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1.
Am J Transl Res ; 16(5): 1740-1748, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883341

RESUMO

OBJECTIVE: To identify factors influencing recurrence after percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) and to develop a predictive model. METHODS: We retrospectively analyzed clinical data from 354 patients with intrahepatic and extrahepatic bile duct stones treated with PTCSL at Qinzhou First People's Hospital between February 2018 and January 2020. Patients were followed for three years and categorized into non-recurrence and recurrence groups based on postoperative outcome. Univariate analysis identified possible predictors of stone recurrence. Data were split using the gradient boosting machine (GBM) algorithm, assigning 70% as the training set and 30% as the test set. The predictive performance of the GBM model was assessed using the receiver operating characteristic (ROC) curve and calibration curve, and compared with a logistic regression model. RESULTS: Six factors were identified as significant predictors of recurrence: age, diabetes, total bilirubin, biliary stricture, number of stones, and stone diameter. The GBM model, developed based on these factors, showed high predictive accuracy. The area under the ROC curve (AUC) was 0.763 (95% CI: 0.695-0.830) for the training set and 0.709 (95% CI: 0.596-0.822) for the test set. Optimal cutoff values were 0.286 and 0.264, with sensitivities of 62.30% and 66.70%, and specificities of 77.20% and 68.50%, respectively. Calibration curves indicated good agreement between predicted probabilities and observed recurrence rates in both sets. DeLong's test revealed no significant differences between the GBM and logistic regression models in predictive performance (training set: D = 0.003, P = 0.997 > 0.05; test set: D = 0.075, P = 0.940 > 0.05). CONCLUSION: Biliary stricture, stone diameter, diabetes, stone number, age, and total bilirubin significantly influence stone recurrence after PTCSL. The GBM model, based on these factors, demonstrates robust accuracy and discrimination. Both GBM and logistic regression models effectively predicted stone recurrence post-PTCSL.

2.
Chin J Integr Med ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816637

RESUMO

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.

3.
J Leukoc Biol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630870

RESUMO

The treatment of non-healing wounds, such as diabetic ulcers, remains a critical clinical challenge. Recent breakthroughs in cell therapy have shown great promise, with one primary focus on preparing cells with comprehensive reparative functions and foreseeable safety. In our previous study, we recapitulated the pro-regenerative and immunosuppressive functions of tumor-associated macrophages (TAMs) in non-tumor-derived macrophages, endowing the latter with characteristics for promoting diabetic wound healing - termed TAMs-educated macrophages (TAMEMs). To eliminate the use of tumor-derived sources and devise a more controllable method to prepare TAMEM-like cells, in this study, we identify a cocktail comprising five recombinant proteins as an essential condition to induce non-polarized macrophages (termed TAMEMs5) into therapeutic cells with pro-healing functions. The screened five factors are osteopontin (OPN), macrophage inflammatory protein (MIP)-2, chemokine (C-C motif) ligand 8 (CCL8), vascular endothelial growth factor (VEGF)-B, and macrophage colony-stimulating factor (M-CSF). We demonstrate the rationale for screening these factors and the phenotype of TAMEMs5 prepared from murine bone marrow-derived macrophages, which exhibit angiogenic and immunomodulatory effects in vitro. Then, we induce primary human monocytes from periphery blood into TAMEMs5, which show pro-healing effects in a human primary cell-based ex vivo model (T-SkinTM). Our study demonstrates a simple, effective, and controllable approach to induce primary macrophages to possess repairing activities, which may provide insights for developing cell-based therapeutics for non-healing wounds clinically.

