Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Más filtros












Base de datos
Intervalo de año de publicación
1.
Appl Opt ; 63(14): 3842-3853, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38856347

RESUMEN

Image quality and resolution are important factors affecting the application value of remote sensing images. Although increasing the optical aperture of space optical remote sensors (SORSs) improves image resolution, it exacerbates the effects of the space environment on imaging quality. Thus, this study proposes thermal active optical technology (TAO) to enhance image quality while increasing the optical aperture of SORSs by actively correcting in-orbit wavefront aberrations. Replacing traditional wavefront detection and reconstruction with numerical calculation and simulation analysis, more realistic in-orbit SORS wavefront aberrations are obtained. Numerical and finite element analyses demonstrate that nonlinearities in TAO control lead to the failure of traditional wavefront correction algorithms. To address this, we use a neural network algorithm combining CNN and ResNet. Simulation results show that the residual of the systematic wavefront RMS error for SORS reduces to 1/100λ. The static and dynamic modular transfer functions are improved, and the structural similarity index is recovered by over 23%, highlighting the effectiveness of TAO in image quality enhancement. The static and thermal vacuum experiments demonstrate the wide applicability and engineering prospects of TAO.

2.
J Colloid Interface Sci ; 673: 395-410, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38878374

RESUMEN

In emergencies, uncontrolled severe bleeding can result in undesired complications and even death of the injured. Designing advanced hemostatic agents is a potential solution for emergency hemostasis, yet it remains challenging to realize the persistent adhesion in a wet wound environment. In this study, based on dynamic reversible Schiff base bond and photo-initiated double-bond polymerization, a novel injectable hemostatic hydrogel (L-COC) consisting of methacrylated carboxymethyl chitosan (CMCSMA), oxidized konjac glucomannan (OKGM) and (+)-catechin hydrate (CH) was synthesized for emergency hemostasis. To our delight, the incorporated CH imparted enhanced blood procoagulantion to the L-COC hydrogel by intensifying the hydrogel-red blood cell interactions. As a result, the hemostatic effect of the engineered L-COC hydrogel was significantly superior to that of fluid gelatin SurgifloTM for liver bleeding wounds in rats (Blood loss: 0.62 ± 0.11 g (L-COC), 0.90 ± 0.08 g (SurgifloTM); hemostasis time: 69.0 ± 2.9 s (L-COC), 84.0 ± 2.2 s (SurgifloTM)). With the favorable antioxidant and antibacterial activities, as well as multifunctional properties, the bio-adhesive L-COC hydrogel and the underlying design principles may facilitate further development of practical hemostatic hydrogels.

3.
J Nanobiotechnology ; 22(1): 217, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725012

RESUMEN

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.


Asunto(s)
Antioxidantes , Vendajes , Quitosano , Hidrogeles , Plasma Rico en Plaquetas , Povidona , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Povidona/química , Povidona/análogos & derivados , Hidrogeles/química , Hidrogeles/farmacología , Plasma Rico en Plaquetas/química , Animales , Ratones , Masculino , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Estrés Oxidativo/efectos de los fármacos , Humanos
4.
Am J Physiol Renal Physiol ; 326(6): F1016-F1031, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38601985

RESUMEN

Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a secreted proteoglycan, with notable expression in kidney, which attenuates inflammation and albuminuria. However, little is known about Esm1 expression in mature tissues in the presence or absence of diabetes. We utilized publicly available single-cell RNA sequencing data to characterize Esm1 expression in 27,786 renal endothelial cells (RECs) obtained from three mouse and four human databases. We validated our findings using bulk transcriptome data from 20 healthy subjects and 41 patients with DKD and using RNAscope. In both mice and humans, Esm1 is expressed in a subset of all REC types and represents a minority of glomerular RECs. In patients, Esm1(+) cells exhibit conserved enrichment for blood vessel development genes. With diabetes, these cells are fewer in number and shift expression toward chemotaxis pathways. Esm1 correlates with a majority of genes within these pathways, delineating a glomerular transcriptional polarization reflected by the magnitude of Esm1 deficiency. Diabetes correlates with lower Esm1 expression and with changes in the functional characterization of Esm1(+) cells. Thus, Esm1 appears to be a marker for glomerular transcriptional polarization in DKD.NEW & NOTEWORTHY Esm-1 is primarily expressed in glomerular endothelium in humans. Cells expressing Esm1 exhibit a high degree of conservation in the enrichment of genes related to blood vessel development. In the context of diabetes, these cells are reduced in number and show a significant transcriptional shift toward the chemotaxis pathway. In diabetes, there is a transcriptional polarization in the glomerulus that is reflected by the degree of Esm1 deficiency.


