RESUMEN

The aim of this study was to investigate the effect of zoledronic acid (ZA) on postoperative healing and functional rehabilitation in osteoporotic patients with rotator cuff (RC) injury. 96 Patients were divided into three groups according to bone mineral density and ZA use (Group A: normal BMD; Group B: osteoporosis and intravenous ZA use; Group C: osteoporosis, without ZA use). Radiologic, functional and Serological outcomes were evaluated 6 months after surgery. The functional scores in all groups exhibited significant improvement 6 months after surgery. Inter-group comparison showed that Constant Shoulder joint function Score (CSS) of group A not significantly differing from that of group B, the other indicators were significantly better than those of group B and C. There were no significant differences in shoulder forward flexion, abductive Range of Motion between group B and C. Other indicators of group B were significantly improved compared to group C. The retear rate in group C (30.3%, 10/33) was higher than group A (6.1%, 2/33) and group B (13.3%, 4/30). In conclusion, the application of ZA can significantly reduce the rate of RC retear in elderly patients with osteoporosis after surgery, which is significant for postoperative shoulder joint functional rehabilitation.

Asunto(s)

Osteoporosis , Lesiones del Manguito de los Rotadores , Ácido Zoledrónico , Humanos , Ácido Zoledrónico/administración & dosificación , Ácido Zoledrónico/uso terapéutico , Femenino , Anciano , Masculino , Osteoporosis/tratamiento farmacológico , Estudios Retrospectivos , Lesiones del Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/tratamiento farmacológico , Rango del Movimiento Articular/efectos de los fármacos , Resultado del Tratamiento , Persona de Mediana Edad , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Anciano de 80 o más Años , Manguito de los Rotadores/cirugía , Densidad Ósea/efectos de los fármacos , Administración Intravenosa

RESUMEN

Reduced glutathione (GSH) is widely used as an antioxidant in clinical practice, but whether GSH affects the development of early lung cancer remains unclear. Herein, we investigated the mechanism underlying the anticancer effect of GSH in patients with pulmonary nodules. Thirty patients with pulmonary nodules were treated with GSH intravenously for 10 days at a dose of 1.8 g/d, followed by oral administration of the drug at a dose of 0.4 g three times daily for 6 months. The results showed that GSH treatment promoted nodule absorption and reduced the IL-6 level in the peripheral blood of the patients. GSH reduced IL-6 expression in inflammatory BEAS-2B and lung cancer cells and inhibited the proliferation of lung cancer cell lines in vitro. In addition, GSH reduced IL-6 expression by decreasing ROS via down-regulating PI3K/AKT/FoxO pathways. Finally, GSH reversed the Warburg effect, restored mitochondrial function, and reduced the IL-6 expression via PI3K/AKT/FoxO pathways. The in vivo experiment confirmed that GSH inhibited lung cancer growth, improved mitochondrial function, and reduced the IL-6 expression by regulating key enzymes via the PI3K/AKT/FoxO pathway. In conclusion, we uncovered that GSH exerts an unprecedentedly potent anti-cancer effect to prevent the transformation of lung nodules to lung cancer by improving the mitochondrial function and suppressing inflammation via PI3K/AKT/FoxO pathway. This investigation innovatively positions GSH as a potentially safe and efficacious old drug with new uses, inhibiting inflammation and early lung cancer. The use of the drug offers a promising preventive strategy when administered during the early stages of lung cancer.

