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1.
Antioxid Redox Signal ; 32(7): 429-446, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31810391

RESUMO

Aims: Carbon monoxide (CO) confers antiproliferative effects on T cells; however, how these effects are produced remains unclear. Reactive oxygen species (ROS) have recently emerged as important modulators of T cell proliferation. In this study, we aimed to determine whether the inhibitory effects of CO on T cell proliferation are dependent on the inhibition of ROS signaling. Results: Pretreatment with CO-releasing molecule-2 (CORM-2) had potent inhibitory effects on mouse T cell proliferation stimulated by anti-CD3/CD28 antibodies. Interestingly, CORM-2 pretreatment markedly suppressed intracellular ROS generation as well as the activity of NADPH oxidase and mitochondrial complexes I-IV in T cells after stimulation. The inhibitory effects of CORM-2 on both ROS production and T cell proliferation were comparable with those produced by the use of antioxidant N-acetylcysteine or a combined administration of mitochondrial complex I-IV inhibitors. Moreover, increasing intracellular ROS via hydrogen peroxide supplementation largely reversed the inhibitory effect of CORM-2 on the proliferation of T cells. The inhibitory effects of CORM-2 on both cell proliferation and intracellular ROS production were also shown in a T cell proliferation model involving stimulation by allogeneic dendritic cells or phorbol 12-myristate 13-actetate/ionomycin, as well as in spontaneous cell proliferation models in EL-4 and RAW264.7 cells. In addition, CORM-2 treatment significantly inhibited T cell activation in vivo and attenuated concanavalin A-induced autoimmune hepatitis. Innovation: CO inhibits T cell proliferation via suppression of intracellular ROS production. Conclusion: The study could supply a general mechanism to explain the inhibitory effects of CO on T cell activation and proliferation, favoring its future application in T cell-mediated diseases.

2.
Phytopathology ; 110(1): 187-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31516080

RESUMO

Potyviral helper component protease (HC-Pro), as a major determinant of symptom expression in susceptible plants, is a likely target candidate in the production of attenuated strains for cross-protection. In this study, single or double mutations of Lys (K) to Glu (E) in the Lys-Ile-Thr-Cys motif and Arg (R) to Ile (I) in the Phe-Arg-Asn-Lys motif of the HC-Pro from the severe papaya leaf distortion mosaic virus strain DF (PLDMV-DF) reduced symptom expression and virus accumulation in infected papaya (Carica papaya) plants. The papaya plants infected with the attenuated double mutant of PLDMV-EI presented as symptomless. PLDMV-EI provided effective protection against PLDMV-DF infection in three papaya cultivars and had no effect on plant growth and development. Our result showed that PLDMV-EI is a promising mild strain for the practical use of cross-protection in the field.


Assuntos
Motivos de Aminoácidos , Carica , Peptídeo Hidrolases , Potyvirus , Motivos de Aminoácidos/genética , Carica/virologia , Mutação/genética , Peptídeo Hidrolases/genética , Potyvirus/enzimologia , Potyvirus/genética
3.
J Virol Methods ; : 113795, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31809783

RESUMO

Two reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assays were developed for the detection of areca palm necrotic ringspot virus (ANRSV) and areca palm necrotic spindle-spot virus (ANSSV), respectively. These two emerging viruses both induce necrotic symptoms in areca palms. The coat protein (CP) gene of ANRSV and the 9 K gene of ANSSV were used to design the respective RT-LAMP primers for the assays. Each set of four primers designed for each of these viruses was found to be highly specific in the detection of the respective targeted virus. The optimal incubation conditions for the RT-LAMP assays were 63 °C for 40 min for ANRSV and at 61 °C for 40 min for ANSSV. The sensitivity of the RT-LAMP method for each of these viruses was 10-fold greater than that of the corresponding conventional reverse-transcription polymerase chain reaction (RT-PCR). The RT-LAMP assays may be useful for the rapid early detection of ANSSV and ANRSV in commercial areca palm production.