Asunto(s)
Nefropatías Diabéticas , Células Endoteliales , Proteoglicanos , Humanos , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Animales , Proteoglicanos/genética , Proteoglicanos/metabolismo , Células Endoteliales/metabolismo , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Estudios de Casos y Controles , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Transcriptoma , Ratones , Transcripción Genética , Quimiotaxis , Proteínas de Neoplasias
5.
Acta Biomater ; 178: 265-286, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38417643

RESUMEN

The clinical treatment of inflammatory bowel disease (IBD) is challenging. We developed copper sulfate (CuS)/disulfiram (DSF)/methacrylic acid-ethyl acrylate copolymer (EL)/polyvinylpyrrolidone (PVP) nanoplatform (CuS/DSF/EL/PVP) and evaluated its efficiency for treating IBD. After oral administration, the pH-sensitive EL protected the CuS/DSF/EL/PVP against degradation by acidic gastric juices. Once the colon was reached, EL was dissolved, releasing DSF and Cu2+. Further, the main in vivo metabolite of DSF can bind to Cu2+ and form copper (II) N, N-diethyldithiocarbamate (CuET), which significantly alleviated acute colitis in mice. Notably, CuS/DSF/EL/PVP outperformed CuS/EL/PVP and DSF/EL/PVP nanoplatforms in reducing colonic pathology and improving the secretion of inflammation-related cytokines (such as IL-4 and IL-10) in the colonic mucosa. RNA-seq analysis revealed that the nanoplatform reduced colonic inflammation and promoted intestinal mucosal repair by upregulating C-type lectin receptor (CLR)-related genes and signaling pathways. Furthermore, CuS/DSF/EL/PVP showed potential for improving colitis Th1/Th17 cells through innate immunity stimulation, down-regulation of inflammatory cytokines, and upregulation of anti-inflammatory cytokines. Additionally, the intervention with CuS/DSF/EL/PVP led to increased intestinal flora diversity, decreased Escherichia-Shigella abundance, and elevated levels of short-chain fatty acid (SCFA)-producing bacteria Prevotella, Lactobacillus, and Bifidobacterium, indicating their potential to modulate the dysregulated intestinal flora and suppress inflammation. STATEMENT OF SIGNIFICANCE: Our study introduces the CuS/DSF/EL/PVP nanoplatform as a therapeutic strategy for treating inflammatory bowel disease (IBD). This approach demonstrates significant efficacy in targeting the colon and alleviating acute colitis in mice. It uniquely modulates gut immunity and microbiota, exhibiting a notable impact on inflammation-related cytokines and promoting intestinal mucosal repair. The nanoplatform's ability to regulate gut flora diversity, combined with its cost-effective and scalable production, positions it as a potentially transformative treatment for IBD, offering new avenues for personalized medical interventions.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Microbiota , Animales , Ratones , Povidona , Disulfiram/uso terapéutico , Cobre/farmacología , Enfermedades Inflamatorias del Intestino/metabolismo , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colitis/patología , Colon/patología , Inflamación/patología , Citocinas/metabolismo , Concentración de Iones de Hidrógeno , Sulfato de Dextran/uso terapéutico , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
6.
Int J Biol Macromol ; 261(Pt 2): 129828, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38296135

RESUMEN

Hydrogels have been widely used as wound dressings to accelerate wound healing. However, due to the impaired skin barrier at the wound site, external bacteria can easily invade the wound and cause infection. In this study, we designed a dopamine-modified sodium alginate/carboxymethyl chitosan/polyvinylpyrrolidone (CPD) hydrogel, which was able to promote wound healing while preventing wound infection. Due to the high content of catechol groups, the CPD hydrogel exhibited good tissue adhesion ability and a significant scavenging ability for DPPH• and PTIO• radicals. Under near-infrared laser irradiation, the temperature of CPD hydrogel increased significantly, which significantly killed the Staphylococcus aureus and Escherichia coli. The cell migration test confirmed that CPD hydrogel could promote the cell migration ratio. In the in vivo wound healing test for infected full-thickness skin defect, CPD hydrogel significantly inhibited bacterial proliferation and enhanced wound healing rate. Therefore, the multifunctional hydrogel is expected to be applied to wound healing.


