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1.
Int J Mol Sci ; 25(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-39000299

RESUMEN

In the rosid species Arabidopsis thaliana, the AP2-type AP2 transcription factor (TF) is required for specifying the sepals and petals identities and confers a major A-function to antagonize the C-function in the outer floral whorls. In the asterid species Petunia, the AP2-type ROB TFs are required for perianth and pistil development, as well as repressing the B-function together with TOE-type TF BEN. In Long-homostyle (LH) Fagopyrum esculentum, VIGS-silencing showed that FaesAP2 is mainly involved in controlling filament and style length, but FaesTOE is mainly involved in regulating filament length and pollen grain development. Both FaesAP2 (AP2-type) and FaesTOE (TOE-type) are redundantly involved in style and/or filament length determination instead of perianth development. However, neither FaesAP2 nor FaesTOE could directly repress the B and/or C class genes in common buckwheat. Moreover, the FaesAP1_2 silenced flower showed tepal numbers, and filament length decreased obviously. Interestingly, yeast one-hybrid (Y1H) and dual-luciferase reporter (DR) further suggested that FaesTOE directly up-regulates FaesAP1_2 to be involved in filament length determination in LH common buckwheat. Moreover, the knockdown of FaesTOE expression could result in expression down-regulation of the directly target FaesAP1_2 in the FaesTOE-silenced LH plants. Our findings uncover a stamen development pathway in common buckwheat and offer deeper insight into the functional evolution of AP2 orthologs in the early-diverging core eudicots.


Asunto(s)
Fagopyrum , Flores , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Fagopyrum/genética , Fagopyrum/crecimiento & desarrollo , Fagopyrum/metabolismo , Flores/genética , Flores/crecimiento & desarrollo , Flores/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación hacia Arriba/genética
2.
Molecules ; 29(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38999080

RESUMEN

External interfaces, such as the air-water and solid-liquid interfaces, are ubiquitous in nature. Hydrophobic interactions are considered the fundamental driving force in many physical and chemical processes occurring in aqueous solutions. It is important to understand the effects of external interfaces on hydrophobic interactions. According to the structural studies on liquid water and the air-water interface, the external interface primarily affects the structure of the topmost water layer (interfacial water). Therefore, an external interface may affect hydrophobic interactions. The effects of interfaces on hydrophobicity are related not only to surface molecular polarity but also to the geometric characteristics of the external interface, such as shape and surface roughness. This study is devoted to understanding the effects of a smooth interface on hydrophobicity. Due to hydrophobic interactions, the solutes tend to accumulate at external interfaces to maximize the hydrogen bonding of water. Additionally, these can be demonstrated by the calculated potential mean forces (PMFs) using molecular dynamic (MD) simulations.

3.
IEEE Trans Image Process ; 33: 4173-4187, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38990738

RESUMEN

Rotation averaging, which aims to calculate the absolute rotations of a set of cameras from a redundant set of their relative rotations, is an important and challenging topic arising in the study of structure from motion. A central problem in rotation averaging is how to alleviate the influence of noise and outliers. Addressing this problem, we investigate rotation averaging under the Cayley framework in this paper, inspired by the extra-constraint-free nature of the Cayley rotation representation. Firstly, for the relative rotation of an arbitrary pair of cameras regardless of whether it is corrupted by noise/outliers or not, a general Cayley rotation constraint equation is derived for reflecting the relationship between this relative rotation and the absolute rotations of the two cameras, according to the Cayley rotation representation. Then based on such a set of Cayley rotation constraint equations, a Cayley-based approach for Rotation Averaging is proposed, called CRA, where an adaptive regularizer is designed for further alleviating the influence of outliers. Finally, a unified iterative algorithm for minimizing some commonly-used loss functions is proposed under this approach. Experimental results on 16 real-world datasets and multiple synthetic datasets demonstrate that the proposed CRA approach achieves a better accuracy in comparison to several typical rotation averaging approaches in most cases.

