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1.
Cell Biochem Biophys ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713401

RESUMO

OBJECTIVE: Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. METHODS: To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2',7'-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. RESULTS: PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. CONCLUSIONS: PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway.

2.
ACS Nano ; 18(11): 7945-7958, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38452275

RESUMO

Ferroptosis is a form of regulated cell death accompanied by lipid reactive oxygen species (ROS) accumulation in an iron-dependent manner. However, the efficiency of tumorous ferroptosis was seriously restricted by intracellular ferroptosis defense systems, the glutathione peroxidase 4 (GPX4) system, and the ubiquinol (CoQH2) system. Inspired by the crucial role of mitochondria in the ferroptosis process, we reported a prodrug nanoassembly capable of unleashing potent mitochondrial lipid peroxidation and ferroptotic cell death. Dihydroorotate dehydrogenase (DHODH) inhibitor (QA) was combined with triphenylphosphonium moiety through a disulfide-containing linker to engineer well-defined nanoassemblies (QSSP) within a single-molecular framework. After being trapped in cancer cells, the acidic condition provoked the structural disassembly of QSSP to liberate free prodrug molecules. The mitochondrial membrane-potential-driven accumulation of the lipophilic cation prodrug was delivered explicitly into the mitochondria. Afterward, the thiol-disulfide exchange would occur accompanied by downregulation of reduced glutathione levels, thus resulting in mitochondria-localized GPX4 inactivation for ferroptosis. Simultaneously, the released QA from the hydrolysis reaction of the adjacent ester bond could further devastate mitochondrial defense and evoke robust ferroptosis via the DHODH-CoQH2 system. This subcellular targeted nanoassembly provides a reference for designing ferroptosis-based strategy for efficient cancer therapy through interfering antiferroptosis systems.


Assuntos
Ferroptose , Compostos Organofosforados , Pró-Fármacos , Pró-Fármacos/farmacologia , Pró-Fármacos/metabolismo , Di-Hidro-Orotato Desidrogenase , Peroxidação de Lipídeos , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Dissulfetos/metabolismo
3.
Int J Biol Macromol ; 257(Pt 1): 128580, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38052283

RESUMO

To reduce the use of petroleum-based plastics and explore multifunctional plastics, this study was conducted to prepare ternary composite plastics by doping Pickering emulsions containing Alpinia galanga essential oil into a polymer network consisting of poly(vinyl alcohol)-acetylated pullulan polysaccharides. Scanning electron microscopy results showed that although incompatible components were present in the composite plastic, compatibility improved with the addition of pullulan polysaccharides, resulting in smooth surfaces and cross-sections, which was consistent with the observation of continuous dark zones and low relative roughness (Ra = 5.51) in Atomic force microscopy. Further, Fourier transform spectroscopy and X-ray diffraction characterization revealed that the composite plastic disrupted the molecular and crystalline structures of the pure PVA, causing the stretching vibration of -OH and the decrease of relative crystallinity. Moreover, this plastic performed optimally at a PVA to pullulan polysaccharide ratio of 75:25, exhibiting good thermal (13.12 J/g) and mechanical properties, low water absorption (70.71 %) and water vapor transmission (1.80 × 10-3 g/m2 s), as well as excellent degradability. In addition, Alpinia galanga essential oil components in the composite plastic provided favorable antioxidant scavenging of DPPH and ABTS and inhibitory effects against Escherichia coli and Staphylococcus aureus. Chicken meat packaging revealed that the plastic maintained sensory parameters such as pH and color by inhibiting the oxidation of proteins and lipids during shelf-life. The findings provide insights into developing innovative, green, multifunctional packaging and broaden the in-depth application of Alpinia galanga essential oil.


Assuntos
Alpinia , Óleos Voláteis , Óleos Voláteis/farmacologia , Alpinia/química , Emulsões , Polissacarídeos , Embalagem de Alimentos
4.
J Mol Med (Berl) ; 102(2): 213-229, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38047923

RESUMO

Cancer is a life-threatening disease worldwide. Nanomedicine and nanodelivery systems are recently developed scientific field that employs specific materials in the nanoscale range to deliver drugs. Lipid-based nanoparticles are an ideal delivery system since they exhibit many advantages, including high bioavailability, self-assembly, formulation simplicity, and the ability to exhibit a plethora of physicochemical properties. Herein, we report that phenobarbital sodium can kill cancer cells by using the DSPE-PEG2000-methotrexate nanoparticle delivery system, which can target folate receptors that are usually overexpressed on a variety of cancer cells. The released phenobarbital then executes cancer cells by inducing pyroptosis. Results from our animal model further indicate that the nanomedicine of nanoparticle-encapsulated phenobarbital sodium is a promising anticancer therapy.


