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Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.
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Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Disbiose/metabolismo , Disbiose/microbiologia , Disbiose/imunologia , Humanos , Camundongos , Masculino , Feminino , Animais , Doença de Depósito de Glicogênio Tipo I/metabolismo , Doença de Depósito de Glicogênio Tipo I/genética , Doença de Depósito de Glicogênio Tipo I/complicações , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologiaRESUMO
BACKGROUND: Mitochondrial dysfunction is key to the pathogenesis of vascular dementia (VaD). Sirtuin-3 (SIRT3), an essential member of the sirtuins family, has been proven to be a critical sirtuin in regulating mitochondrial function. The phenolic glucoside gastrodin (GAS), a bioactive ingredient from Gastrodiae Rhizome (known in Chinese as Tian ma) demonstrates significant neuroprotective properties against central nervous system disorders; however, the precise mechanisms through which GAS modulates VaD remain elusive. PURPOSE: This study aims to investigate whether GAS confers a protective role against VaD, and to figure out the underlying molecular mechanisms. METHODS: A bilateral common carotid artery occlusion (BCCAO)-mediated chronic cerebral hypoperfusion (CCH) VaD rat model and a hypoxia model using HT22 cells were employed to investigate pharmacological properties of GAS in mitigating mitochondrial dysfunction. A SIRT3 agonist resveratrol (RES), a SIRT3 inhibitor 3-TYP and SIRT3-knockdown in vitro were used to explore the mechanism of GAS in association with SIRT3. The ability of SIRT3 to bind and deacetylate mitochondrial transcription factor A (TFAM) was detected by immunoprecipitation assay, and TFAM acetylation sites were further validated using mass spectrometry. RESULTS: GAS increased SIRT3 expression and ameliorated mitochondrial structure, mitochondrial respiration, mitochondrial dynamics along with upregulated TFAM, mitigating oxidative stress and senescence. Comparable results were noted with the SIRT3 agonist RES, indicating an impactful neuroprotection played by SIRT3. Specifically, the attenuation of SIRT3 expression through knockdown techniques or exposure to the SIRT3 inhibitor 3-TYP in HT22 cells markedly abrogated GAS-mediated mitochondrial rescuing function. Furthermore, our findings elucidate a novel facet: SIRT3 interacted with and deacetylated TFAM at the K5, K7, and K8 sites. Decreased SIRT3 is accompanied by hyper-acetylated TFAM. CONCLUSION: The present results were the first to demonstrate that the SIRT3/TFAM pathway is a protective target for reversing mitochondrial dysfunction in VaD. The findings suggest that GAS-mediated modulation of the SIRT3/TFAM pathway, a novel mechanism, could ameliorate CCH-induced VaD, offering a potentially beneficial therapeutic strategy for VaD.
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Álcoois Benzílicos , Demência Vascular , Glucosídeos , Mitocôndrias , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Sirtuína 3 , Sirtuínas , Animais , Glucosídeos/farmacologia , Demência Vascular/tratamento farmacológico , Sirtuína 3/metabolismo , Álcoois Benzílicos/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Masculino , Acetilação , Fármacos Neuroprotetores/farmacologia , Camundongos , Fatores de Transcrição/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Ratos , Modelos Animais de Doenças , Linhagem Celular , Resveratrol/farmacologia , Gastrodia/químicaRESUMO
Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.
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Ferro , Neoplasias , Humanos , Morte Celular , Ferro/metabolismo , Ferritinas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Lisossomos/metabolismoRESUMO
BACKGROUND: Intense pulsed light (IPL) is used for the treatment and improvement of various skin issues. However, patients often experience local skin burning and pain after IPL treatment. Cooling and analgesic measures are indispensable. AIMS: To investigate the clinical effect of thermal shock therapy on pain relief and reduction of adverse reactions during IPL therapy. PATIENTS/METHODS: A total of 60 female patients with facial photoaging who received IPL therapy were enrolled in the study. As a comparative split-face study, one side of the face was randomly selected as the control side. The other side was given thermal shock therapy before and after the IPL treatment immediately as analgesic side. The visual analog scale (VAS) was used to evaluate the pain degree of the patients. The telephone follow-ups regarding the occurrence of adverse reactions were conducted respectively on the 2nd day, 7th day, and 1 month after treatment. RESULTS: The VAS score and skin temperature of analgesia side was lower than that of control side at different stages of treatment. In terms of adverse reactions, the incidence of transient facial redness on the analgesic side was lower than that on the control side. Two patients showed slight secondary pigmentation on the control side, and the other patients showed no other adverse reactions on both sides. CONCLUSIONS: Thermal shock therapy assisted IPL therapy can reduce skin temperature during treatment, effectively relieve patients' pain, reduce the occurrence of adverse reactions caused by heat injury, and improve patients' comfort level.
