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1.
Cardiovasc Res ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38696702

RESUMEN

AIMS: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms. METHODS AND RESULTS: In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation. CONCLUSION: Our findings revealed that LIPUS uses an EV-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM.

2.
Biochem Biophys Res Commun ; 703: 149653, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38364682

RESUMEN

Cellular vesicle long-distance transport along the cytoplasmic actin network has recently been uncovered in several cell systems. In metaphase mouse oocytes, the motor protein myosin-5b (Myo5b) and the actin nucleation factor Spire are recruited to the Rab11a-positive vesicle membrane, forming a ternary complex of Myo5b/Spire/Rab11a that drives the vesicle long-distance transport to the oocyte cortex. However, the mechanism underlying the intermolecular regulation of the Myo5b/Spire/Rab11a complex remains unknown. In this study, we expressed and purified Myo5b, Spire2, and Rab11a proteins, and performed ATPase activity measurements, pulldown and single-molecule motility assays. Our results demonstrate that both Spire2 and Rab11a are required to activate Myo5b motor activity under physiological ionic conditions. The GTBM fragment of Spire2 stimulates the ATPase activity of Myo5b, while Rab11a enhances this activation. This activation occurs by disrupting the head-tail interaction of Myo5b. Furthermore, at the single-molecule level, we observed that the GTBM fragment of Spire2 and Rab11a coordinate to stimulate the Myo5b motility activity. Based on our results, we propose that upon association with the vesicle membrane, Myo5b, Spire2 and Rab11a form a ternary complex, and the inhibited Myo5b is synergistically activated by Spire2 and Rab11a, thereby triggering the long-distance transport of vesicles.


Asunto(s)
Actinas , Miosina Tipo V , Ratones , Animales , Actinas/metabolismo , Miosinas/metabolismo , Citoesqueleto de Actina/metabolismo , Miosina Tipo V/metabolismo , Proteínas de Unión al GTP rab/metabolismo
3.
Polymers (Basel) ; 16(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38337231

RESUMEN

This study investigates the influence of poly(butadiene-isoprene) copolymer rubber (BIR) and TDAE oil on the crystallization and melting behavior of neodymium-based butadiene rubber (Nd-BR). The study demonstrates that the melting points of Nd-BR and its blends decrease with lower crystallization temperatures. Below the critical crystallization temperature (Tc,c), the melting behavior shows dual peaks in distinct temperature ranges, which are attributed to different spherulitic sizes. The addition of BIR or TDAE oil lowers the Tc,c, with TDAE oil exerting a more substantial effect. These diluents mainly influence the nucleation temperature and crystallinity level of Nd-BR while having a minimal effect on the crystallization mechanism. A master curve, which overlaps for various samples, is developed by correlating the peak melting temperature (Tm,peak) with the Tc. This curve facilitates a quantitative assessment of the effects of BIR and TDAE oil on Nd-BR, highlighting the greater influence of TDAE oil on the crystalline structure compared with BIR at equivalent mass fractions. By applying the Lorentz equation and multi-peak fitting, a relationship between the melting points and crystallization temperatures is established, enabling the calculation of the equilibrium melting points (Tm0) for different samples. The findings show a reduction in the Tm0 due to the diluents; specifically, the Tm0 is approximately 0 °C for pure Nd-BR, and it decreases to -4.579 °C and -6.579 °C for samples with 50 PHR TDAE oil and 60 wt.% BIR, respectively.

