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1.
Sensors (Basel) ; 24(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38610291

RESUMO

Deep transfer learning has been widely used to improve the versatility of models. In the problem of cross-domain fault diagnosis in rolling bearings, most models require that the given data have a similar distribution, which limits the diagnostic effect and generalization of the model. This paper proposes a deep reconstruction transfer convolutional neural network (DRTCNN), which satisfies the domain adaptability of the model under cross-domain conditions. Firstly, the model uses a deep reconstruction convolutional automatic encoder for feature extraction and data reconstruction. Through sharing parameters and unsupervised training, the structural information of target domain samples is effectively used to extract domain-invariant features. Secondly, a new subdomain alignment loss function is introduced to align the subdomain distribution of the source domain and the target domain, which can improve the classification accuracy by reducing the intra-class distance and increasing the inter-class distance. In addition, a label smoothing algorithm considering the credibility of the sample is introduced to train the model classifier to avoid the impact of wrong labels on the training process. Three datasets are used to verify the versatility of the model, and the results show that the model has a high accuracy and stability.

2.
Se Pu ; 42(3): 275-281, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38503704

RESUMO

A non-invasive condensation collection-ion chromatography method was established for the determination of organic acids and anions including lactic acid, formic acid, acetic acid, pyruvic acid, chloride, nitrate, nitrite, and sulfate in the exhaled breath of humans. The breath exhaled was condensed and collected using a home-made exhaled breath condensation equipment. This equipment included a disposable mouthpiece as a blow-off port, one-way valve and flow meter, cold trap, disposable condensate collection tube placed in the cold trap, and gas outlet. A standard sampling procedure was used. Before collection, the collection temperature and sampling volume were set on the instrument control panel, and sampling was started when the cold-trap temperature dropped to the set value, while maintaining the balance. Subjects were required to gargle with pure water before sampling. During the sampling process, the subjects were required to inhale deeply until the lungs were full of gas and then exhale evenly through the air outlet. When the set volume was collected, the instrument made a prompt sound; then, the collection was immediately ended, the expiration time was recorded, and the average collection flow was calculated according to the expiration time and sampling volume. After collection, the disposable condensation collection tube was immediately taken out, sealed, and stored in the refrigerator at -20 ℃ away from light, and immediately used for further testing. The organic acids and anions in exhaled breath condensation (EBC) were filtered through a 0.22 µm membrane filter before injection and detected by ion chromatography with conductivity detection. Factors such as collection temperature and collection flow rate during condensation collection were optimized. The optimal cooling temperature was set at -15 ℃, and the optimal exhaled breath flow rate was set at 15 L/min. The mobile phase consisted of a mixture of sodium carbonate (1.5 mmol/L) and sodium bicarbonate (3 mmol/L). The flow rate was 0.8 mL/min, and the injection volume was 100 µL. An IC-SA3 column (250 mm×4.0 mm) was used, and the temperature was set at 45 ℃. An ICDS-40A electrodialysis suppressor was used, and the current was set at 150 mA. The linear ranges of the eight organic acids and anions were 0.1-10.0 mg/L; their correlation coefficients (r) were ≥0.9993. The limits of detection (LODs) for the eight organic acids and anions were 0.0017-0.0150 mg/L based on a signal-to-noise ratio of 3, and the limits of quantification (LOQs) were 0.0057-0.0500 mg/L based on a signal-to-noise ratio of 10. The intra-day precisions were 5.06%-6.33% (n=5), and the inter-day precisions were 5.37%-7.50% (n=5). This method was used to detect organic acids and anions in the exhaled breath of five healthy subjects. The contents of organic acids and anions in the exhaled breath were calculated. The content of lactic acid was relatively high, at 1.13-42.3 ng/L, and the contents of other seven organic acids and anions were 0.18-11.0 ng/L. During a 10 km-long run, the majority of organic acids and anions in the exhaled breath of five subjects first increased and then decreased. However, due to abnormal metabolism, the content changes of lactic acid, acetic acid, pyruvic acid and chloride in one subject were obviously different from others during exercise, showing a continuous rise. This method has the advantages of involving a simple sampling process and exhibiting good precision, few side effects, and no obvious discomfort or risk to the subjects. This study provides experimental ideas and a theoretical basis for future research on human metabolites.


