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1.
Small ; 19(46): e2303876, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37469229

RESUMEN

Inadequate photo-generated charge separation, migration, and utilization efficiency limit the photocatalytic efficiency. Herein, a MoS2 /MIL-53(Fe) photocatalyst/activator with the S-scheme heterojunction structure is designed and the charge migration behavior is modulated by the internal electric field (IEF). The IEF intensity is enhanced to 40 mV by modulating band bending potential and the depletion layer length of MoS2 . The photo-generated electron migration process is boosted by constructing the electron migration bridge (Fe-O-S) and modulating the IEF as the driving force, confirmed by the density functional theory calculation. Compared with the pristine materials, the photocurrent density of MoS2 /MIL-53(Fe) is significantly enhanced 27.5 times. Contributed by the visible-light-driven cooperative catalytic degradation and the high-efficiency direct photo-generated electron reduction dichlorination process, satisfactory chlorinated antibiotics removal and detoxification performances are achieved. This study opens up new insights into the application of heterojunctions in photocatalytic activation of PDS in environmental remediation.

2.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34445669

RESUMEN

Coronavirus Disease 2019 (COVID-19) remains a global health crisis, despite the development and success of vaccines in certain countries. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, uses its spike protein to bind to the human cell surface receptor angiotensin-converting enzyme 2 (ACE2), which allows the virus to enter the human body. Using our unique cell screening technology, we identified two ACE2-binding peptoid compounds and developed dimeric derivatives (ACE2P1D1 and ACE2P2D1) that effectively blocked spike protein-ACE2 interaction, resulting in the inhibition of SARS-CoV-2 pseudovirus entry into human cells. ACE2P1D1 and ACE2P2D1 also blocked infection by a D614G mutant pseudovirus. More importantly, these compounds do not decrease ACE2 expression nor its enzyme activity (which is important in normal blood pressure regulation), suggesting safe applicability in humans.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , COVID-19/prevención & control , Peptidil-Dipeptidasa A/metabolismo , Peptoides/farmacología , SARS-CoV-2/efectos de los fármacos , Internalización del Virus/efectos de los fármacos , COVID-19/virología , Humanos , Células MCF-7 , Peptoides/metabolismo , Unión Proteica/efectos de los fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tratamiento Farmacológico de COVID-19
3.
Angew Chem Int Ed Engl ; 60(18): 10273-10278, 2021 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-33684258

RESUMEN

The receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike (S) protein plays a central role in mediating the first step of virus infection to cause disease: virus binding to angiotensin-converting enzyme 2 (ACE2) receptors on human host cells. Therefore, S/RBD is an ideal target for blocking and neutralization therapies to prevent and treat coronavirus disease 2019 (COVID-19). Using a target-based selection approach, we developed oligonucleotide aptamers containing a conserved sequence motif that specifically targets S/RBD. Synthetic aptamers had high binding affinity for S/RBD-coated virus mimics (KD ≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC50 ≈5 nM). Importantly, aptamers were able to neutralize S protein-expressing viral particles and prevent host cell infection, suggesting a promising COVID-19 therapy strategy.


Asunto(s)
Enzima Convertidora de Angiotensina 2/metabolismo , Antivirales/farmacología , Aptámeros de Nucleótidos/farmacología , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Antivirales/química , Aptámeros de Nucleótidos/química , Secuencia de Bases , COVID-19/metabolismo , Células HEK293 , Humanos , Dominios y Motivos de Interacción de Proteínas/efectos de los fármacos , Mapas de Interacción de Proteínas/efectos de los fármacos , SARS-CoV-2/química , SARS-CoV-2/fisiología , Glicoproteína de la Espiga del Coronavirus/química
4.
BMC Geriatr ; 19(1): 214, 2019 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-31390985

