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1.
BMC Urol ; 23(1): 148, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726767

RESUMO

PURPOSE: To explore the mechanisms of radiotherapy resistance and search for prognostic biomarkers for prostate cancer. METHODS: The GSE192817 and TCGA PRAD datasets were selected and downloaded from the GEO and UCSC Xena databases. Differential expression and functional annotation analyses were applied to 52 tumour cell samples from GSE192817. Then, the ssGSEA or GSVA algorithms were applied to quantitatively score the biological functional activity of samples in the GSE192817 and TCGA PRAD datasets, combined with specific gene sets collected from the Molecular Signatures Database (MSigDB). Subsequently, the Wilcoxon rank-sum test was used to compare the differences in ssGSEA or GSVA scores among cell types or PRAD patients. Moreover, radiotherapy resistance-associated gene screening was performed on DU145 and PC3 cells (prostate cancer cells), and survival analysis was used to evaluate the efficacy of these genes for predicting the prognosis of PRAD patients. RESULTS: A total of 114 genes that were differentially expressed in more than two different cancer cell types and associated with either sham surgery or radiotherapy treatment (X-ray or photon irradiation) were detected in cancer cells from GSE192817. Comparison of DNA damage-related ssGSEA scores between sham surgery and radiotherapy treatment in prostate cancer cells (DU145 and PC3) showed that photon irradiation was potentially more effective than X-ray treatment. In the TCGA PRAD dataset, patients treated with radiotherapy had much higher "GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS", "GOBP_G2_DNA_DAMAGE_CHECKPOINT" and "GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT" GSVA scores, and the Wilcoxon rank-sum test p values were 0.0005, 0.0062 and 0.0800, respectively. Furthermore, SRXN1 was upregulated in DU145 cells (resistant to X-ray irradiation compared to PC3 cells) after radiotherapy treatment, and low SRXN1 expression in patients was beneficial to radiotherapy outcomes. The log-rank test p value for PFS was 0.0072. CONCLUSIONS: Radiotherapy can damage DNA and induce oxidative stress to kill tumour cells. In this study, we found that SRXN1, as an antioxidative stress gene, plays an important role in radiotherapy for prostate cancer treatment, and this gene is also a potential biomarker for predicting the prognosis of patients treated with radiotherapy.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Próstata , Algoritmos , Linhagem Celular , Oxirredutases atuantes sobre Doadores de Grupo Enxofre
2.
Biomed Pharmacother ; 164: 114986, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37295251

RESUMO

BACKGROUND: 5-Fluorouracil (5-Fu) is one of the most commonly used chemotherapy drugs for gastric cancer (GC). But the increase of drug resistance makes the prognosis of patients worse. Studies have shown that Baicalin can not only inhibit various cancers but also increase the sensitivity of cancers to chemotherapy. However, how Baicalin works in chemotherapeutic resistance of GC are unclear. METHODS: CCK8 (Cell Counting Kit 8) was used to detect the IC50 (half maximal inhibitory concentration) of Baicalin and 5-Fu. Proliferation, migration, and invasion of GC were tested through colony formation assay and transwell assay. Fluorescent probes detected intracellular reactive oxygen species (ROS). RNA-seq (RNA sequencing) detected differentially expressed genes and pathways, and qPCR (Quantitative Real-time PCR) tested the expression of ferroptosis-related genes. RESULTS: The combination of Baicalin and 5-Fu inhibited GC progression and increased intracellular ROS levels. Both the inhibition of malignant phenotype of gastric cancer cells and the generation of intracellular ROS caused by Baicalin could be saved by the inhibitor of ferroptosis-Ferrostatin-1 (Fer-1). Heat map of enriched differentially expressed genes identified by RNA-seq included four ferroptosis-related genes, and subsequent GO (Gene Ontology) analysis suggested an association between the ferroptosis pathway and Baicalin treatment. The changes in expression of ferroptosis-related genes were validated by qPCR, and the result confirmed that the combination of Baicalin and 5-Fu promoted ferroptosis in GC. CONCLUSIONS: Baicalin inhibits GC and enhances 5-Fu by promoting ROS-related ferroptosis in GC.


