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1.
Aging Med (Milton) ; 7(3): 258-268, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38975298

RESUMO

This practice guideline focuses on the cognitive assessment for mild cognitive impairment in the Guangdong-Hong Kong-Macao Greater Bay Area. To achieve the standardization and normalization of its clinical practice and generate individualized intervention, the National Core Cognitive Center of the Second Affiliated Hospital of Guangzhou Medical University, the Cognitive Disorders Branch of Chinese Geriatic Society, the Dementia Group of Neurology Branch of Guangdong Medical Association and specialists from Hong Kong and Macao developed guidelines based on China's actual conditions and efficiency, economic cost and accuracy. The article addresses the significance, background, and the process of the assessment and follow-up to realize the promotion and dissemination of cognitive assessment.

2.
Int Immunopharmacol ; 139: 112696, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39018692

RESUMO

BACKGROUND: Anti-PD-1-based immunotherapy has limited benefits in patients with pancreatic cancer. Accumulating data indicate that natural products exert antitumor activity by remodeling the tumor immune microenvironment. It has been reported that neogambogic acid (NGA), an active natural monomer extracted from Garcinia, has anti-inflammatory and antitumor effects. Nevertheless, there are few systematic studies on the antitumor efficacy and immunomodulatory effects of NGA in pancreatic cancer. METHODS: An orthotopic mouse model of pancreatic cancer was established and were treated with different doses of NGA. Tumor growth and ascites were observed. Flow cytometry and immunohistochemistry (IHC) were used to investigate the tumor immune microenvironment. CD11b+ MDSCs were infused back into mice with pancreatic cancer to observe tumor progression after NGA treatment. Bone marrow cells were induced to differentiate into MDSCs, and the effects of NGA on MDSCs were analyzed and the underlying mechanism was explored. The effects of NGA combined with an anti-PD-1 antibody on pancreatic cancer were further tested. RESULTS: NGA significantly inhibited the tumor growth and improve ascites character in pancreatic cancer model mice. Flow cytometry and IHC analysis revealed that NGA decreased the MDSCs proportion and infiltration in the tumor microenvironment. Moreover, adoptive MDSCs largely attenuated the inhibitory effect of NGA on the progression of pancreatic cancer. In addition, we showed that NGA significantly promoted apoptosis and inhibited the differentiation, migration and immunosuppressive function of MDSCs and decreased level of STAT3 and p-STAT3. Furthermore, we demonstrated that NGA synergistically enhanced the efficacy of anti-PD-1 antibodies against pancreatic cancer. CONCLUSION: NGA inhibited the progression of pancreatic cancer by inhibiting MDSCs in the tumor microenvironment, and enhanced the efficacy of anti-PD-1 therapy in the treatment of pancreatic cancer.

3.
Huan Jing Ke Xue ; 45(7): 4332-4351, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022978

RESUMO

Excess agricultural biomass waste is increasing rapidly, leading to many environmental and governance issues. Therefore, increased attention has been paid to the recycling and value-added application of agricultural biomass waste. In recent years, the research of agricultural biomass waste utilization and derived functional materials has mainly included the following two aspects: ① the extraction of natural polymers and value-added applications and ② the direct preparation of new carbon-based materials, including adsorption, catalysis, energy storage electrode, and composite functional materials. The conversion of agricultural biomass waste into functional materials has been gradually realized and widely used. To enable industrial-scale production and the quality and safety of agricultural biomass waste derivatives and to develop highly feasible and cost-effective biomass waste conversion methods should be the focus of future studies.

4.
Microvasc Res ; 155: 104699, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901735

RESUMO

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (ISK1-3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of ISK1-3. H2O2 enhanced ISK1-3 and ET-1 production. Enhancing ISK1-3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1-3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.

