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2.
J Adv Res ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615741

RESUMO

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women with unfavorite prognosis. OBJECTIVES: Tanshinone IIA (Tan IIA) inhibits BC progression, however, the underlying mechanism remains largely undefined. METHODS: The cytotoxicity of Tan IIA was assessed by CCK-8 and LDH assays. Ferroptosis was monitored by the level of MDA, Fe2+, lipid ROS and GSH. IHC and western blot were employed to detect the localization and expression of SLC7A11, PIAS4, KDM1A and other key molecules. The SUMOylation of SLC7A11 was detected by Ni-beads pull-down assay and Co-IP. Luciferase and ChIP assays were employed to detect the direct association between KDM1A and PIAS4 promoter. The proliferative and metastatic properties of BC cells were assessed by colony formation, CCK-8 and Transwell assays, respectively. The in vitro findings were verified in xenograft and lung metastasis models. RESULTS: Tan IIA promoted ferroptosis by suppressing SLC7A11 in BC cells. Silencing of PIAS4 or KDM1A inhibited cell growth and metastasis in BC. Mechanistically, PIAS4 facilitated the SUMOylation of SLC7A11 via direct binding to SLC7A11, and KDM1A acted as a transcriptional activator of PIAS4. Functional studies further revealed that Tan IIA decreased KDM1A expression, thus suppressing PIAS4 expression transcriptionally. The inhibition of PIAS4-dependent SUMOylation of SLC7A11 further induced ferroptosis, thereby inhibiting proliferation and metastasis in BC. CONCLUSION: Tan IIA promoted ferroptosis and inhibited tumor growth and metastasis via suppressing KDM1A/PIAS4/SLC7A11 axis.

3.
World J Clin Cases ; 12(10): 1793-1798, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38660069

RESUMO

BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.

4.
J Adv Res ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636588

RESUMO

INTRODUCTION: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. OBJECTIVES: Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. METHODS AND RESULTS: Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. CONCLUSION: Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.

6.
Med ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38608709

RESUMO

Chimeric antigen receptor (CAR) T cells have made a groundbreaking advancement in personalized immunotherapy and achieved widespread success in hematological malignancies. As CAR technology continues to evolve, numerous studies have unveiled its potential far beyond the realm of oncology. This review focuses on the current applications of CAR-based cellular platforms in non-neoplastic indications, such as autoimmune, infectious, fibrotic, and cellular senescence-associated diseases. Furthermore, we delve into the utilization of CARs in non-T cell populations such as natural killer (NK) cells and macrophages, highlighting their therapeutic potential in non-neoplastic conditions and offering the potential for targeted, personalized therapies to improve patient outcomes and enhanced quality of life.

7.
EJHaem ; 5(2): 333-345, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38633121

RESUMO

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukaemia (ALL) and is associated with favorable outcomes, especially in low-risk children. However, as many as 10% of children relapse within 3 years, and such early relapses have poor survival. Identifying children at risk for early relapse is an important challenge. We interrogated data from 87 children with low-risk ETV6::RUNX1-positive B-cell ALL and with available preserved bone marrow samples (discovery cohort). We profiled somatic point mutations in a panel of 559 genes and genome-wide transcriptome and single-nucleotide variants. We found high TIMD4 expression (> 85th-percentile value) at diagnosis was the most important independent prognostic factor of early relapse (hazard ratio [HR] = 5.07 [1.76, 14.62]; p = 0.03). In an independent validation cohort of low-risk ETV6::RUNX1-positive B-cell ALL (N = 68) high TIMD4 expression at diagnosis had an HR = 4.78 [1.07, 21.36] (p = 0.04) for early relapse. In another validation cohort including 78 children with low-risk ETV6::RUNX1-negative B-cell ALL, high TIMD4 expression at diagnosis had an HR = 3.93 [1.31, 11.79] (p = 0.01). Our results suggest high TIMD4 expression at diagnosis in low-risk B-cell ALL in children might be associated with high risk for early relapse.

8.
Ann Med ; 56(1): 2338604, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38599340

RESUMO

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.