Assuntos
Ferroptose , Neoplasias Gástricas , Humanos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Neoplasias Gástricas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral
3.
Front Oncol ; 13: 1192192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37274227

RESUMO

Objective: The intent of this study was to investigate the relationship between oxidative stress and treatment response in gastric cancer patients undergoing neoadjuvant chemotherapy. Methods: Blood samples from 108 patients and 108 healthy subjects were collected, and all patients were enrolled in SOX chemotherapy. The patients received four cycles of neoadjuvant chemotherapy. Blood samples were collected to determine oxidative stress levels at baseline prior to beginning chemotherapy, and at the end of cycles 2 and 4. The patients receiving neoadjuvant chemotherapy were followed up for several months to years. A survival curve was created according to the follow-up information from the patients. In addition, the correlation between oxidative stress level and treatment effect was evaluated and ROC curves were plotted according to the final collected data. Results: Compared with the normal group, the levels of the antioxidant index decreased while the peroxide index increased in the patients. Conversely, when patients were compared before and after chemotherapy, the antioxidant index increased but the peroxide index decreased. Furthermore, the antioxidant index increased in the response group while the peroxide index decreased in the non-response group. Conclusion: Patients with an increased antioxidant index after chemotherapy have good treatment responsiveness. These indicators can also be used as predictors to judge the patients' response to chemotherapy.

4.
Cancer Sci ; 114(4): 1353-1364, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36522839

RESUMO

Multidrug resistance is a primary factor in the poor response to chemotherapy and subsequent death in gastric cancer patients. However, the molecular mechanisms involved remain unclear. In this study, the high expression of special AT-rich sequence binding protein 1 (SATB1) in gastric cancer was found to be associated with reduced sensitivity to various chemotherapy drugs. Our results demonstrate that SATB1 can promote chemotherapy resistance in gastric cancer in vitro and in vivo. SATB1 exerts its effect by enhancing the activity of multiple ATP-binding cassette (ABC) transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) in gastric cancer cell lines. We also found that SATB1 affects ABC transporters by altering the subcellular localization of the ABC transporter rather than its expression. Subsequently, we confirmed that Ezrin binds to various ABC transporters and affects their subcellular localization. In addition, we found that SATB1 can also bind to the Ezrin promoter and regulate its expression. In the present study, we elucidate the mechanism of SATB1-mediated multidrug resistance in gastric cancer, providing a basis for SATB1 as a potential target for reversal of resistance.


Assuntos
Proteínas de Ligação à Região de Interação com a Matriz , Neoplasias Gástricas , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Neoplasias/metabolismo , Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/farmacologia
5.
Molecules ; 27(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36558097

RESUMO

Chinese Herbal Medicines (CHMs) can be identified by experts according to their odors. However, the identification of these medicines is subjective and requires long-term experience. The samples of Acanthopanacis Cortex and Periplocae Cortex used were dried cortexes, which are often confused in the market due to their similar appearance, but their chemical composition and odor are different. The clinical use of the two herbs is different, but the phenomenon of being confused with each other often occurs. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two species for fast and robust discrimination, in order to provide a scientific basis for avoiding confusion and misuse in the process of production, circulation and clinical use. In this study, the odor and volatile components of these two medicinal materials were detected by the E-nose and by gas chromatography-mass spectrometry (GC-MS), respectively. An E-nose combined with pattern analysis methods such as principal component analysis (PCA) and partial least squares (PLS) was used to discriminate the cortex samples. The E-nose was used to determine the odors of the samples and enable rapid differentiation of Acanthopanacis Cortex and Periplocae Cortex. GC-MS was utilized to reveal the differences between the volatile constituents of Acanthopanacis Cortex and Periplocae Cortex. In all, 82 components including 9 co-contained components were extracted by chromatographic peak integration and matching, and 24 constituents could be used as chemical markers to distinguish these two species. The E-nose detection technology is able to discriminate between Acanthopanacis Cortex and Periplocae Cortex, with GC-MS providing support to determine the material basis of the E-nose sensors' response. The proposed method is rapid, simple, eco-friendly and can successfully differentiate these two medicinal materials by their odors. It can be applied to quality control links such as online detection, and also provide reference for the establishment of other rapid detection methods. The further development and utilization of this technology is conducive to the further supervision of the quality of CHMs and the healthy development of the industry.