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Terapia de Luz Pulsada Intensa , Medição da Dor , Humanos , Feminino , Terapia de Luz Pulsada Intensa/efeitos adversos , Terapia de Luz Pulsada Intensa/métodos , Pessoa de Meia-Idade , Adulto , Envelhecimento da Pele/efeitos da radiação , Temperatura Cutânea , Face , Manejo da Dor/métodos , Manejo da Dor/efeitos adversos , Resultado do Tratamento , Dor Processual/etiologia , Dor Processual/prevenção & controle , Dor Processual/diagnóstico , Dor Processual/terapiaRESUMO
The aim of this study was to explore the effect and mechanism of Sirt6 on DNA damage repair in OA chondrocytes. Cartilage tissues were collected from OA patients with knee arthroplasty and traumatic amputation patients without OA. Besides, 7-week-old male C57BL/6 mice were randomly divided into Control and OA groups; CHON-001 cells of corresponding groups were treated with 10 ng/ml interleukin (IL)-1ß, respectively. Subsequently, Sirt6 or siNrf2 was over-expressed in CHON-001 cells to observe the effect of Sirt6 on DNA damage and senescence of chondrocytes by IL-1ß through the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. The expression level of Sirt6 in human and mouse OA cartilage tissues was significantly decreased. However, 24 h of treatment with IL-1ß significantly decreased the expression of Sirt6 in chondrocytes, induced DNA damage, and promoted cellular senescence. In addition, over-expression of Sirt6 promoted DNA damage repair and inhibited cellular senescence in IL-1ß-induced chondrocytes. Moreover, the overexpression of Sirt6 activated the Keap1/Nrf2/HO-1 signaling pathway in chondrocytes, while knockdown of Nrf2 expression inhibited the DNA damage repair and anti-senescence effects of Sirt6 on IL-1ß-treated chondrocytes. Sirt6 may reduce DNA damage and cellular senescence in OA chondrocytes induced by IL-1ß through activating the Keap1/Nrf2/HO-1 signaling pathway.
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Condrócitos , Reparo do DNA , Osteoartrite , Transdução de Sinais , Sirtuínas , Animais , Humanos , Masculino , Camundongos , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , Senescência Celular/genética , Condrócitos/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Dano ao DNA , Reparo do DNA/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Osteoartrite/patologia , Osteoartrite/metabolismo , Sirtuínas/metabolismo , Sirtuínas/genéticaRESUMO
PURPOSE: To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between groups were compared. RESULTS: Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC-PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC-PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression-free survival (median progression-free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC-PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC-PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression-free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival. CONCLUSION: The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Infusões Intra-Arteriais , Neoplasias Hepáticas , Pontuação de Propensão , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Idoso , Artéria Hepática , Adulto , Intervalo Livre de Progressão , Resultado do TratamentoRESUMO
In this research, the degradation of different types of N-containing heterocycle (NHC) contaminants by Cu-OMS-2 via peroxymonosulfate (PMS) activation in an aqueous environment was investigated. First, the effects of different reaction parameters were optimized using benzotriazole (BTR) as the model contaminant, and the optimal reaction conditions were 8 mM PMS, 0.35 g/L Cu-OMS-2, and 30 °C. Nine different types of NHC contaminants were effectively degraded under these reaction conditions, and the degradation efficiencies and the mineralization rates of those NHCs were more than 68 and 46%, respectively. Moreover, the Cu-OMS-2/PMS process presented excellent performance at a wide pH ranging from 3.0 to 11.0 and in the presence of some representative anions (NO3- and SO42-) and dissolved organic matter (fumaric acid). The inhibition sequence of anions on BTR removal during the Cu-OMS-2/PMS process was H2PO4- > HCO3- > Cl- > CO32- > NO3- > SO42-. It was also found that 74.5 and 71.3% BTR degradation rates were achieved in actual water bodies, such as tap water and Yellow River water, respectively. Besides, the Cu-OMS-2 heterogeneous catalyst had excellent stability and reusability, and the degradation rate of BTR was still at 77.0% after 5 cycles. Finally, electron paramagnetic resonance analysis and scavenging tests showed that 1O2 and SO4-â¯â¢ were the primary reactive oxygen species. Accordingly, Cu-OMS-2 nanomaterial was an efficient and sustainable heterogeneous catalyst to activate PMS for the decontamination of BTR in water remediation.