Asunto(s)
Quitosano , Infección de Heridas , Humanos , Hidrogeles/farmacología , Quitosano/farmacología , Cicatrización de Heridas , Infección de Heridas/tratamiento farmacológico , Alginatos , Escherichia coli , Rayos Infrarrojos , Antibacterianos/farmacología
7.
Gels ; 9(6)2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37367123

RESUMEN

In recent years, multifunctional hydrogel nanoplatforms for the synergistic treatment of tumors have received a great deal of attention. Here, we prepared an iron/zirconium/polydopamine/carboxymethyl chitosan hydrogel with Fenton and photothermal effects, promising for future use in the field of synergistic therapy and prevention of tumor recurrence. The iron (Fe)-zirconium (Zr)@ polydopamine (PDA) nanoparticles were synthesized by a simple one-pot hydrothermal method using iron (III) chloride hexahydrate (FeCl3•6H2O), zirconium tetrachloride (ZrCl4), and dopamine, followed by activation of the carboxyl group of carboxymethyl chitosan (CMCS) using 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/N(4)-hydroxycytidine (NHS). Finally, the Fe-Zr@PDA nanoparticles and the activated CMCS were mixed to form a hydrogel. On the one side, Fe ions can use hydrogen peroxide (H2O2) which is rich in the tumor microenvironment (TME) to produce toxic hydroxyl radicals (•OH) and kill tumor cells, and Zr can also enhance the Fenton effect; on the other side, the excellent photothermal conversion efficiency of the incorporated PDA is used to kill tumor cells under the irradiation of near-infrared light. The ability of Fe-Zr@PDA@CMCS hydrogel to produce •OH and the ability of photothermal conversion were verified in vitro, and swelling and degradation experiments confirmed the effective release and good degradation of this hydrogel in an acidic environment. The multifunctional hydrogel is biologically safe at both cellular and animal levels. Therefore, this hydrogel has a wide range of applications in the synergistic treatment of tumors and the prevention of recurrence.

8.
Int J Biol Macromol ; 242(Pt 3): 124960, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37230448

RESUMEN

The conventional method of using montmorillonite hemostatic materials affects the hemostatic effect due to easy dislodgement on the wound surface. In this paper, a multifunctional bio-hemostatic hydrogel (CODM) was prepared based on hydrogen bonding and Schiff base bonding using modified alginate, polyvinylpyrrolidone (PVP), and carboxymethyl chitosan. The amino group-modified montmorillonite was uniformly dispersed in the hydrogel by its amido bond formation with the carboxyl groups of carboxymethyl chitosan and oxidized alginate. The catechol group, -CHO, and PVP can form hydrogen bonds with the tissue surface to afford the firm tissue adhesion to afford the wound hemostatic. The addition of montmorillonite-NH2 further improves the hemostatic ability, making it better than commercial hemostatic materials. Moreover, the photothermal conversion ability (derived from the polydopamine) was synergized with the phenolic hydroxyl group, quinone group, and the protonated amino group to effectively kill the bacteria in vitro and in vivo. Based on its in vitro and in vivo biosafety and satisfactory degradation ratio anti-inflammatory, antibacterial, and hemostatic properties, the CODM hydrogel holds promising potential for emergency hemostasis and intelligent wound management.


Asunto(s)
Quitosano , Hemostáticos , Bentonita , Hidrogeles/farmacología , Hemostáticos/farmacología , Alginatos , Antibacterianos/farmacología , Hemostasis
9.
Heliyon ; 9(5): e15830, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37159709

