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1.
Mol Biol Evol ; 39(10)2022 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-36063436

RESUMEN

As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral-host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive in silico screening of a large data set of available mammalian genomes for EVEs deriving from members of the viral family Flaviviridae, an important group of viruses including well-known human pathogens, such as Zika, dengue, or hepatitis C viruses. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (Crocidura indochinensis). Homologs of these novel EVEs were subsequently detected in vivo by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily on different continents. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and Flaviviridae in general. Moreover, we provide the first description of Flaviviridae-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known Pestivirus host range and provide novel insight into the ancient evolutionary history of pestiviruses and the Flaviviridae family in general.


Asunto(s)
Pestivirus , Virus , Infección por el Virus Zika , Virus Zika , Animales , Evolución Molecular , Genoma Viral , Humanos , Pestivirus/genética , Filogenia , Musarañas/genética , Virus/genética , Virus Zika/genética
2.
J Virol ; 96(17): e0043922, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-35975997

RESUMEN

Flaviviruses are positive-sense single-stranded RNA viruses, including some well-known human pathogens such as Zika, dengue, and yellow fever viruses, which are primarily associated with mosquito and tick vectors. The vast majority of flavivirus research has focused on terrestrial environments; however, recent findings indicate that a range of flaviviruses are also present in aquatic environments, both marine and freshwater. These flaviviruses are found in various hosts, including fish, crustaceans, molluscs, and echinoderms. Although the effects of aquatic flaviviruses on the hosts they infect are not all known, some have been detected in farmed species and may have detrimental effects on the aquaculture industry. Exploration of the evolutionary history through the discovery of the Wenzhou shark flavivirus in both a shark and crab host is of particular interest since the potential dual-host nature of this virus may indicate that the invertebrate-vertebrate relationship seen in other flaviviruses may have a more profound evolutionary root than previously expected. Potential endogenous viral elements and the range of novel aquatic flaviviruses discovered thus shed light on virus origins and evolutionary history and may indicate that, like terrestrial life, the origins of flaviviruses may lie in aquatic environments.


Asunto(s)
Organismos Acuáticos , Infecciones por Flavivirus , Flavivirus , Animales , Acuicultura , Organismos Acuáticos/aislamiento & purificación , Organismos Acuáticos/virología , Evolución Biológica , Peces/virología , Flavivirus/aislamiento & purificación , Infecciones por Flavivirus/virología , Humanos
3.
Lipids Health Dis ; 21(1): 109, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36303150

RESUMEN

BACKGROUND: Hepatic caveolin-1 (CAV1) is reduced in cholesterol gallstone disease (CGD). Mice with CAV1 deficiency were prone to develop CGD. However, it remains unknown whether restored hepatic CAV1 expression prevents the development of CGD. METHODS: C57BL/6 mice were injected with adeno-associated virus 2/8 (AAV2/8) vectors carrying the CAV1 gene (AAV2/8CAV1) via intravenous (i.v.) or intraperitoneal (i.p.) route and then subjected to a lithogenic diet (LD) for 8 weeks. Uninjected mice were used as controls. The functional consequences of rescuing CAV1 expression by either i.v. or i.p. AAV2/8CAV1 treatment for CGD prevention and its subsequent molecular mechanisms were examined. RESULTS: CAV1 expression was reduced in the liver and gallbladder of LD-fed CGD mice. We discovered that AAV2/8CAV1 i.p. delivery results in higher transduction efficiency in the gallbladder than tail vein administration. Although either i.v. or i.p. injection of AAV2/8CAV1 improved liver lipid metabolic abnormalities in CGD mice but did not affect LD feeding-induced bile cholesterol supersaturation. In comparison with i.v. administration route, i.p. administration of AAV2/8CAV1 obviously increased CAV1 protein levels in the gallbladder of LD-fed mice, and i.p. delivery of AAV2/8CAV1 partially improved gallbladder cholecystokinin receptor (CCKAR) responsiveness and impeded bile cholesterol nucleation via the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling, which induced a reduction in gallbladder mucin-1 (MUC1) and MUC5ac expression and gallbladder cholesterol accumulation. CONCLUSION: CGD prevention by i.p. AAV2/8CAV1 injection in LD-fed mice was associated with the improvement of gallbladder stasis, which again supported the notion that supersaturated bile is required but not sufficient for the formation of cholesterol gallstones. Additionally, AAV treatment via the local i.p. injection offers particular advantages over the systemic i.v. route for much more effective gallbladder gene delivery, which will be an excellent tool for conducting preclinical functional studies on the maintenance of normal gallbladder function to prevent CGD.


