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1.
Mol Carcinog ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092774

RESUMO

Ovarian cancer is the leading cause of death from female gynecological cancers. Cisplatin (DDP) is a first-line drug for ovarian cancer treatment. Due to DDP resistance, there is an urgent need for novel therapeutic drugs with improved antitumor activity. AMPK-mediated metabolic regulatory pathways are related to tumor drug resistance. Our study aimed to determine the relationship between reversing DDP resistance with the anthraquinone derivative KA-4s and regulating AMPK energy metabolism in ovarian cancer. The results showed that KA-4s inhibited the proliferation of ovarian cancer cells. The combination of KA-4s with DDP effectively promoted drug-resistant ovarian cancer cell apoptosis and inhibited cell migration and invasion. Moreover, KA-4s decreased the intracellular ATP level and increased the calcium ion level, leading to AMPK phosphorylation. Further studies suggested that the AMPK signaling pathway may be involved in the mechanism through which KA-4s reduce drug resistance. KA-4s inhibited mitochondrial respiration and glycolysis; downregulated the glucose metabolism-related proteins GLUT1 and GLUT4; the lipid metabolism-related proteins SREBP1 and SCD1; and the drug resistance-related proteins P-gp, MRP1, and LRP. The inhibitory effect of KA-4s on GLUT1 was confirmed by the application of the GLUT1 inhibitor BAY-876. KA-4s combined with DDP significantly increased the expression of p-AMPK and reduced the expression of P-gp. In a xenograft model of ovarian cancer, treatment with KA-4s combined with DDP reduced energy metabolism and drug resistance, inducing tumor apoptosis. Consequently, KA-4s might be evaluated as a new agent for enhancing the chemotherapeutic efficacy of treatment for ovarian cancer.

2.
Front Oncol ; 14: 1409347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39087023

RESUMO

Xanthogranulomatous cholecystitis (XGC) is a rare type of cholecystitis that, despite being benign poses diagnostic challenges due to its low prevalence and need for consensus on diagnostic criteria. Consequently, distinguishing XGC from gallbladder cancer (GBC) is challenging, leading to clinical misdiagnoses. This article presents a case where a patient initially diagnosed with GBC was later found to have XGC.

3.
Biol Trace Elem Res ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995434

RESUMO

The integrity of colonic gland cells is a prerequisite for normal colonic function and maintenance. To evaluate the underlying injury mechanisms in colonic gland cells induced by excessive fluoride (F), forty-eight female Kunming mice were randomly allocated into four groups and treated with different concentrations of NaF (0, 25, 50, and 100 mg F-/L) for 70 days. As a result, the integrity of the colonic mucosa and the cell layer was seriously damaged after F treatment, as manifested by atrophy of the colonic glands, colonic cell surface collapse, breakage of microvilli, and mitochondrial vacuolization. Alcian blue and periodic acid Schiff staining revealed that F decreased the number of goblet cells and glycoprotein secretion. Furthermore, F increased the protein expression of TLR4, NF-κB, and ERK1/2 and decreased IL-6, interfered with NF-κB signaling, following induced colonic gland cells inflammation. The accumulation of F inhibited proliferation via the JAK/STAT signaling pathway, as characterized by decreased mRNA and protein expression of JAK, STAT3, STAT5, PCNA, and Ki67 in colon tissue. Additionally, the expression of CDK4 was up-regulated by increased F concentration. In conclusion, excessive F triggered colonic inflammation and inhibited colonic gland cell proliferation via regulation of the NF-κB and JAK/STAT signaling pathways, leading to histopathology and barrier damage in the colon. The results explain the damaging effect of the F-induced inflammatory response on the colon from the perspective of cell proliferation and provide a new idea for explaining the potential mechanism of F-induced intestinal damage.

