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1.
World J Gastrointest Surg ; 16(9): 2842-2852, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39351564

RESUMEN

BACKGROUND: Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute. AIM: To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor. METHODS: Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006). CONCLUSION: RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.

2.
Int J Biol Macromol ; 280(Pt 2): 135827, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306177

RESUMEN

Cartilage defect repair with optimal efficiency remains a significant challenge due to the limited self-repair capability of native tissues. The development of bioactive scaffolds with biomimicking mechanical properties and degradation rates matched with cartilage regeneration while simultaneously driving chondrogenesis, plays a crucial role in enhancing cartilage defect repair. To this end, a novel composite scaffold with hierarchical porosity was manufactured by incorporating a pro-chondrogenic collagen type I/II-hyaluronic acid (CI/II-HyA) matrix to a 3D-printed poly(glycerol sebacate) (PGS) framework. Based on the mechanical enforcement of PGS framework, the composite scaffold exhibited a compressive modulus of 167.0 kPa, similar to that of native cartilage, as well as excellent fatigue resistance, similar to that of native joint tissue. In vitro degradation tests demonstrated that the composite scaffold maintained structural, mass, and mechanical stability during the initial cartilage regeneration period of 4 weeks, while degraded linearly over time. In vitro biological tests with rat-derived mesenchymal stem cell (MSC) revealed that, the composite scaffold displayed increased cell loading efficiency and improved overall cell viability due to the incorporation of CI/II-HyA matrix. Additionally, it also sustained an effective and high-quality MSC chondrogenesis and abundant de-novo cartilage-like matrix deposition up to day 28. Overall, the biomimetic composite scaffold with sufficient mechanical support, matched degradation rate with cartilage regeneration, and effective chondrogenesis stimulation shows great potential to be an ideal candidate for enhancing cartilage defect repair.

3.
Animals (Basel) ; 14(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39272408

RESUMEN

Mechanical ventilation is an important means of environmental control in multitier laying hen cages. The mainstream ventilation mode currently in use, negative-pressure ventilation (NPV), has the drawbacks of a large temperature difference before and after adjustment and uneven air velocity distribution. To solve these problems, this study designed and analyzed a combined positive and negative-pressure ventilation system for laying hen cages. According to the principle of the conservation of mass to increase the inlet flow in the negative-pressure ventilation system on the basis of the addition of the pressure-wind body-built positive-and-negative-pressure-combined ventilation (PNCV) system, further, computational fluid dynamics (CFD) simulation was performed to analyze the distribution of environmental parameters in the chicken cage zone (CZ) with inlet angles of positive-pressure fans set at 45°, 90°, and 30°. Simulation results showed that the PNCV system increased the average air velocity in the CZ from 0.94 m/s to 1.04 m/s, 1.28 m/s, and 0.99 m/s by actively blowing air into the cage. The maximum temperature difference in the CZ with the PNCV system was 2.91 °C, 1.80 °C, and 3.78 °C, which were all lower than 4.46 °C, the maximum temperature difference in the CZ with the NPV system. Moreover, the relative humidity remained below 80% for the PNCV system and between 80% and 85% for the NPV system. Compared with the NPV system, the PNCV system increased the vertical airflow movement, causing significant cooling and dehumidifying effects. Hence, the proposed system provides an effective new ventilation mode for achieving efficient and accurate environmental control in laying hen cages.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39342820

RESUMEN

The process of counter-current chromatography (CCC) separation for natural products typically necessitates the use of multiple solvent systems to accommodate constituents with a wide range of polarities. However, the incompatibility between these different solvent systems often results in unsuccessful online 2D successive separations. In this study, a 2D CCC system was developed, featuring an interface for online-storage, dilution, and mixing. It facilitated the implementation of online 2D CCC using different solvent systems. The method was subsequently applied for the preparative isolation of flavonoids from Scutellaria baicalensis Georgi roots. For 1D CCC, n-heptane-ethyl acetate-methanol-water (HepEMWat, 5:5:4:6, v/v) was utilized, while for 2D CCC, ethyl acetate-n-butanol-water (EBuWat, 0:5:5, v/v) was employed. The eluent with low resolution in 1D CCC was stored online, diluted three times using the lower phase of EBuWat (0:5:5, v/v), and subsequently transferred into 2D CCC for further isolation utilizing the same EBuWat (0:5:5, v/v) system. As results, six lipophilic compounds were isolated in 1D CCC in a normal mode, while two major hydrophilic constituents were isolated in a pH-peak-focusing mode in 2D CCC. Additionally, two additional compounds were purified through subsequent semi-preparative HPLC separation in order to resolve co-elution in 2D CCC. The developed 2D CCC system with a multifunctional interface demonstrated to be an exceptionally efficient and promising approach for the high-throughput purification of complex natural products.