Assuntos
Cloretos , Ácido Pirúvico , Humanos , Ânions , Ácido Láctico/análise , Cromatografia , Acetatos/análise
3.
Front Oncol ; 14: 1294383, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444672

RESUMO

Background: As lung squamous cell carcinoma (LUSC) patients are at increased risk of developing a second primary cancer, this complicates the patient's condition and thus makes prognostic assessment more difficult, posing a significant prognostic challenge for clinicians. Our goal was to assess the prognosis of LUSC patients with a second primary tumor, and provide insights into appropriate therapy and monitoring strategies. Methods: Data was obtained for LUSC patients from the Surveillance, Epidemiology, and End Results (SEER) database. The LUSC patients were divided into three groups (LS-SPM, OT-LUSC and LUSC-only). Univariate and stratified analyses were performed for the baseline and clinical characteristics of the participants. Multiple regression and Kaplan-Meier survival analyses were also performed, followed by a final life table analysis. Results: In our sample of 101,626 patients, the HR for OS in the LS-SPM group was 0.40 in univariate analysis. Kaplan-Meier survival curves showed that LS-SPM patients had considerably longer lifespans compared to the other groups. The LS-SPM patients had median and mean survival times of 64 months and 89.11 months. Unadjusted and adjusted multiple regression analyses showed that LS-SPM patients had a superior survival compared to LUSC-only and OT-LUSC groups. Conclusion: LS-SPM patients have a good prognosis with aggressive therapy and immune monitoring. The present study offers novel insights into the pathophysiological causes and treatments for LS-SPM.

4.
Adv Sci (Weinh) ; 11(14): e2307143, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308097

RESUMO

Photodynamic therapy (PDT) is a minimally invasive and controllable local cancer treatment for cholangiocarcinoma (CCA). However, the efficacy of PDT is hindered by intratumoral hypoxia and the presence of an antioxidant microenvironment. To address these limitations, combining PDT with gas therapy may be a promising strategy to enhance tumor oxygenation. Moreover, the augmentation of oxidative damage induced by PDT and gas therapy can be achieved by inhibiting NRF2, a core regulatory molecule involved in the antioxidant response. In this study, an integrated nanotherapeutic platform called CMArg@Lip, incorporating PDT and gas therapies using ROS-responsive liposomes encapsulating the photosensitizer Ce6, the NO gas-generating agent L-arginine, and the NRF2 inhibitor ML385, is successfully developed. The utilization of CMArg@Lip effectively deals with challenges posed by tumor hypoxia and antioxidant microenvironment, resulting in elevated levels of oxidative damage and subsequent induction of ferroptosis in CCA. Additionally, these findings suggest that CMArg@Lip exhibits notable immunomodulatory effects, including the promotion of immunogenic cell death and facilitation of dendritic cell maturation. Furthermore, it contributes to the anti-tumor function of cytotoxic T lymphocytes through the downregulation of PD-L1 expression in tumor cells and the activation of the STING signaling pathway in myeloid-derived suppressor cells, thereby reprogramming the immunosuppressive microenvironment via various mechanisms.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/farmacologia , Colangiocarcinoma/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/metabolismo , Microambiente Tumoral
5.
Angiology ; : 33197241227275, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212979

RESUMO

There are numerous causes of abdominal aortic calcification (AAC), among which the relationship between serum uric acid and AAC still needs to be investigated further. The aim of this research was to ascertain whether serum uric acid is correlated with AAC. Our study included 3007 participants. We described the study population characteristics and utilized univariate analysis, stratified analysis, multiple equation regression analysis, smoothed curve fitting, and threshold effects analysis. AAC Total 24 score is used to reflect the range of aortic calcification at each vertebral level. As serum uric acid increased, the AAC Total 24 score first decreased and then increased. The fold point is located when serum uric is at 3.5 mg/dL. After adjusting for 16 covariates, the beta values for the groups with moderate and high serum uric acid levels were 0.34 and 0.53, respectively, compared with the low serum uric acid tertile group (P < .05). Our research indicates a negative correlation between serum acid level and AAC when serum uric acid <3.5 mg/dl, but it is positively correlated with the formation of AAC when serum uric acid >3.5 mg/dl.

