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1.
Pediatr Obes ; : e13153, 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39099236

RESUMEN

BACKGROUND: Parents play a substantial role in improving adolescent dietary behaviours. OBJECTIVES: To examine the interdependent relationships between motivations (autonomous and emotional motivation) and dietary behaviours (fruit and vegetable [F/V] and junk food and sugar-sweetened beverage [JF/SSB] intake) within parent-adolescent dyads. METHODS: This secondary data analysis was conducted on 1522 parent-adolescent dyads using a cross-sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) study. The ratio of boys to girls among the adolescents was approximately equal, and 74% of the parents were mothers. The adolescents were between 12 and 17 years old, and 85.5% of the parents were between 35 and 59 years old. Parents and adolescents completed an online survey on dietary motivations and behaviours. Actor-partner interdependence models were performed within parent-adolescent dyads. RESULTS: F/V and JF/SSB intake was influenced by parents' or adolescents' autonomous motivation (actor-only pattern), except among adolescents with obesity. A dyadic pattern was found in the relationship between autonomous motivation and F/V and JF/SSB intake, but only among adolescents with normal weight. No relationship was found between F/V and JF/SSB controlled motivation and F/V or JF/SSB intake among adolescents with overweight or obesity. CONCLUSIONS: Autonomous motivation had a significant relationship with F/V and JF/SSB intake for both parents and adolescents, but the association varied depending on the adolescents' weight. Personalized programmes that foster autonomous motivation to change dietary behaviours should be provided based on the adolescents' weight status.

2.
J Korean Soc Radiol ; 85(4): 780-784, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39130785

RESUMEN

In this report, we present a case of a radiotherapy-induced tracheoesophageal fistula treated with the fluoroscopy-guided insertion of a covered stent through the gastrostomy route using both the antegrade and retrograde approaches. The initial antegrade endoscopic and fluoroscopic stent insertion procedure failed due to severe esophageal stricture. Compared to the endoscopic approaches, fluoroscopy-guided radiologic procedures are generally less invasive and more successful because they allow for a better understanding of the anatomy outside the lumen during the procedure and enable the use of devices with smaller diameters.

3.
Foods ; 13(14)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39063274

RESUMEN

Allergic contact dermatitis (ACD) is the most common chronic inflammatory skin disease (or immune-mediated disease), causing disruption to our psychological condition and life quality. In this study, the therapeutic properties of probiotic Bifidobacterium longum (B. longum) was investigated by using an ACD-induced animal model. For ACD induction, BALB/c mice ear and dorsal skin were sensitized with 240 µL of 1% (w/v) 2,4-dinitrochlorobenzene (DNCB) twice (3-day intervals). After a week of the first induction, the mice were re-sensitized by painting on their dorsal skin and ear with 0.4% (w/v) DNCB for a further three times (once per week). Before the ACD induction of 2 weeks and throughout the trial period, the BALB/c mice were supplemented daily with 1 mL of 1.0 × 109 CFU or 5.0 × 109 CFU B. longum using an intragastric gavage method. The ACD-induced mice without B. longum supplementation were used as a control. Results show that B. longum supplementation significantly alleviated ACD symptoms (e.g., ear swelling, epidermal damage) and immune response (e.g., reduced immune cell recruitment, serum IgE level, and cytokine production). The therapeutic efficiency of B. longum increased as the supplementation dose increased. Thus, daily supplementation with 5.0 × 109 CFU probiotic B. longum could be an effective method for the prevention and treatment of ACD.

4.
Abdom Radiol (NY) ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38802629

RESUMEN

Magnetic resonance imaging (MRI) is a crucial modality for abdominal imaging evaluation of focal lesions and tissue properties. However, several obstacles, such as prolonged scan times, limitations in patients' breath-hold capacity, and contrast agent-associated artifacts, remain in abdominal MR images. Recent techniques, including parallel imaging, three-dimensional acquisition, compressed sensing, and deep learning, have been developed to reduce the scan time while ensuring acceptable image quality or to achieve higher resolution without extending the scan duration. Quantitative measurements using MRI techniques enable the noninvasive evaluation of specific materials. A comprehensive understanding of these advanced techniques is essential for accurate interpretation of MRI sequences. Herein, we therefore review advanced abdominal MRI techniques.

