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1.
J Virol ; 98(1): e0159923, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38169281

RESUMO

African swine fever virus (ASFV) causes a highly contagious and deadly disease in domestic pigs and European wild boars, posing a severe threat to the global pig industry. ASFV CP204L, a highly immunogenic protein, is produced during the early stages of ASFV infection. However, the impact of CP204L protein-interacting partners on the outcome of ASFV infection is poorly understood. To accomplish this, coimmunoprecipitation and mass spectrometry analysis were conducted in ASFV-infected porcine alveolar macrophages (PAMs). We have demonstrated that sorting nexin 32 (SNX32) is a CP204L-binding protein and that CP204L interacted and colocalized with SNX32 in ASFV-infected PAMs. ASFV growth and replication were promoted by silencing SNX32 and suppressed by overexpressing SNX32. SNX32 degraded CP204L by recruiting the autophagy-related protein Ras-related protein Rab-1b (RAB1B). RAB1B overexpression inhibited ASFV replication, while knockdown of RAB1B had the opposite effect. Additionally, RAB1B, SNX32, and CP204L formed a complex upon ASFV infection. Taken together, this study demonstrates that SNX32 antagonizes ASFV growth and replication by recruiting the autophagy-related protein RAB1B. This finding extends our understanding of the interaction between ASFV CP204L and its host and provides new insights into exploring the relationship between ASFV infection and autophagy.IMPORTANCEAfrican swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with a high mortality near 100% in domestic pigs. ASF virus (ASFV), which is the only member of the family Asfarviridae, is a dsDNA virus of great complexity and size, encoding more than 150 proteins. Currently, there are no available vaccines against ASFV. ASFV CP204L represents the most abundantly expressed viral protein early in infection and plays an important role in regulating ASFV replication. However, the mechanism by which the interaction between ASFV CP204L and host proteins affects ASFV replication remains unclear. In this study, we demonstrated that the cellular protein SNX32 interacted with CP204L and degraded CP204L by upregulating the autophagy-related protein RAB1B. In summary, this study will help us understand the interaction mechanism between CP204L and its host upon infection and provide new insights for the development of vaccines and antiviral drugs.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Fatores de Restrição Antivirais , Autofagia , Nexinas de Classificação , Proteínas rab1 de Ligação ao GTP , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Sus scrofa/virologia , Suínos/virologia , Nexinas de Classificação/metabolismo , Fatores de Restrição Antivirais/metabolismo , Proteínas rab1 de Ligação ao GTP/metabolismo , Macrófagos/virologia , Replicação Viral
2.
J Virol ; 98(4): e0014624, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38440983

RESUMO

Peste des petits ruminants is an acute and highly contagious disease caused by the Peste des petits ruminants virus (PPRV). Host proteins play a crucial role in viral replication. However, the effect of fusion (F) protein-interacting partners on PPRV infection is poorly understood. In this study, we found that the expression of goat plasminogen activator urokinase (PLAU) gradually decreased in a time- and dose-dependent manner in PPRV-infected goat alveolar macrophages (GAMs). Goat PLAU was subsequently identified using co-immunoprecipitation and confocal microscopy as an F protein binding partner. The overexpression of goat PLAU inhibited PPRV growth and replication, whereas silencing goat PLAU promoted viral growth and replication. Additionally, we confirmed that goat PLAU interacted with a virus-induced signaling adapter (VISA) to antagonize F-mediated VISA degradation, increasing the production of type I interferon. We also found that goat PLAU reduced the inhibition of PPRV replication in VISA-knockdown GAMs. Our results show that the host protein PLAU inhibits the growth and replication of PPRV by VISA-triggering RIG-I-like receptors and provides insight into the host protein that antagonizes PPRV immunosuppression.IMPORTANCEThe role of host proteins that interact with Peste des petits ruminants virus (PPRV) fusion (F) protein in PPRV replication is poorly understood. This study confirmed that goat plasminogen activator urokinase (PLAU) interacts with the PPRV F protein. We further discovered that goat PLAU inhibited PPRV replication by enhancing virus-induced signaling adapter (VISA) expression and reducing the ability of the F protein to degrade VISA. These findings offer insights into host resistance to viral invasion and suggest new strategies and directions for developing PPR vaccines.