4.
Cancers (Basel) ; 11(12)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769430

RESUMO

This review highlights recent advances in the understanding of the relevance of altered lipid metabolic pathways contributing to the poor prognosis of high grade serous ovarian cancer, as they relate to cancer metastasis and cancer stemness. Increased lipid uptake regulated by the receptor CD36 and the transport protein FABP4 has been implicated in ovarian cancer metastasis. The symbiotic relationship between ovarian cancer cells and adipocytes was shown to be important for sustaining widespread peritoneal and omental metastasis. Increased lipogenesis dependent on the fatty acid desaturase SCD1 was detected in ovarian cancer stem cells. Furthermore, response to therapy, specifically to platinum, was linked to increased fatty acid biogenesis, while the survival of drug tolerant cells was shown to depend on lipid peroxidation. These recent findings suggest that lipids are necessary elements supporting oncogenic signaling and the energetic needs of rapidly proliferating cancer cells. New strategies targeting key enzymes involved in lipid uptake or utilization in cancer cells have been shown to exert anti-tumor effects and are being developed as cancer interventions in combination with chemotherapy or immunotherapy.

5.
Transplantation ; 103(3): 502-511, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30211824

RESUMO

BACKGROUND: Advances in immunosuppressive therapy have significantly improved short-term but not long-term survival of cardiac transplant recipients; this is largely due to severe cardiac allograft vasculopathy (CAV). Glucagon-like peptide-1 receptor (GLP-1R)-based therapy exerts physiological effects on the cardiovascular system in addition to its traditional role in controlling glucose. We have investigated the effects of liraglutide, a GLP-1R agonist, on the development of CAV in a murine heart transplant model. METHODS: Heterotopic murine cardiac transplantation was performed with a major histocompatibility complex class II-mismatched model. Recipient mice were subcutaneously administered vehicle (0.9% saline solution) or liraglutide (300 µg·kg every 12 hours) from the day of transplantation. Allografts were harvested at 2 or 8 weeks and histologically analyzed. Inflammatory infiltrates were measured by immunohistochemistry, and immunofluorescence and western blotting analyzes were used to evaluate GLP-1R expression and markers of endothelial-to-mesenchymal transition (EndMT) in cardiac allografts and human coronary artery endothelial cells challenged with transforming growth factor-beta 1. RESULTS: Glucagon-like peptide-1 receptor was predominantly localized to vascular endothelial cells and was upregulated in cardiac allografts after liraglutide treatment. Liraglutide ameliorated CAV and cardiac fibrosis with reduced inflammatory cell infiltration and downregulated expression of adhesion molecules. Liraglutide inhibited EndMT in allografts and attenuated EndMT by inhibiting Smad3 activation in transforming growth factor-beta 1-treated human coronary artery endothelial cells. CONCLUSIONS: Administration of liraglutide from the time of transplantation upregulated GLP-1R in the transplanted heart and reduced cardiac fibrosis, inflammation, and CAV development. Therefore, liraglutide may be a novel therapy for CAV.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Liraglutida/farmacologia , Doenças Vasculares/tratamento farmacológico , Animais , Vasos Coronários/patologia , Modelos Animais de Doenças , Células Endoteliais/citologia , Fibrose , Glucose/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Imuno-Histoquímica , Imunossupressão , Imunossupressores/uso terapêutico , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Smad3/metabolismo
6.
Virus Genes ; 54(6): 833-839, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30218292

RESUMO

We used green fluorescent protein (GFP)-tagged Papaya leaf distortion mosaic virus (PLDMV-GFP) to track PLDMV infection by fluorescence. The virus-derived small interfering RNAs (vsiRNAs) of PLDMV-GFP were characterized from papaya plants by next-generation sequencing. The foreign GFP gene inserted into the PLDMV genome was also processed as a viral gene into siRNAs by components involved in RNA silencing. The siRNAs derived from PLDMV-GFP accumulated preferentially as 21- and 22-nucleotide (nt) lengths, and most of the 5'-terminal ends were biased towards uridine (U) and adenosine (A). The single-nucleotide resolution map revealed that vsiRNAs were heterogeneously distributed throughout the PLDMV-GFP genome, and vsiRNAs derived from the sense strand were more abundant than those from the antisense strand. The hotspots were mainly distributed in the P1 and GFP coding region of the antisense strand. In addition, 979 papaya genes targeted by the most abundant 1000 PLDMV-GFP vsiRNAs were predicted and annotated using GO and KEGG classification. Results suggest that vsiRNAs play key roles in PLDMV-papaya interactions. These data on the characterization of PLDMV-GFP vsiRNAs will help to provide insight into the function of vsiRNAs and their host target regulation patterns.


