Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 211
Filtrar
1.
Geriatr Nurs ; 58: 388-398, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880079

RESUMO

BACKGROUND: Malnutrition is prevalent among elderly cancer patients. This study aims to develop a predictive model for malnutrition in hospitalized elderly cancer patients. METHODS: Data from January 2022 to January 2023 on cancer patients aged 60+ were collected, involving 22 variables. Key variables were identified using the LASSO (Least Absolute Shrinkage and Selection Operator) method, and nine machine learning models were tested. SHAP was used to interpret the XGBoost model. Malnutrition prevalence was assessed. RESULTS: Among 450 participants, 46.4 % were malnourished. Key predictors identified were ADL (Activities of Daily Living), ALB (Albumin), BMI (Body Mass Index) and age. XGBoost had the highest AUC of 0.945, accuracy of 0.872, and sensitivity of 0.968. Higher ADL and age increased malnutrition risk, while lower ALB and BMI reduced it. CONCLUSIONS: The XGBoost model is highly effective in detecting malnutrition in elderly cancer patients, enabling early and rapid nutritional assessments.

2.
Phytother Res ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761036

RESUMO

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in-depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT-PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA-induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti-lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine-mediated anti-tumor therapy.

3.
Exp Ther Med ; 27(5): 219, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590572

RESUMO

Disruption of the epithelial-mesenchymal transition (EMT) of activated lung cells is an important strategy to inhibit the progression of idiopathic pulmonary fibrosis (IPF). The present study investigated the role of exosomes derived from airway basal cells on EMT of lung cells and elucidate the underlying mechanism. Exosomes were characterized by nanoparticle tracking analysis, transmission electron microscopy imaging and markers detection. The role of exosome on the EMT of lung epithelial cells and lung fibroblasts induced by TGF-ß1 was detected. RNA sequencing screened dysregulated genes in exosome-treated group, followed by the bioinformatical analysis. One of the candidates, anoctamin-1 (ANO1), was selected for further gain-and-loss phenotype assays. A bleomycin-induced pulmonary fibrosis model was used to evaluate the treatment effect of exosomes. Exosomes were round-like and positively expressed CD63 and tumor susceptibility gene 101 protein. Treatment with exosomes inhibited the EMT of lung cells activated by TGF-ß1. 4158 dysregulated genes were identified in exosome-treated group under the threshold of |log2 fold-change| value >1 and they were involved in the metabolism of various molecules, as well as motility-related biological processes. A key gene, ANO1, was verified by reverse transcription-quantitative PCR, whose overexpression induced the EMT of lung cells. By contrast, ANO1 knockdown reversed the EMT induced by TGF-ß1. In vivo assay indicated that exosome treatment ameliorated pulmonary fibrosis and inhibited the upregulation of ANO1 induced by bleomycin. In conclusion, airway basal cell-derived exosomes suppressed the EMT of lung cells via the downregulation of ANO1. These exosomes represent a potential therapeutic option for patients with IPF.

4.
Diagn Pathol ; 19(1): 61, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641621

RESUMO

BACKGROUND AND OBJECTIVE: EBUS-TBNA has emerged as an important minimally invasive procedure for the diagnosis and staging of lung cancer. Our objective was to evaluate the effect of different specimen preparation from aspirates on the diagnosis of lung cancer. METHODS: 181 consecutive patients with known or suspected lung cancer accompanied by hilar / mediastinal lymphadenopathy underwent EBUS-TBNA from January 2019 to December 2022. Specimens obtained by EBUS-TBNA were processed by three methods: Traditional smear cytology of aspirates (TSC), liquid-based cytology of aspirates (LBC) and histopathology of core biopsies. RESULTS: EBUS-TBNA was performed in 181 patients on 213 lymph nodes, the total positive rate of the combination of three specimen preparation methods was 80.7%. The diagnostic positive rate of histopathology was 72.3%, TSC was 68.1%, and LBC was 65.3%, no significant differences was observed (p = 0.29); however, statistically significant difference was noted between the combination of three preparation methods and any single specimen preparation methods (p = 0.002). The diagnostic sensitivity of histopathology combined with TSC and histopathology combined with LBC were 96.5 and 94.8%, the specificity was 95.0% and 97.5%, the PPV was 98.8% and 99.4%, the NPV was 86.4% and 81.2%, the diagnostic accuracy was 96.2% and 95.3%, respectively; The sensitivity and accuracy of above methods were higher than that of single specimen preparation, but lower than that of combination of three preparation methods. CONCLUSION: When EBUS-TBNA is used for the diagnosis and staging of lung cancer, histopathology combined with TSC can achieve enough diagnostic efficiency and better cost-effectiveness.