5.
J Korean Soc Radiol ; 85(2): 345-362, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38617869

RESUMEN

MRI plays an important role in abdominal imaging because of its ability to detect and characterize focal lesions. However, MRI examinations have several challenges, such as comparatively long scan times and motion management through breath-holding maneuvers. Techniques for reducing scan time with acceptable image quality, such as parallel imaging, compressed sensing, and cutting-edge deep learning techniques, have been developed to enable problem-solving strategies. Additionally, free-breathing techniques for dynamic contrast-enhanced imaging, such as extra-dimensional-volumetric interpolated breath-hold examination, golden-angle radial sparse parallel, and liver acceleration volume acquisition Star, can help patients with severe dyspnea or those under sedation to undergo abdominal MRI. We aimed to present various advanced abdominal MRI techniques for reducing the scan time while maintaining image quality and free-breathing techniques for dynamic imaging and illustrate cases using the techniques mentioned above. A review of these advanced techniques can assist in the appropriate interpretation of sequences.

6.
Cell Rep ; 43(3): 113912, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38446659

RESUMEN

In this study, we explore the dynamic process of colorectal cancer progression, emphasizing the evolution toward a more metastatic phenotype. The term "evolution" as used in this study specifically denotes the phenotypic transition toward a higher metastatic potency from well-formed glandular structures to collective invasion, ultimately resulting in the development of cancer cell buddings at the invasive front. Our findings highlight the spatial correlation of this evolution with tumor cell senescence, revealing distinct types of senescent tumor cells (types I and II) that play different roles in the overall cancer progression. Type I senescent tumor cells (p16INK4A+/CXCL12+/LAMC2-/MMP7-) are identified in the collective invasion region, whereas type II senescent tumor cells (p16INK4A+/CXCL12+/LAMC2+/MMP7+), representing the final evolved form, are prominently located in the partial-EMT region. Importantly, type II senescent tumor cells associate with local invasion and lymph node metastasis in colorectal cancer, potentially affecting patient prognosis.


Asunto(s)
Neoplasias Colorrectales , Metaloproteinasa 7 de la Matriz , Humanos , Metaloproteinasa 7 de la Matriz/genética , Senescencia Celular/genética , Fenotipo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología
7.
J Cardiovasc Aging ; 4(1)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38464671

RESUMEN

Introduction: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model. Aim: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for Ryr2 variant p.Arg176Gln (R176Q/+). Methods and Results: Guide RNA and SaCas9 were delivered using AAV9 vectors injected subcutaneously in 10-day-old mice. At 6 weeks after injection, R176Q/+ mice had a 100% reduction in ventricular arrhythmias compared to controls. When aged to 12 months, injected R176Q/+ mice maintained a 100% reduction in arrhythmia induction. Deep RNA sequencing revealed the formation of insertions/deletions at the target site with minimal off-target editing on the wild-type allele. Consequently, CRISPR/SaCas9 editing resulted in a 45% reduction of total Ryr2 mRNA and a 38% reduction in RyR2 protein. Genome editing was well tolerated based on serial echocardiography, revealing unaltered cardiac function and structure up to 12 months after AAV9 injection. Conclusion: Taken together, AAV9-mediated CRISPR/Cas9 genome editing could efficiently disrupt the mutant Ryr2 allele, preventing lethal arrhythmias while preserving normal cardiac function in the R176Q/+ mouse model of CPVT.

