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1.
Proc Natl Acad Sci U S A ; 120(23): e2217869120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37253016

RESUMO

T cell lymphomas (TCLs) are a group of rare and heterogeneous tumors. Although proto-oncogene MYC has an important role in driving T cell lymphomagenesis, whether MYC carries out this function remains poorly understood. Here, we show that malic enzyme 2 (ME2), one of the NADPH-producing enzymes associated with glutamine metabolism, is essential for MYC-driven T cell lymphomagenesis. We establish a CD4-Cre; Myc flox/+transgenic mouse mode, and approximately 90% of these mice develop TCL. Interestingly, knockout of Me2 in Myc transgenic mice almost completely suppresses T cell lymphomagenesis. Mechanistically, by transcriptionally up-regulating ME2, MYC maintains redox homeostasis, thereby increasing its tumorigenicity. Reciprocally, ME2 promotes MYC translation by stimulating mTORC1 activity through adjusting glutamine metabolism. Treatment with rapamycin, an inhibitor of mTORC1, blocks the development of TCL both in vitro and in vivo. Therefore, our findings identify an important role for ME2 in MYC-driven T cell lymphomagenesis and reveal that MYC-ME2 circuit may be an effective target for TCL therapy.


Assuntos
Glutamina , Malato Desidrogenase , Linfócitos T , Animais , Camundongos , Glutamina/metabolismo , Homeostase , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Linfócitos T/metabolismo , Malato Desidrogenase/genética , Malato Desidrogenase/metabolismo
2.
BMC Cancer ; 24(1): 501, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641773

RESUMO

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.


Assuntos
Neoplasias Retais , Reto , Humanos , Reto/patologia , Estudos Prospectivos , Qualidade de Vida , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como Assunto
3.
Langmuir ; 40(27): 14007-14015, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38916446

RESUMO

Allograft transplantation is an important method for tendon reconstruction after injury, and its clinical success highly relies on the storage and transportation of the grafts. Cryopreservation is a promising strategy for tendon storage. In this study, we report a novel cryopreservation agent (CPA) formulation with a high biocompatibility for tendon cryopreservation. Mainly composed of natural zwitterionic betaine and the biocompatible polymer poly(vinylpyrrolidone) (PVP), it exhibited ideal abilities to depress the freezing point and inhibit ice growth and recrystallization. Notably, after cryopreservation via plunge-freezing for 1 month, Young's modulus (144 MPa, 98% of fresh tendons) and ultimate stress (46.7 MPa, 99% of fresh tendons) remained stable, and the cross-linking of collagen microfibers, protein structures, and glycosaminoglycan (GAG) contents changed slightly. These results indicate that the formulation (5 wt % betaine and 5 wt % PVP in phosphate-buffered saline, PBS solution) effectively maintains the biomechanical properties and tissue structure. This work offers a novel cryopreservation method for tendons and may also provide insights into the long-term preservation of various other tissues.


Assuntos
Betaína , Criopreservação , Tendões , Criopreservação/métodos , Tendões/efeitos dos fármacos , Betaína/química , Animais , Congelamento , Crioprotetores/química , Crioprotetores/farmacologia , Povidona/química , Colágeno/química , Glicosaminoglicanos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
4.
Biometrics ; 80(3)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39101548

RESUMO

We consider the setting where (1) an internal study builds a linear regression model for prediction based on individual-level data, (2) some external studies have fitted similar linear regression models that use only subsets of the covariates and provide coefficient estimates for the reduced models without individual-level data, and (3) there is heterogeneity across these study populations. The goal is to integrate the external model summary information into fitting the internal model to improve prediction accuracy. We adapt the James-Stein shrinkage method to propose estimators that are no worse and are oftentimes better in the prediction mean squared error after information integration, regardless of the degree of study population heterogeneity. We conduct comprehensive simulation studies to investigate the numerical performance of the proposed estimators. We also apply the method to enhance a prediction model for patella bone lead level in terms of blood lead level and other covariates by integrating summary information from published literature.