Asunto(s)
Caveolina 1 , Cálculos Biliares , Animales , Ratones , Caveolina 1/genética , Caveolina 1/metabolismo , Colesterol/metabolismo , Colesterol en la Dieta , Dependovirus/genética , Dependovirus/metabolismo , Vesícula Biliar/metabolismo , Cálculos Biliares/genética , Cálculos Biliares/prevención & control , Hígado/metabolismo , Ratones Endogámicos C57BL
4.
Lipids Health Dis ; 21(1): 97, 2022 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-36209166

RESUMEN

BACKGROUND: Cholesterol gallstone disease (CGD) is accompanied by biliary cholesterol supersaturation. Hepatic Niemann-Pick C1-like 1 (NPC1L1), which is present in humans but not in wild-type (WT) mice, promotes hepatocyte cholesterol uptake and decreases biliary cholesterol supersaturation. In contrast, intestinal NPC1L1 promotes intestinal cholesterol absorption, increasing biliary cholesterol supersaturation. Ezetimibe (EZE) can inhibit both hepatic and intestinal NPC1L1. However, whether hepatic NPC1L1 can affect CGD progress remains unknown. METHODS: Mice expressing hepatic NPC1L1 (NPC1L1hepatic-OE mice) were generated using Adeno-associated viruses (AAV) gene delivery. The protein level and function of hepatic NPC1L1 were examined under chow diet, high fat-cholesterol diet (HFCD), and lithogenic diet (LD) feeding. Gallstone formation rates were examined with or without EZE treatment. Fibroblast growth factor 15 (FGF15) treatment and inhibition of fibroblast growth factor receptor 4 (FGFR4) were applied to verify the mechanism of hepatic NPC1L1 degradation. RESULTS: The HFCD-fed NPC1L1hepatic-OE mice retained the biliary cholesterol desaturation function of hepatic NPC1L1, whereas EZE treatment decreased biliary cholesterol saturation and did not cause CGD. The ubiquitination and degradation of hepatic NPC1L1 were discovered in LD-fed NPC1L1hepatic-OE mice. Treatment of FGF15 during HFCD feeding and inhibition of FGFR4 during LD feeding could affect the protein level and function of hepatic NPC1L1. CONCLUSIONS: LD induces the ubiquitination and degradation of hepatic NPC1L1 via the FGF15-FGFR4 pathway. EZE may act as an effective preventative agent for CGD.


Asunto(s)
Proteínas de Transporte de Membrana , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos , Animales , Colesterol/metabolismo , Dieta Alta en Grasa , Ezetimiba/farmacología , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/metabolismo , Humanos , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Ratones , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo
5.
Entropy (Basel) ; 24(9)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36141100

RESUMEN

Scholars usually ignore the non-equilibrium condensing effects in turbulence-model comparative studies on supersonic steam ejectors. In this study, a non-equilibrium condensation model considering real physical properties was coupled respectively with seven turbulence models. They are the k-ε Standard, k-ε RNG, k-ε Realizable, k-ω Standard, k-ω SST, Transition SST, and Linear Reynolds Stress Model. Simulation results were compared with the experiment results globally and locally. The complex flow phenomena in the steam ejector captured by different models, including shock waves, choking, non-equilibrium condensation, boundary layer separation, and vortices were discussed. The reasons for the differences in simulation results were explained and compared. The relationship between ejector performance and local flow phenomena was illustrated. The novelty lies in the conclusions that consider the non-equilibrium condensing effects. Results show that the number and type of shock waves predicted by different turbulence models are different. Non-equilibrium condensation and boundary layer separation regions obtained by various turbulence models are different. Comparing the ejector performance and the complex flow phenomena with the experimental results, the k-ω SST model is proposed to simulate supersonic steam ejectors.