9.
Mol Ther Methods Clin Dev ; 32(1): 101208, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38414825

RESUMEN

Wiskott-Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from a diversity of mutations distributed across all 12 exons of the WAS gene. WAS encodes a hematopoietic-specific and developmentally regulated cytoplasmic protein (WASp). The objective of this study was to develop a gene correction strategy potentially applicable to most WAS patients by employing nuclease-mediated, site-specific integration of a corrective WAS gene sequence into the endogenous WAS chromosomal locus. In this study, we demonstrate the ability to target the integration of WAS2-12-containing constructs into intron 1 of the endogenous WAS gene of primary CD34+ hematopoietic stem and progenitor cells (HSPCs), as well as WASp-deficient B cell lines and WASp-deficient primary T cells. This intron 1 targeted integration (TI) approach proved to be quite efficient and restored WASp expression in treated cells. Furthermore, TI restored WASp-dependent function to WAS patient T cells. Edited CD34+ HSPCs exhibited the capacity for multipotent differentiation to various hematopoietic lineages in vitro and in transplanted immunodeficient mice. This methodology offers a potential editing approach for treatment of WAS using patient's CD34+ cells.

10.
In Vivo ; 38(2): 849-854, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38418154

RESUMEN

BACKGROUND/AIM: This study aimed to analyze the dosimetric effects of jaw tracking during Volumetric Modulated Arc Therapy (VMAT) planning for facial non-melanoma skin cancer (NMSC). PATIENTS AND METHODS: This study included 50 patients with facial NMSC who underwent VMAT planning with or without jaw tracking. The target volume (TV) included the primary skin lesion with a 1-cm margin around the surface and a depth of 4 mm. A total of 55 Gy in 20 fractions was prescribed, and the plans were considered acceptable if the TV was covered by 95-105% of the isodose curve. A dosimetric comparison was performed for the volumes of the low-dose regions, which were defined as <50% of the prescription dose (V10-50%). Target coverage was evaluated using the homogeneity index (HI) and conformity index (CI). RESULTS: The patients' mean TV was 5.137 cc (range=1.03-15.89 cc). Jaw tracking resulted in mean volume reduction rates of 3.9%, 6.6% 10.6% and 13.8% for V40%, V30%, V20%, and V10%, respectively (all p<0.001). The volume change in V50% between the two groups was 2.7% (p=0.006). No significant differences were observed in HI (p=0.449) or CI (p=0.127). CONCLUSION: The application of jaw tracking during VMAT for facial NMSC is associated with a significant reduction in the volume of low dose delivered in the radiation field (V10-50%), while maintaining target coverage. Future analyses should assess whether this volume difference affects treatment-related cosmetic outcomes.


Asunto(s)
Radiocirugia , Radioterapia de Intensidad Modulada , Neoplasias Cutáneas , Humanos , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Dosificación Radioterapéutica , Radiocirugia/métodos , Neoplasias Cutáneas/radioterapia
11.
J Korean Soc Radiol ; 85(1): 109-123, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38362380

RESUMEN

Xanthogranulomatous (XG) inflammatory disease is a rare benign disease involving various organs, including the gallbladder, bile duct, pancreas, spleen, stomach, small bowel, colon, appendix, kidney, adrenal gland, urachus, urinary bladder, retroperitoneum, and female genital organs. The imaging features of XG inflammatory disease are nonspecific, usually presenting as a heterogeneous solid or cystic mass. The disease may also extend to adjacent structures. Due to its aggressive nature, it is occasionally misdiagnosed as a malignant neoplasm. Herein, we review the radiological features and clinical manifestations of XG inflammatory diseases in various organs of the abdomen and pelvis.

12.
Eur Radiol ; 34(4): 2233-2243, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37731096

RESUMEN

OBJECTIVE: We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15 s and 1.3 × 1.3 × 3 mm3 and 16 s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. RESULTS: CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CONCLUSIONS: CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. CLINICAL RELEVANCE STATEMENT: Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. KEY POINTS: • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Medios de Contraste , Estudios Retrospectivos , Imagenología Tridimensional/métodos , Gadolinio DTPA , Imagen por Resonancia Magnética/métodos , Aceleración , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Artefactos , Aumento de la Imagen/métodos
13.
Antioxid Redox Signal ; 40(1-3): 122-144, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37917113