4.
Mycopathologia ; 189(4): 63, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985209

RESUMO

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Micoses , Sensibilidade e Especificidade , Talaromyces , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Talaromyces/genética , Talaromyces/isolamento & purificação , Masculino , Feminino , Metagenômica/métodos , Adulto , Micoses/diagnóstico , Micoses/microbiologia , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Curva ROC , Adolescente
5.
Medicine (Baltimore) ; 103(27): e38742, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968482

RESUMO

In orthodontic treatment of patients during the mixed dentition period, arch expansion and opening deep overbite are one of the objectives to achieve proper alignment of the teeth and correction of sagittal and vertical discrepancies. However, the expected outcomes of most therapeutic regimens are not clear, making it impossible to standardize early treatment effects. Therefore, this study was designed to evaluate the impact of the Invisalign® First System on the dental arch circumference and incisor inclination in patients during the mixed dentition period. A total of 21 children during the mixed dentition period (10 females and 11 males, with an average age of 8.76 years) were included in this study. The patients received non-extraction treatment through Invisalign® First System clear aligners, and no other auxiliary devices were used except Invisalign® accessories. Subsequently, the cooperation degree of patients during treatment and the oral measurement parameters at the beginning (T1) and the end (T2) of treatment were collected. All patients showed moderate/good cooperation degree during treatment. Besides, horizontal width of the maxillary first molar increased significantly; the designed arch expansion was 4.1 mm (±1.4 mm), while the actual arch expansion was 3.0 mm (±1.7 mm). Furthermore, the torque expression rate of upper anterior teeth reached 56.53%. Invisalign® First System clear aligners can effectively correct the teeth of patients during the mixed dentition period, widen the circumference of dental arch, and control the torque of incisors.


Assuntos
Dentição Mista , Incisivo , Má Oclusão , Dente Molar , Torque , Humanos , Masculino , Feminino , Criança , Má Oclusão/terapia , Aparelhos Ortodônticos Removíveis , Arco Dental , Desenho de Aparelho Ortodôntico , Técnicas de Movimentação Dentária/instrumentação , Técnicas de Movimentação Dentária/métodos
6.
Heliyon ; 10(13): e33904, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39027542

RESUMO

Background: and purpose Prostate cancer is an comparatively prevalent clinical malignant tumor in men, impacting the lives of millions of men globally. This study measured the expression of Karyopherin Subunit Beta 1 (KPNB1) in prostate cancer cells, and made an effort to investigate how astragaloside IV affects the biological behavior, tumor growth, and mechanism of action of prostate cancer through KPNB1. Methods: Human prostate cancer and normal cells were obtained and KPNB1 expression levels in the two cells were determined using qPCR and WB. Prostate cancer cells were grouped according to the addition of astragaloside IV, KPNB1 inhibitor (importazole) alone and in combination. KPNB1, NF-κB, and cycle-related proteins were detected to be expressed at different levels in each group's cells by WB. MTT to assess the viability of the cells. To identify the cell cycle, use flow cytometry, and sphere formation experiment to observe sphere formation ability. Nude mice were purchased and subcutaneously inoculated with prostate cancer cells to establish a prostate cancer model, and grouped by tail vein injection of astragaloside IV and importazole. Tumor size was measured. KPNB1 and NF-κB expression in tumor tissues were detected by WB. The expression of proteins relevant to the cycle is observed by immunohistochemical methods. TUNEL was used to detect apoptosis of tissue cells. Results: KPNB1 expression was upregulated in prostate cancer cells (P < 0.05). KPNB1, NF-κB, and cycle-related protein levels were decreased by astragaloside IV and importazole both separately and together. Decreased viability of the cells and a higher percentage of cell cycle arrest in the G0 phase, apoptosis was increased, and sphere formation was decreased (P < 0.05). In vitro implantation experiments found that the application of astragaloside IV and importazole resulted in tumor growth inhibition, decreased KPNBI, NF-κB, and cyclin expression in tumor tissues, and promoted apoptosis in tumor tissues (P < 0.05). Conclusion: Prostate cancer cells' expression of KPNB1 is downregulated by astragaloside IV, which also prevents the cells from proliferating. It offers a conceptual framework for the use of astragaloside IV in the management of prostate cancer.