RESUMEN

The process of wound healing is intricate and complex, necessitating the intricate coordination of various cell types and bioactive molecules. Despite significant advances, challenges persist in achieving accelerated healing and minimizing scar formation. Herein, a multifunctional hydrogel engineered via dynamic Schiff base crosslinking between oxidized dextran and quaternized chitosan, reinforced with reduced graphene oxide (rGO) is reported. The resulting OQG hydrogels demonstrated injectability to aid in conforming to irregular wound geometries, rapid self-healing to maintain structural integrity and adhesion for intimate integration with wound beds. Moreover, the developed hydrogels possessed antioxidant and antibacterial activities, mitigating inflammation and preventing infection. The incorporation of conductive rGO further facilitated the transmission of endogenous electrical signals, stimulating cell migration and tissue regeneration. In addition, the polydopamine-encapsulated asiaticoside (AC@PDA) nanoparticles were encapsulated in OQG hydrogels to reduce scar formation during in vivo evaluations. In vitro results confirmed the histocompatibility of the hydrogels to promote cell migration. The recovery of the full-thickness rat wounds revealed that these designed OQG hydrogels with the incorporation of AC@PDA nanoparticles could accelerate wound healing, reduce inflammation, facilitate angiogenesis, and minimize scarring when implemented. This multifunctional hydrogel system offers a promising strategy for enhanced wound management and scarless tissue regeneration, addressing the multifaceted challenges in wound care.

Asunto(s)

Vendajes , Quitosano , Dextranos , Grafito , Hidrogeles , Polímeros , Triterpenos , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Quitosano/química , Cicatrización de Heridas/efectos de los fármacos , Dextranos/química , Animales , Ratas , Triterpenos/química , Triterpenos/farmacología , Grafito/química , Polímeros/química , Ratones , Masculino , Antioxidantes/farmacología , Antioxidantes/química , Humanos , Inyecciones , Antibacterianos/farmacología , Antibacterianos/química , Ratas Sprague-Dawley , Cicatriz , Indoles

RESUMEN

OBJECTIVE: There is a lack of evidence to support a consensus on whether surgery or radiotherapy is optimal for elderly or very elderly patients with early-stage non-small cell lung cancer (NSCLC). We aimed to assess the impact of surgery or radiotherapy on survival in elderly (≥70 years) and very elderly (≥80 years) patients with early-stage NSCLC. METHODS: Patients aged ≥70 years diagnosed with early-stage NSCLC between January 1, 1975, and December 31, 2018, were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed based on surgery, radiotherapy, and no-treatment groups. RESULTS: Data for 15,224 NSCLC patients aged ≥70 years were collected, which consisted of 6949 (45.6%) patients who underwent surgery alone, 5014 (32.9%) who underwent radiotherapy alone, and 3261 (21.5%) who received no treatment. Surgery significantly improved patient survival compared with no treatment (MST: 74 months vs. 7 months, HR: 0.201, 95% CI: 0.186-0.217, P < 0.001), as did radiotherapy (MST: 28 months vs. 7 months, HR: 0.440; 95% CI: 0.413-0.469, P < 0.001). Surgery also resulted in improved survival compared with radiotherapy (74 months vs. 28 months, HR: 0.455; 95% CI: 0.430-0.482, P < 0.001). A similar conclusion was made from the analysis of CSS. A subgroup analysis further confirmed the survival benefits. CONCLUSIONS: The results of this large-scale retrospective study indicate that both surgery and radiotherapy significantly enhance survival outcomes in patients aged ≥70 or ≥80 years with early-stage NSCLC. The survival benefits of surgery were particularly notable.

Asunto(s)

Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Programa de VERF , Humanos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Anciano , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Femenino , Masculino , Anciano de 80 o más Años , Programa de VERF/estadística & datos numéricos , Tasa de Supervivencia , Estadificación de Neoplasias , Estudios Retrospectivos , Neumonectomía/mortalidad , Pronóstico

RESUMEN

OBJECTIVES: To explore the impact of social support on CF and further clarify the mediating role of self-efficacy among Geriatric Services and Management interns. METHODS: A cross-sectional survey study examined social support, self-efficacy and CF in 592 interns in Geriatric Services and Management from 46 institutions in China. RESULT: The level of CF among Geriatric Services and Management interns is low but about one-third of the respondents is at high risk of CF. Social support was positively correlated with self-efficacy (ß = 0.114, P < 0.01). Social support significantly reduced CF (ß = -0.322, P < 0.01). Similarly, self-efficacy had significant direct effects on CF (ß = -0.497, P < 0.01). Additionally, self-efficacy played a partial mediating role in the relationship between social support and CF. CONCLUSION: Social support can directly affect the CF of Geriatric Services and Management interns and indirectly through self-efficacy. Accordingly, It is necessary to strengthen social support and self-efficacy to relieve CF among Geriatric Services and Management interns.