Assuntos
Simulação por Computador , Humanos , Modelos Lineares , Biometria/métodos , Chumbo/sangue , Patela , Modelos Estatísticos , Interpretação Estatística de Dados
5.
Colorectal Dis ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020518

RESUMO

AIM: For patients with locally advanced rectal cancer, previous STELLAR studies have shown that a new adjuvant treatment paradigm of short-course radiotherapy followed by neoadjuvant chemotherapy can achieve pathological complete response rates superior to those of standard care; however, the 3-year DFS is inferior to neoadjuvant concurrent radiotherapy. Recent studies have shown that immune checkpoint inhibitors may improve the prognosis of rectal cancer and have good synergy with radiotherapy. Therefore, neoadjuvant chemotherapy combined with immune checkpoint inhibitors after a short course of radiotherapy has the potential to further improve complete response rates and prognosis. METHOD: The STELLAR II study is a multicentre, open label, two-arm randomized, phase II/III trial of short-course radiotherapy followed by neoadjuvant chemotherapy concurrent with immunotherapy for locally advanced rectal cancer. A total of 588 patients with locally advanced rectal cancer (LARC) will be randomly assigned to the experimental and control groups. The experimental group will receive short-course radiotherapy and neoadjuvant chemotherapy in combination with sindilizumab, while the control group will receive short-course radiotherapy and neoadjuvant chemotherapy. Both groups will subsequently receive either total rectal mesenteric resection or a watch & wait (W&W) strategy. The phase II primary endpoint is the complete remission rate, and the secondary endpoints include grade 3-4 adverse events, perioperative complications, R0 resection rate, overall survival, local recurrence rate, distant metastasis rate and quality of life score. A seamless phase II/III randomized controlled design will be used to investigate the effectiveness and safety of the TNT strategy with the addition of immunotherapy. The trial opened, and the first patient was recruited on 31 August 2022. Trial registration number and date of registration: ClinicalTrials.gov NCT05484024, 29 July 2022. DISCUSSION: The STELLAR II trial will prospectively evaluate the efficacy of TNT treatment strategies that incorporate immune checkpoint inhibitors. The trial will yield important information to guide routine management of patients with local advanced rectal cancer.

6.
Orthod Craniofac Res ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715428

RESUMO

INTRODUCTION: An ideal orthodontic treatment involves qualitative and quantitative measurements of dental and skeletal components to evaluate patients' discrepancies, such as facial, occlusal, and functional characteristics. Deciding between orthodontics and orthognathic surgery remains challenging, especially in borderline patients. Advances in technology are aiding clinical decisions in orthodontics. The increasing availability of data and the era of big data enable the use of artificial intelligence to guide clinicians' diagnoses. This study aims to test the capacity of different machine learning (ML) models to predict whether orthognathic surgery or orthodontics treatment is required, using soft and hard tissue cephalometric values. METHODS: A total of 920 lateral radiographs from patients previously treated with either conventional orthodontics or in combination with orthognathic surgery were used, comprising n = 558 Class II and n = 362 Class III patients, respectively. Thirty-two measures were obtained from each cephalogram at the initial appointment. The subjects were randomly divided into training (n = 552), validation (n = 183), and test (n = 185) datasets, both as an entire sample and divided into Class II and Class III sub-groups. The extracted data were evaluated using 10 machine learning models and by a four-expert panel consisting of orthodontists (n = 2) and surgeons (n = 2). RESULTS: The combined prediction of 10 models showed top-ranked performance in the testing dataset for accuracy, F1-score, and AUC (entire sample: 0.707, 0.706, 0.791; Class II: 0.759, 0.758, 0.824; Class III: 0.822, 0.807, 0.89). CONCLUSIONS: The proposed combined 10 ML approach model accurately predicted the need for orthognathic surgery, showing better performance in Class III patients.

