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1.
J Gene Med ; 26(1): e3661, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38282144

RESUMO

BACKGROUND: Upregulation of SMC1A (Structural maintenance of chromosomes 1A) is linked with many types of cancer and its oncogenic function, which has been associated with crucial cellular mechanisms (cell division, cell cycle checkpoints regulation and DNA repair). Recent studies have shown that SMC1A was involved in breast cancer, although the exact mechanisms of SMC1A remain to be determined. METHODS: Using The Cancer Genome Atlas (TCGA) database, we examined SMC1A expression and its relation to other genes, including FOXM1 and STMN1. Short hairpin RNA was used to subsequently examine the biological roles of SMC1A in MDA-MB-231 and MDA-MB-468 cell lines. Bioinformatics were performed to identify the SMC1A-related gene FOXM1. RESULTS: Here, we used the TCGA database to show that SMC1A is overexpressed in breast cancer. Later investigations showed SMC1A's role in breast cancer cell survival, apoptosis and invasion. Using bioinformatics and western blot assays, we confirmed that FOXM1 acted as the downstream of SMC1A, and SMC1A knockdown significantly downregulated the FOXM1 expression via the AKT signal pathway. Interestingly, the inhibition effects induced by SMC1A downregulation could be reversed by FOXM1 overexpression. In the clinic, SMC1A expression is favorably linked with FOXM1 expression in breast cancer tumor tissues. CONCLUSIONS: Collectively, our results not only enhance our knowledge of SMC1A's molecular pathways in breast cancer, but also suggest a potential new therapeutic target.


Assuntos
Neoplasias da Mama , Proteínas de Ciclo Celular , Proteínas Cromossômicas não Histona , Transdução de Sinais , Feminino , Humanos , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estatmina/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Ciclo Celular/genética
2.
Immunotherapy ; 16(2): 107-114, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38112011

RESUMO

The options for treating metastatic colorectal cancer are limited after failure of second-line chemotherapy. In this case report, we present the outcome of a 59-year-old male patient who underwent radical resection for rectal cancer in November 2018 and hepatectomy for liver metastasis in January 2021. His metastatic rectal cancer presented a remarkable response to the combination of fruquintinib and toripalimab after the failure of multiline chemotherapies. The patient achieved partial response within 3 months and clinical complete response of pulmonary masses within 12 months. As of now, the patient maintains a good quality of life, and the progression-free survival has been more than 17 months. In conclusion, the combination of fruquintinib and PD-1 inhibitors can improve the prognosis of metastatic colorectal cancer.


The available antitumor treatment options are very limited for patients with advanced colorectal cancer (a type of colon cancer), especially after multiple treatments have already failed. Often for patients in this situation, the available treatments do not work very well and the patients are not predicted to live very long. However, in this paper we report a case of successful treatment of this condition. A 59-year-old male patient with advanced colorectal cancer was treated with the combination therapy of two different immunotherapy drugs, fruquintinib and toripalimab, after multiple other treatments had failed. Currently, the survival time of this patient is over 17 months, and he has a satisfactory quality of life.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Qualidade de Vida
3.
Dent J (Basel) ; 11(12)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38132407

RESUMO

The management of root caries remains a challenge for clinicians due to its unique anatomical location and structure. There is increasing interest in utilising artificial root caries lesions to develop new strategies for remineralisation. An ideal protocol has not yet been agreed upon. The aim of this review is to provide a structured overview of previously reported in vitro root caries models. The literature was screened and mined for information mainly on substrate selection, model systems utilised, and variables used in the models. Human roots (60%) were the most frequently used substrates, followed by bovine roots (40%). Chemical models (69%) were the most frequently utilised model systems, followed by microbiological models (27%), to form root caries lesions. Acetate buffer solution (80%), pH 5.0 or above (40%), and a demineralisation time of five days (25%) were the common variables used in the chemical systems, while mono-species biofilm was most frequently used (73%) in microbiological models and Streptococcus mutans was the most common bacterial strain utilised in these models (80%). This review highlights the variability amongst the experimental approaches, discusses the advantages and limitations of these approaches, and emphasises that standardisation of experimental conditions along with sustained research will benefit root caries research.