4.
Molecules ; 29(11)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38893477

RESUMEN

According to our recent studies on hydrophobicity, this work is aimed at understanding the dependence of hydrophobic interactions on the shape of a solute's surface. It has been observed that dissolved solutes primarily affect the structure of interfacial water, which refers to the top layer of water at the interface between the solute and water. As solutes aggregate in a solution, hydrophobic interactions become closely related to the transition of water molecules from the interfacial region to the bulk water. It is inferred that hydrophobic interactions may depend on the shape of the solute surface. To enhance the strength of hydrophobic interactions, the solutes tend to aggregate, thereby minimizing their surface area-to-volume ratio. This also suggests that hydrophobic interactions may exhibit directional characteristics. Moreover, this phenomenon can be supported by calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations, where different surfaces, such as convex, flat, or concave, are associated with a sphere. Furthermore, this concept can be extended to comprehend the molecular packing parameter, commonly utilized in studying the self-assembly behavior of amphiphilic molecules in aqueous solutions.

5.
Sci Total Environ ; 935: 173401, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38782269

RESUMEN

Knowing the sources of precipitation chemical composition is essential to understand the biogeochemical cycle and control air pollution. Despite this issue has been directly investigated with precipitation ion contents, the effects of water vapor transport have not been fully considered. Taking the Loess Plateau of China (LPC) as an example study area, this study established nine precipitation monitoring sites considering the variability in topography and rainfall amounts, and collected 435 precipitation samples during 2020-2022 to measure the chemical composition. The correlation analysis, positive matrix factorization model and backward trajectory model were combined to analyze the characteristics, sources and vapor transport effects of precipitation chemical composition. Seasonally, except for NH4+, the concentration of other ions in the dry season was significantly higher than that in the rainy season. Spatially, the concentrations of Ca2+, Na+, K+, SO42- and NO3- peaked in the Mu Us Sandy Land and industrial areas, while the high level of NH4+ was concentrated in the agricultural areas. The source apportionment found that the primary source of precipitation ions was crust (33 %), followed by coal combustion/vehicle (30 %), aged sea salt (21 %) and agriculture (16 %). The trajectory analysis showed that water vapor paths significantly varied with the seasons, but were primarily dominated by the northwestern air mass with proportions of >40 %. The dust aerosols transported by the northwestern air mass were the main contributor to crust-source precipitation ions. The eastern and southeastern air masses transported anthropogenic pollutants to the LPC, and the southeastern air mass also carried sea-salt precipitation ions. This study provides a framework to incorporate hydrochemical method with vapor source identification method for precipitation chemical source identification, and the results can be a theoretical basis for the treatment of atmospheric environmental problems.

6.
Front Oncol ; 14: 1395654, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38720809

RESUMEN

Background: Cases of ALK-rearranged EGFR wild-type lung adenocarcinoma (LUAD) transforming into small cell lung cancer (SCLC) are rarely reported, and diagnosis is often delayed. The emergence of this transformation phenomenon is often regarded as a consequence of acquired resistance mechanisms. Case presentation: A 47-year-old male diagnosed with poorly differentiated adenocarcinoma of the right middle lung (pT2N2M0, stage IIIA) achieved a 46-month progression-free survival (PFS) following surgery and adjuvant chemotherapy. During routine follow-up, tumor recurrence and metastasis was detected. Genetic testing revealed ALK rearrangement and wild-type EGFR, prompting treatment with ALK-TKIs. In May 2023, abdominal CT scans showed significant progression of liver metastases and abnormal elevation of the tumor marker NSE. Immunohistochemical results from percutaneous liver biopsy indicated metastatic SCLC. Results: After resistance to ALK-TKIs and transformation to SCLC, the patient received chemotherapy combined with immunotherapy for SCLC, but the patient's disease progressed rapidly. Currently, the patient is being treated with albumin-bound paclitaxel in combination with oral erlotinib and remains stable. Conclusion: Histological transformation emerges as a compelling mechanism of resistance to ALK-TKIs, necessitating the utmost urgency for repeat biopsies in patients displaying disease progression after resistance. These biopsies are pivotal in enabling the tailor-made adaptation of treatment regimens to effectively counteract the assorted mechanisms of acquired resistance, thus optimizing patient outcomes in the battle against ALK-driven malignancies.