6.
J Cell Biochem ; 117(9): 2118-27, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26875794

RESUMEN

Cholesterol gallstone disease (CGD) is a hepatobiliary disorder which results from a biochemical imbalance in the gallbladder bile. Here we show that loss of CAV1 sensitized mice to lithogenic diet-induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts. The combined effect of increased biliary cholesterol concentration and decreased biliary bile salt secretion in CAV1(-/-) mice led to an increased cholesterol saturation index and the formation of cholesterol crystals. At the signaling level, the ERK/AP-1 pathway seems to mediate the effects of CAV1 on biliary BA homeostasis and might be developed as a therapeutic target for CGD. We propose that CAV1 is an anti-lithogenic factor and that the CAV1(-/-) mice may offer a convenient CGD model to develop therapeutic interventions for this disease. J. Cell. Biochem. 117: 2118-2127, 2016. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Ácidos y Sales Biliares/biosíntesis , Caveolina 1/metabolismo , Colesterol/metabolismo , Vesícula Biliar/metabolismo , Cálculos Biliares/metabolismo , Sistema de Señalización de MAP Quinasas , Animales , Ácidos y Sales Biliares/genética , Transporte Biológico Activo/genética , Caveolina 1/genética , Línea Celular , Colesterol/genética , Vesícula Biliar/patología , Vesícula Biliar/fisiología , Cálculos Biliares/genética , Cálculos Biliares/patología , Ratones , Ratones Noqueados
7.
Int J Phytoremediation ; 18(3): 251-60, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26368658

RESUMEN

Phytoremediation is considered to be a promising approach to restore or stabilize soil contaminated by lead (Pb). Turfgrasses, due to their high biomass yields, are considered to be suitable for use in phytoextraction of soil contaminated with heavy metal. It has been demonstrated that centipedegrass (Eremochloa ophiuroides (Munro) Hack., Poaceae) is a good turfgrass for restore of soil contaminated by Pb. However, the enhanced tolerant mechanisms in metallicolous (M) centipedegrass accessions remain unknown. In this study, we made a comparative study of growth performance, Pb accumulation, antioxidant levels, and phytochelatin concentrations in roots and shoots from M and nonmetallicolous (NM) centipedegrass accessions. Results showed that turf quality and growth rate were less repressed in M accessions than in NM accession. Pb stress caused generation of reactive oxygen species in centipedegrass with relatively lower levels in M accessions. Antioxidant activity analysis indicated that superoxide dismutase and catalase played important roles in Pb tolerance in M accessions. M accessions accumulated more Pb in roots and shoots. Greatly increased phytochelatins and less repressed sulfur contents in roots and shoots of M accessions indicated that they correlated with Pb accumulation and tolerance in centipedegrass.


Asunto(s)
Catalasa/metabolismo , Plomo/metabolismo , Fitoquelatinas/metabolismo , Poaceae/metabolismo , Contaminantes del Suelo/metabolismo , Superóxido Dismutasa/metabolismo , Biodegradación Ambiental , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Poaceae/crecimiento & desarrollo
8.
Cell Tissue Res ; 362(1): 187-99, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25982995