7.
Bull Environ Contam Toxicol ; 112(4): 58, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594479

RESUMO

This study investigated the species, density, biomass and physicochemical factors of benthic macroinvertebrates in Hongze Lake from 2016 to 2020. Redundancy analysis (RDA) was used to analyze the relationship between physicochemical parameters and the community structure of macroinvertebrates. Macroinvertebrate-based indices were used to evaluate the water quality conditions in Hongze Lake. The results showed that a total of 50 benthic species (10 annelids, 21 arthropods and 19 mollusks) were collected. The community structure of benthic macroinvertebrates varied in time and space. The dominant species were Limnodrilus hoffmeisteri (L.hoffmeisteri), Corbicula fluminea (C.fluminea), Nephtys oligobranchia (N.oligobranchia). In 2016, arthropods such as Grandidierella sp. were the dominant species of benthos in Hongze Lake while annelids and mollusks dominated from 2017 to 2020, such as L.hoffmeisteri, N.oligobranchia, C.fluminea. The benthic fauna of Chengzi Lake and Lihewa District were relatively abundant and showed slight variation, while the benthic macroinvertebrates of the Crossing the water area were few and varied greatly. RDA showed that changes in benthic macroinvertebrate structure were significantly correlated with dissolved oxygen (DO), Pondus Hydrogenii (pH) and transparency (SD). The Shannon Wiener, Pielou, and Margalef indices indicate that Hongze Lake is currently in a moderately polluted state. Future studies should focus on the combined effects of various physicochemical indicators and other environmental factors on benthic communities.


Assuntos
Artrópodes , Oligoquetos , Animais , Invertebrados , Lagos , Qualidade da Água , Moluscos , Monitoramento Ambiental , Ecossistema
8.
Small ; 19(35): e2301469, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37098645

RESUMO

Single-atom catalysts (SACs) exhibit remarkable potential for electrochemical reduction of CO2 to value-added products. However, the commonly pursued methods for preparing SACs are hard to scale up, and sometimes, lack general applicability because of expensive raw materials and complex synthetic procedures. In addition, the fine tuning of coordination environment of SACs remains challenging due to their structural vulnerability. Herein, a simple and universal strategy is developed to fabricate Ni SACs with different nitrogen coordination numbers through one-step pyrolysis of melamine, Ni(NO3 )∙6H2 O, and polyvinylpyrrolidone at different temperatures. Experimental measurements and theoretical calculations reveal that the low-coordinate Ni SACs exhibit outstanding CO2 reduction performance and stability, achieving a Faradic efficiency (FECO ) of 98.5% at -0.76 V with CO current density of 24.6 mA cm-2 , and maintaining FECO of over 91.0% at all applied potential windows from -0.56 to -1.16 V, benefiting from its coordinatively unsaturated structure to afford high catalytic activity and low barrier for the formation of *COOH intermediate. No significant performance degradation is observed over 50 h of continuous operation. Additionally, several other metallic single-atom catalysts are successfully prepared by this synthetic method, demonstrating the universality of this strategy.

9.
Nanotechnology ; 34(32)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37080185

RESUMO

SnO2has attracted extensive research attentions as a promising anode material for sodium-ion batteries (SIBs) due to its high theoretical capacity. However, its application is largely hindered by sluggish sodium ion diffusion and drastic volume change during the conversion reaction and alloying process. Herein, ultra-fine SnO2nanocrystals (3-5 nm) anchored on reduced graphene oxide (rGO) is demonstrated as a promising anode material for SIBs. Ultra-fine SnO2nanocrystals are uniformly grown on rGO sheets by a facile one-step hydrothermal process. Nano-scaled SnO2grains tolerate volume expansion and provide shortened diffusion pathway for sodium ions, and meanwhile rGO acts as an excellent conductive matrix, thus endowing the composite electrode with excellent electrochemical performance. More importantly, the ratio of SnO2to rGO in the composite is optimized. The optimized sample delivers an initial charge capacity of 518 mAh g-1at a current density of 50 mA g-1, and 504 mAh g-1after 300 cycles at a current density of 100 mA g-1. Furthermore, a capacity of 287 mAh g-1can be maintained after 1000 cycles at a current density of 1000 mA g-1.