Assuntos
Neoplasias Pulmonares , Linfadenopatia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Mediastino/diagnóstico por imagem , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Linfonodos/patologia , Linfadenopatia/patologia , Broncoscopia/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos
5.
Sci Rep ; 14(1): 9212, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649401

RESUMO

A higher incidence of chronic atrophic gastritis (CAG) is generally considered as a precancerous lesion in gastric cancer (GC). The aim of this study was to identify potential molecules involved in the pathogenesis of CAG in the Tibetan plateau, hoping to help the diagnosis and management of the disease. Atrophic and non-atrophic gastric mucosal tissue samples were collected from seven patients with chronic gastritis (CG). Differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs between CAG and chronic non-atrophic gastritis (CNAG) groups were identified based on DNBSEQ-G99 RNA sequencing. Subsequently, competitive endogenous RNA (ceRNA) regulatory networks (lncRNA/circRNA-miRNA-mRNA networks) were constructed. Two datasets (GSE153224 and GSE163416), involving data from non-Tibetan plateau areas, were used to further screen out Tibetan plateau key mRNAs, followed by the common genes of Tibetan plateau key and ferroptosis-related mRNAs were also identified. Functional enrichment analyses were performed to investigate the biological functions of Tibetan plateau mRNAs in the CAG. A total of seven lncRNA-miRNA-mRNA relationship pairs and 424 circRNA-miRNA-mRNA relationship pairs were identified in this study. The relationship pairs of hsa_circ_0082984-hsa-miR-204-5p-CACNG8, lncRNA DRAIC/has_circ_0008561-hsa-miR-34a-5p-AR/GXYLT2, lncRNA GAS1RR/RGMB-AS1/hsa_circ_0008561-hsa-miR-3614-5p-TMEM216/SUSD5, and LINC00941/hsa_circ_0082984-hsa-miR-873-3p-TMC5 can be involved in the pathogenesis of CAG. Additionally, eight common genes of Tibetan plateau key and ferroptosis-related differentially expressed mRNAs (DEmRNAs) (CBS, SLC2A4, STAT3, ALOX15B, ATF3, IDO1, NOX4, and SOCS1) were identified in CAG. The common genes of Tibetan plateau key and ferroptosis-related DEmRNAs can play a role in the JAK-STAT signaling pathway. This study identified important molecular biomarkers that may be involved in regulating the pathological mechanisms of CAG in the Tibetan plateau, which provides potential research directions for future research.


Assuntos
Gastrite Atrófica , Redes Reguladoras de Genes , MicroRNAs , RNA Circular , RNA Longo não Codificante , RNA Mensageiro , Humanos , Gastrite Atrófica/genética , Tibet , RNA Longo não Codificante/genética , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Circular/genética , Masculino , Feminino , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Análise de Sequência de RNA , Doença Crônica , Ferroptose/genética , Adulto
6.
Phytomedicine ; 128: 155495, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38471317