Assuntos
Carica/virologia , Potyvirus/isolamento & purificação , RNA Interferente Pequeno/genética , RNA Viral/genética , Carica/genética , Carica/crescimento & desenvolvimento , Genoma Viral/genética , Proteínas de Fluorescência Verde/genética , Sequenciamento de Nucleotídeos em Larga Escala , Doenças das Plantas/genética , Doenças das Plantas/virologia , Potyvirus/genética , Potyvirus/patogenicidade , Interferência de RNA
7.
Front Immunol ; 9: 1515, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30013566

RESUMO

Heme oxygenase-1 (HO-1) is critical for the ability of immature dendritic cells (imDCs) to suppress T-cell responses. Induction of high HO-1 expression may markedly improve the tolerogenic capacity of imDCs. Here, we generated bone marrow-derived DCs (BMDCs) from BALB/c mice with low doses of GM-CSF and IL-4. The adherent BMDCs were obtained as imDCs. Upregulation of HO-1 in imDCs (HO-1hi-imDCs) was achieved by cobalt protoporphyrin treatment. HO-1hi-imDCs proved to be more maturation-resistant than conventional imDCs, with an enhanced ability to inhibit allogeneic T-cell proliferation stimulated by anti-CD3/CD28 antibodies. When donor-derived DC adoptive transfer was performed in a stringent mouse cardiac allotransplant model, the extent of graft prolongation observed with HO-1hi imDCs was superior to that obtained with conventional imDCs. T-cell activation and proliferation in cardiac allograft recipients was more strongly suppressed in the HO-1hi imDC transfusion group than that in the untreated imDC group. Furthermore, donor HO-1hi imDCs were able to maintain a status of high HO-1 expression and survived longer in the recipient spleens than did untreated imDCs after adoptive transfer. In vitro-generated HO-1hi imDCs had an enhanced tolerogenic capacity to modulate alloimmune responses both in vitro and in vivo, and thus may offer a novel antigen-specific and cost-effective strategy to induce transplant tolerance.

8.
Phys Rev Lett ; 120(19): 193901, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29799223

RESUMO

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ∼60 nm (∼λ/10). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

9.
Opt Lett ; 43(7): 1423-1426, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29600995

RESUMO

Measuring three-dimensional nanoscale cellular structures is challenging, especially when the structure is dynamic. Owing to the informative total internal reflection fluorescence (TIRF) imaging under varied illumination angles, multi-angle (MA) TIRF has been examined to offer a nanoscale axial and a subsecond temporal resolution. However, conventional MA-TIRF still performs badly in lateral resolution and fails to characterize the depth image in densely distributed regions. Here, we emphasize the lateral super-resolution in the MA-TIRF, exampled by simply introducing polarization modulation into the illumination procedure. Equipped with a sparsity and accelerated proximal algorithm, we examine a more precise 3D sample structure compared with previous methods, enabling live cell imaging with a temporal resolution of 2 s and recovering high-resolution mitochondria fission and fusion processes. We also shared the recovery program, which is the first open-source recovery code for MA-TIRF, to the best of our knowledge.


