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1.
Org Biomol Chem ; 22(26): 5325-5332, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38874178

RESUMO

In this paper, the hydrogenation of aldehydes and ketones using the RANEY® nickel catalyst was successfully applied for the synthesis of alcohol compounds without additional column chromatographic purification. This synthetic strategy features a wide range of substrates, excellent atom economy, high chemical discrimination and the use of a ligand-free catalytic system. Reactions were performed at room temperature in water providing alcohols in high yields and purity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38828494

RESUMO

Background: The comprehensive treatment mode of combining concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (AC) is a commonly used mainstream model in the clinical practice of locally advanced cervical cancer (LACC). However, the necessity for AC after CCRT lacks sufficient evidence-based medical support. This study constructs a predictive model for the survival time dependence of CCRT ± AC for LACC based on the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging with internal validation, the prognosis was assessed with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin, and provides guidance for future stratified treatment. Materials and Methods: The retrospective analysis included 482 patients with LACC who CCRT from January 2016 to January 2023. Patients who used the 2009 FIGO staging were all standardized for the 2018 FIGO staging. The 482 patients with LACC were divided into a training set (n = 290) and a validation set (n = 192) at a ratio of 6:4. COX multivariate regression model and LASSO regression were used to screen for independent prognostic factors affecting progression-free survival (PFS) and overall survival (OS), and a nomogram clinical prediction model was constructed based on these factors. Evaluate the effectiveness of the model through the receiver operating characteristic curve, calibration curve, decision curve, risk heat map, and survival curves for risk stratification. Results: The PFS and OS independent prognostic risk factors affecting the 2018 FIGO staging of LACC during CCRT were validated to be similar to the 2009 FIGO staging prediction model reported in previous literature. In the training cohort, area under the curve (AUC) values at 1, 3, and 5 years were 0.941, 0.882, and 0.885 for PFS, and 0.946, 0.946, and 0.969 for OS, respectively. When applied to a test cohort, the model also showed accurate prediction result (AUC at 1, 3, and 5 years were 0.869, 0.891, and 0.899 for PFS, and 0.891, 0.941 and 0.878 for OS, respectively). Subgroup analysis suggests that patients with LACC, adenocarcinoma, stage IVA, pelvic lymph node metastasis, pretreatment hemoglobin ≤100 g/l and residual tumor diameter >2 cm, who received CCRT in the 2018 FIGO stage, may benefit more from adjuvant chemtherapy. Conclusions: Based on the 2018 FIGO staging, a nomogram prediction model for PFS and OS in patients with LACC undergoing CCRT was developed. The model, established by combining weighted clinical and pathological factors, can provide more personalized treatment predictions in clinical practice. For patients with high-risk factors such as residual tumor diameter > 2 cm after CCRT for LACC, AC may bring benefits.

3.
Phytomedicine ; 131: 155786, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38875812

RESUMO

BACKGROUND: Although AMP-activated protein kinase (AMPK) has been extensively studied in cellular processes, the understanding of its substrates, downstream functions, contributions to cell fate and colorectal cancer (CRC) progression remains incomplete. PURPOSE: The aim of this study was to investigate the effects and mechanisms of naringenin on CRC. METHODS: The biological and cellular properties of naringenin and its anticancer activity were evaluated in CRC. In addition, the effect of combined treatment with naringenin and 5-fluorouracil on tumor growth in vitro and in vivo was evaluated. RESULTS: The present study found that naringenin inhibits the proliferation of CRC and promote its apoptosis. Compared with the naringenin group, naringenin combined with 5-fluorouracil had significant effect on inhibiting cell proliferation and promoting its apoptosis. It is showed that naringenin activates AMPK phosphorylation and mitochondrial fusion in CRC. Naringenin combined with 5-fluorouracil significantly reduces cardiotoxicity and liver damage induced by 5-fluorouracil in nude mice bearing subcutaneous CRC tumors, and attenuates colorectal injuries in azoxymethane/DSS dextran sulfate (AOM/DSS)-induced CRC. The combination of these two drugs alters mitochondrial function by increasing reactive oxygen species (ROS) levels and decreasing the mitochondrial membrane potential (MMP), thereby stimulating AMPK/mTOR signaling. Mitochondrial dynamics are thereby regulated by activating the AMPK/p-AMPK pathway, and mitochondrial homeostasis is coordinated through increased mitochondrial fusion and reduced fission to activate apoptosis in cancer cells. CONCLUSIONS: Our data suggest that naringenin is important for inhibiting CRC proliferation, possibly through the AMPK pathway, to regulate mitochondrial function and induce apoptosis in CRC.


Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Proliferação de Células , Neoplasias Colorretais , Flavanonas , Fluoruracila , Camundongos Nus , Mitocôndrias , Espécies Reativas de Oxigênio , Flavanonas/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fluoruracila/farmacologia , Camundongos , Linhagem Celular Tumoral , Masculino , Camundongos Endogâmicos BALB C , Fosforilação/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38942395

RESUMO

PURPOSE: This study aimed to determine whether radiotherapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH)in left breast cancer patients. METHODS AND MATERIALS: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104/136 plans were selected for RP model training. A total of 32/136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. RESULTS: Two RP models were established for post breast-conserving surgery (BCS) and post modified radical mastectomy (MRM). There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the two plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < 0.05) and moderately correlated in patients after MRM (0.46 ≤ r ≤ 0.58, P < 0.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the two surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. CONCLUSIONS: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH.

7.
Luminescence ; 39(5): e4743, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38692854

RESUMO

A unique luminescent lanthanide metal-organic framework (LnMOF)-based fluorescence detection platform was utilized to achieve sensitive detection of vomitoxin (VT) and oxytetracycline hydrochloride (OTC-HCL) without the use of antibodies or biomolecular modifications. The sensor had a fluorescence quenching constant of 9.74 × 106 M-1 and a low detection limit of 0.68 nM for vomitoxin. Notably, this is the first example of a Tb-MOF sensor for fluorescence detection of vomitoxin. We further investigated its response to two mycotoxins, aflatoxin B1 and ochratoxin A, and found that their Stern-Volmer fluorescence quenching constants were lower than those of VT. In addition, the fluorescence sensor realized sensitive detection of OTC-HCL with a detection limit of 0.039 µM. In conclusion, the method has great potential as a sensitive and simple technique to detect VT and OTC-HCL in water.


Assuntos
Estruturas Metalorgânicas , Oxitetraciclina , Térbio , Oxitetraciclina/análise , Oxitetraciclina/química , Térbio/química , Estruturas Metalorgânicas/química , Espectrometria de Fluorescência , Corantes Fluorescentes/química , Limite de Detecção , Água/química , Fluorescência , Poluentes Químicos da Água/análise
8.
Small ; : e2402284, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801397

RESUMO

2D lamellar nanofiltration membrane is considered to be a promising approach for desalinating seawater/brackish water and recycling sewage. However, its practical feasibility is severely constrained by the lack of durability and stability. Herein, a ternary nanofiltration membrane via a mixed-dimensional assembly of 2D boron nitride nanosheets (BNNS) is fabricated, 1D aramid nanofibers (ANF), and 2D covalent organic frameworks (COF). The abundant 2D and 1D nanofluid channels endow the BNNS/ANF/COF membrane with a high flux of 194 L·m‒2·h‒1. By the synergies of the size sieving and Donnan effect, the BNNS/ANF/COF membrane demonstrates high rejection (among 98%) for those dyes whose size exceeds 1.0 nm. Moreover, the BNNS/ANF/COF membrane also exhibits remarkable durability and mechanical stability, which are attributed to the strong adhesion and interactions between BNNS, ANF, and COF, as well as the superior mechanical robustness of ANF. This work provides a novel strategy to develop robust and durable 2D lamellar nanofiltration membranes with high permeance and selectivity simultaneously.