Assuntos
Nanopartículas , Neoplasias , Fosfatidiletanolaminas , Polietilenoglicóis , Animais , Metotrexato/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Piroptose , Nanopartículas/química
5.
J Agric Food Chem ; 72(3): 1734-1744, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38133486

RESUMO

Mycotoxin ochratoxin A (OTA) is a critical food safety concern due to its nephron-toxic effects and is detected in a wide range of food and feedstuffs. OTA nephrotoxicity is related to oxidative stress and damage. However, the mediator(s) of the excessive oxidative stress is unclear. The current study used human kidney cell lines to investigate whether and how intracellular iron contributed to OTA-induced ROS accumulation and how OTA-induced iron-dependent ferroptotic cell death. Our results showed that OTA treatment affected the cell viability and induced the typical characteristics of cell ferroptosis. Furthermore, gene and protein expression results indicated that OTA disrupted iron homeostasis by upregulating the expression levels of iron importer TFR1 and FTH, while downregulating the expression level of iron exporter FPN and dramatically increasing its negative regulator Hepcidin. The changes were consistent with the induction of intracellular iron accumulation and elevated levels of oxidative stress and lipid peroxidation. Additionally, co-treatment with OTA and an iron chelator significantly improved cell viability, reduced cellular total iron and ROS, and reversed OTA-induced changes in iron metabolism gene expression levels. Interestingly, the addition of a ROS scavenger also reversed cell death and changes in mRNA and protein expression levels of iron metabolism genes but to a lesser degree than that of the iron-chelating agent. Our results revealed that OTA induced ferroptosis in renal cells by disrupting iron homeostasis and increasing ROS.


Assuntos
Ferroptose , Ocratoxinas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Rim/metabolismo , Ferro/metabolismo , Homeostase
7.
Int J Biochem Cell Biol ; 165: 106491, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38149579

RESUMO

Cancer cells prefer to utilizing aerobic glycolysis to generate energy and anabolic metabolic intermediates for cell growth. However, whether the activities of glycolytic enzymes can be regulated by specific posttranslational modifications, such as SUMOylation, in response to oncogenic signallings, thereby promoting the Warburg effect, remain largely unclear. Here, we demonstrate that phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key glycolytic enzyme, interacts with SUMO-conjugating enzyme UBC9 and is SUMOylated at K302 in glioblastoma cells. Expression of UBC9, which competitively prevents the binding of ubiquitin E3 ligase APC/C to PFKFB3 and subsequent PFKFB3 polyubiquitination, increases PFKFB3 stability and expression. Importantly, EGFR activation increases the interaction between UBC9 and PFKFB3, leading to increased SUMOylation and expression of PFKFB3. This increase is blocked by inhibition of EGFR-induced AKT activation whereas expression of activate AKT by itself was sufficient to recapitulate EGF-induced effect. Knockout of PFKFB3 expression decreases EGF-enhanced lactate production and GBM cell proliferation and this decrease was fully rescued by reconstituted expression of WT PFKFB3 whereas PFKFB3 K302R mutant expression abrogates EGF- and UBC9-regulated lactate production and GBM cell proliferation. These findings reveal a previously unknown mechanism underlying the regulation of the Warburg effect through the EGFR activation-induced and UBC9-mediated SUMOylation and stabilization of PFKFB3.


Assuntos
Glioblastoma , Humanos , Glioblastoma/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glicólise , Lactatos/farmacologia , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo
8.
Huan Jing Ke Xue ; 44(11): 6172-6180, 2023 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-37973100