5.
Foods ; 13(18)2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39335848

RESUMEN

The use of Generally Recognized as Safe (GRAS)-grade microbial cell factories to produce recombinant protein-based nutritional products is a promising trend in developing food and health supplements. In this study, GRAS-grade Kluyveromyces marxianus was employed to express recombinant human heavy-chain ferritin (rhFTH), achieving a yield of 11 g/L in a 5 L fermenter, marking the highest yield reported for ferritin nanoparticle proteins to our knowledge. The rhFTH formed 12 nm spherical nanocages capable of ferroxidase activity, which involves converting Fe2+ to Fe3+ for storage. The rhFTH-containing yeast cell lysates promoted cytokine secretion (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1ß (IL-1ß)) and enhanced locomotion, pharyngeal pumping frequency, egg-laying capacity, and lifespan under heat and oxidative stress in the RAW264.7 mouse cell line and the C. elegans model, respectively, whereas yeast cell lysate alone had no such effects. These findings suggest that rhFTH boosts immunity, holding promise for developing ferritin-based food and nutritional products and suggesting its adjuvant potential for clinical applications of ferritin-based nanomedicine. The high-yield production of ferritin nanoparticles in K. marxianus offers a valuable source of ferritin for the development of ferritin-based products.

7.
Am J Clin Oncol ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39319705

RESUMEN

OBJECTIVES: Surveillance imaging for HPV-associated oropharyngeal carcinomas (OPCs) differs among physicians and institutions. Surveillance imaging can detect disease progression earlier, but can also contribute to anxiety and cost, without proven survival benefits. We sought to determine practice patterns of surveillance imaging and the number of surveillance scans needed to detect one recurrence in patients with HPV-associated OPCs. METHODS: We performed a retrospective cohort study between 2017 and 2019 (median follow-up: 39.9 mo) of consecutive patients with locally advanced HPV-associated OPC who received definitive concurrent chemoradiotherapy (CRT) with 70 Gy at a single institution. Patients were followed post-CRT and their surveillance scans were recorded. Recurrences were classified as detected by first post-treatment scans, surveillance scans, clinical exams, or incidental findings. The number of surveillance scans needed to detect 1 recurrence was determined by dividing the number of surveillance scans by the number of recurrences detected by surveillance scans. RESULTS: Among 276 patients with a median follow-up of 39.9 months, there were 28 recurrences. Of all recurrences, 11 (39.3%) were detected by the first post-treatment scan, 11 (39.3%) by surveillance scan, 5 (17.9%) by clinical exam, and 1 (3.6%) was incidentally found. A total of 694 surveillance scans were taken. The number of surveillance scans needed to detect 1 recurrence was 64 overall, 45 within 2 years, and 248 beyond 2 years from treatment. CONCLUSIONS: First post-treatment scans and surveillance scans detected more recurrences than clinical exams. A high burden of surveillance scans is needed to detect 1 recurrence, especially beyond 2 years from treatment.