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The lifting operation of offshore pipelines is an important step in ocean pipeline engineering. An effective analytical method is developed for investigating the mechanical properties of the pipeline based on mechanical, physical, and geometric relationships. By using the shooting and the secant methods to transform the boundary value problem into an initial value one and then solving them with the Runge-Kutta method, the deformation and mechanical properties of the pipeline are calculated. Furthermore, based on the Det Norske Veritas (DNV) offshore standard, the mechanical properties of the pipeline are checked. The finite element method (FEM) by Orcaflex is employed to verify the accuracy of the analytical model. The effects of some factors such as the current velocity and lifting point position on the mechanical properties of the pipeline are analyzed based on the analytical model. The results indicate that the change in current velocity during the lifting process has a minimal effect on the pipeline, but the change in lifting point position significantly affects the deformation and mechanical properties of the pipeline.
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Objective: Creatine kinase (CK) and its myocardial band isoenzyme (CK-MB) were considered important diagnostic indicators for identifying suspected acute myocardial infarction. However, the serum level of CK-MB is frequently exaggerated in some pathological states without cardiogenic damage, like cancer. Sometimes, the CK-MB level is even greater than the total CK. This study intended to investigate the association between malignancy and an abnormally high ratio of CK-MB to total CK (CK-MB/CK) and to assess the diagnostic relevance of this ratio as a biomarker for cancer. Methods: Patients hospitalized between September 2019 and September 2022 at Shandong Provincial Qianfoshan Hospital (Jinan, Shandong, China) with serum CK-MB activity greater than total CK activity (CK-MB/CK > 1.0) were recruited as research subjects. Then the demographic and clinical characteristics of these patients were systemically analyzed. The correlation between clinical characteristics (such as cancer types, tumor locations, and tumor metastasis) and laboratory test results (such as serum CK-MB activity, total CK activity, and the CK-MB/CK ratio) was also investigated. Results: We found that over 44% of the patients with CK-MB/CK > 1.0 were diagnosed with malignancies, and the CK-MB/CK ratio in malignancies patients was significantly higher than in non-malignancies patients. The increase of CK-MB/CK ratio was most obvious in patients with colorectal carcinoma and prostatic carcinoma. Additionally, extremely elevated CK-MB/CK ratios were observed in individuals with metastatic neoplasms, especially in those who suffered from numerous sites of metastasis. Conclusions: The serum CK-MB/CK ratio can be utilized as a readily accessible supplement diagnostic biomarker in screening for primary and metastatic cancers.
