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1.
Heliyon ; 10(17): e36949, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39281481

RESUMEN

In this work, we prepared sulfur-zinc nanoparticles (ZnS-TGA) functionalized with thioglycolic acid by a hydrothermal method and tested their photodegradation ability by solar irradiation. ZnS-TGA were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), high-resolution transmission electron microscope (HR-TEM), UV-Vis spectrophotometer and photoluminescence spectroscopy. In the characterization of these nanoparticles, thioglycolic acid proved to be a strong capping ligand, with a specific surface area of 36.82 m2/g and an average size of 7.15 nm. To test the photocatalytic degradability of the product, methylene blue (MB) was used as a model pollutant. Various operational variables were investigated, including pH, amount of nanoparticles, dye concentration, contact time and temperature. The equilibrium adsorption tests, and the statistical physical calculations allowed the analysis of the energetic and steric variables of the adsorption of MB dye molecules on the surface of these nanoparticles. The equilibrium data were well fitted with Langmuir-Freundlich (L-F) and the adsorption kinetics with pseudo-first order. The maximum adsorption capacity of the MB dye removal process was 30.92 mg g-1 at pH 7 and 298 K, and this process was spontaneous and exothermic. The dye molecules and the surface of the nanoparticles exhibited physical interactions with adsorption energies of 23.31-25.92 kJ/mol. The photocatalytic activity of these nanoparticles resulted in a dye degradation efficiency of 91.1 % in 180 min. The photocatalytic efficiency remained almost unchanged after five consecutive degradation cycles, resulting in a methylene blue degradation of 85 %. According to these results, these environmentally friendly nanoparticles have the potential to purify industrial and urban liquids contaminated with harmful organic compounds such as dye molecules.

2.
Int J Biol Macromol ; 279(Pt 1): 134992, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39214214

RESUMEN

Herein, this work reports an efficient acephate adsorption using chitosan (CS) incorporating varying amounts of magnetite. A co-precipitation methodology was employed for the functionalization of chitosan with iron nanoparticles, using Fe2+ as the sole iron source and with a low energy requirement. The adsorbents were characterized by FTIR, XRD, VSM, and nitrogen porosimetry techniques. The CS∙Fe3O4 1:1 NPs showed the highest acephate removal percentage (74.96 %) at pH 9 and ambient temperatures. The adsorption process exhibited high dependencies on pH, adsorbent dosage, initial concentration of adsorbate, and ionic strength. Sips and pseudo-second-order kinetics models best adjusted the experimental data, suggesting that the process occurs on a heterogeneous surface. Thermodynamic evaluation showed that the adsorption was exothermic, favorable, and predominately through chemical interactions. Finally, the CS∙Fe3O4 showed no significant decrease after several cycles of adsorption/desorption, avoiding centrifugation-filtration steps.

3.
RSC Adv ; 14(32): 23058-23072, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39040707

RESUMEN

The increasing demand for eco-friendly and stable optoelectronic materials has led to interest in all-inorganic lead-free halide perovskites. This study reports the synthesis of A3Bi2I9 (A = Cs, Rb) perovskites via a solvothermal technique. The materials crystallize in hexagonal and monoclinic structures, with micrometer-sized particles. Optical investigations reveal direct band-gaps of 2.03 eV for Cs3Bi2I9 and 1.90 eV for Rb3Bi2I9. Raman spectroscopy highlights distinct vibrational modes, influenced by their structural differences. Space charge limited current (SCLC) measurements indicate varying threshold voltages and trap densities. Impedance spectroscopy and Jonscher's power law analysis reveal different polaron tunneling mechanisms in each compound. Ultrafast transient absorption spectroscopy shows the formation of self-trapped states upon photoexcitation, linked to lattice distortion and the formation of small polarons, which affect electrical conductivity.