7.
ACS Omega ; 9(26): 28754-28763, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38973896

RESUMO

Gassy coal seams generally have low permeability and dry coal bodies, which are susceptible to coal and gas outburst hazards in the process of mining. Water injection into coal seams can significantly alter the gas release rate and flow behavior. However, water has dual effects on coal seams: gas displacement and water-locking, and the coupling mechanism of these two effects is not clear in the whole process of coal seam water injection. By measuring high-pressure gas adsorption isotherms and gas diffusion initial velocity, it was found that both the Langmuir adsorption constant a and gas diffusion initial velocity ΔP decrease with the increase of water content, which would reduce outburst risks. Through the self-developed integrated experimental device of "gas adsorption + water injection displacement + gas desorption″, the changing rules of gas displacement amount, desorption amount, and water lock amount under different water injection conditions were studied. The results show that when the water injection ratio increases from 6 to 25%, the gas displacement would increase from 0.62 to 1.16 mL/g, with an increase of 87.09%. Also, at the same time, the gas desorption capacity would decrease from 4.86 to 4.05 mL/g after pressure relief, with a decrease of 16.67%. The amount of water-locking increased from 0.11 to 0.38 mL/g. The effect of water injection to control coal and gas outburst occurs in two different water injection stages. In the process of water injection, water plays a major role in gas displacement, which is conducive to reducing the gas content of the coal seam. After the completion of water injection, the static water pressure remaining in the coal seam can reduce the gas emission rate. The combination of these two effects can effectively reduce the risk of outbursts.

8.
Cell Rep ; 43(7): 114514, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39002126

RESUMO

The regenerative potential of injured axons displays considerable heterogeneity. However, the molecular mechanisms underlying the heterogeneity have not been fully elucidated. Here, we establish a method that can separate spinal motor neurons (spMNs) with low and high regenerative capacities and identify a set of transcripts revealing differential expression between two groups of neurons. Interestingly, oligodendrocyte transcription factor 1 (Olig1), which regulates the differentiation of various neuronal progenitors, exhibits recurrent expression in spMNs with enhanced regenerative capabilities. Furthermore, overexpression of Olig1 (Olig1 OE) facilitates axonal regeneration in various models, and down-regulation or deletion of Olig1 exhibits an opposite effect. By analyzing the overlapped differentially expressed genes after expressing individual Olig factor and functional validation, we find that the role of Olig1 is at least partially through the neurite extension factor 1 (Nrsn1). We therefore identify Olig1 as an intrinsic factor that promotes regenerative capacity of injured axons.


Assuntos
Axônios , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Perfilação da Expressão Gênica , Regeneração Nervosa , Animais , Axônios/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Camundongos , Neurônios Motores/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Camundongos Endogâmicos C57BL , Transcriptoma/genética
9.
BMC Pediatr ; 24(1): 423, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956525

RESUMO

BACKGROUND: Growth charts are an important method for evaluating a child's health, growth, and nutritional status. It is essential to monitor the growth of children and adolescents using growth charts. OBJECTIVES: To present body mass index (BMI)-for-age references reflecting children's growth in Shanxi. We also compare our new data with growth references of other cities of China and World Health Organization (WHO) growth standards. METHODS: A stratified cluster random sampling method was used to recruit 5461 children and adolescents aged 6-17 years. Height and weight were measured and BMI was calculated. The LMS method was used to calculate the percentile values of body mass index by sex and age. Smoothed BMI-for-age growth curves were presented for both sexes and compared with reference data from other cities of China and WHO. RESULTS: BMI centiles increased with age but with different patterns in both boys and girls. The centile curves from the 3rd to the 50th had a slight increase, while a sharp increase was seen from 11 to 17 years in boys and from 6 to 14 years in girls in the higher centiles. In comparison with other cities of China, the values for the 50th percentile are higher than those reported for children from China 2009, Shanghai, Changsha and China 2010 in both sexes. In comparison with WHO growth references, Chinese girls and boys had higher values in all percentiles, whereas curves of girls look roughly the same. The medians for BMI in Shanxi increase linearly from 6 to 17 years in boys. CONCLUSIONS: The BMI percentiles of children aged 6-17 years in Shanxi differed significantly from the growth reference curves of other cities of China and WHO. Recommending the provision of BMI reference curves for local children and adolescents to assess their growth and development and monitor their nutritional status. Early detection of overweight and obesity in children provides a scientific basis for the prevention and control of overweight and obesity in children.