8.
Endocr Relat Cancer ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39324992

RESUMEN

Hormone therapy (HT) to treat prostate cancer is reported to cause adverse changes in body composition. Clinically, interpatient body composition changes are heterogeneous, but the biologic and clinical determinants of body composition toxicity are unknown. Herein, we test the hypothesis that inherited polymorphisms in steroidogenic genes are associated with differential change in body composition after HT. Men with biochemically recurrent prostate cancer (BCR) who received 8 months of LHRH analog (LHRHa) +/- abiraterone acetate (AAP) were eligible if they had: 1) CT imaging of L3 prior to and after treatment, and 2) nucleated cells collected. Cardiometabolic co-morbidities were retrospectively extracted. Body composition was measured using an AI-based segmentation tool. Germline DNA whole exome or genome sequencing was performed. In 162 men treated with 8 months of HT, median skeletal muscle mass (SMMi) loss was 6.6% and subcutaneous adipose gain was 12.3%. Men with type 2 diabetes had higher loss of SMMi after treatment (-11.1% vs. -6.3%, p = 0.003). For the 150 men with germline NGS, SRD5A2 rs523349 genotype was associated with differential loss in skeletal muscle density after HT, (-1.3% vs. -7.1%, p=0.04). In addition, HSD3B1 rs104703 genotype was associated with decreased baseline visceral adipose tissue (63.0 cm2/m2 vs. 77.9, p=0.05). In men with BCR, HT induced notable loss of skeletal muscle and increased subcutaneous adipose tissue. An inherited polymorphism in SRD5A2 and T2DM were associated with differential skeletal muscle toxicity. These findings suggest that inherited polymorphisms may contribute to the body composition toxicity observed with HT.

9.
Biochim Biophys Acta Mol Basis Dis ; 1871(1): 167518, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39307290

RESUMEN

RNA-binding proteins (RBPs) play central roles in post-transcriptional gene regulation. However, the function of RBP in retinal progenitor cell differentiation and synaptic signal transmission are largely unexplored. Previously we have shown that Elavl2 regulates amacrine cell (AC) differentiation during retinogenesis, by directly binding to Nr4a2 and Barhl2. Elavl2 is expressed in early neuronal progenitors to mature neurons, and Elavl4 expression begins slightly later, during cortical neuron development as a paralog. Here, Retinal-specific Elavl2 and Elavl4 double knockout mice were made to further explore the role of Elavl2 and Elavl4 in retinal development and signal transduction. We disclose that Elavl4 binds to Satb1 to regulate Neurod1, then promoting retinal progenitor and amacrine cells differentiation. We were also surprised to find that Elavl2 interacted with GABAB receptors at the RNA and protein levels. In conclusion, Elavl2 and Elavl4 regulate amacrine cells differentiation through different pathways, leading to decreased scotopic vision. Our findings reveal the roles of Elavl2 and Elavl4 in retinal amacrine cells differentiation in modulating visual functions.

10.
PLoS One ; 19(9): e0310889, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39321199

RESUMEN

B-cell lymphoma, clinically, comprises a heterogeneous group of malignancies that encompass various subtypes. CD20 is an optimal target for therapeutic antibodies in B-cell lymphoma immunotherapy since approximately 90% of B-cell malignancies typically exhibit CD20 expression on their surface, while its presence is limited in normal tissues. In this study, we have developed a series of novel non-IgG-like T cell-dependent bispecific antibodies by constructing Fab-FabCH3, referred to as Tandem Antigen-binding Fragment 002 (TFAB002), which specifically target CD20 for the treatment of malignant B-cell lymphoma. TFAB002s display strong binding affinity with CD20 and moderate binding affinity with CD3, thereby triggering target-specific T-cell activation, cytokine release, and tumor cell lysis in vitro. Furthermore, TFAB002s exhibit potent cytotoxicity against B-cell malignancies that express varying levels of CD20. Besides, the TFAB002s show potent pharmacodynamic activity in vivo in the WIL2-S cells CDX mouse model. Collectively, these results underscore the potential of TFAB002s as a highly promising therapeutic approach for selectively depleting CD20-positive B cells, thereby warranting further clinical evaluation as a viable treatment option for CD20-expressing B-cell malignancies.