10.
Environ Monit Assess ; 195(12): 1503, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37987869

RESUMO

This study investigated zooplankton species, density, biomass, and water physicochemical factors in Hongze Lake between 2016 and 2020. The correlation between zooplankton community changes and physicochemical factors was explored using canonical correspondence analysis and Spearman correlation analysis. The investigation found 48 species of protozoa, 52 species of rotifers, 36 species of cladocera, and 32 species of copepoda. The yearly mean density fluctuated between 529.01 and 2234.51 individuals per liter. The yearly mean zooplankton biomass was 950.14 mg/L, ranging from 271.92 to 1365.835 mg/L. A high diversity of zooplankton was found in the Overwater Area, with a large proportion of protozoa and copepoda. Correlation analysis revealed that nitrogen content, pH, water temperature, chemical oxygen demand, biochemical oxygen demand, water transparency, and chlorophyll a were important factors influencing the distribution of zooplankton in Hongze Lake. These factors collectively contributed to the evolution of the zooplankton community structure in Hongze Lake.


Assuntos
Copépodes , Lagos , Animais , Clorofila A , Monitoramento Ambiental , Água , Zooplâncton
11.
Zhongguo Zhong Yao Za Zhi ; 48(22): 5985-5992, 2023 Nov.
Artigo em Zh | MEDLINE | ID: mdl-38114204

RESUMO

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Adjuvantes Imunológicos/farmacologia , Medicina Tradicional Chinesa , Influenza Humana/prevenção & controle , Adjuvantes Farmacêuticos
12.
Acc Chem Res ; 54(7): 1711-1722, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33576600

RESUMO

Organonitrogen chemicals are essential in many aspects of modern life. Over 80% of the top 200 prescribed pharmaceutical products contain at least one nitrogen atom in the molecule, while all top 10 agrochemicals contain nitrogen, just to name a few. At present, the prevailing industrial processes for manufacturing organonitrogen chemicals start from nonrenewable fossil resources, but eventually we have to make these chemicals in a more sustainable manner. Biomass represents the largest renewable carbon resource on earth, which is inexpensive and widely available. Integrating biomass into the organonitrogen chemical supply chain will mitigate the carbon footprint, diversify the product stream, and enhance the economic competitiveness of biorefinery. Short-cut synthesis routes can be created for oxygen-containing organonitrogen compounds by exploiting the inherent oxygen functionalities in the biomass resources. Moreover, for nitrogen-containing biomass components such as chitin, a unique opportunity to make organonitrogen chemicals bypassing the energy-intensive Haber-Bosch ammonia synthesis process arises. Estimated at 100 billion tons of annual production in the world, chitin captures more nitrogen than the Haber-Bosch process in the form of amide functional groups in its polymer side chain.In this Account, we intend to summarize our efforts to establish new reaction routes to synthesize valuable organonitrogen chemicals from renewable resources. Enabled by tailor-designed catalytic systems, diverse nitrogen-containing products including amines, amino acids, nitriles, and N-heterocycles have been obtained from a range of biomass feedstock either directly or via intermediate platform compounds. Two strategies to produce organonitrogen chemicals are presented. For platform chemicals derived from cellulose, hemicellulose, lignin, and lipids, which are enriched with oxygen functionalities, in particular, hydroxyl groups, the key chemistry to be developed is the catalytic transformation of hydroxyl groups into nitrogen-containing groups using NH3 as the nitrogen source. Along this line, Ru- and Ni-based heterogeneous catalysts are developed to convert alcohols to amines and/or nitriles via a thermal catalytic pathway, while CdS nanomaterials are explored to promote -OH to -NH2 conversion under visible-light irradiation. Metal-zeolite multifunctional systems are further established to enable the synthesis of N-heterocycles from O-heterocycles. The second strategy involves the use of chitin and chitin derivatives as the starting materials. Under the concept of shell biorefinery, distinctive protocols have been established to chemically transform chitin as the sole feedstock to amino sugars, amino alcohols, furanic amides, and N-heterocycles. By combining mechanochemistry with biotransformation, an integrated process to convert shrimp shell waste to complex, high-value, chiral compounds including tyrosine and l-DOPA is also demonstrated.