Assuntos
Doenças das Cabras , Cabras , Interações Hospedeiro-Patógeno , Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Ativador de Plasminogênio Tipo Uroquinase , Proteínas Virais de Fusão , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteína DEAD-box 58/metabolismo , Doenças das Cabras/imunologia , Doenças das Cabras/metabolismo , Doenças das Cabras/virologia , Cabras/imunologia , Cabras/virologia , Macrófagos Alveolares , Peste dos Pequenos Ruminantes/imunologia , Peste dos Pequenos Ruminantes/metabolismo , Peste dos Pequenos Ruminantes/virologia , Vírus da Peste dos Pequenos Ruminantes/crescimento & desenvolvimento , Vírus da Peste dos Pequenos Ruminantes/imunologia , Vírus da Peste dos Pequenos Ruminantes/metabolismo , Ligação Proteica , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Proteínas Virais de Fusão/metabolismo
3.
BMC Vet Res ; 20(1): 198, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745180

RESUMO

BACKGROUND: Primary sheep fetal fibroblasts (SFFCs) have emerged as a valuable resource for investigating the molecular and pathogenic mechanisms of orf viruses (ORFV). However, their utilization is considerably restricted due to the exorbitant expenses associated with their isolation and culture, their abbreviated lifespan, and the laborious procedure. RESULTS: In our investigation, the primary SFFCs were obtained and immortalized by introducing a lentiviral recombinant plasmid containing the large T antigen from simian virus 40 (SV40). The expression of fibronectin and vimentin proteins, activity of SV40 large T antigen, cell proliferation assays, and analysis of programmed cell death revealed that the immortalized large T antigen SFFCs (TSFFCs) maintained the same physiological characteristics and biological functions as the primary SFFCs. Moreover, TSFFCs demonstrated robust resistance to apoptosis, extended lifespan, and enhanced proliferative activity compared to primary SFFCs. Notably, the primary SFFCs did not undergo in vitro transformation or exhibit any indications of malignancy in nude mice. Furthermore, the immortalized TSFFCs displayed live ORFV vaccine susceptibility. CONCLUSIONS: Immortalized TSFFCs present valuable in vitro models for exploring the characteristics of ORFV using various techniques. This indicates their potential for secure utilization in future studies involving virus isolation, vaccine development, and drug screening.


Assuntos
Fibroblastos , Animais , Fibroblastos/virologia , Ovinos , Camundongos , Vírus do Orf/genética , Camundongos Nus , Proliferação de Células , Vírus 40 dos Símios , Linhagem Celular , Apoptose , Antígenos Virais de Tumores/genética
4.
Funct Integr Genomics ; 23(2): 163, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37188892

RESUMO

The Orf virus (ORFV) is a member of the Parapoxvirus genus of the Poxviridae family and can cause contagious diseases in sheep, goats, and wild ungulates. In the present study, two ORFV isolates (ORFV-SC isolated from Sichuan province and ORFV-SC1 produced by 60 passages of ORFV-SC in cells) were sequenced and compared to multiple ORFVs. The two ORFV sequences had entire genome sizes of 14,0707 bp and 141,154 bp, respectively, containing 130 and 131 genes, with a G + C content of 63% for the ORFV-SC sequence and 63.9% for the ORFV-SC1 sequence. Alignment of ORFV-SC and ORFV-SC1 with five other ORFV isolates revealed that ORFV-SC, ORFV-SC1, and NA1/11 shared > 95% nucleotide identity with 109 genes. Five genes (ORF007, ORF20, ORF080, ORF112, ORF116) have low amino acids identity between ORFV-SC and ORFV-SC1. Mutations in amino acids result in changes in the secondary and tertiary structure of ORF007, ORF020, and ORF112 proteins. The phylogenetic tree based on the complete genome sequence and 37 single genes revealed that the two ORFV isolates originated from sheep. Finally, animal experiments demonstrated that ORFV-SC1 is less harmful to rabbits than ORFV-SC. The exploration of two full-length viral genome sequences provides valuable information in ORFV biology and epidemiology research. Furthermore, ORFV-SC1 demonstrated an acceptable safety profile following animal vaccination, indicating its potential as a live ORFV vaccine.