Asunto(s)
Anticuerpos Biespecíficos , Antígenos CD20 , Fragmentos Fab de Inmunoglobulinas , Linfoma de Células B , Linfocitos T , Animales , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/inmunología , Antígenos CD20/inmunología , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfoma de Células B/tratamiento farmacológico , Ratones , Humanos , Fragmentos Fab de Inmunoglobulinas/inmunología , Linfocitos T/inmunología , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Activación de Linfocitos/inmunología , Activación de Linfocitos/efectos de los fármacos , Femenino
11.
Hereditas ; 161(1): 29, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223679

RESUMEN

BACKGROUND: Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. METHODS: The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. RESULTS: In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3ß/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. CONCLUSIONS: Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment.


Asunto(s)
Trióxido de Arsénico , Proliferación Celular , Sinergismo Farmacológico , Neoplasias Pulmonares , Proteínas Proto-Oncogénicas c-akt , Piridinas , Transducción de Señal , Carcinoma Pulmonar de Células Pequeñas , Serina-Treonina Quinasas TOR , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Trióxido de Arsénico/uso terapéutico , Trióxido de Arsénico/farmacología , Humanos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proliferación Celular/efectos de los fármacos , Animales , Piridinas/farmacología , Piridinas/uso terapéutico , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteína Adaptadora GRB10/genética , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación hacia Abajo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología
12.
Curr Issues Mol Biol ; 46(9): 10130-10139, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39329956

RESUMEN

Statins inhibit 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, and reduce cholesterol synthesis. They also have been demonstrated to improve prognosis in patients with various cancers, suggesting a potential anti-cancer effect of statins. However, there is no consensus on the molecular targets of statins for their anti-cancer effects. Docetaxel (DOC) is a microtubule-stabilizing agent currently used as a chemotherapeutic drug in several cancers, including lung cancer. Interestingly, the anti-cancer effects of either drug that are related to abnormal or wild-type TP53 gene have been implied. Therefore, the drug sensitivity of DOC and lovastatin in human lung cancer cells was evaluated. We found that H1355 (mutant TP53-E285K), CL1 (mutant TP53-R248W), and H1299 (TP53-null) human non-small cell lung cancer cells were more sensitive to lovastatin than A549 and H460 cells expressing wild-type TP53. Conversely, A549 and H460 cells showed higher sensitivity to DOC than H1299 and CL1 cells, as demonstrated by the MTT assay. When endogenous TP53 activity was inhibited by pifithrin-α in A549 and H460 cells, lovastatin sensitivities significantly increased, and cancer cell viabilities markedly reduced. These results indicate that TP53 status is associated with the anti-cancer effect of statins in human lung cancer cells. Mutated or null TP53 status is correlated with higher statin sensitivity. Furthermore, DOC-resistant H1299 (H1299/D8) cells showed significant sensitivity to lovastatin treatment compared to DOC-resistant A549 (A549/D16) cells, indicating a potential application of statins/chemotherapy combination therapy to control wild-type and abnormal TP53-containing human lung tumors.

13.
PeerJ ; 12: e18158, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39346086

RESUMEN

Background: Cervical cancer (CC) is a neoplasia with a high heterogeneity. We aimed to explore the characteristics of tumor microenvironment (TME) for CC treatment. Methods: HPV positive (+) and negative (-) samples from cervical cancer (CC) patients were sourced from the Gene Expression Omnibus (GEO) database. The single-cell RNA sequencing (scRNA-seq) data were processed and annotated for cell types utilizing the Seurat package. Following this, the expression levels and biological roles of the marker genes were analyzed applying real-time PCR (RT-PCR) and transwell assays. Furthermore, the enrichment of genes with significantly differential expressions and copy number variations was assessed by the ClusterProlifer and inferCNV software packages. Results: Seven main cell clusters were classified based on a total of 12,431 cells. The HPV- CC samples exhibited a higher immune cell infiltration level, while epithelial cells and myofibroblasts had higher proportion in the HPV+ CC samples with extensive heterogeneity. Immune pathways including antigen treatment and presentation, immunoglobulin production and T cell mediated immunity were significantly activated in the HPV- CC group with lower cell cycle and proliferation activity. However, the anti-tumor immunity of these cells was inhibited in HPV+ CC group with higher cell proliferation activity. Moreover, the amplification and loss of CNVs also supported that these cells in HPV- CC samples were prone to anti-tumor activation. Further cell validation results showed that except GZMA, the levels of APOC1, CEACAM6, FOXP3, SFRP4 and TFF3 were all higher in CC cells Hela, and that silencing TFF3 could inhibit the migration and invasion of CC cells in-vitro. Conclusion: This study highlighted the critical role of HPV infection in CC progression, providing a novel molecular basis for optimizing the current preventive screening and personalized treatment for the cancer.


