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Rapid isolation and identification of lactic acid bacteria and yeasts during fermentation is of great significance for quality control and regulation of fermented foods. In this study, we prepared a multi-channel magnetic flow device for rapid separation and purification of lactic acid bacteria and yeast, and based on SERS spectrum, we made rapid qualitative and quantitative analysis of Lactobacillus plantarum, Lactococcus lactis and Saccharomyces cerevisiae. The results showed that the synthesized Synthesized Fe3O4-Van antibiotic magnetic beads are paramagnetic; Fe3O4-Van antibiotic magnetic beads achieved capture efficiencies of more than 98.5 % for both L. plantarum and L. lactis at 102-104 CFU/mL, respectively. Separation and purification efficiency of single S. cerevisiae, L. plantarum and L. lactis by multi-channel magnetic flow device all reached more than 98 % with good isolation and purification results. The SERS spectra of the three microorganisms were classified and analyzed using linear discriminant analysis (LDA), and the accuracy of the established LDA model was 100 %, which completely differentiated the SERS spectra of the three microorganisms,and realized the qualitative identification of L. plantarum, L. lactis, and S. cerevisiae, and finally, quantitative model was established with the logarithmic values (lg C) of different concentrations of L. plantarum, L. lactis, and S. cerevisiae as the horizontal coordinates, and the Raman intensities at their strongest characteristic peaks of 512 cm-1, 1669 cm-1, and 1125 cm-1, respectively, were used as vertical coordinates to establish a quantitative model, with the lowest detection limit of 10 CFU/mL, and the digital quantification of lactic acid bacteria and yeast were achieved. It provided an effective means for real-time monitoring and tracking of the dynamics of lactic acid bacteria and yeast in the fermentation process and the quality control of fermented foods.
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Background: Dexamethasone in conjunction with type 3 serotonin receptor antagonists are being used to the prevention and treatment of chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting in clinic. The present study aimed to investigates the stability of ramosetron with dexamethasone in infusions, with the goal of enhancing the safety and clinical applicability of their combined use. Methods: Ramosetron hydrochloride (3.0 µg/mL) combining with dexamethasone (0.05, 0.1, 0.2 mg/mL) were prepared with 0.9% sodium chloride injection and then packaged in polyolefin bags or glass bottles. The stability were investigated kept in the dark at refrigeration for 14 days and at room temperature for 48 h. Results: The concentration of both drugs maintained at least 97% in the various solutions for both storage conditions with light protection. In the light exposure conditions, as the extension of storage time, the concentration of both drugs had declined. All antiemetic mixture solutions remained clear and no changes in color, turbidity, precipitation, and the pH remained stable. The insoluble particles were in line with Chinese Pharmacopoeia. Conclusion: Our findings suggest that combinations of ramosetron hydrochloride with dexamethasone sodium phosphate in 0.9% sodium chloride injection remain stable for 14 days at 4°C and 48 h at 25°C when protected from light.
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Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural and functional changes of glycoprotein, which is closely related to the occurrence and development of various diseases. Consequently, exploring protein glycosylation can shed light on the mechanisms behind disease manifestation and pave the way for innovative diagnostic and therapeutic strategies. Nonetheless, the study of clinical glycoproteomics is fraught with challenges due to the low abundance and intricate structures of glycosylation. Recent advancements in mass spectrometry-based clinical glycoproteomics have improved our ability to identify abnormal glycoproteins in clinical samples. In this review, we aim to provide a comprehensive overview of the foundational principles and recent advancements in clinical glycoproteomic methodologies and applications. Furthermore, we discussed the typical characteristics, underlying functions, and mechanisms of glycoproteins in various diseases, such as brain diseases, cardiovascular diseases, cancers, kidney diseases, and metabolic diseases. Additionally, we highlighted potential avenues for future development in clinical glycoproteomics. These insights provided in this review will enhance the comprehension of clinical glycoproteomic methods and diseases and promote the elucidation of pathogenesis and the discovery of novel diagnostic biomarkers and therapeutic targets.
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An organometallic iridium (Ir)-complex-functionalized nanographene catalyst Ir-PyPh-GC was prepared via a two-step strategy involving amide ligand modification and metal Ir coordination. Ir-PyPh-GC showed ultrahigh hydrogenation capability, good recyclability, and selectivity for carbonyl derivatives (ketones, aldehydes, and quinones) at a low temperature (40 °C). The as-prepared Ir-complex-based catalyst is less expensive, making it feasible for industrial application.
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Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.