Assuntos
Vírus do Orf , Coelhos , Animais , Ovinos/genética , Vírus do Orf/genética , Filogenia , Genoma Viral , Genômica , Cabras/genética , China/epidemiologia
5.
J Virol ; 96(10): e0030922, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35502911

RESUMO

Inflammatory responses play a central role in host defense against invading pathogens. Peste des petits ruminants virus (PPRV) causes highly contagious acute or subacute disease of small ruminants. However, the precise mechanism by which PPRV regulates inflammatory responses remains unknown. Here, we revealed a novel mechanism by which PPRV induces inflammation. Our study showed that PPRV induced the secretion of interleukin 1ß (IL-1ß) by activating the NF-κB signaling pathway and the NLRP3 inflammasome. Moreover, PPRV replication and protein synthesis were essential for NLRP3 inflammasome activation. Importantly, PPRV N protein promoted NF-κB signaling pathway and NLRP3 inflammasome via direct binding of MyD88 and NLPR3, respectively, and induced caspase-1 cleavage and IL-1ß maturation. Biochemically, N protein interacted with MyD88 to potentiate the assembly of MyD88 complex and interacted with NLPR3 to facilitate NLRP3 inflammasome complex assembly by forming an N-NLRP3-ASC ring-like structure, leading to IL-1ß secretion. These findings demonstrate a new function of PPRV N protein as an important proinflammation factor and identify a novel underlying mechanism modulating inflammasome assembly and function induced by PPRV. IMPORTANCE An important part of the innate immune response is the activation of NF-κB signaling pathway and NLPR3 inflammasome, which is induced upon exposure to pathogens. Peste des petits ruminants virus (PPRV) is a highly contagious virus causing fever, stomatitis, and pneumoenteritis in goats by inducing many proinflammatory cytokines. Although the NF-κB signaling pathway and NLRP3 inflammasome play an important role in regulating host immunity and viral infection, the precise mechanism by which PPRV regulates inflammatory responses remains unknown. This study demonstrates that PPRV induces inflammatory responses. Mechanistically, PPRV N protein facilitates the MyD88 complex assembly by directly binding to MyD88 and promotes the NLRP3 inflammasome complex assembly by directly binding to NLRP3 to form ring-like structures of N-NLRP3-ASC. These findings provide insights into the prevention and treatment of PPRV infection.


Assuntos
Fator 88 de Diferenciação Mieloide , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas do Nucleocapsídeo , Vírus da Peste dos Pequenos Ruminantes , Animais , Cabras , Inflamassomos/metabolismo , Inflamação/virologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Peste dos Pequenos Ruminantes
6.
BJOG ; 130(6): 645-652, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36660801

RESUMO

OBJECTIVE: To investigate the long-term outcomes for Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) patients undergoing vaginoplasty using acellular porcine small intestinal submucosa grafts (SIS). DESIGN: A case series. POPULATION: Seventy-eight MRKH syndrome patients and a post-SIS patient who delivered a baby following the world's first robot-assisted uterus transplantation. METHODS: Mayer-Rokitansky-Küster-Hauser syndrome patients were grouped based on the postoperative time and the diagnosis-surgery interval. Outcomes of sexual function and psychological status were assessed using the female sexual function index (FSFI), self-rating scale of body image (SSBI) and self-acceptance questionnaire (SAQ). Anatomical outcomes were measured by clinicians. MAIN OUTCOME MEASURES: The primary outcome was restoration of sexual function, defined by an FSFI score in the 'good' range. Anatomical and psychological outcomes were also analysed. RESULTS: Sexual function was restored in 42.3% (33/78) of patients and the total FSFI score was 23.44 ± 4.43. Three factors (body defect, recognition of physical appearance and willingness to change physical appearance scores) in the SSBI and two in the SAQ decreased as the postoperative time increased. Based on the interval between diagnosis and surgery, the total SSBI score was lower in the short-interval group than in the long-interval group (7.25 ± 5.55 versus 12.04 ± 10.21, p = 0.038). CONCLUSIONS: Nearly half of MRKH patients in our study had good long-term sexual function after SIS vaginoplasty. Sexual function and psychological status improved as postoperative time increased. In addition, reducing the diagnosis to surgery interval was associated with improved psychological function.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual , Anormalidades Congênitas , Procedimentos de Cirurgia Plástica , Feminino , Suínos , Animais , Humanos , Vagina/cirurgia , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Útero/cirurgia , Anormalidades Congênitas/cirurgia
7.
BMC Pregnancy Childbirth ; 23(1): 171, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36915067

