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1.
Chin J Integr Med ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38941044

RESUMEN

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.

2.
Int Immunopharmacol ; 136: 112338, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38850787

RESUMEN

Cardiac fibrosis is a typical feature of cardiac pathological remodeling, which is associated with adverse clinical outcomes and has no effective therapy. Nicotine is an important risk factor for cardiac fibrosis, yet its underlying molecular mechanism remains poorly understood. This study aimed to identify its potential molecular mechanism in nicotine-induced cardiac fibrosis. Our results showed nicotine exposure led to the proliferation and transformation of cardiac fibroblasts (CFs) into myofibroblasts (MFs) by impairing autophagy flux. Through the use of drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) technology, it was discovered that nicotine directly increased the stability and protein levels of lactate dehydrogenase A (LDHA) by binding to it. Nicotine treatment impaired autophagy flux by regulating the AMPK/mTOR signaling pathway, impeding the nuclear translocation of transcription factor EB (TFEB), and reducing the activity of cathepsin B (CTSB). In vivo, nicotine treatment exacerbated cardiac fibrosis induced in spontaneously hypertensive rats (SHR) and worsened cardiac function. Interestingly, the absence of LDHA reversed these effects both in vitro and in vivo. Our study identified LDHA as a novel nicotine-binding protein that plays a crucial role in mediating cardiac fibrosis by blocking autophagy flux. The findings suggest that LDHA could potentially serve as a promising target for the treatment of cardiac fibrosis.


Asunto(s)
Autofagia , Fibrosis , Nicotina , Animales , Autofagia/efectos de los fármacos , Ratas , Masculino , Ratas Endogámicas SHR , Transducción de Señal/efectos de los fármacos , Miocardio/patología , Miocardio/metabolismo , Lactato Deshidrogenasa 5/metabolismo , Células Cultivadas , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Ratas Sprague-Dawley
3.
Mol Plant ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38851887
4.
J Clin Med ; 13(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38930025

RESUMEN

Objective: The objective of this work was to assess the effect of physical therapy in patients with somatosensory tinnitus (ST) and explore the influence of physical therapy on clinical variables obtained before treatment. Methods: A total of 43 patients with ST were randomized to the immediate-start group (n = 20) and delayed-start group (n = 23). All patients received physical therapy for 1 week (seven sessions). Each session lasted 60 min. The Visual Analogue Scale (VAS), Tinnitus Handicap Inventory (THI), and numerical pain rating scale (NPRS) scores were documented at baseline and after treatment (week 1) for all patients. For subjects in the immediate-start group, the THI, VAS, and NPRS scores were measured after therapy (weeks 6, 9, and 12, respectively). Medical history characteristic functional activity scale (HCFA) scores were measured at baseline to assess the association between somatic symptoms and tinnitus. Results: At week 1, VAS, THI, and NPRS scores of patients in the immediate-start group were improved by 1.25 ± 1.59, 11.10 ± 15.10, and 0.95 ± 1.54 points, respectively, and were significantly higher than those in the delayed-start group (p < 0.05). The change in VAS, THI, and NPRS scores in the treatment group was significantly positively correlated with the scores of the HCFA before treatment (r = 0.786, p < 0.001; r = 0.680, p = 0.001; r = 0.796, p < 0.001). There was no significant difference in THI, VAS, and NPRS scores among patients in the immediate-start group between weeks 1, 6, 9, and 12 after treatment (p > 0.05). Conclusions: Although more participants were necessary in the further study, the study implies that physical therapy can reduce physical pain, improve tinnitus symptoms, and quality of life in ST patients without hearing loss, and the short-term curative effect is stable, especially for tinnitus patients with clear somatic symptoms.

5.
Appl Opt ; 63(12): 3130-3137, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38856457

RESUMEN

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

6.
Int J Gen Med ; 17: 2513-2525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846346

RESUMEN

Background: This study addresses the predictive modeling of Enlarged Perivascular Spaces (EPVS) in neuroradiology and neurology, focusing on their impact on Cerebral Small Vessel Disease (CSVD) and neurodegenerative disorders. Methods: A retrospective analysis was conducted on 587 neurology inpatients, utilizing LASSO regression for variable selection and logistic regression for model development. The study included comprehensive demographic, medical history, and laboratory data analyses. Results: The model identified key predictors of EPVS, including Age, Hypertension, Stroke, Lipoprotein a, Platelet Large Cell Ratio, Uric Acid, and Albumin to Globulin Ratio. The predictive nomogram demonstrated strong efficacy in EPVS risk assessment, validated through ROC curve analysis, calibration plots, and Decision Curve Analysis. Conclusion: The study presents a novel, robust EPVS predictive model, providing deeper insights into EPVS mechanisms and risk factors. It underscores the potential for early diagnosis and improved management strategies in neuro-radiology and neurology, highlighting the need for future research in diverse populations and longitudinal settings.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38829052