4.
Water Sci Technol ; 88(10): 2661-2676, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38017684

RESUMO

Rural water environment governance in China still lacks a systematic and comprehensive assessment protocol to help analyze and improve such governance performance. The Analytic Hierarchy Process (AHP) method was employed in this study to build a governance assessment system that integrates ecological conditions, water pollution control, and public satisfaction. To cover these topics, the assessment system is composed of an indicator layer that is customized to rural water environment governance in China. The Beitang River, located in the rural region of Hangzhou, Zhejiang, China, was presented as a case study. Field investigation provided raw data for this assessment. A questionnaire survey was conducted to interview local residents on the governance performance. An additional survey with executives who played major roles in the governance was performed to reconstruct a water environment assessment on the Beitang River prior to the governance, in order to highlight the effects of the governance through contrast. The results showed consistency in the questionnaire survey and the assessment system. The AHP assessment system was able to reflect the improvement in the water quality, river ecology, and residential welfare after the governance, and suggested limits and future directions in the following upgrade programs for the river basin.


Assuntos
Processo de Hierarquia Analítica , Rios , Qualidade da Água , Conservação dos Recursos Naturais , China
5.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4147-4155, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37802783

RESUMO

Based on the androgen receptor(AR)/mammalian target of rapamycin(mTOR)signaling pathway, the effects of Xihuang Pills-medicated serum on the proliferation and apoptosis of prostate cancer LNCaP cells were investigated. The drug-containing serum of SD rats was prepared by intragastric administration of Xihuang Pills suspension. The effects of low-, medium-, and high-dose Xihuang Pills-containing serum on the in vitro proliferation of LNCaP cells were detected by cell counting kit-8(CCK-8). Flow cytometry was used to detect the apoptosis level of LNCaP cells after intervention with different concentrations of Xihuang Pills. Protein expression of cleaved cysteinyl aspartate-specific proteinase caspase-3(cleaved caspase-3), B-cell lymphoma-2(Bcl-2), and AR as well as the phosphorylation level of mTOR protein were detected by Western blot. The results showed that compared with the blank serum, the drug-medicated serum could blunt the activity of LNCaP cells. Low-, medium-, and high-dose Xihuang Pills-containing serum could significantly increase the cell apoptosis rate, increase the expression of cleaved caspase-3 protein, decrease the expression of Bcl-2 protein, reduce the expression of AR protein, and down-regulate the level of phosphorylated mTOR(p-mTOR). To study the effect of Xihuang Pills on the growth of LNCaP cells in vivo, different doses of Xihuang Pills were used to intervene in the subcutaneous graft model in nude mice inoculated with LNCaP cells. The expression levels of AR, mTOR, p-mTOR, Bcl-2, and cleaved caspase-3 were detected by Western blot. The results showed that the volumes of subcutaneous graft tumor in the low-dose, medium-dose, and high-dose Xihuang Pills groups significantly decreased compared with that in the model group. The weight of subcutaneous transplanted tumor in each group with drug intervention was significantly lower than that in the model group. Compared with the model group, the low-dose, medium-dose, and high-dose Xihuang Pills groups showed increased cleaved caspase-3 protein expression, decreased Bcl-2 and AR protein expression, and reduced p-mTOR protein expression. Further experiments showed that AR agonist R1881 could block the anti-proliferation and pro-apoptotic effects of Xihuang Pills. The mechanism of Xihuang Pills against prostate cancer is related to the inhibition of the AR/mTOR signaling pathway, inhibition of LNCaP cell proliferation, and induction of apoptosis in cancer cells.


Assuntos
Neoplasias da Próstata , Transdução de Sinais , Humanos , Masculino , Camundongos , Ratos , Animais , Caspase 3/genética , Caspase 3/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Proliferação de Células , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Mamíferos/metabolismo
6.
Aging Clin Exp Res ; 35(7): 1497-1504, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37142943

