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1.
ACS Nano ; 18(35): 24306-24316, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39172688

RESUMO

Tin-lead (Sn-Pb) perovskite solar cells (PSCs) hold considerable potential for achieving efficiencies near the Shockley-Queisser (S-Q) limit. Notably, the inverted structure stands as the preferred fabrication method for the most efficient Sn-Pb PSCs. In this regard, it is imperative to implement a strategic customization of the hole selective layer to facilitate carrier extraction and refine the quality of perovskite films, which requires effective hole selectivity and favorable interactions with Sn-Pb perovskites. Herein, we propose the development of Co-Self-Assembled Monolayers (Co-SAM) by integrating both [2-(9H-carbazol-9-yl)ethyl]phosphonic acid (2PACz) and glycine at the buried contacts. The one-step deposition process employed in the fabrication of the Co-SAM ensures uniform coverage, resulting in a homogeneous surface potential. This is attributed to the molecular interactions occurring between 2PACz and glycine in the processing solution. Furthermore, the amine (-NH2) and ammonium (-NH3+) groups in glycine effectively passivate Sn4+ defects at the buried interface of Sn-Pb perovskite films, even under thermal stress. Consequently, the synergistic buried interface regulation of Co-SAM leads to a power conversion efficiency (PCE) of 23.46%, which outperforms devices modified with 2PACz or glycine alone. The Co-SAM-modified Sn-Pb PSC demonstrates enhanced thermal stability, maintaining 88% of its initial PCE under 65 °C thermal stress for 590 h.

2.
Adv Mater ; : e2404597, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38975985

RESUMO

Photomultiplication (PM)-type organic photodetectors (OPDs), which typically form a homogeneous distribution (HD) of n-type dopants in a p-type polymer host (HD PM-type OPDs), have achieved a breakthrough in device responsivity by surpassing a theoretical limit of external quantum efficiency (EQE). However, they face limitations in higher dark current and slower dynamic characteristics compared to p-n heterojunction (p-n HJ) OPDs due to inherent long lifetime of trapped electrons. To overcome this, a new PM-type OPD is developed that demonstrates ultrafast dynamic properties through a vertical phase separation (VPS) strategy between the p-type polymer and n-type acceptor, referred to as VPS PM-type OPDs. Notably, VPS PM-type OPDs show three orders of magnitude increase in -3 dB cut-off frequency (120 kHz) and over a 200-fold faster response time (rising time = 4.8 µs, falling time = 8.3 µs) compared to HD PM-type OPDs, while maintaining high EQE of 1121% and specific detectivity of 2.53 × 1013 Jones at -10 V. The VPS PM-type OPD represents a groundbreaking advancement by demonstrating the coexistence of p-n HJ and PM modes within a single photoactive layer for the first time. This innovative approach holds the potential to enhance both static and dynamic properties of OPDs.

3.
J Med Virol ; 96(4): e29605, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634474

RESUMO

Interferon lambda (IFNλ), classified as a type III IFN, is a representative cytokine that plays an important role in innate immunity along with type I IFN. IFNλ can elicit antiviral states by inducing peculiar sets of IFN-stimulated genes (ISGs). In this study, an adenoviral vector expression system with a tetracycline operator system was used to express human IFNλ4 in cells and mice. The formation of recombinant adenovirus (rAd-huIFNλ4) was confirmed using immunohistochemistry assays and transmission electron microscopy. Its purity was verified by quantifying host cell DNA and host cell proteins, as well as by confirming the absence of the replication-competent adenovirus. The transduction of rAd-huIFNλ4 induced ISGs and inhibited four subtypes of the influenza virus in both mouse-derived (LA-4) and human-derived cells (A549). The antiviral state was confirmed in BALB/c mice following intranasal inoculation with 109 PFU of rAd-huIFNλ4, which led to the inhibition of four subtypes of the influenza virus in mouse lungs, with reduced inflammatory lesions. These results imply that human IFNλ4 could induce antiviral status by modulating ISG expression in mice.