6.
Aging (Albany NY) ; 15(23): 13888-13900, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38070140

RESUMO

BACKGROUND: Heart failure is a prevalent and life-threatening medical condition characterized by abnormal atrial electrical activity, contributing to a higher risk of ischemic stroke. Atrial remodelling, driven by oxidative stress and structural changes, plays a central role in heart failure progression. Recent studies suggest that HACE1, a regulatory gene, may be involved in cardiac protection against heart failure. METHODS: Clinical data analysis involved heart failure patients, while an animal model utilized C57BL/6J mice. RT-PCR, microarray analysis, histological examination, ELISA, and Western blot assays were employed to assess gene and protein expression, oxidative stress, and cardiac function. Cell transfection and culture of mouse atrial fibroblasts were performed for in-vitro experiments. RESULTS: HACE1 expression was reduced in heart failure patients and correlated negatively with collagen levels. In mouse models, HACE1 up-regulation reduced oxidative stress, mitigated fibrosis, and improved cardiac function. Conversely, HACE1 knockdown exacerbated oxidative stress, fibrosis, and cardiac dysfunction. HACE1 also protected against ferroptosis and mitochondrial damage. NRF2, a transcription factor implicated in oxidative stress, was identified as a target of HACE1, with HACE1 promoting NRF2 activity through ubiquitination. CONCLUSIONS: HACE1 emerges as a potential therapeutic target and diagnostic marker for heart failure. It regulates oxidative stress, mitigates cardiac fibrosis, and protects against ferroptosis and mitochondrial damage. The study reveals that HACE1 achieves these effects, at least in part, through NRF2 activation via ubiquitination, offering insights into novel mechanisms for heart failure pathogenesis and potential interventions.


Assuntos
Ferroptose , Insuficiência Cardíaca , Animais , Humanos , Camundongos , Fibrose , Átrios do Coração/patologia , Insuficiência Cardíaca/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/fisiologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
7.
Transl Androl Urol ; 12(11): 1713-1722, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38106691

RESUMO

Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.

8.
Microorganisms ; 11(11)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-38004675

RESUMO

An outbreak of stem rot in eggplants was observed in Heshuo County, Xinjiang, during winter 2021-2022 in about 12-35% of the eggplants in the region (about 40 hm2). The infected tissues yielded a total of four bacterial strains, which were subsequently subjected to physiological and biochemical assays as well as molecular identification. Based on these analyses, the pathogen was identified as Pectobacterium carotovorum subsp. brasiliense. The pathogenicity was confirmed through the fulfillment of Koch's postulates. The host range test confirmed the broad spectrum of species susceptible to infection by the strains. This study represents the first case of infection caused by P. carotovorum subsp. brasiliense resulting in stem rot in eggplant.

9.
BMC Cardiovasc Disord ; 23(1): 582, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012584

RESUMO

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown to play critical roles in protecting cardiomyocytes against MIRI, but their specific protective mechanism, their interact between the two and their relationship with ferroptosis are still unclear. Hence, in this study, we investigated the interact and specific mechanism of SIRT1 and SIRT3 in protecting cardiomyocytes against MIRI, as well as their association with ferroptosis. METHODS: Bioinformatics analysis methods were used to explore the expression of SIRT1 and SIRT3 during MIRI, and then a cell hypoxia/reoxygenation injury model was constructed to verify the results. Then, Pearson correlation analysis was further used to explore the relationship between SIRT1 and SIRT3, whose roles in the regulation of ferroptosis were also analysed by gene knock down, Western Blotting and flow cytometry. Several biomarkers, such as Fe2+ concentration, lipid peroxidation marker MDA and mitochondrial membrane potential (MMP), were used to evaluate changes in ferroptosis. RESULTS: The expression of SIRT1 and SIRT3 was abnormal during MIRI, and SIRT1 was significantly negatively correlated with SIRT3 in the SIRT1-SIRT3 axis. Further analysis revealed that the SIRT1-SIRT3 axis was closely correlated with ferroptosis, and its silencing effectively increase the incidence of ferroptosis. Furthermore, SIRT1-SIRT3 axis silencing was accompanied by changes in PINK1, Parkin, P62/SQSTM1 and LC3 expression. PINK1 silencing significantly increased the incidence of ferroptosis, while resveratrol (Res) and/or honokiol (HKL) effectively reversed the outcome. CONCLUSION: Abnormalities in the SIRT1-SIRT3 axis promote MIRI through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.