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BACKGROUND: Stroke is a major cause of death globally and the leading cause in China. Excessive fluoride exposure has been linked to cardiovascular conditions related to stroke risk factors such as hypertension, atherosclerosis, dyslipidemia, and cardiomyopathy. However, evidence supporting the association between fluoride exposure and stroke risk is limited. METHODS: We constructed an ecological study in Changwu Town, Heilongjiang Province, China, a typical endemic fluorosis area caused by excessive fluoride exposure from drinking water. We collected demographic data, stroke prevalence, and mortality information from 2017 to 2021. Fluoride exposure data were obtained from the national monitoring project on endemic fluorosis. Water fluoride concentrations were measured using the standardized methods. Trend changes in stroke rates were assessed using annual percentage change (APC). Differences in stroke rates among fluoride exposure groups were analyzed using chi-square tests. RESULTS: From 2017 to 2021, the all-ages and age-standardized stroke prevalence rates of permanent residents in Changwu Town increased year by year, while the all-ages and age-standardized mortality rates did not change significantly. The prevalence rates of stroke were significantly higher in endemic fluorosis areas compared to non-endemic areas (p < 0.001). Stratifying the population into tertile groups based on the water fluoride cumulative exposure index (WFCEI) revealed statistically significant differences in stroke prevalence rates (p < 0.001), showing a dose-response relationship with the WFCEI. However, the all-ages and age-standardized mortality rates of stroke were not found to be related to fluoride exposure. CONCLUSIONS: Long-term excessive fluoride exposure from drinking water may increase the risk of stroke prevalence, indicating fluoride overexposure as a potential risk factor for stroke.
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Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell cell migration and invasion assay data shown in Fig. 3B were strikingly similar to data appearing in different form in a pair of other articles written by different authors at different research institutes, one of which had already been published elsewhere prior to the submission of this paper to International Journal of Molecular Medicine, and one of which was under consideration for publication at around the same time. In view of the fact that the abovementioned data had already apparently been published previously, the Editor of International Journal of Molecular Medicine has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 147, 2021; DOI: 10.3892/ijmm.2021.4980].
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Porcine rotavirus (PoRV), a member of the Reoviridae family, constitutes a principal etiological agent of acute diarrhea in piglets younger than eight weeks of age, and it is associated with considerable morbidity and mortality within the swine industry. The G5 genotype rotavirus strain currently predominates in circulation. To develop a safe and effective porcine rotavirus vaccine, we generated an insect cell-baculovirus expression system, and successfully expressed these three viral proteins and assembled them into virus-like particles (VLPs) co-displaying VP2, VP6, and VP7. Transmission electron microscopy (TEM) analysis revealed that the VP2-VP6-VP7 VLPs exhibited a "wheeled" morphology resembling that of native rotavirus particles, with an estimated diameter of approximately 65â¯nm. To evaluate the immunogenicity and protective efficacy of these VP2-VP6-VP7 VLPs, we immunized BALB/C mice with four escalating doses of the VLPs, ranging from 5 to 40⯵g of VLP protein per dose. ELISA-based assessments of PoRV-specific antibodies and T cell cytokines, including IL-4, IL-2, and IFN-γ, demonstrate that immunization with VP2-VP6-VP7 VLPs can effectively elicit both humoral and cellular immune responses in mice, resulting in a notable induction of neutralizing antibodies. On days 4, 6, 8, and 10 post-infection (dpi), the VLP-vaccinated group exhibited significantly reduced levels of PoRV RNA copy numbers when compared to the PBS controls. Histological examination of the duodenum, ileum, and kidneys revealed that VP2-VP6-VP7 VLPs provided effective protection against PoRV induced intestinal injury. Collectively, these findings indicate that the VLPs generated in this study possess strong immunogenicity and suggest the considerable promise of the VLP-based vaccine candidate in the prevention and containment of Porcine Rotavirus infections.
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Death receptor-mediated extrinsic apoptosis system had been developed as a promising therapeutic strategy in clinical oncology, such as TRAIL therapy. However, multiple studies have demonstrated that TRAIL resistance is the biggest problem for disappointing clinical trials despite preclinical success. Targeting cellular FLICE inhibitory protein (cFLIP) is one strategy of combinatorial therapies to overcome resistance to DR-mediated apoptosis due to its negative regulator of extrinsic apoptosis. E × 527 (Selisistat) is a specific inhibitor of SIRT1 activity with safe and well tolerance in clinical trials. Here, we show that E × 527 could strengthen significantly activation of rhFasL-mediated apoptotic signaling pathway and increased apoptotic rate of T leukemia cells with high expression of cFLIP. Mechanically, Inhibition of SIRT1 by E × 527 increased polyubiquitination level of cFLIP via increasing acetylation of Ku70, which could promote proteosomal degradation of cFLIP protein. It implied that combinatorial therapies of E × 527 plus TRAIL may have a potential as a novel clinical application for TRAIL-resistant hematologic malignancies.