9.
Ital J Pediatr ; 50(1): 84, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38650007

RESUMO

BACKGROUND: The COVID-19 pandemic have impacts on the prevalence of other pathogens and people's social lifestyle. This study aimed to compare the pathogen, allergen and micronutrient characteristics of pediatric inpatients with pneumonia prior to and during the COVID-19 pandemic in a large tertiary hospital in Shanghai, China. METHODS: Patients with pneumonia admitted to the Department of Pediatric Pulmonology of Xinhua Hospital between March-August 2019 and March-August 2020 were recruited. And clinical characteristics of the patients in 2019 were compared with those in 2020. RESULTS: Hospitalizations for pneumonia decreased by 74% after the COVID-19 pandemic. For pathogens, virus, mycoplasma pneumoniae (MP) and mixed infection rates were all much lower in 2020 than those in 2019 (P < 0.01). Regarding allergens, compared with 2019, the positive rates of house dust mite, shrimp and crab were significantly higher in 2020 (P < 0.01). And for micronutrients, the levels of vitamin B2, B6, C and 25-hydroxyvitamin D (25(OH)D) in 2020 were observed to be significantly lower than those in 2019 (P < 0.05). For all the study participants, longer hospital stay (OR = 1.521, P = 0.000), milk allergy (OR = 6.552, P = 0.033) and calcium (Ca) insufficiency (OR = 12.048, P = 0.019) were identified as high-risk factors for severe pneumonia by multivariate analysis. CONCLUSIONS: The number of children hospitalized with pneumonia and incidence of common pathogen infections were both reduced, and that allergy and micronutrient status in children were also changed after the outbreak of the COVID-19 pandemic.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Criança , China/epidemiologia , Pré-Escolar , Hospitalização/estatística & dados numéricos , Lactente , SARS-CoV-2 , Pneumonia/epidemiologia , Adolescente
10.
Artigo em Inglês | MEDLINE | ID: mdl-38649427

RESUMO

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

11.
Int J Cardiol ; 407: 131973, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508321

RESUMO

BACKGROUND: This study purposed to design and establish a nomogram to predict the risk of having heart failure with preserved ejection fraction. METHOD: The clinical data of 1031 patients diagnosed with heart failure (HF) in the First Affiliated Hospital of Jinan University from January 2018 to December 2022 were retrospectively analyzed, among which 618 patients were diagnosed with heart failure with preserved ejection fraction (HFpEF). Patients were randomly divided into a training set (70%, n = 722) and a validation set (30%, n = 309). The prediction model of HFpEF was established by using clinical characteristic data parameters, and the risk of having HFpEF was predicted by using a nomogram. Single-factor analysis was used to select independent risk factors (P < 0.05), and then binary logistic regression was used to screen predictive variables (P < 0.05). The discrimination ability of the model was evaluated by the ROC curve and calculating the area under the curve (AUC). In addition, the predictive ability of the established nomogram was evaluated using calibration curves and the Hosmer-Lemeshow goodness of fit test (HL test), and the clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS: The results of binary logistic regression analysis showed that age, gender, hypertension, coronary heart disease, glycosylated hemoglobin, serum creatinine, E/e' septal, relative wall thickness (RWT), left ventricular mass index (LVMI) and pulmonary hypertension (PH) were independent influencing factors for the risk of having HFpEF (P < 0.05). Based on the results of logistic regression analysis, a nomogram was established and calibration curves were made. The prediction model showed that the AUC of the training dataset was 0.876 (95%CI, 0.851-0.902), and 0.837 (95%CI, 0.791-0.883) in the validation set. According to the calibration curves and HL test, the nomogram shows good calibration, and DCA shows that our model is clinically useful. CONCLUSION: A nomogram prediction model was constructed to predict the patient's risk of having HFpEF. This prediction model indicated that the combination of creatinine, E/e', RWT, LVMI and PH may be valuable in the diagnosis of HFpEF.


Assuntos
Insuficiência Cardíaca , Nomogramas , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Masculino , Feminino , Volume Sistólico/fisiologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Medição de Risco/métodos , Valor Preditivo dos Testes , Fatores de Risco
12.
Arh Hig Rada Toksikol ; 75(1): 81-84, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548379

RESUMO

Organophosphorus poisoning is a critical condition that can cause central nervous system depression, respiratory failure, and death early on. As its clinical manifestations closely resemble those of carbamate pesticide poisoning, the aim of this case study is to present a case of misdiagnosis, initially identifying carbofuran poisoning as organophosphate in a patient suspect of a heatstroke. We also present a case of intentional self-poisoning with organophosphate dichlorvos to underline the likelihood of pesticide poisoning in patients exhibiting acute cholinergic symptoms when the ingested substance is not known. In such cases, empirical treatment with atropine and oxime can be started pending timely differential diagnosis to adjust treatment as necessary.