RESUMEN

BACKGROUND: Hearing loss is one of the most common modifiable factors associated with cognitive and functional decline in geriatric populations. An accurate, easy-to-apply, and inexpensive hearing screening method is needed to detect hearing loss in community-dwelling elderly people, intervene early and reduce the negative consequences and burden of untreated hearing loss on individuals, families and society. However, available hearing screening tools do not adequately meet the need for large-scale geriatric hearing detection due to several barriers, including time, personnel training and equipment costs. This study aimed to propose an efficient method that could potentially satisfy this need. METHODS: In total, 1793 participants (≥60 years) were recruited to undertake a standard audiometric air conduction pure tone test at 4 frequencies (0.5-4 kHz). Audiometric data from one community were used to train the decision tree model and generate a pure tone screening rule to classify people with or without moderate or more serious hearing impairment. Audiometric data from another community were used to validate the tree model. RESULTS: In the decision tree analysis, 2 kHz and 0.5 kHz were found to be the most important frequencies for hearing severity classification. The tree model suggested a simple two-step screening procedure in which a 42 dB HL tone at 2 kHz is presented first, followed by a 47 dB HL tone at 0.5 kHz, depending on the individual's response to the first tone. This approach achieved an accuracy of 91.20% (91.92%), a sensitivity of 95.35% (93.50%) and a specificity of 86.85% (90.56%) in the training dataset (testing dataset). CONCLUSIONS: A simple two-step screening procedure using the two tones (2 kHz and 0.5 kHz) selected by the decision tree analysis can be applied to screen moderate-to-profound hearing loss in a community-based geriatric population in Shanghai. The decision tree analysis is useful in determining the optimal hearing screening criteria for local elderly populations. Implanting the pair of tones into a well-calibrated sound generator may create a simple, practical and time-efficient screening tool with high accuracy that is readily available at healthcare centers of all levels, thereby facilitating the initiation of extensive nationwide hearing screening in older adults.


Asunto(s)
Árboles de Decisión , Evaluación Geriátrica/métodos , Pérdida Auditiva/diagnóstico , Vida Independiente , Tamizaje Masivo/métodos , Vigilancia de la Población/métodos , Anciano , Anciano de 80 o más Años , Audiometría de Tonos Puros/métodos , Audiometría de Tonos Puros/tendencias , China/epidemiología , Femenino , Pérdida Auditiva/epidemiología , Humanos , Vida Independiente/tendencias , Masculino , Tamizaje Masivo/tendencias , Persona de Mediana Edad
5.
BMC Cancer ; 15: 964, 2015 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-26674012

RESUMEN

BACKGROUND: Many commonly used xenograft tumor models do not spontaneously metastasize to distant organs following subcutaneous or orthotopic implantation, limiting their usefulness in preclinical studies. It is generally believed that natural killer cells are the key component of the innate immune system in determining tumor metastatic potential in xenograft models. However, recent studies suggest that macrophages may play an important role, as resident macrophages can eliminate the invading tumor cells if they do not express adequate levels of the CD47 molecule. METHODS: We investigated the effect of overexpressing murine CD47 (mCD47) in PC-3 cells, a commonly used human prostate cancer line, on the metastatic potential in three mouse strains with different genetic background and varying degrees of immunodeficiency. We implanted the tumor cells either subcutaneously or orthotopically and then examined their local and distant metastases. RESULTS: Our results show that mCD47-expressing PC-3 cells subcutaneously implanted in NSG and CB17. Scid mice metastasized to the sentinel lymph node, lung and liver significantly more efficiently than the control cells. When implanted orthotopically to NOD. Scid mice, these cells spontaneously metastasized to lung and liver. CONCLUSIONS: Our data demonstrate that mCD47 can facilitate human tumor cell metastasis in murine models, and that these mCD47-expressing tumor cells may be useful for in vivo studies where spontaneous metastases are desirable.


Asunto(s)
Antígeno CD47/biosíntesis , Modelos Animales de Enfermedad , Neoplasias de la Próstata/patología , Animales , Antígeno CD47/inmunología , Línea Celular Tumoral , Separación Celular , Citometría de Flujo , Xenoinjertos , Humanos , Macrófagos/inmunología , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Invasividad Neoplásica/inmunología , Trasplante de Neoplasias , Neoplasias de la Próstata/inmunología , Transfección
6.
J Reprod Immunol ; 162: 104213, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38364342