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Apoptosis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Sirtuina 1 , Ligando Inductor de Apoptosis Relacionado con TNF , Humanos , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Apoptosis/efectos de los fármacos , Sirtuina 1/metabolismo , Sirtuina 1/antagonistas & inhibidores , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/metabolismo , Leucemia de Células T/patología , Carbazoles/farmacología , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Autoantígeno Ku/metabolismo , Animales , Transducción de Señal/efectos de los fármacos , Ratones , Azocinas , Compuestos de BencidriloRESUMEN
BsCotA laccase is a promising candidate for industrial application due to its excellent thermal stability. In this research, our objective was to enhance the catalytic efficiency of BsCotA by modifying the active site pocket. We utilized a strategy combining the diversity design of the active site pocket with molecular docking screening, which resulted in selecting five variants for characterization. All five variants proved functional, with four demonstrating improved turnover rates. The most effective variants exhibited a remarkable 7.7-fold increase in catalytic efficiency, evolved from 1.54 × 105 M-1 s-1 to 1.18 × 106 M-1 s-1, without any stability loss. To investigate the underlying molecular mechanisms, we conducted a comprehensive structural analysis of our variants. The analysis suggested that substituting Leu386 with aromatic residues could enhance BsCotA's ability to accommodate the 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonate (ABTS) substrate. However, the inclusion of charged residues, G323D and G417H, into the active site pocket reduced kcat. Ultimately, our research contributes to a deeper understanding of the role played by residues in the laccases' active site pocket, while successfully demonstrating a method to lift the catalytic efficiency of BsCotA. KEY POINTS: ⢠Active site pocket design that enhanced BsCotA laccase efficiency ⢠7.7-fold improved in catalytic rate ⢠All tested variants retain thermal stability.
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Bacillus subtilis , Dominio Catalítico , Lacasa , Simulación del Acoplamiento Molecular , Lacasa/metabolismo , Lacasa/genética , Lacasa/química , Bacillus subtilis/enzimología , Bacillus subtilis/genética , Estabilidad de Enzimas , Cinética , Ácidos Sulfónicos/metabolismo , Catálisis , BenzotiazolesRESUMEN
Chinese traditional fermented sour meat has a unique flavor and nutritional value. The antioxidant activity of sour meat peptides is related to their molecular weights, amino acid compositions, and structural characteristics. Therefore, this study explores the relationships between them. The results indicate that sour meat peptides with molecular weights <1 kDa exhibit significant antioxidant properties both in vitro and in vivo. The smaller the molecular weights, the higher the content of typical amino acids with antioxidant activity (p <0.05), and the characteristic peaks of ultraviolet absorption decrease. The absorption peak at 284.5 nm blue-shifted, and the polarity of the microenvironment increased. The peak intensity and peak area of the Raman characteristic peaks of tyrosine residues and aliphatic amino acids were enhanced. In the secondary structure, there is a high content of ß-turns and a low content of α-helix, which are closely related to the enhancement of antioxidant activity.
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Antioxidantes , Fermentación , Péptidos , Antioxidantes/química , Péptidos/química , Animales , Productos de la Carne/análisis , Peso Molecular , Aminoácidos/química , Estructura Secundaria de Proteína , Ratones , Alimentos Fermentados/análisisRESUMEN
We present CO-Net++, a cohesive framework that optimizes multiple point cloud tasks collectively across heterogeneous dataset domains with a two-stage feature rectification strategy. The core of CO-Net++ lies in optimizing task-shared parameters to capture universal features across various tasks while discerning task-specific parameters tailored to encapsulate the unique characteristics of each task. Specifically, CO-Net++ develops a two-stage feature rectification strategy (TFRS) that distinctly separates the optimization processes for task-shared and task-specific parameters. At the first stage, TFRS configures all parameters in backbone as task-shared, which encourages CO-Net++ to thoroughly assimilate universal attributes pertinent to all tasks. In addition, TFRS introduces a sign-based gradient surgery to facilitate the optimization of task-shared parameters, thus alleviating conflicting gradients induced by various dataset domains. In the second stage, TFRS freezes task-shared parameters and flexibly integrates task-specific parameters into the network for encoding specific characteristics of each dataset domain. CO-Net++ prominently mitigates conflicting optimization caused by parameter entanglement, ensuring the sufficient identification of universal and specific features. Extensive experiments reveal that CO-Net++ realizes exceptional performances on both 3D object detection and 3D semantic segmentation tasks. Moreover, CO-Net++ delivers an impressive incremental learning capability and prevents catastrophic amnesia when generalizing to new point cloud tasks.
