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1.
Artigo em Inglês | MEDLINE | ID: mdl-38940778

RESUMO

Objective: To analyze the effects of trimetazidine on ventricular remodeling and serum cystatin C (Cys C) and endothelin-1 (ET-1) levels in patients with chronic heart failure (CHF). Methods: A total of 96 patients with CHF admitted to the fifth affiliated hospital of Xinjiang medical university. were enrolled as the research objects between June 2012 and June 2023. They were randomly divided into a control and observation groups, with 48 cases in each group. The control group was given routine treatment, while the observation group was additionally treated with trimetazidine hydrochloride tablets. All were continuously treated for 6 months. The clinical curative effect between the two groups was compared. The left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were measured by cardiac echocardiography before and after treatment. 6MVT before and after treatment was recorded. A full-automatic biochemical analyzer detected the level of serum Cys C before and after treatment. The levels of serum ET-1, galectin-3 (Gal-3), brain natriuretic peptide (BNP), and atrial natriuretic peptide (ANP) were detected by enzyme-linked immunosorbent assay before and after treatment. The incidence of adverse events in the two groups of CHF patients was compared. Results: The total response rate of treatment in the observation group was significantly higher than that in the control group (91.67% vs 79.17%) (P = .037). After treatment, LVEDD and LVESD decreased, while LVEF and 6MVT increased in both groups. LVEDD and LVESD in the observation group were significantly lower than those in the control group, while LVEF and 6MVT were significantly higher than those in the control group (P < .05). After treatment, serum Cys C, ET-1, Gal-3, BNP, and ANP levels in both groups were significantly decreased, significantly lower in the observation group than in the control group (P < .05). The readmission rate of the observation group was lower than that of the control group (P = .045). There was no significant difference in mortality between the two groups (P = .315). Conclusion: Trimetazidine is effective in treating patients with CHF. It can improve cardiac function and reduce the rate of re-hospitalization.

2.
Psychooncology ; 33(7): e6370, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38937093

RESUMO

OBJECTIVE: To compare and rank the effectiveness of four primary categories of exercise modalities (aerobic, resistance, mind-body, and combined exercise [CE]) in improving the Quality of life (QoL) of women with breast cancer in a network meta-analysis (NMA). METHODS: Articles published in English and indexed in the PubMed (MEDLINE), EBSCO, Web of Science, SPORTDiscus, The Cochrane Library, Google Scholar, PsycINFO, EMBASE, and CINAHL Plus databases were identified from inception to 12 October 2023. Studies that met the eligibility criteria were assessed for risk of bias. A frequentist NMA was conducted to appraise the efficacy of different exercise types. RESULTS: This study included 56 studies with 3904 participants. Aerobic, mind-body, and combined exercises effectively improved QoL compared to controls. The surface under the cumulative ranking curve (SUCRA) indicated that CE best improved patients' QoL (SUCRA = 96.7%). Analysis of the secondary outcomes suggests that exercise reduced patients' depression (standardized mean difference [SMD] = -0.38, 95% confidence interval [CI] = -0.70 to -0.06, p < 0.001; I2 = 79%) and anxiety (SMD = -0.50, 95% CI = -0.69 to -0.31, p < 0.001; I2 = 27.4%) but did not affect self-esteem. CONCLUSION: All exercise types but resistance were effective in improving the QoL of women with breast cancer, CE (the combination of aerobic and resistance exercise) had the highest likelihood of being optimal for improving QoL.


Assuntos
Ansiedade , Neoplasias da Mama , Terapia por Exercício , Metanálise em Rede , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Feminino , Terapia por Exercício/métodos , Ansiedade/psicologia , Depressão/psicologia , Exercício Físico/psicologia
3.
Nanomaterials (Basel) ; 14(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38921884

RESUMO

Photocatalysis represents a sustainable strategy for addressing energy shortages and global warming. The main challenges in the photocatalytic process include limited light absorption, rapid recombination of photo-induced carriers, and poor surface catalytic activity for reactant molecules. Defect engineering in photocatalysts has been proven to be an efficient approach for improving solar-to-chemical energy conversion. Sulfur vacancies can adjust the electron structure, act as electron reservoirs, and provide abundant adsorption and activate sites, leading to enhanced photocatalytic activity. In this work, we aim to elucidate the role of sulfur vacancies in photocatalytic reactions and provide valuable insights for engineering high-efficiency photocatalysts with abundant sulfur vacancies in the future. First, we delve into the fundamental understanding of photocatalysis. Subsequently, various strategies for fabricating sulfur vacancies in photocatalysts are summarized, along with the corresponding characterization techniques. More importantly, the enhanced photocatalytic mechanism, focusing on three key factors, including electron structure, charge transfer, and the surface catalytic reaction, is discussed in detail. Finally, the future opportunities and challenges in sulfur vacancy engineering for photocatalysis are identified.