RESUMEN

The great need and tendency to apply online classes ask for using new technologies in language teaching. Social Networking (SN) tools, in particular, Mobile-Assisted Language Learning (MALL), open new perspectives in language learning and teaching. The employment of SN in language learning may affect the learners' mental health and emotional safety. Despite the attributions of the Telegram application in learning and the contributions of academic buoyancy (AB), academic emotion regulation (AER), and management of foreign language anxiety (FLA) to English achievement (EA), this field was left unexplored. To this end, the current study attempted to gauge the impact of the Telegram-based instruction on AB, AER, FLA, as well as EA. 79 EFL learners took part in the research and were randomly divided in to control group (CG) and experimental group (EG). The instruction for the CG was through regular online instruction (webinar platforms). The EG received Telegram-based instruction. The results of MANOVA displayed significant differences between the post-tests of CG and EG. The findings illustrated that the Telegram instruction improved the levels of AB, AER, and FLA management, which accelerated EA. The pedagogical implications of the study were discussed and may assist learners, teachers, teacher educators, policymakers, materials developers, as well as curriculum designers.

10.
Int J Pharm ; 636: 122848, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-36931536

RESUMEN

Glucose is used as an important nutrient to support cell growth. The glucose oxidase (GOx) can transform glucose into gluconic acid and toxic H2O2, which can be used for tumor starvation therapy. However, the leakage of GOx may cause severe side effects to the normal tissue. To prevent the accidental leakage of GOx, this study proposes the chemical modification of GOx on the photothermal transducing agent surface, to realize the safe and combined starvation and photothermal therapy of colorectal tumors. Polyvinylpyrrolidone (PVP)-modified WS2 nanobowls (WS2-PVP) as a photothermal transducing agent were produced using a one-pot preparation method. Then, α-lipoic acid (LA) molecules were immobilized at the sulfur-deficient sites on the surface of WS2 nanobowls to afford the chemical loading of GOx through amide bonds. Under the irradiation of a near-infrared laser (808 nm), thermal energy is generated by WS2 to kill colorectal cancer cells locally. The photothermal conversion efficiency of WS2-PVP-LA was 27.2%. This study is anticipated to open up an alternative avenue for the rational design of multifunctional nanotherapeutics for tumor therapy.


Asunto(s)
Neoplasias Colorrectales , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Glucosa Oxidasa/química , Peróxido de Hidrógeno/química , Neoplasias Colorrectales/tratamiento farmacológico , Povidona , Glucosa , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Nanopartículas/química
11.
bioRxiv ; 2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36993439

RESUMEN

Background: Esm-1, endothelial cell-specific molecule-1, is a susceptibility gene for diabetic kidney disease (DKD) and is a cytokine- and glucose-regulated, secreted proteoglycan, that is notably expressed in kidney and attenuates inflammation and albuminuria. Esm1 has restricted expression at the vascular tip during development but little is known about its expression pattern in mature tissues, and its precise effects in diabetes. Methods: We utilized publicly available single-cell RNA sequencing data to explore the characteristics of Esm1 expression in 27,786 renal endothelial cells obtained from four adult human and three mouse databases. We validated our findings using bulk transcriptome data from an additional 20 healthy subjects and 41 patients with DKD and using RNAscope. Using correlation matrices, we relate Esm1 expression to the glomerular transcriptome and evaluated these matrices with systemic over-expression of Esm-1. Results: In both mice and humans, Esm1 is expressed in a subset of all renal endothelial cell types and represents a minority of glomerular endothelial cells. In patients, Esm1 (+) cells exhibit a highly conserved enrichment for blood vessel development genes. With diabetes, these cells are fewer in number and profoundly shift expression to reflect chemotaxis pathways. Analysis of these gene sets highlight candidate genes such as Igfbp5 for cross talk between cell types. We also find that diabetes induces correlations in the expression of large clusters of genes, within cell type-enriched transcripts. Esm1 significantly correlates with a majority genes within these clusters, delineating a glomerular transcriptional polarization reflected by the magnitude of Esm1 deficiency. In diabetic mice, these gene clusters link Esm1 expression to albuminuria, and over-expression of Esm-1 reverses the expression pattern in many of these genes. Conclusions: A comprehensive analysis of single cell and bulk transcriptomes demonstrates that diabetes correlates with lower Esm1 expression and with changes in the functional characterization of Esm1 (+) cells. Esm1 is both a marker for glomerular transcriptional polarization, and a mediator that re-orients the transcriptional program in DKD.