RESUMO

BACKGROUND: Delayed neurocognitive recovery (DNR) is a common complication after radical gastrectomy and closely associated with poor outcomes. This study aimed to investigate predictors and develop a nomogram prediction model for DNR. METHODS: Elderly gastric cancer (GC) patients (≥ 65 years) undergoing elective laparoscopic radical gastrectomy between 2018 and 2022 were prospectively included in this study. DNR was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V, 2013). Independent risk factors for DNR were screened by the multivariate logistic regression analysis. Based on these factors, the nomogram model was established and validated by R. RESULTS: A total of 312 elderly GC patients were enrolled in the training set, with an incidence of DNR within postoperative 1 month of 23.4% (73/312). Multivariate logistic regression analysis indicated that age (OR: 1.207, 95%CI: 1.113-1.309, P < 0.001), nutritional risk screening 2002 (NRS2002) score (OR: 1.716, 95%CI: 1.211-2.433, P = 0.002), neutrophil-to-lymphocyte ratio (NLR) (OR: 1.976, 95%CI: 1.099-3.552, P = 0.023), albumin-to-fibrinogen ratio (AFR) (OR: 0.774, 95%CI: 0.620-0.966, P = 0.024), and prognostic nutritional index (PNI) (OR: 0.768, 95%CI: 0.706-0.835, P < 0.001) were five independent factors for DNR in elderly GC patients. The constructed nomogram model based on these five factors has a good predictive value for DNR with an area under the curve (AUC) of 0.863. CONCLUSIONS: In conclusions, the established nomogram model based on age, NRS-2002, NLR, AFR, and PNI has a well predictive value for postoperative DNR in elderly GC patients.


Assuntos
Nomogramas , Neoplasias Gástricas , Humanos , Idoso , Neoplasias Gástricas/cirurgia , Fatores de Risco , Linfócitos , Neutrófilos
7.
J Exp Bot ; 74(17): 4978-4993, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37235693

RESUMO

Brassinosteroids (BRs) are a class of polyhydroxylated steroidal phytohormones that are essential for plant growth and development. Rice BRASSINOSTEROID-INSENSITIVE1 (BRI1)-ASSOCIATED RECEPTOR KINASES (OsBAKs) are plasma membrane-localized receptor kinases belonging to the subfamily of leucine-rich repeat receptor kinases. It has been found that in Arabidopsis, BRs induce the formation of a BRI1-BAK1 heterodimer complex and transmit the cascade signal to BRASSINAZOLE RESISTANT1/bri1-EMS-SUPPRESSOR1 (BZR1/BES1) to regulate BR signaling. Here, in rice (Oryza sativa ssp. japonica), we found that OsBZR1 binds directly to the promoter of OsBAK2, but not OsBAK1, and represses the expression of OsBAK2 to form a BR feedback inhibition loop. Additionally, the phosphorylation of OsBZR1 by OsGSK3 reduced its binding to the OsBAK2 promoter. The osbak2 mutant displays a typical BR-deficiency phenotype and negative modulates the accumulation of OsBZR1. Interestingly, the grain length of the osbak2 mutant was increased whereas in the cr-osbak2/cr-osbzr1 double mutant, the reduced grain length of the cr-osbzr1 mutant was restored, implying that the increased grain length of osbak2 may be due to the rice somatic embryogenesis receptor kinase-dependent pathway. Our study reveals a novel mechanism by which OsBAK2 and OsBZR1 engage in a negative feedback loop to maintain rice BR homeostasis, facilitating a deeper understanding of the BR signaling network and grain length regulation in rice.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Oryza , Brassinosteroides/metabolismo , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Transdução de Sinais , Arabidopsis/genética , Grão Comestível/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Arabidopsis/metabolismo
8.
Cancer ; 129(13): 2013-2022, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36951498