Assuntos
Polarização de Fluorescência/métodos , Imagem Tridimensional/métodos , Microscopia de Fluorescência/métodos , Microtúbulos/ultraestrutura , Tubulina (Proteína)/análise , Animais , Células Vero
10.
Opt Lett ; 42(19): 3734-3737, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957131

RESUMO

We report a new approach to achieving super-resolution in point-scanning microscopy through polarization modulation for the first time, to the best of our knowledge. By modulating linearly polarized incident light, the emission extent of fluorescent dyes changes periodically, adding sparsity in each recording, which contributes to the super-resolution reconstruction. To recover the super-resolution result, a sparse penalty-based deconvolution method is implemented onto the polarization-modulated dataset subsequently. By simply inserting a vortex half-wave retarder into a typical confocal microscope, we obtain the super-resolution experimental results of both nuclear pore complex proteins and tubulins in vero cells, which evidence a sub-diffraction resolution of λ/5. In addition, three-dimensional (3D) super-resolution on spatial distributed single molecules is simulated, where the significant resolution improvement in both lateral and axial directions further confirms its capacity in 3D imaging applications. Considering no constraint on fluorescence dyes and easy implementation in a point-scanning microscope, we envision that the polarization-modulated confocal microscope would be a helpful alternative in biological imaging.

11.
Opt Lett ; 42(19): 3956-3959, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957171

RESUMO

By analyzing the statistics of the temporal fluctuations from the blinking emitters, super-resolution fluctuation imaging (SOFI) achieves super-resolution while imposing fewer constraints on the blinking behavior of the probes and is more suitable for low signal-to-noise ratio acquisition than localization methods. However, determined by the square root of cumulation orders, the resolution improvement of SOFI highly restricts its promotion into high-resolution observations. In this Letter, abandoning the default flat illumination in stochastic imaging methods, we introduce structured illumination (SI) (e.g., Gaussian or sinusoidal pattern) into SOFI (SI-SOFI) to render greatly enhanced resolution. Through simulation with parameters of both real acquisition procedures and microscope properties, we examine the feasibility of SI-SOFI and obtain a resolution improvement of four-six folds at just second-order cumulation compared to wide-field imaging. In addition, a practical pathway for the SI-SOFI reconstruction is offered.

12.
Proc Natl Acad Sci U S A ; 114(33): E6932-E6941, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28760985

RESUMO

Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by controlling actin nucleation and microtubule (MT) stabilization to facilitate processes such as cell polarization and migration; yet the full extent of their activities remains unknown. Here, we uncover two discrete roles and functions of DRFs during early human immunodeficiency virus type 1 (HIV-1) infection. Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1-induced MT stabilization and the intracellular motility of virus particles. However, DRFs also bound in vitro assembled capsid-nucleocapsid complexes and promoted the disassembly of HIV-1 capsid (CA) shell. This process, also known as "uncoating," is among the most poorly understood stages in the viral lifecycle. Domain analysis and structure modeling revealed that regions of Dia2 that bound viral CA and mediated uncoating as well as early infection contained coiled-coil domains, and that these activities were genetically separable from effects on MT stabilization. Our findings reveal that HIV-1 exploits discrete functions of DRFs to coordinate critical steps in early infection and identifies Dia family members as regulators of the poorly understood process of HIV-1 uncoating.


Assuntos
Proteínas de Transporte/metabolismo , HIV-1/metabolismo , Desenvelopamento do Vírus , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transporte Biológico , Capsídeo/metabolismo , Proteínas de Transporte/genética , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , HIV-1/fisiologia , Humanos , Células Jurkat , Microscopia Confocal , Microtúbulos/metabolismo , Imagem com Lapso de Tempo/métodos
13.
Opt Lett ; 42(7): 1448-1451, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28362789

RESUMO

We propose a novel common-path quantitative phase imaging (QPI) method based on a digital micromirror device (DMD). The DMD is placed in a plane conjugate to the objective back-aperture plane for the purpose of generating two plane waves that illuminate the sample. A pinhole is used in the detection arm to filter one of the beams after sample to create a reference beam. Additionally, a transmission-type liquid crystal device, placed at the objective back-aperture plane, eliminates the specular reflection noise arising from all the "off" state DMD micromirrors, which is common in all DMD-based illuminations. We have demonstrated high sensitivity QPI, which has a measured spatial and temporal noise of 4.92 nm and 2.16 nm, respectively. Experiments with calibrated polystyrene beads illustrate the desired phase measurement accuracy. In addition, we have measured the dynamic height maps of red blood cell membrane fluctuations, showing the efficacy of the proposed system for live cell imaging. Most importantly, the DMD grants the system convenience in varying the interference fringe period on the camera to easily satisfy the pixel sampling conditions. This feature also alleviates the pinhole alignment complexity. We envision that the proposed DMD-based common-path QPI system will allow for system miniaturization and automation for a broader adaption.