Assuntos
Índice de Massa Corporal , Gráficos de Crescimento , Organização Mundial da Saúde , Humanos , Adolescente , Criança , China , Masculino , Feminino , Valores de Referência , Estatura , Peso Corporal
10.
Int J Antimicrob Agents ; : 107287, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39084574

RESUMO

This phase I clinical study aimed to assess the safety, tolerability, and population pharmacokinetic-pharmacodynamics (PK-PD) target attainment analysis of etimicin sulfate in healthy participants and provide scientific reference for further development of clinical breakpoints. Twenty-four healthy Chinese subjects were enrolled and received etimicin sulfate infusion in this study. A population PK model was constructed for the estimation of the PK profiles of etimicin sulfate. The area under the concentration-time curve divided by minimum inhibitory concentration (AUC0-24h/MIC) and the peak concentration divided by MIC (Cmax/MIC) were selected as the PK/PD indices. The probability of target attainment (PTA) was calculated for each designed dosing regimen using Monte Carlo Simulations. The minimum MIC value with a PTA ≥ 90% for each regimen was considered as the PK/PD cutoff values. Etimicin sulfate demonstrated safety, tolerability and predictable PK characteristics. No deaths or serious adverse events appeared, and seven treatment emergent adverse events (TEAEs) were reported by five participants. All TEAEs were minor and relieved rapidly. A two-compartment model was developed and validated for describing the PK features of etimicin sulfate among Chinese healthy participants. The diagnostic goodness-of-fit plots and visual predictive check plots showed that this developed model could describe these data well. The PTA results showed that etimicin sulfate provided clinical improvement against strains with MIC of 0.5-1 mg/l and below, and antibacterial effect against strains with MIC of 0.25 mg/l and below. However, etimicin sulfate had limited clinical efficacy for clinical isolates with MIC values > 1 mg/l.

11.
Technol Health Care ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39031409

RESUMO

BACKGROUND: Irrational pharmacotherapy and increasing pharmacy costs remain major concerns in healthcare systems. Pharmacists are expected to employ diagnosis-related group (DRG) data to analyse inpatient pharmacy utilization. OBJECTIVE: This project aimed to pilot an efficient pharmacist-led programme to analyse factors related to pharmacy expenses, evaluate the rational use of drugs in batch processing, and make further interventions based on DRG data. METHODS: Patients from the OB25 (caesarean section without comorbidities or complications) DRG were selected in 2018, and the most relevant factors were identified through statistical analysis. Interventions were implemented by sending monthly reports on prescribing data and drug review results for the same DRGs to the department starting in 2019. Pre-post comparisons were conducted to demonstrate changes in pharmacy costs and appropriateness at a tertiary teaching hospital with 2,300 beds in China. RESULTS: A total of 1,110 patients were identified from the OB25 DRG data in 2018. Multivariate linear analysis indicated that the number of items prescribed and wards substantially influenced pharmacy expenditure. Drugs labelled as vital, essential, and non-essential revealed that 46.6% of total pharmacy costs were spent on non-essential drugs, whereas 38.7% were spent on vital drugs. The use of inappropriate pharmaceuticals and drug items was substantially reduced, and the average pharmacy cost after intervention was 336.7 RMB in 2020. The benefit-cost ratio of the programme was 9.86. CONCLUSION: Interventions based on DRG data are highly efficient and feasible for reducing inpatient pharmacy costs and non-essential drug use.

12.
Chem Sci ; 15(28): 11084-11091, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39027284

RESUMO

The continuing growth of the digital world requires new ways of constructing memory devices to process and store dynamic data, because the current ones suffer from inefficiency, limited reads, and difficulty to manufacture. Here we propose a supramolecular dynamic memory (SDM) strategy based on an enzymolysis-induced energy transfer co-assembly derived from a naphthalene-based cationic monomer and organic dye sulforhodamine 101, enabling the construction of spontaneously recoverable dynamic memory devices. Benefitting from the large exciton migration rate (4.48 × 1015 L mol-1 s-1) between the monomer and sulforhodamine 101, the energy transfer process between the two is effectively achieved. Since alkaline phosphatase can selectively hydrolyze adenosine triphosphate, leading to the disruption of the co-assemblies, an enzyme-mediated time-dependent fluorochromic system is realized. On this basis, a SDM system featuring spontaneous recovery and enabling the memory of dynamic information in optical and electrical modes is successfully constructed. The current study represents a promising step in the nascent development of supramolecular materials for computational systems.