Assuntos
Inseticidas , Intoxicação por Organofosfatos , Praguicidas , Intoxicação , Humanos , Carbamatos/uso terapêutico , Intoxicação por Organofosfatos/diagnóstico , Intoxicação por Organofosfatos/tratamento farmacológico , Diclorvós/uso terapêutico , Intoxicação/terapia
13.
Front Pediatr ; 12: 1308887, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464894

RESUMO

Objective: Childhood obesity has become a prominent issue in the society, which can lead to left ventricular remodeling and severe cardiovascular complications in adulthood. It is beneficial to identify the causes of left ventricular remodeling so that targeted measures can be taken to prevent the cardiovascular disease. Therefore, this study aimed to explore the relationship between left ventricular remodeling and changes in blood lipid indexes in obese children. Methods: This study was conducted on 40 healthy non-obese children and 140 obese children diagnosed in the pediatric health department of our hospital. Clinical data collected from the two groups were compared. Echocardiography was performed to examine left ventricular configuration and cardiac function. Multiple linear regression analysis was conducted to assess the independent effects of blood lipid levels on echocardiographic parameters. Blood lipid indicators among different left ventricular structural patterns which were classified according to left ventricular mass indexes and relative wall thickness were compared. Results: Obese children exhibited significantly increased height, weight, body mass index (BMI), body fat percentage (BFP), blood pressure, triglycerides, total cholesterol, left ventricular internal diameter (LVIDd), interventricular septum (IVSd), left ventricular posterior wall diastolic thickness (LVPWd), myocardial mass (LVM) and relative wall thickness (RWT), as well as lower high-density lipoprotein cholesterol (HDL-C) and left ventricular ejection fraction (LVEF) compared to the non-obese children (P < 0.05). Multiple linear correlation analysis showed LVM had a significantly positive correlation with BMI (r = 3.21, P = 0.002) and SBP (r = 2.61, P = 0.01); LVMI had a significantly negative correlation with HDL-C (r = -2.45, P = 0.015); RWT had a significantly positive correlation with SBP (r = 2.50, P = 0.013) but a significantly negative correlation with HDL-C (r = -2.35, P = 0.02). Furthermore, there were significant differences in HDL-C values among children with different ventricular configurations (P < 0.05), with the lowest HDL-C value recorded in the concentric hypertrophy group. Conclusion: Obese children will develop left ventricular remodeling. The left ventricular configuration indexes are most significantly associated with serum HDL-C. Lower HDL-C level contributes to severer left ventricular hypertrophy, indicating a concentric hypertrophy pattern.

14.
RSC Adv ; 14(11): 7601-7608, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38440271

RESUMO

The construction of a class of novel triazole molecules containing sulfonyl fluoride functionalities was achieved through Cu-catalyzed click chemistry in good to excellent yields. The sulfonyl fluoride moieties were cleaved completely under base conditions to produce N-unsubstituted triazoles quantitatively, which provides a strategy to combine SuFEx click chemistry with Cu-catalyzed click chemistry ingeniously.

15.
Cell Mol Life Sci ; 81(1): 123, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459149

RESUMO

Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5F/F; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair. PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair. Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.