14.
Sci Rep ; 7: 46272, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28382970

RESUMO

Hepatocyte-specific HMGB1 deletion has been found to worsen the injury and inflammation in liver ischemia-reperfusion injury (IRI), highlighting a role for intracellular HMGB1 in cellular protection. Down-regulation of nuclear HMGB1 by small interfering RNA (siRNA) might not only decrease its injurious extracellular role by reducing its release but also serve to maintain its beneficial intracellular role, thus protecting against IRI. We established a non-lethal liver IRI model in mice via segmental hepatic warm ischemia for 1 h and reperfusion for 6 h. HMGB1-siRNA achieved a reduction of ~60-70% in the nuclear HMGB1 expression in the liver at 48 h post-treatment. Knockdown of nuclear HMGB1 expression dramatically reduced both the degree of nuclear-cytoplasmic translocation of HMGB1 during hepatic ischemia and of HMGB1 release after hepatic reperfusion, resulting in significant preservation of liver function and a marked reduction in pathological damage. Also, HMGB1-siRNA pretreatment markedly inhibited the increases in hepatic expression of TLR4, TLR2, RAGE, TNF-α, IL-1ß, IL-6, MCP-1, iNOS, and COX-2 seen in control mice after hepatic reperfusion. We demonstrated for the first time that down-regulation of nuclear HMGB1 reduces ischemia-induced HMGB1 release and protects against liver IRI, which is helpful for better understanding the role of HMGB1 in organ IRI.


Assuntos
Regulação da Expressão Gênica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Fígado/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Animais , Apoptose/genética , Núcleo Celular/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Inativação Gênica , Hepatócitos/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/patologia , Testes de Função Hepática , Masculino , Camundongos , Camundongos Transgênicos , Transporte Proteico , RNA Interferente Pequeno/genética , Traumatismo por Reperfusão/patologia
16.
J Huazhong Univ Sci Technolog Med Sci ; 36(6): 791-795, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27924516

RESUMO

Carbon monoxide (CO), as a vital small molecule in signaling pathways, is found to be involved in ischemia-reperfusion injury (IRI) in renal transplantation. CO-releasing molecule-2 (CORM-2), a CO-releasing molecule, is a type of metal carbonyl complexes which can quickly release CO in vivo. In this study, an in vitro oxidative stress injury model was established to examine the effect of CORM-2 pretreatment on the nuclear-cytoplasmic translocation of high mobility group box 1 protein (HMGB1) in mouse primary renal proximal tubular epithelial cells (RPTECs). Immunofluorescence staining showed that HMGB1 in the medium- and CORM-2-treated groups was predominantly localized in the nucleus of the cells, whereas higher amounts of HMGB1 translocated to the cytoplasm in the H2O2- and inactive CORM-2 (iCORM-2)-treated groups. Western blotting of HMGB1 showed that the total amounts of cytoplasmic HMGB1 in the H2O2-treated (0.59±0.27) and iCORM-2-treated (0.57±0.22) groups were markedly higher than those in the medium-treated (0.19±0.05) and CORM-2-treated (0.21±0.10) groups (P<0.05). Co-immunoprecipitation showed that the levels of acetylated HMGB1 in the H2O2-treated (642.98±57.25) and iCORM-2-treated (342.11±131.25) groups were markedly increased as compared with the medium-treated (78.72±74.17) and CORM-2-treated (71.42±53.35) groups (P<0.05), and no significant difference was observed between the medium-treated and CORM-2-treated groups (P>0.05). In conclusion, our study demonstrated that in the in vitro oxidative stress injury model of primary RPTECs, CORM-2 can significantly inhibit the nuclear-cytoplasmic translocation of HMGB1, which is probably associated with the prevention of HMGB1 acetylation.