RESUMEN

Our aim is to elucidate the effects of osteoproteogerin (OPG) on cartilage destruction in rats as a model of collagen-induced arthritis (CIA). To establish the CIA model, Sprague Dawley rats were injected with bovine type II collagen solution subcutaneously via the tails. Adenovirus-mediated OPG (Ad-OPG) was then injected intra-articularly either at the beginning of CIA (early OPG treatment) or one week after CIA establishment (late OPG treatment); vehicle or Ad-green fluorescent protein were injected as controls. The rats were killed 4 weeks after treatment. Ankle-joint sections were obtained for histology. Serum samples were collected for enzyme-linked immunosorbent assay. Safranin O staining showed that proteoglycan loss was inhibited in the early and late Ad-OPG groups. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining revealed that both early and late Ad-OPG treatments significantly prevented chondrocyte apoptosis in CIA rats. Furthermore, disintegrin and metalloproteinase with thrombospondin motif-5 expression decreased remarkably in the early and late OPG treatment groups. However, the cartilage destruction score, cartilage oligomeric matrix protein level and caspase-3 expression were only decreased in the early Ad-OPG treatment group. Additionally, ankle-joint swelling and the interleukin-1ß expression level in CIA rats were not notably altered by Ad-OPG treatment. Taken together, our results suggest that early Ad-OPG treatment has potent protective effects against cartilage destruction during rheumatoid arthritis progression, mainly by reducing proteoglycan loss and chondrocyte apoptosis.


Asunto(s)
Adenoviridae/metabolismo , Artritis Experimental/metabolismo , Condrocitos/metabolismo , Colágeno Tipo II/metabolismo , Osteoprotegerina/metabolismo , Proteoglicanos/metabolismo , Animales , Ratas , Ratas Sprague-Dawley
9.
Haematologica ; 99(12): 1834-45, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25193962

RESUMEN

Germinal center lymphoma is a heterogeneous human lymphoma entity. Here we report that constitutive activity of SHP2 (PTPN11) and its downstream kinase ERK is essential for the viability of germinal center lymphoma cells and disease progression. Mechanistically, SHP2/ERK inhibition impedes c-Myc transcriptional activity, which results in the repression of proliferative phenotype signatures of germinal center lymphoma. Furthermore, SHP2/ERK signaling is required to maintain the CD19/c-Myc loop, which preferentially promotes survival of a distinct subtype of germinal center lymphoma cells carrying the MYC/IGH translocation. These findings demonstrate a critical function for SHP2/ERK signaling upstream of c-Myc in germinal center lymphoma cells and provide a rationale for targeting SHP2 in the therapy of germinal center lymphoma.


Asunto(s)
Centro Germinal/patología , Cadenas Pesadas de Inmunoglobulina/genética , Linfoma/patología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Translocación Genética/genética , Apoptosis , Western Blotting , Ciclo Celular , Proliferación Celular , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Centro Germinal/metabolismo , Humanos , Técnicas para Inmunoenzimas , Inmunoprecipitación , Linfoma/genética , Linfoma/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/antagonistas & inhibidores , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Células Tumorales Cultivadas
10.
ScientificWorldJournal ; 2014: 916595, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25097893

RESUMEN

Sulfur dioxide (SO2), a major air pollutant in developing countries, is highly toxic to plants. To achieve better air quality and landscape, planting appropriate grass species in severe SO2 polluted areas is very critical. Cynodon dactylon, a widely used warm season turfgrass species, has good SO2-tolerant ability. In this study, we selected 9 out of 38 C. dactylon accessions from Southwest China as representatives of high, intermediate SO2-tolerant and SO2-sensitive accessions to comparatively analyze their physiological differences in leaves under SO2 untreated and treated conditions. Our results revealed that SO2-tolerant C. dactylon accessions showed higher soluble sugar, proline, and chlorophyll a contents under both SO2 treated and untreated conditions; higher chlorophyll b and carotenoid under SO2 treated condition; lower reactive oxygen species (ROS) level, oxidative damages, and superoxide dismutase (SOD) activities under SO2 treated condition; and higher peroxidase (POD) activities under SO2 untreated condition. Further results indicated that SO2-tolerant C. dactylon accessions had higher sulfur contents under both SO2 treated and untreated conditions, consistent with higher SO activities under both SO2 treated and untreated conditions, and higher SiR activities under SO2 treated condition. Taken together, our results indicated that SO2 tolerance of C. dactylon might be largely related to soluble sugar, proline and chlorophyll a contents, and SO enzyme activity.