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BACKGROUND: The risk factors for mortality might differ between patients with acute exacerbation of chronic pulmonary heart disease in plains and plateaus, while there is a lack of evidence. METHOD: Patients diagnosed with cor pulmonale at Qinghai Provincial People's Hospital were retrospectively included between January 2012 and December 2021. The symptoms, physical and laboratory examination findings, and treatments were collected. Based on the survival within 50 days, we divided the patients into survival and death groups. RESULTS: After 1:10 matching according to gender, age, and altitude, 673 patients were included in the study, 69 of whom died. The multivariable Cox proportional hazards analysis showed that NYHA class IV (HR = 2.03, 95%CI: 1.21-3.40, P = 0.007), type II respiratory failure (HR = 3.57, 95%CI: 1.60-7.99, P = 0.002), acid-base imbalance (HR = 1.82, 95%CI: 1.06-3.14, P = 0.031), C-reactive protein (HR = 1.04, 95%CI: 1.01-1.08, P = 0.026), and D-dimer (HR = 1.07, 95%CI: 1.01-1.13, P = 0.014) were risk factors for death in patients with cor pulmonale at high altitude. Among patients living below 2500 m, cardiac injury was a risk factor for death (HR = 2.47, 95%CI: 1.28-4.77, P = 0.007), while no significant association was observed at ≥ 2500 m (P = 0.057). On the contrary, the increase of D-dimer was only a risk factor for the death of patients living 2500 m and above (HR = 1.23, 95% CI: 1.07-1.40, P = 0.003). CONCLUSION: NYHA class IV, type II respiratory failure, acid-base imbalance, and C- reactive protein may increase the risk of death in patients with cor pulmonale. Altitude modified the association between cardiac injury, D-dimer, and death in patients with cor pulmonale.
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Doença Cardiopulmonar , Fatores de Risco , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Doença Cardiopulmonar/epidemiologiaRESUMO
Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated P62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/AKT pathway-related proteins expression, which regulates autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive autophagy and apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/AKT pathway-mediated autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.
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Disfunção Cognitiva , Demência Vascular , Fármacos Neuroprotetores , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Demência Vascular/tratamento farmacológico , Demência Vascular/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Autofagia , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Disfunção Cognitiva/metabolismo , Hipóxia/tratamento farmacológicoRESUMO
To investigate efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib (HAIC-Len) and HAIC alone for the treatment of advanced hepatocellular carcinoma (Ad-HCC). Totally 349 patients with Ad-HCC participated in the research from February 2018 to October 2020. On the basis of propensity score matching (PSM), 132 and 110 cases were assigned to the HAIC group and the HAIC-Len group, respectively, with a ratio of 1:1. Progression-free survival (PFS), overall survival (OS), and complications were compared between two groups. The Kaplan-Meier method and log-rank test were utilized to estimate cumulative OS and PFS. Additionally, uni- and multi-variate Cox regression models were employed to identify significant independent factors. The median follow-up period in this study was set to be 20.8 months. Following PSM, the one-, two- and three-year cumulative OS rates in the HAIC-Len and HAIC groups were 63.6%, 12.1%, and 3.0%, and 47.2%, 11.8%, and 2.7%, respectively, with a significant difference (P < 0.001). The first-three-year cumulative incidence rates PFS in the HAIC-Len and the HAIC groups were 15.2%, 1.5%, and ND, and 11.8%, 4.5%, and 3.6%, respectively, with no significant difference detected (P = 0.092). BMI (HR 0.709. 95% CI 0.549, 0.915. P = 0.008) and AST (HR 1.005. 95% CI 1.003, 1.007. P < 0.001) represented independent prognostic factors for OS. Additionally, the two groups exhibited no significant difference in the incidence rates of adverse events. HAIC-Len significantly improved survival outcomes of patients with Ad-HCC and demonstrated acceptable toxicity compared to HAIC alone.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Infusões Intra-ArteriaisRESUMO
Background: The results of previous clinical trials evaluating the efficacy and safety of recombinant human interleukin-2 (rhuIL-2) for adult patients with pulmonary tuberculosis showed inconsistent results. Accordingly, a comprehensive systematic review and meta-analysis was performed. Methods: Relevant randomized controlled trials (RCTs) were retrieved by searching the PubMed, Embase, Cochrane's Library, Web of Science, Wanfang, and CNKI databases. A random-effects model was used to combine the results. Results: 18 RCTs with 2630 patients were included in this meta-analysis. Pooled results showed that adjunctive rhuIL-2 significantly increased the odds of sputum culture conversion to negative (risk ratio [RR]: 1.27, 95% CI: 1.09 to 1.47, p=0.002, I 2 = 80%), sputum smear conversion to negative (RR: 1.35, 95% CI: 1.17 to 1.57, p < 0.001, I 2 = 83%), radiographic focus absorption (RR: 1.17, 95% CI: 1.06 to 1.30, p=0.002, I 2 = 72), and cavity closure (RR: 1.24, 95% CI: 1.09 to 1.40, p < 0.001, I 2 = 23). The use of rhuIL-2 was not related to any severe adverse events which led to discontinuation of the treatment. Results showed that rhuIL-2 was related to an increased risk of fever (RR: 2.46, 95% CI: 1.29 to 4.70, p=0.006, I 2 = 0%). The incidence of other adverse events, such as musculoskeletal pain, hepatic injury, and renal toxicity, was not significantly different between groups (p all >0.05). Conclusions: rhuIL-2 is an effective adjunctive immunotherapy for patients with pulmonary tuberculosis.