Assuntos
Aminas/metabolismo , Aminoácidos/metabolismo , Quitina/metabolismo , Nitrilas/metabolismo , Aminas/química , Aminoácidos/química , Biomassa , Quitina/química , Estrutura Molecular , Nitrilas/química
13.
Exp Cell Res ; 389(1): 111861, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31981592

RESUMO

SET domain-containing 5 (SETD5) is an uncharacterized member of the protein lysine methyltransferase family. Although it was reported that SETD5 gene mutations are associated with the several types of human cancer, its functional role in esophageal squamous cell carcinoma (ESCC) progression has not been fully elucidated. In the present study, we used tissue samples from 147 patients with ESCC and ESCC cell lines to determine the clinicopathological significance of SETD5 in ESCC and its effects on ESCC stemness. We performed immunohistochemical staining, immunofluorescence imaging, and tumor sphere formation, colony formation, flow cytometry, wound healing, Transwell, and western blotting assays. SETD5 expression was upregulated in ESCC tissue and associated with primary tumor (pT) stage, clinical stage, lymph node metastasis, shorter overall survival rate, and disease-free survival rate. Cox regression analyses indicated that SETD5 is an independent poor prognostic factor of ESCC. In addition, SETD5 expression was correlated with cancer stemness-related protein, hypoxia-inducible factor-1α (HIF-1α), and CD68 expression. Moreover, immunofluorescence analysis revealed that SETD5 was co-localized with CD44 and SOX2 in TE10 and TE11 cells and that exposing cells to cobalt chloride increased HIF-1α, SETD5, and stemness-related protein expression in a time-dependent manner. Furthermore, SETD5 expression was significantly correlated with the expression of cell cycle-related genes and PI3K/Akt signaling pathway-related proteins. Finally, knocking down SETD5 downregulated the expression of stemness-related and PI3K/Akt signaling pathway proteins, while inhibiting tumor spheroid formation, cell proliferation, migration, and invasion in ESCC cells. These results indicate that SETD5 expression is associated with cancer stemness and that SETD5 is a potential prognostic biomarker and therapeutic target for ESCC.


Assuntos
Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/patologia , Metiltransferases/fisiologia , Células-Tronco Neoplásicas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/fisiologia , Progressão da Doença , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Prognóstico , RNA Interferente Pequeno/farmacologia , Células Tumorais Cultivadas
14.
Zhongguo Zhong Yao Za Zhi ; 46(24): 6295-6302, 2021 Dec.
Artigo em Zh | MEDLINE | ID: mdl-34994121

RESUMO

Lancang-Mekong Cooperation is a new type of subregional cooperation mechanism initiated and built by China and other five countries of the Lancang-Mekong subregion, namely Laos, Myanmar, Thailand, Cambodia, and Vietnam. Countries in the Lancang-Mekong subregion are geographically and culturally connected, and they have nurtured their unique traditional medicine. By combing the history of traditional medicine exchanges between China and other Lancang-Mekong countries and their progress of modern research, this paper summarized the challenges and opportunities of traditional medicine cooperation in the Lancang-Mekong subregion. It has been found that many regional cooperation mechanisms coexist for a long time in the Lancang-Mekong subregion and the medicinal resources are abundant. However, the degree of their development and utilization varies, and modern scientific research is insufficient. Lancang-Mekong Cooperation has provided a strong support for integrating the advantageous resources in Lancang-Mekong subregion countries and making progress together. Focusing on the development and protection of medicinal resources, this paper puts forward a new path of cooperation in the intellectual property rights and characteristic seed resource protection, the compilation of universal herbal pharmacopoeia in various countries, the research and development of public health products, and the construction of traditional herbal industry bases, thus enabling the traditional medicine to better protect the public health and building a human health community.


Assuntos
Materia Medica , Rios , China , Humanos , Medicina Tradicional , Tailândia
15.
Exp Mol Pathol ; 112: 104333, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31705880