4.
Nano Lett ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38920089

RESUMO

Two-dimensional (2D) lead halide perovskites are excellent candidates for X-ray detection due to their high resistivity, high ion migration barrier, and large X-ray absorption coefficients. However, the high toxicity and long interlamellar distance of the 2D perovskites limit their wide application in high sensitivity X-ray detection. Herein, we demonstrate stable and toxicity-reduced 2D perovskite single crystals (SCs) realized by interlamellar-spacing engineering via a distortion self-balancing strategy. The engineered low-toxicity 2D SC detectors achieve high stability, large mobility-lifetime product, and therefore high-performance X-ray detection. Specifically, the detectors exhibit a record high sensitivity of 13488 µC Gy1- cm-2, a low detection limit of 8.23 nGy s-1, as well as a high spatial resolution of 8.56 lp mm-1 in X-ray imaging, all of which are far better than those of the high-toxicity 2D lead-based perovskite detectors. These advances provide a new technical solution for the low-cost fabrication of low-toxicity, scalable X-ray detectors.

5.
Mol Neurobiol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922485

RESUMO

Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.

6.
J Nanobiotechnology ; 22(1): 319, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849938

RESUMO

Myeloid-derived suppressor cells (MDSCs) have played a significant role in facilitating tumor immune escape and inducing an immunosuppressive tumor microenvironment. Eliminating MDSCs and tumor cells remains a major challenge in cancer immunotherapy. A novel approach has been developed using gemcitabine-celecoxib twin drug-based nano-assembled carrier-free nanoparticles (GEM-CXB NPs) for dual depletion of MDSCs and tumor cells in breast cancer chemoimmunotherapy. The GEM-CXB NPs exhibit prolonged blood circulation, leading to the preferential accumulation and co-release of GEM and CXB in tumors. This promotes synergistic chemotherapeutic activity by the proliferation inhibition and apoptosis induction against 4T1 tumor cells. In addition, it enhances tumor immunogenicity by immunogenic cell death induction and MDSC-induced immunosuppression alleviation through the depletion of MDSCs. These mechanisms synergistically activate the antitumor immune function of cytotoxic T cells and natural killer cells, inhibit the proliferation of regulatory T cells, and promote the M2 to M1 phenotype repolarization of tumor-associated macrophages, considerably enhancing the overall antitumor and anti-metastasis efficacy in BALB/c mice bearing 4T1 tumors. The simplified engineering of GEM-CXB NPs, with their dual depletion strategy targeting immunosuppressive cells and tumor cells, represents an advanced concept in cancer chemoimmunotherapy.


Assuntos
Desoxicitidina , Gencitabina , Imunoterapia , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides , Nanopartículas , Animais , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Células Supressoras Mieloides/efeitos dos fármacos , Camundongos , Imunoterapia/métodos , Feminino , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Proliferação de Células/efeitos dos fármacos
7.
J Coll Physicians Surg Pak ; 34(6): 672-676, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840349

RESUMO

OBJECTIVE: To explore the preventive efficacy of antibiotics following surgical removal of the impacted mandibular third molars and screen the potential risk factors. STUDY DESIGN: A cohort trial. Place and Duration of the Study: Department of Oral and Maxillofacial Surgery, Zhejiang University School of Medicine, Stomatology Hospital, Hangzhou, China, from August 2021 to 2022. METHODOLOGY: Cases with impacted mandibular third molar were divided into two groups based on antibiotics use. The primary outcome variable post-operative infection, secondary clinical parameter analgesics intake, and other variables (the operative time, the history of pericoronitis, and wound closure) were documented. RESULTS: The post-operative infections occurred in 3.64% (n = 12) of the 330 cases (n = 330); 3.01% in the antibiotic group (n = 166) and 4.27% in the control group (n = 164, OR = 1.44, 95% CI: 0.49 to 4.06; p = 0.54). Concerning secondary outcome measures, the analgesics that the antibiotic group took was 5.40, and the control group took was 5.95 (95% CI = -0.21 to 1.30; p = 0.16). For those with post-operative infections, the average operative time was 22.83 minutes, whereas for those without post-operative infections it was 14.87 minutes (95% CI = -0.26 to 15.67; p = 0.04). When the operative time was greater than or equal to 15 minutes, it was related to more analgesics use (95% CI: -0.43 to 1.93; p <0.05), also was the history of pericoronitis (95% CI = 0.04 to 1.54; p = 0.04). CONCLUSION: Antibiotics are unnecessary for preventing post-operative infections or minimising analgesic requirements following extraction of the impacted mandibular third molars; operative time and pericoronitis showed a suppressive influence on post-operative recovery. KEY WORDS: Impacted molars, Antibiotics, Analgesics, Operative time, Pericoronitis.