RESUMEN

Endometriosis (EMS) is known to be closely associated with inflammation. We evaluate the possible mechanism linking the PI3K/AKT signaling pathway with pyroptosis and inflammation in EMS. We collected 30 patients undergoing laparoscopic for endometriosis as the EMS group and those undergoing surgery for uterine fibroids as the control group, from whom we collected serum, normal endometrium, eutopic endometrium and ectopic endometrium. Transmission electron microscopy (TEM) was used to observe the internal structure of endometrial cells. Western Blot was used to detect the protein expression of PI3K, P-PI3K, AKT, P-AKT, NLRP3, Caspase-1, GSDMD, and GSDMD-N. Immunohistochemistry (IHC) staining was used to detect the expression of PI3K, AKT, NLRP3, Caspase-1, GSDMD, and GSDMD-N proteins. Immunofluorescence (IF) staining was used to observe the expression of GSDMD-N. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the mRNA levels of PI3K, AKT, NLRP3, Caspase-1, GSDMD, and GSDMD-N. ELISA was used to detect serum levels of IL-1ß, IL-18, TLR4, and NF-κB. We found that activation of PI3K/AKT signaling pathway in endometriosis significantly increased the level of cellular pyroptosis and inflammatory factors. Our results suggest that there is a positive correlation between the PI3K/AKT signaling pathway and pyroptosisas well as inflammation in EMS patients.


Asunto(s)
Endometriosis , Piroptosis , Femenino , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Inflamación , Caspasa 1 , Transducción de Señal
7.
J Clin Med ; 13(12)2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38930025

RESUMEN

Objective: The objective of this work was to assess the effect of physical therapy in patients with somatosensory tinnitus (ST) and explore the influence of physical therapy on clinical variables obtained before treatment. Methods: A total of 43 patients with ST were randomized to the immediate-start group (n = 20) and delayed-start group (n = 23). All patients received physical therapy for 1 week (seven sessions). Each session lasted 60 min. The Visual Analogue Scale (VAS), Tinnitus Handicap Inventory (THI), and numerical pain rating scale (NPRS) scores were documented at baseline and after treatment (week 1) for all patients. For subjects in the immediate-start group, the THI, VAS, and NPRS scores were measured after therapy (weeks 6, 9, and 12, respectively). Medical history characteristic functional activity scale (HCFA) scores were measured at baseline to assess the association between somatic symptoms and tinnitus. Results: At week 1, VAS, THI, and NPRS scores of patients in the immediate-start group were improved by 1.25 ± 1.59, 11.10 ± 15.10, and 0.95 ± 1.54 points, respectively, and were significantly higher than those in the delayed-start group (p < 0.05). The change in VAS, THI, and NPRS scores in the treatment group was significantly positively correlated with the scores of the HCFA before treatment (r = 0.786, p < 0.001; r = 0.680, p = 0.001; r = 0.796, p < 0.001). There was no significant difference in THI, VAS, and NPRS scores among patients in the immediate-start group between weeks 1, 6, 9, and 12 after treatment (p > 0.05). Conclusions: Although more participants were necessary in the further study, the study implies that physical therapy can reduce physical pain, improve tinnitus symptoms, and quality of life in ST patients without hearing loss, and the short-term curative effect is stable, especially for tinnitus patients with clear somatic symptoms.

8.
Int J Cancer ; 133(10): 2483-92, 2013 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23661285

RESUMEN

Converting T cells into tumor cell killers by grafting them with a chimeric antigen receptor (CAR) has shown promise as a cancer immunotherapeutic. However, the inability of these cells to actively migrate and extravasate into tumor parenchyma has limited their effectiveness in vivo. Here we report the construction of a CAR containing an echistatin as its targeting moiety (eCAR). As echistatin has high binding affinity to αvß3 integrin that is highly expressed on the surface of endothelial cells of tumor neovasculature, T cells engrafted with eCAR (T-eCAR) can efficiently lyse human umbilical vein endothelial cells and tumor cells that express αvß3 integrin when tested in vitro. Systemic administration of T-eCAR led to extensive bleeding in tumor tissues with no evidence of damage to blood vessels in normal tissues. Destruction of tumor blood vessels by T-eCAR significantly inhibited the growth of established bulky tumors. Moreover, when T-eCAR was codelivered with nanoparticles in a strategically designed temporal order, it dramatically increased nanoparticle deposition in tumor tissues, pointing to the possibility that it may be used together with nanocarriers to increase their capability to selectively deliver antineoplastic drugs to tumor tissues.