Assuntos
Nariz Eletrônico , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas/métodos , Análise Multivariada , Controle de Qualidade , Odorantes/análise , Compostos Orgânicos Voláteis/análise
6.
Front Public Health ; 10: 936686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211656

RESUMO

Introduction: Chemotherapy drug wasting is a huge problem in oncology that not only results in excessive expenses on chemotherapy drugs but also increases the cost of disposing of chemotherapy waste and the risk of occupational exposure in the environment. The main objective of this study was to evaluate the potential for hospitals in China to employ a real-time vial-sharing strategy that can save drug costs. Method: This study was conducted retrospectively at Pharmacy Intravenous Admixture Services (PIVAS), People's Hospital of Sichuan Province, China, from September to November 2021. Data on prescription drugs wasted were collected from the Hospital Information System (HIS). To assess the real-time vial-sharing strategy, we estimated drug wastage and drug waste costs using intelligent robots that dispense multiple prescriptions simultaneously. Results: 24 of the 46 wasted drugs were cost-saved. The vial-sharing strategy saved 186,067 mg of drugs, or ~59.08% of the total amount wasted, resulting in savings of 150,073.53 China Yuan (CNY), or 47.51% of the cost of the total waste. Conclusion: Our investigation established that employing a real-time vial-sharing strategy using an intelligent robot to dispense multiple prescriptions simultaneously is cost-effective. Additionally, this approach presented no safety issue concerns, such as the introduction of impurities to sterile compounding via repeated interspersing or the incorrect registration of information during drug storage, often encountered with traditional vial-sharing strategies.


Assuntos
Robótica , Análise Custo-Benefício , Custos de Medicamentos , Hospitais , Humanos , Estudos Retrospectivos
7.
Pharmaceutics ; 14(10)2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-36297544

RESUMO

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Silver nanoparticles (Ag-NPs) have been increasingly used in the diagnosis and treatment of cancer due to their physicochemical properties. This study investigated the role of a kind of biosynthetic silver nanoparticle (b-Ag) in the development of GC, the enhancement of 5-fluorouracil (5F), and its mechanism. (2) Methods: X-ray, transmission electron microscopy (TEM), and UV absorbance were used to detect the characterizations of AgNPs. CCK8, Colony formation and a Transwell assay were performed to confirm the malignant behaviors of GC. DCFH-DA and DHE were used to detect intracellular reactive oxygen species (ROS). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of apoptosis-related genes. (3) Results: Compared with the chemosynthetic silver nanoparticles (c-Ag), b-Ag had a stronger cytokilling effect, and it had a better inhibition on the malignant phenotype of GC when combined with 5F. The b-Ag increased the expression of Bax and P53 while decreasing the expression of Bcl2. It also promoted the generation of intracellular ROS. (4) Conclusions: By promoting cell apoptosis and increasing intracellular ROS, b-Ag inhibited the development of GC and enhanced the inhibition of 5F on GC.

