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1.
Biol Reprod ; 111(2): 406-413, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38582608

RESUMEN

The aim of this study was to evaluate the role of angiotensin-converting enzyme 1 (ACE1) in H2O2-induced trophoblast cell injury and the potential molecular mechanisms. Oxidative stress was modeled by exposing HTR-8/SVneo cells to 200 µM H2O2. Western blot and real-time quantitative PCR methods were used to detect protein and mRNA expression level of ACE1 in chorionic villus tissue and trophoblast HTR-8/SVneo cell. Inhibition of ACE1 expression was achieved by transfection with small interfering RNA. Then flow cytometry, Cell Counting Kit-8, and Transwell assay was used to assess apoptosis, viability, and migration ability of the cells. Reactive oxygen species (ROS) were detected by fluorescent probes, and malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) activities were determined by corresponding detection kits. Angiotensin-converting enzyme 1 expression was upregulated in chorionic villus tissue of patients with missed abortion (MA) compared with individuals with normal early pregnancy abortion. H2O2 induced elevated ACE1 expression in HTR-8/SVneo cells, promoted apoptosis, and inhibited cell viability and migration. Knockdown of ACE1 expression inhibited H2O2-induced effects to enhance cell viability and migration and suppress apoptosis. Additionally, H2O2 stimulation caused increased levels of ROS and MDA and decreased SOD and GSH activity in the cells, whereas knockdown of ACE1 expression led to opposite changes of these oxidative stress indicators. Moreover, knockdown of ACE1 attenuated the inhibitory effect of H2O2 on the Nrf2/HO-1 pathway. Angiotensin-converting enzyme 1 was associated with MA, and it promoted H2O2-induced injury of trophoblast cells through inhibiting the Nrf2 pathway. Therefore, ACE1 may serve as a potential therapeutic target for MA.


Asunto(s)
Aborto Retenido , Peróxido de Hidrógeno , Peptidil-Dipeptidasa A , Trofoblastos , Humanos , Trofoblastos/metabolismo , Trofoblastos/efectos de los fármacos , Peróxido de Hidrógeno/farmacología , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Femenino , Embarazo , Aborto Retenido/genética , Aborto Retenido/metabolismo , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Línea Celular , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Adulto , Movimiento Celular/efectos de los fármacos
2.
Liver Int ; 44(6): 1351-1362, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38436551

RESUMEN

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.


Asunto(s)
Carcinoma Hepatocelular , Aprendizaje Profundo , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Invasividad Neoplásica , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Microvasos/diagnóstico por imagen , Microvasos/patología , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia
3.
Anticancer Drugs ; 35(6): 584-596, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38518088

RESUMEN

Human epidermal growth factor receptor 2-tyrosine kinase inhibitors (HER2-TKIs) have been extensively utilized for treating HER2-positive metastatic breast cancer (MBC), with numerous clinical trial reports available. We aim to systematically perform a comprehensive clinical evaluation on HER2-TKIs, provide a reference for the clinical rational use of drugs, and serve for the decision-making of the national drug policy. We performed comprehensive clinical evaluation in six dimensions including safety, effectiveness, economy, suitability, accessibility, and innovation through meta-analysis, literature review, drug administration websites, and other relevant medication data to analyze HER2-TKIs in treating HER2-positive MBC. For safety, the risk of ≥ grade 3 adverse events among pyrotinib, lapatinib, and neratinib is not significantly different. Furthermore, pyrotinib and neratinib were found to be higher in the risk of ≥ grade 3 diarrhea than lapatinib, however the risk could be reversed and prevented with loperamide. Regarding effectiveness and economy, pyrotinib was confirmed to have the best efficacy and cost-utility value, neratinib the second, and lapatinib the third. As regards innovation and suitability, pyrotinib showed better than other HER2-TKIs. In addition, pyrotinib received a higher recommendation than other HER2-TKIs in patients with HER2-positive MBC. The accessibility of pyrotinib was found to be the best with better urban, rural, and national affordability and lower annual treatment costs. Pyrotinib is more valuable in clinics with better safety, effectiveness, economy, suitability, accessibility, and innovation in HER2-positive MBC. This study could provide references for the clinical application of HER2-TKIs in treating HER2-positive MBC.