RESUMO

BACKGROUND: To assess the prevalence, risk factors, clinical characteristics of Acute fatty liver of pregnancy (AFLP) patients, and outcomes of AFLP patients treated with plasma exchange (PE). METHODS: We retrospectively reviewed the AFLP patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University and Xijing Hospital of Air Force Medical University from January 2012 to May 2022. Final prediction model for death among AFLP by means of stepwise backward elimination with p value < 0.05. Patients treated with and without PE were compared by propensity-matched cohort study. RESULTS: Two hundred ninety eight patients with the diagnosis of AFLP, and finally 290 patients were enrolled in the cohort study, 50 of whom (17.2%) were dead. Compared with AFLP patients alive, the dead of patients were more likely to be combined encephalopathy (p < 0.01), postpartum hemorrhage (p < 0.01), and found significantly higher frequency of fetal distress (p = 0.04), fetal death (p < 0.01). we developed a predicted probability value and with an area under the receiver operating characteristics (ROC) curve of 0.94 (95%CI 0.87 to 1.00), indicating AFLP patients' death. The patients treated with PE had a significantly lower 60-day mortality rate (OR 0.42, 95% CI 0.29 to 2.64, p = 0.04), and significantly shorter duration of hospital-free days at day 28 (p = 0.01). CONCLUSIONS: In conclusion, our study indicated that liver function were risk factors for maternal mortality, and PE was a protective factor for maternal 60-day mortality and hospital-free days at day 28 in AFLP patients.


Assuntos
Fígado Gorduroso , Complicações na Gravidez , Gravidez , Feminino , Humanos , Troca Plasmática , Estudos Retrospectivos , Estudos de Coortes , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/terapia , Fígado Gorduroso/diagnóstico , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/terapia , Complicações na Gravidez/diagnóstico
8.
Int J Obes (Lond) ; 46(11): 1970-1982, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35922561

RESUMO

BACKGROUND: FAM132b (myonectin) has been identified as a muscle-derived myokine with exercise and has hormone activity in circulation to regulate iron homeostasis and lipid metabolism via unknown receptors. Here, we aim to explore the potential of adeno-associated virus to deliver FAM132b in vivo to develop a gene therapy against obesity. METHODS: Adeno-associated virus AAV9 were engineered to induce overexpression of FAM132b with two mutations, A136T and P159A. Then, AAV9 was delivered into high-fat diet mice through tail vein, and glucose homeostasis and obesity development of mice were observed. Methods of structural biology were used to predict the action site or receptor of the FAM132b mutant. RESULTS: Treatment of high-fat diet-fed mice with AAV9 improved glucose intolerance and insulin resistance, and resulted in reductions in body weight, fat depot, and adipocyte size. Codon-optimized FAM132b (coFAM132b) reduced the glycemic response to epinephrine (EPI) in the whole body and increased the lipolytic response to EPI in adipose tissues. However, FAM132b knockdown by shRNA significantly increased the glycemic response to EPI in vivo and reduced adipocyte response to EPI and adipose tissue browning. Structural analysis predicted that the FAM132b mutant with A136T and P159A may form a weak bond with ß2 adrenergic receptor (ADRB2) and may have more affinity for insulin and insulin-receptor complexes. CONCLUSIONS: Our study underscores the potential of FAM132b gene therapy with codon optimization to treat obesity by modulating the adrenergic response and insulin action. Both structural biological analysis and in vivo experiments suggest that the adrenergic response and insulin action are most likely blockaded by FAM132b mutants.