5.
J Hazard Mater ; 475: 134835, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878429

RESUMO

Developing efficient and eco-friendly technologies for treating the antibiotic wastewaters is crucial. At present, the catalysts with metal-nitrogen (M-Nx) coordination showed excellent Fenton-like performance but were always difficult to realize practical antibiotics degradation because of their complicated preparation methods and inferior stability. In this work, the Co-Nx configuration was facilely reconstructed on the surface of Co3O4 (Co-Nx/Co3O4), which exhibited superior catalytic activity and stability towards various antibiotics. DFT results indicated that stronger ETP oxidation will be triggered by the electron-donating pollutants since more electrons can be easily migrated from these pollutants to the Co-Nx/Co3O4/PMS complex. The Co-Nx/Co3O4/PMS system could maintain superior oxidation capacity, high catalytic stability and anti-interference due to (i) the strong nonradical ETP oxidation with superior degradation selectivity in Co-Nx/Co3O4/PMS system, and (ii) the synchronously enhanced radical oxidation with high populations of non-selective radicals generated via activating PMS by the Co-Nx/Co3O4. As a result, the synergies of synchronously enhanced dual oxidation pathways guaranteed the self-cleaning properties, maintaining 98 % of activity after eight cycles and stability across a wide pH range. Basically, these findings have significant implications for developing technologies for purifying antibiotic wastewater.


Assuntos
Antibacterianos , Cobalto , Oxirredução , Óxidos , Poluentes Químicos da Água , Antibacterianos/química , Cobalto/química , Poluentes Químicos da Água/química , Óxidos/química , Catálise , Nitrogênio/química , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos
6.
Cell Transplant ; 33: 9636897241257568, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832653

RESUMO

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.


Assuntos
Anticorpos Monoclonais , Basiliximab , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Proteínas Recombinantes de Fusão , Humanos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Basiliximab/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Proteínas Recombinantes de Fusão/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Estudos Retrospectivos , Adolescente , Irmãos , Adulto Jovem , Imunossupressores/uso terapêutico , Esteroides/uso terapêutico , Doença Aguda , Criança , Resultado do Tratamento , Doadores de Tecidos
7.
Sci Rep ; 14(1): 11778, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782966

RESUMO

We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , COVID-19/complicações , COVID-19/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante Homólogo/efeitos adversos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Idoso , Infecções por Citomegalovirus/complicações , Estudos Retrospectivos , Adulto Jovem
8.
Chem Asian J ; : e202301151, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782735

RESUMO

Combining exogenous and endogenous antibacterial mechanisms has been demonstrated to enhance therapeutic efficacy significantly. This study constructs an innovative type of exogenous and endogenous antibacterial nanocomposite hydrogels with injectable dual-crosslinked networks and dual-stimuli responsiveness. The primary network establishes imine bonds between the functionalized dextran featuring norbornenes and aldehydes (NorAld-Dex) and the quaternized chitosan (QCS). The imine bonds provide self-healing, injectability, and pH-responsiveness to the hydrogel network. The secondary network is established by integrating thiolated mesoporous silica-coated titanium dioxide nanoparticles (TiO2@MS-SH) into the hydrogel network via an ultrasound-activated thiol-norbornene reaction with NorAld-Dex. The microstructures and properties of NorAld-Dex/QCS/TiO2@MS-SH hydrogels can be fine-tuned by adjusting the sonication time to increase the amount of thiol-norbornene crosslinks in the network. Effective antibacterial performance of NorAld-Dex/QCS/TiO2@MS-SH hydrogels at low pH has been demonstrated with the synergistic effect of the acid-induced dissociation of the hydrogel network, protonated QCS, and the reactive oxygen species (ROS) generated by TiO2@MS-SH nanoparticles under ultrasound irradiation. In summary, NorAld-Dex/QCS/TiO2@MS-SH nanocomposite hydrogel is an advanced dual stimuli-responsive antibacterial platform with customizable microstructures and properties, offering great potential for biomedical applications.

9.
Medicine (Baltimore) ; 103(18): e38003, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701295

RESUMO

This study aims to investigate the ability of bone marrow imaging using third-generation dual-energy computed tomography (CT) virtual noncalcium (VNCa) to differentiate between multiple myeloma (MM) with diffuse bone marrow infiltration and red bone marrow (RBM). Bone marrow aspiration or follow-up results were used as reference. We retrospectively reviewed 188 regions of interests (ROIs) from 21 patients with confirmed MM and diffuse bone marrow infiltrations who underwent VNCa bone marrow imaging between May 2019 and September 2022. At the same time, we obtained 98 ROIs from 11 subjects with RBM for comparative study, and 189 ROIs from 20 subjects with normal yellow bone marrow for the control group. The ROIs were delineated by 2 radiologists independently, the interobservers reproducibility was evaluated by interclass correlation coefficients. The correlation with MRI grade results was analyzed by Spearman correlation coefficient. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal threshold for differentiating between these groups and to assess diagnostic performance. There were statistically significant differences in VNCa CT values of bone marrow among the MM, RBM, and control groups (all P < .001), with values decreasing sequentially. A strong positive rank correlation was observed between normal bone marrow, subgroup MM with moderately and severe bone marrow infiltration divided by MRI and their corresponding CT values (ρ = 0.897, 95%CI: 0.822 to 0.942, P < .001). When the CT value of VNCa bone marrow was 7.15 HU, the area under the curve (AUC) value for differentiating RBM and MM was 0.723, with a sensitivity of 50.5% and a specificity of 89.8%. When distinguishing severe bone marrow infiltration of MM from RBM, the AUC value was 0.80 with a sensitivity 70.9% and a specificity 78.9%. The AUC values for MM, RBM, and the combined group compared to the control group were all >0.99, with all diagnostic sensitivity and specificity exceeding 95%. VNCa bone marrow imaging using third-generation dual-energy CT accurately differentiates MM lesions from normal bone marrow or RBM. It demonstrates superior diagnostic performance in distinguishing RBM from MM with diffuse bone marrow infiltration.