RESUMEN

Despite several accomplishments in addressing malnutrition, the issue of food scarcity remains a persistent concern all over the globe, particularly in the South Asian region. One recommended solution to address this situation involves advocating for further liberalization of global food trading and opening employment opportunities. In this context, using panel data spanning 2000-2019, this study makes a novel attempt to quantify the impact of agricultural trade openness and agricultural employment on food security in countries belonging to the South Asian region while controlling the tariff and agricultural production. Using "Fully Modified Ordinary Least Square (FMOLS)" and "Dynamic Ordinary Least Square (DOLS)" modeling, this article concludes that increased agricultural trade openness hinders food security in this region. Because, the member countries of South Asia are heavily reliant on food imports to meet their domestic needs, implying that the expenses of food imports exceed the potential benefits of increasing exports. Moreover, tariffs have a detrimental impact on food security in this region. However, production and employment in the agricultural industry augment earnings, strengthen the capacity to buy food, and ensure adequate nutrition intake over the long term. The study's findings suggest that these nations should prioritize food self-sufficiency to expand agricultural exports and lessen their reliance on imported food. More than that, economies should provide rewards to broaden their agricultural production locally, which aids in reducing hunger and uplifting food security.

RESUMEN

Cisplatin (CDDP) is a standard non-small cell lung cancer (NSCLC) chemotherapy, but its efficacy is hampered by resistance, partly due to the Warburg effect. This study investigates how thyroid hormones enhance the Warburg effect, increasing sensitivity to cisplatin in lung cancer. Clinical data from advanced NSCLC patients were analyzed based on thyroid hormone levels, categorizing patients into high and low groups. Cellular experiments involved Control, 10uM CDDP, 10uM CDDP + 0.1uM T3, and 10uM CDDP + 0.1uM T4 categories. Parameters were measured in A549 and PC9 lung cancer cells, including proliferation, apoptosis, mitochondrial membrane potential, ROS production, glycolysis enzyme activity, lactic acid level, and ATP content. Gene and protein expressions were assessed using qPCR and Western Blot. Analysis revealed higher FT3 levels correlated with prolonged progression-free survival before chemotherapy (median PFS: high FT3 group = 12.67 months, low FT3 group = 7.03 months, p = 0.01). Cellular experiments demonstrated that thyroid hormones increase lung cancer cell sensitivity to cisplatin, inhibiting proliferation and enhancing efficacy. The mechanism involves thyroid hormones and cisplatin jointly down-regulating MSI1/AKT/GLUT1 expression, reducing lactic acid and glycolysis. This Warburg effect reversal boosts ATP levels, elevates ROS, and decreases MMP, enhancing cisplatin effectiveness in A549 and PC9 cells. In conclusion, elevated free T3 levels in advanced NSCLC patients correlate with prolonged progression-free survival under cisplatin chemotherapy. Cellular experiments reveal that thyroid hormones enhance lung cancer cell sensitivity to cisplatin by reversing the Warburg effect, providing a mechanistic basis for improved therapeutic outcomes.