Assuntos
Antivirais , Influenza Humana , Interferon lambda , Orthomyxoviridae , Animais , Humanos , Camundongos , Antivirais/farmacologia , Imunidade Inata , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Interferon lambda/metabolismo , Interferon lambda/farmacologia , Interferon Tipo I/genética , Interferons/metabolismo , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Vetores Genéticos
4.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396957

RESUMO

This study aimed to identify and evaluate drug candidates targeting the kinase inhibitory region of suppressor of cytokine signaling (SOCS) 3 for the treatment of allergic rhinitis (AR). Utilizing an artificial intelligence (AI)-based new drug development platform, virtual screening was conducted to identify compounds inhibiting the SH2 domain binding of SOCS3. Luminescence assays assessed the ability of these compounds to restore JAK-2 activity diminished by SOCS3. Jurkat T and BEAS-2B cells were utilized to investigate changes in SOCS3 and STAT3 expression, along with STAT3 phosphorylation in response to the identified compounds. In an OVA-induced allergic rhinitis mouse model, we measured serum levels of total IgE and OVA-specific IgE, performed real-time PCR on nasal mucosa samples to quantify Th2 cytokines and IFN-γ expression, and conducted immunohistochemistry to analyze eosinophil levels. Screening identified 20 hit compounds with robust binding affinities. As the concentration of SOCS3 increased, a corresponding decrease in JAK2 activity was observed. Compounds 5 and 8 exhibited significant efficacy in restoring JAK2 activity without toxicity. Treatment with these compounds resulted in reduced SOCS3 expression and the reinstatement of STAT3 phosphorylation in Jurkat T and BEAS-2B cells. In the OVA-induced allergic rhinitis mouse model, compounds 5 and 8 effectively alleviated nasal symptoms and demonstrated lower levels of immune markers compared to the allergy group. This study underscores the promising nonclinical efficacy of compounds identified through the AI-based drug development platform. These findings introduce innovative strategies for the treatment of AR and highlight the potential therapeutic value of targeting SOCS3 in managing AR.


Assuntos
Inteligência Artificial , Rinite Alérgica , Camundongos , Animais , Ovalbumina , Mucosa Nasal/metabolismo , Citocinas/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Imunoglobulina E/metabolismo , Camundongos Endogâmicos BALB C , Modelos Animais de Doenças
5.
Food Chem Toxicol ; 185: 114446, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38244666

RESUMO

The aberrant increase or dysregulation of cytosolic Zn2+ concentration ([Zn2+]cyt) has been associated with cellular dysfunction and cytotoxicity. In this study, we postulated that Zn2+ mediates the cytotoxicity of thiol-reactive electrophiles. This notion was grounded on earlier research, which revealed that thiol-reactive electrophiles may disrupt Zn2+-binding motifs, consequently causing Zn2+ to be released from Zn2+-binding proteins, and leading to a surge in [Zn2+]cyt. The thiol-reactive electrophiles N-ethylmaleimide (NEM) and diamide were observed to induce an increase in [Zn2+]cyt, possibly through the impairment of Zn2+-binding motifs, and subsequent stimulation of reactive oxygen species (ROS) formation, resulting in cytotoxicity in primary cultured rat vascular smooth muscle cells. These processes were negated by the thiol donor N-acetyl-L-cysteine and the Zn2+ chelator TPEN. Similar outcomes were detected with co-treatment involving Zn2+ and Zn2+ ionophores such as pyrithione or disulfiram. Moreover, TPEN was found to inhibit cytotoxicity triggered by short-term exposure to various thiol-reactive electrophiles including hydrogen peroxide, acrylamide, acrylonitrile, diethyl maleate, iodoacetic acid, and iodoacetamide. In conclusion, our findings suggest that cytosolic Zn2+ acts as a universal mediator in the cytotoxic effects produced by thiol-reactive electrophiles.