RESUMEN

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

8.
Chembiochem ; : e202400128, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842537

RESUMEN

We present an atomistic model for the outermost layer of the hair surface derived through molecular dynamics simulations, which comprises 18-Methyleicosanoic acid (18-MEA) fatty acid chains covalently bonded onto the keratin-associated protein 10-4 (KAP10-4) at a spacing distance of ~ 1 nm. Remarkably, this surface model facilitates the inclusion of free fatty acids (free 18-MEA) into the gaps between chemically bound 18-MEA chains, up to a maximum number that results in a packing density of 0.22 nm2 per fatty acid molecule, consistent with the optimal spacing identified through free energy analysis. Atomistic insights are provided into the organization of fatty acid chains, structural features, and interaction energies on protein-inclusive hair surface models with varying amounts of free 18-MEA (FMEA) depletion, as well as varying degrees of anionic cysteic acid from damaged bound 18-MEA (BMEA), under both dry and wet conditions. Our simulation results reveal that, while the depletion of FMEA can induce a pronounced impact on the thickness, tilt angle, and order parameters of fatty acid chains , the removal of BMEA has a marked effect on water penetration. There is a "sweet spot" spacing between the 18-MEA whereby damaged hair surface properties can be reinstated by  replenishing FMEA.

9.
Biomed Eng Online ; 23(1): 56, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890695

RESUMEN

OBJECTIVES: This study was designed to explore and validate the value of different machine learning models based on ultrasound image-omics features in the preoperative diagnosis of lymph node metastasis in pancreatic cancer (PC). METHODS: This research involved 189 individuals diagnosed with PC confirmed by surgical pathology (training cohort: n = 151; test cohort: n = 38), including 50 cases of lymph node metastasis. Image-omics features were extracted from ultrasound images. After dimensionality reduction and screening, eight machine learning algorithms, including logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), extra trees (ET), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to establish image-omics models to predict lymph node metastasis in PC. The best omics prediction model was selected through ROC curve analysis. Machine learning models were used to analyze clinical features and determine variables to establish a clinical model. A combined model was constructed by combining ultrasound image-omics and clinical features. Decision curve analysis (DCA) and a nomogram were used to evaluate the clinical application value of the model. RESULTS: A total of 1561 image-omics features were extracted from ultrasound images. 15 valuable image-omics features were determined by regularization, dimension reduction, and algorithm selection. In the image-omics model, the LR model showed higher prediction efficiency and robustness, with an area under the ROC curve (AUC) of 0.773 in the training set and an AUC of 0.850 in the test set. The clinical model constructed by the boundary of lesions in ultrasound images and the clinical feature CA199 (AUC = 0.875). The combined model had the best prediction performance, with an AUC of 0.872 in the training set and 0.918 in the test set. The combined model showed better clinical benefit according to DCA, and the nomogram score provided clinical prediction solutions. CONCLUSION: The combined model established with clinical features has good diagnostic ability and can be used to predict lymph node metastasis in patients with PC. It is expected to provide an effective noninvasive method for clinical decision-making, thereby improving the diagnosis and treatment of PC.


Asunto(s)
Metástasis Linfática , Aprendizaje Automático , Neoplasias Pancreáticas , Ultrasonografía , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Femenino , Anciano , Procesamiento de Imagen Asistido por Computador/métodos , Adulto
10.
Environ Res ; 258: 119456, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906445

RESUMEN

Anaerobic biological treatment technology, especially denitrification and anaerobic ammonia oxidation (anammox) technology as mainstream process, played dominant role in the field of biological wastewater treatment. However, the above process was prone to sludge floating during high load operation and thereby affecting the efficient and stable operation of the system. Excessive production of extracellular polymeric substance (EPS) was considered to be the main reason for anaerobic granular sludge flotation, but the summaries in this area were not comprehensive enough. In this review, the potential mechanisms of denitrification and anammox sludge floatation were discussed from the perspective of granular sludge structural characteristics, nutrient transfer, and microbial flora change respectively, and the corresponding control strategies were also summarized. Finally, this paper indicated that future research on sludge flotation should focus on reducing the negative effects of EPS in sludge particles.