Asunto(s)
Melanoma Experimental/irrigación sanguínea , Melanoma Experimental/terapia , Nanopartículas/administración & dosificación , Linfocitos T/fisiología , Secuencia de Aminoácidos , Animales , Antígenos de Neoplasias/biosíntesis , Antígenos de Neoplasias/genética , Vasos Sanguíneos/patología , Línea Celular , Línea Celular Tumoral , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Integrina alfaVbeta3/metabolismo , Masculino , Melanoma Experimental/metabolismo , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Datos de Secuencia Molecular , Proteínas Mutantes Quiméricas/biosíntesis , Proteínas Mutantes Quiméricas/genética , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Receptores de Antígenos/metabolismo , Linfocitos T/inmunología
9.
Mol Ther ; 20(10): 1871-81, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22692498

RESUMEN

Interferon (IFN) antiviral defense mechanism plays a critical role in controlling virus infection. It thus represents a formidable hurdle for virotherapy. Despite the reported ability of herpes simplex virus (HSV) to counteract this defense, the duration and extent of HSV infection in vivo is still largely dictated by host's IFN activity status. Because the HSV genes that have been reported to block IFN activity mainly act intracellularly, we hypothesized that their inhibitory effect could be enhanced by exploiting a gene whose product acts extracellularly. The B18R gene from vaccinia virus encodes a secreted decoy receptor with a broad antagonizing effect against type I IFNs. We therefore cloned B18R into an HSV-1-based oncolytic virus to generate Synco-B18R. In the presence of increased IFN levels in vitro, Synco-B18R largely retained its oncolytic effect, whereas the tumor-killing ability of the parental virus, Synco-2D, was severely compromised. When injected intratumorally in vivo, Synco-B18R showed significantly greater oncolytic activity than Synco-2D. Our results suggest that incorporation of the vaccinia virus B18R gene can safely potentiate the antitumor effect of an oncolytic HSV, and that similar strategies may be useful with other types of oncolytic viruses.


Asunto(s)
Herpesvirus Humano 1/genética , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , Virus Vaccinia/genética , Proteínas Virales/genética , Animales , Antivirales/farmacología , Línea Celular Tumoral , Chlorocebus aethiops , Clonación Molecular , Femenino , Herpesvirus Humano 1/fisiología , Humanos , Interferones/farmacología , Ratones , Ratones Endogámicos BALB C , Virus Oncolíticos/fisiología , Plásmidos , Recombinación Genética , Células Vero , Replicación Viral
10.
Mol Ther ; 20(2): 339-46, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22146341

RESUMEN

Selective replication in tumor cells is a highly desirable feature for oncolytic viruses. Recent studies have shown that microRNAs (miRNAs) play important roles in controlling gene expression, and that certain tissue-specific miRNAs are frequently downregulated in malignant cells. miR-122 is a liver-specific microRNA. It is abundantly expressed in normal hepatocytes but is absent in many hepatocellular carcinoma (HCC) cells. We hypothesized that expression of an essential viral gene by a liver-specific promoter would initially restrict virus replication to cells of hepatic origin and that adding miR-122 complementary sequences to the viral gene would make the transcripts degradable by miR-122 in normal hepatocytes, thus further confining its replication to HCC. We have constructed such an oncolytic herpes simplex virus by linking the essential viral glycoprotein H gene with the liver-specific apolipoprotein E (apoE)-AAT promoter and by adding the miR-122a complimentary sequence to the 3' untranslated region (3'UTR). To further increase the safety of this virus, complementary sequences from miR-124a and let-7 were also engineered into the same 3'UTR. Designated liver-cancer specific oncolytic virus (LCSOV), it was highly selective in killing HCC cells and in shrinking HCC xenografts. We conclude that LCSOV is a highly specific oncolytic virus that can precisely target HCC.


Asunto(s)
Carcinoma Hepatocelular/terapia , Vectores Genéticos/genética , Neoplasias Hepáticas/terapia , Virus Oncolíticos/genética , Simplexvirus/genética , Tropismo Viral , Animales , Apolipoproteínas E/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular , Chlorocebus aethiops , Femenino , Expresión Génica , Orden Génico , Genes Reporteros , Vectores Genéticos/administración & dosificación , Vectores Genéticos/efectos adversos , Humanos , Hígado/metabolismo , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Desnudos , MicroARNs/genética , Virus Oncolíticos/fisiología , Especificidad de Órganos/genética , Regiones Promotoras Genéticas , Simplexvirus/fisiología , Replicación Viral/genética , Ensayos Antitumor por Modelo de Xenoinjerto
11.
J Ethnopharmacol ; 308: 116277, 2023 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-36806342