4.
Materials (Basel) ; 17(1)2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38204108

RESUMEN

Utilizing neodymium-based butadiene rubber as a baseline, this study examines the effect of eco-friendly aromatic TDAE oil, fillers, and crosslinking reactions on neodymium-based rare-earth butadiene rubber (Nd-BR) crystallization behavior. The findings suggest that TDAE oil hinders crystallization, resulting in decreased crystallization temperatures and heightened activation energies (Ea). The crystallization activation energies for 20 parts per hundreds of rubber (PHR) and 37.5 PHR oil stand at -116.8 kJ/mol and -48.1 kJ/mol, respectively, surpassing the -264.3 kJ/mol of the unadulterated rubber. Fillers act as nucleating agents, hastening crystallization, which in turn elevates crystallization temperatures and diminishes Ea. In samples containing 20 PHR and 37.5 PHR oil, the incorporation of carbon black and silica brought the Ea down to -224.9 kJ/mol and -239.1 kJ/mol, respectively. Crosslinking considerably restricts molecular motion and crystallization potential. In the examined conditions, butadiene rubber containing 37.5 PHR oil displayed no crystallization following crosslinking, albeit crystallization was discernible with filler inclusion. Simultaneously, the crystallinity level sharply declined, manifesting cold crystallization behavior. The crosslinking process elevates Ea, while the equilibrium melting point (Tm0) noticeably diminishes. For instance, the Tm0 of pure Nd-BR is approximately -0.135 °C. When blended with carbon black and silica, the Tm0 values are -3.13 °C and -5.23 °C, respectively. After vulcanization, these values decrease to -21.6 °C and -10.16 °C. Evaluating the isothermal crystallization kinetics of diverse materials via the Avrami equation revealed that both the oil and crosslinking process can bring about a decrease in n values, with the Avrami index n for various samples oscillating between 1.5 and 2.5. Assessing the dynamic mechanical attributes of different specimens reveals that Nd-BR crystallization notably curtails its glass transition, marked by a modulus shift in the transition domain and a decrement in loss factor. The modulus in the rubbery state also witnesses a substantial augmentation.

5.
MethodsX ; 11: 102465, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37954968

RESUMEN

The nano/microelectromechanical system (N/MEMS) has triggered worldwide concern, and its applications have revolutionized technologies in various advanced fields from wearable sensors, 5 G communication technology, to energy harvesting, to aerospace. However, when the applied force is sufficiently large, the pull-in instability arises, and reliable operation is forbidden. Therefore, it is extremely important to insight fast and accurately into the periodic motion of the system to prevent the system from its pull-in motion. The basic aim of this study is to demonstrate the applicability of the well-known variational iteration method (VIM) for predicting the dynamic behavior of N/MEMS. For this, a nanobeam-based microstructure with van der Waals force for actuation is used as an example to reveal its periodic properties. The governing equation for the oscillation of the microsystem is obtained from the Euler-Bernoulli beam principle, considering the midplane stretching effect. We then employ the Galerkin technique to transform the governing partial differential equation into an ordinary differential equation, which is highly nonlinear, making it extremely difficult to solve by some traditional analytical methods, however, the VIM shows its ability to elucidate accurately the basic properties of the N/MEMS by simple calculation. This paper offers a new road for fast and accurate prediction of the microsystem's properties, and the result can be used for optimizing the N/MEMS.•A nanobeam-based N/MEMS system with van der Waals force is considered.•A strongly governing equation without a linear term is obtained.•The variational iteration method is applied to figure out the basic properties of the system.

6.
Artículo en Inglés | MEDLINE | ID: mdl-37877565

RESUMEN

BACKGROUND: Bipolymeric nanofibers have gained significant attention in various fields due to their enhanced functionality, improved mechanical properties, and controlled release capabilities. However, the fabrication of these composite fibers with a well-defined polymer-polymer interface remains a challenging task. METHODS: The double bubble electrospinning setup was developed and simulated using Maxwell 3D to analyze the electric field. PVP and PVA polymers were electrospun simultaneously to create bipolymer nanofibers with an interface. The resulting nanofibers were compared with nanofibers made from pure PVA, PVP, and a PVA/PVP blend. The characterization of the nanofibers was performed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). RESULTS: The SEM images showed the formation of PVA/PVP interfacial nanofibers aligned side by side, with a diameter of a few thousand nanometers on each side. By increasing the voltage from 20 kV to 40 kV during electrospinning, the diameter of the nanofibers on the PVA and PVP sides was successfully reduced by 60.8% and 66.3%, respectively. FTIR analysis confirmed the presence of both PVA and PVP in the bipolymeric interfacial nanofibers. TGA analysis demonstrated a weight retention of 14.28% compared to PVA, PVP, and the PVA/PVP blend even after degradation at 500°C. The Maxwell simulation of double bubble electrospinning revealed a stronger and more uniform electric field pattern at 40 kV compared to 20 kV. CONCLUSION: The study has demonstrated the potential of double bubble electrospinning for the fabrication of bipolymer nanofibers with an interface, opening new avenues for the development of functional nanofibers.