Asunto(s)
Neoplasias de la Mama , Inhibidores de Proteínas Quinasas , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Femenino , Inhibidores de Proteínas Quinasas/uso terapéutico , Lapatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Acrilamidas , Aminoquinolinas
4.
J Phys Chem A ; 128(43): 9486-9496, 2024 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-39418636

RESUMEN

Changes in atmospheric humidity affect the number of water molecules surrounding o-nitrophenol (ONP), creating an anisotropic chemical environment. It, in turn, influences the photodynamic behaviors of ONP, differing from those observed in the gas phase and in solution. Recently, we explored the excited-state decay and the generation of the hydroxyl (OH) radical before proton transfer of ONP in the microsolvated environment using the MS-CASPT2//CASSCF approach. As is well known, ONP is capable of converting to its aci-nitro isomer (aciONP) via an excited-state intramolecular proton transfer (ESIPT) process. In the present work, the photoinduced dynamics of aciONP, which can lead to an OH radical and nitrous acid (HONO), was studied using the same computational model. Our calculations demonstrated that increasing the number of water molecules affects the molecular geometries, particularly the key bond lengths and dihedral angles of the HONO group, while also reducing the relative energies of minima and intersections. Moreover, we identified two distinct types of minimum structures: one that retains the intramolecular hydrogen bond and the other that breaks the hydrogen bond with the H atom flipping outward. The latter structure, compared with the former, has a different electronic-state character and facilitates intersystem crossing processes. Subsequently, two major excited-state decay paths were proposed: (PATH I) ESIPT → S1 → S1S0 → S0; (PATH II) ESIPT → S1 → S1-2 → S1T1 → T1 → S0T1 → S0. Furthermore, the T1 state has a relatively long lifetime, allowing for the formation of the OH radical and HONO, and the corresponding energy barriers decrease as the number of water molecules increases. These theoretical findings provide valuable insights into the photodynamics of aciONP in the microsolvated atmospheric environment.

5.
J Phys Chem A ; 128(43): 9497-9509, 2024 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-39425687

RESUMEN

As a potential source of the hydroxyl (OH) radical and nitrous acid (HONO), photolysis of o-nitrophenol (ONP) is of significant interest in both experimental and theoretical studies. In the atmospheric environment, the number of water molecules surrounding ONP changes with the humidity of the air, leading to an anisotropic chemical environment. This may have an impact on the photodynamics of ONP and provide a mechanism that differs from previously reported ones in the gas phase or in solution. Herein, the high-level MS-CASPT2//CASSCF method was performed to elucidate the excited-state decay and the generation of the OH radical for ONP before proton transfer in the microsolvated surrounding. We found that the varying number of water molecules affects the ground-state structures and alters the energy levels of nπ* and ππ* at the Franck-Condon (FC) region. Nevertheless, this is not the case for the excited-state minima, which exhibit very similar adiabatic excitation properties. In addition, the presence of water molecules also significantly influences the intersection structures since hydrogen bonds will hinder or alleviate the rotation or pyramidalization of the nitro (NO2) group. This will, in turn, change the excited-state relaxation mechanism of ONP. Finally, we speculated that the OH radical might be formed in the hot ground state of ONP in the microsolvated surrounding after exploring all possible electronic states.