Assuntos
Ferroptose , Traumatismo por Reperfusão Miocárdica , Sirtuína 3 , Humanos , Traumatismo por Reperfusão Miocárdica/genética , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Ferroptose/genética , Transdução de Sinais , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
10.
Zhen Ci Yan Jiu ; 48(9): 946-50, 2023 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-37730266

RESUMO

OBJECTIVE: To compare the clinical effect of "initial scheme" and "improved scheme" of acupuncture-aided anesthesia for patients undergoing thoracoscopic lobectomy. METHODS: A retrospective analysis about 2 groups ("initial scheme" and "improved scheme") of patients (40 cases in each group) who underwent thoracoscopic lobectomy was conducted in the present paper. Patients of the "initial scheme" group received thoracoscopic operation with three incisions under acupuncture-aided anesthesia i.e., electroacupuncture (EA) stimulation of bilateral Hegu (LI4), Neiguan (PC6), Houxi (SI3) and Zhigou (SJ6), combined with Lidocaine and ropivacaine epidural anesthesia and propofol intravenous anesthesia from January of 2013 to December of 2017. Patients of the "improved scheme" group received thoracoscopic operation with single incision under acupuncture-aided anesthesia by EA, combined with ropivacaine paravertevinal block and lidocaine and remifentanil intravenous anesthesia from August 2018 to August 2021. The incidence of intraoperative deep breathing, resuscitation time, ambulatory rate on day after surgery and postoperative incision pain of the two schemes were compared. RESULTS: The incidence of intraoperative deep breathing and the degree of postoperative incision pain were significantly lower (P<0.05), the postoperative resuscitation time was obviously shorter (P<0.05), and the ambulatory rate on day after surgery was higher (P<0.05) in the "improved scheme" group than in the "initial scheme" group. CONCLUSION: The "improved scheme" is better than the "initial scheme" in stabilizing the patient's breathing during thoracoscopic lobectomy operation, shortening the resuscitation time, and ameliorating the postoperative recovery state and pain reaction, thus being a better technical solution in clinical practice.


Assuntos
Terapia por Acupuntura , Anestesia , Humanos , Estudos Retrospectivos , Ropivacaina , Lidocaína , Dor Pós-Operatória/terapia
11.
Medicine (Baltimore) ; 102(34): e34545, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653755

RESUMO

RATIONALE: With the advancement of targeted therapies, epidermal growth factor receptor tyrosine kinase inhibitors have become the preferred initial treatment for patients with advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer. Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is effective against exon 19 and 21 mutations as well as the T790M mutation. It has been approved by both the food and drug administration and European Medicines Agency for the treatment of non-small cell lung cancer patients with locally advanced or metastatic EGFR-mutated tumors, including those who have acquired T790M mutations. PATIENT CONCERNS: To evaluate the effectiveness of osimertinib in treating patients with EGFR-mutated advanced lung adenocarcinoma and bone metastases, we present the treatment outcomes of 3 patients with EGFR 19 deletion-mutated advanced lung adenocarcinoma and bone metastases who received osimertinib treatment in recent years. All 3 cases involved elderly female patients, aged 62, 62, and 54, respectively. DIAGNOSES: All 3 cases exhibited a diagnosis of pulmonary adenocarcinoma accompanied by osseous metastases, with genetic testing revealing the presence of an EGFR 19del mutation. INTERVENTIONS: In the first case, following 17 months of gefitinib therapy, disease progression prompted a switch to osimertinib treatment. In the second case, bone metastases were detected after 20 months of pemetrexed-carboplatin chemotherapy, leading to a transition to osimertinib therapy. In the third case, after 11 months of erlotinib treatment, bone metastases were identified. Subsequent interventions, including radiation therapy, pemetrexed-carboplatin chemotherapy, pemetrexed-bevacizumab maintenance therapy, and docetaxel chemotherapy, failed to arrest the progression of bone metastases. As a result, a combination of osimertinib and anlotinib targeted therapy was administered. OUTCOMES: All 3 patients experienced relatively good and favorable survival outcomes, with a progression-free survival of 22.7 months, 12 months, and 17.7 months, respectively. LESSONS: These cases suggest that osimertinib is a promising treatment option for patients with EGFR 19 deletion-mutated lung adenocarcinoma and bone metastases, although further clinical studies are needed to confirm its efficacy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Feminino , Humanos , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Carboplatina , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Pemetrexede , Inibidores de Proteínas Quinases/uso terapêutico , Estados Unidos , /uso terapêutico
14.
Clin Respir J ; 17(11): 1145-1157, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37723579