13.
Neurogastroenterol Motil ; : e14875, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39077771

RESUMO

BACKGROUND: The traditional herbal medicine Atractylodes macrocephala Koidz. (A. macrocephala) is commonly utilized for alleviating symptoms associated with spleen deficiency, abdominal distension, diarrhea, and constipation. These pharmacological effects are attributed to a variety of active constituents. However, the specific bioactive compounds responsible for promoting defecation and gastrointestinal transit in A. macrocephala remain unidentified. METHODS: The primary polysaccharide characteristics of PAMK was elucidated by HPLC, FT-IR, and HGPGC. Efficacy of PAMK (0.07, 0.14, and 0.28 mg/g) on mice was evaluated in a spleen deficiency constipation mouse model by analyzing stool parameters, constipation-related physiological indexes, and SCFAs. The expression levels of 5-HT3R, 5-HT4R, and related receptor genes were examined by RT-qPCR, and neurotransmitters were examined using ELISA. Finally, the diversity of gut microbiota was analyzed with 16S rDNA sequencing. KEY RESULTS: The results showed that PAMK significantly reduced the gastrointestinal transport time and increased the number of fecal pellets and fecal water content in spleen deficiency constipation model mice. PAMK kept the balance of 5-HT, SCFAs, TPH-1, SERT, CgA, and neurotransmitter levels (VIP, SP, MTL) in mice colon. In addition, PAMK could regulate the abundance of gut microbiota such as Alistopes, Bacteroides, and Odoribacter in spleen deficiency constipation model mice gut. CONCLUSIONS AND INFERENCES: It can be concluded that PAMK effectively ameliorated the symptoms of spleen deficiency constipation in mice by modulating the expression of 5-HT and its associated receptors. The underlying mechanism was elucidated, providing a solid theoretical foundation for the therapeutic application of A. macrocephala in treating spleen deficiency constipation and offering potential for developing novel approaches to address this condition.

14.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877445

RESUMO

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hepatectomia , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Idoso , Curva ROC , Estudos Retrospectivos , Estimativa de Kaplan-Meier , Adulto , Fatores de Risco
15.
Front Immunol ; 15: 1371379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881888

RESUMO

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , DNA Helicases , Fatores de Transcrição , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , DNA Helicases/genética , DNA Helicases/deficiência , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Transcrição/genética , Proteínas Nucleares/genética , Proteínas Nucleares/deficiência , Etoposídeo/uso terapêutico , Etoposídeo/administração & dosagem , Masculino , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Resultado do Tratamento , Feminino
16.
Beilstein J Nanotechnol ; 15: 569-579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887527

RESUMO

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (Fe3O4 NCs), - CUR layer, - and MnO2 (CUR-Fe@MnO2 NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO2 NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO2 NFs to release Mn2+ and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO2 NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO2 NFs were effective T 1/T 2 contrast agents for molecular magnetic resonance imaging due to the release of Mn2+ and Fe3O4 NCs.

17.
Neurochem Res ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862726

RESUMO

Idebenone, an antioxidant used in treating oxidative damage-related diseases, has unclear neuroprotective mechanisms. Oxidative stress affects cell and mitochondrial membranes, altering Adp-ribosyl cyclase (CD38) and Silent message regulator 3 (SIRT3) protein expression and possibly impacting SIRT3's ability to deacetylate Tumor protein p53 (P53). This study explores the relationship between CD38, SIRT3, and P53 in H2O2-injured HT22 cells treated with Idebenone. Apoptosis was detected using flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining after determining appropriate H2O2 and Idebenone concentrations.In this study, Idebenone was found to reduce apoptosis and decrease P53 and Caspase3 expression in H2O2-injured HT22 cells by detecting apoptosis-related protein expression. Through bioinformatics methods, CD38 was identified as the target of Idebenone, and it further demonstrated that Idebenone decreased the expression of CD38 and increased the level of SIRT3. An increased NAD+/NADH ratio was detected, suggesting Idebenone induces SIRT3 expression and protects HT22 cells by decreasing apoptosis-related proteins. Knocking down SIRT3 downregulated acetylated P53 (P53Ac), indicating SIRT3's importance in P53 deacetylation.These results supported that CD38 was used as a target of Idebenone to up-regulate SIRT3 to deacetylate activated P53, thereby protecting HT22 cells from oxidative stress injury. Thus, Idebenone is a drug that may show great potential in protecting against reactive oxygen species (ROS) induced diseases such as Parkinson's disease, and Alzheimer's disease. And it might be able to compensate for some of the defects associated with CD38-related diseases.