4.
Commun Biol ; 7(1): 486, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649430

RESUMEN

The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for innovative therapies with high genetic barriers to resistance. Therefore, there is pronounced interest in identifying new pharmacological targets in the SARS-CoV-2 viral life cycle. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. In this study, we investigate the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). We show that PAV-104 inhibits >99% of infection with diverse SARS-CoV-2 variants in immortalized AECs, and in primary human AECs cultured at the air-liquid interface (ALI) to represent the lung microenvironment in vivo. Our data demonstrate that PAV-104 inhibits SARS-CoV-2 production without affecting viral entry, mRNA transcription, or protein synthesis. PAV-104 interacts with SARS-CoV-2 nucleocapsid (N) and interferes with its oligomerization, blocking particle assembly. Transcriptomic analysis reveals that PAV-104 reverses SARS-CoV-2 induction of the type-I interferon response and the maturation of nucleoprotein signaling pathway known to support coronavirus replication. Our findings suggest that PAV-104 is a promising therapeutic candidate for COVID-19 with a mechanism of action that is distinct from existing clinical management approaches.


Asunto(s)
Antivirales , Células Epiteliales , SARS-CoV-2 , Replicación Viral , Humanos , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/fisiología , Replicación Viral/efectos de los fármacos , Células Epiteliales/virología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Antivirales/farmacología , Ensamble de Virus/efectos de los fármacos , COVID-19/virología , Tratamiento Farmacológico de COVID-19
5.
Environ Sci Pollut Res Int ; 31(19): 27980-27987, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38526713

RESUMEN

The adsorption of ammonium from water was studied on an activated carbon obtained using raw oil palm shell and activated with acetic acid. The performance of this adsorbent was tested at different operating conditions including the solution pH, adsorbent dosage, and initial ammonium concentration. Kinetic and equilibrium studies were carried out, and their results were analyzed with different models. For the adsorption kinetics, the pseudo-first order equation was the best model to correlate this system. Calculated adsorption rate constants ranged from 0.071 to 0.074 g/mg min. The ammonium removal was 70-80% at pH 6-8, and it was significantly affected by electrostatic interaction forces. Ammonium removal (%) increased with the adsorbent dosage, and neutral pH condition favored the adsorption of this pollutant. The best ammonium adsorption conditions were identified with a response surface methodology model where the maximum removal was 91.49% with 2.27 g/L of adsorbent at pH 8.11 for an initial ammonium concentration of 36.90 mg/L. The application of a physical monolayer model developed by statistical physics theory indicated that the removal mechanism of ammonium was multi-ionic and involved physical interactions with adsorption energy of 29 kJ/mol. This activated carbon treated with acetic acid is promising to depollute aqueous solutions containing ammonium.


Asunto(s)
Ácido Acético , Compuestos de Amonio , Contaminantes Químicos del Agua , Adsorción , Ácido Acético/química , Compuestos de Amonio/química , Contaminantes Químicos del Agua/química , Cinética , Concentración de Iones de Hidrógeno , Arecaceae/química , Carbón Orgánico/química , Purificación del Agua/métodos
6.
bioRxiv ; 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38328062

RESUMEN

Gene therapy-based HIV cure strategies typically aim to excise the HIV provirus directly, or target host dependency factors (HDFs) that support viral persistence. Cure approaches will likely require simultaneous co-targeting of multiple sites within the HIV genome to prevent evolution of resistance, and/or co-targeting of multiple HDFs to fully render host cells refractory to HIV infection. Bulk cell-based methods do not enable inference of co-editing within individual viral or target cell genomes, and do not discriminate between monoallelic and biallelic gene disruption. Here, we describe a targeted single-cell DNA sequencing (scDNA-seq) platform characterizing the near full-length HIV genome and 50 established HDF genes, designed to evaluate anti-HIV gene therapy strategies. We implemented the platform to investigate the capacity of multiplexed CRISPR-Cas9 ribonucleoprotein complexes (Cas9-RNPs) to simultaneously 1) inactivate the HIV provirus, and 2) knockout the CCR5 and CXCR4 HDF (entry co-receptor) genes in microglia and primary monocyte-derived macrophages (MDMs). Our scDNA-seq pipeline revealed that antiviral gene editing is rarely observed at multiple loci (or both alleles of a locus) within an individual cell, and editing probabilities across sites are linked. Our results demonstrate that single-cell sequencing is critical to evaluate the true efficacy and therapeutic potential of HIV gene therapy.