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Wenyang Huayu Decoction (BWHD) is a traditional Chinese medicine for tonifying kidney and warming Yang, thereby resolving blood stasis and relieving pain. BWHD can significantly improve the clinical symptoms of patients with endometriosis (EMs), but its mechanism is still unclear. AIM OF THE STUDY: We evaluated the expression and role of the SIRT1-FoxO-1 pathway and autophagy levels in EMs rats. The therapeutic effects and potential therapeutic mechanisms of BWHD were also investigated. METHODS: Twenty rats were randomized into the sham group and eighty rats were used for model establishment by autologous transplantation. After successful modeling, they were randomized into the model, BWHD, EX527+BWHD and EX527 groups, with 20 rats in each group. All rats were intragastrically administered with for 3 weeks. Localization of Sirtuin 1 (SIRT1), Forkhead boxO-1 (FoXO-1), Beclin-1, autophagy-related 5 (Atg5) and autophagy-related 7 (Atg7) was determined by immunohistochemical staining. The expression of the above proteins was determined by Western blot and their messenger RNA (mRNA) levels were detected by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). RESULTS: The protein and mRNA expressions of FoXO-1, Beclin-1, Atg5 and Atg7 in the model group were markedly increased, while that of SIRT1 was markedly decreased relative to the sham group (p < 0.05 and p<0.01, respectively). Results showed that the protein and mRNA expressions of FoXO-1, Beclin-1, Atg5 and Atg7 in eutopic and ectopic endometrium of BWHD group were lower, while SIRT1 expression was higher than in the model group (p < 0.05 and p<0.01, respectively). Furthermore, protein and mRNA expression levels of FoXO-1, Beclin-1, Atg5 and Atg7 in eutopic and ectopic endometrium of EX527 group were higher, while SIRT1 level was significantly lower than in the model group (p < 0.05 and p < 0.01, respectively). The EX527-induced changes in protein and mRNA expressions were reversed in the EX527+BWHD group (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: BWHD inhibits autophagy by up-regulating SIRT1 and down-regulating FoXO-1 expression in EMs via the SIRT1-FoXO-1 signaling pathway. Therefore, it is a potential treatment for EMs.


Asunto(s)
Endometriosis , Humanos , Femenino , Ratas , Animales , Endometriosis/metabolismo , Sirtuina 1/metabolismo , Beclina-1/metabolismo , Autofagia , ARN Mensajero
12.
Mol Ther Methods Clin Dev ; 25: 136, 2022 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-35402631

RESUMEN

[This corrects the article DOI: 10.1016/j.omtm.2021.08.007.].

13.
ACS Nano ; 16(11): 18898-18909, 2022 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-36278901

RESUMEN

Freshwater production is critical in terms of solving the global water shortage. Aiming at improving freshwater production capability and ensuring its quality, an interfacial charge-modulated MoS2/Ti3C2Tx-modified carbon fiber (CF/MoS2/Ti3C2Tx) penetrating electrode is designed. To maximize the desalination and degradation efficiencies of CF/MoS2/Ti3C2Tx, a photocatalytic component is introduced into the membrane capacitive deionization (PMCDI) device. High desalination capability is derived from the lamellar architecture structure of MoS2/Ti3C2Tx. Meanwhile, excellent degradation performance is due to the formation of two photoelctrocatalytic activity centers, directionally generating singlet oxygen (1O2) and hydroxyl radical (•OH). The intercalated Cl- (desalination) as the electron transfer bridge optimizes the charge distribution of MoS2/Ti3C2Tx, reinforcing the photoelectrocatalytic activity (degradation). The formation of the electron-deficient (desalination) and electron-rich (regeneration) regions at the terminated O atom of Ti3C2Tx accelerate the generations of •OH and 1O2, respectively. In perspective, a mutual promotion process of desalination and degradation is achieved for high-efficiency production of high-quality freshwater.

14.
Artículo en Inglés | MEDLINE | ID: mdl-36437825

RESUMEN

Endometriosis has been found to be closely related to autophagy. This study aimed to elucidate the possible mechanism of Bushen Wenyang Huayu Decoction (BWHD) in treating endometriosis (EMs) by targeting TLR4/NF-κB-mediated autophagy. Autologous grafting was used to generate the EMs model in rats. Once the model was developed, BWHD high-dose and low-dose groups received intragastric administration of BWHD, and the gestrinone group served as a positive control. Immunofluorescence labeling and Western blotting were used for the protein expression of toll-like receptor 4 (TLR4), nuclear transcription factor-κB (NF-κB), Beclin-1, and selective autophagy connector protein P62 (P62). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze mRNA levels of TLR4, NF-κB, Beclin-1, and P62. We found that BWHD significantly reduced the size of ectopic lesions in rats with EMs, regulated reproductive hormone levels, and alleviated the cell autophagy level. It suggested that BWHD could be an effective treatment of EMs by targeting TLR4/NF-κB signaling pathway.