RESUMO

BACKGROUND: Minimal residual disease (MRD) is an important prognostic factor for survival in adults with acute leukemia. The role of pretransplantation MRD status in myelodysplastic syndrome with excess blasts (MDS-EB) is unknown. This study retrospectively analyzed the relationship between pretransplantation MRD status and long-term survival. MATERIALS AND METHODS: Patients with MDS-EB who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from March 5, 2005, to November 8, 2020, were included. The relationship between pretransplantation MRD status and long-term survival was analyzed using univariate and multivariate logistic regression models. RESULTS: Of 220 patients with MDS-EB who underwent allo-HSCT, 198 were eligible for inclusion in this multicenter, retrospective cohort study. Complete remission was attained in 121 (61.1%) patients, and 103 patients underwent detection of MRD pretransplantation, with 67 patients being MRD-positive and 36 patients being MRD-negative. The median follow-up time was 16 months, the median age was 41 years (6-65 years), and 58% of the patients were men. The 3-year disease-free survival (DFS) and overall survival (OS) probabilities for all patients were 70.1% and 72.9%, respectively. For patients in complete remission, the 3-year DFS and OS probabilities were 72.2% and 74.8%, respectively. Further analysis found that the 3-year DFS rates of MRD-negative and MRD-positive patients were 85.6% and 66.5% (p = .045), respectively, whereas the 3-year OS rates were 91.3% and 66.4% (p = .035), respectively. Univariate and multivariate analyses showed that poor pretransplantation MRD clearance was an independent prognostic risk factor for DFS and OS. CONCLUSION: Poor pretransplantation MRD clearance is an independent prognostic risk factor for long-term survival after allo-HSCT for patients with MDS-EB. PLAIN LANGUAGE SUMMARY: Poor minimal residual disease clearance pretransplanation is an independent prognostic risk factor for long-term survival after allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome with excess blasts.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Masculino , Humanos , Feminino , Prognóstico , Estudos Retrospectivos , Neoplasia Residual/diagnóstico , Síndromes Mielodisplásicas/terapia , Fatores de Risco
9.
Blood Rev ; 60: 101074, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36963988

RESUMO

Because of successful thalassaemia prevention programmes in resource-rich countries and it's huge population China now has the greatest number of new cases of thalassaemia globally as well as more people with thalassaemia than any other country. 30 million Chinese have thalassaemia-associated mutations and about 300,000 have thalassaemia major or intermedia requiring medical intervention. Over the past 2 decades there has been tremendous economic growth in China including per capita spending on health care. There is now nation-wide availability and partial or full insurance for prenatal genetic testing, RBC-transfusions, iron-chelating drugs and haematopoietic cell transplants. Prenatal screening and educational programmes have reduced the incidence of new cases. However, substantial challenges remain. For example, regional differences in access to medical care and unequal economic development require innovations to reduce the medical, financial and psychological burdens of Chinese with thalassaemia and their families. In this review we discuss success in preventing and treating thalassaemia in China highlighting remaining challenges. Our discussion has important implications for resource-poor geospaces challenged with preventing and treating thalassaemia.


Assuntos
Talassemia , Talassemia beta , Gravidez , Feminino , Humanos , Talassemia/diagnóstico , Talassemia/epidemiologia , Talassemia/terapia , Quelantes de Ferro/uso terapêutico , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/genética , Testes Genéticos , Transfusão de Sangue
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(1): 221-226, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36765503

RESUMO

OBJECTIVE: To investigate the expression and its relative mechanism of hypoxia-inducible factor-1α(HIF-1α) in bone marrow(BM) of mice during G-CSF mobilization of hematopoietic stem cells (HSC) . METHODS: Flow cytometry was used to detect the proportion of Lin-Sca-1+ c-kit+ (LSK) cells in peripheral blood of C57BL/6J mice before and after G-CSF mobilization. And the expression of HIF-1α and osteocalcin (OCN) mRNA and protein were detected by RQ-PCR and immunohistochemistry. The number of osteoblasts in bone marrow specimens of mice was counted under the microscope. RESULTS: The proportion of LSK cells in peripheral blood began to increase at day 4 of G-CSF mobilization, and reached the peak at day 5, which was significantly higher than that of control group (P<0.05). There was no distinct difference in the expression of HIF-1α mRNA between bone marrow nucleated cells and osteoblasts of steady-state mice (P=0.073), while OCN mRNA was mainly expressed in osteoblasts, which was higher than that in bone marrow nucleated cells (P=0.034). After mobilization, the expression level of HIF-1α increased, but OCN decreased, and the number of endosteum osteoblasts decreased. The change of HIF-1α expression was later than that of OCN and was consistent with the proportion of LSK cells in peripheral blood. CONCLUSION: The expression of HIF-1α in bone marrow was increased during the mobilization of HSC mediated by G-CSF, and one of the mechanisms may be related to the peripheral migration of HSC induced by osteoblasts inhibition.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Camundongos , Animais , Fator Estimulador de Colônias de Granulócitos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos Endogâmicos C57BL , Células da Medula Óssea/metabolismo , Osteocalcina/metabolismo , RNA Mensageiro/metabolismo
11.
Transplant Cell Ther ; 29(2): 136.e1-136.e7, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36402457