Assuntos
Antibacterianos , Antibioticoprofilaxia , Dente Serotino , Infecção da Ferida Cirúrgica , Extração Dentária , Dente Impactado , Humanos , Dente Serotino/cirurgia , Masculino , Dente Impactado/cirurgia , Feminino , Extração Dentária/efeitos adversos , Adulto , Infecção da Ferida Cirúrgica/prevenção & controle , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Mandíbula/cirurgia , Adulto Jovem , China/epidemiologia , Duração da Cirurgia , Estudos de Coortes , Resultado do Tratamento
8.
Molecules ; 29(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38930807

RESUMO

Squaric-acid-linked zwitterionic covalent organic frameworks (Z-COFs), assembled through interlayer interactions, are emerging as potential materials in the field of photocatalysis. However, the study of their interlayer interactions has been largely overlooked. To address this, this work systematically calculated interlayer interactions via density functional theory (DFT) and analyzed the differences in interlayer interactions of different structures of Z-COFs through interlayer slippage, planarity, and an independent gradient model based on the Hirshfeld partition (IGMH). Furthermore, it revealed the relationship between the interactions and the macroscopic photocatalytic carrier transport performance of the material. The results indicated that both preventing interlayer slippage and enhancing planarity can enhance the interlayer interactions of Z-COFs, thereby improving their macroscopic carrier transport performance in photocatalysis.

10.
BMC Genomics ; 25(1): 543, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822270

RESUMO

Recent studies on co-transformation of the growth regulator, TaGRF4-GIF1 chimera (Growth Regulating Factor 4-GRF Interacting Factor 1), in cultivated wheat varieties (Triticum aestivum), showed improved regeneration efficiency, marking a significant breakthrough. Here, a simple and reproducible protocol using the GRF4-GIF1 chimera was established and tested in the medicinal orchid Dendrobium catenatum, a monocot orchid species. TaGRF4-GIF1 from T. aestivum and DcGRF4-GIF1 from D. catenatum were reconstructed, with the chimeras significantly enhancing the regeneration efficiency of D. catenatum through in planta transformation. Further, mutating the microRNA396 (miR396) target sites in TaGRF4 and DcGRF4 improved regeneration efficiency. The target mimicry version of miR396 (MIM396) not only boosted shoot regeneration but also enhanced plant growth. Our methods revealed a powerful tool for the enhanced regeneration and genetic transformation of D. catenatum.


Assuntos
Dendrobium , MicroRNAs , Brotos de Planta , Regeneração , Dendrobium/genética , Dendrobium/crescimento & desenvolvimento , MicroRNAs/genética , MicroRNAs/metabolismo , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Regeneração/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética
11.
Nat Med ; 30(6): 1680-1688, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38740994

RESUMO

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Angústia Psicológica , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Depressão/tratamento farmacológico , Ansiedade/tratamento farmacológico , Resultado do Tratamento , Intervalo Livre de Progressão , Adulto , Idoso de 80 Anos ou mais
12.
Dalton Trans ; 53(20): 8843-8849, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38716691

RESUMO

Heteroatomic anion doping represents a powerful approach for manipulating the electronic configuration of the active metal locus in electrocatalysts, resulting in enhanced multifunctional electrocatalytic properties in hydrogen/oxygen evolution reactions (HER/OER). Here, fluorine-tailored Ni2P-F3 nanosheets were synthesized and evaluated as a robust multifunctional electrocatalyst for HER, OER, and UOR. Our comprehensive experimental and theoretical investigations reveal that the anionic F effectively tailored the electronic states of the Ni2P-F3 nanosheets, resulting in an elevated d-band center and optimizing the sorption capacity of intermediates. In addition to thermodynamically and kinetically favoured redox reactions, F doping facilitates the reconstruction and generation of active γ-NiOOH. Resulting from the optimized electronic configuration and nanosheet architecture, outstanding catalytic activities are demonstrated by Ni2P-F3 with low overpotentials to reach 100 mA cm-2 for HER (177 mV) and OER (293 mV), surpassing Ni2P by 234 and 205 mV, respectively. Notably, 1.618 V is required for full-water-diversion to reach 10 mA cm-2, while 1.414 V is required with urea oxidation for 100 mA cm-2.