7.
Cell Rep ; 42(11): 113285, 2023 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-37910505

RESUMEN

Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (HIV) infection. Here, we implement a systems approach to discover molecular signatures of HIV latently infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ T cells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells are capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation in vitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence in vivo. Our findings warrant development of HIV-cure strategies targeting the hypoxia-CD73-adenosine axis.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Adenosina/metabolismo , Linfocitos T CD4-Positivos , Activación Viral , Latencia del Virus/fisiología , Replicación Viral/fisiología
8.
Res Sq ; 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37292622

RESUMEN

The ongoing evolution of SARS-CoV-2 to evade vaccines and therapeutics underlines the need for novel therapies with high genetic barriers to resistance. The small molecule PAV-104, identified through a cell-free protein synthesis and assembly screen, was recently shown to target host protein assembly machinery in a manner specific to viral assembly. Here, we investigated the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). Our data demonstrate that PAV-104 inhibited > 99% of infection with diverse SARS-CoV-2 variants in primary and immortalized human AECs. PAV-104 suppressed SARS-CoV-2 production without affecting viral entry or protein synthesis. PAV-104 interacted with SARS-CoV-2 nucleocapsid (N) and interfered with its oligomerization, blocking particle assembly. Transcriptomic analysis revealed that PAV-104 reversed SARS-CoV-2 induction of the Type-I interferon response and the 'maturation of nucleoprotein' signaling pathway known to support coronavirus replication. Our findings suggest that PAV-104 is a promising therapeutic candidate for COVID-19.

9.
J Mol Cell Biol ; 15(4)2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37127426

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a ß-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. In this study, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including immortalized AECs and primary AECs cultured at the air-liquid interface. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2 (ACE2)-dependent manner, enhancing the binding of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs, including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.


Asunto(s)
COVID-19 , Galectinas , SARS-CoV-2 , Replicación Viral , Humanos , Enzima Convertidora de Angiotensina 2 , COVID-19/metabolismo , COVID-19/virología , Células Epiteliales/metabolismo , Células Epiteliales/virología , Galectinas/metabolismo , Inflamación/metabolismo , Inflamación/virología , SARS-CoV-2/fisiología
10.
Environ Sci Pollut Res Int ; 30(6): 15789-15796, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36173520

RESUMEN

An activated carbon (AC) deriving from sludge is used in this research for the adsorption of two water pollutants, namely Reactive Black 5 (RB5) and Green Alizarin (GA) dyes, at different temperatures. The adsorption capacities varied from 277.2 to 312.69 mg/g for GA and from 225.82 to 256.02 mg/g for RB5. Comparatively, this adsorbent presents good performances in removing these dyes from wastewater. The application of physical models to adsorption experiments is advantageous to provide new insights into the dyes' adsorption mechanism. A dedicated physical adsorption model suggests that RB5 and GA dyes are adsorbed in a monolayer. Moreover, the orientation of RB5 and GA dyes on AC resulted in an angled position, determining a multi-molecular process. In addition, both dyes are adsorbed by the occurrence of an aggregation process, forming a dimer. The impact of temperature can be also interpreted, allowing concluding that it plays a relevant role in removing these dyes. The calculation and interpretation of adsorption energies show that the dyes are removed via an endothermic process, and physical forces are involved.