Assuntos
Adrenérgicos , Resistência à Insulina , Camundongos , Animais , RNA Interferente Pequeno , Obesidade/genética , Obesidade/terapia , Obesidade/metabolismo , Resistência à Insulina/genética , Dieta Hiperlipídica , Insulina/metabolismo , Glicemia/metabolismo , Terapia Genética , Códon , Epinefrina , Receptores Adrenérgicos/genética , Ferro , Camundongos Endogâmicos C57BL
9.
Pharmacology ; 107(7-8): 376-385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35640539

RESUMO

INTRODUCTION: Cervical cancer is a severe malignant tumor that endangers the health of women worldwide. Eukaryotic initiation factor-5A2 (EIF5A2) expression has been reported to be increased in cervical cancer and correlates with prognosis. An attempt was made in this paper to explore the impact and potential mechanisms of EIF5A2 in the cell biology of cervical cancer. METHODS: We first knocked down EIF5A2 in cervical cancer cells. Then, we examined the proliferation, migration, invasion, and apoptosis of these cells by cell counting kit 8, wound healing, Transwell, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Cells were processed with different concentrations of cisplatin to observe their sensitivity to cisplatin. Next, the relationship between EIF5A2 and anterior gradient 2 (AGR2) was verified by co-immunoprecipitation. Following AGR2 overexpression, the biological processes of these cells were examined. RESULTS: EIF5A2 knockdown inhibited cell proliferation, migration, and invasion, and it promoted apoptosis and enhanced the sensitivity to cisplatin in cervical cancer cells. Additionally, AGR2 expression was positively correlated with EIF5A2, and its overexpression alleviated the reduction in proliferation, migration, and invasion of cervical cancer cells induced by EIF5A2 knockdown. Overexpression of AGR2 also reduced apoptosis and their sensitivity to cisplatin in EIF5A2-knockdwon cervical cancer cells. CONCLUSION: EIF5A2 knockdown inhibited the biological process of cervical cancer cells through modulation of AGR2. The in-depth investigation of the molecular mechanism of EIF5A2 in cervical cancer cells provides new strategies for the prevention and treatment of clinical malignancies.


Assuntos
Fenômenos Biológicos , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Feminino , Humanos , Mucoproteínas/genética , Mucoproteínas/metabolismo , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Fator de Iniciação de Tradução Eucariótico 5A
10.
Am J Dent ; 35(2): 146-151, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35798710

RESUMO

PURPOSE: To evaluate the plaque removal efficacy of a compacted dual-head power toothbrush (DH) in comparison with a single-head power toothbrush (SH). METHODS: 24 healthy university students were included in this split-mouth and single-center clinical trial. The DH and SH were randomly assigned to brush the left/right half mouth in the first visit. Testing time points were 30 and 60 seconds. Additionally, 15 and 45 seconds were set for the DH period. The overall, buccal, lingual, gingival marginal, and proximal plaque scores at different time points were recorded and determined by Rustogi Modification of the Navy Plaque Index. To avoid the influence of the right handedness, subjects were brushed in the second visit after 4 weeks, and the SH and the DH were assigned to the right/left half mouth in an opposite period to that of the first visit. RESULTS: 21 participants completed this study. Overall plaque score reductions of the SH and DH were 29% and 59% (P< 0.05) at 30 seconds, and the reductions were 47% and 77% respectively (P< 0.05) at 60 seconds. Using the DH for 45 seconds reduced significantly more overall, buccal, lingual, and gingival marginal plaque than that of using SH for 60 seconds (P< 0.05). The SH reduced plaque scores significantly less in the right and lower dentitions than left and upper dentitions respectively, while DH reduced comparable plaque scores between these dentitions. The DH is more effective in removing overall, buccal, lingual, gingival marginal, and proximal plaque in healthy university students than the SH, meanwhile DH showed comparable overall plaque reduction rates between different regions of the dentitions. CLINICAL SIGNIFICANCE: This compact dual-head power toothbrush provides a new option to carry out daily plaque control effectively.


Assuntos
Placa Dentária , Gengivite , Índice de Placa Dentária , Desenho de Equipamento , Humanos , Método Simples-Cego , Escovação Dentária , Resultado do Tratamento
11.
J Cell Biochem ; 120(2): 2058-2069, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30246300