Assuntos
Medula Óssea , Mieloma Múltiplo , Tomografia Computadorizada por Raios X , Humanos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/patologia , Mieloma Múltiplo/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Idoso , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X/métodos , Adulto , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Sci Rep ; 14(1): 11936, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38789505

RESUMO

Green infrastructure networks enhance the protection and improvement of urban ecological environments, augment the efficiency and quality of ecosystem services, and furnish residents with healthier and more comfortable living conditions. Although previous research has investigated the construction or optimization methods of green infrastructure networks, these studies have been relatively isolated and lacking in case studies for mountainous cities. In the development of green infrastructure, mountainous cities must specifically consider the impact of terrain on network construction. Taking Fuzhou, a mountainous city in China, as an example, this study constructs and optimizes the green infrastructure network by employing morphological spatial pattern analysis, connectivity analysis, the Minimum Cumulative Resistance model, and circuit theory. These methodologies increase the connectivity of the Green Infrastructure within the study area, thereby promoting the health of the local ecosystem and creating conducive circumstances for the city's sustainable development. The findings reveal that: (1) Green infrastructure in Fuzhou takes up 5366.38 ha, constituting 21.76% of the study area, primarily situated in the northwest and south; (2) Fuzhou's Green Infrastructure network comprises 10 hubs and 17 corridors with a hub area of 1306.98 ha, predominantly distributed in the mountains encircling the city, including Meifeng Mountain, Gaogai Mountain, and Qingliang Mountain; (3) Based on optimization, the circuit centrality index categorizes hub importance into three protection levels, pinpointing nine crucial protected areas in the corridors and 680 areas requiring enhancement, including 68 areas for first-level improvement, 149 areas for second-level improvement, and 463 areas for third-level improvement. This research offers a methodological reference for constructing and optimizing green infrastructure networks in mountainous cities, providing both theoretical and practical foundations for optimizing green infrastructure networks in Fuzhou City.

11.
Future Sci OA ; 10(1): FSO955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817375

RESUMO

Aim: To assess the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with porcine small intestinal submucosa (SIS) on full-thickness skin injuries in rats. Methods: We established full-thickness skin injury models in Sprague-Dawley rats, dividing them into blank control, SIS, hUCMSCs and hUCMSCs combined with SIS. We monitored wound healing, scores and area, and analyzed inflammatory cells, microvessel density and collagen fibers after 12 days. Results: The blank group showed no healing, forming a scar of 0.6 × 0.5 cm2, while SIS and hUCMSCs groups exhibited incomplete healing with 0.4 × 0.5 cm2 scabs. Wound healing was significantly better in the hUCMSCs combined with the SIS group. Conclusion: Local application of hUCMSCs combined with SIS enhances full-thickness skin injury wound healing in rats.


Our skin protects us from infections and injuries, but severe damage can lead to health problems. In this study, we explored a promising new treatment to enhance skin healing. We used mesenchymal stem cells derived from umbilical cords in combination with a biological material called porcine small intestinal submucosa (SIS) to conduct experiemnts on rats with skin wounds. This treatment led to much better healing in rats with deep skin wounds compared with standard approaches. This approach is promising for treating severe skin injuries, offering hope for quicker recovery and better outcome, including faster recovery, reduced pain and inflammation and less scarring.