There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Plasmócitos/patologia , Prognóstico , Biomarcadores , Modelos de Riscos Proporcionais
9.
Sci Rep ; 14(1): 8227, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589462

RESUMO

Colorectal cancer (CRC) patients who receive cancer surgeries from higher-volume providers may have better outcomes. However, the definitions of surgical volume may affect the results. We aim to analyze the effects of different definitions of surgical volume on patient outcomes. We conducted a nationwide population-based study in Taiwan that enrolled all patients who underwent definitive surgery for newly diagnosed CRC. We used three common definitions of surgical volume: total volume means the total surgical number conducted by the same provider during the study period; cumulative volume was calculated as the number of operations the surgeon performed before the index procedure; annual volume was calculated as the number of times the surgeon had been responsible for surgery during the index year. In this study, we included 100,009 newly diagnosed CRC patients, including 55.8% males, of median age 66 years at diagnosis (range 20-105 years). After adjustment for the patient and provider characteristics, we found that CRC patients receiving definitive surgery by higher-volume providers had better outcomes, especially where surgeon volume may play a more important role than hospital volume. The cumulative volume could predict the 5-year mortality of the study cohort better than the total and annual volume.


Assuntos
Neoplasias Colorretais , Hospitais , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Taiwan/epidemiologia
11.
J Pharm Anal ; 14(2): 211-224, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38464783

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

12.
Int Urol Nephrol ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436825

RESUMO

PURPOSE: The objective of this study is to investigate the associated risk factors of pulmonary infection in individuals diagnosed with chronic kidney disease (CKD). The primary goal is to develop a predictive model that can anticipate the likelihood of pulmonary infection during hospitalization among CKD patients. METHODS: This retrospective cohort study was conducted at two prominent tertiary teaching hospitals. Three distinct models were formulated employing three different approaches: (1) the statistics-driven model, (2) the clinical knowledge-driven model, and (3) the decision tree model. The simplest and most efficient model was obtained by comparing their predictive power, stability, and practicability. RESULTS: This study involved a total of 971 patients, with 388 individuals comprising the modeling group and 583 individuals comprising the validation group. Three different models, namely Models A, B, and C, were utilized, resulting in the identification of seven, four, and eleven predictors, respectively. Ultimately, a statistical knowledge-driven model was selected, which exhibited a C-statistic of 0.891 (0.855-0.927) and a Brier score of 0.012. Furthermore, the Hosmer-Lemeshow test indicated that the model demonstrated good calibration. Additionally, Model A displayed a satisfactory C-statistic of 0.883 (0.856-0.911) during external validation. The statistical-driven model, known as the A-C2GH2S risk score (which incorporates factors such as albumin, C2 [previous COPD history, blood calcium], random venous blood glucose, H2 [hemoglobin, high-density lipoprotein], and smoking), was utilized to determine the risk score for the incidence rate of lung infection in patients with CKD. The findings revealed a gradual increase in the occurrence of pulmonary infections, ranging from 1.84% for individuals with an A-C2GH2S Risk Score ≤ 6, to 93.96% for those with an A-C2GH2S Risk Score ≥ 18.5. CONCLUSION: A predictive model comprising seven predictors was developed to forecast pulmonary infection in patients with CKD. This model is characterized by its simplicity, practicality, and it also has good specificity and sensitivity after verification.