RESUMO

Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is closely linked to the occurrence and development of many malignant tumors. Many studies have reported that enhanced expression of LETM1 in several types of human cancers was associated with poor clinical outcomes; however, its clinical significance in gastric adenocarcinoma (GA) has not been elucidated. In this study, we assessed the expression of LETM1 along with the genes related to cancer stemness, cell cycle, and PI3K/Akt signaling in 189 paraffin-embedded GA tissue samples and GA-derived cell lines using immunohistochemistry (IHC), western blotting, and immunofluorescence. Our results showed that the expression of LETM1 was strongly correlated with the tumor grade, primary tumor (pT) stage, lymph node metastasis, clinical stage, and tumor gross type of GA. The Kaplan-Meier survival analysis revealed that patients with GA with high expression of LETM1 exhibit a shorter overall survival (OS) rate. Univariate and multivariate Cox regression analysis indicated that LETM1 is an independent poor prognostic factor of GA. Significantly, LETM1 expression was positively correlated with the expression of cancer stemness-related genes such as CD44 and LGR5 and expression of cell-cycle related gene, cyclin D1. Further, the expression of proteins involved in PI3K/Akt signaling pathway, such as pPI3K-p85 and pAkt-Thr308, was also increased. Additionally, small interfering RNA (esiRNA)-mediated silencing of LETM1 expression in GA-derived cell lines MKN28 and MKN74 strongly inhibited the expression of stemness and cell cycle-related proteins, suppressed cancer cell spheroid formation, migration and invasion ability, and affected cell cycle distribution. Furthermore, the GA-derived cell line AGS exhibited enhanced expression of LETM1, CD44, LGR5, and HIF1-α under hypoxic conditions. Lastly, we blocked PI3K expression using an inhibitor LY294002, which downregulated the expression of LETM1, pPI3K-p85, and pAkt-Thr308. Taken together, our results demonstrate that LETM1 regulates cell proliferation and promotes tumorigenicity of GA, and its overexpression is associated with the poor progression of GA. Therefore, LETM1 could serve as a potential prognostic biomarker and a therapeutic target for the better clinical management of GA.


Assuntos
Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas de Membrana/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Proliferação de Células/genética , Ciclina D1/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Receptores de Hialuronatos/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Neoplasias Gástricas/patologia
16.
Exp Mol Pathol ; 114: 104406, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32088189

RESUMO

B7-H4 is a member of B7 family which regulates immune responses by delivering costimulatory signals. However, it negatively regulates T cell-mediated immunity and may play an important role in tumor immune evasion. Although several studies have been reported that expression of B7-H4 is elevated in the several types of human cancer with a poor clinical outcome, its clinical significance in the prostate cancer (PCa) has not been well studied. In this study, we investigated the clinical significance of B7-H4 in human PCa and determined if B7-H4 expression is associated with the cancer cell stemness in PCa. Our studies show that expression of B7-H4 is correlated with the pathologic tumor (pT) stage and the clinical stage of PCa. The Kaplan-Meier survival analysis revealed that PCa patients with high expression of B7-H4 exhibits a shorter overall survival (OS) rate. Univariate and multivariate Cox regression analysis indicated that B7-H4 is an independent poor prognostic factor of PCa. In addition, the expression of B7-H4 is correlated with the cancer cell stemness associated genes expression in PCa. Further, our studies show that B7-H4 regulates cancer cell stemness associated genes expression and effects on the cell cycle and PI3K/Akt signaling related genes expression in PCa. These results indicate that B7-H4 expression is associated with cancer cell stemness, and B7-H4 is a potential prognostic biomarker and a therapeutic target of PCa.


Assuntos
Biomarcadores Tumorais/genética , Prognóstico , Neoplasias da Próstata/genética , Inibidor 1 da Ativação de Células T com Domínio V-Set/genética , Idoso , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia
17.
Exp Mol Pathol ; 117: 104560, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33127342

RESUMO

SETD8 is a lysine methyltransferase containing an SET domain, which is involved in the carcinogenesis of many cancer types through monomethylation of the histone H4 lysine 20. However, its prognostic value and underlying mechanisms in gastric adenocarcinoma (GA) have not been extensively studied. Here, we assessed SETD8 expression and its relationship with clinicopathological parameters, cancer stemness-related proteins, cell cycle-related proteins, and PI3K/Akt pathway proteins in GA. SETD8 expression in GA tissues was correlated with the primary tumor stage, lymph node metastasis, tumor size, gross type, and clinical stage. SETD8 was an independent predictor of poor overall survival of patients with GA. Cox regression analysis showed that SETD8 is a potential biomarker of unfavorable clinical outcomes in patients with GA. Moreover, SETD8 overexpression was associated with cancer stemness-related genes, cell cycle-related genes, and PI3K/Akt/NF-κB pathway genes in clinical GA tissue samples. SETD8 silencing downregulated the expression of cancer stemness-associated genes (LSD1 and SOX2) and inhibited GA cell proliferation, spheroid formation, invasion, and migration. Additionally, LY294002 significantly reduced the expression of SETD8, pAkt-Ser473, pPI3K-p85, and NFκB-p65 in MKN74 and MKN28 cells. SETD8 may be a novel cancer stemness-associated protein and potential prognostic biomarker in GA.