12.
Front Oncol ; 14: 1390438, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595816

RESUMO

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%-26.1%), 22.8% (95% CI 14.2%-31.4%) and 32.8% (95% CI 24.1%-41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%-84.9%), 72.7% (95% CI 63.7%-81.7%), and 62.3% (95% CI 53.5%-71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

13.
Bone Marrow Transplant ; 59(7): 991-996, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565964

RESUMO

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.


Assuntos
Terapia de Salvação , Transplante Haploidêntico , Humanos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Transplante Haploidêntico/métodos , Adolescente , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Rejeição de Enxerto/etiologia , Adulto Jovem , Transplante Homólogo/métodos
14.
PLoS One ; 19(4): e0300548, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578740

RESUMO

Biomechanical cue within the tissue microenvironment is known to play a critical role in regulating cell behaviors and maintaining tissue homeostasis. As hydrostatic pressure often increases in biliary system under pathological states, we investigated the effect of the moderate elevation of the hydrostatic pressure on biliary epithelial cells, especially on the epithelial-mesenchymal transition (EMT). Human intrahepatic biliary epithelial cells were loaded to hydrostatic pressure using a commercial device. We found that loading the cells to 50 mmHg hydrostatic pressure induced obvious morphological changes and significantly upregulated vimentin, ZEB1, and pSmad2/3, fibronectin, and collagen 1α. All changes induced by hydrostatic pressure loading were effectively mitigated by either ROCK inhibitor (Y-27632) or ALK5 inhibitor (SB-431542). Our in vitro experimental data suggests that hydrostatic pressure loading induces EMT of cholangiocytes through RhoA/ROCK and TGF-ß/Smad pathways. Elevated hydrostatic pressure in biliary duct system under pathological states may promote the biliary epithelial cells shifting to profibrotic and mesenchymal characteristics.


Assuntos
Transdução de Sinais , Fator de Crescimento Transformador beta , Humanos , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Pressão Hidrostática , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
15.
J Hazard Mater ; 470: 134259, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626687

RESUMO

Seeking for a safe, efficient, inexpensive, and eco-friendly oxidizer is always a big challenge for in-situ chemical oxidation (ISCO) technology. This study adopted the potassium peroxoborate (PPB), a novel peroxide, for soil remediation for the first time. PPB based chemical oxidation system (PPB-CO) could efficiently degrade polycyclic aromatic hydrocarbons (PAHs) without other reagents added, reaching 72.1 %, 64.2 %, and 50.0 % removal rates for naphthalene, phenanthrene, and pyrene after 24 h reaction, respectively. The superior total PAHs removal efficiency (60.6 %) was 3.6-4.7 times higher than that of other commercial peroxides (2Na2CO3•3H2O, CaO2, and H2O2). Mechanism analysis revealed that varieties of reactive oxygen species (ROS) can be generated by PPB through Fenton-like or non-Fenton routines, including H2O2, perborates species, O2•-, •OH, and 1O2. The sustainable generation of H2O2 reduced the disproportionation effect of H2O2 by 86 %, significantly improving the utilization rate. Moreover, sandbox experiments and actual contaminated soil remediation experiments verified the feasibility of PPB-CO in a real polluted site. This work provides a novel strategy for effectively soil remediation, highlighting the selection and application of new oxidants.

16.
Nat Commun ; 15(1): 3165, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605010

RESUMO

The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes. Moreover, HGF promotes thyrocyte migration, which is probably mediated by downregulation of E-cadherin expression. The delayed bifurcation of the thyroid primordium is also observed in thyroid-specific Met knockout mice. Together, our findings reveal that HGF/Met is indispensable for the bifurcation of the thyroid primordium during thyroid development mediated by downregulation of E-cadherin in thyrocytes via MAPK-snail pathway.


Assuntos
Fator de Crescimento de Hepatócito , Disgenesia da Tireoide , Animais , Camundongos , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Caderinas/genética , Disgenesia da Tireoide/genética , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/metabolismo
17.
Med Oncol ; 41(5): 113, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602586