6.
Med Sci Monit ; 30: e942888, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38576138

RESUMEN

BACKGROUND This retrospective study aimed to compare patient outcomes from standard total knee arthroplasty (TKA) vs navigation-guided arthroplasty using the Brainlab software-guided surgical system at Cangzhou Hospital of Integrated TCM-WM, Hebei, Hebei Province, China from January 2021 to July 2023. MATERIAL AND METHODS A total of 239 patients who underwent total knee arthroplasty in Cangzhou Hospital of Integrated TCM-WM, Hebei from January 2021 to July 2023 were retrospectively analyzed. According to the inclusion criteria, 212 eligible patients were selected for analysis and divided into a Navigation Group (NG) (n=105) and a Traditional Group (TG) (n=107) according to surgical method used. Outcomes measured included duration of disease, operative time, intraoperative blood loss volume, postoperative length of hospital stay, and pain measured by the hospital for special surgery knee score (HSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and forgotten joint score (FJS). RESULTS The comparison of perioperative results between the 2 groups showed that the incision length in the NG was significantly longer than that in the TG (P<0.001, 95% Cl 2.59-3.35). At 3 months after surgery, the HSS score of the NG was statistically higher than that of the TG (P=0.002, 95% Cl 3.42-4.46); the WOMAC score of the NG was lower than that of the TG (P<0.001, 95% Cl -4.41-2.87); and the FJS score of the NG was significantly higher than that of the TG (P=0.003, 95% Cl 2.39-3.67). CONCLUSIONS Compared with conventional TKA, use of the Brainlab navigation system is associated with a longer incision, more accurate implantation position of the prosthesis, faster recovery of knee joint function, and helps patients to "forget" about their knee prosthesis in the short term.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Herida Quirúrgica , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Resultado del Tratamiento
7.
J Integr Neurosci ; 23(5): 89, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38812380

RESUMEN

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.


Asunto(s)
Sensibilización del Sistema Nervioso Central , Neuralgia , Neuralgia/terapia , Neuralgia/fisiopatología , Humanos , Sensibilización del Sistema Nervioso Central/fisiología , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo
8.
Sensors (Basel) ; 24(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39275437

RESUMEN

Maglev vehicles apply the entire vehicle load uniformly onto bridges through levitation forces. In assessing the dynamic characteristics of the maglev train-bridge coupling system, it is reasonable to simplify the distributed levitation force as a concentrated force. This article theoretically derives the analytical response of bridge dynamics under the action of a single constant force and conducts numerical simulations for a moving single constant force and a series of equally spaced constant forces passing over simply supported beams and two-span continuous beams, respectively. The topic of discussion is the response of bridge dynamics when different degrees of force concentration are involved. High-precision displacement and acceleration sensors were utilized to conduct tests on the Shanghai maglev line to verify the accuracy of the simulation results. The results indicate that when simplifying the distributed levitation force into a concentrated force model, a frequency ratio can be used to analyze the conditions for resonance between the train and the bridge and to calculate the critical speed of the train; the levitation distribution force of a high-speed maglev vehicle can be simplified into four groups of concentrated forces based on the number of levitation frames to achieve sufficient accuracy, with the dynamic response of the bridge being close to that under distributed loads.

9.
Oncology ; 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38061334

RESUMEN

INTRODUCTION: Atypical small acinar proliferation (ASAP) is detected in approximately 5% of prostate biopsies. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. However, clinical significance and outcomes of repeat biopsy are conflicting. Based on this situation, we conducted a meta-analysis to report the rate of clinically significant prostate cancer (csPCa) on repeat biopsy after a diagnosis of atypical small acinar proliferation (ASAP) to determine the safety and validity of deferring repeat biopsy. METHODS: We searched PubMed, Medline, Web of Science, and Embase databases for articles published until July 2023. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias for the included studies. Pooled ratios and 95% confidence intervals (CIs) were calculated using Stata 17. RESULTS: Sixteen studies and 1,796 patients were included in the meta-analysis. A total of 553 patients were diagnosed with prostate cancer, and 204 had csPCa. The pooled rate of csPCa on repeat biopsy after ASAP diagnosis was 12.1% (95%CI: 0.09, 0.15), which is a relatively low progression rate. However, we observed heterogeneity among the 16 articles. Subgroup analysis was performed, and patients who underwent repeat biopsy within 6 months according to the guidelines had a lower csPCa incidence (effective size (ES)=0.09, 95%CI: 0.060, 0.120) than those who underwent biopsy after more than 6 months (ES=0.221, 95%CI: 0.094, 0.349). CONCLUSION: Repeat biopsy can be safely deferred for patients diagnosed with ASAP. We believe our results may help to improve management strategies and encourage clinicians to choose more patient-friendly or non-invasive diagnostic evaluations.