13.
Front Cell Neurosci ; 18: 1364164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711616

RESUMO

Introduction: Fused in sarcoma (FUS) mutations represent the most common genetic etiology of juvenile amyotrophic lateral sclerosis (JALS), for which effective treatments are lacking. In a prior report, we identified a novel FUS mutation, c.1509dupA: p. R503fs (FUSR503fs), in a sporadic JALS patient. Methods: The physicochemical properties and structure of FUSR503fs protein were analyzed by software: Multi-electrode array (MEA) assay, calcium activity imaging assay and transcriptome analysis were used to explore the pathophysiological mechanism of iPSC derived motor neurons. Results: Structural analysis and predictions regarding physical and chemical properties of this mutation suggest that the reduction of phosphorylation and glycosylation sites, along with alterations in the amino acid sequence, may contribute to abnormal FUS accumulation within the cytoplasm and nucleus of induced pluripotent stem cell- derived motor neurons (MNs). Multi-electrode array and calcium activity imaging indicate diminished spontaneous electrical and calcium activity signals in MNs harboring the FUSR503fs mutation. Transcriptomic analysis reveals upregulation of genes associated with viral infection and downregulation of genes involved in neural function maintenance, such as the ATP6V1C2 gene. Treatment with ropinirole marginally mitigates the electrophysiological decline in FUSR503fs MNs, suggesting the utility of this cell model for mechanistic exploration and drug screening. Discussion: iPSCs-derived motor neurons from JALS patients are promising tools for drug screening. The pathological changes in motor neurons of FUSR503fs may occur earlier than in other known mutation types that have been reported.

14.
Acta Pharm Sin B ; 14(5): 2097-2118, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799640

RESUMO

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

15.
World J Gastrointest Surg ; 16(5): 1291-1300, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38817277

RESUMO

BACKGROUND: The prognostic nutritional index (PNI), a marker of immune-nutrition balance, has predictive value for the survival and prognosis of patients with various cancers. AIM: To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December 2020. All patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve analysis. We compared disease-free survival (DFS) and overall survival (OS) between these groups and assessed prognostic factors through univariate and multivariate analyses. RESULTS: The optimal cutoff value for the PNI was established at 45.3. Patients with a PNI ≥ 45.3 were categorized into the PNI-high group, while those with a PNI < 45.3 were assigned to the PNI-low group. Patients within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high group. The 5-year OS rates for patients with a PNI ≥ 45.3 and a PNI < 45.3 were 61.8% and 43.4%, respectively, while the 5-year DFS rates were 53.5% and 38.3%, respectively. Patients in the PNI- low group had shorter OS (P = 0.006) and DFS (P = 0.012). In addition, multivariate analysis revealed that the PNI, pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and DFS. CONCLUSION: The PNI is a straightforward and valuable marker for predicting long-term survival after pancreatoduodenectomy. The PNI should be incorporated into the standard assessment of patients with AC.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38814831

RESUMO

AIMS: Down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffered ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. RESULTS: The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species while decreases in the activities of anti-oxidative enzymes, concomitant with a down-regulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1, and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), and subsequently disrupted the assembly of CARD11, B-cell lymphoma 10 (BCL10) and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. INNOVATION AND CONCLUSION: The E3 ubiquitin ligase function of MALT1 accounts for the down-regulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and subsequent activation of MALT1.