7.
Immun Inflamm Dis ; 12(5): e1266, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38804848

RESUMEN

BACKGROUND: Esophageal cancer (ESCA) is a highly invasive malignant tumor with poor prognosis. This study aimed to discover a generalized and high-sensitivity immune prognostic signature that could stratify ESCA patients and predict their overall survival, and to discover potential therapeutic drugs by the connectivity map. METHODS: The key gene modules significantly related to clinical traits (survival time and state) of ESCA patients were selected by weighted gene coexpression network analysis (WCGNA), then the univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to construct a 15-immune-related gene prognostic signature. RESULTS: The immune-related risk model was related to clinical and pathologic factors and remained an effective independent prognostic factor. Enrichment analyses revealed that the differentially expressed genes (DEGs) of the high- and low-risk groups were associated with tumor cell proliferation and immune mechanisms. Based on the gathered data, a small molecule drug named perphenazine (PPZ) was elected. The pharmacological analysis indicates that PPZ could help in adjuvant therapy of ESCA through regulation of metabolic process and cellular proliferation, enhancement of immunologic functions, and inhibition of inflammatory reactions. Furthermore, molecular docking was performed to explore and verify the PPZ-core target interactions. CONCLUSION: We succeed in structuring the immune-related prognostic model, which could be used to distinguish and predict patients' survival outcome, and screening a small molecule drug named PPZ. Prospective studies also are needed to further validate its analytical accuracy for estimating prognoses and confirm the potential use of PPZ for treating ESCA.


Asunto(s)
Biología Computacional , Neoplasias Esofágicas , Farmacología en Red , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/inmunología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Humanos , Pronóstico , Biología Computacional/métodos , Redes Reguladoras de Genes , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Simulación del Acoplamiento Molecular , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Masculino , Femenino
8.
Medicine (Baltimore) ; 103(17): e37759, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669410

RESUMEN

This study aimed to identify risk factors for early death in elderly small cell lung cancer (SCLC) patients and develop nomogram prediction models for all-cause and cancer-specific early death to improve patient management. Data of elderly patients diagnosed with SCLC were extracted from the SEER database, then randomly divided into training and validation cohorts. Univariate and stepwise multivariable Logistic regression analyses were performed on the training cohort to identify independent risk factors for early death in these patients. Nomograms were developed based on these factors to predict the overall risk of early death. The efficacy of the nomograms was validated using various methods, including ROC analysis, calibration curves, DCA, NRI, and IDI. Among 2077 elderly SCLC patients, 773 died within 3 months, 713 due to cancer-specific causes. Older age, higher AJCC staging, brain metastases, and lack of surgery, chemotherapy, or radiotherapy increase the risk of all-cause early death, while higher AJCC staging, brain metastases, lung metastases, and lack of surgery, chemotherapy, or radiotherapy increase the risk of cancer-specific death (P < .05). These identified factors were used to construct 2 nomograms to predict the risk of early death. The ROC indicated that the nomograms performed well in predicting both all-cause early death (AUC = 0.823 in the training cohort and AUC = 0.843 in the validation cohort) and cancer-specific early death (AUC = 0.814 in the training cohort and AUC = 0.841 in the validation cohort). The results of calibration curves, DCAs, NRI and IDI also showed that the 2 sets of nomograms had good predictive power and clinical utility and were superior to the commonly used TNM staging system. The nomogram prediction models constructed in this study can effectively assist clinicians in predicting the risk of early death in elderly SCLC patients, and can also help physicians screen patients at higher risk and develop personalized treatment plans for them.


Asunto(s)
Neoplasias Pulmonares , Nomogramas , Programa de VERF , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/terapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Anciano , Femenino , Factores de Riesgo , Estadificación de Neoplasias , Anciano de 80 o más Años , Factores de Edad , Curva ROC
9.
Sci Rep ; 14(1): 8319, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594332

RESUMEN

Analyzing the stability of footings is a significant step in civil/geotechnical engineering projects. In this work, two novel predictive tools are suggested based on an artificial neural network (ANN) to analyze the bearing capacity of a footing installed on a two-layered soil mass. To this end, backtracking search algorithm (BSA) and equilibrium optimizer (EO) are employed to train the ANN for approximating the stability value (SV) of the system. After executing a set of finite element analyses, the settlement values lower/higher than 5 cm are considered to indicate the stability/failure of the system. The results demonstrated the efficiency of these algorithms in fulfilling the assigned task. In detail, the training error of the ANN (in terms of root mean square error-RMSE)) dropped from 0.3585 to 0.3165 (11.72%) and 0.2959 (17.46%) by applying the BSA and EO, respectively. Moreover, the prediction accuracy of the ANN climbed from 93.7 to 94.3% and 94.1% (in terms of area under the receiving operating characteristics curve-AUROC). A comparison between the elite complexities of these algorithms showed that the EO enjoys a larger accuracy, while BSA is a more time-effective optimizer. Lastly, an explicit mathematical formula is derived from the EO-ANN model to be conveniently used in predicting the SV.