4.
J Drug Target ; 31(9): 962-975, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37772906

RESUMO

Neutrophil extracellular traps (NETs) play a crucial role in breast cancer metastasis. However, the therapeutic target of NETs in breast cancer metastasis is still unknown. Using a natural metabolite library and single-cell sequencing data analysis, we identified resveratrol (RES), a polyphenolic natural phytoalexin, and agonist of silent information regulator-1 (SIRT1) that suppressed NETs formation after cathepsin C (CTSC) treatment. In vivo, RES significantly hindered breast cancer metastasis in a murine orthotopic 4T1 breast cancer model. Serum levels of myeloperoxidase-DNA and neutrophil elastase-DNA in mouse breast cancer model were significantly lower after RES treatment. Correspondingly, the tumour infiltrated CD8+T cells in the lungs increased after the treatment. Mechanistically, RES targets SIRT1 in neutrophils and significantly inhibits the citrullination of histones H3, which is essential for chromatin decondensation and NETs formation. Furthermore, we identified that the NETs were suppressed by RES in bone marrow neutrophils after CTSC treatment, while specific deficiency of SIRT1 in neutrophils promoted NETs formation and breast cancer to lung metastasis. Thus, our results revealed that RES could be potentially identified as a viable therapeutic drug to prevent neutrophil cell death and breast cancer metastasis.


Assuntos
Armadilhas Extracelulares , Neoplasias Pulmonares , Animais , Camundongos , Armadilhas Extracelulares/metabolismo , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Pulmão , Neoplasias Pulmonares/patologia , DNA
5.
Oral Oncol ; 146: 106541, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37595449

RESUMO

BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is a neoplasm of the salivary gland that causes 3.6% of salivary gland tumors and 12% of salivary gland malignancies. Its prognosis is determined by the histological progression beyond the adenoma capsule. CXPA is thought to be a malignant transformation of a primary or recurrent pleomorphic adenoma and is associated with both benign and malignant lesions. Salivary gland cancers represent a rare heterogeneous group of neoplasms with complex clinicopathological characteristics and distinct biological behavior. CASE DESCRIPTION: This case report summarizes the treatment of a 57-year-old male patient with CXPA of the left parotid gland, harboring HER2 amplification with poor prognosis. The overall survival of the patient has been > 3.5 years. The application and outcome of an immune checkpoint inhibitor and targeted therapy combination regimens in the treatment of CXPA carcinoma are discussed. CONCLUSION: Targeted therapy combined with immunotherapy has long-term clinical benefits and targeted therapy which has a high clinical response rate (immunotherapy + dual-targeting three-drug regimens) may present an ideal choice for the treatment of patients with rare and/or refractory tumors without compromising patient safety.


Assuntos
Adenocarcinoma , Adenoma Pleomorfo , Neoplasias das Glândulas Salivares , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma Pleomorfo/genética , Adenoma Pleomorfo/terapia , Adenoma Pleomorfo/patologia , Mutação , Cuidados Paliativos , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/genética , Genes erbB-2/genética
6.
Bioengineering (Basel) ; 10(4)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37106660

RESUMO

Large oral bone defects require grafting of bone blocks rather than granules to give physically robust, biocompatible and osteoconductive regeneration. Bovine bone is widely accepted as a source of clinically appropriate xenograft material. However, the manufacturing process often results in both reduced mechanical strength and biological compatibility. The aim of this study was to assess bovine bone blocks at different sintering temperatures and measure the effects on mechanical properties and biocompatibility. Bone blocks were divided into four groups; Group 1: Control (Untreated); Group 2: Initial boil for 6 h; Group 3: Boil 6 h followed by sintering at 550 °C for 6 h; Group 4: Boil 6 h followed by sintering at 1100 °C for 6 h. Samples were assessed for their purity, crystallinity, mechanical strength, surface morphology, chemical composition, biocompatibility and clinical handling properties. Statistical analysis was performed using one-way ANOVA and post-hoc Tukey's tests for normally distributed and Friedman test for abnormally distributed quantitative data from compression tests and PrestoBlue™ metabolic activity tests. The threshold for statistical significance was set at p < 0.05. The results showed that higher temperature sintering (Group 4) removed all organic material (0.02% organic components and 0.02% residual organic components remained) and increased crystallinity (95.33%) compared to Groups 1-3. All test groups (Group 2-4) showed decreased mechanical strength (MPa: 4.21 ± 1.97, 3.07 ± 1.21, 5.14 ± 1.86, respectively) compared with raw bone (Group 1) (MPa: 23.22 ± 5.24, p <0.05), with micro-cracks seen under SEM in Groups 3 and 4. Group 4 had the highest biocompatibility (p < 0.05) with osteoblasts as compared to Group 3 at all time points in vitro. Clinical handling tests indicated that Group 4 samples could better withstand drilling and screw placement but still demonstrated brittleness compared to Group 1. Hence, bovine bone blocks sintered at 1100 °C for 6 h resulted in highly pure bone with acceptable mechanical strength and clinical handling, suggesting it is a viable option as a block grafting material.