RESUMO

Leukemia is a malignant disease of the hematopoietic system, in which clonal leukemia cells accumulate and inhibit normal hematopoiesis in the bone marrow and other hematopoietic tissues as a result of uncontrolled proliferation and impaired apoptosis, among other mechanisms. In this study, the anti-leukemic effect of a compound (SGP-17-S) extracted from Chloranthus multistachys, a plant with anti-inflammatory, antibacterial and anti-tumor effects, was evaluated. The effect of SGP-17-S on the viability of leukemic cell was demonstrated by MTT assay, cell cycle, and apoptosis were assessed by flow cytometry using PI staining and Annexin V/PI double staining. Combinations of network pharmacology and cellular thermal shift assay (CETSA) with western blot were used to validate agents that act on leukemia targets. The results showed that SGP-17-S inhibited the growth of leukemia cells in a time- and dose-dependent manner. SGP-17-S blocked HEL cells in the G2 phase, induced apoptosis, decreased Bcl-2 and caspase-8 protein expression, and increased Bax and caspase-3 expression. In addition, CETSA revealed that PARP1 is an important target gene for the inhibition of HEL cell growth, and SGP-17-S exerted its action on leukemia cells by targeting PARP1. Therefore, this study might provide new solutions and ideas for the treatment of leukemia.


Assuntos
Leucemia , Humanos , Leucemia/tratamento farmacológico , Ciclo Celular , Proliferação de Células , Divisão Celular , Anexina A5 , Poli(ADP-Ribose) Polimerase-1
18.
J Hazard Mater ; 469: 133987, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38461668

RESUMO

Plastic additives such as the antioxidant 2,4-di-tert-butylphenol (2,4-DTBP) have been widely detected in aquatic environments, over a wide range of concentrations reaching 300 µg/L in surface water, potentially threatening the health of aquatic organisms and ecosystems. However, knowledge of the specific effects of 2,4-DTBP on aquatic vertebrates is still limited. In this study, adult zebrafish were exposed to different concentrations of 2,4-DTBP (0, 0.01, 0.1 and 1.0 mg/L) for 21 days in the laboratory. The amplicon sequencing results indicated that the diversity and composition of the zebrafish gut microbiota were significantly changed by 2,4-DTBP, with a shift in the dominant flora to more pathogenic genera. Exposure to 2,4-DTBP at 0.1 and 1.0 mg/L significantly increased the body weight and length of zebrafish, suggesting a biological stress response. Structural assembly defects were also observed in the intestinal tissues of zebrafish exposed to 2,4-DTBP, including autolysis of intestinal villi, adhesions and epithelial detachment of intestinal villi, as well as inflammation. The transcriptional expression of some genes showed that 2,4-DTBP adversely affected protein digestion and absorption, glucose metabolism and lipid metabolism. These results are consistent with the PICRUSt2 functional prediction analysis of intestinal microbiota of zebrafish exposed to 2,4-DTBP. This study improves our understanding of the effects of 2,4-DTBP on the health of aquatic vertebrates and ecosystems.


Assuntos
Microbioma Gastrointestinal , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Ecossistema , Fenóis/química
19.
Mol Cell Biochem ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38466467

RESUMO

Nicaraven has been reported to inhibit the activity of poly (ADP-ribose) polymerase (PARP). In this study, we investigated the probable ability of nicaraven to attenuate cancer radioresistance during fractionated radiotherapy. Tumor models were established in C57BL/6 mice and BALB/c nude mice by subcutaneous injection of Lewis mouse lung carcinoma cancer cells and A549 human lung cancer cells, respectively. When the tumors had grown to approximately 100 mm3, we initiated fractionated radiotherapy. Nicaraven or saline was administered immediately after each irradiation exposure. Compared to saline treatment, nicaraven administration significantly induced gamma-H2AX foci formation and cell apoptosis in tumors at 1 or 3 days after an additional challenge exposure to 10 Gy and inhibited tumor growth during the short-term follow-up period, suggesting increased radiosensitivity of cancer cells. Moreover, the expression of PARP in tumor tissue was decreased by nicaraven administration. Our data suggest that nicaraven likely attenuates the acquired radioresistance of cancers through PARP inhibition.

20.
World J Gastrointest Oncol ; 16(2): 527-542, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425409

RESUMO

BACKGROUND: An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM: To analyze the development in the field of "glucose metabolism" (GM), "amino acid metabolism" (AM), "lipid metabolism" (LM), and "nucleotide metabolism" (NM) in CRC by visualization. METHODS: Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS: The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. "Gut microbiota" and "epithelial-mesenchymal transition" emerged as the newest burst words in GM, "gut microbiota" was the latest outburst word in AM, "metastasis", "tumor microenvironment", "fatty acid metabolism", and "metabolic reprogramming" were the up-to-date outbreaking words in LM, while "epithelial-mesenchymal transition" and "apoptosis" were the most recently occurring words in NM. CONCLUSION: Research in "cellular metabolism in CRC" is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

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