RESUMEN

Significance: Hydrogen sulfide (H2S) is a recently recognized gasotransmitter involved in physiological and pathological conditions in mammals. It protects organs from oxidative stress, inflammation, hypertension, and cell death. With abundant expression of H2S-production enzymes, the liver is closely linked to H2S signaling. Recent Advances: Hepatic H2S comes from various sources, including gut microbiota, exogenous sulfur salts, and endogenous production. Recent studies highlight the importance of hepatic H2S in liver diseases such as nonalcoholic fatty liver disease (NAFLD), liver injury, and cancer, particularly at advanced stages. Endogenous H2S production deficiency is associated with severe liver disease, while exogenous H2S donors protect against liver dysfunction. Critical Issues: However, the roles of H2S in NAFLD, liver injury, and liver cancer are still debated, and its effects depend on donor type, dosage, treatment duration, and cell type, suggesting a multifaceted role. This review aimed to critically evaluate H2S production, metabolism, mode of action, and roles in liver function and disease. Future Direction: Understanding H2S's precise roles and mechanisms in liver health will advance potential therapeutic applications in preclinical and clinical research. Targeting H2S-producing enzymes and exogenous H2S sources, alone or in combination with other drugs, could be explored. Quantifying endogenous H2S levels may aid in diagnosing and managing liver diseases. Antioxid. Redox Signal. 40, 122-144.


Asunto(s)
Sulfuro de Hidrógeno , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Animales , Humanos , Sulfuro de Hidrógeno/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Inflamación/tratamiento farmacológico , Mamíferos/metabolismo
14.
Lymphat Res Biol ; 22(1): 37-42, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37971868

RESUMEN

Background: We previously devised an ultrasonographic evaluation to calculate subcutaneous tissue cross-sectional area (△CSA). The reliability and accuracy of this method were demonstrated in healthy individuals and in patients with lymphedema. The purpose of this study was to estimate the optimal cut-off value of the ratio of the △CSA of the involved side (lesion side) to the contralateral side for detecting breast cancer-related lymphedema (BCRL) using ultrasonography. Methods and Results: Ultrasonographic measurements were performed 290 times in 150 patients. BCRLD was defined as a confirmed difference of >2 cm in arm circumference. BCRL confirmed by a clinician (BCRLC) was defined as the patient group that included not only BCRLD but also patients with subcutaneous thickening and abnormal findings on lymphoscintigraphy, even if the difference in arm circumference was <2 cm. The △CSAs of both upper arms and forearms were calculated by measuring the thickness of the subcutaneous tissue at four locations using ultrasonography (superior, medial, inferior, lateral) at 10 cm above the elbow and 10 cm below the elbow. With a 1.35 △CSA ratio as the cut-off value for detecting BCRLD, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were 0.88, 0.87, and 0.95, respectively. With a 1.20 △CSA ratio as the cut-off value for detecting BCRLC, the sensitivity, specificity, and AUC were 0.92, 0.89, and 0.97, respectively. Conclusions: Our findings suggest that a 1.20 △CSA ratio as determined using ultrasonography, corresponding to a tape measurement of 1.05 cm, can be considered as a diagnostic criterion for lymphedema.


Asunto(s)
Linfedema del Cáncer de Mama , Neoplasias de la Mama , Linfedema , Humanos , Femenino , Reproducibilidad de los Resultados , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/diagnóstico por imagen , Linfedema del Cáncer de Mama/diagnóstico por imagen , Linfedema del Cáncer de Mama/etiología , Linfedema/diagnóstico por imagen , Linfedema/etiología , Ultrasonografía/métodos
15.
Biomed Pharmacother ; 170: 115913, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38154270