Asunto(s)
Colorantes , Contaminantes Químicos del Agua , Aguas del Alcantarillado , Carbón Orgánico , Adsorción , Contaminantes Químicos del Agua/análisis , Cinética , Concentración de Iones de Hidrógeno
11.
Environ Sci Pollut Res Int ; 29(48): 72747-72763, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35610458

RESUMEN

In this study, mercaptosuccinic acid capped CdSe nanocrystals were successfully synthesized and used as photocatalyst for the effective removal of methylene blue (MB) inaqueous solution under visible light and sunlight irradiations including its analysis with statistical physics theory. Dye adsorption properties of these nanocrystals were investigated via experimental kinetics and equilibrium studies. These experimental data were modeled via the application of statistical physics theory to explain the corresponding adsorption mechanism and to characterize the steric and energetic parameters involved in the dye removal. A maximum adsorption capacity of 27.07 mg g-1 (80% of dye removal) was observed in 10 min using an initial concentration of 30 mg L-1. Statistical physics calculations indicated that the adsorption energy was lower than 40 kJ mol-1. It was also established that the dye adsorption was associated to the electrostatic interactions and hydrogen bonding where dye aggregation and multi-molecular adsorption were expected. Overall, the dye removal was a spontaneous, feasible and exothermic. It was concluded that adsorption properties of CdSe-MSA nanocrystals improved the dye photo-catalytic degradation efficiency under visible light thus achieving up to 80% degradation efficiency in 60 min. The synergic effect of adsorption and photo-catalytic degradation performance was mainly due to the surface area (136.43 m2 g-1), small size (3.7 nm), and structural defects (selenium vacancies Se, interstitial of cadmium ICd) of CdSe nanocrystals, which enhanced both the response of these nanomaterials to visible light and their photo-catalytic activity. In summary, these nanocrystals are promising materials to be used in wastewater treatment under sunlight for the removal of organic compounds like dyes.


Asunto(s)
Compuestos de Cadmio , Nanopartículas , Compuestos de Selenio , Selenio , Contaminantes Químicos del Agua , Adsorción , Cadmio , Colorantes/química , Concentración de Iones de Hidrógeno , Cinética , Azul de Metileno/química , Nanopartículas/química , Física , Agua
12.
bioRxiv ; 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35378763

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a ß-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. Here, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including primary AECs in air-liquid interface (ALI) culture. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an ACE2-dependent manner, enhancing the binding affinity of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induce the expression of key pro-inflammatory programs in AECs including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection. Importance: COVID-19 continues to have a major global health and economic impact. Identifying host molecular determinants that modulate SARS-CoV-2 infectivity and pathology is a key step in discovering novel therapeutic approaches for COVID-19. Several recent studies have revealed that plasma concentrations of the human ß-galactoside-binding protein galectin-9 (Gal-9) are highly elevated in COVID-19 patients. In this study, we investigated the impact of Gal-9 on SARS-CoV-2 pathogenesis ex vivo in airway epithelial cells (AECs), the critical initial targets of SARS-CoV-2 infection. Our findings reveal that Gal-9 potently enhances SARS-CoV-2 replication in AECs, interacting with glycans to enhance the binding between viral particles and entry receptors on the target cell surface. Moreover, we determined that Gal-9 accelerates and exacerbates several virus-induced pro-inflammatory programs in AECs that are established signature characteristics of COVID-19 disease and SARS-CoV-2-induced acute respiratory distress syndrome (ARDS). Our findings suggest that Gal-9 is a promising pharmacological target for COVID-19 therapies.