12.
Int J Biol Macromol ; 230: 123196, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36634799

RESUMEN

The postoperative recurrence has adversely affected the treatment of tumors. Besides, the potential bacterial infection at the wound site may lead to a series of tissue necrosis. Here, we developed an injectable γ-polyglutamic acid/carboxymethyl chitosan/polydopamine hydrogel (PCP) for simultaneously reducing the postoperative infection and preventing the tumor recurrence. On the one hand, the aqueous solution of carboxymethyl chitosan oxidized the dopamine into polydopamine; on the other, the carboxymethyl chitosan was cross-linked with the activated γ-polyglutamic acid to form a hydrogel. After local implantation, the PCP hydrogel effectively killed tumor cells and bacteria under 808 nm laser irradiation. In addition, carboxymethyl chitosan rendered the hydrogel with anti-bacterial properties as well as anti-tumor efficiencies. The anti-tumor recurrence and anti-bacterial efficiencies of PCP hydrogel were proved on a tumor-removed mouse model and a Staphylococcus aureus-infected mouse model, respectively. Moreover, the hydrogel has the advantages of good biocompatibility and simple preparation, and thus has potential application prospects in the prevention of tumor recurrence and wound bacterial infection.


Asunto(s)
Quitosano , Hidrogeles , Ratones , Animales , Hidrogeles/farmacología , Ácido Poliglutámico , Bacterias , Antibacterianos
13.
Colloids Surf B Biointerfaces ; 221: 113010, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36375292

RESUMEN

The degradation of extracellular matrix (ECM) to increase drug permeability is an attractive approach to enhancing pancreatic cancer therapy efficiency. Herein, polypyrrole nanoparticles (PPy NPs) were prepared by a template-guided chemical oxidation method. These PPy NPs with abundant surface pores were used to load the anticancer drug doxorubicin (DOX). In order to intelligently control the DOX release, PPy/DOX NPs were further entrapped with a thermoresponsive ligand, lauric acid (LA), to form PPy-LA/DOX NPs. Bromelain (BL) was then grafted onto the surface of PPy-LA NPs or PPy-LA/DOX NPs through an amidation reaction with the carboxyl group of LA. It was found that the DOX release of PPy-LA/DOX NPs was pH and temperature responsive, reaching a maximum amount of 85.9% within 48 h at pH = 5.4 and 50 °C. Moreover, it was demonstrated that the resultant PLB (PPy-LA-BL) NPs could efficiently hydrolyze the collagen in ECM and enhance the permeability of DOX to the pancreatic tumor. Remarkably, PLB NPs not only featured admirable photothermal conversion but also exhibited obvious photoacoustic imaging capability, which enabled imaging-guided enhanced tumor ablation. This study is anticipated to provide a feasible strategy to improve the permeability of nanoparticles to tumors.


Asunto(s)
Neoplasias Pancreáticas , Polímeros , Humanos , Pirroles , Doxorrubicina/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Matriz Extracelular
14.
Molecules ; 27(21)2022 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-36364064

RESUMEN

Acute pancreatitis (AP) is a complex inflammatory disease caused by multiple etiologies, the pathogenesis of which has not been fully elucidated. Oxidative stress is important for the regulation of inflammation-related signaling pathways, the recruitment of inflammatory cells, the release of inflammatory factors, and other processes, and plays a key role in the occurrence and development of AP. In recent years, antioxidant therapy that suppresses oxidative stress by scavenging reactive oxygen species has become a research highlight of AP. However, traditional antioxidant drugs have problems such as poor drug stability and low delivery efficiency, which limit their clinical translation and applications. Nanomaterials bring a brand-new opportunity for the antioxidant treatment of AP. This review focuses on the multiple advantages of nanomaterials, including small size, good stability, high permeability, and long retention effect, which can be used not only as effective carriers of traditional antioxidant drugs but also directly as antioxidants. In this review, after first discussing the association between oxidative stress and AP, we focused on summarizing the literature related to antioxidant nanomaterials for the treatment of AP and highlighting the effects of these nanomaterials on the indicators related to oxidative stress in pathological states, aiming to provide references for follow-up research and promote clinical application.