10.
Sci Rep ; 14(1): 8342, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594336

RESUMEN

Concrete-filled steel tube columns (CFSTCs) are important elements in the construction sector and predictive analysis of their behavior is essential. Recent works have revealed the potential of metaheuristic-assisted approximators for this purpose. The main idea of this paper, therefore, is to introduce a novel integrative model for appraising the axial compression capacity (Pu) of CFSTCs. The proposed model represents an artificial neural network (ANN) supervised by satin bowerbird optimizer (SBO). In other words, this metaheuristic algorithm trains the ANN optimally to find the best contribution of input parameters to the Pu. In this sense, column length and the compressive strength of concrete, as well as the characteristics of the steel tube (i.e., diameter, thickness, yield stress, and ultimate stress), are considered input data. The prediction results are compared to five ANNs supervised by backtracking search algorithm (BSA), earthworm optimization algorithm (EWA), social spider algorithm (SOSA), salp swarm algorithm (SSA), and wind-driven optimization. Evaluating various accuracy indicators showed that the proposed model surpassed all of them in both learning and reproducing the Pu pattern. The obtained values of mean absolute percentage error of the SBO-ANN was 2.3082% versus 4.3821%, 17.4724%, 15.7898%, 4.2317%, and 3.6884% for the BSA-ANN, EWA-ANN, SOSA-ANN, SSA-ANN and WDA-ANN, respectively. The higher accuracy of the SBO-ANN against several hybrid models from earlier literature was also deduced. Moreover, the outcomes of principal component analysis on the dataset showed that the yield stress, diameter, and ultimate stress of the steel tube are the three most important factors in Pu prediction. A predictive formula is finally derived from the optimized SBO-ANN by extracting and organizing the weights and biases of the ANN. Owing to the accurate estimation shown by this model, the derived formula can reliably predict the Pu of concrete-filled steel tube columns.

11.
Lasers Med Sci ; 39(1): 92, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38499897

RESUMEN

Acne is a long-lasting inflammatory skin condition that impacts the sebaceous units of the hair follicles, affecting around 85-90% of the population. Due to the potential for permanent facial scarring and negative social consequences, as well as the limitations of conventional medications like drug resistance and difficulties following treatment plans, it's crucial to investigate non-pharmacological options for treating acne, among which radiofrequency(RF) shows distinct superiority. To assess the impact of RF in the management of acne vulgaris, we conducted a thorough examination of scientific literature (including clinical trials and scientific reviews) through electronic databases like MEDLINE and PubMed. Our analysis indicates that RF could be a viable substitute for acne treatment due to its notable effectiveness and minimal adverse effects.


Asunto(s)
Acné Vulgar , Humanos , Acné Vulgar/radioterapia , Acné Vulgar/tratamiento farmacológico , Piel , Cicatriz/radioterapia , Folículo Piloso , Resultado del Tratamiento
12.
Ying Yong Sheng Tai Xue Bao ; 35(2): 457-468, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38523104

RESUMEN

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.


Asunto(s)
Ecosistema , Ríos , Conservación de los Recursos Naturales/métodos , Suelo , Carbono , Nitrógeno , Fósforo , China
13.
Molecules ; 29(4)2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38398605

RESUMEN

Ion channels exhibit strong selectivity for specific ions over others under electrochemical potentials, such as KcsA for K+ over Na+. Based on the thermodynamic analysis, this study is focused on exploring the mechanism of ion selectivity in nanopores. It is well known that ions must lose part of their hydration layer to enter the channel. Therefore, the ion selectivity of a channel is due to the rearrangement of water molecules when entering the nanopore, which may be related to the hydrophobic interactions between ions and channels. In our recent works on hydrophobic interactions, with reference to the critical radius of solute (Rc), it was divided into initial and hydrophobic solvation processes. Additionally, the different dissolved behaviors of solutes in water are expected in various processes, such as dispersed and accumulated distributions in water. Correspondingly, as the ion approaches the nanopore, there seems to exist the "repulsive" or "attractive" forces between them. In the initial process (