10.
Epilepsia ; 64(10): 2667-2678, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37522416

RESUMEN

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

11.
Langmuir ; 39(7): 2808-2817, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36763097

RESUMEN

After an oil spill incident, the spilled oil slicks are observed to migrate to the shoreline area. Under the turbulent conditions, they break into small droplets and are suspended in the water column. The dispersed droplets are expected to interact with the suspended particles and form the oil-particle aggregates (OPAs), which significantly changes the transport of the oil. Instead of an earlier assumption that particles cover the oil surface, thus preventing further breakage or aggregation of OPAs, recent studies demonstrated that particles act like projectiles penetrating the oil droplets, resulting in the breakage of OPAs over a longer period of time. A model looking into the OPA breakup through two breakup mechanisms was proposed for the first time. The first method depicted the breakup of one large OPA into two daughter droplets owing to the turbulent nature, while the second method demonstrated the tear of the OPA surface layer caused by particle uprooting. The model was then calibrated by an experimental study targeting crude oil with varied viscosities, along with previous experimental investigations. Three key factors were identified accounting for the breakage of OPAs, where the increase in particle concentration in the natural environment and the increase in turbulent energy of the surrounding flows benefited the breakage of OPAs, and the increase in oil viscosity suppressed the breakage due to large resistance to shear stress. Besides these elements, the impact of the particle shape on the penetration depth was discussed. The model serves as a fundamental theory to describe the evolution of OPAs for fragmentation behavior.

12.
Environ Sci Technol ; 57(6): 2341-2350, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36723450

RESUMEN

Spilled oil slicks are likely to break into droplets in the subtidal and intertidal zones of seashores due to wave energy. The nonliving suspended fine particles in coastal ecosystems can interact with the dispersed oil droplets, resulting in the formation of Oil Particle Aggregates (OPAs). Many investigations assumed that these aggregates will settle due to the particles' high density. Recent studies, however, reported that some particles penetrate the oil droplets, which results in further breakup while forming smaller OPAs that remain suspended in the water column. Here, we investigated the interaction of crude oil droplets with intertidal and subtidal sediments, as well as artificial pure kaolinite, in natural seawater. Results showed that the interaction between oil droplets and intertidal sediments was not particularly stable, with an Oil Trapping Efficiency (OTE) < 25%. When using subtidal sediments, OTE reached 56%. With artificial kaolinite, OPA formation and breakup were more significant (OTE reaching up to 67%) and occurred faster (within 12 h). Oil chemistry analysis showed that the biodegradation of oil in seawater (half-life of 485 h) was significantly enhanced with the addition of sediments, with half-lives of 305, 265, and 150 h when adding intertidal sediments, subtidal sediments, and pure kaolinite, respectively. Such results reveal how the sediments' shape and size affect the various oil-sediment interaction mechanisms, and the subsequent impact on the microbial degradation of petroleum hydrocarbons. Future studies should consider investigating the application of fine (several microns) and sharp (elongated-sheeted) sediments as a nondestructive and nontoxic technique for dispersing marine oil spills.


Asunto(s)
Contaminación por Petróleo , Petróleo , Contaminantes Químicos del Agua , Sedimentos Geológicos , Ecosistema , Caolín , Contaminantes Químicos del Agua/análisis , Agua de Mar , Biodegradación Ambiental
13.
Clin Lab ; 69(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37145070

RESUMEN

BACKGROUND: Altered anti-CD25 antibody levels in plasma have been observed in patients with various solid malignancies. The present study aimed to determine whether circulating anti-CD25 antibody levels were altered in bladder cancer (BC). METHODS: An enzyme-linked immunosorbent assay was developed in-house to detect plasma IgG antibodies against three CD25-derived linear peptide antigens in 132 patients with BC and 120 control subjects. RESULTS: The Mann-Whitney U-test indicated that the plasma levels of anti-CD25a (Z = -10.11, p < 0.001), anti-CD25b (Z = -12.79, p < 0.001), and anti-CD25c IgG (Z = -11.95, p < 0.001) were significantly lower in BC patients than in the control group. Further analysis indicated that the plasma levels of anti-CD25a IgG antibody were stage-dependent and associated with different postoperative histological grades (U = 977.5, p = 0.003). The receiver operating characteristic curve analysis showed that the area under the ROC curve (AUC) was 0.869 for anti-CD25a IgG (95%, 0.825 - 0.913), 0.967 for anti-CD25b IgG (95%, 0.945 - 0.988), and 0.936 for anti-CD25c IgG (95%, 0.905 - 0.967), with a sensitivity of 91.3% for the anti-CD25a IgG assay, 98.8% for the anti-CD25b IgG assay, and 96.7% for the anti-CD25c IgG assay, against a specificity of 95%. CONCLUSIONS: The present study suggests that circulating anti-CD25 IgG may have a potential predictive value for clinical staging and histological grading of BC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias Pulmonares/patología , Péptidos , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G
14.
Int J Urol ; 30(12): 1122-1132, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37602677

RESUMEN

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.