Asunto(s)
Nanoestructuras , Pancreatitis , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/metabolismo , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
15.
Exp Mol Pathol ; 125: 104751, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35122807

RESUMEN

We have identified the novel protein GASP-1 (G protein coupled receptor-associated sorting protein 1) that appears to be a universal cancer marker and the expression of which in tumor tissue and patient sera is predictive of cancer severity (Tuszynski et al. 2011; Zheng et al. 2012; Zheng 2013; Chang and Tuszynski, 2020). In preliminary results we discovered that a GASP-1 antibody inhibited the growth of the triple negative breast cancer cell line MDA-MB-231 and transient reduction of GASP-1 in these cells decreased their proliferation. To further substantiate these results, we over and under-expressed GASP-1 in stable clones of MDA-MB-231 cells and evaluated their growth and invasive activities. Cells under-expressing GASP-1 failed to grow after 4 days in culture and eventually died. In contrast GASP-1 expressing cells grew exponentially. Similarly, GASP-1 under-expressing cells formed 30% fewer colonies in soft agar as compared to controls and whereas GASP-1 over-expressing cells formed 2-fold more colonies than controls. In tumor cell invasion assays GASP-1 over-expressing cells were over 10-fold more invasive than controls whereas GASP-1 under-expressing cells were over 10-fold less invasive than controls. In IHC staining studies of breast cancer cells, we found that the overexpressed GASP-1 appear in granules of different sizes that are directly correlated with cancer invasiveness. Our results strongly indicate that GASP-1 promotes proliferation and invasion of the triple negative breast cancer cell line MDA-MB-231 and targeting GASP-1 for treatment of breast cancer is indicated.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular , Neoplasias de la Mama Triple Negativas , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Invasividad Neoplásica , Neoplasias de la Mama Triple Negativas/patología
16.
Front Oncol ; 12: 1026268, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36686766

RESUMEN

Background: Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. As clinical trials involving PC are increasingly being conducted, the transparency of the generated data has become an important issue of concern. In other areas of medicine, clinical trial transparency presents a worrying state of affairs. However, at present, there has been no study examining the transparency of data derived from PC clinical trials. Methods: A comprehensive search was conducted in the ClinicalTrial.gov database for clinical trials investigating pancreatic cancer as of June 2022. We examined the availability of clinical trial results and recorded the characteristics of the trials. Results: A total of 856 trials were included in this study, of which 668 were completed and 188 were terminated or suspended. The results of 626 trials (73.13%) were available, of these 230 trials (26.87%) did not disclose any information on the trial data in any form. The publication rate for trials with available results was 86.10%, but the report rate on ClinicalTrial.gov was only 39.78%. Conclusion: Although approximately 90% of clinical trial investigating interventions on patients with PC have published study results, 30% of trials did not report any findings, and the disclosure of trial results from ClinicalTrial.gov was unsatisfactory. In general, there is still room for improvement in the transparency of PC clinical trials.

17.
Kidney360 ; 3(12): 2059-2076, 2022 12 29.
Artículo en Inglés | MEDLINE | ID: mdl-36591362

RESUMEN

Background: Diabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored. Methods: Using hydrodynamic tail-vein injection, we overexpress Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli. Results: In DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that overexpression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury, independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease-promoting and interferon (IFN)-related genes, including Ackr2 and Cxcl11. Conclusions: We demonstrate that, in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select IFN signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.


Asunto(s)
Albuminuria , Diabetes Mellitus Experimental , Nefropatías Diabéticas , Células Endoteliales , Inflamación , Animales , Ratones , Albuminuria/inmunología , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/inmunología , Susceptibilidad a Enfermedades/metabolismo , Células Endoteliales/metabolismo , Inflamación/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Factores de Transcripción/metabolismo
18.
Biomed Res Int ; 2021: 3187388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34901268