8.
J Immunol Res ; 2022: 1709360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846430

RESUMO

Vascular cognitive impairment (VCI) has emerged as the second major disease responsible for dementia, and there is still a lack of effective treatment methods for this disorder to date. Clinical medications have found that Yisui Fuyongtang (YSFYT) Decoction is effective in improving neurological signs and learning-memory functions in patients who develop white matter lesions and whole brain atrophy. To clarify the effect and molecular regulation mechanism of YSFYT Decoction on model rats, this research analyzed the influence of YSFYT Decoction on the learning-memory ability and lipid metabolism of rats based on behavioral and biochemical analysis. Further pathology and protein detection methods were adopted to investigate the action of YSFYT Decoction on the neurons in the hippocampus of model rats and the regulation of the brain derived neurotrophic factor (BDNF)-tyrosine protein kinase receptor B (TrkB) signaling pathway. Compared with the VCI group, after YSFYT Decoction administration, the ratio of swimming time in the platform, number of crossing the platform, number of active avoidance, and proportion of active avoidance of the rats were markedly increased, whereas the response latency was substantially reduced (p < 0.05). Biochemical tests indicated that contents of lipoprotein lipase (LPL), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) of the model rats in YSFYT Decoction treatment group were greatly reduced, whereas those of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) were elevated (p < 0.05). Additionally, Bcl-2 expression in YSFYT Decoction treatment group was significantly increased, but neuron apoptosis of the hippocampus tissue was reduced. Meanwhile, neuron number was apparently higher than that in VCI model group. Following Yisui Decoction treatment, expressions of growth-associated protein 43 (GAP43), synaptophysin (SYP), postsynaptic density 95 (PSD95), NMDAR subunit 2B (NR2B), BDNF, TrkB, phospho-mitogen-activated protein kinase (p-MAPK), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and phospho-protein kinase B (p-AKT) were markedly elevated. Taken together, YSFYT Decoction could activate the BDNF-TrkB signaling pathway, elevate Bcl-2 expression, and minimize neuronal apoptosis in hippocampus, thereby improving the behavioral characteristics and biochemical indicators of the VCI rat model.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Colesterol/metabolismo , Cognição , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo , Plasticidade Neuronal/fisiologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos
9.
Mediators Inflamm ; 2022: 1894379, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712055

RESUMO

Intestinal epithelial cells are an essential barrier in human gastrointestinal tract, and healing of epithelial wound is a key process in many intestinal diseases. α-Lipoic acid (ALA) was shown to have antioxidative and anti-inflammatory effects, which could be helpful in intestinal epithelial injury repair. The effects of ALA in human colonic epithelial cells NCM460 and human colorectal adenocarcinoma cells Caco-2 were studied. ALA significantly promoted NCM460 and Caco-2 migration, increased mucosal tight junction factors ZO-1 and OCLN expression, and ALA accelerated cell injury repair of both cells in wound healing assay. Western blot analysis indicated that ALA inhibited a variety of mitogen-activated protein kinase (MAPK) signaling pathways in the epithelial cells. In conclusion, ALA was beneficial to repair of intestinal epithelial injury by regulating MAPK signaling pathways.


Assuntos
Mucosa Intestinal , Sistema de Sinalização das MAP Quinases , Ácido Tióctico , Células CACO-2 , Células Epiteliais/metabolismo , Humanos , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Intestinos/patologia , Ácido Tióctico/farmacologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-35754679

RESUMO

This study clarified the regulatory effect of Yisui multipurpose Soup towards D-galactose-induced cognitive impairment cell model on the molecular level. We first constructed and cultured the cell model of cognitive impairment induced by D-galactose in neurons in vitro and then cultured the cells in the medium supplemented with different doses of drug-containing serum of Yisui multipurpose soup. Expressions of inflammatory cytokine tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), nitric oxide (NO), and interleukin-1ß (IL-1ß) were assessed by the ELISA and western blot, and cell apoptosis was determined by flow cytometry and TUNEL. The expression changes of apoptosis-related proteins Bcl-2 and Bax were estimated by immunofluorescence, qPCR, and western blot. Finally, we analyzed and made the network interaction diagram of Yisui multipurpose soup-components-targets through the network pharmacology method, from which we could learn that there were 1104 gene targets related to vascular cognitive impairment (VCI) and 1071 component targets of Yisui multipurpose soup. And there were 251 overlapping genes, mainly gathering in protein binding, protein modification, MAPK signaling pathway, and calcium signaling pathway. The expressions of TNF-α, iNOS, NO, and IL-1ß were significantly decreased after the culture medium was replaced by medium containing drug serum. We also found that the effect of high-dose drug-containing serum on the expression of inflammatory factors was better than that of low dose. The Yisui multipurpose soup drug serum in the medium not only significantly increased Bcl-2 expression and effectively reduced Bax expression, but also inhibited the apoptosis of neurons induced by D-galactose. In conclusion, Yisui multipurpose soup could effectively protect D-galactose-induced neuronal cell cognitive impairment by orchestrating expressions of the inflammatory factors TNF-α, iNOS, NO, and IL-1ß and the apoptosis-related proteins Bcl-2 and Bax.