15.
Int J Cancer ; 129(6): 1503-10, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21128236

RESUMEN

Oncolytic herpes simplex virus (HSV) is currently in phase III clinical trials for development as a novel therapeutic agent against a broad range of human tumors. Although results have been promising, clinical outcome is likely to be compromised by intrinsic and acquired resistance to HSV replication, leading us to test agents that may overcome this obstacle. We found that, despite showing no effect on HSV replication in tumor cells fully permissive to the virus growth, the mTOR inhibitor rapamycin markedly increased the yield and dissemination of oncolytic HSVs in semipermissive tumor cells. Similar results were obtained in tumor-bearing mice. Co-administration of rapamycin with an HSV-derived oncolytic virus either blocked or reversed the growth of tumor xenografts established from semipermissive human tumor cells, while use of either agent alone produced only transient inhibitory effect. Together, our results suggest that rapamycin could be used to potentiate the activity of oncolytic HSVs against difficult-to-treat human tumors or perhaps to prevent the emergence of resistant tumor cells during virotherapy.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Viroterapia Oncolítica/métodos , Virus Oncolíticos , Simplexvirus , Sirolimus/farmacología , Replicación Viral/efectos de los fármacos , Animales , Línea Celular , Línea Celular Tumoral , Terapia Combinada , Femenino , Humanos , Ratones , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 42(2): 152-6, 2011 Mar.
Artículo en Zh | MEDLINE | ID: mdl-21500543

RESUMEN

OBJECTIVE: To observe the killing effect of recombinant type I herpes simplex virus (HSV-I) with Gibbon ape leukemia virus membrane fusion glycoprotein (GALV.fus) gene on lung adenocarcinoma in vitro and in vivo. METHODS: Recombinant HSV-I plasmids (HSV-UL38P-GALV.fus, HSV-CMVP-GALV.fus, HSV-CMVP-EGFP) was introduced into green monkey kidney cells (Vero) by liposome to amplify the virus, which were propagated in Vero cells and purified by cesium chloride density purification, titrated by TCID50 method. The three recombinant viruses were named as Synco-2, Synco-1 and Baco-1 respectively, and were transfected into lung adenocarcinoma cell line A549 cell and human lung adenocarcinoma xenografts which were established in nude mice subcutaneously to observe the expression and transfection of recombinant plasmids; mice model was divided to A (Control) group, B (Baco-1) group, C (Synco-1) group, D (Synco-2) group and E (Synco-2) group. The antitumor and cytotoxic effects of the virus in vitro or in vivo were investigated simultaneously. RESULTS: Recombinated HSV-I virus were packed successfully, the titre of Baco-1, Synco-1 and Synco-2 were 3 x 10(10) pfu/mL, 1X 10(11) pfu/mL and 4 x 10(10) pfu/mL respectively. The virus produced clear antitumor effects in vitro, the oncolytic activity of Synco-2 and Synco-1 was superior to that of Baco-1 (P < 0.01). The striking antitumor effect was seen when the virus was given subcutaneously in established xenografts in the animals. Tumor volume in Group C and D decreased significantly compared those in Group A and B (P < 0.01). The same result was observed in tumour weight (P < 0.01), and we also find that there was statistical significance between Group C and D in tumour quality at last two weeks (P < 0.01). CONCLUSIONS: The three recombinant HSV-I were packaged, amplificated and purified successfully. Recombinant GALV. fus gene system controlled by special promoter and mediated by available carrier has potent activity against lung cancer both in vitro or in vivo, and maybe a new promising candidate for investigative gene therapy of this malignancy.