7.
J Oncol ; 2023: 7022337, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36942262

RESUMO

Neutrophil extracellular traps (NETs) are network structures comprised of decondensed DNA strands coated with granule proteins. There have been three types of NETs recorded. NETs have been discovered concerning the progression of some malignancies, including gastric cancer, breast cancer, ovarian cancer, hepatocellular carcinoma, colorectal cancer, glioblastoma, diffuse large B cell lymphoma (DLBCL), and lung cancer, among others. In various methods, tumors encourage the formation of NETs, and NETs, in turn, promote tumor growth. NETs can stimulate primary tumor cell proliferation, suppress immune cells to create a tumor-friendly immune microenvironment, and stimulate epithelial-mesenchymal transition (EMT). NETs significantly promote liver and lung metastasis, possibly by altering vascular permeability, inducing cytoskeleton rearrangement and directional cell migration, and reawakening dormant cancer cells. NETs are therapeutically promising targets for cancer patients. Cancer patients may benefit from anti-NETs therapy, especially when combined with immune checkpoint inhibitors.

8.
Thorac Cancer ; 14(4): 371-380, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36525508

RESUMO

BACKGROUND: ß-elemene is known to play a critical role in tumorigenesis as well as tyrosine kinase inhibitor (TKI) resistance in lung cancer. However, the biological function and molecular mechanism remain largely unknown. METHODS: In this study, the common genes involved in gefitinib resistance and ß-elemene were identified using bioinformatic analysis. The expression of FBP1 was examined by qRT-PCR and Western blot analysis. Cell proliferation, flow cytometry, clone formation and IC50 assays were performed to assess the effects of ß-elemene and FBP1. Western blot analysis was used to evaluate apoptosis-related gene expression. Finally, in vivo experiments were conducted to assess the crucial role of FBP1 in gefitinib-resistant HCC827/GR cells in nude mice. RESULTS: Screening analysis demonstrated that fructose-1,6-bisphosphatase (FBP1) was induced by ß-elemene and downregulated in gefitinib-resistant lung cells. Functionally, overexpression of FBP1 inhibited proliferation and gefitinib resistance and promoted apoptosis of PC9/GR and HCC827/GR cells in vitro. Mechanistically, FBP1 impeded the nuclear translocation of p-STAT3. The FBP1/STAT3 axis was required for FBP1-mediated apoptosis-related gene expression. In vivo experiments further confirmed the enhanced effects of FBP1 on lung cancer cell sensitivity to gefitinib. CONCLUSION: Our research indicated that ß-elemene suppressed proliferation and enhanced sensitivity to gefitinib by inducing apoptosis through the FBP1/STAT3 axis in gefitinib-resistant lung cancer cells.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos Nus
9.
Colloids Surf B Biointerfaces ; 220: 112927, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36283185

RESUMO

The translation of nanoparticles in cancer treatment is limited by their low drug-loading capacity, poor colloidal stability, insufficient tumor penetration, and uncontrolled drug release. Herein, gelatin/nanochitosan/doxorubicin nanoparticles (GND) are developed by crosslinking nanochitosan (NCT) with gelatin for doxorubicin delivery. The hydrophilicity and stability properties of GND allow it to be protected and have a long circulation time in blood. The GND formulation exhibited shedding and triggered release effects as well as improved colloidal stability. When reaching the tumor site, matrix metallopeptidase-2 (MMP-2) from the tumor environment degrades gelatin from 178-nm GND to release smaller 4 nm nanochitosan/doxorubicin (ND) nanoparticles for deep tumor penetration and efficient tumor cell endocytosis. Following endocytosis by tumor cells, the intracellular low pH and MMP-2 further trigger doxorubicin release, resulting in superior inhibitory capacity against cancer cells. Using a mouse tumor-bearing model, the superior anticancer activity and good in vivo biocompatibility of GND were verified. The rational design of tumor-penetrating GND enables MMP-2/pH sequentially triggered intelligent drug delivery, providing a practical approach for anticancer therapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Liberação Controlada de Fármacos , Gelatina/química , Metaloproteinase 2 da Matriz/metabolismo , Doxorrubicina , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/patologia , Portadores de Fármacos/uso terapêutico , Linhagem Celular Tumoral , Concentração de Íons de Hidrogênio
10.
Drug Deliv ; 29(1): 3186-3196, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36226475