RESUMEN

The plant Justicia procumbens is traditionally used in Asia to treat fever, cough, and pain. Previous studies have reported its anticancer and anti-asthmatic properties. However, its potential for preventing androgenic alopecia (AGA) has not yet been reported. AGA is a widespread hair loss condition primarily caused by male hormones. In this study, we examined the hair loss-preventing effects of an aqueous extract of J. procumbens (JPAE) using human hair follicle dermal papilla cell (HFDPC) and a mouse model of testosterone-induced AGA. JPAE treatment increased HFDPC proliferation by activating the Wnt/ß-catenin signaling pathway. Additionally, JPAE increased the expression of Wnt targets, such as cyclin D1 and VEGF, by promoting the translocation of ß-catenin to the nucleus. Administration of JPAE reduced hair loss, increased hair thickness, and enhanced hair shine in an AGA mouse model. Furthermore, it increased the expression of p-GSK-3ß and ß-catenin in the dorsal skin of the mice. These findings imply that JPAE promotes the proliferation of HFDPC and prevents hair loss in an AGA mouse model. JPAE can therefore be used as a functional food and natural treatment option for AGA to prevent hair loss.


Asunto(s)
Género Justicia , beta Catenina , Humanos , Ratones , Animales , beta Catenina/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Alopecia/inducido químicamente , Alopecia/prevención & control , Alopecia/metabolismo , Cabello/metabolismo , Vía de Señalización Wnt
16.
Phytomedicine ; 123: 155281, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38103316

RESUMEN

BACKGROUND: Geniposide (GP) is an iridoid glycoside that is present in nearly 40 species, including Gardenia jasminoides Ellis. GP has been reported to exhibit neuroprotective effects in various Alzheimer's disease (AD) models; however, the effects of GP on AD models of Caenorhabditis elegans (C. elegans) and aging-accelerated mouse predisposition-8 (SAMP8) mice have not yet been evaluated. PURPOSE: To determine whether GP improves the pathology of AD and sarcopenia. METHODS: AD models of C. elegans and SAMP8 mice were employed and subjected to behavioral analyses. Further, RT-PCR, histological analysis, and western blot analyses were performed to assess the expression of genes and proteins related to AD and muscle atrophy. RESULTS: GP treatment in the AD model of C. elegans significantly restored the observed deterioration in lifespan and motility. In SAMP8 mice, GP did not improve cognitive function deterioration by accelerated aging but ameliorated physical function deterioration. Furthermore, in differentiated C2C12 cells, GP ameliorated muscle atrophy induced by dexamethasone treatment and inhibited FoxO1 activity by activating AKT. CONCLUSION: Although GP did not improve the AD pathology in SAMP8 mice, we suggest that GP has the potential to improve muscle deterioration caused by aging. This effect of GP may be attributed to the suppression of FoxO1 activity.


Asunto(s)
Enfermedad de Alzheimer , Caenorhabditis elegans , Iridoides , Ratones , Animales , Enfermedad de Alzheimer/patología , Envejecimiento , Atrofia Muscular/tratamiento farmacológico
18.
J Korean Soc Radiol ; 84(6): 1266-1289, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38107695

RESUMEN

Malignant lymphoma typically presents with homogeneous enhancement of enlarged lymph nodes without internal necrotic or cystic changes on multiphasic CT, which can be suspected without invasive diagnostic methods. However, some subtypes of malignant lymphoma show atypical imaging features, which makes diagnosis challenging for radiologists. Moreover, there are several lymphoma-mimicking diseases in current clinical practice, including leukemia, viral infections in immunocompromised patients, and primary or metastatic cancer. The ability of diagnostic processes to distinguish malignant lymphoma from mimicking diseases is necessary to establish effective management strategies for initial radiological examinations. Therefore, this study aimed to discuss the typical and atypical imaging features of malignant lymphoma as well as mimicking diseases and discuss important diagnostic clues that can help narrow down the differential diagnosis.

19.
J Pathol Transl Med ; 57(6): 305-314, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37926982

RESUMEN

BACKGROUND: Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells. METHODS: Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated ß-galactosidase (SA-ß-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase-tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-ß-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model. RESULTS: Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-ß-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-ß-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength. CONCLUSIONS: Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

20.
Nat Commun ; 14(1): 7619, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37993434

RESUMEN

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed "mid-old status" cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.


Asunto(s)
Envejecimiento , Senescencia Celular , Humanos , Anciano , Senescencia Celular/genética , Envejecimiento/genética , Células Epiteliales/fisiología , Fibroblastos , Miocitos del Músculo Liso
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