Asunto(s)
Cynodon/efectos de los fármacos , Dióxido de Azufre/toxicidad , Metabolismo de los Hidratos de Carbono , Clorofila/metabolismo , Cynodon/metabolismo , Proteínas de Plantas/metabolismo , Prolina/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Azufre/metabolismo , Superóxido Dismutasa/metabolismo
11.
Artículo en Inglés | MEDLINE | ID: mdl-38928927

RESUMEN

The rapid aging and increasing care demands among the elderly population present challenges to China's health and social care system. The concept of aging in place has prompted the implementation of integrated community care (ICC) in the country. This study aims to provide empirical insights into the practices of integrated care policies and approaches at the community level. Data for this study were collected through six months of participatory observations at a local community health service center in a southern Chinese city. Semi-structured interviews were conducted with the multidisciplinary community care team to gather frontline formal caregiver perceptions of ICC, thereby facilitating a better understanding of the obstacles and opportunities. Qualitative analysis revealed four themes: the ICC delivery model and development strategies within the community care scheme, the person-centered guiding principle, and the challenges and struggles encountered by formal caregivers within China's current ICC system. The case study presented herein serves as a notable example of the pivotal role of primary care in the successful implementation of elderly care within a community setting. The adoption of a private organization-led approach to medico-social integration care in the community holds significant potential as a service delivery model for effectively addressing a wide range of elderly care issues.


Asunto(s)
Servicios de Salud Comunitaria , Prestación Integrada de Atención de Salud , China , Humanos , Anciano , Prestación Integrada de Atención de Salud/organización & administración , Servicios de Salud Comunitaria/organización & administración , Investigación Cualitativa , Servicios de Salud para Ancianos/organización & administración , Cuidadores , Femenino , Masculino
12.
Int J Neurosci ; 123(11): 810-22, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23668883

RESUMEN

BACKGROUND/AIMS: Multiple sclerosis is a neurodegenerative autoimmune disease characterized by diffuse oligodendrocyte injury, axonal loss and multifocal demyelination of myelin sheaths in the central nervous system. TRO19622 is a small cholesterol-like compound, which displays remarkable neuroprotective and neuroregenerative properties in neural cell culture and rodent models of nerve trauma. Therefore, the aim of the present study is to evaluate the pharmacological action of TRO19622 on the demyelination/remyelination processes by using a rat model of cuprizone-induced demyelination. METHODS: Using Female Sprague-Dawley rats models of demyelination, we morphologically and functionally assessed the effect of TRO19622 on myelination in vivo. RESULTS: In this study, we first provided in vivo proof that cuprizone intoxication contributed to spatial learning and memory ability injury and that TRO19622 restored neurological function. The structure of myelin injury and repair in cuprizone intoxication rats was then measured by T2-weighted magnetic resonance imaging. These magnetic resonance imaging-based results and trends were confirmed by histological, immunohistochemistry and electron microscopy analyses. CONCLUSIONS: The results clearly showed that TRO19622 promoted myelin formation with consequent functional improvement.


Asunto(s)
Colestenonas/uso terapéutico , Enfermedades Desmielinizantes/tratamiento farmacológico , Modelos Animales de Enfermedad , Animales , Enfermedades Desmielinizantes/patología , Femenino , Ratas , Ratas Sprague-Dawley
13.
Ann Transl Med ; 11(5): 207, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-37007585