11.
Front Aging Neurosci ; 16: 1414855, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903898

RESUMEN

Objective: To identify cortical and subcortical volume, thickness and cortical area features and the networks they constituted related to anxiety in Parkinson's disease (PD) using structural magnetic resonance imaging (sMRI), and to integrate multimodal features based on machine learning to identify PD-related anxiety. Methods: A total of 219 patients with PD were retrospectively enrolled in the study. 291 sMRI features including cortical volume, subcortical volume, cortical thickness, and cortical area, as well as 17 clinical features, were extracted. Graph theory analysis was used to explore structural networks. A support vector machine (SVM) combination model, which used both sMRI and clinical features to identify participants with PD-related anxiety, was developed and evaluated. The performance of SVM models were evaluated. The mean impact value (MIV) of the feature importance evaluation algorithm was used to rank the relative importance of sMRI features and clinical features within the model. Results: 17 significant sMRI variables associated with PD-related anxiety was used to build a brain structural network. And seven sMRI and 5 clinical features with statistically significant differences were incorporated into the SVM model. The comprehensive model achieved higher performance than clinical features or sMRI features did alone, with an accuracy of 0.88, a precision of 0.86, a sensitivity of 0.81, an F1-Score of 0.83, a macro-average of 0.85, a weighted-average of 0.92, an AUC of 0.88, and a result of 10-fold cross-validation of 0.91 in test set. The sMRI feature right medialorbitofrontal thickness had the highest impact on the prediction model. Conclusion: We identified the brain structural features and networks related to anxiety in PD, and developed and internally validated a comprehensive model with multimodal features in identifying.

12.
Technol Cancer Res Treat ; 23: 15330338241260331, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38860337

RESUMEN

OBJECTIVE: To compare the ability of gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA) and gadobenate dimeglumine (Gd-BOPTA) to display the 3 major features recommended by the Liver Imaging Reporting and Data System (LI-RADS 2018v) for diagnosing hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this retrospective study, we included 98 HCC lesions that were scanned with either Gd-EOB-DTPA-MR or Gd-BOPTA-M.For each lesion, we collected multiple variables, including size and enhancement pattern in the arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). The lesion-to-liver contrast (LLC) was measured and calculated for each phase and then compared between the 2 contrast agents. A P value < .05 was considered statistically significant. The display efficiency of the LLC between Gd-BOPTA and Gd-EOB-DTPA for HCC features was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Between Gd-BOPTA and Gd-EOB-DTPA, significant differences were observed regarding the display efficiency for capsule enhancement and the LLC in the AP/PVP/DP (P < .05), but there was no significant difference regarding the LLC in the TP/HBP. Both Gd-BOPTA and Gd-EOB-DTPA had good display efficiency in each phase (AUCmin > 0.750). When conducting a total evaluation of the combined data across the 5 phases, the display efficiency was excellent (AUC > 0.950). CONCLUSION: Gd-BOPTA and Gd-EOB-DTPA are liver-specific contrast agents widely used in clinical practice. They have their own characteristics in displaying the 3 main signs of HCC. For accurate noninvasive diagnosis, the choice of agent should be made according to the specific situation.


Asunto(s)
Carcinoma Hepatocelular , Medios de Contraste , Gadolinio DTPA , Neoplasias Hepáticas , Imagen por Resonancia Magnética , Meglumina , Compuestos Organometálicos , Curva ROC , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Meglumina/análogos & derivados , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Aumento de la Imagen/métodos , Anciano de 80 o más Años
13.
Abdom Radiol (NY) ; 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38824474