RESUMO

BACKGROUND: Lymph node (LN) metastasis is crucial in non-small cell lung cancer (NSCLC) prognosis and treatment, but the TNM system lacks LN quantity consideration. Our goal is to investigate the role of positive LNs (nPLN) and positive LN rate (LNR) in overall survival (OS) and assess whether they offer higher value in prognostic assessment of NSCLC than N-stage. METHODS: Patients were stratified into four subgroups using X-Tile software. Statistical analysis was conducted using the Kaplan-Meier method, univariate analysis, and multivariate Cox regression analysis. Model performance was evaluated using the Harrell consistency index (C-index), Akaike information criterion (AIC), and Bayesian information criterion (BIC). The prognostic performance of the nodal classification was validated using overall survival as the endpoint. RESULTS: The survival curves demonstrate distinct disparities between each nPLN and LNR category. A pronounced trend toward deteriorating overall survival from N-PLN 1 to N-PLN 2+ was observed across all tumor size categories. However, the differences between each LNR category were only significant for tumors ≤3 cm and 5-7 cm. Notably, both nPLN and LNR classifications displayed a higher C-index, lower AIC, and lower BIC compared with the N staging. Furthermore, the LNR classification provided superior prognostic stratification when compared with the nPLN classification. CONCLUSIONS: Our results demonstrate that nPLN and LNR classifications may offer improved prognostic performance compared with the current N classification for LN-positive NSCLC patients. Nonetheless, more studies are needed to assess the feasibility of incorporating these classifications into the next TNM staging system.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linfonodos/patologia , Neoplasias Pulmonares/patologia , Teorema de Bayes , Excisão de Linfonodo , Prognóstico , Estadiamento de Neoplasias , Metástase Linfática/patologia , Estudos Retrospectivos
15.
Phys Chem Chem Phys ; 25(35): 23770-23782, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37622171

RESUMO

As a type of smart dimming film, polymer-dispersed liquid crystals (PDLCs) show great prospects in the fields of indoor partition, electronic curtains, and automobile windows. However, its high off-axis haze greatly impacts the application scope. This obvious shortcoming is mainly caused by the serious mismatch between the effective refractive index of the liquid crystal (neff) and the refractive index of the polymer matrix (np) at large viewing angles. Thereby, factors affecting the viewing angle of a PDLC film are analyzed in this research, including the birefringence of the liquid crystal (Δn), film thickness, and the refractive index of the polymer matrix (np). Balanced electro-optical properties are guaranteed simultaneously. It is found that high on-state transmittance and low off-axis haze can be achieved at large viewing angles in the suggested optimized case where Δn is within the range of 0.1-0.13; the film thickness is between 20 µm and 15 µm; and np approaches no but the difference does not exceed 0.03.

16.
In Vivo ; 37(5): 2105-2127, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37652508

RESUMO

BACKGROUND/AIM: High-fat diets induce shifts in the gut microbial community structure in patients or animals with non-alcoholic steatohepatitis (NASH). The objective of this study was to investigate the influence of metformin (MET) and berberine (BER) on the intestinal microbiota of rats with NASH. MATERIALS AND METHODS: Forty specific pathogen-free male Sprague-Dawley rats were randomized into 4 groups. Model rats were fed high-fat diets to create NASH models. MET or BER rats were administrated MET or BER, respectively, at the onset of induction of NASH. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, and triglycerides were examined. Plasma endotoxin levels were measured using the turbidimetric endotoxin assay. The incidence of bacterial translocation describes the passage of bacteria of the gastrointestinal tract through the intestinal mucosa barrier to mesenteric lymph nodes and other organs. Hematoxylin and eosin and oil red O staining were used for histopathological analysis. High throughput 16S rRNA sequencing was carried out for analyzing the composition of intestinal microbiota. RESULTS: High-fat diets caused NASH after 16-week induction. Administration of MET and BER ameliorated NASH by attenuating hepatic steatosis and inflammation and decreasing the plasma levels of endotoxin. MET and BER restored the composition of the intestinal microbiota disrupted by NASH. Both MET and BER altered the abundance of Atopobiaceae, Brevibacterium, Christensenellaceae, Coriobacteriales, Papillibacter, Pygmaiobacter, and Rikenellaceae RC9 in rats with NASH. The screened intestinal microbiota may be responsible for the improvement in fat accumulation and glucose metabolism. CONCLUSION: MET and BER demonstrated beneficial effects on the intestinal microbiota, which was disturbed in NASH. This finding may explain the functional mechanism of MET and BER in NASH.