RESUMO

Nanoparticles can promote the accumulation of drugs in tumors. However, they find limited clinical applications because they cannot easily penetrate the stroma of cancer tissues, and it is difficult to control drug release. We developed a multiresponse multistage drug-delivery nanogel with improved tumor permeability and responsiveness to the tumor microenvironment for the controlled delivery of anticancer agents. For this purpose, ∼100 nm multistage drug delivery nanogels with pH, redox, near-infrared stimulation, and enzyme responsiveness were grown in situ using 20 nm gold nanoparticles (AuNPs) via an emulsion-aiding crosslinking technique with cysteine crosslinker. An alginate cysteine AuNP (ACA) nanocarrier can efficiently load the cationic drug doxorubicin (DOX) to produce a multistage drug delivery nanocarrier (DOX@ACA). DOX@ACA can maintain the slow release of DOX and reduce its toxicity. In cancer tissues, the high pH and reductase microenvironment combined with the in vitro delivery of alginate and near-infrared light drove drug release. The developed nanoparticles effectively inhibited cancer cells, and in vivo evaluations showed that they effectively enhanced antitumor activity while having negligible in vivo toxicity to major organs.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Nanopartículas , Alginatos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cisteína , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emulsões , Ouro , Concentração de Íons de Hidrogênio , Nanogéis , Sistemas de Liberação de Fármacos por Nanopartículas , Oxirredutases
11.
Acta Pharm Sin B ; 12(7): 3124-3138, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35865102

RESUMO

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

12.
Psychol Health Med ; 27(6): 1334-1346, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33434073

RESUMO

This study aimed to comprehensively analyze the effect of empty-nest on mental health and behaviors of the older population and explore the urban-rural differences. Data from the Cohort of Older People Health and Environment Controllable Factors were used, including 1071 older people aged 60 or over from a rural and an urban. Mental health, daily life behaviors, chronic physical diseases, and activities of daily living were evaluated. Logistic regression was used. The prevalence of empty-nest in older people was 55.0% in urban and 58.7% in rural. The empty-nest older people in urban were more likely to participate in physical exercise (OR[95%CI]: 1.55[1.03-2.31]), while the empty-nest older people in rural had lower rate of smoking (OR[95%CI]: 0.46[0.28-0.76]) and religious belief (OR[95%CI]: 1.61[1.01-2.58]), and higher prevalence of depression (OR[95%CI]: 1.55[1.03-2.35]) and higher level of total cholesterol (OR[95%CI]: 1.51[1.03-2.19]) compared with the non-empty-nest older people. In conclusion, the prevalence of empty-nest in older people was high both in rural and urban in China. Empty-nest exerts greater influences on the older people in rural than in urban, which should be given more attention, especially the depression and high total cholesterol.


Assuntos
Atividades Cotidianas , Saúde Mental , Idoso , China/epidemiologia , Colesterol , Doença Crônica , Depressão/epidemiologia , Comportamentos Relacionados com a Saúde , Humanos , População Rural , Inquéritos e Questionários
13.
Life Sci ; 284: 119895, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34450166