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Gastrodia elata Bl. has a long edible history and is considered an important functional food raw material. Gastrodin (GAS) is one of the main functional substances in G. elata BI. and can be used as a health care product for the elderly to enhance resistance and delay aging. This study investigated the ameliorative effect and mechanism of GAS on cognitive dysfunction in vascular dementia (VaD) rats, which provides a theoretical basis for development and utilization of functional food. The water maze test shows that GAS improves learning and memory impairment in VaD rats. Meanwhile; GAS significantly decreased the levels of Fe2+ and malondialdehyde (MDA); increased the content of glutathione (GSH); and significantly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPx4), the key regulatory factors of ferroptosis; while it down-regulated the expression of kelch-like ECH-associated protein (Keap1) and cyclooxygenase 2 (COX2). However, GAS does not directly regulate GPx4 and COX2 to inhibit ferroptosis. Furthermore, compared with GAS alone, GAS combined with Bardoxolone (an agonist of Nrf2) did not further affect the increase in GPx4 levels and decrease in COX2 levels, nor did it further affect the regulation of GAS on the biochemical parameters of ferroptosis in HT22 hypoxia injury. These findings revealed that GAS inhibited ferroptosis in hippocampal neurons by activating the Nrf2/Keap1-GPx4 signaling pathway, suggesting its possible application as a functional food for improving vascular dementia by inhibiting ferroptosis.
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Disfunção Cognitiva , Demência Vascular , Ferroptose , Animais , Álcoois Benzílicos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Ciclo-Oxigenase 2/metabolismo , Demência Vascular/tratamento farmacológico , Glucosídeos , Glutationa/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Malondialdeído , Fator 2 Relacionado a NF-E2/metabolismo , Ácido Oleanólico/análogos & derivados , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Ratos , Transdução de SinaisRESUMO
Hyaluronic acid (HA)-based antioxidant hydrogels have achieved remarkable results in diabetic wound repair. However, the realization of their glucose-responsive antioxidant functions remains a significant challenge. In this study, we modified hyaluronic acid methacrylate (HAMA) with phenylboronic acid (PBA) and developed a glucose-responsive HA derivative (HAMA-PBA). A glucose-responsive HAMA-PBA/catechin (HMPC) hydrogel platform was then fabricated by forming a borate ester bond between HAMA-PBA and catechin. The results showed that the HMPC hybrid hydrogel not only had a three-dimensional network structure and Young's modulus similar to those of skin tissue, but also possessed biocompatibility. The HMPC hydrogel also showed unique glucose-responsive catechin release behavior and remarkable antioxidant capability, which could effectively eliminate intracellular reactive oxygen species and protect cells from oxidative stress damage (increased superoxide dismutase activity, stabilized reduced glutathione/oxidized glutathione ratio, and reduced malondialdehyde content). Additionally, in vitro and in vivo experimental results showed that the HMPC hydrogel effectively promoted angiogenesis (enhanced VEGF and CD31 expression) and reduced inflammatory responses (decreased IL-6 level and increased IL-10 level), thus rapidly repairing diabetic wounds (within three weeks). This was a significant improvement as compared to that observed for the untreated control group and the HMP hydrogel group. These results indicated the potential for the application of the HMPC hydrogel for treating diabetic wounds. STATEMENT OF SIGNIFICANCE: At present, the delayed closure rate of diabetic chronic wounds caused by excessive reactive oxygen species (ROS) remains a worldwide challenge. Hyaluronic acid (HA)-based antioxidant hydrogels have made remarkable achievements in diabetic wound repair; however, the realization of their glucose-responsive antioxidant functions is a tough challenge. In this work, we developed a novel HA-based hydrogel platform with glucose-responsive antioxidant activity for rapid repair of diabetic wounds. In vitro and in vivo experimental results showed that the HMPC hydrogel could effectively promote angiogenesis (enhanced VEGF and CD31 expression) and reduce inflammatory response (decreased IL-6 level and increased IL-10 level), thus rapidly repairing diabetic wounds (within 3 weeks). These results indicated the potential of the HMPC hydrogel for application in diabetic wound treatment.