14.
Int Immunopharmacol ; 130: 111638, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38373387

RESUMEN

L-arginine, as an essential substance of the immune system, plays a vital role in innate immunity. MiR155, a multi-functional microRNA, has gained importance as a regulator of homeostasis in immune cells. However, the immunoregulatory mechanism between L-arginine and miR155 in bacterial infections is unknown. Here, we investigated the potential role of miR155 in inflammation and the molecular regulatory mechanisms of L-arginine in Streptococcus uberis (S. uberis) infections. And we observed that miR155 was up-regulated after infection, accompanying the depletion of L-arginine, leading to metabolic disorders of amino acids and severe tissue damage. Mechanically, the upregulated miR155 mediated by the p65 protein played a pro-inflammatory role by suppressing the suppressor of cytokine signaling 6 (SOCS6)-mediated p65 ubiquitination and degradation. This culminated in a violently inflammatory response and tissue damage. Interestingly, a significant anti-inflammatory effect was revealed in L-arginine supplementation by reducing miR155 production via inhibiting p65. This work firstly uncovers the pro-inflammatory role of miR155 and an anti-inflammatory mechanism of L-arginine in S.uberis infection with a mouse mastitis model. Collectively, we provide new insights and strategies for the prevention and control of this important pathogen, which is of great significance for ensuring human food health and safety.


Asunto(s)
Arginina , Mastitis , MicroARNs , Infecciones Estreptocócicas , Animales , Femenino , Humanos , Ratones , Arginina/metabolismo , Inflamación/metabolismo , MicroARNs/genética , Infecciones Estreptocócicas/metabolismo , Streptococcus/fisiología , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Mastitis/inmunología , Mastitis/metabolismo
15.
Lasers Med Sci ; 39(1): 80, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38396012

RESUMEN

PURPOSE: This split-face randomized study compared the efficacy and safety between 1064-nm picosecond laser with fractionated microlens array (MLA) and 1565-nm nonablative fractional laser to treat enlarged pores. METHODS: Participants with enlarged facial pores were enrolled and underwent three consecutive sessions at 2-week intervals with either a 1064-nm picosecond laser with MLA or a 1565-nm nonablative fractional laser. Images were captured at each visit. Objective (pore number) and subjective assessments, including patient self-evaluations and quartile improvement scales, were used to evaluate the treatment efficacy. The pain levels and adverse effects were recorded at each subsequent visit. RESULTS: The participants were 3 men and 22 women with enlarged facial pores. At the initial and 2-month checkups after the last treatment, the pore numbers were significantly decreased bilaterally for both lasers. The respective quartile improvement scale scores for the 1064-nm picosecond and 1565-nm fractional lasers were 2.22 ± 1.06 and 2.14 ± 1.11, while those for patient self-assessment were 3.72 ± 0.74 and 3.68 ± 0.75. The pore number, quartile improvement scale score, and patients' self-assessments did not differ significantly between the two lasers. Treatment with the 1064-nm picosecond laser better reduced pain compared with the 1565-nm nonablative fractional laser (4.11 ± 1.33 vs. 4.83 ± 1.17). The occurrence of pigmentation did not differ significantly between the lasers. CONCLUSION: Both the 1064-nm picosecond laser with MLA and the 1565-nm nonablative fractional laser are viable options for treating enlarged pores, and showed comparable respective efficacies; however, the former was less likely to cause hyperpigmentation and was better tolerated.