18.
Acad Radiol ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38906780

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to investigate the prognostic value of preoperative CT scan-derived myocardial biomarkers in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: In April 2024, three databases (PubMed, Web of Science and Embase) were searched to identify studies. A random-effects model for meta-analysis was conducted to calculate pooled hazard ratios (HR) and 95% confidence intervals (CI) to assess the prognostic value. The I2 statistic was used to assess heterogeneity. Meta-regression analysis was conducted to appraise which variables yielded a significant impact on the HR of included biomarkers. RESULTS: 11 studies were identified, of which six studies involved 678 patients reporting extracellular volume fraction (ECV), one study involved 300 patients reporting ECV and left ventricular global longitudinal strain (LVGLS), three studies involved 868 patients reporting LVGLS and one study involved 376 patients reporting LVGLS and peak left atrial longitudinal strain (PALS). The endpoints included all-cause mortality, major adverse cardiovascular events (MACE) and a composite outcome of the previous two. The meta-analysis revealed that ECV, whether considered as a dichotomous variable (pooled HR: 3.87, 95% CI: 2.63-5.70, I2 = 0%), or as a continuous variable (pooled HR: 1.12, 95% CI: 1.05-1.19, I2 = 66%), and LVGLS, whether considered as a dichotomous variable (pooled HR: 1.70, 95% CI: 1.30-2.22, I2 = 0%) or a continuous variable (pooled HR: 1.07, 95% CI: 1.04-1.10, I2 = 0%) were all significant predictors for outcomes in patients with severe AS after TAVR. Age, sex, follow-up time and mean pressure gradient had a significant impact on the model of ECV (continuous). CONCLUSION: The higher CT-derived ECV and impaired LVGLS are able to predict worse outcomes in patients with severe AS who have undergone TAVR.

19.
Int J Biol Macromol ; 272(Pt 1): 132776, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823750

RESUMO

Uranium as a nuclear fuel, its source and aftertreatment has been a hot topic of debate for developers. In this paper, amidoxime and guanidino-modified cotton fibers (DC-AO-PHMG) were synthesized by the two-step functionalization approach, which exhibited remarkable antimicrobial and high uranium recovery property. Adsorption tests revealed that DC-AO-PHMG had excellent selectivity and anti-interference properties, the maximum adsorption capacity of 609.75 mg/g. More than 85 % adsorption capacity could still be kept after 10 adsorption-desorption cycles, and it conformed to the pseudo-second-order kinetic model and the Langmuir adsorption isotherm model as a spontaneous heat-absorbing chemical monolayer process. FT-IR, EDS and XPS analyses speculated that the amidoxime and amino synergistically increased the uranium uptake. The inhibitory activities of DC-AO-PHMG against three aquatic bacteria, BEY, BEL (from Yellow River water and lake bottom silt, respectively) and B. subtilis were significantly stronger, and the uranium adsorption was not impacted by the high bacteria content. Most importantly, DC-AO-PHMG removed up to 94 % of uranium in simulated seawater and extracted up to 4.65 mg/g of uranium from Salt Lake water, which demonstrated its great potential in the field of uranium resource recovery.


Assuntos
Fibra de Algodão , Oximas , Urânio , Urânio/química , Adsorção , Oximas/química , Esgotos/química , Esgotos/microbiologia , Cinética , Antibacterianos/farmacologia , Antibacterianos/química , Purificação da Água/métodos
20.
Environ Sci Technol ; 58(28): 12498-12508, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38900106

RESUMO

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.


Assuntos
Carbono , Desnitrificação , Aprendizado de Máquina , Águas Residuárias/química , Nitrogênio , Eliminação de Resíduos Líquidos/métodos , Esgotos/microbiologia
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