13.
Huan Jing Ke Xue ; 45(3): 1692-1701, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471881

RESUMO

In rice-vegetable rotation systems in tropical areas, a large amount of nitrate nitrogen accumulates after fertilization in the melon and vegetable season, which leads to the leaching of nitrate nitrogen and a large amount of N2O emission after the seasonal flooding of rice, which leads to nitrogen loss and intensification of the greenhouse effect. How to improve the utilization rate of nitrate nitrogen and reduce N2O emissions has become an urgent problem to be solved. Six treatments were set up [200 mg·kg-1 KNO3 (CK); 200 mg·kg-1 KNO3 + 2% biochar addition (B); 200 mg·kg-1 KNO3+1% peanut straw addition (P); 200 mg·kg-1 KNO3 + 2% biochar + 1% peanut straw addition (P+B); 200 mg·kg-1 KNO3 + 1% rice straw addition (R); 200 mg·kg-1 KNO3 + 2% biochar+1% rice straw addition (R+B)] and cultured at 25℃ for 114 d to explore the effects of organic material addition on greenhouse gas emissions and nitrogen use after flooding in high nitrate nitrogen soil. The results showed that compared with that in CK, adding straw or combining straw with biochar significantly increased soil pH (P<0.05). The B and P treatments significantly increased the cumulative N2O emissions by 41.6% and 28.5% (P<0.05), and the P+B, R, and R+B treatments significantly decreased the cumulative N2O emissions by 14.1%, 24.7%, and 36.7% (P<0.05), respectively. The addition of straw increased the net warming potential of greenhouse gases (NGWP). The addition of coir biochar significantly reduced the effect of straw on NGWP (P<0.05). The combined application of straw and biochar decreased NGWP, and P+B significantly decreased NGWP, but that with R+B was not significant (P>0.05). Adding straw or biochar significantly increased soil microbial biomass carbon (MBC) (P<0.05), and that of P+B was the highest (502.26 mg·kg-1). The combined application of straw and biochar increased soil microbial biomass nitrogen (MBN), and that of P+B was the highest. The N2O emission flux was negatively correlated with pH (P<0.01) and positively correlated with NH4+-N and NO3--N (P<0.01). The cumulative emission of N2O was negatively correlated with MBN (P<0.05). There was a significant negative correlation between NO3--N and MBN (P<0.01), indicating that the reduction in NO3--N was likely to be held by microorganisms, and the increase in the microbial hold of NO3--N also reduced N2O emission. In conclusion, the combined application of peanut straw and coconut shell biochar could significantly inhibit N2O emission and increase soil MBC and MBN, which is a reasonable measure to make full use of nitrogen fertilizer, reduce nitrogen loss, and slow down N2O emission after the season of Hainan vegetables.


Assuntos
Gases de Efeito Estufa , Oryza , Solo/química , Gases de Efeito Estufa/análise , Verduras , Agricultura/métodos , Nitratos , Nitrogênio , Óxido Nitroso/análise , Carvão Vegetal , China , Fertilizantes
14.
J Chin Med Assoc ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478012

RESUMO

BACKGROUND: Pancreatic adenocarcinoma is often not diagnosed until an advanced stage, and so most patients are not eligible for resection. For patients who are inoperable, definitive radiotherapy is crucial for local disease control. However, the pancreas is located close to other vulnerable gastrointestinal organs, making it challenging to deliver an adequate radiation dose. The surgical insertion of spacers or injection of fluids such as hydrogel before radiotherapy has been proposed, however no study has discussed which patients are suitable for the procedure. METHODS: In this study, we reviewed 50 consecutive patients who received definitive radiotherapy at our institute to determine how many could have benefitted from hydrodissection to separate the pancreatic tumor from the adjacent gastrointestinal tract. By hypothetically injecting a substance using either computed tomography (CT)-guided or endoscopic methods, we aimed to increase the distance between the pancreatic tumor and surrounding hollow organs, as this would reduce the radiation dose delivered to the organs at risk. RESULTS: An interventional radiologist considered that hydrodissection was feasible in 23 (46%) patients with a CT-guided injection, while a gastroenterologist considered that hydrodissection was feasible in 31 (62%) patients with an endoscopic injection. Overall, we found 14 (28%) discrepancies among the 50 patients reviewed. Except for one patient who had no available trajectory with a CT-guided approach but in whom hydrodissection was considered feasible with an endoscopic injection, the other 13 patients had different interpretations of whether direct invasion was present in the CT images. CONCLUSION: Our results suggested that about half of the patients could have benefited from hydrodissection prior to radiotherapy. This finding could allow for a higher radiation dose and potentially better disease control.