Asunto(s)

Cisplatino , Transportador de Glucosa de Tipo 1 , Neoplasias Pulmonares , Hormonas Tiroideas , Humanos , Cisplatino/farmacología , Cisplatino/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Hormonas Tiroideas/metabolismo , Efecto Warburg en Oncología/efectos de los fármacos , Femenino , Masculino , Línea Celular Tumoral , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Persona de Mediana Edad , Células A549 , Glucólisis/efectos de los fármacos , Anciano , Apoptosis/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos

RESUMEN

Gastric cancer (GC) remains a prominent malignancy that poses a significant threat to human well-being worldwide. Despite advancements in chemotherapy and immunotherapy, which have effectively augmented patient survival rates, the mortality rate associated with GC remains distressingly high. This can be attributed to the elevated proliferation and invasive nature exhibited by GC. Our current understanding of the drivers behind GC cell proliferation remains limited. Hence, in order to reveal the molecular biological mechanism behind the swift advancement of GC, we employed single-cell RNA-sequencing (scRNA-seq) to characterize the tumour microenvironment in this study. The scRNA-seq data of 27 patients were acquired from the Gene Expression Omnibus database. Differential gene analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were employed to investigate 38 samples. The copy number variation level exhibited by GC cells was determined using InferCNV. The CytoTRACE, Monocle and Slingshot analysis were used to discern the cellular stemness and developmental trajectory of GC cells. The CellChat package was utilized for the analysis of intercellular communication crosstalk. Moreover, the findings of the data analysis were validated through cellular functional tests conducted on the AGS cell line and SGC-7901 cell line. Finally, this study constructed a risk scoring model to evaluate the differences of different risk scores in clinical characteristics, immune infiltration, immune checkpoints, functional enrichment, tumour mutation burden and drug sensitivity. Within the microenvironment of GC, we identified the presence of 8 cell subsets, encompassing NK_T cells, B_Plasma cells, epithelial cells, myeloid cells, endothelial cells, mast cells, fibroblasts, pericytes. By delving deeper into the characterization of GC cells, we identified 6 specific tumour cell subtypes: C0 PSCA+ tumour cells, C1 CLDN7+ tumour cells, C2 UBE2C+ tumour cells, C3 MUC6+ tumour cells, C4 CHGA+ tumour cells and C5 MUC2+ tumour cells. Notably, the C2 UBE2C+ tumour cells demonstrated a close association with cell mitosis and the cell cycle, exhibiting robust proliferative capabilities. Our findings were fortified through enrichment analysis, pseudotime analysis and cell communication analysis. Meanwhile, knockdown of the transcription factor CREB3, which is highly active in UBE2C+ tumour cells, significantly impedes the proliferation, migration and invasion of GC cells. And the prognostic score model constructed with CREB3-related genes showcased commendable clinical predictive capacity, thus providing valuable guidance for patients' prognosis and clinical treatment decisions. We have identified a highly proliferative cellular subgroup C2 UBE2C+ tumour cells in GC for the first time. The employment of a risk score model, which is based on genes associated with UBE2C expression, exhibits remarkable proficiency in predicting the prognosis of GC patients. In our investigation, we observed that the knockdown of the transcription factor CREB3 led to a marked reduction in cellular proliferation, migration and invasion in GC cell line models. Implementing a stratified treatment approach guided by this model represents a judicious and promising methodology.

Asunto(s)

Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Análisis de la Célula Individual , Neoplasias Gástricas , Microambiente Tumoral , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Microambiente Tumoral/genética , Proliferación Celular/genética , Análisis de la Célula Individual/métodos , Línea Celular Tumoral , Perfilación de la Expresión Génica , Variaciones en el Número de Copia de ADN/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Comunicación Celular/genética

RESUMEN

BACKGROUND: TTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants. METHODS: Whole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed. RESULTS: TTN c.38,876-2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases. CONCLUSIONS: Here we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.

Asunto(s)

Conectina , Linaje , Humanos , Femenino , Conectina/genética , Masculino , Secuenciación del Exoma , Artrogriposis/genética , Contractura/genética , Mutación , Embarazo , Feto , Adulto