Assuntos
Berberina , Microbioma Gastrointestinal , Metformina , Hepatopatia Gordurosa não Alcoólica , Humanos , Ratos , Masculino , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Berberina/farmacologia , Berberina/metabolismo , Metformina/farmacologia , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ratos Sprague-Dawley , Dieta Hiperlipídica/efeitos adversos , Endotoxinas/metabolismo , Endotoxinas/farmacologia , Fígado/patologia , Modelos Animais de Doenças
19.
Bioengineering (Basel) ; 10(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37370598

RESUMO

OBJECTIVE: To construct an in vitro lung cancer model using 3D bioprinting and evaluate the feasibility of the model. Transcriptome sequencing was used to compare the differential genes and functions of 2D and 3D lung cancer cells. METHODS: 1. A549 cells were mixed with sodium alginate/gelatine/fibrinogen as 3D-printed biological ink to construct a hydrogel scaffold for the in vitro model of lung cancer; 2. A hydrogel scaffold was printed using a extrusion 3D bioprinter; 3. The printed lung cancer model was evaluated in vitro; and 4. A549 cells cultured in 2D and 3D tumour models in vitro were collected, and RNA-seq conducted bioinformatics analysis. RESULTS: 1. The in vitro lung cancer model printed using 3D-bioprinting technology was a porous microstructure model, suitable for the survival of A549 cells. Compared with the 2D cell-line model, the 3D model is closer to the fundamental human growth environment; 2. There was no significant difference in cell survival rate between the 2D and 3D groups; 3. In the cell proliferation rate measurement, it was found that the cells in the 2D group had a speedy growth rate in the first five days, but after five days, the growth rate slowed down. Cell proliferation showed a declining process after the ninth day of cell culture. However, cells in the 3D group showed a slow growth process at the beginning, and the growth rate reached a peak on the 12th day. Then, the growth rate showed a downward trend; and 4. RNA-seq compared A549 cells from 2D and 3D lung cancer models. A total of 3112 genes were differentially expressed, including 1189 up-regulated and 1923 down-regulated genes, with p-value ≤ 0.05 and |Log2Ratio| ≥ 1 as screening conditions. After functional enrichment analysis of differential genes, these differential genes affect the biological regulation of A549 cells, thus promoting lung cancer progression. CONCLUSION: This study uses 3D-bioprinting technology to construct a tumour model of lung cancer that can grow sustainably in vitro. Three-dimensional bioprinting may provide a new research platform for studying the lung cancer TME mechanism and anticancer drug screening.

20.
Colloids Surf B Biointerfaces ; 226: 113283, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37030033

RESUMO

Tumor-associated macrophage (TAM) is regarded as an appealing cell target for cancer immunotherapy. However, it remains challenging to selectively eliminate M2-like TAM in tumor microenvironment. In this work, we employed a legumain-sensitive dual-coating nanosystem (s-Tpep-NPs) to deliver CSF-1R inhibitor pexidartinib (PLX3397) for targeting TAM therapy. The PLX3397-loaded NPs exhibited uniform size of ∼240 nm in diameter, good drug loading capacity and efficiency, as well as sustained drug release profile. Compared to non-sensitive counterpart ns-Tpep-NPs, s-Tpep-NPs showed distinguished selectivity upon M1 and M2 macrophage uptake with relation to incubation time and dose. Besides, the selectivity of anti-proliferation effect was also identified for s-Tpep-NPs against M1 and M2 macrophage. In vivo imaging demonstrated that s-Tpep-NPs exhibited much higher tumoral accumulation and TAM recognition specificity as compared to non-sensitive ns-Tpep-NPs. In vivo efficacy verified that s-Tpep-NPs formulation was much more effective than ns-Tpep-NPs and other PLX3397 formulations to treat B16F10 melanoma via targeting TAM depletion and modulating tumor immune microenvironment. Overall, this study provides a robust and promising nanomedicine strategy for TAM-targeted cancer immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Macrófagos Associados a Tumor , Linhagem Celular Tumoral , Imunoterapia/métodos , Microambiente Tumoral
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