Asunto(s)
Terapia Genética/métodos , Herpesvirus Humano 1/metabolismo , Virus de la Leucemia del Gibón/genética , Neoplasias Pulmonares/terapia , Glicoproteínas de Membrana/genética , Proteínas Virales de Fusión/farmacología , Adenocarcinoma/patología , Adenocarcinoma/terapia , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Chlorocebus aethiops , Herpesvirus Humano 1/genética , Humanos , Neoplasias Pulmonares/patología , Glicoproteínas de Membrana/metabolismo , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Transfección , Células Vero , Proteínas Virales de Fusión/genética
17.
Mol Ther Methods Clin Dev ; 23: 78-86, 2021 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-34631928

RESUMEN

The current methods for detecting circulating tumor cells (CTCs) suffer from several drawbacks. We report a novel method that is based on a chimeric virus probe and can detect CTCs with extremely high specificity and sensitivity. Moreover, it exclusively detects live CTCs, and its detection efficacy is not impacted by the variation of epithelial cell adhesion molecule (EpCAM) expression. The chimeric virus probe is composed of a capsid from human papillomavirus that provides the detection with high specificity and an SV40-based genome that can amplify extensively inside CTCs and, hence, endows the detection with high sensitivity. Furthermore, different marker genes can be incorporated into the probe to provide detection with versatility. These unique capabilities will likely improve the validity and utility of this CTC detection in several clinical applications, which is one of the drawbacks suffered by many of the current CTC detection methods.

18.
Mol Ther Methods Clin Dev ; 20: 350-356, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33521163

RESUMEN

Virus neutralization assay is principally conducted by measuring the ability of the antibodies in patient sera to prevent the infection of susceptible cells by the virus. As SARS-CoV-2 is classified as a risk group 3 pathogen, neutralization assay using a live virus needs to be handled in a biosafety level 3 laboratory. To overcome this limitation, pseudotyped viruses have been developed as an alternative for the live SARS-CoV-2. However, one of the issues that we and others have encountered during the production of pseudotyped virus with SARS-CoV-2 spike protein was the low virus yield. In our own experience, we were only able initially to produce a stock with a virus titer that is more than two orders of magnitude lower than what we usually get with a vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vector. We have conducted a series of improvements, including using a C-terminal truncated form of spike protein and a D614G mutated spike. Together, these have led to a significant improvement in the yield of the pseudotyped virus. Finally, our data show that using a high-affinity ACE2-expressing cell line resulted in a reduction in detection sensitivity of the neutralization assay.

19.
Exp Ther Med ; 22(5): 1240, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34539836

RESUMEN

Endometriosis (EM), a benign aseptic inflammatory disease, is associated with the presence of endometrial foci. Pain, one of its typical symptoms, has been reported as a constant stressor, but the etiology and pathogenesis of EM-associated pain are unclear. In the present study, eutopic and ectopic endometrium samples from women with EM (n=50) and normal endometrium samples from control subjects (n=20) were collected. Serum levels of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) and bradykinin (BK) were measured using commercial ELISA kits. The expression of the BKB1 receptor (BKB1R) protein was evaluated by immunohistochemical staining and western blot assay. The mRNA expression of BKB1R was measured by reverse transcription-quantitative PCR. The results revealed that there was a substantial increase in the protein and mRNA expression of BKB1R, as well as the release of PGE2, PGF2α and BK in the blood, in the EM group compared with that in the control group. Moreover, PGE2, PGF2α and BK levels were significantly correlated with each other, as well as with the pain intensity of EM. The increased expression levels of BKB1R protein and mRNA were positively correlated with the pain degree of EM. Thus, these data indicated that BK and BKB1R were involved in the pathological onset of EM-associated pain and that they may play an important role in EM-related pain by inducing PGE2 and PGF2α. The data indicate a potential new therapeutic target for EM-related pain.

20.
Angew Chem Weinheim Bergstr Ger ; 133(18): 10361-10366, 2021 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-34230707

RESUMEN

The receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 spike (S) protein plays a central role in mediating the first step of virus infection to cause disease: virus binding to angiotensin-converting enzyme 2 (ACE2) receptors on human host cells. Therefore, S/RBD is an ideal target for blocking and neutralization therapies to prevent and treat coronavirus disease 2019 (COVID-19). Using a target-based selection approach, we developed oligonucleotide aptamers containing a conserved sequence motif that specifically targets S/RBD. Synthetic aptamers had high binding affinity for S/RBD-coated virus mimics (K D≈7 nM) and also blocked interaction of S/RBD with ACE2 receptors (IC50≈5 nM). Importantly, aptamers were able to neutralize S protein-expressing viral particles and prevent host cell infection, suggesting a promising COVID-19 therapy strategy.

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