11.
BMC Urol ; 22(1): 37, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305591

RESUMO

BACKGROUND: Among malignant tumors, bone metastasis is frequently associated with prostate cancer which is seen in about 80% of patients. During cancer treatments, some tumor cells switch to a "dormant mode" to help tumor cells avoid attack from the immune system and anti-tumor therapies. In this dormant mode, tumor cells can be resuscitated, causing cancer to reoccur. The generally accepted explanation for this phenomenon is that the tumor cells have spread to the bone marrow before treatment and are dormant in the bone marrow. However, the key mechanism for inducing and maintaining the dormancy of these prostate cancer disseminated tumor cells in the bone marrow is still unclear. Therefore, studying the dormancy mechanism of tumor cells in bone metastasis is of great significance for the treatment and the prevention of recurrence of prostate cancer. METHODS: We obtained single-cell RNA-seq data of tumors from mouse models of prostate cancer bone metastasis mouse model numbered (GSE147150) from the GEO database, and obtained RNA-seq expression data and clinical information from The Cancer Genome Atlas Program (TCGA) of prostate cancer patients from the USCS Xena database. Screening of differential genes and annotation of GO functions were performed separately. Subsequently, the screened differential genes were compared and analyzed with 50 classic Hallmark signaling pathways, and the prognosis analysis of prostate cancer patients in TCGA data was performed to discover the key genes of the dormant mechanism of tumor cells in bone metastasis, and obtain new biomarkers that can be used to predict the prognosis of patients. RESULTS: A total of 378 differentially expressed genes were screened, of which 293 were significantly up-regulated and 85 were significantly down-regulated. Among them, the up-regulated genes were mainly related to the immune response, and the down-regulated genes were mainly related to the cell cycle. Through GSVA (Gene set variation analysis), it is found that there are differences in a total of 3 signal pathways: COMPLEMENT, MYC_TARGETS_V1 and MYC_TARGETS_V2. By comparing and analyzing the significantly down-regulated genes in dormant tumor cells with MYC_TARGETS_V1, MYC_TARGETS_V2, three significantly down-regulated genes were obtained: Ccna2, Mad2L1 and Plk1. CONCLUSION: In summary, our findings indicate that the MYC targeting gene Mad2L1 is potentially related to the dormancy mechanism of prostate cancer. At the same time, Mad2L1, a gene associated with dormant prostate cancer cells, may be used as a biomarker for prognostic survival.


Assuntos
Neoplasias Ósseas/secundário , Proteínas Mad2/genética , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Estudos Retrospectivos
12.
Front Cell Dev Biol ; 9: 721505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650974

RESUMO

Genetic variants such as copy number variation (CNV), microsatellite instability (MSI), and tumor mutation burden (TMB) have been reported to associate with the immune microenvironment and prognosis of patients with breast cancer. In this study, we performed an integrated analysis of CNV, MSI, and TMB data obtained from The Cancer Genome Atlas, thereby generating two genetic variants-related subgroups. We characterized the differences between the two subgroups in terms of prognosis, MSI burden, TMB, CNV, mutation landscape, and immune landscape. We found that cluster 2 was marked by a worse prognosis and lower TMB. According to these groupings, we identified 130 differentially expressed genes, which were subjected to univariate and least absolute shrinkage and selection operator-penalized multivariate modeling. Consequently, we constructed an 11-gene signature risk model called the genomic variation-related prognostic risk model (GVRM). Using ROC analysis and a calibration plot, we estimated the prognostic prediction of this GVRM. We confirmed the predictive efficiency of this GVRM by validating it in another independent International Cancer Genome Consortium cohort. Our results conclude that an 11-gene signature developed by integrated analysis of CNV, MSI, and TMB has a high potential to predict breast cancer prognosis, which provided a strong rationale for further investigating molecular mechanisms and guiding clinical decision-making in breast cancer.