Asunto(s)
Síndrome Nefrótico , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Vejiga Urinaria , Inmunoterapia , Microambiente Tumoral , Pronóstico , Proteínas del Tejido Nervioso
15.
Chem Biodivers ; 20(2): e202201020, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36536172

RESUMEN

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase  H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the  H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC50 ) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC50 =18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.


Asunto(s)
Insecticidas , Mariposas Nocturnas , Animales , Simulación del Acoplamiento Molecular , Insecticidas/farmacología , Larva , Sulfonamidas , Adenosina Trifosfatasas , Piridinas , Sulfanilamida , Estructura Molecular , Relación Estructura-Actividad
16.
Drug Dev Ind Pharm ; 49(2): 217-231, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36994666

RESUMEN

OBJECTIVE: To prepare porous core-shell composite particles (PCPs) in order to improve the flowability and compactibility of powder materials for direct compaction (DC), as well as the dissolution of tablets. SIGNIFICANCE: The results obtained are meaningful to boosting the development and further research of PCPs on DC. Methods: In this study, hydroxypropyl methylcellulose (HPMC E3) and polyvinylpyrrolidone (PVP K30) were selected as shell materials, the Xiao Er Xi Shi formulation powder (XEXS) was used as the core materials, ammonium bicarbonate (NH4HCO3), and sodium bicarbonate (NaHCO3) were employed as pore-forming agent. Using co-spray drying method to prepare composite particles (CPs). Then, the physical properties and comparison between different CPs were characterized comprehensively. Finally, the different CPs were directly compacted as tablets to explore the effect on the dissolution behavior of DC tablets, respectively. RESULTS: (i) The XEXS PCPs were prepared successfully by co-spray drying, and the yield of PCPs is almost 80%; (ii) The TS values of PCP-X-P-Na, PCP-X-P-NH4, PCP-X-H-Na and PCP-X-P-Na were 5.70, 7.56, 3.98, and 6.88 times higher than that of raw material (X); (iii) The disintegration time of PCPs tablets decreased 10-25% when compared with CPs tablets; (iv) The values of Carr's index (CI), Hausner ratio (HR), Caking strength (CS), and Cohesion index (CoI) of PCP-X-H-NH4 were 19.16%, 19.29%, 40.14%, and 6.39% lower than that of X, respectively. CONCLUSIONS: The PCPs prepared by co-spray drying did improve the flowability and compactibility of powder, as well as the dissolution of tablets.


Asunto(s)
Povidona , Polvos , Porosidad , Composición de Medicamentos/métodos , Comprimidos , Solubilidad
17.
J Asian Nat Prod Res ; 25(4): 379-386, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35866233

RESUMEN

Sixty-nine 4-propargyloxybenzene sulfonamide derivatives with different amino acids as amino substituent were synthesized and evaluated for their insecticidal activity against third-instar Mythimna separate. The bioassay results revealed that some derivatives bearing amino acid ester group performed good insecticidal activity against third-instar M.separata, such as the LC50 values of D18 and D19 were 4.28 and 2.96 mg/ml after 48 h, in particular, the LC50 of D16 was 2.38 mg/ml and the activity was improved by 14 times compared to celangulin V (34.48 mg/ml). The above results provided theoretical and experimental basis for the discovery of novel insecticidal active compounds.