RESUMO

Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , SARS-CoV-2 , Medula Óssea , População do Leste Asiático , Pandemias , COVID-19/epidemiologia , Sistema de Registros
12.
Curr Med Sci ; 42(5): 925-931, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36260269

RESUMO

Gene therapy refers to introducing normal exogenous genes into target cells to correct or compensate for the diseases caused by defective and abnormal genes for the purpose of therapy. It holds out hope of a cure for single-gene genetic diseases such as thalassemia, hemophilia, etc. At present, gene therapy is performed in two ways: introducing exogenous genes, and gene editing. A great number of clinical trials of gene therapy in hemophilia have been carried out using viral vectors to introduce foreign genes into target cells. However, the production of neutralizing antibodies following injection and the inability to prepare viral vectors in large quantities limit their application. Although gene-editing methods like CRISPR avoid the above problems, the potential risks of off-target effects are still unknown. More trials and evidence are needed to elucidate the safety and accuracy of gene therapy. This paper will review the bench and clinical work of gene therapy in hemophilia in recent years, and summarize the challenges and prospects of gene therapy, so as to provide directions for future scientific research in this field.


Assuntos
Hemofilia A , Humanos , Hemofilia A/genética , Hemofilia A/terapia , Sistemas CRISPR-Cas , Edição de Genes/métodos , Terapia Genética/métodos , Anticorpos Neutralizantes
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(2): 149-153, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-36031573

RESUMO

Objective: To investigate the possible protective effects of combined dexamethasone and valsartan against cigarette induced chronic obstructive pulmonary disease (COPD) in mice. Methods: Forty C57BL/6 mice were randomly divided into control group, COPD group, dexamethasone treated group, valsartan treated group and dexamethasone + valsartan combined treatment group, with 8 mice in each group. Mice in COPD group were exposed to cigarette for 8 weeks. On the basis of cigarette exposure, mice in dexamethasone treated group were intraperitoneally injected with dexamethasone (2 mg / kg) before cigarette exposure for 5-8 weeks. Mice in valsartan treated group were intraperitoneally injected with valsartan (30 mg/kg) before cigarette exposure for 1-8 weeks. Dexamethasone (2 mg/kg) and valsartan (30 mg/kg) were injected intraperitoneally into mice in the dexamethasone + valsartan combined treatment group. After 8 weeks, the lung tissues and bronchoalveolar lavage fluid (BALF) of mice in each group were collected. The pathological score of lung tissue was evaluated. The activities of superoxide dismutase(SOD) and matrix metalloproteinase-9 (MMP-9), and the contents of malondialdehyde (MDA), intracellular adhesion molecule-1 (ICAM-1), C-reactive protein (CRP) and nitric oxide (NO) in BALF were determined. Results: Compared with the control group, COPD mice had emphysema and alveolar congestion, the levels of MDA, ICAM-1, MMP-9, CRP and lymphocytes in BALF were increased, while the levels of SOD, macrophages and NO were decreased (all P<0.05). Compared with COPD group, there was no significant improvement in emphysema and alveolar congestion, the levels of SOD and NO in BALF were increased, and the levels of MDA, lymphocytes and macrophages were decreased in dexamethasone or valsartan group (all P<0.05). Compared with dexamethasone or valsartan group, the dexamethasone + valsartan combined treatment was more effective in preventing pulmonary emphysema and alveolar congestion caused by cigarette smoke. The levels of MDA, ICAM-1, MMP-9, CRP and lymphocyte in BALF were decreased, while the levels of SOD, macrophage and NO were increased (all P<0.05). Conclusion: Compared with dexamethasone or valsartan, dexamethasone combined with valsartan has a more effective protective effect in COPD mice by inhibiting oxidative stress and inflammation.