Assuntos
Etilenodiaminas , Compostos de Sulfidrila , Zinco , Ratos , Animais , Compostos de Sulfidrila/metabolismo , Zinco/metabolismo , Músculo Liso Vascular/metabolismo , Citosol , Ácidos/metabolismo
6.
Int J Mol Sci ; 24(24)2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38139201

RESUMO

Chronic rhinosinusitis (CRS) is an inflammation of the nasal and paranasal sinus mucosa, and eosinophilic CRS (eCRS) is a subtype characterized by significant eosinophil infiltration and immune response by T-helper-2 cells. The pathogenesis of eCRS is heterogeneous and involves various environmental and host factors. Proteases from external sources, such as mites, fungi, and bacteria, have been implicated in inducing type 2 inflammatory reactions. The balance between these proteases and endogenous protease inhibitors (EPIs) is considered important, and their imbalance can potentially lead to type 2 inflammatory reactions, such as eCRS. In this review, we discuss various mechanisms by which exogenous proteases influence eCRS and highlight the emerging role of endogenous protease inhibitors in eCRS pathogenesis.


Assuntos
Hipersensibilidade , Rinite , Rinossinusite , Sinusite , Humanos , Rinite/patologia , Peptídeo Hidrolases , Sinusite/patologia , Doença Crônica , Endopeptidases , Inibidores de Proteases , Hipersensibilidade/patologia , Eosinófilos
7.
Emerg Infect Dis ; 29(11): 2275-2284, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37877548

RESUMO

SARS-CoV-2 induces illness and death in humans by causing systemic infections. Evidence suggests that SARS-CoV-2 can induce brain pathology in humans and other hosts. In this study, we used a canine transmission model to examine histopathologic changes in the brains of dogs infected with SARS-CoV-2. We observed substantial brain pathology in SARS-CoV-2-infected dogs, particularly involving blood-brain barrier damage resembling small vessel disease, including changes in tight junction proteins, reduced laminin levels, and decreased pericyte coverage. Furthermore, we detected phosphorylated tau, a marker of neurodegenerative disease, indicating a potential link between SARS-CoV-2-associated small vessel disease and neurodegeneration. Our findings of degenerative changes in the dog brain during SARS-CoV-2 infection emphasize the potential for transmission to other hosts and induction of similar signs and symptoms. The dynamic brain changes in dogs highlight that even asymptomatic individuals infected with SARS-CoV-2 may develop neuropathologic changes in the brain.


Assuntos
COVID-19 , Doenças Neurodegenerativas , Humanos , Animais , Cães , SARS-CoV-2 , COVID-19/veterinária , Encéfalo
8.
Antioxidants (Basel) ; 12(9)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37760035

RESUMO

Smoking is recognized as a significant risk factor for numerous disorders, including cardiovascular diseases, respiratory conditions, and various forms of cancer. While the exact pathogenic mechanisms continue to be explored, the induction of oxidative stress via the production of excess reactive oxygen species (ROS) is widely accepted as a primary molecular event that predisposes individuals to these smoking-related ailments. This review focused on how cigarette smoke (CS) promotes ROS formation rather than the pathophysiological repercussions of ROS and oxidative stress. A comprehensive analysis of existing studies revealed the following key ways through which CS imposes ROS burden on biological systems: (1) ROS, as well as radicals, are intrinsically present in CS, (2) CS constituents generate ROS through chemical reactions with biomolecules, (3) CS stimulates cellular ROS sources to enhance production, and (4) CS disrupts the antioxidant system, aggravating the ROS generation and its functions. While the evidence supporting these mechanisms is chiefly based on in vitro and animal studies, the direct clinical relevance remains to be fully elucidated. Nevertheless, this understanding is fundamental for deciphering molecular events leading to oxidative stress and for developing intervention strategies to counter CS-induced oxidative stress.