RESUMO

The production and use of plastic blends have been gradually increasing owing to their versatility and low cost. However, the photodegradation of plastic blends in seawater and the potential risk to the marine environment are still not well understood. In this study, plastic blends including polypropylene/thermoplastic starch blends(PP/TPS) and polylactic acid/poly(butylene adipate-co-terephthalate)/thermoplastic starch blends(PLA/PBAT/TPS) were investigated. The corresponding neat polymers, namely polypropylene(PP) and polylactic acid(PLA), were set as control groups. We investigated the formation of MPs and the changes in the physicochemical properties of plastic blends after photodegradation in seawater. The size distribution of MPs indicated that PP/TPS and PLA/PBAT/TPS were more likely to produce small-sized particles after photodegradation than PP and PLA owing to their poorer mechanical properties and lower resistance to UV irradiation. Noticeable surface morphology alterations, including cracks and wrinkles, were observed for plastic blends following photodegradation, whereas PP and PLA were relatively resistant. After photodegradation, the ATR-FTIR spectrum of PP/TPS and PLA/PBAT/TPS showed a significant decrease in the characteristic bands of thermoplastic starch(TPS), indicating the degradation of their starch fractions. The C 1s spectra demonstrated that aged plastic blends contained fewer -OH groups than the pristine MPs did, further confirming the photodegradation of TPS. These results indicate that PP/TPS and PLA/PBAT/TPS had a higher degree of photodegradation than PP and PLA and thereby generated more small-sized MPs. In summary, plastic blends may pose a higher risk to the marine environment than neat polymers, and caution should be taken in the production and use of plastic blends.

9.
Hepatology ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38016019

RESUMO

BACKGROUND AND AIMS: Base editing has shown great potential for treating human diseases with mutated genes. However, its potential for treating HCC has not yet been explored. APPROACH AND RESULTS: We employed adenine base editors (ABEs) to correct a telomerase reverse transcriptase ( TERT ) promoter mutation, which frequently occurs in various human cancers, including HCC. The mutated TERT promoter -124 C>T is corrected to -124 C by a single guide (sg) RNA-guided and deactivated Campylobacter jejuni Cas9 (CjCas9)-fused adenine base editor (CjABE). This edit impairs the binding of the E-twenty six/ternary complex factor transcription factor family, including E-twenty six-1 and GABPA, to the TERT promoter, leading to suppressed TERT promoter and telomerase activity, decreased TERT expression and cell proliferation, and increased cell senescence. Importantly, injection of adeno-associated viruses expressing sgRNA-guided CjABE or employment of lipid nanoparticle-mediated delivery of CjABE mRNA and sgRNA inhibits the growth of liver tumors harboring TERT promoter mutations. CONCLUSIONS: These findings demonstrate that a sgRNA-guided CjABE efficiently converts the mutated TERT promoter -124 C>T to -124 C in HCC cells and underscore the potential to treat HCC by the base editing-mediated correction of TERT promoter mutations.

10.
Heliyon ; 9(11): e21300, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37920523

RESUMO

Background: Infantile hemangioma (IH) has received global attention, resulting in a significant volume of literature. However, there is a lack of bibliometric analyses specifically focusing on IH publications. This study aims to fill this gap by conducting a comprehensive analysis of IH publications, investigating their characteristics, contribution distribution, and developmental trends. By enhancing our understanding of IH and identifying potential research topics and collaborators, this study will contribute to the advancement of the field. Methods: A total of 4333 articles and reviews on IH were collected from the Web of Science (WoS) database, spanning the years 2000-2022. The study encompassed a comprehensive analysis of IH publications, evaluating their quantity and quality. Additionally, we profiled publishing groups based on country, institution, author publication records, and collaboration networks. Lastly, we identified and summarized the prominent research topics. Results: Annual publications on IH have increased over the past 20 years. The United States has the highest number of publications and the highest total number of citations. Pediatric Dermatology was the most influential journal in the IH field. The citation analysis indicated that the articles published by Léauté-Labrèze in 2008 had the highest number of citations. The articles published by North PE in 2000 and Boye E in 2001 laid a certain research foundation for this field. Concerning institutions, most of the cooperative relationships were established in the same country/region. The United States has the largest number of scientific research institutions and IH researchers, leading most of the cross-country collaboration. The University of California, San Francisco, Medical College of Wisconsin, Harvard University, and Shanghai Jiaotong University were the research centers that published the most IH-related research. Frieden IJ, Mulliken JB, and Drolet BA were the top three most influential authors. Frieden IJ, Garzon MC, and Mulliken JB were the top three authors with the most cited frequency. In addition, keywords and keyword co-occurrence networks prompted that the pathological mechanism of IH, clinical analysis, and other vascular anomalies are research hotspots. Analysis of trending topics suggests that research on IH has evolved from treatment-focused studies towards investigations of other vascular diseases and a series of clinical case studies. Currently, clinical case studies receive the most attention in the field. Conclusions: This comprehensive bibliometric study provides a thorough analysis of post-2000 publications in the field of IH, offering insights into current research trends for the first time. The findings suggest that future investigations will continue to prioritize understanding IH mechanisms, treatment approaches, and treatment evaluation. Furthermore, the exploration of other vascular diseases and the inclusion of clinical case studies are expected to contribute to advancements in IH clinical practice. By identifying potential collaborators, partner institutions, and new research avenues, this study offers valuable guidance for future in-depth research on IH.