RESUMO

BACKGROUND AND OBJECTIVES: In this study, we aimed to study the molecular mechanisms underlying the symptoms of hyperresponsiveness during intubation. METHOD: The value of circulating long noncoding RNA (lncRNA)-prognosis-associated gallbladder cancer (PAGBC) in the prediction of hyperresponsiveness upon intubation during general anesthesia was evaluated via the receiver operating characteristic analyses of serum miR-511, serum PAGBC, and serum nitric oxide (NO). In addition, the possible association between lncRNA-PAGBC/NOS1 messenger RNA (mRNA) and miR-511 was further validated via real-time quantitative polymerase chain reaction, immunohistochemistry assay, computational analysis, and luciferase assay. Enzyme-linked immunosorbent assay and Western blot analysis were also conducted to establish the regulatory relationship among PAGBC, miR-511, and NO synthase 1 (NOS1). RESULTS: Compared with circulating miR-511 and serum NO, circulating PAGBC was associated with a higher predictive value. In addition, a negative correlation was found between serum miR-511 and serum PAGBC (multicorrelation coefficient: -0.5) as well as between serum miR-511 and serum NO (multicorrelation coefficient: -0.6). In addition, both lncRNA-PAGBC and NO were decreased in patients with hyperresponsiveness, whereas the levels of miR-511 and NOS1 in these patients were similar to those in normal patients. Furthermore, our computational analyses and luciferase assays validated the direct binding between miR-511 and lncRNA-PAGBC, whereas NOS1 mRNA was identified as a virtual target gene of miR-511. Moreover, in the presence of lncRNA-PAGBC, we also observed an evident increase in the levels of NOS1 and NO accompanied by an obvious decrease of miR-511 expression. CONCLUSION: LncRNA-PAGBC downregulated the expression of miR-511, which in turn upregulated the expression of NOS1 mRNA and led to the increase in NOS1 expression, thus leading to the inhibited responsiveness (normal-responsiveness rather than hyperresponsiveness) to intubation in patients.

12.
Respir Res ; 20(1): 163, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331325

RESUMO

BACKGROUND: Pulmonary fibrosis is a progressive and irreversible disease for which therapeutic options are currently limited. A recent in vivo study showed that tenofovir, a nucleotide analogue reverse transcriptase inhibitor, had direct antifibrotic effects on skin and liver fibrosis. Another study in vitro revealed that NS5ATP9 inhibited the activation of human hepatic stellate cells. Because of the similarity of fibrotic diseases, we hypothesized that tenofovir alafenamide fumarate (TAF), the prodrug of tenofovir, and NS5ATP9, is related to and plays a role in the suppression of pulmonary fibrosis. METHODS: We investigated the influence of NS5ATP9 on fibrosis in vitro. Human lung fibroblasts (HFL1) were transfected with short interfering RNAs or overexpression plasmids of NS5ATP9 before stimulation by human recombinant transforming growth factor-ß1. The effect of TAF was evaluated in a bleomycin-induced fibrosis murine model. Male C57BL/6 mice were treated with bleomycin on day 0 by intratracheal injection and intragastrically administered TAF or vehicle. Left lung sections were fixed for histological analysis, while homogenates of the right lung sections and HFL1 cells were analyzed by western blotting and quantitative reverse transcription polymerase chain reaction. RESULTS: NS5ATP9 suppressed the activation of lung fibroblasts. Upregulation of collagen type 3 (α 1 chain) and α-smooth muscle actin was observed in HFL1 cells when NS5ATP9 was silenced, and vice-versa. TAF also showed anti-fibrotic effects in mice, as demonstrated by histological analysis of fibrosis and expression of extracellular matrix components in the lung sections. Additionally, TAF inhibited transforming growth factor-ß1 and phosphorylated-Smad3 synthesis in HFL1 cells and the murine model, which was accompanied by upregulation of NS5ATP9. CONCLUSIONS: Our results suggest that NS5ATP9 forms a negative feedback pathway in pulmonary fibrosis and TAF has anti-fibrotic properties as it upregulates the expression level of NS5ATP9. As TAF has been shown to be safe and well-tolerated in humans, TAF and NS5ATP9 may be useful for developing novel therapeutics for pulmonary fibrosis.


Assuntos
Adenina/análogos & derivados , Bleomicina/toxicidade , Proteínas de Ligação a DNA/biossíntese , Fibrose Pulmonar/metabolismo , Proteína Smad3/biossíntese , Fator de Crescimento Transformador beta1/biossíntese , Adenina/farmacologia , Adenina/uso terapêutico , Alanina , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Tenofovir/análogos & derivados , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
13.
Gynecol Oncol ; 154(3): 583-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31307665