9.
Vet Sci ; 9(12)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36548854

RESUMO

Torque teno canis virus (TTCaV) is an approximately 2.8 kb circular single-stranded DNA virus known to cause infections in dogs. However, its incidence in Republic of Korea remains unknown. In this study, 135 dog fecal samples were collected to determine TTCaV infection status in Republic of Korea. Based on polymerase chain reaction (PCR) analysis, 13 of 135 (9.6%) dogs tested positive for TTCaV. Three full-length genome sequences (GenBank IDs: MZ503910, MZ503911, and MZ503912) were obtained from the positive specimens. Phylogenetic tree construction and sequence identity, similarity plot, and recombination analyses were performed using these three full-length genomic sequences. Among the three full-length genomes, MZ503912 was determined to be a recombinant virus based on analysis with the reference TTCaV strains. This novel virus strain might have been generated by recombination between TTCaV strain KX827768 discovered in China and MZ503910 discovered in Republic of Korea. This is the first report to determine the incidence, genetic variation, and recombination of TTCaV in dogs in Republic of Korea. Further studies are needed to elucidate TTCaV pathogenesis in dogs.

10.
Vet Res Commun ; 46(4): 1363-1368, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36155869

RESUMO

Canine coronavirus (CCoV), canine parvovirus (CPV), and canine distemper virus (CDV) are highly contagious canine pathogens; dogs with these diseases are difficult to treat. In a previous study, we developed a recombinant adenovirus expressing canine interferon lambda 3 (Ad-caIFNλ3) in canine epithelial cells. In this study, we aimed to investigate the antiviral activity of Ad-caIFNλ3 against CCoV, CPV, and CDV in two canine cell lines, A72 and MDCK. Ad-caIFNλ3 transduction suppressed replication of these viruses without cytotoxicity. Our results suggest that Ad-caIFNλ3 may be a therapeutic candidate for canine viral diseases.


Assuntos
Infecções por Adenoviridae , Coronavirus Canino , Vírus da Cinomose Canina , Cinomose , Doenças do Cão , Infecções por Parvoviridae , Parvovirus Canino , Cães , Animais , Parvovirus Canino/genética , Vírus da Cinomose Canina/genética , Coronavirus Canino/genética , Adenoviridae , Antivirais , Infecções por Parvoviridae/veterinária , Anticorpos Antivirais , Infecções por Adenoviridae/veterinária
11.
Vaccines (Basel) ; 10(7)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35891218

RESUMO

We investigated the cross-species transmission of rabbit hepatitis E virus (rb HEV) to pigs and evaluated the cross-protection of a swine (sw) HEV-3 virus-like particle (VLP) vaccine against rb HEV infection in pigs. Twelve 4-week-old conventional pigs were divided into negative control (n = 3), positive control (rb HEV-infected, n = 4), and vaccinated (vaccinated and rb HEV-challenged, n = 5) groups. The vaccine was administered at weeks 0 and 2, and viral challenge was conducted at week 4. Serum HEV RNA, anti-HEV antibody, cytokine, and liver enzyme levels were determined. Histopathological lesions were examined in abdominal organs. Viral RNA was detected and increased anti-HEV antibody and alanine aminotransferase (ALT) levels were observed in positive control pigs; liver fibrosis, inflammatory cell infiltration in the lamina propria of the small intestine and shortened small intestine villi were also observed. In vaccinated pigs, anti-HEV antibody and Th1 cytokine level elevations were observed after the second vaccination; viral RNA was not detected, and ALT level elevations were not observed. The results verified the cross-species transmission of rb HEV to pigs and cross-protection of the sw HEV-3 VLP vaccine against rb HEV infection in pigs. This vaccine may be used for cross-protection against HEV infection in other species.

