffold biofabrication technique, as well as the ideal biocompatible biodegradable biomaterial for scaffold construction. Finally, there are many suitable options for researchers to obtain scaffolds that promote cell-electrical interactions and tissue repair, reaching the goal of cardiac tissue engineering.

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