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Acquired bronchobiliary fistula (ABBF) is very rare among the complications that occur in patients with hepatocellular carcinoma (HCC) after treatment. Although surgery and drainage have been the main methods for treating ABBF for a long time, they are not entirely suitable for patients with refractory ABBF resulting from HCC therapy. In this study, we present four cases of ABBF caused by HCC treatment, who were treated using selective bronchial occlusion (SBO). Among the 4 patients with ABBF treated with SBO, 3 cases successfully blocked ABBF with SBO, and the treatment success rate was 75%. All successfully treated patients reported disappearance of symptoms of bilioptysis and cough was alleviated. No life-threatening adverse reactions were reported following SBO intervention, and no deaths occurred. We believe that the use of video bronchoscopy to place a self-made silicone plug in the bronchus to treat refractory ABBF is a feasible palliative treatment, which can significantly improve the condition of ABBF patients.
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Aim: To determine the efficacy and safety of pharmacogenomics (PGx)-guided antidepressant prescribing in patients with depression through an umbrella review and updated meta-analysis. Methods: A comprehensive systematic search was conducted on PsycINFO, PubMed, Embase and the Cochrane databases. The pooled effect sizes of randomized controlled trials (RCTs) were expressed as mean differences for continuous data and risk ratios for noncontinuous data. Results: Patients who received PGx-guided medications were 41% to 78% more likely to achieve remission and 20% to 49% more likely to respond to antidepressants than patients receiving treatment-as-usual (TAU). Conclusion: PGx-guided antidepressant prescribing improves the treatment of depression. However, the significance and magnitude of the benefit varies widely between studies and different PGx testing panels. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022321324.
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Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.
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Tejido Adiposo Pardo , Ácidos y Sales Biliares , Metabolismo Energético , Microbioma Gastrointestinal , Síndrome Metabólico , Ratones Endogámicos C57BL , Quercetina , Termogénesis , Quercetina/farmacología , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Metabolismo Energético/efectos de los fármacos , Síndrome Metabólico/metabolismo , Síndrome Metabólico/microbiología , Síndrome Metabólico/tratamiento farmacológico , Masculino , Ácidos y Sales Biliares/metabolismo , Termogénesis/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Modelos Animales de Enfermedad , Trasplante de Microbiota FecalRESUMEN
AIM: To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. METHODS: Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. RESULTS: In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. CONCLUSIONS: In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.
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Diabetes Mellitus Tipo 2 , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Longitudinales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , China/epidemiología , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/complicaciones , Factores de Riesgo , Análisis de la Aleatorización Mendeliana , Encuestas Nutricionales , Adulto , Anciano , Estudios de Cohortes , Estudio de Asociación del Genoma CompletoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.
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OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.
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Cuerpo Estriado , Ferroptosis , Ratones Endogámicos C57BL , Moxibustión , Neuronas , Enfermedad de Parkinson , Animales , Ferroptosis/genética , Ratones , Cuerpo Estriado/metabolismo , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Masculino , Humanos , Neuronas/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Regulación hacia Abajo , Actividad Motora , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. METHODS: This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People's Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. RESULTS: 702 EEC patients with stage I and grade 1-2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). CONCLUSIONS: LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.
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Carcinoma Endometrioide , Neoplasias Endometriales , Invasividad Neoplásica , Estadificación de Neoplasias , Humanos , Femenino , Estudios Retrospectivos , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/cirugía , Persona de Mediana Edad , Pronóstico , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/terapia , Tasa de Supervivencia , Estudios de Seguimiento , China/epidemiología , Histerectomía/estadística & datos numéricos , Histerectomía/métodos , Clasificación del Tumor , Anciano , Metástasis Linfática , Vasos Linfáticos/patología , Adulto , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Pueblos del Este de AsiaRESUMEN
AIM: To report a one-year clinical outcomes of low-dose laser cycloplasty (LCP) among malignant glaucoma patients. METHODS: In this prospective, multicenter, non-comparative clinical study, participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China. Patients were followed up at 1wk, 1, 3, 6, and 12mo. Intraocular pressure (IOP), number of glaucoma medications, anterior chamber depth (ACD), and complications were recorded. Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy. Recurrence was defined by the presence of a shallow or ï¬at anterior chamber after initial recovery from treatment. RESULTS: A total of 34 eyes received LCP. Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg (P<0.001) with 2.9±1.6 medications (P=0.046) at 1d, and 17.4±6.7 mm Hg (P<0.001) with 1.3±1.7 medications (P<0.001) at 12mo. The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo, respectively. A total of 32 (94.1%) eyes achieved initial anatomical success. During follow-up, 2 (5.9%) eyes failed and 8 (23.5%) eyes relapsed, yielding a 12-month anatomical success rate of 64.3%. Complications including anterior synechia (8.82%), choroidal/ciliary detachment (5.88%) and hypopyon (2.94%) were observed within 1wk. CONCLUSION: LCP is simple, safe, and effective in reforming the anterior chamber in malignant glaucoma.