13.
IDCases ; 27: e01455, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35242561

RESUMEN

Echinococcosis is endemic in Mediterranean countries. Liver then lungs are the most affected organs. Gallbladder hydatid cyst is an exceptional localization. A 64-year-old patient was referred to our surgical outpatient department by his physician for suspicion of liver hydatid cyst based on right upper quadrant abdominal pain, associated with nausea. Physical examination showed mild tenderness of the right upper quadrant of the abdomen. A computed tomography abdominal scan showed a multivesicular cystic lesion of the segment IV measuring 9.5 × 7.5 × 13 cm with exophytic component abutting the gallbladder. The patient underwent right subcostal laparotomy. The exploration has found that the hydatid cyst is developed from the fundus of the gallbladder, without any connections or fistulas to nearby organs. A cholecystectomy was performed. Histopathological examination confirmed the diagnosis of gallbladder echinococcosis. Primary gallbladder hydatid cysts (PGHC) is an extremely rare condition, occurring in less than 0.4% of echinococcosis localizations. After literature research of case reports, only twenty-three such cases, including our case, have been reported in English literature. Due to its uncommon nature, radiologists rarely consider a PHGB as the first diagnosis. Preoperative diagnosis of hydatid cyst was possible only in 50% of cases. Therefore, a careful attention is necessary to assist in making the diagnosis preoperatively, leading to the appropriate treatment.

14.
Am J Physiol Lung Cell Mol Physiol ; 322(3): L495-L502, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35107021

RESUMEN

Cx3cr1+ monocyte-derived macrophages (moMacs) are recruited to tissues after injury and are known to have profibrotic effects, but the cell-cell interactions and specific pathways that regulate this polarization and function are incompletely understood. Here we investigate the role of moMac-derived Pdgfa in bleomycin-induced lung fibrosis in mice. Deletion of Pdgfa with Cx3cr1-CreERT2 decreased bleomycin-induced lung fibrosis. Among a panel of in vitro macrophage polarizing stimuli, robust induction of Pdgfa was noted with IL10 in both mouse and human moMacs. Likewise, analysis of single-cell data revealed high expression of the receptor IL10RA in moMacs from human fibrotic lungs. Studies with IL10-GFP mice revealed that IL10-expressing cells were increased after injury in mice and colocalized with moMacs. Notably, deletion of IL10ra with Csf1r-Cre: IL10ra fl/fl mice decreased both Pdgfa expression in moMacs and lung fibrosis. Taken together, these findings reveal a novel, IL10-dependent mechanism of macrophage polarization leading to fibroblast activation after injury.


Asunto(s)
Interleucina-10/metabolismo , Lesión Pulmonar , Fibrosis Pulmonar , Animales , Bleomicina/farmacología , Interleucina-10/genética , Pulmón/metabolismo , Lesión Pulmonar/patología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo
15.
Case Rep Dent ; 2022: 5545333, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35087691

RESUMEN

After surgical excision of tumors involving the maxilla, depending on their location and size, maxillary defects can have harmful consequences, both esthetic and functional. These effects disrupt all the functions of the manducatory system, namely breathing, swallowing, and especially phonation, thus affecting negatively the patient's psychological state. Despite the evolution of reconstructive surgical techniques and the development of microsurgery, conventional obturator prostheses are still relevant. In fact, these prostheses restore the main functions of chewing, phonation, and swallowing. They also provide the patient with a satisfactory esthetic appearance. Moreover, they have an advantage in regard to oncology, making the possibility of surveying much easier. Maxillary defects are characterized by their highly polymorphic aspect, having a great impact on the nature of prosthetic rehabilitation. The aim of this work was to present the different clinical and laboratory steps of prosthetic rehabilitation of an acquired maxillary defect following excision of a mucoepidermoid carcinoma.

16.
Cell Rep ; 35(6): 109105, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33979618

RESUMEN

Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+ human monocytes purified from peripheral blood, leading to high rates of precise gene knockout. These cells can be efficiently differentiated into monocyte-derived macrophages or dendritic cells. This process yields genetically edited cells that retain transcript and protein markers of myeloid differentiation and phagocytic function. Genetic ablation of the restriction factor SAMHD1 increased HIV-1 infection >50-fold, demonstrating the power of this system for genotype-phenotype interrogation. This fast, flexible, and scalable platform can be used for genetic studies of human myeloid cells in immune signaling, inflammation, cancer immunology, host-pathogen interactions, and beyond, and could facilitate the development of myeloid cellular therapies.