RESUMO

BACKGROUND: Ginsenosides have received increased amounts of attention due to their ability to modulate the intestinal flora, which may subsequently alleviate alcoholic liver disease (ALD). The effects of ginseng fermentation solution (GFS) on the gut microbiota and metabolism in ALD patients have not been explored. PURPOSE: This research aimed to explore the regulatory effect of GFS on ALD both in vitro and in vivo. METHOD: This study assessed the anti-ALD efficacy of GFS using an LO2 cell model and a zebrafish model. Untargeted metabolomics was used for differentially abundant metabolite analysis, and high-throughput 16S rRNA sequencing was used to examine the effect of GFS on ALD. RESULTS: The LO2 cell line experiments demonstrated that GFS effectively mitigated alcohol-induced oxidative stress and reduced apoptosis by upregulating PI3K and Bcl-2 expression and decreasing the levels of malondialdehyde, total cholesterol, and triglycerides. In zebrafish, GFS improved morphological and physiological parameters and diminished oxidative stress-induced ALD. Meanwhile, the results from Western blotting indicated that GFS enhanced the expression of PI3K, Akt, and Bcl-2 proteins while reducing Bax protein expression, thereby ameliorating the ALD model in zebrafish. Metabolomics data revealed significant changes in a total of 46 potential biomarkers. Among them, metabolites such as prostaglandin F2 alpha belong to arachidonic acid metabolism. In addition, GFS also partly reversed the imbalance of gut microbiota composition caused by alcohol. At the genus level, alcohol consumption elevated the presence of Flectobacillus, Curvibacter, among others, and diminished Elizabethkingia within the intestinal microbes of zebrafish. Conversely, GFS reversed these effects, notably enhancing the abundance of Proteobacteria and Archaea. Correlation analyses further indicated a significant negative correlation between prostaglandin F2 alpha, 11,14,15-THETA, Taurocholic acid and Curvibacter. CONCLUSION: This study highlights a novel mechanism by which GFS modulates anti-ALD activity through the PI3K/Akt signalling pathway by influencing the intestinal flora-metabolite axis. These results indicate the potential of GFS as a functional food for ALD treatment via modulation of the gut flora.


Assuntos
Microbioma Gastrointestinal , Hepatopatias Alcoólicas , Panax , Animais , Humanos , Apoptose/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Ginsenosídeos/farmacologia , Hepatopatias Alcoólicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
7.
Front Oncol ; 14: 1353592, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38347842

RESUMO

Background: Cavernous haemangiomas (CHs) commonly occurred in the skin, subcutaneous tissue, muscles, and liver. Pulmonary cavernous haemangiomas (PCHs) are quite rare and usually present with nonspecific clinical symptoms. When lung cancer patients are complicated with pulmonary cavernous haemangiomas, radiologically, these haemangioma lesions can be easily misinterpreted as intrapulmonary metastases, potentially resulting in misdiagnosis, or missed diagnosis. Case presentation: The present study reported the case of a 53-year-old female patient with pulmonary adenocarcinoma coexisting with multiple PCHs. 18F-FDG-Positron emission tomography-computed tomography (PET-CT) showed an elevated glucose metabolism in the apicoposterior segment of the left upper lobe; however, the other nodules were not hypermetabolic. Percutaneous lung biopsy was performed on the nodule in the apicoposterior segment of the left upper lobe, which were diagnosed as primary adenocarcinoma. Some nodules in the upper left lobe underwent wedge resection by video-assisted thoracic surgery (VATS) and intraoperative frozen section identified as PCHs. Finally, the patient underwent lobectomy of the left upper lobe via VATS, cancerous nodule in the apicoposterior segment of the left upper lobe underwent genetic molecular testing of PCR-Sanger sequencing, suggested EGFR mutation, and patient received treatment with Osimertinib. During the 4-months follow-up, contrast-enhanced CT showed no recurrence of either disease. PCHs are rare benign tumours of the lung, which can lead to misdiagnosis due to their non-specific clinical symptoms and radiological features, especially when they coexist with lung cancer. PCHs is easily misunderstood as metastatic lung cancer, in this case, PET-CT can assist in differentiating benign from malignant. For the cases of early lung cancer complicated with PCHs, lung cancer can be surgically resected, and whether PCHs should be removed or not should be determined according to the size and distribution of the lesions.

8.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338959

RESUMO

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doenças das Aves Domésticas , Animais , Masculino , Galinhas , Interferon-alfa/farmacologia , Interferon-alfa/genética , Sorogrupo , Adenoviridae/genética , Antivirais/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico
9.
Cell Death Dis ; 15(1): 50, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38221520