RESUMEN

OBJECTIVE: To compare the ability to depict MRI features of hepatobiliary agents in microvascular infiltration (MVI) of hepatocellular carcinoma (HCC) during different stages of dynamic enhancement MRI. MATERIALS AND METHODS: A retrospective study included 111 HCC lesions scanned with either Gd-EOB-DTPA or Gd-BOPTA. All cases underwent multiphase dynamic contrast-enhanced scanning before surgery, including arterial phase (AP), portal venous phase (PVP), transitional phase (TP), delayed phase (DP), and hepatobiliary phase (HBP). Two abdominal radiologists independently evaluated MRI features of MVI in HCC, such as peritumoral hyperenhancement, incomplete capsule, non-smooth tumor margins, and peritumoral hypointensity. Finally, the results were reviewed by the third senior abdominal radiologist. Chi-square (χ2) Inspection for comparison between groups. P < 0.05 is considered statistically significant. Receiver operating characteristic (ROC) curve was used to evaluate correlation with pathology, and the area under the curve (AUC) and 95% confidence interval (95% CI) were calculated. RESULTS: Among the four MVI evaluation signs, Gd-BOPTA showed significant differences in displaying two signs in the HBP (P < 0.05:0.000, 0.000), while Gd-EOB-DTPA exhibited significant differences in displaying all four signs (P < 0.05:0.005, 0.006, 0.000, 0.002). The results of the evaluations of the two contrast agents in the DP phase with incomplete capsulation showed the highest correlation with pathology (AUC: 0.843, 0.761). By combining the four MRI features, Gd-BOPTA and Gd-EOB-DTPA have correlated significantly with pathology, and Gd-BOPTA is better (AUC: 0.9312vs0.8712). CONCLUSION: The four features of hepatobiliary agent dynamic enhancement MRI demonstrate a good correlation with histopathological findings in the evaluation of MVI in HCC, and have certain clinical significance.

14.
Mil Med Res ; 11(1): 30, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764065

RESUMEN

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.


Asunto(s)
Interleucina-6 , Porphyromonas gingivalis , Hiperplasia Prostática , Receptores de Interleucina-6 , Masculino , Hiperplasia Prostática/complicaciones , Porphyromonas gingivalis/patogenicidad , Ratas , Humanos , Animales , Interleucina-6/análisis , Interleucina-6/metabolismo , Próstata , Periodontitis/complicaciones , Periodontitis/microbiología , Anciano , Persona de Mediana Edad , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Transducción de Señal/fisiología
15.
Eur J Pharmacol ; 976: 176665, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38797312

RESUMEN

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.


Asunto(s)
Giberelinas , Lipopolisacáridos , Ratones Endogámicos C57BL , Microglía , FN-kappa B , Sepsis , Animales , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Ratones , FN-kappa B/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Giberelinas/farmacología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Transducción de Señal/efectos de los fármacos , Línea Celular , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo
16.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2355-2363, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812136

RESUMEN

This study explored the effects of 4-hydroxy-2(3H)-benzoxazolone(HBOA) on the proliferation and apoptosis of pancreatic cancer cells and its molecular mechanism. The L3.6 cells cultured in vitro were treated with HBOA of 0-1.0 mmol·L~(-1). The cell viability was detected by the cell counting kit-8(CCK-8) method, and the half inhibitory concentration(IC_(50)) was analyzed to determine the drug concentration and time. The cell morphology was observed under an inverted microscope and by acridine orange(AO) staining. The ability of proliferation and self-renewal were evaluated through live cell counting and colony formation experiments. The cell cycle progression and cell apoptosis rate were detected by flow cytometry. The morphology of cell apoptosis was observed by scanning electron microscopy. The mRNA expression of proliferating cell nuclear antigen(PCNA), cyclinA1, cyclinA2, cyclin dependent kinase 2(CDK2), and cyclin dependent kinase inhibitor 1A(P21) were determined by qPCR. The level of reactive oxygen species(ROS), lipid peroxide, and mitochondrial membrane potential were measured by flow cytometry. The activity of protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway was detected by Western blot. Compared with the control group, the cells treated with HBOA exhibited a significant decrease in viability. Then the optimal concentration and intervention time of HBOA were determined to be 0.4 mmol·L~(-1), 0.6 mmol·L~(-1), and 48 h. Compared with the control group, groups with HBOA of 0.4 mmol·L~(-1 )and 0.6 mmol·L~(-1) showed a significant suppression in cell proliferation and colony formation ability, down-regulated mRNA of PCNA, cyclinA1, cyclinA2, and CDK2, up-regulated P21 mRNA, S-phase cell cycle arrest, and increased cell apoptosis rate. There was an appearance of apoptotic bodies, increased ROS and lipid peroxide, decreased mitochondrial membrane potential(with a significant decrease in 0.6 mmol·L~(-1) group), and down-regulated p-Akt and p-mTOR proteins. The results show that HBOA inhibits the proliferation of pancreatic cancer L3.6 cells and induces cell apoptosis, which may be related to the increase in reactive oxygen species and the inhibition of the Akt/mTOR pathway.