Asunto(s)
Sistemas CRISPR-Cas/genética , Genoma/genética , Células Mieloides/metabolismo , Ribonucleoproteínas/metabolismo , Animales , Humanos , Ratones
17.
FASEB J ; 34(11): 14615-14630, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32901981

RESUMEN

A critical barrier to the development of a human immunodeficiency virus (HIV) cure is the lack of a scalable animal model that enables robust evaluation of eradication approaches prior to testing in humans. We established a humanized mouse model of latent HIV infection by transplanting "J-Lat" cells, Jurkat cells harboring a latent HIV provirus encoding an enhanced green fluorescent protein (GFP) reporter, into irradiated adult NOD.Cg-Prkdcscid Il2rgtm1Wjl /SzJ (NSG) mice. J-Lat cells exhibited successful engraftment in several tissues including spleen, bone barrow, peripheral blood, and lung, in line with the diverse natural tissue tropism of HIV. Administration of tumor necrosis factor (TNF)-α, an established HIV latency reversal agent, significantly induced GFP expression in engrafted cells across tissues, reflecting viral reactivation. These data suggest that our murine latency ("µ-Lat") model enables efficient determination of how effectively viral eradication agents, including latency reversal agents, penetrate, and function in diverse anatomical sites harboring HIV in vivo.


Asunto(s)
Trasplante de Células/métodos , Modelos Animales de Enfermedad , Infecciones por VIH/virología , VIH/fisiología , Latencia del Virus , Animales , Médula Ósea/virología , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , VIH/genética , VIH/patogenicidad , Infecciones por VIH/patología , Infecciones por VIH/terapia , Humanos , Células Jurkat , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos NOD , Provirus/genética , Bazo/virología , Transfección/métodos
18.
Int Wound J ; 17(2): 449-454, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31854119

RESUMEN

Tissue adhesives have gained increasing use as a possible method of wound closure. We compared the use of 2-octyl cyanoacrylate (OCA) or subcuticular suture in incisions sutures for the closure of laparoscopic cholecystectomy port incisions. A prospective randomised controlled trial was performed. Patients were randomised to have closure of laparoscopic port sites using either OCA or sutures. Patients were reviewed at 24 hours and returned for follow-up 1 week and 1 month after postoperatively. At these times, different wound characteristics were documented: Two tools were used to measure the cosmetic result using Hollander wound evaluation scale (HWES) and the patient and observer scar assessment scale (POSAS). A total of 70 patients, 35 in each group were enrolled. The wounds were closed significantly faster in the OCA group (mean 229.16 [±43.7] seconds versus 258.82 [±51.7] seconds, P = .01). Statistically significant difference in favour of using OCA was found for dehiscence (17.1% versus none in the suture group, P = .025) after 1 week. However, no difference was found for wound dehiscence after 1 month. OCA and suture groups did not differ significantly on patient satisfaction. There were no differences in the percentage of wounds achieving optimal scores on the HWES (suture 85.7% versus OCA 74.2%, P = .169). Nerveless, wound evolution was judged to be significantly better in the OCA group using POSAS. Patients' median POSAS was 9.45 (6-11) and 11.43 (10-13) in the OCA and suture groups, respectively (P = .005), and surgeon's median POSAS was 9.42 (6-11) and 11.48 (10-13) in the OCA and suture groups, respectively (P = .006). N-butyl-cyanoacrylate tissue adhesive is an acceptable technique for the closure of laparoscopic wounds with less operative time, and cosmetic results are comparable to suturing.