RESUMEN

Background: Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their specific markers and acquire mesenchymal or myofibroblastic phenotypes. Studies have demonstrated the importance of endothelial-derived vascular smooth muscle cells (VSMCs) through EndMT in neointimal hyperplasia. Histone deacetylases (HDACs) are epigenetic modification enzymes involved in the epigenetic control of important cellular functions. Recent studies found that HDAC3, a class I HDAC, causes posttranslational modifications, including deacetylation and decrotonylation. However, the effect of HDAC3 on EndMT in neointimal hyperplasia via posttranslational modifications remains to be seen. Therefore, we investigated the effects of HDAC3 on EndMT in carotid artery-ligated mice and human umbilical vein endothelial cells (HUVECs) and the underlying posttranslational modifications. Methods: HUVECs were treated with transforming growth factor (TGF)-ß1 or the inflammatory cytokine tumor necrosis factor (TNF)-α at different concentrations and durations. In HUVECs, HDAC3 expression, the expression of endothelial and mesenchymal markers, and posttranslational modifications were analyzed with Western blotting, quantitative real-time polymerase chain reaction (PCR), and immunofluorescence. C57BL/6 mice underwent left carotid artery ligation. Mice were treated with the HDAC3-selective inhibitor RGFP966 (10 mg/kg, i.p.) from 1 day before to 14 days after ligation. Then, the sections of the carotid arteries were examined histologically using hematoxylin and eosin (HE) and immunofluorescence staining. The carotid arteries from other mice were examined for the expression of EndMT markers and inflammatory cytokines. Furthermore, the acetylation and crotonylation of carotid arteries were immunostained in mice. Results: In HUVECs, TGF-ß1 and TNF-α induced EndMT by decreasing CD31 expression and increasing α-smooth muscle actin expression. TGF-ß1 and TNF-α also upregulated HDAC3 expression in HUVECs. The in vivo study in mice indicated that RGFP966 significantly alleviated neointimal hyperplasia of the carotid artery compared with vehicle treatment. Furthermore, RGFP966 suppressed EndMT and the inflammatory response in carotid artery-ligated mice. Further investigation revealed that HDAC3 regulated EndMT by posttranslational modifications of deacetylation and decrotonylation. Conclusions: These results suggest that HDAC3 regulates EndMT in neointimal hyperplasia through posttranslational modifications.

14.
Virus Evol ; 7(1): veab036, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34221451

RESUMEN

Hepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about three per cent of the human population. Because no animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain unresolved. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a large collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, eighty were found positive for the presence of hepaciviruses in twenty-nine different host species. We, here, report fifty-six novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages. Furthermore, we provide strong evidence for hepacivirus co-infections in rodents, which were exclusively found in four sampled species of brush-furred mice. We also detect evidence of recombination within specific host lineages. Our study expands the available hepacivirus genomic data and contributes insights into the relatively deep evolutionary history of these pathogens in rodents. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.

15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 39(3): 272-7, 2010 05.
Artículo en Zh | MEDLINE | ID: mdl-20544989

RESUMEN

OBJECTIVE: To investigate the effects of formaldehyde inhalation on the morphological damage, and Glu, GABA and NOS contents in olfactory bulb and hippocampus of rats. METHODS: Twenty SD rats were equally divided into two groups: rats in the control group inhaled fresh air, while the animals in experimental group were exposed to the air containing formaldehyde (12.5 mg/m(3), 4 h/d) for 7 days. Then rats were sacrificed and frozen sections of olfactory bulb and hippocampus were prepared. The morphological changes were examined and the Glu, GABA and NOS contents were detected using Nissl-staining, immunohistochemistry and Western blot, respectively. RESULT: Compared with the control group, there was a significant confusion and shrink of neuron morphology in experimental group, the number and staining intensity of Glu and NOS positive cells and protein contents were reduced. The protein expression of GABA was also decreased in the formaldehyde group. CONCLUSION: Formaldehyde inhalation can cause a severe morphological damage of olfactory bulb and hippocampus in SD rats,which may further impair memory and learning ability through the reduction of Glu, GABA and NOS expression.