Asunto(s)
Apoptosis , Proliferación Celular , Neoplasias Pancreáticas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Humanos , Línea Celular Tumoral , Benzoxazoles/farmacología , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ciclo Celular/efectos de los fármacos , Quinasa 2 Dependiente de la Ciclina/genética , Quinasa 2 Dependiente de la Ciclina/metabolismo , Supervivencia Celular/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
17.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2699-2709, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38812170

RESUMEN

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 µg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.


Asunto(s)
Dispepsia , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Dispepsia/tratamiento farmacológico , Dispepsia/fisiopatología , Dispepsia/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Humanos , Flavonoides/química , Flavonoides/farmacología , Motilina , Péptido Intestinal Vasoactivo/metabolismo , Ghrelina , Somatostatina
18.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1717-1724, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38812184

RESUMEN

Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.


Asunto(s)
Medicamentos Herbarios Chinos , Panax , Panax/química , Humanos , Medicamentos Herbarios Chinos/química , Animales
19.
Arch Gerontol Geriatr ; 124: 105481, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38733920

RESUMEN

OBJECTIVE: The aim of this study was to investigate the combined effect of handgrip strength (HGS) and obesity phenotype on the risk of stroke in Chinese middle-aged and elderly people. METHODS: The data was used from the China Health and Retirement Longitudinal Study (CHARLS). Middle-aged and older adults who participated in surveys between 2011 and 2018 were included in the study. They were divided into 4 different types of obesity phenotypes based on obesity and metabolic status: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically abnormal non-overweight/obesity (MANO), and metabolically abnormal overweight/obesity (MAO). The HGS level was divided into low and high groups according to the median values. Cox proportional risk regression model was used to analyze the joint effect of HGS and obesity phenotype on the risk of stroke among participants. RESULTS: A total of 7904 participants aged 58.89±9.08 years were included in this study. After adjusting for potential confounders, high HGS&MHO (HR=1.86, 95 % CI=1.12-3.09), high HGS&MANO (HR=2.01, 95 %CI=1.42-2.86), high HGS&MAO (HR=2.01, 95 % CI=1.37-2.93), low HGS&MHNO (HR=1.57, 95 % CI=1.00-2.46), low HGS&MHO (HR=2.09, 95 % CI=1.29-3.38), low HGS&MANO (HR=2.02, 95 % CI=1.35-3.03), and low HGS&MAO (HR=2.48, 95 % CI=1.72-3.58) group had significantly higher risks of stroke than the high HGS&MHNO group. CONCLUSION: The coexistence of metabolically unhealthy and low HGS can synergistically increase the risk of stroke in Chinese middle-aged and elderly people.


Asunto(s)
Fuerza de la Mano , Obesidad , Fenotipo , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Fuerza de la Mano/fisiología , Obesidad/epidemiología , Obesidad/complicaciones , China/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Factores de Riesgo , Estudios Longitudinales , Estudios de Cohortes , Pueblos del Este de Asia
20.
Talanta ; 276: 126264, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38761661

RESUMEN

The outbreak of SARS-CoV-2 poses a serious threat to human life and health. A rapid nucleic acid tests can effectively curb the spread of the disease. With the advantages of fluorescent RNA aptamers, low background and high sensitivity. A variety of fluorescent RNA aptamer sensors have been developed for the detection of nucleic acid. Here, we report a hypersensitive detection platform in which SARS-CoV-2 initiates RTF-EXPAR to amplify trigger fragments. This activation leads to the reassembled of the SRB2 fluorescent RNA aptamer, restoring its secondary structure for SR-DN binding and turn-on fluorescence. The platform completes the assay in 30 min and all reactions occur in one tube. The detection limit is as low as 116 aM. Significantly, the platform's quantitative analyses were almost identical to qPCR results in simulated tests of positive samples. In conclusion, the platform is sensitive, accurate and provides a new protocol for point-of-care testing of viruses.


Asunto(s)
Aptámeros de Nucleótidos , COVID-19 , Límite de Detección , Técnicas de Amplificación de Ácido Nucleico , ARN Viral , SARS-CoV-2 , Aptámeros de Nucleótidos/química , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Viral/análisis , COVID-19/diagnóstico , COVID-19/virología , Colorantes Fluorescentes/química , Prueba de Ácido Nucleico para COVID-19/métodos
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