7.
Front Physiol ; 14: 1187743, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37389122

RESUMEN

Encarsia formosa is a natural enemy of the invasive pest Bemisia tabaci and is known to be a dominant parasitic. The frequency and magnitude of climate extremes, particularly temperature extremes, have increased, which has put insect populations at risk. However, the effects of temperature extremes on E. formosa are not well understood. To examine the impact of short-term extreme temperature exposure on the development and reproduction of E. formosa, eggs, larvae, pupae, and adults were exposed to high/low temperature treatments (HLT25, HLT50, LLT25, and LLT50). Our findings indicate that the pupal stage of E. formosa exhibited the strongest tolerance to both heat and cold, while adults exhibited a weaker tolerance. The shortest egg-to-adult development period of 12.65 days was observed in E. formosa exposed to HLT50 treatment during the egg-larval stage. The parasitism peak of the adult stage was delayed by 1-6 days after exposure to extreme temperatures during the egg-larval stage. Conversely, the parasitism peak was advanced by 1-3 days after exposure to extreme temperatures during the pupal and adult stages. The eclosion rate, total parasitism, eclosion rate of the F1 generation, and adult longevity of the F1 generation were lower in the treatment groups than in the control groups. The F1 generation's development period was prolonged to 15.49 and 15.19 days after exposure to HLT25 and HLT50 treatments, respectively, during the egg-larval stage. The F1 generation's development period was shortened to 13.33 days after exposure to LLT50 treatment during the pupal stage. Male individuals appeared in the F1 generation after exposure to HLT50 treatment during the pupal stage, with females accounting for only 56.38%. Our results demonstrate that short-term exposure to extreme temperatures has detrimental effects on the growth and reproduction of E. formosa. In field biocontrol against E. formosa, the release of E. formosa should be avoided as much as possible when the ambient temperature is higher than 35°C or lower than 0°C. During extreme temperature conditions, timely supplementation and release of E. formosa population, along with ventilation and cooling in greenhouse facilities during summer, are necessary for better pest control efficacy.

8.
Math Biosci Eng ; 20(5): 8190-8207, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-37161192

RESUMEN

This paper presents the Elzaki homotopy perturbation transform scheme (EHPTS) to analyze the approximate solution of the multi-dimensional fractional diffusion equation. The Atangana-Baleanu derivative is considered in the Caputo sense. First, we apply Elzaki transform (ET) to obtain a recurrence relation without any assumption or restrictive variable. Then, this relation becomes very easy to handle for the implementation of the homotopy perturbation scheme (HPS). We observe that HPS produces the iterations in the form of convergence series that approaches the precise solution. We provide the graphical representation in 2D plot distribution and 3D surface solution. The error analysis shows that the solution derived by EHPTS is very close to the exact solution. The obtained series shows that EHPTS is a very simple, straightforward, and efficient tool for other problems of fractional derivatives.

9.
Polymers (Basel) ; 16(1)2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38201700

RESUMEN

The crystallization behavior of neodymium-based rare earth polybutadiene rubber (Nd-BR) is studied in the presence of small-molecule treated distillate aromatic extract (TDAE) and high-molecular-weight polybutadiene-isoprene copolymer rubber (BIR). Pronounced inhibitory effects on the crystallization of Nd-BR are exhibited by both materials, as evidenced by reductions in the crystallization temperature (Tc), melting point (Tm), and corresponding enthalpy change. It is found that, at equal concentrations, a greater influence on the crystallization rate is exerted by TDAE oils, whereas nucleation inhibition is more potently affected by BIR. Incomplete crystallization during cooling is exhibited by Nd-BR when the TDAE oil concentration reaches 40 parts per hundreds of rubber (PHR) (31 wt.%), or BIR achieves a 60 wt.% concentration; subsequently, a noticeable cold crystallization phenomenon is observed upon heating. Insights into the isothermal crystallization kinetics are offered by the data, which reveal that the Avrami index n value for Nd-BR predominantly ranges between 2.5 and 3.0. A decrease in the n value is induced by a small amount of TDAE oil, while a noticeable decline in the n value is observed only when the BIR concentration is 60 wt.%. A correlation between the crystallization activation energy, the concentration of TDAE oil and BIR, and the crystallization temperature is established; a negative activation energy is recorded, and a decrease in the crystallization rate is noted when both concentrations are low and the crystallization temperature exceeds -50 °C. In contrast, positive activation energy and an increase in the crystallization rate are observed when the BIR concentration reaches 60%, and the crystallization temperature resides between -50 °C and -70 °C.