RESUMO

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) in locally advanced cervical cancer (LACC) patients treated with neoadjuvant concurrent chemoradiation (CCRT) or radiation (RT) alone followed by radical surgery (RS). METHODS: In a single-center retrospective study from a prospective database, 275 FIGO Stage IB2-IIIB patients who underwent CCRT/RT + RS were included. HRQOL was prospectively assessed by EORTC QLQ-C30 and EORTC QLQ-CX24 prior to any treatment (baseline) and 6 months after surgery, respectively. RESULTS: A statistically significant and clinically relevant improvement in physical functioning (P < 0.001) and role functioning (P = 0.002, P = 0.031) was observed in patients receiving either CCRT+RS or RT + RS at follow-up. In addition, quality of life (QoL), physical functioning, and social functioning were better in the RT + RS group than the CCRT+RS group after treatment (P = 0.028, P = 0.010, P = 0.014). Symptom scores of fatigue decreased in both groups over time (P < 0.001, P = 0.004) while insomnia decreased only in the RT + RS group (P = 0.042). Worsened menopausal symptoms were documented in both groups at follow-up (P = 0.001, P = 0.047), while lymphedema was deteriorated only in patients receiving CCRT + RS (P < 0.001). Sexuality scores did not differ between groups or over time with the exception of sexual worry, which was deteriorated in patients receiving RT + RS (P = 0.042). CONCLUSIONS: QLQ-C30 functioning and tumor-related symptoms scores improved while lymphedema and menopausal symptoms worsened 6 months after neoadjuvant CCRT or RT alone followed by RS in LACC patients. Patients treated with RT + RS had a generally better HRQOL compared with those receiving CCRT+RS, though further validation with prospective randomized clinical trials is warranted.


Assuntos
Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Qualidade de Vida , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias do Colo do Útero/fisiopatologia , Neoplasias do Colo do Útero/cirurgia
14.
BMC Med Imaging ; 19(1): 36, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046697

RESUMO

BACKGROUND: Low-grade myofibroblastic sarcoma (LGMS) is a rare type of tumor. Previous research has paid much attention to reporting pathological analyses of LGMS. However, only few systematic clinical and/or radiological studies have been conducted. METHODS: This study recruited 14 cases (8 males and 6 females) of LGMS. X-ray or computer tomography (CT) scan were performed on 11 cases. MRI was performed on 5 cases. RESULTS: X-Ray and CT scan: Five cases developed LGMS in bones, including 3 cases in the distal femur, 1 in the right shoulder blade, and another 1 in the right inferior ramus. Massive infiltrative and vermiform bone destruction with poorly-circumscribed lesion margins and partial soft tissue masses were observed. The other 9 cases were developed in soft tissues. Out of them, 4 cases presented slightly irregular hyper- or lower-density masses with poorly-circumscribed margins. 2 cases presented massive calcification and ossification. Significant enhancement was observed in 1 case, while no obvious enhancement was seen in the other 2 cases. MRI: MR images of 5 cases revealed homogeneous iso- or hyper-signal intensity on T1WI and homogeneous or heterogeneous hyper-signal intensity on T2WI. Enhanced MRI revealed homogeneous enhancement in 2 cases and rim enhancement in 1 case. CONCLUSIONS: Our findings show that LGMS is characterized by invasiveness, metastases and calcification. Different radiological tools should be employed to make an accurate diagnosis.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Neoplasias de Tecido Muscular/diagnóstico por imagem , Neoplasias Ósseas/patologia , Calcinose/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias de Tecido Muscular/patologia , Tomografia Computadorizada por Raios X
16.
Molecules ; 23(4)2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29570685

RESUMO

A series of novel fused heterocyclic compounds bearing benzo[4,5]imidazo[1,2-d][1,2,4]triazine 4a-4w were designed and conveniently synthesized via the intermediates 2-(halogenated alkyl)-1H-benzo[d]imidazoles 2a, 2b, and 2-((1-(substituted phenyl)hydrazinyl)alkyl)-1H-benzo[d]imidazoles 3a-3g. The structures of all target compounds were characterized by FT-IR, ¹H NMR, 13C NMR, and EI-MS, of which, the structure of compound 4n was further determined by the single crystal X-ray diffraction. The crystal structure of 4n was crystallized in the triclinic crystal system, space group P 1 ¯ with a = 9.033 (6) Å, b = 10.136 (7) Å, c = 10.396 (7) Å, α = 118.323 (7)°, ß = 91.750 (8)°, γ = 104.198 (7)°, Z = 2, V = 800.2 (9) ų; total R indices: R1 = 0.0475, wR2 = 0.1284. The antifungal activity of title compounds 4a-4w in vitro against the phytopathogenic fungi Botrytis cinerea (B. cinerea), Rhizoctonia solani (R. solani) and Colletotrichum capsici (C. capsici) were evaluated, the bioassay results demonstrated that most of the title compounds exhibited obvious fungicidal activities at 50 µg/mL. This work indicated that benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives could be considered as a new leading structure in searching for novel agricultural fungicides.