Assuntos
Células-Tronco Neurais , Reparo de DNA por Recombinação , Animais , Camundongos , Arginina/metabolismo , Reparo do DNA , Instabilidade Genômica , Genômica , Histonas/genética , Histonas/metabolismo , Células-Tronco Neurais/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo
16.
Environ Pollut ; 348: 123813, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38537801

RESUMO

The removal of trace amounts of antibiotics from water environments while simultaneously avoiding potential environmental hazards during the treatment is still a challenge. In this work, green, harmless, and novel asymmetric mesoporous TiO2 (A-mTiO2) was combined with peroxodisulfate (PDS) as active components in a controlled-release material (CRM) system for the degradation of tetracycline (TC) in the dark. The formation of reactive oxygen species (ROS) and the degradation pathways of TC during catalytic PDS activation by A-mTiO2 powder catalysts and the CRMs were thoroughly studied. Due to its asymmetric mesoporous structure, there were abundant Ti3+/Ti4+ couples and oxygen vacancies in A-mTiO2, resulting in excellent activity in the activation of PDS for TC degradation, with a mineralization rate of 78.6%. In CRMs, ROS could first form during PDS activation by A-mTiO2 and subsequently dissolve from the CRMs to degrade TC in groundwater. Due to the excellent performance and good stability of A-mTiO2, the resulting constructed CRMs could effectively degrade TC in simulated groundwater over a long period (more than 20 days). From electron paramagnetic resonance analysis and TC degradation experiments, it was interesting to find that the ROS formed during PDS activation by A-mTiO2 powder catalysts and CRMs were different, but the degradation pathways for TC were indeed similar in the two systems. In PDS activation by A-mTiO2, besides the free hydroxyl radical (·OH), singlet oxygen (1O2) worked as a major ROS participating in TC degradation. For CRMs, the immobilization of A-mTiO2 inside CRMs made it difficult to capture superoxide radicals (·O2-), and continuously generate 1O2. In addition, the formation of sulfate radicals (·SO4-), and ·OH during the release process of CRMs was consistent with PDS activation by the A-mTiO2 powder catalyst. The eco-friendly CRMs had a promising potential for practical application in the remediation of organic pollutants from groundwater.


Assuntos
Antibacterianos , Tetraciclina , Espécies Reativas de Oxigênio , Preparações de Ação Retardada , Pós , Antibacterianos/química , Tetraciclina/química
17.
Zhongguo Zhong Yao Za Zhi ; 49(1): 185-196, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403351

RESUMO

This study investigated the effect of trametenolic acid(TA) on the migration and invasion of human hepatocellular carcinoma HepG2.2.15 cells by using Ras homolog gene family member C(RhoC) as the target and probed into the mechanism, aiming to provide a basis for the utilization of TA. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of HepG2.2.15 cells exposed to TA, and scratch and Transwell assays to examine the cell migration and invasion. The pull down assay was employed to determine the impact of TA on RhoC GTPase activity. Western blot was employed to measure the effect of TA on the transport of RhoC from cytoplasm to cell membrane and the expression of RhoC/Rho-associated kinase 1(ROCK1)/myosin light chain(MLC)/matrix metalloprotease 2(MMP2)/MMP9 pathway-related proteins. RhoC was over-expressed by transient transfection of pcDNA3.1-RhoC. The changes of F-actin in the cytoskeleton were detected by Laser confocal microscopy. In addition, the changes of cell migration and invasion, expression of proteins in the RhoC/ROCK1/MLC/MMP2/MMP9 pathway, and RhoC GTPase activity were detected. The subcutaneously transplanted tumor model of BALB/c nude mice and the low-, medium-, and high-dose(40, 80, and 120 mg·kg~(-1), respectively) TA groups were established and sorafenib(20 mg·kg~(-1)) was used as the positive control. The tumor volume and weight in each group were measured, and the expression of related proteins in the tumor tissue was determined by Western blot. The results showed that TA inhibited the proliferation of HepG2.2.15 cells in a concentration-dependent manner, with the IC_(50) of 66.65 and 23.09 µmol·L~(-1) at the time points of 24 and 48 h, respectively. The drug administration groups had small tumors with low mass. The tumor inhibition rates of sorafenib and low-, medium-and high-dose TA were 62.23%, 26.48%, 55.45%, and 62.36%, respectively. TA reduced migrating and invading cells and inhibited RhoC protein expression and RhoC GTPase activity in a concentration-dependent manner, dramatically reducing RhoC and membrane-bound RhoC GTPase. The expression of ROCK1, MLC, p-MLC, MMP2, and MMP9 downstream of RhoC can be significantly inhibited by TA, as confirmed in both in vitro and in vivo experiments. After HepG2.2.15 cells were transfected with pcDNA3.1-RhoC to overexpress RhoC, TA down-regulated the protein levels of RhoC, ROCK1, MLC, p-MLC, MMP2, and MMP9 and decreased the activity of RhoC GTPase, with the inhibition level comparable to that before overexpression. In summary, TA can inhibit the migration and invasion of HepG2.2.15 cells. It can inhibit the RhoC/ROCK1/MLC/MMP2/MMP9 signaling pathway by suppressing RhoC GTPase activity and down-regulating RhoC expression. This study provides a new idea for the development of autophagy modulators targeting HSP90α to block the proliferation and inhibit the invasion and migration of hepatocellular carcinoma cells via multiple targets of active components in traditional Chinese medicines.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Proteína de Ligação a GTP rhoC/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Metaloproteinase 9 da Matriz/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Sorafenibe , Camundongos Nus , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Movimento Celular , Proliferação de Células
18.
J Org Chem ; 89(5): 3618-3628, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38358945