Asunto(s)
Hiperpigmentación , Láseres de Estado Sólido , Masculino , Humanos , Femenino , Satisfacción del Paciente , Láseres de Estado Sólido/uso terapéutico , Resultado del Tratamiento , Hiperpigmentación/etiología , Dolor/etiología
16.
World J Gastroenterol ; 30(4): 367-380, 2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38313237

RESUMEN

BACKGROUND: L-type calcium channels are the only protein channels sensitive to calcium channel blockers, and are expressed in various cancer types. The Cancer Genome Atlas database shows that the mRNA levels of multiple L-type calcium channel subunits in esophageal squamous cell carcinoma tumor tissue are significantly higher than those in normal esophageal epithelial tissue. Therefore, we hypothesized that amlodipine, a long-acting dihydropyridine L-type calcium channel blocker, may inhibit the occurrence and development of esophageal cancer (EC). AIM: To investigate the inhibitory effects of amlodipine on EC through endoplasmic reticulum (ER) stress. METHODS: Cav1.3 protein expression levels in 50 pairs of EC tissues and corresponding paracancerous tissues were examined. Subsequently, the inhibitory effects of amlodipine on proliferation and migration of EC cells in vitro were detected using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and Transwell assays. In vivo experiments were performed using murine xenograft model. To elucidate the underlying mechanisms, in vitro cell studies were performed to confirm that ER stress plays a role in inhibition proliferation and migration of EC cells treated with amlodipine. RESULTS: The expression level of Cav1.3 in esophageal carcinoma was 1.6 times higher than that in paracancerous tissues. Amlodipine treatment decreased the viability of esophageal carcinoma cells in a dose- and time-dependent manner. In vivo animal experiments also clearly indicated that amlodipine inhibited the growth of EC tumors in mice. Additionally, amlodipine reduces the migration of tumor cells by inhibiting epithelial-mesenchymal transition (EMT). Mechanistic studies have demonstrated that amlodipine induces ER stress-mediated apoptosis and suppresses EMT. Moreover, amlodipine-induced autophagy was characterized by an increase in autophagy lysosomes and the accumulation of light chain 3B protein. The combination of amlodipine with the ER stress inhibitor 4-phenylbutyric acid further confirmed the role of the ER stress response in amlodipine-induced apoptosis, EMT, and autophagy. Furthermore, blocking autophagy increases the ratio of apoptosis and migration. CONCLUSION: Collectively, we demonstrate for the first time that amlodipine promotes apoptosis, induces autophagy, and inhibits migration through ER stress, thereby exerting anti-tumor effects in EC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Ratones , Animales , Amlodipino/farmacología , Amlodipino/uso terapéutico , Neoplasias Esofágicas/patología , Apoptosis , Proliferación Celular , Estrés del Retículo Endoplásmico , Línea Celular Tumoral
17.
J Sep Sci ; 47(1): e2300606, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38095460

RESUMEN

QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.


Asunto(s)
Medicamentos Herbarios Chinos , Saponinas , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Glicósidos , Saponinas/análisis , Cromatografía Líquida con Espectrometría de Masas
18.
Photodiagnosis Photodyn Ther ; 45: 103928, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070633

RESUMEN

BACKGROUND: The treatment of acne vulgaris is often challenging due to the antibiotic resistance frequently observed in Cutibacterium acnes (C.acnes), a prevalent bacterium linked to this condition. OBJECTIVE: The objective of this research was to examine the impact of curcumin photodynamic therapy (PDT) on the survival of C.acnes and activity of biofilms produced by this microorganism. METHODS: Following the Clinical and Laboratory Standards Institute (CLSI) guidelines, we assessed the drug sensitivity of 25 clinical C.acnes strains to five antibiotics (erythromycin, clindamycin, tetracycline, doxycycline, minocycline) and curcumin by implementing the broth microdilution technique. In addition, we established C.acnes biofilms in a laboratory setting and subjected them to curcumin-PDT(curcumin combined with blue light of 180 J/cm2). Afterwards, we evaluated their viability using the XTT assay and observed them using confocal laser scanning microscopy. RESULTS: The result revealed varying resistance rates among the tested antibiotics and curcumin, with erythromycin, clindamycin, tetracycline, doxycycline, minocycline, and curcumin exhibiting resistance rates of 72 %, 44 %, 36 %, 28 %, 0 %, and 100 %, respectively. In the curcumin-PDT inhibition tests against four representative antibiotic-resistant strains, it was found that the survival rate of all strains of planktonic C. acnes was reduced, and the higher the concentration of curcumin, the lower the survival rate. Furthermore, in the biofilm inhibition tests, the vitality and three-dimensional structure of the biofilms were disrupted, and the inhibitory effect became more significant with higher concentrations of curcumin. CONCLUSION: The results emphasize the possibility of using curcumin PDT as an alternative approach for the treatment of C.acnes, especially in instances of antibiotic-resistant variations and infections related to biofilms.