Asunto(s)
Formaldehído/toxicidad , Hipocampo/patología , Neuronas/patología , Bulbo Olfatorio/patología , Animales , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Exposición por Inhalación , Aprendizaje/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Óxido Nítrico Sintasa/metabolismo , Bulbo Olfatorio/efectos de los fármacos , Bulbo Olfatorio/metabolismo , Ratas , Ratas Sprague-Dawley , Ácido gamma-Aminobutírico/metabolismo
16.
Zookeys ; 959: 137-159, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32879614

RESUMEN

Niviventer confucianus sacer Thomas, 1908, which has been regarded as a subspecies of N. confucianus, was found to be a distinct species from N. confucianus based on molecular, karyotyping, and morphological characteristics in this study. Niviventer c. sacer was found to belong to a distinct phylogenetic clade in phylogenetic tree constructed using the mitochondrial gene Cytb, it clustered with N. bukit (Bonhote, 1903) from Vietnam and N. confucianus (Milne-Edwards, 1871) from Yunnan, but showed a distant relationship with N. confucianus from adjacent areas. The genetic distance between N. c. sacer and N. confucianus was more than 5.8%, reaching the level of interspecific differentiation. The species delimitation indicates that N. c. sacer is a monophyletic group. The karyotype of N. c. sacer (FN = 55, 8m+4st+32t+X(sm)Y(t)) differed from that of N. confucianus (FN = 59, 6m+4sm+2st+32t+X(sm)Y(t)). In terms of morphological features, the length of incisive foramen (LIF) and length of auditory bulla (LAB) of N. c. sacer is significantly larger than that of N. confucianus and N. bukit (P < 0.05) and the proportion of white tail tip to total tail length is significantly longer at N. c. sacer (≥ 1/3) than that at N. confucianus (≤ 1/3). Therefore, integrated analysis confirmed that N. c. sacer is a distinct species of genus Niviventer rather than a subspecies of N. confucianus or N. bukit, namely N. sacer, which is only distributed in Shandong.

17.
Int J Mol Med ; 42(1): 115-122, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29620171

RESUMEN

Tripterygium glycoside (TG), an active ingredient of the widely used Chinese herb Tripterygium wilfordii Hook F, has immunosuppressive and anti­inflammatory effects. Previous studies have indicated that TG is a potentially effective therapeutic option to treat nephrotic syndrome. The mechanism underlying the therapeutic effect of TG, including its effect on autophagy and apoptosis in podocyte injury, remains to be fully elucidated. The present study aimed to assess the protective effect of TG on podocytes via its potential role in the activation of autophagic and phosphatidylinositol 3­kinase (PI3K) pathways. Using flow cytometry, western blot analysis, cell counting kit­8 assays and transmission electron microscopy analysis, the effects of TG on puromycin aminonucleoside (PAN)­induced podocyte injury were investigated. Chloroquine (CQ), an inhibitor of autophagy, was used to assess the importance of autophagy in the protective effect of TG. In addition, LY294002, an inhibitor of class III PI3K, was used to identify which signaling pathways TG is involved in. PAN caused marked apoptosis of podocytes, which was significantly antagonized by TG. The expression of microtubule­associated protein 1A/1B­light chain 3 and the appearance of autophagosomes increased significantly following TG treatment, whereas the expression levels of p62 and cleaved caspase-3 were markedly decreased. Podocyte apoptosis decreased significantly when the podocytes were treated with TG compared with the levels of apoptosis in the PAN­ and PAN+CQ­treated groups. The expression of phosphorylated AKT was increased significantly in the TG­treated groups, and the effects of TG on the podocytes were significantly inhibited by LY294002. In conclusion, TG protected podocytes from PAN­induced injury, and the effects were attributable to the activation of autophagy, mainly via a PI3K­dependent pathway.