RESUMO

A one-pot, sequential three-component reaction between salicylaldehyde, indole, and 2-bromoprop-2-ene-1-sulfonyl fluoride (BPESF) has been demonstrated for the synthesis of sulfonyl fluoride substituted 4H-chromene derivatives in moderate to excellent yields (45%-94%). This one-pot sequential method features easily available starting materials, wide substrate scope, mild conditions, and great efficiency.

19.
Biochem Med (Zagreb) ; 34(1): 010901, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38361737

RESUMO

Introduction: Internal quality control (IQC) is a core pillar of laboratory quality control strategies. Internal quality control commercial materials lack the same characteristics as patient samples and IQC contributes to the costs of laboratory testing. Patient data-based quality control (PDB-QC) may be a valuable supplement to IQC; the smaller the biological variation, the stronger the ability to detect errors. Using the potassium concentration in serum as an example study compared error detection effectiveness between PDB-QC and IQC. Materials and methods: Serum potassium concentrations were measured by using an indirect ion-selective electrode method. For the training database, 23,772 patient-generated data and 366 IQC data from April 2022 to September 2022 were used; 15,351 patient-generated data and 246 IQC data from October 2022 to January 2023 were used as the testing database. For both PDB-QC and IQC, average values and standard deviations were calculated, and z-score charts were plotted for comparison purposes. Results: Five systematic and three random errors were detected using IQC. Nine systematic errors but no random errors were detected in PDB-QC. The PDB-QC showed systematic error warnings earlier than the IQC. Conclusions: The daily average value of patient-generated data was superior to IQC in terms of the efficiency and timeliness of detecting systematic errors but inferior to IQC in detecting random errors.


Assuntos
Laboratórios , Humanos , Controle de Qualidade
20.
J Imaging Inform Med ; 37(1): 374-385, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38343259

RESUMO

Fully supervised medical image segmentation methods use pixel-level labels to achieve good results, but obtaining such large-scale, high-quality labels is cumbersome and time consuming. This study aimed to develop a weakly supervised model that only used image-level labels to achieve automatic segmentation of four types of uterine lesions and three types of normal tissues on magnetic resonance images. The MRI data of the patients were retrospectively collected from the database of our institution, and the T2-weighted sequence images were selected and only image-level annotations were made. The proposed two-stage model can be divided into four sequential parts: the pixel correlation module, the class re-activation map module, the inter-pixel relation network module, and the Deeplab v3 + module. The dice similarity coefficient (DSC), the Hausdorff distance (HD), and the average symmetric surface distance (ASSD) were employed to evaluate the performance of the model. The original dataset consisted of 85,730 images from 316 patients with four different types of lesions (i.e., endometrial cancer, uterine leiomyoma, endometrial polyps, and atypical hyperplasia of endometrium). A total number of 196, 57, and 63 patients were randomly selected for model training, validation, and testing. After being trained from scratch, the proposed model showed a good segmentation performance with an average DSC of 83.5%, HD of 29.3 mm, and ASSD of 8.83 mm, respectively. As far as the weakly supervised methods using only image-level labels are concerned, the performance of the proposed model is equivalent to the state-of-the-art weakly supervised methods.

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