11.
Front Oncol ; 13: 1154107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664026

RESUMO

Background: Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR). Methods: A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy. Results: The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP). Conclusion: The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.

12.
Pak J Med Sci ; 39(5): 1473-1477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680796

RESUMO

Objective: To determine the effect of laparoscopic complete mesocolic excision combined with immunotherapy and its impact on immune function and tumor markers in elderly patients with colon cancer. Methods: This is a clinical comparative study. Eighty elderly patients with colon cancer hospitalized in the No.2 Hospital of Baoding from May 2020 to May 2022 were randomly divided into two groups, with 40 cases in each group. Patients in the study group received laparoscopic complete mesocolic resection combined with ubenimex orally. While patients in the control group received routine open surgery. The surgical indexes, surgical complications, and the changes of immune molecules and tumor markers before and after treatment were compared between the two groups. Results: The amount of intraoperative bleeding, retention time of drainage tube and postoperative length of stay in the hospital in the study group were significantly better than those in the control group (p=0.000). The incision length of the study group was significantly shorter than that of the control group, the number of lymph nodes removed during the operation was significantly higher than that of the control group, and the incidence of surgical complications was significantly lower than that of the control group (p<0.05). After treatment, the levels of immune molecules in the study group were remarkably higher than those in the control group (p<0.05), while the levels of tumor markers were much lower than those in the latter group (p=0.000). Conclusion: Laparoscopic complete mesocolic excision combined with immunotherapy exhibits a superior therapeutic effect to traditional open surgery in elderly patients with colon cancer, and is worthy of clinical promotion.

13.
Pharm Biol ; 61(1): 1260-1273, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37602438

RESUMO

CONTEXT: Yiqi Liangxue Shengji prescription (YQLXSJ) is a traditional Chinese medicine (TCM) formula that has long been used for treatment after percutaneous coronary intervention (PCI). OBJECTIVE: To investigate the putative pharmacological mechanism of YQLXSJ on restenosis through an integrated approach utilizing metabolomics and network pharmacology. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were divided into sham, model, YQLXSJ, and positive groups. YQLXSJ group received the treatment of YQLXSJ (6 g/kg/d, i.g.) and the positive group was treated with atorvastatin (2 mg/kg/d, i.g.). After 4 weeks, the improvement in intimal hyperplasia was evaluated by ultrasound, H&E staining, and immunofluorescence. UPLC-MS/MS technology was utilized to screen the differential metabolites. Network pharmacology was conducted using TCMSP, GeneCards, and Metascape, etc., in combination with metabolomics. Eventually, the core targets were acquired and validated. RESULTS: Compared to models, YQLXSJ exhibited decreased intima-media thickness on ultrasound (0.23 ± 0.02 mm vs. 0.20 ± 0.01 mm, p < 0.01) and reduced intima thickness by H&E (30.12 ± 6.05 µm vs. 14.32 ± 1.37 µm, p < 0.01). We identified 18 differential metabolites and 5 core targets such as inducible nitric oxide synthase (NOS2), endothelial nitric oxide synthase (NOS3), vascular endothelial growth factor-A (VEGFA), ornithine decarboxylase-1 (ODC1) and group IIA secretory phospholipase A2 (PLA2G2A). These targets were further confirmed by molecular docking and ELISA. DISCUSSION AND CONCLUSIONS: This study confirms the effects of YQLXSJ on restenosis and reveals some biomarkers. TCM has great potential in the prevention and treatment of restenosis by improving metabolic disorders.