10.
Front Plant Sci ; 13: 1068769, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36531377

RESUMEN

Cadmium is one of the most common heavy metal contaminants found in agricultural fields. MutSα, MutSß, and MutSγ are three different MutS-associated protein heterodimer complexes consisting of MSH2/MSH6, MSH2/MSH3, and MSH2/MSH7, respectively. These complexes have different mismatch recognition properties and abilities to support MMR. However, changes in mismatch repair genes (OsMSH2, OsMSH3, OsMSH6, and OsMSH7) of the MutS system in rice, one of the most important food crops, under cadmium stress and their association with E2Fs, the key transcription factors affecting cell cycles, are poorly evaluated. In this study, we systematically categorized six rice E2Fs and confirmed that OsMSHs were the downstream target genes of E2F using dual-luciferase reporter assays. In addition, we constructed four msh mutant rice varieties (msh2, msh3, msh6, and msh7) using the CRISPR-Cas9 technology, exposed these mutant rice seedlings to different concentrations of cadmium (0, 2, and 4 mg/L) and observed changes in their phenotype and transcriptomic profiles using RNA-Seq and qRT-PCR. We found that the difference in plant height before and after cadmium stress was more significant in mutant rice seedlings than in wild-type rice seedlings. Transcriptomic profiling and qRT-PCR quantification showed that cadmium stress specifically mobilized cell cycle-related genes ATR, CDKB2;1, MAD2, CycD5;2, CDKA;1, and OsRBR1. Furthermore, we expressed OsE2Fs in yeasts and found that heterologous E2F expression in yeast strains regulated cadmium tolerance by regulating MSHs expression. Further exploration of the underlying mechanisms revealed that cadmium stress may activate the CDKA/CYCD complex, which phosphorylates RBR proteins to release E2F, to regulate downstream MSHs expression and subsequent DNA damage repairment, thereby enhancing the response to cadmium stress.

11.
Front Bioeng Biotechnol ; 10: 926253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35957639

RESUMEN

Polar bears can live in an extremely cold environment due to their hairs which possess some remarkable properties. The hollow structure of the hair enables the bear to absorb energy from water, and the white and transparent hairs possess amazing optical properties. However, the surface morphology function of bear hairs has been little-studied. Herein, we demonstrate that the micro-structured scales distributed periodically along the hair can absorb maximal radiative flux from the Sun. This polar bear hair effect has the ability for the hair surface not to reflect radiation with a wavelength of about 500 nm. Mimicking the polar bears' solar performance in the fabrication of nanofibers will certainly stimulate intelligent nanomaterials for efficient solar energy absorption. Therefore, a new technology is discussed in this work for the fabrication of periodic unsmooth nanofibers toward solar energy harvesting.

12.
Front Pharmacol ; 13: 896104, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35847000

RESUMEN

The objective of this study was to apply a machine learning method to evaluate the risk factors associated with serious adverse events (SAEs) and predict the occurrence of SAEs in cancer inpatients using antineoplastic drugs. A retrospective review of the medical records of 499 patients diagnosed with cancer admitted between January 1 and December 31, 2017, was performed. First, the Global Trigger Tool (GTT) was used to actively monitor adverse drug events (ADEs) and SAEs caused by antineoplastic drugs and take the number of positive triggers as an intermediate variable. Subsequently, risk factors with statistical significance were selected by univariate analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, using the risk factors after the LASSO analysis as covariates, a nomogram based on a logistic model, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), adaptive boosting (AdaBoost), light-gradient-boosting machine (LightGBM), random forest (RF), gradient-boosting decision tree (GBDT), decision tree (DT), and ensemble model based on seven algorithms were used to establish the prediction models. A series of indicators such as the area under the ROC curve (AUROC) and the area under the PR curve (AUPR) was used to evaluate the model performance. A total of 94 SAE patients were identified in our samples. Risk factors of SAEs were the number of triggers, length of stay, age, number of combined drugs, ADEs occurred in previous chemotherapy, and sex. In the test cohort, a nomogram based on the logistic model owns the AUROC of 0.799 and owns the AUPR of 0.527. The GBDT has the best predicting abilities (AUROC = 0.832 and AUPR = 0.557) among the eight machine learning models and was better than the nomogram and was chosen to establish the prediction webpage. This study provides a novel method to accurately predict SAE occurrence in cancer inpatients.