Assuntos
Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Animais , Líquido da Lavagem Broncoalveolar , Dexametasona , Molécula 1 de Adesão Intercelular , Pulmão , Metaloproteinase 9 da Matriz , Camundongos , Camundongos Endogâmicos C57BL , Superóxido Dismutase , Valsartana
14.
World J Gastrointest Oncol ; 14(4): 872-886, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35582102

RESUMO

BACKGROUND: The phosphoinositide 3-kinase/protein kinase-B/mechanistic target of rapamycin (PI3K/Akt/mTOR) signalling pathway is crucial for cell survival, differentiation, apoptosis and metabolism. Xihuang pills (XHP) are a traditional Chinese preparation with antitumour properties. They inhibit the growth of breast cancer, glioma, and other tumours by regulating the PI3K/Akt/mTOR signalling pathway. However, the effects and mechanisms of action of XHP in hepatocellular carcinoma (HCC) remain unclear. Regulation of the PI3K/Akt/mTOR signalling pathway effectively inhibits the progression of HCC. However, no study has focused on the XHP-associated PI3K/Akt/mTOR signalling pathway. Therefore, we hypothesized that XHP might play a role in inhibiting HCC through the PI3K/Akt/mTOR signalling pathway. AIM: To confirm the effect of XHP on HCC and the possible mechanisms involved. METHODS: The chemical constituents and active components of XHP were analysed using ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Cell-based experiments and in vivo xenograft tumour experiments were utilized to evaluate the effect of XHP on HCC tumorigenesis. First, SMMC-7721 cells were incubated with different concentrations of XHP (0, 0.3125, 0.625, 1.25, and 2.5 mg/mL) for 12 h, 24 h and 48 h. Cell viability was assessed using the CCK-8 assay, followed by an assessment of cell migration using a wound healing assay. Second, the effect of XHP on the apoptosis of SMMC-7721 cells was evaluated. SMMC-7721 cells were stained with fluorescein isothiocyanate and annexin V/propidium iodide. The number of apoptotic cells and cell cycle distribution were measured using flow cytometry. The cleaved protein and mRNA expression levels of caspase-3 and caspase-9 were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-qPCR), respectively. Third, Western blotting and RT-qPCR were performed to confirm the effects of XHP on the protein and mRNA expression of components of the PI3K/Akt/mTOR signalling pathway. Finally, the effects of XHP on the tumorigenesis of subcutaneous hepatocellular tumours in nude mice were assessed. RESULTS: The following 12 compounds were identified in XHP using high-resolution mass spectrometry: Valine, 4-gingerol, myrrhone, ricinoleic acid, glycocholic acid, curzerenone, 11-keto-ß-boswellic acid, oleic acid, germacrone, 3-acetyl-9,11-dehydro-ß-boswellic acid, 5ß-androstane-3,17-dione, and 3-acetyl-11-keto-ß-boswellic acid. The cell viability assay results showed that treatment with 0.625 mg/mL XHP extract decreased HCC cell viability after 12 h, and the effects were dose- and time-dependent. The results of the cell scratch assay showed that the migration of HCC cells was significantly inhibited in a time-dependent manner by the administration of XHP extract (0.625 mg/mL). Moreover, XHP significantly inhibited cell migration and resulted in cell cycle arrest and apoptosis. Furthermore, XHP downregulated the PI3K/Akt/mTOR signalling pathway, which activated apoptosis executioner proteins (e.g., caspase-9 and caspase-3). The inhibitory effects of XHP on HCC cell growth were determined in vivo by analysing the tumour xenograft volumes and weights. CONCLUSION: XHP inhibited HCC cell growth and migration by stimulating apoptosis via the downregulation of the PI3K/Akt/mTOR signalling pathway, followed by the activation of caspase-9 and caspase-3. Our findings clarified that the antitumour effects of XHP on HCC cells are mediated by the PI3K/Akt/mTOR signalling pathway, revealing that XHP may be a potential complementary therapy for HCC.