Assuntos
Antifúngicos/farmacologia , Antifúngicos/química , Botrytis/efeitos dos fármacos , Cristalografia por Raios X , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Espectrometria de Massas por Ionização por Electrospray , Relação Estrutura-Atividade
17.
Opt Lett ; 42(15): 3020-3023, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957234

RESUMO

In order to improve the performance of transparent conductive Al-doped ZnO (AZO)/Cu/Al-doped ZnO multilayer thin films, multilayer thin films of titanium-embedded AZO/Cu/AZO structures have been designed and deposited onto flexible polycarbonate substrates to develop an indium-free transparent flexible electrode. The effect of Ti layer on the structural, optical, and electrical properties of multilayer thin films was investigated. The experiments reveal that the AZO/Ti/Cu/AZO fabricated in argon-oxygen mixtures has the best performance (commutation quality factor of 422.0): resistivity of 3.85×10-5 Ω·cm, sheet resistance of 4.31 Ω/sq, carrier concentration of 1.65×1022 cm-3, mobility of 9.87 cm2/Vs, and acceptable luminous transmittance of above 82% in the visible range.

18.
Phys Chem Chem Phys ; 17(26): 16692-8, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26063124

RESUMO

(Nd1-xLax)NbO4 ceramics were prepared via a conventional solid-state reaction route and the correlations among bond ionicity, lattice energy, phase stability and microwave dielectric properties were investigated. The diffraction patterns showed that the (Nd1-xLax)NbO4 ceramics possessed a monoclinic fergusonite structure. The chemical bond ionicity, bond covalency and lattice energy were calculated using the empirical method. The phase structure stability varied with the lattice energy which resulted due to the substitution content of La(3+) ions. With the increase of La(3+) ion contents, the decrease of Nd/La-O bond ionicity was observed, which could be attributed to the electric polarization. εr has a close relationship with the Nd/La-O bond covalency. The increase of the Q × f values and τf values could be attributed to the change in the lattice energy. The microwave dielectric properties of (Nd1-xLax)NbO4 ceramics with a monoclinic fergusonite structure were strongly dependent on the chemical bond ionicity, bond covalency and lattice energy.

19.
Medicine (Baltimore) ; 103(20): e38112, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758904

RESUMO

RATIONALE: Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case. PATIENT CONCERNS: A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days. DIAGNOSES: TTP. INTERVENTIONS: At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective. OUTCOMES: The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged. LESSONS SUBSECTIONS: The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.


Assuntos
Troca Plasmática , Complicações Hematológicas na Gravidez , Púrpura Trombocitopênica Trombótica , Humanos , Feminino , Gravidez , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Púrpura Trombocitopênica Trombótica/complicações , Troca Plasmática/métodos , Adulto Jovem , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia
20.
ACS Appl Mater Interfaces ; 16(30): 40111-40122, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39031063

RESUMO

The conceptualization and deployment of electrode materials for rechargeable sodium-ion batteries are key concerns for next-generation energy storage systems. In this contribution, the configuration stability of single-layer GeSiBi2 is systematically discussed based on first-principles calculations, and its potential as an anode material is further investigated. It is demonstrated that the phonon spectrum confirms the dynamic stability and the adsorption energy identifies a strong interaction between Na atoms and the substrate material. The electronic bands indicative of inherent metallicity contribute to the enhancement of electronic conductivity after Na adsorption. The multilayer adsorption of Na provides a theoretical capacity of 361.7 mAh/g, which is comparable to that of other representative two-dimensional anode materials. Moreover, the low diffusion barriers of 0.19 and 0.15 eV further guarantee the fast diffusion kinetics. These contributions signal that GeSiBi2 can be a compatible candidate for sodium-ion batteries anodes.

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