13.
World J Clin Cases ; 9(21): 6009-6016, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34368321

RESUMO

BACKGROUND: Prostatitis caused by Brucella infection is rare and usually lacks typical lower urinary tract symptoms. However, Brucella infection can cause serum prostate-specific antigen levels to become abnormally elevated. When concurrent with lumbar vertebra infection and erosion, brucellosis can easily be misdiagnosed as prostate cancer with bone metastasis. CASE SUMMARY: A 45-year-old man complained of recurrent low back pain and fever for 2 wk. Magnetic resonance imaging of the lumbar vertebrae showed abnormal signs at the rear of the L4-5 vertebral body. Serum prostate-specific antigen level was 17.64 ng/mL, and positron emission tomography/computed tomography suggested the possibility of prostate cancer with liver and lumbar metastases. The patient was transferred to our department for further treatment. He experienced repeated bouts of fever and low back pain during hospitalization. Biopsy results indicated prostatitis. There was no significant increase in white blood cell count or procalcitonin levels. The Mycobacterium tuberculosis smear and antibody detection results were negative. Cefoperazone sulbactam was not effective. Blood culture test results were positive for brucellosis, confirming the diagnosis of brucellosis. After oral anti-infection treatment with doxycycline and rifampicin, the body temperature gradually returned to normal, and lumbago improved. After continuous treatment for 6 mo, the patient recovered. CONCLUSION: In patients with low back pain and fever accompanied by elevated prostate-specific antigen levels and lesions of the prostate and lumbar spine, a detailed medical history and blood and urine cultures should be obtained, and attention should be given to the local epidemic infectious disease situation.

14.
Gut ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122176

RESUMO

OBJECTIVE: Macrophages are among the most abundant cells in the colon tumour microenvironment, and there is a close relationship among monocytes, macrophages and the gut microbiota. Alterations in the gut microbiota are involved in tumour development, but the underlying mechanisms remain unclear. We aim to elucidate the temporal changes in macrophage subsets and functions, and how these dynamics are regulated by microbial cues in the initiation of colitis-associated cancer. DESIGN: A mouse model of colitis-associated tumourigenesis was established to determine macrophage dynamics. The role of monocyte-like macrophage (MLM) was confirmed by targeting its chemotaxis. The effects of the gut microbiota were assessed by antibiotic treatment and faecal microbiota transplantation. RESULTS: A selective increase in MLMs was observed in the initial stages of colitis-associated cancer, with an enhanced secretion of inflammatory cytokines. MLM accumulation was regulated by CCL2 expression of colonic epithelial cells, which was influenced by bacteria-derived lipopolysaccharide (LPS). LPS further stimulated interleukin 1ß production from MLMs, inducing interleukin-17-producing T-helper cell activation to promote inflammation. These observations were also supported by altered microbial composition associated with human colitis and colorectal cancer, evolving transcriptional signature and immune response during human colitis-associated tumourigenesis. CONCLUSIONS: The gut microbiota uses LPS as a trigger to regulate MLM accumulation in a chemokine-dependent manner and generate a precancerous inflammatory milieu to facilitate tumourigenesis.

15.
BMC Pediatr ; 20(1): 454, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993580

RESUMO

BACKGROUND: The Global Trigger Tool (GTT),which is a method using "triggers" to review medical record retrospectively to identify possible adverse events. Several studies showed that the GTT was effective. However, there were only a few localized trigger tools that had been established to detect pediatric adverse drug events (ADEs) in China. This study aimed to establish a pediatric trigger tool based on GTT, to examine the performance by detecting pediatric inpatients ADEs in a Chinese hospital (a retrospective review), and to investigate the factors associating with the occurrence of ADEs. METHODS: The triggers were established by three steps including literature search, triggers extraction and revision, and experts investigation. A retrospective cohort study was conducted to detect ADEs by using 200 pediatric inpatient records of Sichuan Provincial People's Hospital. RESULTS: Thirty-three preliminary triggers were established, and 2 rounds of experts investigation were conducted. Finally, 33 triggers were established. In the retrospective review, the positive trigger rate was 64.0%, while the positive predictive value (PPV) was 24.9%. The occurrence of inpatients with ADEs was 20.5%. ADEs/100 admissions were 49.0. ADEs/1000 patient days were 46.89. The most common ADE categories were leukocyte disorders, skin disorders and platelet disorders. The severity of 39 ADEs was grade 1, 55 ADEs was grade 2, 4 ADEs was grade 3. The highest frequency of ADE-related drugs was antineoplastic, followed by antibacterial. The length of stay and the leukemia in the diagnosed diseases were positively correlated with ADEs. CONCLUSIONS: The 33 pediatric triggers may detect ADEs effectively, but still need to be optimized. This study may provide some references for further research in order to improve the rationality and safety of medication.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Criança , China/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hospitalização , Hospitais , Humanos , Estudos Retrospectivos
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(3): 407-412, 2020 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-32376579