Assuntos
Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Monóxido de Carbono/farmacologia , Células Epiteliais/metabolismo , Proteína HMGB1/metabolismo , Túbulos Renais/citologia , Estresse Oxidativo , Animais , Núcleo Celular/metabolismo , Células Cultivadas , Células Epiteliais/efeitos dos fármacos , Camundongos , Compostos Organometálicos/farmacologia
17.
Opt Express ; 24(20): 23596-23609, 2016 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-27828421

RESUMO

Fluorescence emission difference microscopy (FED) obtains resolution-enhanced images by subtracting acquired solid and doughnut confocal images. Because of the mismatch of the outer contours of the two subtraction components, negative values are inevitable in the conventional FED method, giving rise to deformations. In this study, by using a saturation effect, we obtain imaging results with a profile-extended solid and center-shrunken doughnut point spread function. Owing to the nonlinear effect, two better-matched saturated images not only eliminate the deformations, but also enhance the resolving ability and signal to noise ratio compared to conventional FED. Simulations based on the saturated model of rhodamine 6G, as well as experiments on biological samples, are presented to verify the capability of the proposed concept, while experimental results show the unprecedented resolving ability of the saturated FED method.

18.
J Huazhong Univ Sci Technolog Med Sci ; 36(5): 634-638, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27752902

RESUMO

Tumor necrosis factor-alpha (TNF-α) has been found to be centrally involved in the development of ischemia-reperfusion injury (IRI)-induced inflammation and apoptosis. Knockdown of TNF-α gene using small interfering RNA (siRNA) may protect renal IRI. Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min. TNF-α siRNA was administered intravenously to silence the expression of TNF-α. The therapeutic effects of siRNA were evaluated in terms of renal function, histological examination, and overall survival following lethal IRI. A single systemic injection of TNF-α siRNA resulted in significant knockdown of TNF-α expression in ischemia-reperfusion injured kidney. In comparison with control mice, levels of BUN and serum creatinine were significantly reduced in mice treated with siRNA. Pathological examination demonstrated that tissue damage caused by IRI was markedly reduced as a result of TNF-α siRNA treatment. Furthermore, survival experiments showed that nearly 90% of control mice died from lethal IRI, whereas more than 50% of siRNApretreated mice survived until the end of the eight-day observation period. We have demonstrated for the first time that silencing TNF-α by specific siRNA can significantly reduce renal IRI and protect mice against lethal kidney ischemia, highlighting the potential for siRNA-based clinical therapy.


Assuntos
Inflamação/genética , RNA Interferente Pequeno/administração & dosagem , Traumatismo por Reperfusão/genética , Fator de Necrose Tumoral alfa/genética , Animais , Apoptose , Modelos Animais de Doenças , Terapia Genética , Humanos , Inflamação/patologia , Inflamação/terapia , Rim/efeitos dos fármacos , Rim/lesões , Rim/patologia , Camundongos , RNA Interferente Pequeno/genética , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
19.
Theriogenology ; 86(7): 1631-6, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27423729

RESUMO

In the modern biological area, the applications of pig as a laboratory model have extensive prospects, such as gene transfer, IVF, SCNT, and xenotransplantation. However, the risk of pathogen transmission by porcine embryos is always a topic to be investigated, especially the viruses related to reproductive failure, for instance, pseudorabies virus, porcine reproductive and respiratory syndrome virus, porcine parvovirus, and porcine circovirus type 2. It should be mentioned that the zona pellucida (ZP) of porcine embryos can be a barrier against the viruses, but certain pathogens may stick to or even pass through the ZP. With intact, free, and damaged ZP, porcine preimplantation embryos are susceptible to these viruses in varying degrees, which may be associated with the virus-specific receptor on embryonic cell membrane. These topics are discussed in the present review.


Assuntos
Blastocisto/virologia , Embrião de Mamíferos/virologia , Suínos/embriologia , Vírus/classificação , Animais , Zona Pelúcida/fisiologia
20.
Genome Announc ; 3(5)2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26358610

RESUMO

The complete genome sequence (10,326 nucleotides) of a papaya ringspot virus isolate infecting genetically modified papaya in Hainan Island of China was determined through reverse transcription (RT)-PCR. The virus shares 92% nucleotide sequence identity with the isolate that is unable to infect PRSV-resistant transgenic papaya.

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