Assuntos
Espessura Intima-Media Carotídea , Intervenção Coronária Percutânea , Masculino , Ratos , Animais , Ratos Sprague-Dawley , Cromatografia Líquida , Simulação de Acoplamento Molecular , Farmacologia em Rede , Espectrometria de Massas em Tandem , Fator A de Crescimento do Endotélio Vascular , Constrição Patológica , Metabolômica
15.
Int Immunopharmacol ; 124(Pt A): 110856, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37647680

RESUMO

BACKGROUND: Electroacupuncture (EA) is given to assist in the treatment of MS, which is an effective therapeutic method. However, the therapy mechanism of EA related to stem cells in the treatment of MS is not yet known. In this study, we used a classic animal model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) to evaluate the therapeutic effect of EA at Zusanli (ST36) acupoint in EAE and shed light on its potential roles in the effects of stem cells in vivo. METHODS: The EAE animal models were established. From the first day after immunization, EAE model mice received EA at ST36 acupoint, named the EA group. The weight and clinical score of the three groups were recorded for 28 days. The demyelination, inflammatory cell infiltration, and markers of neural stem cells (NSCs), hematopoietic stem cells (HSCs), and mesenchymal stem cells (MSCs) were compared. RESULTS: We showed that EAE mice treated with EA at ST36 acupoint, were suppressed in demyelination and inflammatory cell infiltration, and thus decreased clinical score and weight loss and mitigated the development of EAE when compared with the EAE group. Moreover, our data revealed that the proportions of NSCs, HSCs, and MSCs increased in the EA group compared with the EAE group. CONCLUSIONS: Our study suggested that EA at ST36 acupoint was an effective nonpharmacological therapeutic protocol that not only reduced the CNS demyelination and inflammatory cell infiltration in EAE disease but also increased the proportions of various stem cells. Further study is necessary to better understand how EA at the ST36 acupoint affects EAE.

16.
J Am Med Inform Assoc ; 30(10): 1657-1664, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37451682

RESUMO

OBJECTIVE: To assess large language models on their ability to accurately infer cancer disease response from free-text radiology reports. MATERIALS AND METHODS: We assembled 10 602 computed tomography reports from cancer patients seen at a single institution. All reports were classified into: no evidence of disease, partial response, stable disease, or progressive disease. We applied transformer models, a bidirectional long short-term memory model, a convolutional neural network model, and conventional machine learning methods to this task. Data augmentation using sentence permutation with consistency loss as well as prompt-based fine-tuning were used on the best-performing models. Models were validated on a hold-out test set and an external validation set based on Response Evaluation Criteria in Solid Tumors (RECIST) classifications. RESULTS: The best-performing model was the GatorTron transformer which achieved an accuracy of 0.8916 on the test set and 0.8919 on the RECIST validation set. Data augmentation further improved the accuracy to 0.8976. Prompt-based fine-tuning did not further improve accuracy but was able to reduce the number of training reports to 500 while still achieving good performance. DISCUSSION: These models could be used by researchers to derive progression-free survival in large datasets. It may also serve as a decision support tool by providing clinicians an automated second opinion of disease response. CONCLUSIONS: Large clinical language models demonstrate potential to infer cancer disease response from radiology reports at scale. Data augmentation techniques are useful to further improve performance. Prompt-based fine-tuning can significantly reduce the size of the training dataset.


Assuntos
Neoplasias , Radiologia , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Neoplasias/diagnóstico por imagem , Relatório de Pesquisa , Processamento de Linguagem Natural
17.
Pak J Med Sci ; 39(4): 1074-1079, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492316

RESUMO

Objective: To evaluate the clinical effect and safety of immunotherapy combined with chemotherapy in patients with advanced colon cancer. Methods: This is a retrospective study. The subjects of this study were 120 patients with advanced colon cancer who were admitted to The No.2 Hospital of Baoding from November 30, 2019 to November 30, 2021. The enrolled patients were randomly divided into two groups, with 60 cases in each group. Patients in the control group were given F0LF0X4 regimen, while those in the study group were provided with Bevacizumab therapy on the basis of the method in the control group. All patients were evaluated after two cycles of treatment. The comparison of outcome measures included the curative effects, adverse drug reactions, improvement of quality-of-life scores and changes in tumor markers between the two groups. Results: The total effective rate of the study group was significantly better than that of the control group. There was no significant difference in the incidence of adverse drug reactions between the two groups. After treatment, the study group had a significantly higher rate of improved quality of life score, while the obviously lower rate of the aggravated score than those in the control group. The levels of CEA, CA19-9 and CA125 in the study group were significantly lower than those in the control group after treatment. Conclusion: Targeted therapy combined with chemotherapy is a safe and effective therapeutic option that has a definite curative effect in the treatment of patients with advanced colon cancer.