13.
Cell Transplant ; 31: 9636897221083549, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35315295

RESUMEN

Under endoplasmic reticulum (ER) stress, tumor plays multifaceted roles in endothelial cell dysfunction through secreting exosomal miRNAs. However, for the head and neck squamous cell carcinoma (HNSCC), it is still unclear about the impact of ER-stressed HNSCC cell derived exosomes on vascular endothelial cells. To address this gap, herein, systemic research was conducted including isolation and characterization of ER-stressed HNSCC cell (HN4 cell line as an in vitro model) derived exosomes, identification of regulatory exosomal miRNAs, target exploration and downstream signaling pathway investigation of exosomal miRNAs in human umbilical vein endothelial cell (HUVEC). ER-stressed HN4 cell-derived exosomes inhibited angiogenesis and migration of HUVEC cells in vitro. Furthermore, RNA-seq analysis demonstrated that miR-424-5p was highly upregulated in ER-stressed HN4 cell-derived exosomes. Through matrigel tube formation and transwell assays of HUVEC cells, miR-424-5p displayed great capabilities on inhibiting angiogenesis and migration. Finally, based on western blot and luciferase reporter, it was demonstrated that LAMC1 is the target of miR-424-5p which could inhibit the angiogenesis and migration of HUVEC cells by repressing the LAMC1-mediated Wnt/ß-catenin signaling pathway. ER-stressed HNSCC cell-induced exosomal miR-424-5p inhibits angiogenesis and migration of HUVEC cells through LAMC1-mediated Wnt/ß-catenin signaling pathway. This study offers a new insight for understanding the complicated mechanism behind ER-stress induced anti-angiogenesis of HNSCC.


Asunto(s)
Exosomas , Neoplasias de Cabeza y Cuello , MicroARNs , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Retículo Endoplásmico/metabolismo , Exosomas/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neovascularización Patológica/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Vía de Señalización Wnt
14.
Cell Calcium ; 103: 102549, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35144093

RESUMEN

In Drosophila compound eyes, myosin-5 (DmMyo5) plays a key role in organelle transportation, including transporting pigment granules from the distal end to the proximal end of the photoreceptor cells to regulate the amount of light reaching the photosensitive membrane organelle rhabdomere. It is generally accepted that, upon exposure to light, the dark-adapted compound eyes produce a rapid rise of free Ca2+ concentration, which in turn activates DmMyo5 to transport pigment granules. Considering the dynamic and compartmentation of Ca2+ signaling in photoreceptor cells during light exposure, it is necessary to understand the kinetics of Ca2+ interaction with DmMyo5. Here, we investigated the interaction of Ca2+ with Drosophila calmodulin (CaM) in complex with the IQ1 of DmMyo5 using steady-state and kinetic approaches. Our results show that IQ1 binding substantially increases the Ca2+ affinity of CaM and decreases the dissociation rate of Ca2+ from CaM. In addition, we found that Mlc-C, the light chain associated with the IQ2 of DmMyo5, has little effect on the Ca2+ kinetics of CaM in IQ1. We propose that, by decreasing the Ca2+ dissociation rate from CaM, IQ1 delays the deactivation of DmMyo5 after Ca2+ transition, thereby prolonging the DmMyo5-driven transportation of pigment granules.


Asunto(s)
Calcio , Calmodulina , Animales , Calcio/metabolismo , Calmodulina/metabolismo , Drosophila/metabolismo , Miosinas/química , Miosinas/metabolismo , Unión Proteica/fisiología
15.
J Anat ; 240(2): 398-409, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34590312

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted through droplets. All human tissues with the angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serines 2 (TRMPRSS2) are potential targets of SARS-CoV-2. The role of saliva in SARS-CoV-2 transmission remains obscure. In this study, we attempted to reveal ACE2 and TRMPRSS2 protein expression in human parotid, submandibular, and sublingual glands (three major salivary glands). Then, the binding function of spike protein to ACE2 in three major salivary glands was detected. The expression of ACE2 and TMPRSS2 in human saliva from parotid glands were both examined. Exogenous recombined ACE2 and TMPRSS2 anchoring and fusing to oral mucosal epithelial cells in vitro were also unraveled. ACE2 and TMPRSS2 were found mainly to be expressed in the cytomembrane and cytoplasm of epithelial cells in the serous acinus cells in parotid and submandibular glands. Our research also discovered that the spike protein of SARS-CoV-2 binds to ACE2 in salivary glands in vitro. Furthermore, exogenous ACE2 and TMPRSS2 can anchor and fuse to oral mucosa in vitro. Thus, the expression of ACE2 and TMPRSS2 in human saliva might have implications for SARS-CoV-2 infection.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Epitelio , Humanos , Mucosa Bucal , SARS-CoV-2 , Saliva , Serina Endopeptidasas
16.
Antimicrob Agents Chemother ; 66(1): e0166821, 2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-34662186