Asunto(s)
Células Epiteliales , Miofibroblastos , Infecciones por Papillomavirus , Análisis de la Célula Individual , Microambiente Tumoral , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Femenino , Análisis de la Célula Individual/métodos , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Células Epiteliales/virología , Células Epiteliales/patología , Células Epiteliales/metabolismo , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/patología , Miofibroblastos/virología , Miofibroblastos/patología , Miofibroblastos/metabolismo , Progresión de la Enfermedad , Análisis de Secuencia de ARN , Variaciones en el Número de Copia de ADN/genética , Regulación Neoplásica de la Expresión Génica , Papillomaviridae/genética
14.
Org Lett ; 26(36): 7607-7613, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39231445

RESUMEN

A rhodium-catalyzed one-pot access to valuable polycyclic frameworks of fluorenone-4-carboxylic acids and diphenic anhydrides via the oxidative dimeric cyclization of aromatic acids has been developed. This transformation proceeded via carboxyl-assisted 2-fold C-H activation followed by intramolecular Friedel-Crafts or dehydration reactions. The silver salt additive plays a vital role in the chemoselectivity of the products. Diphenic anhydride 3l exhibits a maximum fluorescence quantum yield of up to 59%.

15.
Commun Eng ; 3(1): 128, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251731

RESUMEN

To address the growing demand from emerging applications, high transmission capacity is essential for both fibre backbones and last-mile communications. This can be achieved by integrating optical fibre with optical wireless technologies, facilitating the development of fibre-free-space optical communications. Here we report a bidirectional wavelength-division-multiplexing fibre-free-space optical communication employing polarisation multiplexing technique and tunable optical vestigial sideband filter. The transmission capacity is considerably increased by integrating the polarisation multiplexing technique with the wavelength-division-multiplexing scheme. The transmission performance is extensively enhanced by using a tunable optical vestigial sideband filter and vestigial sideband-four-level pulse amplitude modulation. Moreover, the optical wireless link is substantially extended through the operation of triplet lenses. Low bit error rates and clear vestigial sideband-four-level pulse amplitude modulation eye diagrams are attained with a high aggregate transmission capacity of 480 Gb/s for downstream/upstream transmission. This capability of bidirectional fibre-free-space optical communications holds substantial potential for enhancing advanced wired-wireless communications.

16.
Int J Biol Macromol ; 278(Pt 2): 134779, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151850

RESUMEN

Excessive iron in the liver may exacerbate Non-alcoholic fatty liver disease (NAFLD) by increasing the risk of liver cell expansion, inflammation and fibrosis. Ferroptosis in liver cells may lead the progression of simple fatty liver degeneration to steatohepatitis (NASH). More and more studies shew that ferroptosis played a crucial role in the pathological process of NAFLD. Based on the mechanism of ferroptosis, this study first synthesized a liver targeted 18-ß-Glycyrrhetinic-acid-chitosan oligosaccharide -N-acetylcysteine polymer (GCNp), and further curcumin (Cur) was used as model drug to prepare Cur loaded nanodelivery system (GCNp-Cur NPs). The particle size of GCNp-Cur NPs was 132.5 ± 9.8 nm, PDI was 0.148 ± 0.026 and the potential was 23.8 mV. GCNp-Cur NPs can regulate the GPX4/GSH pathway, inhibit lipid peroxidation, restore cellular oxidative environment, reduce free Fe2+, improve cellular lipid metabolism and iron metabolism, thereby NPs inhibited liver cell ferroptosis through multiple pathways. Additionally, GCNp-Cur NPs could also alleviate liver tissue lipid accumulation and oxidative damage, delaying disease progression, and providing a new method and theoretical basis for the treatment of NAFLD.