18.
Front Pharmacol ; 14: 1166022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465523

RESUMO

The purpose of this experiment was to investigate the effects of Litsea cubeba essential oil (LCO) on the growth performance, blood antioxidation, immune function, apparent digestibility of nutrients, and fecal microflora in fattening pigs. A total of 120 pigs were randomly assigned to five groups, with six replicate pens per treatment and four pigs per pen, and they were fed basal diet, chlortetracycline (CTC), and low-, medium-, and high-concentration LCO. The results of the study showed that compared with the control treatment and CTC addition treatment of the basic diet, the catalase level in the serum of the pigs treated with 500 mg/kg LCO in the diet of finishing pigs was significantly increased (p < 0.05). The apparent digestibility of crude protein, crude ash, and calcium in pigs with different levels of LCO was significantly increased compared with the control treatments fed the basal diet (p < 0.05). In addition, compared with the control treatment fed the basal diet and the treatment with CTC, the apparent digestibility of ether extract in pigs treated with medium-dose LCO was significantly increased (p < 0.05), and the apparent digestibility of pigs was significantly increased after the addition of low-dose LCO (p < 0.05). Among the genera, the percentage abundance of SMB53 (p < 0.05) was decreased in the feces of the CTC group when compared to that in the medium-LCO group. At the same time, the relative abundance of L7A_E11 was markedly decreased in the feces of the control and medium- and high-concentration LCO group than that in the CTC group (p < 0.05). In conclusion, adding the level of 250 mg/kg LCO in the diet of pig could improve the growth performance and blood physiological and biochemical indicators of pigs, improve the antioxidant level of body and the efficiency of digestion and absorption of nutrients, and show the potential to replace CTC.

19.
Biosensors (Basel) ; 13(6)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37367012

RESUMO

In this study, a label-free and antibody-free impedimetric biosensor based on molecularly imprinting technology for exosomes derived from non-small-cell lung cancer (NSCLC) cells was established. Involved preparation parameters were systematically investigated. In this design, with template exosomes anchored on a glassy carbon electrode (GCE) by decorated cholesterol molecules, the subsequent electro-polymerization of APBA and elution procedure afforded a selective adsorption membrane for template A549 exosomes. The adsorption of exosomes caused a rise in the impedance of the sensor, so the concentration of template exosomes can be quantified by monitoring the impedance of GCEs. Each procedure in the establishment of the sensor was monitored with a corresponding method. Methodological verification showed great sensitivity and selectivity of this method with an LOD = 2.03 × 103 and an LOQ = 4.10 × 104 particles/mL. By introducing normal cells and other cancer cells derived exosomes as interference, high selectivity was proved. Accuracy and precision were measured, with an obtained average recovery ratio of 100.76% and a resulting RSD of 1.86%. Additionally, the sensors' performance was retained at 4 °C for a week or after undergoing elution and re-adsorption cycles seven times. In summary, the sensor is competitive for clinical translational application and improving the prognosis and survival for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exossomos , Neoplasias Pulmonares , Impressão Molecular , Humanos , Polímeros Molecularmente Impressos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Impressão Molecular/métodos , Polímeros , Neoplasias Pulmonares/diagnóstico , Anticorpos , Eletrodos , Técnicas Eletroquímicas/métodos , Limite de Detecção
20.
J Bioinform Comput Biol ; 21(3): 2350012, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37325865

RESUMO

Based on the colorectal cancer microarray sets gene expression data series (GSE) GSE10972 and GSE74602 in colon cancer and 222 autophagy-related genes, the differential signature in colorectal cancer and paracancerous tissues was analyzed by RankComp algorithm, and a signature consisting of seven autophagy-related reversal gene pairs with stable relative expression orderings (REOs) was obtained. Scoring based on these gene pairs could significantly distinguish colorectal cancer samples from adjacent noncancerous samples, with an average accuracy of 97.5% in two training sets and 90.25% in four independent validation GSE21510, GSE37182, GSE33126, and GSE18105. Scoring based on these gene pairs also accurately identifies 99.85% of colorectal cancer samples in seven other independent datasets containing a total of 1406 colorectal cancer samples.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Perfilação da Expressão Gênica , Neoplasias do Colo/genética , Algoritmos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica
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