RESUMEN

Objective: Obesity is defined as excess body fat and is a current health epidemic associated with increased risk for type 2 diabetes and cardiovascular disease. The ClC-3 chloride channel/antiporter, encoded by the Clcn3, is associated with some diseases, like carcinoma, nervous system diseases, and metabolic diseases. To verify the relationship between the Clcn3 and weight including metabolic changes, searching for a new target for metabolic therapy of obesity, we designed the experiment. Methods: The mice were divided into 4 different groups: Clcn3+/+ mice + high-fat diet (HFD), Clcn3-/- mice + HFD, Clcn3+/+ mice + normal diet (ND), Clcn3-/- mice + ND, and fed for 16 weeks. After the glucose tolerance test and insulin tolerance test, peripheral blood and adipose tissues were collected. Moreover, we performed transcriptome sequencing for the epididymal white adipose tissue from Clcn3+/+ and Clcn3-/- mice with the high-fat diet. Western blotting verified the changes in protein levels of relevant metabolic genes. Results: We found that the Clcn3-/- mice had lower body weight and visceral fat, refining glucose and lipid metabolism in HFD-induced mice, but had no effect in normal diet mice. RNA-seq and Western blotting indicated that Clcn3 deficiency may inhibit obesity through the AMPK-UCP1 axis. Conclusion: Modulation of Clcn3 may provide an appealing therapeutic target for obesity and associated metabolic syndrome.

RESUMEN

Although finasteride (FNS) tablets are considered the most effective drug for the treatment of androgenetic alopecia (AGA), their clinical applications are limited due to the associated side effects including decreased libido, breast enlargement, and liver dysfunction. In this study, we have developed a personalized microneedle (PMN) with a double-layer structure that incorporates FNS-loaded microspheres (MPs) to accommodate irregular skin surfaces. This design enables the sustained release of FNS, thereby reducing potential side effects. The needle body was synthesized with high-strength hyaluronic acid (HA) as the base material substrate. The backing layer utilized methacrylate gelatin (GelMA) with specific toughness, enabling PMN to penetrate the skin while adapting to various skin environments. The length of PMN needles (10 × 10) was approximately 600 µm, with the bottom of the needles measuring about 330 µm × 330 µm. The distance between adjacent tips was around 600 µm, allowing the drug to penetrate the stratum corneum of the skin. The results of the drug release investigation indicated the sustained and regulated release of FNS from PMN, as compared to that of pure FNS and FNS-MPs. Further, the cytotoxicity assay demonstrates that PMS displays good cytocompatibility. Altogether, this mode of administration has immense potential for the development of delivery of other drugs, as well as in the medical field.

Asunto(s)

Administración Cutánea , Finasterida , Microesferas , Agujas , Finasterida/administración & dosificación , Finasterida/farmacocinética , Finasterida/química , Ácido Hialurónico/química , Animales , Humanos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Piel/metabolismo , Piel/efectos de los fármacos

RESUMEN

Bacterial infection can lead to various complications, such as inflammations on surrounding tissues, which can prolong wound healing and thus represent a significant clinical and public healthcare problem. Herein, a report on the fabrication of a novel genipin/quaternized chitosan (CS) hydrogel for wound dressing is presented. The hydrogel was prepared by mixing quaternized CS and genipin under 35 °C bath. The hydrogels showed porous structure (250-500 µm) and mechanical properties (3000-6000 Pa). In addition, the hydrogels displayed self-healing ability and adhesion performance on different substrates. Genipin crosslinked quaternized CS hydrogels showed antibacterial activities againstE. coliandS. aureus. The CCK-8 and fluorescent images confirmed the cytocompatibility of hydrogels by seeding with NIH-3T3 cells. The present study showed that the prepared hydrogel has the potential to be used as wound dressing.

Asunto(s)

Antibacterianos , Vendajes , Quitosano , Reactivos de Enlaces Cruzados , Escherichia coli , Hidrogeles , Iridoides , Compuestos de Amonio Cuaternario , Staphylococcus aureus , Cicatrización de Heridas , Quitosano/química , Iridoides/química , Animales , Ratones , Hidrogeles/química , Cicatrización de Heridas/efectos de los fármacos , Células 3T3 NIH , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Compuestos de Amonio Cuaternario/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ensayo de Materiales , Porosidad