15.
BMC Health Serv Res ; 24(1): 326, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475797

RESUMO

BACKGROUND: In the past 40 years, China has experienced tremendous economic development, but the current situation of hematologists has rarely been reported. A landscape survey of human resources is essential for healthcare development and policy formulation in the future. METHODS: The Chinese Society of Hematology initiated a survey of Chinese hematologists in mainland China for evaluating demographic and practice characteristics. Respondents were anonymous, and there were no limitations regarding their age, sex, etc. RESULTS: Totally 2032 hematologists responded, with a median age bracket of 36-45 years. Respondents were well engaged into subspecialties, and 28.1% acquired doctorates of philosophy. Hematopoietic cell transplantation (HCT) centers have been established all over China. Higher-GDP regions reported more advantages, including bigger scale of transplant centers (P < 0.001), younger age structure (P = 0.039), better education qualifications (P = 0.001) and less turnover intentions (P = 0.004), despite of increased risk of medical disputes (P = 0.028). Although females accounted for 65.5% of hematologists, males were older (P < 0.001), and had more senior professional titles (P < 0.001), academic positions (P < 0.001), opportunities for continuing education (P < 0.001), and paper publishing in the recent two years (P = 0.001). For turnover intention, the higher GDP regions led to an independently reduced risk (HR = 0.673, 95%CI [0.482-0.940], P = 0.020), whereas medical disputes resulted in an increased the risk (HR = 2.037, 95%CI [1.513-2.743], P < 0.001). Considering the impact of the COVID-19 pandemic, majority of respondents believed that the decline in patient visits and delay in treatment was within 30%. 67.9% of respondents reported a decrease of the use of bone marrow as grafts but 18.8% reported an increase of cord blood units. 35.0% of the respondents switched their daily work to support the anti-epidemic medical activities. CONCLUSIONS: We concluded the discipline of hematology in China has flourished in recent years with a young workforce, while regional economic and gender disparities warrant further continuous optimization. Joint efforts against the impact of COVID-19 are needed in the post-pandemic era.


Assuntos
COVID-19 , Hematologia , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Pandemias , Inquéritos e Questionários , Atenção à Saúde , Serviços de Saúde
16.
Biochem Biophys Res Commun ; 707: 149513, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38508051

RESUMO

Cancer is a significant global health concern, and finding effective methods to treat it has been a focus of scientific research. It has been discovered that the growth, invasion, and metastasis of tumors are closely related to the environment in which they exist, known as the tumor microenvironment (TME). The immune response interacting with the tumor occurring within the TME constitutes the tumor immune microenvironment, and the immune response can lead to anti-tumor and pro-tumor outcomes and has shown tremendous potential in immunotherapy. A channel called the P2X7 receptor (P2X7R) has been identified within the TME. It is an ion channel present in various immune cells and tumor cells, and its activation can lead to inflammation, immune responses, angiogenesis, immunogenic cell death, and promotion of tumor development. This article provides an overview of the structure, function, and pharmacological characteristics of P2X7R. We described the concept and components of tumor immune microenvironment and the influence immune components has on tumors. We also outlined the impact of P2X7R regulation and how it affects the development of tumors and summarized the effects of drugs targeting P2X7R on tumor progression, both past and current, assisting researchers in treating tumors using P2X7R as a target.


Assuntos
Neoplasias , Receptores Purinérgicos P2X7 , Microambiente Tumoral , Humanos , Neoplasias/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Animais
17.
Front Immunol ; 15: 1346211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464531

RESUMO

Multiple myeloma is the second most common malignant hematologic malignancy which evolved different strategies for immune escape from the host immune surveillance and drug resistance, including uncontrolled proliferation of malignant plasma cells in the bone marrow, genetic mutations, or deletion of tumor antigens to escape from special targets and so. Therefore, it is a big challenge to efficiently treat multiple myeloma patients. Despite recent applications of immunomodulatory drugs (IMiDS), protease inhibitors (PI), targeted monoclonal antibodies (mAb), and even hematopoietic stem cell transplantation (HSCT), it remains hardly curable. Summarizing the possible evasion strategies can help design specific drugs for multiple myeloma treatment. This review aims to provide an integrative overview of the intrinsic and extrinsic evasion mechanisms as well as recently discovered microbiota utilized by multiple myeloma for immune evasion and drug resistance, hopefully providing a theoretical basis for the rational design of specific immunotherapies or drug combinations to prevent the uncontrolled proliferation of MM, overcome drug resistance and improve patient survival.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Medula Óssea/patologia , Anticorpos Monoclonais/uso terapêutico , Plasmócitos/patologia , Imunoterapia
18.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38473759