RESUMO

AIMS: Dipeptidyl peptidase-4 inhibitor (DPP4i), a new antidiabetic agent, is reported to affect the progression of chronic liver diseases. The study aims to investigate the effects of DPP4i on contractile response, splanchnic hemodynamics, and portal pressure in cirrhotic rats. MATERIALS AND METHODS: A rat model of carbon tetrachloride-induced cirrhosis was used in this study. Sixteen rats with cirrhosis were treated with DDP4i sitagliptin for 5 consecutive days. Portal and systemic pressures and portal blood flow were measured. Mesenteric arterioles were isolated, and concentration-response curves to norepinephrine (NE) were evaluated. The expression of NADPH oxidase (Nox)1, Nox2, Nox4, and soluble epoxide hydrolase (sEH) were detected. Reactive oxygen species (ROS) and epoxyeicosatrienoic acid (EET) levels in mesenteric arteries were also measured. KEY FINDINGS: In cirrhotic rats, sitagliptin significantly reduced portal blood flow and portal pressure without effects on systemic pressure and reversed the decreased response of mesenteric arterioles to NE in an endothelium-dependent manner. Sitagliptin suppressed the increased Nox4 expression and ROS production. In vitro studies showed that Nox4 inhibitor enhanced arteriolar response to NE and reduced hydrogen peroxide (H2O2) level in cirrhotic rats. Sitagliptin also reduced EET levels and increased sEH expression of mesenteric vessels. Pre-incubation with sEH inhibitor in vitro reversed sitagliptin-induced augmentation of response to NE in cirrhotic rats. SIGNIFICANCE: DPP4 inhibition by sitagliptin in vivo has beneficial effects on portal hypertension in cirrhotic rats through normalizing arterial hypocontractility. DDP4 inhibitor may be a novel strategy in the treatment of patients with cirrhosis and portal hypertension.


Assuntos
Artérias/fisiopatologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Vasoconstrição , Animais , Artérias/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Hemodinâmica/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Hipertensão Portal/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/tratamento farmacológico , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , NADPH Oxidase 4/metabolismo , Norepinefrina/farmacologia , Ratos Sprague-Dawley , Fosfato de Sitagliptina/farmacologia , Regulação para Cima/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos
14.
Acta Trop ; 223: 106072, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34358513

RESUMO

OBJECTIVE: On May 2, 2017, an outbreak of unexplained fever with rashes was reported in Lu'an, China. In this study, we aimed to identify the possible pathogens, epidemiological characteristics, and risk factors of this outbreak. METHODS: We conducted descriptive field epidemiological studies. Blood samples were tested using an indirect immunofluorescence assay for Rickettsia rickettsii antibody, and nested polymerase chain reaction and gene sequencing assays were performed. RESULTS: We recruited 39 cases who had symptomatic onset from April 20 to June 8, 2017. Among these, 9 were suspected cases, 18 were probable cases, and 12 were confirmed cases. No one died. The main clinical manifestations were fever (100%), rash (100%), fatigue (97.3%), myalgia (83.8%), and anorexia (83.8%). None of the patients died. Thirty-seven patients who were treated with antibiotics during hospitalization showed significant improvement. The cases were distributed across 14 townships in 2 counties. The median age was 59 (43.0-81.0) years, of which 93.3% had a history of tea picking (28/30), and 77.3% (17/22) had a history of tick bites. The mean incubation period was 5.0 days (2.0-13.0 days). Serum IgG titers were higher in convalescent patients than in the general population (p = 0.016). Phylogenetic analysis revealed that the ompA sequences of Rickettsia sp. Lu'an-2018 had an 86.8%-99.0% sequence identity with the 23 strains of Rickettsia found worldwide. CONCLUSIONS: This was the first reported outbreak of an undetermined species of a human infection with the spotted fever group of Rickettsia in China, which might be caused by ticks biting local residents when picking tea.


Assuntos
Rickettsia , Febre Maculosa das Montanhas Rochosas , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Mordeduras e Picadas , China/epidemiologia , Surtos de Doenças , Humanos , Pessoa de Meia-Idade , Filogenia , Rickettsia/genética , Febre Maculosa das Montanhas Rochosas/epidemiologia , Carrapatos
15.
Nat Metab ; 3(5): 651-664, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33972798

RESUMO

Metabolism negotiates cell-endogenous requirements of energy, nutrients and building blocks with the immediate environment to enable various processes, including growth and differentiation. While there is an increasing number of examples of crosstalk between metabolism and chromatin, few involve uptake of exogenous metabolites. Solute carriers (SLCs) represent the largest group of transporters in the human genome and are responsible for the transport of a wide variety of substrates, including nutrients and metabolites. We aimed to investigate the possible involvement of SLC-mediated solutes uptake and cellular metabolism in regulating cellular epigenetic states. Here, we perform a CRISPR-Cas9 transporter-focused genetic screen and a metabolic compound library screen for the regulation of BRD4-dependent chromatin states in human myeloid leukaemia cells. Intersection of the two orthogonal approaches reveal that loss of transporters involved with purine transport or inhibition of de novo purine synthesis lead to dysfunction of BRD4-dependent transcriptional regulation. Through mechanistic characterization of the metabolic circuitry, we elucidate the convergence of SLC-mediated purine uptake and de novo purine synthesis on BRD4-chromatin occupancy. Moreover, adenine-related metabolite supplementation effectively restores BRD4 functionality on purine impairment. Our study highlights the specific role of purine/adenine metabolism in modulating BRD4-dependent epigenetic states.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Cromatina/metabolismo , Proteínas de Transporte de Nucleosídeos/metabolismo , Purinas/metabolismo , Proteínas Carreadoras de Solutos/metabolismo , Fatores de Transcrição/metabolismo , Adenina/metabolismo , Vias Biossintéticas , Proteínas de Ciclo Celular/antagonistas & inibidores , Linhagem Celular , Cromatina/genética , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteínas de Membrana Transportadoras , Modelos Biológicos , Proteínas Carreadoras de Solutos/genética , Fatores de Transcrição/antagonistas & inibidores , Transcrição Gênica
16.
Technol Cancer Res Treat ; 20: 15330338211004954, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34056977