RESUMO

Immunotherapy has rapidly evolved in the past decades in the battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success in certain hematologic malignancies, although they still face certain limitations, including high costs and toxic effects. Natural killer cells (NK cells), as a vital component of the immune system, serve as the "first responders" in the context of cancer development. In this literature review, we provide an updated understanding of NK cell development, functions, and their applications in disease therapy. Furthermore, we explore the rationale for utilizing engineered NK cell therapies, such as CAR-NK cells, and discuss the differences between CAR-T and CAR-NK cells. We also provide insights into the key elements and strategies involved in CAR design for engineered NK cells. In addition, we highlight the challenges currently encountered and discuss the future directions in NK cell research and utilization, including pre-clinical investigations and ongoing clinical trials. Based on the outstanding antitumor potential of NK cells, it is highly likely that they will lead to groundbreaking advancements in cancer treatment in the future.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Células Matadoras Naturais , Neoplasias/patologia , Imunoterapia , Imunoterapia Adotiva
10.
Photodiagnosis Photodyn Ther ; 45: 103917, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042236

RESUMO

OBJECTIVE: Photodynamic therapy (PDT) primarily treats skin diseases or cancer by generating reactive oxygen species (ROS) to damage cellular DNA, yet drug resistance limits its application. To tackle this problem, the present study was carried out to improve the efficacy of chlorin e6 (Ce6)-PDT using Cepharanthine (CEP) as well as to reveal the potential molecular mechanism. MATERIALS AND METHODS: Lewis lung cancer cell line (LLC) was utilized as the cancer cell model. chlorin e6 (Ce6) acted as the photosensitizer to induce PDT. The in vitro anti-cancer efficacy was measured by CCK-8, Annexin-V/PI staining, and migration assay. The Ce6 uptake was observed using flow cytometry and confocal microscopy. The ROS generation was detected by the DCFH-DA probe. The analysis of MutT Homolog 1 (MTH1) expression, correlation, and prognosis in databases was conducted by bioinformatic. The MTH1 expression was detected through western blots (WB). DNA damage was assayed by WB, immunofluorescent staining, and comet assay. RESULTS: Ce6-PDT showed robust resistance in lung cancer cells under certain conditions, as evidenced by the unchanged cell viability and apoptosis. The subsequent findings confirmed that the uptake of Ce6 and MTH1 expression was enhanced, but ROS generation with laser irradiation was not increased in LLC, which indicated that the ROS scavenge may be the critical reason for resistance. Surprisingly, bioinformatic and in vitro experiments identified that MTH1, which could prevent the DNA from damage of ROS, was highly expressed in lung cancer and thereby led to the poor prognosis and could be further up-regulated by Ce6 PDT. CEP exhibited a dose-dependent suppressive effect on the lung cancer cells. Further investigations presented that CEP treatment boosted ROS production, thereby resulting in DNA double-strand breakage (DDSB) with activation of MTH1, indicating that CEP facilitated Ce6-PDT-mediated DNA damage. Finally, the combination of CEP and Ce6-PDT exhibited prominent ROS accumulation, MTH1 inhibition, and anti-lung cancer efficacy, which had synergistic pro-DNA damage properties. CONCLUSION: Collectively, highly expressed MTH1 and the failure of ROS generation lead to PDT resistance in lung cancer cells. CEP facilitates ROS generation of PDT, thereby promoting vigorous DNA damage, inactivating MTH1, alleviating PDT resistance, and ameliorating the anti-cancer efficacy of Ce6-PDT, provides a novel approach for augmented PDT.


Assuntos
Benzodioxóis , Benzilisoquinolinas , Neoplasias Pulmonares , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Neoplasias Pulmonares/tratamento farmacológico , Dano ao DNA , DNA
11.
Int J Pharm ; 650: 123718, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38104849