RESUMO

Osteoarthritis (OA) causes joint pain and disability due to the abnormal production of inflammatory cytokines and reactive oxygen species (ROS) in chondrocytes, leading to cell death and cartilage matrix destruction. Selenium (Se) intake can protect cells against oxidative damage. It is still unknown whether Se supplementation is beneficial for OA. This study investigated the effects of Se on sodium iodoacetate (MIA)-imitated OA progress in human chondrocyte cell line (SW1353 cells) and rats. The results showed that 0.3 µM of Se treatment could protect SW1353 cells from MIA-induced damage by the Nrf2 pathway by promoting the gene expression of glutathione-synthesis-related enzymes such as the glutamate-cysteine ligase catalytic subunit, the glutamate-cysteine ligase modifier subunit, and glutathione synthetase. In addition, glutathione, superoxide dismutase, glutathione peroxidase, and glutathione reductase expressions are also elevated to eliminate excessive ROS production. Moreover, Se could downregulate NF-κB, leading to a decrease in cytokines, matrix proteases, and glycosaminoglycans. In the rats, MIA-induced cartilage loss was lessened after 2 weeks of Se supplementation by oral gavage; meanwhile, glutathione synthesis was increased, and the expressions of pro-inflammatory cytokines were decreased. These results suggest that Se intake is beneficial for OA due to its effects of decreasing cartilage loss by enhancing antioxidant capacity and reducing inflammation.


Assuntos
Cartilagem Articular , Osteoartrite , Selênio , Humanos , Ratos , Animais , NF-kappa B/metabolismo , Condrócitos/metabolismo , Selênio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Glutamato-Cisteína Ligase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Osteoartrite/metabolismo , Estresse Oxidativo , Citocinas/metabolismo , Glutationa/metabolismo , Cartilagem Articular/metabolismo
19.
Eur J Pharmacol ; 968: 176368, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316246

RESUMO

Spinal cord injury (SCI) is a traumatic neuropathic condition that results in motor, sensory and autonomic dysfunction. Mitochondrial dysfunction caused by primary trauma is one of the critical pathogenic mechanisms. Moderate levels of zinc have antioxidant effects, promote neurogenesis and immune responses. Zinc normalises mitochondrial morphology in neurons after SCI. However, how zinc protects mitochondria within neurons is unknown. In the study, we used transwell culture, Western blot, Quantitative Real-time Polymerase Chain Reaction (QRT-PCR), ATP content detection, reactive oxygen species (ROS) activity assay, flow cytometry and immunostaining to investigate the relationship between zinc-treated microglia and injured neurons through animal and cell experiments. We found that zinc promotes mitochondrial transfer from microglia to neurons after SCI through Sirtuin 3 (SIRT3) regulation of Mitofusin 2 protein (Mfn2). It can rescue mitochondria in damaged neurons and inhibit oxidative stress, increase ATP levels and promote neuronal survival. Therefore, it can improve the recovery of motor function in SCI mice. In conclusion, our work reveals a potential mechanism to describe the communication between microglia and neurons after SCI, which may provide a new idea for future therapeutic approaches to SCI.


Assuntos
Sirtuína 3 , Traumatismos da Medula Espinal , Camundongos , Animais , Medula Espinal/metabolismo , Sirtuína 3/metabolismo , Zinco/metabolismo , Traumatismos da Medula Espinal/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , GTP Fosfo-Hidrolases/metabolismo
20.
Int J Mol Sci ; 25(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38338784

RESUMO

Kiwiberry (Actinidia arguta) is a perennial fruit tree belonging to the family Actinidiaceae. Kiwiberries are known to have an extremely high concentration of sugars, phenolics, flavonoids, and vitamin C, and possess delicious taste and health-promoting properties. Numerous studies have focused on kiwiberry fruits, demonstrating that they possess a higher phytochemical content and greater antioxidant activities than other berry fruits. The purpose of this study was to compare the phytochemical content and antioxidant potential of leaf, stem, root, and fruit extracts from twelve kiwiberry cultivars grown in Wonju, Korea, characterized by a Dwa climate (Köppen climate classification). In most kiwiberry cultivars, the total phenolic (TPC) and total flavonoid (TFC) phytochemical content was significantly higher in leaf and stem tissues, while the roots exhibited higher antioxidant activity. In fruit tissues, the TPC and TFC were higher in unripe and ripe kiwiberry fruits, respectively, and antioxidant activity was generally higher in unripe than ripe fruit across most of the cultivars. Based on our results, among the 12 kiwiberry cultivars, cv. Daebo and cv. Saehan have a significantly higher phytochemical content and antioxidant activity in all of the tissue types, thus having potential as a functional food and natural antioxidant.


Assuntos
Actinidia , Antioxidantes , Antioxidantes/química , Extratos Vegetais/química , Ácido Ascórbico/análise , Fenóis/análise , Frutas/química , Flavonoides/análise , Compostos Fitoquímicos/química
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