RESUMEN

Patulin (PAT) is the most common mycotoxin found in moldy fruits and their derived products, and is reported to cause diverse toxic effects, including hepatotoxicity, nephrotoxicity, cardiotoxicity, neurotoxicity, immunotoxicity, gastrointestinal toxicity and dermal toxicity. The cell death induction by PAT is suggested to be a key cellular mechanism involved in PAT-induced toxicities. Accumulating evidence indicates that the multiple forms of cell death are induced in response to PAT exposure, including apoptosis, autophagic cell death, pyroptosis and ferroptosis. Mechanistically, the cell death induction by PAT is associated the oxidative stress induction via reducing the antioxidant capacity or inducing pro-oxidant NADPH oxidase, the activation of mitochondrial pathway via regulating BCL-2 family proteins, the disruption of iron metabolism through ferritinophagy-mediated ferritin degradation, and the induction of the NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome/caspase-1/gasdermin D (GSDMD) pathway. In this review article, we summarize the present understanding of the cell death induction by PAT, discuss the potential signaling pathways underlying PAT-induced cell death, and propose the issues that need to be addressed to promote the development of cell death-based approach to counteract PAT-induced toxicities.

Asunto(s)

Muerte Celular , Patulina , Patulina/toxicidad , Humanos , Muerte Celular/efectos de los fármacos , Animales , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Inflamasomas/metabolismo

RESUMEN

Antibiotics are extensively utilized in the livestock and poultry industry and can accumulate in animals and the environment, leading to potential health risks for humans via food and water consumption. Research on antibiotic toxicity, particularly their impact as endocrine disruptors on the male reproductive system, is still in its nascent stages. This review highlights the toxic effect of antibiotics on the male reproductive system, detailing the common routes of exposure and the detrimental impact and mechanisms of various antibiotic classes. Additionally, it discusses the protective role of food-derived active substances against the reproductive toxicity induced by antibiotics. This review aims to raise awareness about the reproductive toxicity of antibiotics in males and to outline the challenges that must be addressed in future research.

Asunto(s)

Antibacterianos , Disruptores Endocrinos , Masculino , Antibacterianos/toxicidad , Animales , Humanos , Disruptores Endocrinos/toxicidad , Reproducción/efectos de los fármacos , Genitales Masculinos/efectos de los fármacos

RESUMEN

One primary focus of skin tissue engineering has been the creation of innovative biomaterials to facilitate rapid wound healing. Extracellular matrix (ECM), an essential biofunctional substance, has recently been discovered to play a crucial role in wound healing. Consequently, we endeavored to decellularize ECM from pig achilles tendon and refine its mechanical and biological properties through modification by utilizing cross-linking agents. Glutaraldehyde (GA), 1-ethyl-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), double aldol starch (DAS), and microbial transglutaminase (MTG) were utilized to produce crosslinked ECM variants (GA-ECM, EDC/NHS-ECM, DAS-ECM, and MTG-ECM). Comprehensive assessments were conducted to evaluate the physical properties, biocompatibility, and wound healing efficacy of each material. The results indicated that MTG-ECM exhibited superior tensile strength, excellent hydrophilicity, minimal cytotoxicity, and the best pro-healing impact among the four modified scaffolds. Staining analysis of tissue sections further revealed that MTG-ECM impeded the transition from type III collagen to type I collagen in the wound area, potentially reducing the development of wound scar. Therefore, MTG-ECM is expected to be a potential pro-skin repair scaffold material to prevent scar formation.

Asunto(s)

Reactivos de Enlaces Cruzados , Matriz Extracelular , Transglutaminasas , Cicatrización de Heridas , Transglutaminasas/metabolismo , Transglutaminasas/química , Cicatrización de Heridas/efectos de los fármacos , Matriz Extracelular/metabolismo , Animales , Reactivos de Enlaces Cruzados/química , Porcinos , Andamios del Tejido/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Resistencia a la Tracción

RESUMEN

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Asunto(s)

Antineoplásicos , Ferroptosis , Furanos , Lignanos , Síndromes de Neurotoxicidad , Humanos , Cisteína , Cistina , Fluorouracilo , Antineoplásicos/farmacología , Sistema de Transporte de Aminoácidos y+

RESUMEN

Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.