RESUMO

The emergence of multidrug resistance (MDR) is the leading cause of mortality in patients with breast cancer. Overexpressed P-glycoprotein (P-gp) that can pump out chemotherapeutics from multidrug-resistant cancer cells is the main cause of chemotherapy failure. P-gp inhibitors are hence increasingly used to sensitize chemotherapy to breast cancer with MDR by reducing the efflux of drugs. However, representative P-gp inhibitors usually have severe side effects and the effect of their release behavior on chemotherapy are neglected in current studies. We constructed a nano-in-thermogel delivery system with the sequential release of ginsenoside Rh2 (GRh2) and a chemotherapeutic drug in the tumor microenvironment as a drug compounding "reservoir" to combat MDR in breast cancer. Briefly, paclitaxel (PTX) and GRh2 were encapsulated in solid lipid nanoparticles (SLNs) and dispersed in a poloxamer-based thermogel (SLNs-Gel). GRh2 was used as an innovative and safe P-gp inhibitor to lower P-gp expression and cellular adenosine triphosphate context, thereby sensitizing PTX-resistant breast cancer cells (MCF-7/PTX) to PTX. Pharmacodynamic and in vivo safety studies confirmed that intratumoral injection of SLNs-Gel significantly suppressed the proliferation of PTX-resistant breast cancer and alleviated the PTX-induced hematotoxicity. The GRh2-irrigated nano-in-thermogel delivery system shows great potential in combating multidrug-resistant cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/patologia , Resistência a Múltiplos Medicamentos , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Paclitaxel , Linhagem Celular Tumoral , Células MCF-7 , Microambiente Tumoral
12.
Vet Microbiol ; 289: 109949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128444

RESUMO

Newcastle disease (ND) is a highly pathogenic, contagious, and fatal infectious disease in poultry caused by the Newcastle disease virus (NDV). The PI3K/AKT signaling pathway is a phosphorylation cascade that participates in regulating several cellular functions. Viruses reportedly regulate the course of infection through the PI3K/AKT axis. Here, we aimed to analyze the pathogenesis of NDV infection mediated by the PI3K/AKT signaling pathway activation. We found that NDV infection can phosphorylate AKT to activate the PI3K/AKT axis both in vitro and in vivo. Flow cytometry and Caspase-3 activity assay showed that NDV infection could inhibit cell apoptosis. The activation or inhibition of the PI3K/AKT signaling pathway activity significantly inhibited or promoted NDV-mediated apoptosis. Furthermore, inhibition of cell apoptosis significantly promoted NDV replication. Overall, our results showed that NDV infection activates the PI3K/AKT signaling pathway and inhibits cell apoptosis, thus promoting viral replication. In this context, the reduced expression of PHLPP2 protein mediated by NDV infection could be inhibited by MG132. PHLPP2 expression reversely and positively regulated NDV replication and cell apoptosis, respectively. These results indicated that NDV infection-mediated activation of the PI3K/AKT signaling pathway and the inhibition of apoptosis depend on the ubiquitin-proteasome degradation of the PHLPP2 protein. Co-IP and indirect immunofluorescence results showed that NDV V protein could interact with PHLPP2 protein, indicating that NDV targeted PHLPP2 protein degradation through V protein to activate the PI3K/AKT signaling pathway. This study deepens our understanding of the molecular mechanisms of NDV infection, providing a theoretical basis for ND prevention and control.


Assuntos
Doença de Newcastle , Vírus da Doença de Newcastle , Animais , Vírus da Doença de Newcastle/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Apoptose , Replicação Viral
13.
Respir Res ; 24(1): 300, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38017523

RESUMO

BACKGROUND: The accumulation of myofibroblasts is the key pathological feature of pulmonary fibrosis (PF). Aberrant differentiation of lung-resident mesenchymal stem cells (LR-MSCs) has been identified as a critical source of myofibroblasts, but the molecular mechanisms underlying this process remain largely unknown. In recent years, N6-methyladenosine (m6A) RNA modification has been implicated in fibrosis development across diverse organs; however, its specific role in promoting the differentiation of LR-MSCs into myofibroblasts in PF is not well defined. METHODS: In this study, we examined the levels of m6A RNA methylation and the expression of its regulatory enzymes in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. The downstream target genes of m6A and their related pathways were identified according to a literature review, bioinformatic analysis and experimental verification. We also assessed the expression levels of myofibroblast markers in treated LR-MSCs and confirmed the involvement of the above-described pathway in the aberrant differentiation direction of LR-MSCs under TGF-ß1 stimulation by overexpressing or knocking down key genes within the pathway. RESULTS: Our results revealed that METTL3-mediated m6A RNA methylation was significantly upregulated in both TGF-ß1-treated LR-MSCs and fibrotic mouse lung tissues. This process directly led to the aberrant differentiation of LR-MSCs into myofibroblasts by targeting the miR-21/PTEN pathway. Moreover, inhibition of METTL3 or miR-21 and overexpression of PTEN could rescue this abnormal differentiation. CONCLUSION: Our study demonstrated that m6A RNA methylation induced aberrant LR-MSC differentiation into myofibroblasts via the METTL3/miR-21/PTEN signaling pathway. We indicated a novel mechanism to promote PF progression. Targeting METTL3-mediated m6A RNA methylation and its downstream targets may present innovative therapeutic approaches for the prevention and treatment of PF.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Fibrose Pulmonar , Animais , Camundongos , Diferenciação Celular , Fibrose , Pulmão/metabolismo , Células-Tronco Mesenquimais/metabolismo , Metilação , MicroRNAs/genética , MicroRNAs/metabolismo , Miofibroblastos/metabolismo , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/farmacologia
14.
Oncol Lett ; 26(6): 517, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37927412