Assuntos
Adenocarcinoma/genética , Histona Desmetilases/genética , Histona-Lisina N-Metiltransferase/genética , Fatores de Transcrição SOXB1/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Idoso , Biomarcadores Tumorais/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromonas/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteína Oncogênica v-akt/genética , Prognóstico , Neoplasias Gástricas/patologia
18.
Opt Express ; 25(24): 29856-29863, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29221021

RESUMO

Non-orthogonal multiple access (NOMA) has recently attracted significant attention as a promising multiple access scheme for the 5th generation (5G) wireless communication due to its superior spectral efficiency, which has also been studied and shown to achieve a superior performance in visible light communication (VLC) networks. However, the error propagation (EP) problem due to successive interference cancellation (SIC) decoding has not yet been resolved, which degrades the system BER performance and causes user unfairness. In this work, symmetric superposition coding (SSC) and symmetric SIC (SSIC) decoding are proposed for a downlink NOMA-based VLC network, in which the distribution of the demodulation regions of the user allocated with more power will be symmetrical in terms of the decision threshold of the user allocated with less power. Furthermore, the proposed method is experimentally tested and the results show that more than 90% demodulation errors caused by EP are eliminated compared with traditional NOMA VLC.

19.
Int J Biol Macromol ; 273(Pt 1): 132965, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851615

RESUMO

Curcumin demonstrated therapeutic potential for cancer. However, its medical application is limited due to low solubility, poor stability and low absorption rate. Here, we used the mussel-inspired functional protein (MPKE) to fabricate the curcumin-carrying nanoparticle (Cur-MPKE) for encapsulating and delivering curcumin. The protein MPKE is composed of the mussel module and zwitterionic peptide. The Dopa group bonding characteristic of the mussel module was leveraged for the self-assembly of nanoparticles, while the superhydrophilic property of the zwitterionic peptide was utilized to enhance the stability of nanoparticles. As expected, MPKE and Cur are tightly bound through hydrogen bonds and dynamic imide bonds to form nanoparticles. Cur-MPKE showed improved solubility and stability in aqueous solutions as well as excellent biocompatibility. Besides, Cur-MPKE also exhibited pH-triggered release and enhanced uptake of curcumin by tumor cells, promoting the antioxidant activity and antitumor effect of curcumin. Moreover, systemic experiments of Cur-MPKE to rats demonstrated that Cur-MPKE significantly inhibited tumor tissue growth and proliferation without causing obvious systemic toxicity. This work provides a new strategy for fabricating the delivery system of curcumin with improved stability, sustainability and bioavailability.


Assuntos
Antineoplásicos , Bivalves , Curcumina , Nanopartículas , Curcumina/química , Curcumina/farmacologia , Curcumina/administração & dosagem , Animais , Nanopartículas/química , Bivalves/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Humanos , Ratos , Portadores de Fármacos/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Proteínas/química , Antioxidantes/química , Antioxidantes/farmacologia , Solubilidade
20.
Math Biosci Eng ; 21(1): 650-678, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303438

RESUMO

In recent years, the growing pervasiveness of wearable technology has created new opportunities for medical and emergency rescue operations to protect users' health and safety, such as cost-effective medical solutions, more convenient healthcare and quick hospital treatments, which make it easier for the Internet of Medical Things (IoMT) to evolve. The study first presents an overview of the IoMT before introducing the IoMT architecture. Later, it portrays an overview of the core technologies of the IoMT, including cloud computing, big data and artificial intelligence, and it elucidates their utilization within the healthcare system. Further, several emerging challenges, such as cost-effectiveness, security, privacy, accuracy and power consumption, are discussed, and potential solutions for these challenges are also suggested.


Assuntos
Inteligência Artificial , Internet das Coisas , Big Data , Computação em Nuvem , Internet
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