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Catequina , Diabetes Mellitus , Antioxidantes/farmacologia , Glucose , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Interleucina-10 , Interleucina-6 , Espécies Reativas de Oxigênio , Fator A de Crescimento do Endotélio Vascular , CicatrizaçãoRESUMO
Most oil source correlation indicators are invalid because of the high maturity of the deep marine strata. Thus, a suitable indicator with high thermal stability requires to be established. In this study, to understand the effect of thermal maturation on the carbon isotopic composition of unsubstituted aromatics, we performed a number of anhydrous thermal simulation experiments involving two typical Chinese shales (lacustrine and marine shales), their corresponding expelled oils, three crude oils, and their associated oil fractions, that is, saturates, aromatics, resins, and asphaltenes (SARA). The generated unsubstituted aromatics were examined in terms of molecular distributions and carbon isotopic composition. The results show that unsubstituted aromatics in different types of samples demonstrated similar variation characteristics. Phenanthrene can be formed continuously in 0.45%/0.55-2.30% R o (equivalent vitrinite reflectance), especially in the high-over maturity stage. However, their carbon isotope composition shows minor variations. The unsubstituted aromatic carbon isotopic information in source rocks can be preserved during the whole pyrolysis process. Their carbon isotopic values in source rocks and their corresponding expelled oils are extremely similar. Furthermore, no evident difference exists in the carbon isotopes of unsubstituted aromatics formed by crude oil and associated oil fractions. These results indicate that these types of parameters are suitable for oil-oil/source correlation in deep marine strata with high-over maturity.
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Salt lakes considerably affect the regional climate, environment, and ecology of semiarid regions characterized by low rainfall and high evaporation. However, under the stresses of global change and human disturbance, anthropogenic pollution is the primary factor threatening the lake's ecological environment. Surface sediment samples collected from four salt lakes in the Ordos Plateau were used to investigate the salinity, concentration, pollution status, potential sources of heavy metals, and influencing factors. The surface sediments of Beida Pond and Gouchi Pond were weakly alkaline (pH < 9) due to the presence of Na2SO4, whereas those of Chaigannaoer and Hongjiannao were strongly alkaline (pH > 9) due to the presence of Na2CO3. The concentration range of Cr, Ni, Cu, Zn, As, Cd, and Pb in the sediment samples collected from the salt lakes in the Ordos Plateau followed the order of Cr > Zn > Ni > Pb > Cu > As > Cd. The Cr concentration values were higher in Chagannaoer and Hongjiannao; however, the Ni, Cu, and Zn values were higher in Beida Pond and Gouchi Pond. The geoaccumulation index (Igeo) and enrichment factor (EF) consistently indicated that Cr posed the greatest potential ecological risk and that Ni, Cu, and Zn pollution was more severe in Beida Pond and Gouchi Pond than in Chagannaoer or Hongjiannao. However, the ecological risk index and potential ecological risk value indicated that these heavy metals posed low risks to the environment. The risk assessment code (RAC) revealed that Pb and Cr exhibited no mobility and had low potential bioavailability risk. Meanwhile, Zn, Ni, and As were categorized as medium risk. Cu had the highest mobility and was categorized as high risk. Principal component analysis for the four salt lakes revealed that the source of Ni, Cu, Zn, and Cd might be associated with water-soluble elements associated with aqueous migration, while the source of Cr, Pb, and As might be the lithospheric minerals carried by dust storms. Pearson's correlation analysis indicated that clay minerals were the primary adsorbers of Ni, Cu, Zn, and Cd. Moreover, pH was identified as the main environmental factor controlling the distribution of heavy metals in the salt lakes.