Asunto(s)
Quitosano , Ferroptosis , Nanopartículas , Enfermedad del Hígado Graso no Alcohólico , Oligosacáridos , Ferroptosis/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Nanopartículas/química , Animales , Oligosacáridos/farmacología , Oligosacáridos/química , Humanos , Ratones , Curcumina/farmacología , Curcumina/química , Masculino , Peroxidación de Lípido/efectos de los fármacos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hierro/química , Hierro/metabolismo , Polímeros/química , Polímeros/farmacología , Metabolismo de los Lípidos/efectos de los fármacos
17.
Cancer Imaging ; 24(1): 109, 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39155364

RESUMEN

OBJECTIVES: This study aimed to investigate the intra- and inter-observer consistency of the Visually Accessible Rembrandt Images (VASARI) feature set before and after dichotomization, and the association between dichotomous VASARI features and the overall survival (OS) in glioblastoma (GBM) patients. METHODS: This retrospective study included 351 patients with pathologically confirmed IDH1 wild-type GBM between January 2016 and June 2022. Firstly, VASARI features were assessed by four radiologists with varying levels of experience before and after dichotomization. Cohen's kappa coefficient (κ) was calculated to measure the intra- and inter-observer consistency. Then, after adjustment for confounders using propensity score matching, Kaplan-Meier curves were used to compare OS differences for each dichotomous VASARI feature. Next, patients were randomly stratified into a training set (n = 211) and a test set (n = 140) in a 3:2 ratio. Based on the training set, Cox proportional hazards regression analysis was adopted to develop combined and clinical models to predict OS, and the performance of the models was evaluated with the test set. RESULTS: Eleven VASARI features with κ value of 0.61-0.8 demonstrated almost perfect agreement after dichotomization, with the range of κ values across all readers being 0.874-1.000. Seven VASARI features were correlated with GBM patient OS. For OS prediction, the combined model outperformed the clinical model in both training set (C-index, 0.762 vs. 0.723) and test set (C-index, 0.812 vs. 0.702). CONCLUSION: The dichotomous VASARI features exhibited excellent inter- and intra-observer consistency. The combined model outperformed the clinical model for OS prediction.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Puntaje de Propensión , Humanos , Glioblastoma/mortalidad , Glioblastoma/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Encefálicas/mortalidad , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Estimación de Kaplan-Meier , Variaciones Dependientes del Observador
18.
J Exp Bot ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39171750

RESUMEN

Amino acid homeostasis is interconnected with the immune network of plants. During plant-pathogen interaction, amino acid transporters (AATs) have been shown to be involved in plant immune responses. However, the molecular mechanism by which how AATs function in this process remains elusive. In this study, we identify OsMP1 that acts as a quantitative trait locus against blast fungus from a joint analysis of GWAS and QTL mapping in rice. Heterogeneous expression of OsMP1 in yeast supports its function in transporting a wide range of amino acids, including Thr, Ser, Phe, His and Glu. OsMP1 could also mediate 15N-Glu efflux and influx in Xenopus oocyte cells. The expression of OsMP1 is dramatically induced by Magnaporthe oryzae in the resistant landrace Heikezijing, while remaining unresponsive in the susceptible landrace Suyunuo. Overexpressing OsMP1 in Suyunuo enhances disease resistance to blast fungus and leaf-blight bacterium without yield penalty. Furthermore, the overexpression of OsMP1 leads to increased accumulation of Thr, Ser, Phe and His in the leaves. And the heightened levels of these amino acids contribute to reduced disease susceptibility, which is associated with upregulated jasmonic acid pathway. Thus, our results elucidate the pivotal role of OsMP1 in disease resistance and provide a potential target for breeding more resistant rice cultivars without compromising yield.