RESUMO

OBJECTIVE: To investigate the correlation between sarcopenia and albuminuria in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 360 T2DM patients (including 206 male and 154 female patients) hospitalized in our hospital between January, 2015 and December, 2018 were enrolled. According to their medical history and laboratory test results, the patients were divided into albuminuria group (n=122) and non-albuminuria group (n=238). The clinical and anthropological data were collected and skeletal muscle index (SMI), appendage lean mass, muscle index, total body fat, bone mineral capacity and bone mineral density were measured using dual-energy X-ray absorptiometry. Logistic regression was used to analyze the correlation of these body composition parameters with albuminuria or chronic kidney disease (CKD) in the diabetic patients. RESULTS: The disease course of T2DM, history of hypertension, age, systolic blood pressure, low density lipoprotein cholesterol, triglyceride, uric acid, waistline, Urinary albumin creatinine ratio, serum creatinine, and glomerular filtration rate differed significantly between the diabetic patients with albuminuria and those without albuminuria (P < 0.05). The prevalence rate of sarcopenia was significantly higher in patients with albuminuria (31.4% vs 13.1%, P < 0.01). Compared with those without albuminuria, the patients with albuminuria had significantly decreased SMI (t=-2.304, P=0.021) and body mass index (Z=- 5.534, P < 0.01) and significantly increased total body fat (Z=- 2.838, P=0.005). Multivariate logistic regression analysis showed that after adjustment for age, gender, total body fat, smoking history, drinking history, duration of diabetes, HbA1c, history of hypertension, systolic blood pressure, low density lipoprotein cholesterol, body mass index, and triglyceride, the patients with a decreased SMI had a significantly increased risk of albuminuria (P=0.011 and 0.010), but SMI was not correlated with the risk of CKD in patients with T2DM (P > 0.05). CONCLUSIONS: Sarcopenia is probably an independent risk factor for albuminuria in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Sarcopenia , Albuminúria , Creatinina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Fatores de Risco
17.
Biomed Pharmacother ; 125: 109986, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32058221

RESUMO

The promoting roles of the long non-coding RNA (lncRNA) MACC1-AS1 have been indicated in gastric and pancreatic cancer, however, its roles in nasopharyngeal carcinoma (NPC) progression are never been revealed. In this work, it was shown that lncRNA MACC1-AS1 was highly expressed in NPC tissues and cells relative to the adjacent tissues and nasal mucosa cells, respectively. Additionally, MACC1-AS1 expression was positively correlated with the high rate of lymph node metastasis and large tumor size. in vitro and in vivo experiments revealed that MACC1-AS1 knockdown reduced the stemness of NPC cells, which was indicated by the decrease of sphere-forming ability, ALDH1 activity, stemness marker expression and tumor-initiating capacity. Mechanistic research showed that MACC1-AS1 antagonized the activity of miR-145, which could target Smad2. In turn, smad2 directly bound to MACC1-AS1 promoter and thus increased MACC1-AS1 expression. Notably, knockdown of miR-145 or overexpression of Smad2 rescued the inhibition of MACC1-AS1 knockdown on the stemness of NPC cells. Therefore, these results demonstrate a novel MACC1-AS1/miR-145/Smad2 negative loop responsible for NPC cell stemness.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , RNA Antissenso , RNA Longo não Codificante/genética , Proteína Smad2/genética , Transativadores/genética , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Genes Reporter , Humanos , Masculino , Camundongos , Modelos Biológicos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Gradação de Tumores
18.
Exp Ther Med ; 19(1): 557-568, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31897099