RESUMO

Malignant melanoma (MM) commonly presents as a primary skin tumor and respiratory MM cases are almost all metastatic. Primary lung MM (PMML) is quite rare, especially when manifested as an endobronchial pigmented mass, its diagnosis is relatively difficult and MM has a poor prognosis. Only a few cases have been described previously and the pathologic features, clinical behavior and therapeutic options are not well established. The present study reports the case of a 72-year-old female patient with PMML who denied any history of tumors. The patient complained of chest pain and coughing for 2 weeks. Chest computed tomography (CT) revealed a mass in the right upper lobe and an enlarged mediastinal lymph node. Positron emission tomogram-CT suggested a hypermetabolic tumor. To confirm the diagnosis, the patient underwent a transbronchial forceps biopsy and endobronchial ultrasound-guided transbronchial needle aspiration, which confirmed the diagnosis of PMML. Genetic testing identified a BRAF V600E mutation, so the patient received treatment with dabrafenib plus trametinib. PMML is extremely rare and is easily misdiagnosed as lung cancer due to its nonspecific clinical manifestations and imaging features. The diagnosis of PMML remains challenging due to its morphologic and immunophenotypic variability. Targeted therapy is a good option for advanced PMML patients with BRAF V600E mutations.

16.
Microorganisms ; 11(11)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-38004643

RESUMO

Fowl adenovirus-induced hepatitis-pericardial effusion syndrome outbreaks have been increasingly reported in China since 2015, resulting in substantial economic losses to the poultry industry. The genetic diversity of indigenous chicken results in different immune traits, affecting the evolution of these viruses. Although the molecular epidemiology of fowl adenovirus serotype 4 (FAdV-4) has been well studied in commercial broiler and layer chickens, the prevalence and genetic characteristics of FAdV-4 in indigenous chickens remain largely unknown. In this study, samples were collected from six indigenous chicken breeds in Yunnan province, China. FAdV-positive samples were identified in five of the six indigenous chicken populations via PCR and 10 isolates were obtained. All FAdVs belonged to serotype FAdV-4 and species FAdV-C. The hexon, fiber, and penton gene sequence comparison analysis demonstrated that the prevalence of FAdV-4 isolates in these chickens might have originated from other provinces that exported chicks and poultry products to Yunnan province. Moreover, several distinct amino acid mutations were firstly identified in the major structural proteins. Our findings highlighted the need to decrease inter-regional movements of live poultry to protect indigenous chicken genetic resources and that the immune traits of these indigenous chickens might result in new mutations of FAdV-4 strains.

17.
Exp Hematol Oncol ; 12(1): 94, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946295

RESUMO

Recurrence is one of the main causes of treatment failure in early-stage non-small cell lung cancer (NSCLC). However, there are no predictors of the recurrence of early-stage NSCLC, and the molecular mechanism of its recurrence is not clear. In this study, we used clinical sample analysis to demonstrate that low levels of expression of precursor surfactant protein B (pro-SFTPB) in primary NSCLC tissue compared to their adjacent tissues are closely correlated with recurrence and poor prognosis in early-stage NSCLC patients. In vitro and in vivo experiments showed that downregulation of pro-SFTPB expression activates the Akt pathway by upregulating PGK1, which promotes metastasis and tumorigenicity in NSCLC cells. We then demonstrated that pro-SFTPB suppresses the formation of the ADRM1/hRpn2/UCH37 complex by binding to ADRM1, which inhibits PGK1 deubiquitination, thus accelerating ubiquitin-mediated PGK1 degradation. In summary, our findings indicate that low expression of pro-SFTPB in primary NSCLC compared to their adjacent tissue has potential as a predictor of recurrence and poor prognosis in early-stage NSCLC. Mechanistically, downregulation of pro-SFTPB attenuates inhibition of ADRM1-deubiquitinated PGK1, resulting in elevated levels of PGK1 protein; this activates the Akt pathway, ultimately leading to the progression of early-stage NSCLC.