Asunto(s)
Acné Vulgar , Curcumina , Fotoquimioterapia , Humanos , Clindamicina/farmacología , Clindamicina/uso terapéutico , Doxiciclina/farmacología , Doxiciclina/uso terapéutico , Curcumina/farmacología , Curcumina/uso terapéutico , Minociclina/farmacología , Minociclina/uso terapéutico , Pruebas de Sensibilidad Microbiana , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fotoquimioterapia/métodos , Acné Vulgar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Eritromicina/farmacología , Eritromicina/uso terapéutico , Tetraciclina/farmacología , Tetraciclina/uso terapéutico , Biopelículas , Propionibacterium acnes
19.
Respir Physiol Neurobiol ; 321: 104204, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38128772

RESUMEN

BACKGROUND: Chronic intermittent hypoxia (CIH) increases the hypoxic ventilation response (HVR). The downstream cytokine IL-1ß of the NLRP3 inflammasome regulates respiration by acting on the carotid body (CB) and neurons in the respiratory center, but the effect of the NLRP3 inflammasome on HVR induced by CIH remains unclear. OBJECTIVE: To investigate the effect of NLRP3 on the increased HVR and spontaneous apnea events and duration induced by CIH, the expression and localization of NLRP3 in the respiratory regulatory center of the rostral ventrolateral medulla (RVLM), and the effect of CIH on the activation of the NLRP3 inflammasome in the RVLM. METHODS: Eighteen male, 7-week-old C57BL/6 N mice and eighteen male, 7-week-old C57BL/6 N NLRP3 knockout mice were randomly divided into CON-WT, CON-NLRP3-/-, CIH-WT and CIH-NLRP3-/- groups. Respiratory changes in mice were continuously detected using whole-body plethysmography. The expression and localization of the NLRP3 protein and the formation of apoptosis-associated speck-like protein containing CARD (ASC) specks were detected using immunofluorescence staining. RESULTS: NLRP3 knockout reduced the increased HVR and the incidence and duration of spontaneous apnea events associated with CIH. The increase in HVR caused by CIH partially recovered after reoxygenation. After CIH, NLRP3 inflammasome activation in the RVLM, which is related to respiratory regulation after hypoxia, increased, which was consistent with the trend of the ventilation response. CONCLUSION: The NLRP3 inflammasome may be involved in the increase in the HVR and the incidence and duration of spontaneous apnea induced by CIH. NLRP3 inhibitors may help reduce the increase in the HVR after CIH, which is important for ensuring sleep quality at night in patients with obstructive sleep apnea.


Asunto(s)
Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Ratones , Masculino , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Apnea/complicaciones , Ratones Endogámicos C57BL , Respiración , Hipoxia
20.
Int Immunopharmacol ; 127: 111424, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38141413

RESUMEN

Acne is a chronic inflammatory skin disease, and the pathogenesis of acne induced by Cutibacterium acnes (C.acnes) is not well understood. Recently, circular RNAs (circRNAs) have attracted much attention because of its involvement in various diseases. However, the mechanisms by which circRNAs regulated acne have rarely been reported. We identified several differentially expressed circRNAs by sequencing patient-derived acne tissues. Among them, hsa_circ_0105040 was determined to be low expressed in acne tissues and localized in the cytoplasm of human primary keratinocytes. We established a C.acnes biofilms model of acne in vitro and showed that hsa_circ_0105040 promoted inflammation via MAPK and NF-κB pathway. Mechanistically, hsa_circ_0105040 could directly bind to miR-146a and inhibit the expression of miR-146a. Moreover, hsa_circ_0105040 promoted the expression of IRAK1 and TRAF6 by sponging miR-146a, thereby elevating the level of inflammation in acne. Collectively, our data suggested that hsa_circ_0105040- miR-146a -IRAK1/TRAF6 axis was involved in regulating the inflammatory response in acne, which provided a potential therapeutic target for acne and a novel insight into the pathogenesis of inflammatory acne.


Asunto(s)
Acné Vulgar , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Queratinocitos/metabolismo , Inflamación/genética , Acné Vulgar/genética , Biopelículas
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