RESUMEN

We aimed to estimate the risk of varied antifungal therapy with azoles causing the syndrome of acquired apparent mineralocorticoid excess (AME) in real-world practice. First, we conducted a disproportionality analysis based on data from the FDA Adverse Event Reporting System (FAERS) database to characterize the signal differences of triazoles-related AME. Second, a systematic review was conducted, and clinical features of AME cases reported in clinical practice were described. In the FAERS database, we identified 27 cases of triazoles-AME, posaconazole [ROR = 865.37; 95%CI (464.14; 1613.45)], and itraconazole [ROR = 556.21; 95% (303.05; 1020.85)] significantly increased the risk of AME events, while fluconazole, voriconazole, and isavuconazole did not affect any of the mineralocorticoid excess targets. Eighteen studies with 39 cases raised evidence of AME following posaconazole and itraconazole treatment, and another 27 cases were identified by analysis of the description of clinical features in the FAERS database. The average age of 66 patients was 55.5 years (6-87 years). AME mainly occurs in patients with posaconazole concentrations above 3 µg/mL (mean = 4.4 µg/mL, range 1.8∼9.5 µg/mL), and is less likely to occur when levels are below 2 µg/mL (6%). The median time to event onset was 11.5 weeks, and 50% of the adverse events occurred within 3 months for posaconazole. The presented study supports very recent findings that posaconazole and itraconazole, but not the other three azole antifungals investigated, are associated with AME and that the effects are dose-dependent, which allows for a dose de-escalation strategy and for substitution with fluconazole, isavuconazole, or voriconazole to resolve the adverse effects.


Asunto(s)
Antifúngicos , Síndrome de Exceso Aparente de Mineralocorticoides , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/efectos adversos , Azoles/efectos adversos , Niño , Humanos , Itraconazol/efectos adversos , Persona de Mediana Edad , Síndrome de Exceso Aparente de Mineralocorticoides/inducido químicamente , Voriconazol , Adulto Joven , Síndrome de Exceso Aparente de Mineralocorticoides
18.
J Transl Med ; 19(1): 423, 2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34641907

RESUMEN

This research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/ß-catenin signaling pathway. Rescue experiment demonstrated the inhibition of ß-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt-ß-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/ß-catenin signaling pathway in HNSCC.


Asunto(s)
Neoplasias de Cabeza y Cuello , Vía de Señalización Wnt , Animales , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Ratones , Ratones Desnudos , Proteínas de Neoplasias , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , beta Catenina/metabolismo
19.
Sci Rep ; 11(1): 21196, 2021 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-34707102

RESUMEN

Traditional preparation of ZnO nanocrystal requires heating zinc acetate to a temperature over 350 °C, whereas in this work, zinc acetate was first electrospun with PVDF to form a nanofiber, followed by thermal treatment at only 140 °C to give nanocrystalline ZnO. The much lower temperature required in thermal treatment is attributed to the high reactivity of zinc acetate at nano dimension. The as-prepared ZnO-doped PVDF nanofiber mat shows excellent effect in the photocatalytic degradation of Rhodamine B, comparable to ZnO particle thermally treated at 600 °C. Highly-oriented ZnO nanorods were obtained by further hydrothermal synthesis of the electrospun nanofiber mat, giving nanostructured ZnO of different morphologies well-aligned on the surface of organic nanofiber. Notably, the hydrothermal synthesis of the successful preparation of these nanostructured ZnO requires a processing temperature below 100 °C at atmospheric pressure, showing great potential to be scaled up for vast manufacturing.

20.
Polymers (Basel) ; 12(10)2020 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-33050056

RESUMEN

Mechanical property is one of the most important properties of nanofiber membranes. Electrospinning is widely used in the preparation of nanofibers due to its advantages such as good stability and easy operation. Compared with some nature silk, the mechanical properties of nanofibers prepared by electrospinning are poor. Based on the principle of vortex spinning and DNA structure, this paper designed an air vortex electrospinning device that can control the structure of macromolecular chains in nanofibers. When a weak air vortex is generated in the electrospinning process, the macromolecule chains will entangle with each other and form a DNA-like structure so as to improve the mechanical property. In addition, when a strong air vortex is generated during the electrospinning process, the nanofibers will adhere to each other, thereby enhancing the mechanical property and enlarging the pore size.

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