Asunto(s)

Lesión Renal Aguda , Animales , Ratones , Flavonoides , Técnicas de Cultivo de Célula , Ácido Fólico

RESUMEN

PURPOSE: We identified limb misalignment by applying personalized axial force while the limb was in a supine position to mimic a standing posture. This study aimed to confirm the accuracy of evaluating lower limb alignment using supine weight-bearing CT scanograms. METHODS: We prospectively compared measurements of the weight-bearing line ratio (WBL), hip-knee-ankle (HKA) angle, and joint convergence angle (JLCA) in 46 sets of supine weight-bearing CT scanograms with those obtained from full-length standing anteroposterior lower extremity radiographs. We achieved the weight-bearing CT scanograms by applying six different levels of axial force: zero, 1/5 of body weight, 2/5 of body weight, 3/5 of body weight, 4/5 of body weight, and full body weight. We assessed the impact of age, body mass index, HKA, and JLCA on the observed mechanical axis deviation differences between the two methods. RESULT: The average absolute difference between standing radiographs and supine CT scanograms was 4.32% for the WBL ratio (p < 0.05), 1.25° for HKA (p < 0.05), and 0.46 for JLCA (p < 0.05). The mean absolute difference was minimal when applying full body weight axial pressure during CT scanograms (p > 0.05). Age, body mass index, HKA, and JLCA had no effect on the deviation in the mechanical axis measurements obtained through supine weight-bearing CT scanograms with full body weight. CONCLUSION: No significant differences were found in assessing lower limb alignment between standing radiographs and supine weight-bearing CT scanograms with full body weight. Weight-bearing CT scanograms prove to be a valuable method for assessing lower limb alignment while in a supine position.

Asunto(s)

Extremidad Inferior , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Extremidad Inferior/diagnóstico por imagen , Estudios Prospectivos , Reproducibilidad de los Resultados , Posición de Pie , Posición Supina , Tomografía Computarizada por Rayos X/métodos , Soporte de Peso

RESUMEN

Background and Objective: Lung cancer is a prevalent global malignancy, and investigating the metabolic reprogramming of tumor cells has significant therapeutic implications. This study aims to explore the molecular mechanism driving the progression of non-small cell lung cancer (NSCLC), with a specific emphasis on the STAT3-ACC1-FAS axis involved in fatty acid synthesis. Methods: The levels of Signal transducer and activator of transcription 3 (STAT3) and acetyl-CoA carboxylase 1 (ACC1) were determined in mouse NSCLC specimens and cell lines using Western blot and qPCR methods. Various assays such as CCK-8, colony formation, EDU, wound-healing, and transwell migration were employed to assess cancer cell proliferation, migration, and invasion. Additionally, a nude mouse xenograft model was utilized for in vivo tumor growth analysis. The interaction between STAT3 and ACC1 was examined through chromatin immunoprecipitation and dual-luciferase assays. Results: The study observed upregulation of STAT3 and ACC1 in NSCLC tissues. Notably, the suppression of STAT3 and ACC1 inhibited the in vitro progression and lipid synthesis of NSCLC cells. Furthermore, STAT3 enhanced lipid synthesis by upregulating ACC1 expression. Mechanistic assays revealed that this process occurred through direct activation of ACC1 transcription by STAT3. STAT3 played a vital role in regulating lipid metabolism and supporting NSCLC progression. Conclusion: The findings of this study underscore the significance of the STAT3-ACC1-FAS axis in NSCLC. The activation of ACC1 through STAT3-mediated transcription serves as a crucial mechanism for stimulating the progression of NSCLC tumors and promoting lipid synthesis. Consequently, targeting the STAT3-ACC1 axis may present a promising avenue for the diagnosis and treatment of NSCLC patients.

RESUMEN

Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.