RESUMO

Apocynum venetum is a traditional medicine that is rich in polyphenols. Apocynum venetum polyphenol extract (AVP) contains the active substances neochlorogenic acid, chlorogenic acid, rutin, isoquercitrin, astragaloside and rosmarinic acid. In the present study, the preventive effect of AVP against D-galactose-induced oxidative stress was studied in a mouse model. The sera, skin, livers and spleens of mice were examined using hematoxylin and eosin staining, reverse transcription-quantitative PCR and western blot analysis. The biochemical results showed that AVP improved the thymus, brain, heart, liver, spleen and kidney indices in a mouse model of oxidative stress. AVP was also able to reverse the reduction in levels of superoxide dismutase (SOD), glutathione peroxidase and glutathione, and increased the levels of nitric oxide and malondialdehyde identified in the serum, liver, spleen and brain of mice exposed to oxidative stress. Pathological observations confirmed that AVP could inhibit oxidative damage to the skin, liver and spleen of mice caused by D-galactose. Further molecular biological experiments also demonstrated that AVP increased the expression of neuronal nitric oxide synthase, endothelial nitric oxide synthase, Cu/Zn-SOD, Mn-SOD, catalase, heme oxygenase-1, nuclear factor-erythroid 2-related factor 2, γ-glutamylcysteine synthetase and NAD(P)H quinone dehydrogenase 1 and reduced the expression of inducible nitric oxide synthase in the liver and spleen of treated mice compared to controls. Notably, the preventive effect of AVP against D-galactose-induced oxidative damage in mice was better than that of the confirmed antioxidant vitamin C. In conclusion, AVP exhibited an antioxidant effect and the AVP-rich Apocynum venetum may be considered a plant resource with potential antioxidative benefits.

19.
Med Sci Monit ; 25: 9752-9769, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856144

RESUMO

BACKGROUND Thyroid carcinoma is a malignancy with high morbidity and mortality. Genetic alterations play pivot roles in the pathogenesis of thyroid carcinoma, where long noncoding RNA (lncRNA) have been identified to be crucial. This study sought to investigate the biological functions of lncRNA expression profiles in thyroid carcinoma. MATERIAL AND METHODS The lncRNAs expression profiles were acquired from The Cancer Genome Atlas (TCGA) database according to 510 thyroid cancer tissues and 58 normal thyroid tissues. By using R package edgeR, differentially expressed RNAs were obtained. Also, an overall survival model was established based on Cox regression and clinical data then testified by Kaplan-Meier plot, receiver operating characteristic (ROC)-curve and C-index analysis. We investigated the co-expressed genes with lncRNAs involved in the prognostic model, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted R package clusterProfile. RESULTS A total of 352 lncRNAs were identified as differentially expressed in thyroid carcinoma, and an overall survival model consisting of 8 signature lncRNAs was proposed (ROC=0.862, C-index=0.893, P<0.05), 3 of which (DOCK9-DT, FAM111A-DT, and LINC01736) represent co-expressed mRNAs. However, as an oncogene, only FAM111A-DT increased the prognostic risk in thyroid carcinoma. Furthermore, we found differential genes LINC01016, LHX1-DT, IGF2-AS, ND MIR1-1HG-AS1, significantly related to lymph node metastasis (P<0.05). CONCLUSIONS In this study, we clarified the differential lncRNA expression profiles which were related to the tumorigenesis and prognosis in thyroid carcinoma. Our results provide new rationale and understandings to the pathogenesis and regulatory mechanisms of thyroid carcinoma.


Assuntos
RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/genética , Transcriptoma/genética , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , Curva ROC , Receptores Virais/genética , Análise de Sobrevida
20.
Sci Rep ; 9(1): 12486, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462670

RESUMO

Surfaces with reversible wettability have broad applications but remain challenging since the switching process is usually energy intensive and complex. In this paper, a pyramid shaped Cu2S film with hierarchical micro/nanostructures is formed on a commercial copper mesh. This film is formed by a spontaneous redox sulfuration reaction and results in a roughened surface, which enables reversible wetting transition between superhydrophilicity to superhydrophobicity. This switching occurs by simple processes such as alternately storing in air or using an ethanol solution treatment and yields cyclic wettability switching for many cycles. This convenient wetting transition behavior, as well as strong stability and efficient oil/water separation with efficiency exceeding 98%, renders it as a potentially useful mesh material for switchable surfaces.

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