17.
Int J Surg ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38759693

RESUMO

BACKGROUND: There was no consistent evidence whether perioperative blood transfusion (PBT) affects the long-term survival of gastric cancer (GC) patients after undergoing gastrectomy. This study aimed to investigate the effects of PBT on long-term survival of GC patients, as well as to determine the threshold of PBT and provide evidence for future surgical practice. METHODS: We performed this real-world study of GC patients undergoing gastrectomy in China National Cancer Center from January 1, 2000 to December 30, 2019. Overall survival (OS) curves were plotted using the Kaplan-Meier method and compared statistically using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to determine the risk factors for OS. RESULTS: In total, 13470 GC patients undergoing gastrectomy from 2000 to 2019 was included, of whom 3465 (34.6%) GC patients received PBT. PBT ratios declined from 29.1% (114/392) in 2000 to 11.2% in 2019 (149/1178), with the highest blood transfusion ratio in 2005 at 43.7% (220/504). For patients transfused with red blood cells, the median value of hemoglobin (Hb) before transfusion in the PBT group decreased from 110 g/L in 2000 to 87 g/L in 2019. Compared with patients who not receiving perioperative blood transfusion (NPBT), PBT group are more likely to be older (≥65, 39.1% vs. 30.1%, P<0.001), open operation (89.7% vs. 78.1%, P<0.001), higher ASA score (>2, 25.3% vs. 14.9%, P<0.001) and in the later pTNM stage (pTNM stage III, 68.5% vs. 51.5%, P<0.001). Results of multivariable Cox regression analysis showed that PBT was an independent prognostic factor for worse OS in GC patients undergoing gastrectomy (HR=1.106, 95% CI, 1.01-1.211, P=0.03). After stratified according to tumor stage, we found that PBT group had a worse prognosis only in pTNM stage III (HR=1.197, 95% CI, 1.119-1.281, P<0.001). OS was obviously poor in the PBT group when Hb levels were higher than 90 g/L (90 g/L120 g/L:HR= 1.207, 95% CI, 1.098-1.327, P<0.001), while there was no difference between the two groups when Hb levels were lower than or equal to 90 g/L (Hb≤90 g/L: HR=1.162, 95% CI, 0.985-1.370, P=0.075). CONCLUSION: In conclusion, PBT was an independent prognostic factor for worse OS. Blood transfusion might not be recommended for gastric cancer patients with perioperative minimum Hb values higher than 90 g/L.

18.
Molecules ; 29(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38611941

RESUMO

In this study, a novel green fluorescent probe material, nitrogen-doped carbon quantum dots (N-CQDs), was prepared by a one-step hydrothermal synthesis method using walnut green skin as a carbon source and acetamide-glycolic acid deep eutectic solvent (AGADES) as a modifier. By covalent coupling, the amide chromophore in AGADES is designed to cover the surface of walnut green skin carbon quantum dots (W-CQDs), forming a fluorescence energy resonance effect and improving the fluorescence performance of the carbon quantum dots. The prepared N-CQDs have a uniform particle size distribution, and the fluorescence quantum efficiency has increased from 12.5% to 32.5%. Within the concentration range of 0.01~1000 µmol/L of Pb2+, the linear detection limit is 1.55 nmol/L, which can meet the trace detection of Pb2+ in the water environment, and the recycling rate reaches 97%. This method has been successfully applied to the fluorescence detection and reuse of Pb2+ in actual water bodies, providing new ideas and methods for the detection of heavy metal ions in environmental water.

19.
Nanomaterials (Basel) ; 14(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38607144

RESUMO

Psoriasis, a chronic inflammatory skin disease induced by various factors, including genetic factors, immune factors, environmental factors, and psychological factors, is characterized by thickening of the epidermis, excessive proliferation of keratinocytes, abnormal differentiation, and an excessive inflammatory response. Traditional treatments for psoriasis still face challenges because of limited curative effects, notable side effects, and a tendency for recurrence. In contrast, topical therapy provides a favorable option for psoriasis treatment because of its noninvasive and self-administered method. In this study, gentiopicrin (Gen) is encapsulated in the liposomes to form a nanodrug, and then chitosan is covered on the nanodrug to assemble the nanodrug delivery system (CS@Gen), which is used as a topical agent for treating psoriasis. Then M5 (a mixture of five pro-inflammatory cytokines, i.e., IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α)-induced HacaT cells and imiquimod-induced psoriasis mouse models are established, whose results show that CS@Gen induces apoptosis and inhibits the proliferation and cell migration of psoriasis keratinocytes. Additionally, the application of CS@Gen cream can significantly reduce epidermal thickness, diminish skin scaling, and improve other related mechanisms in mice affected by psoriasis. Meanwhile, the prepared CS@Gen can significantly reduce the expression levels of IL-17a, Cxcl2, S100a, Mki67, and other related inflammatory factors, resulting in indirectly inhibiting the inflammation of keratinocytes. In summary, the present study provides an ideal loading for an anti-inflammatory and immunomodulatory drug delivery system for the treatment of psoriasis.

20.
Trials ; 25(1): 275, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650028

RESUMO

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD. METHODS: This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded. DISCUSSION: This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.


Assuntos
Doença de Parkinson , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Ultrassom , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/complicações , Método Duplo-Cego , Estudos Prospectivos , Resultado do Tratamento , Terapia por Ultrassom/métodos , Masculino , Dispositivos Eletrônicos Vestíveis , Idoso , Pessoa de Meia-Idade , Feminino , Fatores de Tempo , China
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