Asunto(s)
Insecticidas , Mariposas Nocturnas , Animales , Aminoácidos , Sulfonamidas , Ésteres , Sulfanilamida , Larva , Relación Estructura-Actividad , Estructura Molecular
18.
J Asian Nat Prod Res ; 25(6): 571-580, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36125926

RESUMEN

A series of 4-(propargyloxy) benzenesulfonamide derivatives with different substituents on the benzene ring were synthesized and evaluated for their insecticidal activity. Some of the compounds showed good insecticidal activity against Mythimna separata, and the LC50 value of the most active compound B2.5 was 0.235 mg/ml. Ultrastructural changes in the midgut epithelial cells of Mythimna separata were observed using transmission electron microscopy, and severe structural damage was found in microvilli, mitochondria and rough endoplasmic reticulum. It indicates that the possible site of action of these benzenesulfonamides is the cytoplasmic membrane and endomembrane system of the midgut epithelial cells. The above provides a basis for the development of novel insecticidal active compounds with a novel mechanism of action.


Asunto(s)
Insecticidas , Mariposas Nocturnas , Animales , Larva , Insecticidas/farmacología , Mariposas Nocturnas/ultraestructura , Estructura Molecular , Bencenosulfonamidas
19.
Int J Mol Sci ; 24(13)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37446356

RESUMEN

In order to explore the effects of high temperature stress on the physiological characteristics of Paeonia ostii, the Paeonia ostii were subjected to 25 °C, 35 °C, 38 °C, and 40 °C for 7 days. Meanwhile, the physiological indicators of oxidative stress (hydrogen peroxide, H2O2; malondialdehyde, MDA; relative electrical conductivity, REC), antioxidant enzyme activity (superoxide dismutase, SOD; ascorbate peroxidase, APX; catalase, CAT; peroxidase, POD), photosynthetic pigment content (chlorophyll a, Chla; chlorophyll b, Chlb), photosynthetic characteristics (net photosynthetic rate, Pn; intercellular CO2 concentration, Ci; stomatal conductance, Gs; transpiration rate, Tr), and osmoregulatory substances content (soluble protein, SP; soluble sugar, SS) were determined. The results showed that, with the increase in temperature and stress time, the H2O2 content, MDA content, REC value, CAT activity, and APX activity increased, while Chla content, Chlb content, SS content, and SP content decreased. With the extension of stress time, the SOD activity, POD activity, and Tr value of each high temperature stress group first increased and then decreased; Ci first decreased, then increased, and then decreased; meanwhile, Pn and Gs showed an overall downward trend. PLS-DA (partial least squares discriminant analysis) was used to analyze the changes in physiological and biochemical indexes of peony leaves under 40 °C stress for different days. SOD was found to be the biggest factor affecting the changes in physiological and biochemical indexes of peony leaves treated with different days of stress.


Asunto(s)
Paeonia , Paeonia/metabolismo , Clorofila A , Temperatura , Peróxido de Hidrógeno/metabolismo , Clorofila/metabolismo , Fotosíntesis , Antioxidantes/farmacología , Superóxido Dismutasa/metabolismo , Hojas de la Planta/metabolismo , Estrés Fisiológico
20.
Medicina (Kaunas) ; 59(10)2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37893490

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has clearly had a great influence on the lifestyles of the population, especially on patients with type 2 diabetes mellitus. During the COVID-19 outbreak, many countries/regions implemented social-isolation measures, leading to an increase in negative behaviors and impairing the capability of diabetic patients to resist COVID-19, ultimately causing severe prognoses. Moreover, as the epidemic progressed, multiple studies emphasized the significance of physical exercise in the management of type 2 diabetic patients infected with COVID-19. In this study, we selected research from 1 December 2019 to 9 August 2023 that focused on COVID-19-infected diabetic patients to investigate the impact of type 2 diabetes on the immune functions, inflammation factor levels, lung injuries, and mental disorders of such patients, as well as to assess the risk of novel coronavirus pneumonia in these patients. Additionally, the effects of high-intensity, moderate-intensity, and low-intensity exercises on novel coronavirus pneumonia infection in type 2 diabetic patients and the mechanisms of the effects of such exercise were considered. We concluded that elderly diabetic patients with COVID-19 should perform low-intensity exercises to facilitate their recoveries. This study offers guidance for a proper understanding of the dangers of diabetes and the use of appropriate measures to reduce the risk of novel coronavirus pneumonia infections in type 2 diabetic patients.


Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Trastornos Mentales , Humanos , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , SARS-CoV-2 , Trastornos Mentales/epidemiología , Ejercicio Físico
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