19.
Nutrients ; 16(15)2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39125294

RESUMEN

Immunodeficiency can disrupt normal physiological activity and function. In this study, donkey bone collagen peptide (DP) and its iron chelate (DPI) were evaluated their potential as immunomodulators in cyclophosphamide (Cytoxan®, CTX)-induced Balb/c mice. The femoral tissue, lymphocytes, and serum from groups of mice were subjected to hematoxylin and eosin (H&E) staining, methylthiazolyldiphenyl-tetrazolium bromide (MTT) cell proliferation assays, and enzyme-linked immunosorbent assay (ELISA), respectively. Furthermore, a non-targeted metabolomics analysis based on UPLC-MS/MS and a reverse transcription polymerase chain reaction (RT-qPCR) technology were used to explore the specific metabolic pathways of DPI regulating immunocompromise. The results showed that CTX was able to significantly reduce the proliferative activity of mouse splenic lymphocytes and led to abnormal cytokine expression. After DP and DPI interventions, bone marrow tissue damage was significantly improved. In particular, DPI showed the ability to regulate the levels of immune factors more effectively than Fe2+ and DP. Furthermore, metabolomic analysis in both positive and negative ion modes showed that DPI and DP jointly regulated the levels of 20 plasma differential metabolites, while DPI and Fe2+ jointly regulated 14, and all 3 jointly regulated 10. Fe2+ and DP regulated energy metabolism and pyrimidine metabolism pathways, respectively. In contrast, DPI mainly modulated the purine salvage pathway and the JAK/STAT signaling pathway, which are the key to immune function. Therefore, DPI shows more effective immune regulation than Fe2+ and DP alone, and has good application potential in improving immunosuppression.


Asunto(s)
Colágeno , Ciclofosfamida , Equidae , Quelantes del Hierro , Ratones Endogámicos BALB C , Animales , Colágeno/metabolismo , Quelantes del Hierro/farmacología , Ratones , Proliferación Celular/efectos de los fármacos , Péptidos/farmacología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Inmunosupresores/farmacología , Metabolómica , Citocinas/metabolismo , Masculino , Huesos/efectos de los fármacos , Huesos/metabolismo , Terapia de Inmunosupresión
20.
Artículo en Inglés | MEDLINE | ID: mdl-39208869

RESUMEN

BACKGROUND: Reconstruction of maxillary defects may lead to changes in the upper airway. These changes may cause postoperative airway obstruction issues. PURPOSE: The purpose was to evaluate the postoperative changes in the upper airway following maxillary reconstruction with an anterolateral thigh flap (ALTF) and to identify the factors associated with these changes. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study involved 26 patients who underwent maxillectomy for maxillary tumors, followed by reconstruction using an ALTF. Patients with a history of upper respiratory system disease and sleep-disorder breathing were excluded. PREDICTOR VARIABLE: The predictor variable was the residual rate of ALTF volume (ALTF-RS), calculated as the ratio of ALTF volume at 6 months postsurgery (T2) to that at 2 weeks postsurgery (T1). THE OUTCOME VARIABLES: The outcome variables were the upper airway parameters. The upper airway was assessed at 3 time points: 1 week preoperatively (T0), T1, and T2. Ratios were used to represent airway changes over time. COVARIATES: The covariates are age, sex, Brown classification, body mass index, hypertension, neck dissection, and tracheostomy, etc. ANALYSES: Airway measurement differences between the three time points were analyzed by one-way analysis of variance. Pearson correlation and Spearman correlation analysis were used to analyze the correlation coefficients between airway changes and ALTF-RS. Statistical significance was established at a P value < .05. RESULTS: The sample included 26 subjects with a mean age of 55.6 ± 15.2 years and 15/26 (57.7%) were male. Compared to T0, the nasopharyngeal and retropalatal airway volumes at T1 significantly decreased (P < .05) but recovered or surpassed preoperative levels by T2. The minimum cross-sectional airway area significantly decreased by T1 (P < .05), but increased by T2 (P < .05). The narrowest airway section was predominantly in the palatopharyngeal airway. The airway changes of T2/T1 and ALTF-RS were not correlated (P > .05) except for anterior-inferior point of the 4th cervical vertebra cross-sectional area (P < .05). CONCLUSION AND RELEVANCE: The volumetric changes in the airway were not associated with ALTF-RS. The substantial narrowing of minimum cross-sectional airway area at T1 emphasized the need for vigilant airway management in these patients.

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