RESUMEN

The occult pulmonary infection is the most common complications in elderly patients with type 2 diabetes mellitus (T2DM). Since its etiological characteristics has not been clarified, infection control remains a serious problem for public health. To investigate the prevalence and clinical significance of occult pulmonary infection in elderly T2DM patients, in this study, 573 elderly patients cochallenged with T2DM and community-acquired pulmonary infection from January 2018 to December 2020 were selected in the hospitals and divided into occult pneumonia group (OP, n = 249) and nonoccult pneumonia group (NOP, n = 324) according to the nature of infection. Clinical medical records were analyzed retrospectively to summarize the infection characteristics of elderly diabetics with occult pneumonia. The prevalence of the cases (278/324, 85.8%) in NOP group was not higher than that in OP group (206/249, 82.7%; P > 0.05). Also, there was not significant difference in the distribution of isolated pathogens among the positive patients. The length of hospitalization and mortality of OP patients were significantly higher than those NOP patients. Multivariate logistic regression showed that advanced age, comorbidities, hypothyroidism, senile dementia, and prolonged bed rest were independent risk factors for occult pneumonia in elderly diabetic patients. Therefore, the results demonstrated that the pulmonary infection in elderly patients with diabetes mellitus is often occult. Gram-negative bacteria are the predominant pathogens and cause poor prognosis. Advanced age, comorbidities (senile dementia, hypothyroidism), and prolonged bed rest are the independent risk factors for occult pneumonia.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Infecciones/epidemiología , Enfermedades Pulmonares/epidemiología , Anciano , Enfermedad de Alzheimer/epidemiología , Infecciones Comunitarias Adquiridas/epidemiología , Comorbilidad , Diabetes Mellitus Tipo 2/microbiología , Femenino , Bacterias Gramnegativas/patogenicidad , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Hospitalización , Humanos , Infecciones/microbiología , Modelos Logísticos , Enfermedades Pulmonares/microbiología , Masculino , Neumonía/epidemiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo
19.
Appl Opt ; 60(2): 417-426, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33448967

RESUMEN

This paper presents an integrated flexure mount (IFM) to unload the lateral gravity of a lightweight mirror. The significance of the position relationship between the plane of mirror centroid and the center of flexure pivot is analyzed using the coupling kinematic stiffness model of the flexure mounts derived in this paper. Based on the analysis, an IFM with S-type flexure hinges was designed, and the structure and assembly are described. Then, the optimal position and size parameters of an S-type flexure hinge were obtained by optimization. The optimization results attained by finite element analysis (FEA) indicate that the optimization objectives and constraints were satisfied. Moreover, the degradation of the mirror's optical performance caused by lateral gravity was minimized, and the effects of temperature variation and assembly tolerance were reduced. The IFMs were fabricated based on the optimization results and assembled with a mirror prototype for a pointing precision test and sine-frequency sweep test. A FEA and test results for the IFMs confirm the validity and feasibility of the flexure mounts model and structure design, and we believe the IFM meets the requirements of a lightweight mirror for space application.

20.
Front Microbiol ; 11: 1113, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32719658

RESUMEN

Excessive alcohol consumption causes liver injury-induced mortality. Here we systematically analyzed the structure of triterpenoids extracted from Antrodia cinnamomea mycelia (ACT) and investigated their protective effects against acute alcohol-induced liver injury in mice. Liquid chromatography-mass spectrometry and liquid chromatography with tandem mass spectrometry were performed to determine the structures of ACT constituents. Alcohol-induced liver injury was generated in C57BL/6 mice by oral gavage of 13 g/kg white spirit (a wine at 56% ABV). Mice were treated with either silibinin or ACT for 2 weeks. Liver injury markers and pathological signaling were then quantified with enzyme-linked immunosorbent assays, antibody array assays, and Western blots, and pathological examinations were performed using hematoxylin-eosin staining and periodic acid-Schiff staining. Triterpenoids extracted from A. cinnamomea mycelia contain 25 types of triterpenoid compounds. A 2-weeks alcohol consumption treatment caused significant weight loss, liver dyslipidemia, and elevation of alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, and alkaline phosphatase activities in the serum and/or liver. These effects were markedly reversed after 2-weeks ACT administration. Triterpenoids extracted from A. cinnamomea mycelia alleviated the organ structural changes and inflammatory infiltration of alcohol-damaged tissues. Triterpenoids extracted from A. cinnamomea mycelia inhibited proinflammatory cytokine levels and enhanced anti-inflammatory cytokine levels. Acute alcohol treatment promoted inflammation with significant correlations to hypoxia-inducible factor 1α (HIF-1α), which was reduced by ACT and was partially related to modulation of the protein kinase B (Akt)/70-kDa ribosomal protein S6 kinase phosphorylation (p70S6K) and Wnt/ß-catenin signaling pathways. In conclusion, ACT protected against acute alcohol-induced liver damage in mice mainly through its suppression of the inflammatory response, which may be related to HIF-1α signaling.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...