Asunto(s)
Implantes Absorbibles , Colecistectomía Laparoscópica/métodos , Cianoacrilatos/farmacología , Herida Quirúrgica/cirugía , Técnicas de Sutura/instrumentación , Suturas , Cicatrización de Heridas , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Satisfacción del Paciente , Estudios Prospectivos , Adhesivos Tisulares/farmacología
19.
Nat Microbiol ; 4(7): 1196-1207, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30936483

RESUMEN

Numerous human APOBEC3 cytidine deaminases have proven to be, inter alia, host cell restriction factors for retroviruses and hepadnaviruses. Although they can bind to genomic RNA and become encapsidated, they are only catalytically active on single-stranded DNA. As there are many cellular deoxyribonucleases (DNases), we hypothesized that a parallel could be struck between APOBEC3 and DNases. For human hepatitis B virus (HBV), we show that DNase I can considerably reduce the virion genome copy number from a variety of transfected or infected cells. DNASE1 is overexpressed and encapsidated in HBV particles in vitro in hypoxic environments and in vivo in cirrhotic patient livers as well as in the serum of infected patients. The use of CoCl2 and dimethyloxalylglycine, mimetic agents used to induce hypoxia by inhibiting prolyl hydroxylase enzymes that stabilize hypoxia-inducible factor (HIF)-1α, showed that the formation of HIF-1α/HIF-1ß heterodimers results in the induction of DNASE1. Indeed, transfection with HIF-1α and HIF-1ß expression constructs upregulated DNASE1. These findings suggest that human DNase I can impact HBV replication through the catabolism of the DNA genome within the capsid. The activity of DNases in general may explain in part the high frequency of empty or 'light' hepatitis B virions observed in vivo.


Asunto(s)
Desoxirribonucleasa I/metabolismo , Virus de la Hepatitis B/fisiología , Hipoxia , Replicación Viral , Línea Celular , Cobalto/farmacología , ADN Viral/metabolismo , Desoxirribonucleasa I/genética , Expresión Génica , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hepatitis B/enzimología , Antígenos del Núcleo de la Hepatitis B/metabolismo , Humanos , Hipoxia/inducido químicamente , Factor 1 Inducible por Hipoxia/metabolismo , Cirrosis Hepática/enzimología , Mutación , Virión/metabolismo , Replicación Viral/efectos de los fármacos
20.
PLoS One ; 14(3): e0213390, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30840709

RESUMEN

The NAC family is one of the largest plant-specific transcription factor families, and some of its members are known to play major roles in plant development and response to biotic and abiotic stresses. Here, we inventoried 488 NAC members in bread wheat (Triticum aestivum). Using the recent release of the wheat genome (IWGS RefSeq v1.0), we studied duplication events focusing on genomic regions from 4B-4D-5A chromosomes as an example of the family expansion and neofunctionalization of TaNAC members. Differentially expressed TaNAC genes in organs and in response to abiotic stresses were identified using publicly available RNAseq data. Expression profiling of 23 selected candidate TaNAC genes was studied in leaf and grain from two bread wheat genotypes at two developmental stages in field drought conditions and revealed insights into their specific and/or overlapping expression patterns. This study showed that, of the 23 TaNAC genes, seven have a leaf-specific expression and five have a grain-specific expression. In addition, the grain-specific genes profiles in response to drought depend on the genotype. These genes may be considered as potential candidates for further functional validation and could present an interest for crop improvement programs in response to climate change. Globally, the present study provides new insights into evolution, divergence and functional analysis of NAC gene family in bread wheat.


Asunto(s)
Triticum/genética , Cromosomas de las Plantas/genética , Bases de Datos Genéticas , Sequías , Evolución Molecular , Duplicación de Gen , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Genoma de Planta , Respuesta al Choque Térmico/genética , Respuesta al Choque Térmico/fisiología , Familia de Multigenes , Filogenia , Proteínas de Plantas/genética , Estrés Fisiológico/genética , Estrés Fisiológico/fisiología , Factores de Transcripción/genética , Triticum/crecimiento & desarrollo , Triticum/fisiología
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