18.
Oncol Lett ; 26(5): 472, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37809044

RESUMO

Numerous agents such as near-infrared dyes that are characterized by specialized cancer imaging and cytotoxicity effects have key roles in cancer diagnosis and therapy via molecularly targeting special biological tissues, organelles and processes. In the present study, a novel fluorescent compound was demonstrated to inhibit cancer cell proliferation in a zebrafish model with slight in vivo toxicity. Further studies demonstrated selective staining of cancer cells and even putative cancer stem cells via accumulation of the dye in the mitochondria of cancer cells, compared with normal cells. Moreover, this compound was also used to image cancer cells in vivo using a zebrafish model. The compound displayed no apparent toxicity to the host animal. Overall, the data indicated that this compound was worthy of further evaluation due to its low toxicity and selective cancer cell imaging and killing effects. It could be a useful tool in cancer research.

19.
Orthop J Sports Med ; 11(8): 23259671231180854, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37655249

RESUMO

Background: There is no clinical gold standard for the indications for single-row (SR) versus double-row (DR) repair according to small, large, or massive rotator cuff tear size. Purpose: To conduct a meta-analysis to compare the clinical outcomes and retear rates after arthroscopic SR and DR repair for rotator cuff injuries with different tear sizes. Study Design: Systematic review; Level of evidence, 3. Methods: On the basis of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria, the PubMed, Embase, Cochrane Library databases, Web of Science, China National Knowledge Infrastructure, and China BioMedical Literature database were searched for relevant studies published before November 1, 2021, using the following search terms: "Rotator Cuff Injuries," "Rotator Cuff Tears," "Arthroscopy," "Arthroscopic Surgery," "single-row," and "double-row"; a total of 489 articles were retrieved. Quality evaluation was conducted for all the studies that met the inclusion criteria. This study evaluated the Constant-Murley score, American Shoulder and Elbow Surgeons (ASES) score, University of California, Los Angeles (UCLA) score, and range of motion (ROM) as well as retear rate. A fixed-effects or random-effects model was adopted to calculate the results and assess risk. Results: A total of 10 clinical studies were included, with 404 cases of DR and 387 cases of SR. Regarding overall results, DR had better forward elevation ROM (mean difference [MD] = -4.03° [95% CI, -6.00° to -2.06°]; P < .0001; I 2 = 46%) and a lower retear rate (MD = 2.39 [95% CI, 1.40 to 4.08]; P = .001; I 2 = 0%) compared with SR repair. With regard to small tears (<3 cm), there was no noticeable difference on any of the 3 outcome scores between SR and DR. For large rotator cuff tears (≥3 cm), DR repair showed significantly better ASES scores (MD = -3.09 [95% CI, -6.19 to 0.02]; P = .05; I 2 = 73%) and UCLA scores (MD = -1.47 [95% CI, -2.21 to -0.72]; P = .0001; I 2 = 31%) compared with SR repair. Conclusion: Our meta-analysis revealed that DR had better UCLA scores, ASES scores, and ROM in forward elevation and lower retear rates. In rotator cuff tears <3 cm, there were no statistical differences in clinical outcome between SR and DR.

20.
Chin Herb Med ; 15(3): 349-359, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37538862

RESUMO

Natto is a soybean product fermented by natto bacteria. It is rich in a variety of amino acids, vitamins, proteins and active enzymes. It has a number of biological activities, such as thrombolysis, prevention of osteoporosis, antibacterial, anticancer, antioxidant and so on. It is widely used in medicine, health-care food, biocatalysis and other fields. Natto is rich in many pharmacological active substances and has significant medicinal research value. This paper summarizes the pharmacological activities and applications of natto in and outside China, so as to provide references for further research and development of natto.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA