Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.810
Filtrar
1.
Epilepsia ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39110151

RESUMO

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

2.
Life Sci ; 354: 122945, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39127319

RESUMO

Renal fibrosis is the common final pathway of progressive renal diseases, in which the macrophages play an important role. ELISA was used to detect CD5 antigen-like (CD5L) in serum samples from end-stage renal disease (ESRD), as well as in mice serum with unilateral ureteral occlusion (UUO). Recombinant CD5L was injected into UUO mice to assess renal injury, fibrosis, and macrophage infiltration. The expression of CD5L was significantly upregulated in the serum of patients with ESRD and UUO mice. Histological analysis showed that rCD5L-treated UUO mice had more severe renal injury and fibrosis. Furthermore, rCD5L promoted the phenotypic transfer of monocytes from Ly6Chigh to LyC6low. RCD5L promoted TGF-ß signaling pathway activation by promoting Smad2/3 phosphorylation. We used Co-IP to identify HSPA5 interact with CD5L on cell membrane could inhibit the formation of the Cripto/HSPA5 complex, and promote the activation of the TGF-ß signaling pathway. The CD5L antibody could reduce the degree of renal fibrosis in UUO mice.

3.
Adv Mater ; : e2407741, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39091050

RESUMO

The metal-catalyzed sulfur reaction in lithium-sulfur (Li-S) batteries usually suffers from the strong binding of sulfur species to the catalyst surface, which destroys the electric double layer (EDL) region there. This causes rapid catalyst deactivation because it prevents the desorption of sulfur species and mass transport through the EDL is hindered. This work introduces a competitive adsorption factor (fsulfur) as a new indicator to quantify the competitive adsorption of sulfur species in the EDL and proposes an alloying method to change it by strengthening the p-d hybridization of alloying metals with electrolyte solvents. A cobalt-zinc alloy catalyst with a moderate fsulfur lowers the activation energy of the rate-limiting step of the conversion of lithium polysulfides to lithium sulfide, giving a platform capacity proportion that is 96% of the theoretical value and has a greatly improved anti-passivation ability, especially at high sulfur loadings and lean electrolyte conditions (a low E/S ratio of 5 µL mgS -1). A pouch cell using this approach has a high energy density of up to 464 Wh kg-1. Such a competitive adsorption indicator and alloying strategy offer a new guideline for catalyst design and a practical electrocatalysis solution for Li-S batteries.

4.
Pediatric Health Med Ther ; 15: 265-272, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39135906

RESUMO

Objective: This study aimed to assess the growth of full-term infants with different sizes at birth and examine catch-up and catch-down growth in their first year. Methods: This retrospective population-based cohort study was based on the Guangdong Provincial Women and Children Health Information System. 194797 full-term singleton live births were extracted. Measurements for weight and length were taken at birth, 6 months, and 12 months. The size-for-gestational age was categorized as small (SGA, <10th centile), appropriate (AGA, 10th-90th centiles), or large (LGA, >90th centile) based on the international newborn size for gestational age and sex INTERGROWTH-21st standards. Catch-up and catch- down growth were defined as a change in standard deviation in z-score greater than 0.67 in the growth curves. Results: Of the 194797 full-term singletons, the average gestational age was 39.28 ± 1.03 weeks, and the average weight of the newborns was 3205 ± 383 grams. 15632 infants were identified as SGA (8.0%) and 12756 were LGA (6.5%). At 1 year of age, catch-up growth in weight was observed in 63.0% of SGA infants, 29.5% of AGA infants, and 5.4% of LGA infants. Conversely, catch-down growth occurred in 3.3% of SGA infants, 17.8% of AGA infants, and 54.7% of LGA infants. The proportions of catch-up growth in length for SGA, AGA, and LGA infants within the first year were 31.4%, 22.5%, and 17.1%, respectively. Catch-up or catch-down growth predominantly occurred before 6 months of age. However, from 6 to 12 months, there was no significant variation in WAZ among children with different birth sizes. Conclusion: In their first year of life, full-term singleton live births tend towards regression to the mean in their postnatal weight and length. The average delay in the growth of LGA is compensated by an increase in it of the SGA. Early monitoring and intervention are crucial for optimizing growth in infants with different birth sizes.

5.
J Control Release ; 374: 194-204, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39142356

RESUMO

Recent advancements in cancer treatment have underscored the inadequacy of conventional monotherapies in addressing complex malignant tumors. Consequently, there is a growing interest in synergistic therapies capable of overcoming the limitations of monotherapies, leading to more personalized and effective approaches. Among these, the combination of photothermal therapy (PTT) and chemotherapy has emerged as a promising avenue for tumor management. In this study, we present a novel approach utilizing thermoresponsive mesoporous silica nanoparticles (MSN) as a delivery system for the chemotherapeutic drug doxorubicin. By incorporating photothermal agent copper sulfide (CuS) nanoparticles into the MSN, the resulting composite material exhibits potent photothermal properties. Furthermore, the integration of an upper critical solution temperature (UCST) polymer within the silica outer layer serves as a "gatekeeper", enabling precise control over drug release kinetics. This innovative nanomaterial effectively merges thermoresponsive behavior with PTT, thereby minimizing the collateral damage associated with traditional chemotherapy on healthy tissues. Moreover, in both in vitro studies using mouse breast carcinoma cells (4 T1) and in vivo experiments utilizing a 4 T1 tumor-bearing mouse model, our nanomaterials demonstrated synergistic effects, enhancing the anti-tumor efficacy of combined PTT and chemotherapy. With its remarkable photothermal conversion efficiency, robust stability, and biocompatibility, the UCST-responsive nanoplatform holds immense potential for clinical applications.

6.
J Pharmacol Sci ; 156(2): 57-68, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39179335

RESUMO

Metformin is an important antidiabetic drug that has the potential to reduce skeletal muscle atrophy and promote the differentiation of muscle cells. However, the exact molecular mechanism underlying these functions remains unclear. Previous studies revealed that the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1), which participates in tumor progression, inhibits muscle atrophy. Therefore, we hypothesized that the protective effect of metformin might be related to ZEB1. We investigated the positive effect of metformin on IL-1ß-induced skeletal muscle atrophy by regulating ZEB1 in vitro and in vivo. Compared with the normal cell differentiation group, the metformin-treated group presented increased myotube diameters and reduced expression levels of atrophy-marker proteins. Moreover, muscle cell differentiation was hindered, when we artificially interfered with ZEB1 expression in mouse skeletal myoblast (C2C12) cells via ZEB1-specific small interfering RNA (si-ZEB1). In response to inflammatory stimulation, metformin treatment increased the expression levels of ZEB1 and three differentiation proteins, MHC, MyoD, and myogenin, whereas si-ZEB1 partially counteracted these effects. Moreover, marked atrophy was induced in a mouse model via the administration of lipopolysaccharide (LPS) to the skeletal muscles of the lower limbs. Over a 4-week period of intragastric administration, metformin treatment ameliorated muscle atrophy and increased the expression levels of ZEB1. Metformin treatment partially alleviated muscle atrophy and stimulated differentiation. Overall, our findings may provide a better understanding of the mechanism underlying the effects of metformin treatment on skeletal muscle atrophy and suggest the potential of metformin as a therapeutic drug.


Assuntos
Diferenciação Celular , Hipoglicemiantes , Metformina , Músculo Esquelético , Atrofia Muscular , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Metformina/farmacologia , Animais , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Atrofia Muscular/prevenção & controle , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/etiologia , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Camundongos , Diferenciação Celular/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Masculino , Proteína MyoD/metabolismo , Proteína MyoD/genética , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/patologia , Lipopolissacarídeos , Miogenina/metabolismo , Miogenina/genética , Linhagem Celular
7.
Cancer Med ; 13(16): e70132, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39162366

RESUMO

BACKGROUND: Pancreatoblastoma (PB) is one of the rare malignant tumors that typically occurs in children. Cases of PB in adults are highly unusual. This disease often presents with subtle symptoms and lacks characteristic clinical manifestations, leading to diagnostic challenges. OBJECTIVE: This study integrates the relevant literature on adult PB, conducting data analysis on clinical features, laboratory and imaging results, pathological characteristics, and treatments according to inclusion and exclusion criteria. Kaplan-Meier univariate analysis and Log-rank tests are employed to analyze survival data from adult PB follow-up, exploring factors influencing prognosis. RESULTS: A total of 65 articles were included, encompassing 103 cases of adult PB. The average age of PB patients was 41.78 years (range 19-81 years), and the male-to-female ratio was 1.06:1. Patients frequently presented with abdominal pain as the initial symptom. Laboratory results lacked specificity and imaging findings often presented as large, well-defined masses. PB exhibited distinctive pathological features, including squamous corpuscles (n = 76, 89.41%) and acinar differentiation (n = 34, 40%), with frequent positive expression of Trypsin, Chymotrypsin, and AACT (Alpha-1-Antichymotrypsin). APC (Adenomatous Polyposis Coli) gene mutation was the most common molecular alteration in adult PB. During the follow-up period, 43.59% of patients died (range 3 days to 348 months). The primary factors affecting prognosis were the presence of metastasis (χ2 = 3.996, p = 0.046) and incomplete surgical resection (χ2 = 5.586, p = 0.018), with mean survival times of 48 months and 27 months, respectively. CONCLUSIONS: PB in adults is an invasive tumor. The key to distinguishing PB from other pancreatic tumors lies in recognizing its unique pathological feature, the squamous corpuscles. Timely and complete surgical resection is the preferred treatment following diagnosis. Patients with incomplete resection or the presence of lymph nodes or (and) distant metastases have a poor prognosis.


Assuntos
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Adulto , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem
8.
J Asthma ; : 1-11, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39163002

RESUMO

BACKGROUND: Previous observational studies have indicated a potential association between metabolic syndrome (MetS) and asthma, though the causal nature of this connection is still uncertain. Our study used Mendelian randomization (MR) to examine the causal relationship between metabolic syndrome (MetS) and its components with asthma. METHODS: This study utilized single nucleotide polymorphisms (SNPs) related to MetS and its components, sourced from publicly available genome-wide association studies (GWAS) data, in combination with asthma data from the FinnGen database. Statistical analyses were conducted using the inverse variance weighted method (IVW), MR-Egger, and weighted median method. The robustness of the findings was confirmed through various sensitivity analyses. RESULTS: The IVW analysis indicated that MetS was associated with an increased risk of asthma (OR = 1.0781, 95% CI = 1.0255-1.1333, p = 0.0032). Among the components of MetS, waist circumference (WC) showed a strong association with asthma (OR = 1.4777, 95% CI = 1.3412-1.6281, p = 2.8707 × 10-15). Conversely, high-density lipoprotein cholesterol (HDL-C) was found to be inversely related to the risk of asthma (OR = 0.9186, 95% CI = 0.8669-0.9734, p = 0.0041). CONCLUSION: The findings of this study support that MetS and its specific components, particularly abdominal obesity, are linked to a higher risk of asthma, while HDL-C might offer protective effects against asthma. These findings provide a foundation both for further research and possible therapeutic interventions.

9.
Ann Med ; 56(1): 2394582, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39183464

RESUMO

BACKGROUND: Haemodialysis (HD) patients are predisposed to physical ailments, and their occurrence of coronavirus disease 2019 (COVID-19) could potentially lead to a more unfavourable prognosis. However, the impact of SARS-CoV-2 (Omicron variant) infection on the prognosis of HD patients remains unclear. This study aimed to explore the impact of Omicron variant infection on the prognosis of HD patients. METHODS: Eligible participants were patients undergoing maintenance HD treatment during a large-scale outbreak of COVID-19 (Omicron variant) in Shanghai, China, from April 7 to May 30, 2022. According to SARS-CoV-2 infection status of participants, the HD patients were divided into two groups: a COVID-19 group and a non-COVID-19 group. The primary outcome assessed was in-hospital mortality, and secondary outcomes encompassed the incidence of severe cases, admission to intensive care, length of hospital stay, and blood indices. Statistical analysis was conducted by comparative analysis and multiple logistic regression. RESULTS: This study recruited 588 HD patients, including 199 cases in the COVID-19 group and 389 in the non-COVID-19 group. In the COVID-19 group, the mortality rate was 8.45% (17/199), whereas in the non-COVID-19 group, the rate was 3.34% (13/389) (p < 0.05). Compared with the non-COVID-19 group, the COVID-19 group had a risk ratio (RR) with 95% confidence interval (CI) of 2.56 (1.27-5.15) for mortality, and the absolute risk difference (ARD) with 95% CI of 5.20% (1.34%-9.06%). Multiple logistic regression confirmed Omicron variant as a risk factor for mortality among HD patients. Additionally, the COVID-19 group had a higher proportion of severe cases, intensive care admission, hypocalcaemia and hyperphosphatemia and longer hospitalization duration, compared to the non-COVID-19 group (p < 0.05). CONCLUSIONS: Omicron variant infection was associated with increased mortality risk in HD patients, and Omicron infection worsen the prognosis of HD patients. Enhancing immune protection against SARS-CoV-2 is crucial for HD patients during the ongoing COVID-19 pandemic.


Assuntos
COVID-19 , Mortalidade Hospitalar , Diálise Renal , SARS-CoV-2 , Humanos , COVID-19/mortalidade , COVID-19/epidemiologia , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Tempo de Internação/estatística & dados numéricos , Adulto
10.
Front Immunol ; 15: 1404669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185408

RESUMO

Background: Various trials have demonstrated the clinical benefits of lenvatinib plus pembrolizumab in patients with advanced or recurrent endometrial cancer, regardless of mismatch repair (MMR) status or histologic subtype. The majority of the previously published trials had small sample sizes. Here, we aimed to assess the reported efficacy and safety profile of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. Methods: We utilized the Cochrane Library, PubMed, Web of Science and Embase databases to identify clinical trials evaluating the efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced and recurrent endometrial cancer. The outcomes analyzed were progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR) and the incidence of adverse events (AEs). Subgroup analysis was conducted on the basis of MMR status (deficient, dMMR or proficient, pMMR). Results: Four trials (582 patients) were included. The pooled ORR was 32.7% [95% confidence interval (CI): 28.9-36.5]. Subgroup analysis revealed an ORR of 48.1% (95% CI: 26.1-70.2) for dMMR group and 33.1% (95% CI: 25.7-40.6) for pMMR group. The pooled DCR was 74.9% (95% CI: 71.3-78.4%). Subgroup analysis revealed a DCR of 81.0% (95% CI: 64.5-97.6) for the dMMR group and 76.3% (95% CI: 66.3-86.3) for the pMMR group. Follow-up was reported in all included studies. The median range time of PFS and OS was 5.3 months-258 days and 17.2 months-not reached, respectively. Regarding safety, the overall pooled proportions of any-grade AE and AEs ≥ grade 3 were 95.8% (95% CI: 89.5-100.0) and 80.2% (95% CI: 59.9-100.0), respectively. Conclusion: Lenvatinib plus pembrolizumab showed a relevant clinical benefit and significant toxicity in patients with advanced and recurrent endometrial cancer. Further studies encompassing long-term outcomes are warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=522160/, identifier CRD42024522160.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Recidiva Local de Neoplasia , Compostos de Fenilureia , Quinolinas , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/mortalidade , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
11.
Am J Cancer Res ; 14(6): 2921-2933, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005667

RESUMO

Double expressor lymphoma (DEL), characterized by high expressions of both MYC and BCL-2, displays poor prognosis after current therapies. The HDAC inhibitor chidamide has been approved for treatment of T cell lymphoma, but its efficacy on B cell lymphoma is unclear. Here, by combining inhibition screening and transcriptomic analyses, we found that the sensitivity of B lymphoma cells to chidamide was positively correlated with the expression levels of MYC. Chidamide treatment reduced MYC protein levels and repressed MYC pathway in B lymphoma cells with high MYC expressions. Ectopic expression of MYC in chidamide-insensitive B lymphoma cells increased their response to chidamide. Thus, we proposed that adding chidamide into R-CHOP (CR-CHOP) might be effective for DEL, and retrospectively analyzed 185 DEL patients treated in West China Hospital. 80% of patients showed response to CR-CHOP treatment. In the median follow-up of 42 months, CR-CHOP significantly improve the survival for DEL patients with R-IPI ≤2. Totally 35 patients underwent autologous stem cell transplantation (ASCT) in remission and demonstrated a trend for better survival. Combining CR-CHOP with ASCT resulted in the most superior PFS and OS above all. For response patients, CR-CHOP reduced relapse with better PFS than R-CHOP-like regimens with or without ASCT. Taken together, our data indicated that chidamide repressed the MYC pathway in B lymphoma and is potentially efficacious to treat DEL.

12.
IEEE Trans Image Process ; 33: 4215-4230, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39008385

RESUMO

Real-world data often follows a long-tailed distribution, where a few head classes occupy most of the data and a large number of tail classes only contain very limited samples. In practice, deep models often show poor generalization performance on tail classes due to the imbalanced distribution. To tackle this, data augmentation has become an effective way by synthesizing new samples for tail classes. Among them, one popular way is to use CutMix that explicitly mixups the images of tail classes and the others, while constructing the labels according to the ratio of areas cropped from two images. However, the area-based labels entirely ignore the inherent semantic information of the augmented samples, often leading to misleading training signals. To address this issue, we propose a Contrastive CutMix (ConCutMix) that constructs augmented samples with semantically consistent labels to boost the performance of long-tailed recognition. Specifically, we compute the similarities between samples in the semantic space learned by contrastive learning, and use them to rectify the area-based labels. Experiments show that our ConCutMix significantly improves the accuracy on tail classes as well as the overall performance. For example, based on ResNeXt-50, we improve the overall accuracy on ImageNet-LT by 3.0% thanks to the significant improvement of 3.3% on tail classes. We highlight that the improvement also generalizes well to other benchmarks and models. Our code and pretrained models are available at https://github.com/PanHaulin/ConCutMix.

13.
Stem Cell Res Ther ; 15(1): 194, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956719

RESUMO

BACKGROUND: Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis. METHODS: The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair. RESULTS: The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects. CONCLUSION: NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.


Assuntos
Células-Tronco Mesenquimais , Fator de Crescimento Neural , Osteogênese , Ratos Sprague-Dawley , Alicerces Teciduais , Animais , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Neural/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Ratos , Alicerces Teciduais/química , Regeneração Óssea , Aloenxertos , Masculino , Engenharia Tecidual/métodos , Piroptose , Sulfonamidas/farmacologia , Diferenciação Celular , Transplante de Células-Tronco Mesenquimais/métodos , Transplante Ósseo/métodos
14.
Adv Med Sci ; 69(2): 339-348, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004219

RESUMO

PURPOSE: The process of osteogenic differentiation hinges upon the pivotal role of mechanical signals. Previous studies found that mechanical tensile strain of 2500 microstrain (µÎµ) at a frequency of 0.5 â€‹Hz promoted osteogenesis in vitro. However, the mechanism of the mechanical strain influencing osteogenesis at the cellular and molecular levels are not yet fully understood. This study aimed to explore the mechanism of mechanical strain on osteogenic differentiation of MC3T3-E1 cells. MATERIALS AND METHODS: Proteomics analysis was conducted to explore the mechanical strain that significantly impacted the protein expression. Bioinformatics identified important mechanosensitive proteins and the expression of genes was investigated using real-time PCR. The dual-luciferase assay revealed the relationship between the miRNA and its target gene. Overexpression and downexpression of the gene, to explore its role in mechanically induced osteogenic differentiation and transcriptomics, revealed further mechanisms in this process. RESULTS: Proteomics and bioinformatics identified an important mechanosensitive lowexpression protein ATP13A3, and the expression of Atp13a3 gene was also reduced. The dual-luciferase assay revealed that microRNA-3070-3p (miR-3070-3p) targeted the Atp13a3 gene. Furthermore, the downexpression of Atp13a3 promoted the expression levels of osteogenic differentiation-related genes and proteins, and this process was probably mediated by the tumor necrosis factor (TNF) signaling pathway. CONCLUSION: Atp13a3 responded to mechanical tensile strain to regulate osteogenic differentiation, and the TNF signaling pathway regulated by Atp13a3 was probably involved in this process. These novel insights suggested that Atp13a3 was probably a potential osteogenesis and bone formation regulator.

15.
J Microbiol Biotechnol ; 34(7): 1464-1474, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-38973400

RESUMO

Soil extracellular enzyme plays a vital role in changing soil nitrogen (N) mineralization of rice field. However, the effects of soil extracellular enzyme activities (EEA) and microbial community composition response to N mineralization of rice field under short-term tillage treatment needed to be further explored. In this study, we investigated the impact of short-term (8-year) tillage practices on rhizosphere soil N transformation rate, soil enzyme activities, soil microbial community structure, and the N mineralization function gene abundances in double-cropping rice field in southern China. The experiment consisted of four tillage treatments: rotary tillage with crop straw input (RT), conventional tillage with crop straw input (CT), no-tillage with crop straw retention (NT), and rotary tillage with all crop straw removed as a control (RTO). The results indicated that the rhizosphere soil N transformation rate in paddy field under the NT and RTO treatments was significantly decreased compared to RT and CT treatments. In comparison to the NT and RTO treatments, soil protease, urease, ß-glucosaminidase, and arginase activities were significantly improved by the CT treatment, as were abundances of soil sub, npr, and chiA with CT and RT treatments. Moreover, the overall diversity of soil bacterial communities in NT and RTO treatments was significantly lower than that in RT and CT treatments. Soil chitinolytic and bacterial ureolytic communities were also obviously changed under a combination of tillage and crop straw input practices.


Assuntos
Agricultura , Bactérias , Microbiota , Nitrogênio , Oryza , Rizosfera , Microbiologia do Solo , Solo , Oryza/crescimento & desenvolvimento , Nitrogênio/metabolismo , Nitrogênio/análise , Solo/química , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , China , Agricultura/métodos
17.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930842

RESUMO

Efficient recovery of gallium (Ga) from vanadium slag processing residue (VSPR) solution is of great significance for environmental protection and resource utilization, but improving its selective adsorption against the coexisting Sc3+ and In3+ is still challenging. Herein, a novel adsorbent consisting of 4-amino-3-hydrazino-1,2,4-triazol-5-thiol (AHTZT)-modified graphene oxide (GO-AHTZT) was successfully synthesized that exhibits a higher adsorption selectivity for Ga3+ in VSPR solution with coexisting Sc3+ and In3+. Under optimal conditions, the adsorption capacity of GO-AHTZT for Ga3+ can reach 23.92 mg g-1, which is 4.9 and 12.6 times higher than that for Sc3+ (4.87 mg g-1) and In3+ (1.90 mg g-1) adsorption, indicating the excellent anti-interference ability of GO-AHTZT against Sc3+ and In3+. The process and mechanism of Ga3+ adsorption onto GO-AHTZT was also studied and discussed in detail. By measuring the adsorption process and by characterizing the adsorbent before and after adsorption, we demonstrate that the selective interaction between the Ga3+- and N-containing groups in AHTZT is the main reason for the improved adsorption selectivity. This work opens up an avenue for the design and synthesis of highly selective adsorbents for Ga3+ in complex VSPR solutions.

18.
Clin Exp Pharmacol Physiol ; 51(7): e13900, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38843865

RESUMO

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.


Assuntos
Proliferação de Células , Medicamentos de Ervas Chinesas , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares , Neoplasias de Mama Triplo Negativas , Animais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Camundongos , Proliferação de Células/efeitos dos fármacos , Feminino , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-38875098

RESUMO

Deep neural networks have exhibited remarkable performance in image super-resolution (SR) tasks by learning a mapping from low-resolution (LR) images to high-resolution (HR) images. However, the SR problem is typically an ill-posed problem and existing methods would come with several limitations. First, the possible mapping space of SR can be extremely large since there may exist many different HR images that can be super-resolved from the same LR image. As a result, it is hard to directly learn a promising SR mapping from such a large space. Second, it is often inevitable to develop very large models with extremely high computational cost to yield promising SR performance. In practice, one can use model compression techniques to obtain compact models by reducing model redundancy. Nevertheless, it is hard for existing model compression methods to accurately identify the redundant components due to the extremely large SR mapping space. To alleviate the first challenge, we propose a dual regression learning scheme to reduce the space of possible SR mappings. Specifically, in addition to the mapping from LR to HR images, we learn an additional dual regression mapping to estimate the downsampling kernel and reconstruct LR images. In this way, the dual mapping acts as a constraint to reduce the space of possible mappings. To address the second challenge, we propose a dual regression compression (DRC) method to reduce model redundancy in both layer-level and channel-level based on channel pruning. Specifically, we first develop a channel number search method that minimizes the dual regression loss to determine the redundancy of each layer. Given the searched channel numbers, we further exploit the dual regression manner to evaluate the importance of channels and prune the redundant ones. Extensive experiments show the effectiveness of our method in obtaining accurate and efficient SR models.

20.
J Ethnopharmacol ; 333: 118411, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38824980

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies have revealed that a high-fat diet (HFD) promotes the progression of colorectal cancer (CRC) in close association with disturbances in the intestinal flora and metabolic disorders. Xianglian pill (XLP) is a well-established traditional prescription with unique advantages in controlling intestinal flora imbalance and inflammation. However, its therapeutic effects on HFD-related CRC remain largely unknown. AIM OF THE STUDY: The primary objective of this research was to investigate the anticancer mechanism of XLP in countering HFD-related CRC. MATERIALS AND METHODS: The protective effect of XLP was evaluated using azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced CRC model of mice exposed to a HFD. The degree of colorectal carcinogenesis, including body weight, colon length, and histopathology, was measured in mice treated with XLP and untreated mice. The effect of XLP on gut microbiota and its metabolites was detected using 16S rDNA and liquid chromatography/mass spectrometry analysis. Furthermore, a "pseudo-sterile" mouse model was constructed using antibiotics (Abx) to verify whether the gut microbiota and metabolites play a role in the pathogenesis of CRC. RESULTS: XLP inhibited colorectal tumorigenesis in a dose-dependent fashion. Our findings also highlighted that XLP protected the integrity of the intestinal barrier by reducing the expression of pro-inflammatory cytokines, such as IL-6 and TNF-α, as well as the infiltration of pro-inflammatory macrophages. Mechanistically, XLP inhibited the TLR4/MyD88 pathway. Notably, the XLP treatment increased the proportion of probiotics (particularly Akkermansia) and significantly reduced fecal deoxycholic acid (DCA), a microbiota-derived metabolite of bile acids (BA) closely related to Muribaculaceae. Furthermore, after Abx treatment, XLP showed no clear antitumor effects on CRC. Simultaneously, DCA-supplemented feedings promoted colorectal tumorigenesis and provoked obvious colonic inflammation, M1 macrophage infiltration, and colonic injury. In vitro, the results of RAW-264.7 macrophages and normal intestinal epithelial cells treated with DCA corroborated our in vivo findings, demonstrating consistent patterns in inflammatory responses and intestinal barrier protein expression. CONCLUSION: Our findings suggest that XLP inhibits colorectal cancer associated with HFD via inactivating TLR4/MyD88 by remodeling gut microbiota composition and BA metabolism.


Assuntos
Ácidos e Sais Biliares , Neoplasias Colorretais , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Transdução de Sinais , Animais , Masculino , Camundongos , Azoximetano/toxicidade , Ácidos e Sais Biliares/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Sulfato de Dextrana , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...