Asunto(s)
Autofagia/efectos de los fármacos , Glicósidos/farmacología , Podocitos/patología , Sustancias Protectoras/farmacología , Puromicina Aminonucleósido/efectos adversos , Tripterygium/química , Regulación hacia Arriba/efectos de los fármacos , Animales , Autofagosomas/efectos de los fármacos , Autofagosomas/metabolismo , Autofagosomas/ultraestructura , Muerte Celular/efectos de los fármacos , Línea Celular , Citoprotección/efectos de los fármacos , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Transducción de Señal/efectos de los fármacos
18.
Mol Med Rep ; 14(1): 963-8, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27220778

RESUMEN

Increasing evidence indicates that diabetes-mediated renal interstitial fibrosis through extracellular matrix (ECM) protein accumulation is an important event in the development of diabetic kidney disease (DKD), however, the underlying mechanism remains unclear. In the current study, it was observed that high levels of glucose (HG) time­ and dose-dependently increased the production of the ECM protein, fibronectin (FN), in primary rat mesangial cells. Inhibition of the Rho pathway blocked HG­induced FN upregulation. HG­induced RhoA activation was prevented by inhibiting caveolae with filipin III or caveolin­1 siRNA and rescued by exogenous caveolin­1. HG also increased caveolin-1/Src association and activated Src kinase, whereas the inhibition of Src blocked RhoA activation and FN upregulation. Src-mediated phosphorylation of caveolin­1 on Y14 has also been implicated in signaling responses. Overexpression of the nonphosphorylatable caveolin­1 Y14A mutant prevented the HG­induced RhoA activation and FN upregulation. In conclusion, HG­induced FN upregulation requires caveolae and caveolin­1 to interact with RhoA and Src kinases. Interference with Src/caveolin-1/RhoA signaling may provide novel mechanistic targets for the treatment of DKD.


Asunto(s)
Caveolina 1/metabolismo , Fibronectinas/metabolismo , Glucosa/metabolismo , Células Mesangiales/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Familia-src Quinasas/metabolismo , Animales , Glucemia , Caveolas/metabolismo , Células Cultivadas , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Activación Enzimática/efectos de los fármacos , Glucosa/farmacología , Células Mesangiales/efectos de los fármacos , Fosforilación , Ratas , Regulación hacia Arriba
19.
Mitochondrial DNA B Resour ; 1(1): 343-344, 2016 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-33644377

RESUMEN

In this study, the complete mitochondrial genome of Inez's red-backed vole Caryomys inez was sequenced and analyzed as the first species in genus Caryomys. The complete mitochondrial genome of C. inez is 16,354 bp in length and shows a typical vertebrate pattern with 13 PCGs, 22 tRNAs, 2 rRNAs and 2 non-coding regions. To gain a clear phylogenetic position of C. inez, a ML phylogenetic tree was constructed based on 12 PCGs on H-strand from 23 rodent species except for ND6 gene which is on L-strand. As a result, C. inez is clustered with genera Eothenomys and Myodes, showing their close phylogenetic relationships. The present study may facilitate further investigation of the taxonomic studies and phylogenetic analyses of the genus Caryomys.

20.
Mol Med Rep ; 12(1): 37-44, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25738883

RESUMEN

Following spinal cord trauma, mitochondrial dysfunction associated with increased oxidative stress is a critical event leading to leukocyte inflammatory responses, neuronal cell death and demyelination, contributing to permanent locomotor and neurological disability. The present study demonstrated that the mitochondrial enhancer N-acetylcysteine (NAC) may restore redox balance via enhancement of mitochondrial respiratory activity following traumatic spinal cord injury (SCI). In addition, NAC ameliorates oxidative stress-induced neuronal loss, demyelination, leukocyte infiltration and inflammatory mediator expression and improves long-term locomotor function. Furthermore, neuronal survival and neurological recovery are significantly correlated with increased mitochondrial bioenergetics in SCI following treatment with NAC. Therefore, NAC may represent a potential therapeutic agent for preserving mitochondrial dynamics and integrity following traumatic SCI.


Asunto(s)
Acetilcisteína/administración & dosificación , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/administración & dosificación , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología
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