RESUMO

Salinomycin (Sal) is a potent inhibitor with effective anti-breast cancer properties in clinical therapy. The occurrence of various side effect of Sal greatly limits its application. The epidermal growth factor receptor (EGFR) family is a family of receptors highly expressed in most breast cancer cells. GE11 is a dodecapeptide which shows excellent EGFR affinity. A series of nanoparticles derivatives with GE11 peptide conjugated PLGA/TPGS were synthesized. Nanoprecipitation method was used to prepare the Sal loaded nanoparticles at the optimized concentration. The characterization, targeting efficacy, and antitumor activity were detected both in vitro and in vivo. Encapsulation of Sal in GE11 modified PLGA/TPGS nanoparticles shows an improved therapy efficacy and lower systemic side effect. This represents the delivery system a promising strategy to enhance the therapeutic effect against EGFR highly expressed breast cancer.


Assuntos
Antibacterianos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Peptídeos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Piranos/farmacologia , Vitamina E/química , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Piranos/administração & dosagem , Piranos/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Biosci Rep ; 41(4)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33734319

RESUMO

BACKGROUND: The aim of the present study was to confirm the role of Brachyury in breast cancer and to verify whether four types of machine learning models can use Brachyury expression to predict the survival of patients. METHODS: We conducted a retrospective review of the medical records to obtain patient information, and made the patient's paraffin tissue into tissue chips for staining analysis. We selected 303 patients for research and implemented four machine learning algorithms, including multivariate logistic regression model, decision tree, artificial neural network and random forest, and compared the results of these models with each other. Area under the receiver operating characteristic (ROC) curve (AUC) was used to compare the results. RESULTS: The chi-square test results of relevant data suggested that the expression of Brachyury protein in cancer tissues was significantly higher than that in paracancerous tissues (P=0.0335); patients with breast cancer with high Brachyury expression had a worse overall survival (OS) compared with patients with low Brachyury expression. We also found that Brachyury expression was associated with ER expression (P=0.0489). Subsequently, we used four machine learning models to verify the relationship between Brachyury expression and the survival of patients with breast cancer. The results showed that the decision tree model had the best performance (AUC = 0.781). CONCLUSIONS: Brachyury is highly expressed in breast cancer and indicates that patients had a poor prognosis. Compared with conventional statistical methods, decision tree model shows superior performance in predicting the survival status of patients with breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Proteínas Fetais/metabolismo , Proteínas com Domínio T/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Retículo Endoplasmático/metabolismo , Feminino , Proteínas Fetais/genética , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Análise de Sobrevida , Proteínas com Domínio T/genética
18.
Biol Trace Elem Res ; 199(4): 1280-1290, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32651944

RESUMO

Our objective was to evaluate the relationship of blood metal levels including strontium, cadmium, lead, vanadium, aluminum, cobalt, and manganese with dyslipidemia in the elderly Chinese population. In this study, stratified cluster sampling was adopted in the elderly in two communities of Lu'an City from June to September 2016, and 1013 participants were finally included. The inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the metals' concentrations in whole blood. After multivariable adjustment, the odds ratios (95% confidence interval [CI]) of dyslipidemia associated with the highest quartile of metal concentrations were 1.32 (0.89 ~ 1.96), 1.28 (0.83 ~ 1.97), 1.86 (1.23 ~ 2.80), 0.80 (0.55 ~ 1.16), 0.76 (0.51 ~ 1.13), 0.76 (0.53 ~ 1.11), and 1.14 (0.78 ~ 1.67) for strontium, cadmium, lead, vanadium, aluminum, cobalt, and manganese, respectively, compared with the lowest quartile. After reducing the dimensionality of metal elements by principal component analysis, we found that the combined exposure of aluminum, cobalt, and vanadium was the protective factor of non-dyslipidemia, while the combined exposure of cadmium, strontium, and lead was the risk factor of dyslipidemia.