16.
Animals (Basel) ; 12(7)2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35405881

RESUMO

Gastrointestinal nematodes (GINs), such as Trichostrongylidae, are important pathogens in small ruminants, causing significant losses in these livestock species. Despite their veterinary importance, GINs have not been studied in certain regions of the world. Therefore, much of their epidemiology and economic impact on production remain unknown. In the present study, a systematic epidemiological survey based on the modified McMaster technique was conducted to investigate the type and infection of GINs in sheep and cattle. In 9622 fecal samples from 491 sampling sites in the four main banner districts of Ordos, the prevalence of GIN infection was found to be 38.84% and 4.48% in sheep and cattle, respectively. At the same time, the effects of four pasture types on the distribution of GINs were analyzed. This study also found severe resistance to ivermectin and albendazole in GINs and suspected anthelmintic resistance in nitroxynil, levamisole and closantel. We report the type and infection of GINs in Ordos, with the aim to help the prevention and control of GINs. Based on the results of the questionnaire survey and GIN resistance test, we found several reasons for the anthelmintic resistance of GINs, consequently providing new ideas for controlling the occurrence of anthelmintic resistance.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 292-297, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35123642

RESUMO

OBJECTIVE: To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT). METHODS: The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed. RESULTS: Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001). CONCLUSION: The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words  ;


Assuntos
Bacteriemia , Transplante de Células-Tronco Hematopoéticas , Sepse , Bacteriemia/epidemiologia , Bactérias , Humanos , Estudos Retrospectivos
19.
ACS Omega ; 7(3): 2604-2612, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35097258

RESUMO

Four complexes from lanthanides, 3-pyridylacetate, and 1,10-phenanthroline, formulated as [Ln2(3-PAA)2(µ-Cl)2(phen)4](ClO4)2 [Ln = Gd(1), Dy(2), Eu(3), Tb(4), 3-PAA = 3-pyridylacetic acid, phen = 1,10-phenanthroline], were obtained. The four compounds were characterized by IR spectra, thermogravimetric analyses, powder X-ray diffraction, and single-crystal X-ray diffraction. Compounds 1-4 are isomorphous, and they have a dinuclear structure. Magnetic studies reveal that 1 shows the magnetocaloric effect with -ΔS m max = 19.03 J kg-1 K-1 at 2 K for ΔH = 5 T, and 2 displays a field-induced single-molecule magnet with U eff = 19.02 K. The photoluminescent spectra of 3 and 4 exhibit strong characteristic emission, which demonstrate that the ligand-to-EuIII/TbIII energy transfer is efficient.

20.
Cancer Manag Res ; 13: 9117-9126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34924772

RESUMO

BACKGROUND: Pulmonary infection is one of the most common postoperative complications after radical gastrectomy for gastric cancer (GC) and is associated with a poorer prognosis. This study aimed to investigate potential predictive factors for pulmonary infection in elderly GC patients. METHODS: This study retrospectively enrolled 346 elderly GC patients undergoing elective radical gastrectomy between January 2017 and December 2020. Pulmonary infection within postoperative 30 days was set as the primary observational endpoint. The baseline demographic, clinicopathological, and laboratory data were compared between patients with or without pulmonary infection. ROC curves were plotted to evaluate the cut-off and predictive values of factors. Binary univariate and multivariate logistic regression analyses were employed to determine risk factors for postoperative pulmonary infection. RESULTS: Of the enrolled 346 patients, pulmonary infection was observed in 51 patients within postoperative 30 days, with an incidence of 14.7%. mFI was a significant predictor for pulmonary infection by ROC curve analysis (AUC: 0.770, P < 0.001). Moreover, preoperative mFI was the only independent risk factor for pulmonary infection (OR: 2.72, 95% CI: 2.02-3.31, P = 0.011) by univariate and multivariate logistic regression analyses. CONCLUSION: Our study indicates that mFI independently predicts pulmonary infection in elderly GC patients.

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