Assuntos
Dislipidemias , Metais Pesados , Idoso , Cádmio , Cobre , Dislipidemias/induzido quimicamente , Dislipidemias/epidemiologia , Humanos , Metais Pesados/sangue , Zinco
19.
Biol Trace Elem Res ; 199(2): 403-412, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32323131

RESUMO

This study aimed to evaluate the association between aluminum (Al), arsenic (As), barium (Ba), cobalt (Co), manganese (Mn), selenium (Se), strontium (Sr), thallium (Tl), and vanadium (V) levels in whole blood and the cognitive ability of people over 60 years old. A total of 1217 eligible participants were enrolled in our study in Lu'an city, Anhui province, China. The inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the concentration of nine trace elements in the whole blood, which reflect their exposure levels. Mini-mental State Examination (MMSE) scale was employed to screen the cognitive function of the elderly. Logistic regression was applied to assess the associations of nine whole blood trace elements with cognition. In the work, it has found that high levels of whole blood As and Se are risk factors for cognitive dysfunction. As and Se quartile were correlated with increased risk of cognitive dysfunction, and with the odds ratio (OR) of 2.06 (95% CI 1.30-3.25; p-trend = 0.002), 1.947 (95% CI 1.20-3.17; p-trend = 0.007) in the highest quartile. However, high concentration of Al, V, and Ba in whole blood were protective factors for cognitive function [OR = 0.63 (95% CI 0.40-0.98; p-trend = 0.040), 0.549 (95% CI 0.36-0.85; p-trend = 0.007), 0.460 (95% CI 0.28-0.75; p-trend = 0.002) respectively]. The study suggested that the exposure of some trace elements (As, Se) were associated with the increased risk of cognitive dysfunction; on the contrary, other elements (Al, V, Ba) could be protective factor for cognitive function. These findings need to be confirmed in additional research of a large elderly population.


Assuntos
Oligoelementos , Idoso , China , Cobalto/análise , Cognição , Humanos , Manganês/análise , Pessoa de Meia-Idade , Oligoelementos/análise
20.
Epidemiol Infect ; 148: e132, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32611465

RESUMO

Hubei province in China has had the most confirmed coronavirus disease 2019 (COVID-19) cases and has reported sustained transmission of the disease. Although Lu'an city is adjacent to Hubei province, its community transmission was blocked at the early stage, and the impact of the epidemic was limited. Therefore, we summarised the overall characteristics of the entire epidemic course in Lu'an to help cities with a few imported cases better contain the epidemic. A total of 69 confirmed COVID-19 cases and 11 asymptomatic carriers were identified in Lu'an during the epidemic from 12 January to 21 February 2020. Fifty-two (65.0%) cases were male, and the median age was 40 years. On admission, 56.5% of cases had a fever as the initial symptom, and pneumonia was present in 89.9% of cases. The mean serial interval and the mean duration of hospitalisation were 6.5 days (95% CI: 4.8-8.2) and 18.2 days (95% CI: 16.8-19.5), respectively. A total of 16 clusters involving 60 cases (17 first-generation cases and 43 secondary cases) were reported during the epidemic. We observed that only 18.9% (7/37) index cases resulted in community transmission during the epidemic in Lu'an, indicating that the scale of the epidemic was limited to a low level in Lu'an city. An asymptomatic carrier caused the largest cluster, involving 13 cases. Spread of COVID-19 by asymptomatic carriers represents an enormous challenge for countries responding to the pandemic.


Assuntos
Portador Sadio/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Adolescente , Adulto , Idoso , COVID-19 , Portador Sadio/epidemiologia , Portador Sadio/transmissão , Criança , Pré-Escolar , China/epidemiologia , Cidades/epidemiologia , Análise por Conglomerados , Infecções por Coronavirus/transmissão , Feminino , Febre , Humanos , Lactente , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/transmissão , Vigilância da População/métodos , Fatores de Tempo , Adulto Jovem
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