12.
Viruses ; 14(7)2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35891413

RESUMO

Here, rabbits were immunized with a virus-like particle (VLP) vaccine prepared by expressing 239 amino acids of the swine hepatitis E virus (HEV)-3 capsid protein using a baculovirus system. Thirty specific-pathogen-free rabbits were divided into five groups (negative and positive control and 10, 50, and 100 µg VLP-vaccinated). Positive control group rabbits showed viremia and fecal viral shedding, whereas rabbits vaccinated with 10 µg VLP showed transient fecal viral shedding, and rabbits vaccinated with 50 and 100 µg VLP did not show viremia or fecal viral shedding. Serum anti-HEV antibody titers increased in a dose-dependent manner. Anti-HEV antibody titers were significantly higher (p < 0.05) in 100 µg VLP-vaccinated rabbits than in the negative control rabbits at week 4. Anti-HEV antibody titers were significantly higher in 50 and 10 µg VLP-vaccinated rabbits than in the negative control rabbits at weeks 8 and 11, respectively. Serum IFN-γ and IL-12 levels were significantly higher (p < 0.01) in rabbits vaccinated with 50 and 100 µg VLP than in the negative control rabbits at weeks 4 and 6. Liver tissues of 50 and 100 µg VLP-vaccinated rabbits displayed significantly less (p < 0.05) fibrosis than those of the positive control rabbits. The prepared VLP vaccine demonstrated dose-dependent immunogenicity sufficient for inducing anti-HEV antibody production, thus protecting rabbits against swine HEV-3.


Assuntos
Vírus da Hepatite E , Hepatite E , Vacinas de Partículas Semelhantes a Vírus , Animais , Anticorpos Antivirais , Anticorpos Anti-Hepatite , Imunização , Coelhos , Suínos , Viremia/prevenção & controle
13.
Sci Rep ; 11(1): 21462, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728736

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Heme Oxigenase-1/metabolismo , Hemina/uso terapêutico , Animais , Antivirais/química , Antivirais/farmacologia , COVID-19/virologia , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Heme Oxigenase-1/antagonistas & inibidores , Heme Oxigenase-1/genética , Hemina/química , Hemina/farmacologia , Humanos , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia , Regulação para Cima/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacos
14.
Vaccines (Basel) ; 9(11)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34835195

RESUMO

In this study, we generated the HEV virus-like particle (VLP) vaccine expressing 239 amino acids (367-605 aa) of the HEV-3 ORF2 using the baculovirus expression system. The HEV-3-239-VLP vaccine efficacy was evaluated by dividing 12 pathogen-free pigs into four groups: negative control, positive control, 100 µg VLP-, and 200 µg VLP-vaccinated groups for 10 weeks. The pigs in either of the vaccinated groups were administered the corresponding first and booster doses on weeks 0 and 2. At week 4, the positive control and two vaccinated groups were challenged with 106 HEV-3 genomic equivalent copies; viremia and fecal shedding of the virus were identified in pigs in the positive control and 100 µg VLP-vaccinated pigs showed transient viremia and fecal viral shedding. However, no viruses were detected in the serum or fecal samples of the 200 µg VLP-vaccinated pigs. The 100 and 200 µg VLP-vaccinated pigs had significantly higher (p < 0.01) anti-HEV antibodies than the negative control pigs from weeks 6-10 with normal levels of liver enzymes. The 200 µg VLP-vaccinated pigs showed statistically less liver tissue fibrosis (p < 0.05) than that of the positive control pigs. Thus, the novel baculovirus expression system-generated VLP vaccine dose-dependently protects against HEV-3 challenge and may be useful in other animal species, including humans.

15.
Sci Rep ; 11(1): 20152, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635731

RESUMO

Treatment outcomes between FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and GNP (gemcitabine with albumin-bound paclitaxel) as first-line chemotherapy regimens for metastatic pancreatic cancer (PC) were assessed according to ethnic groups categorized as Western or Asian subgroups. PubMed, EMBASE, and Cochrane library were searched. Thirteen studies were eligible in this meta-analysis. Overall survival was not significantly different between FOLFIRINOX and GNP (HR 1.00, 95% CI 0.83-1.20, P = 0.990). However, the Western subgroup showed a higher survival benefit for FOLFIRINOX over GNP (HR 0.84, 95% CI 0.74-0.95, P = 0.006) whereas the Asian subgroup showed the survival benefit for GNP over FOLFIRINOX (HR 1.29, 95% CI 1.03-1.60, P = 0.030). Progression free survival was not significantly different between the two regimens in the Western subgroup (HR 1.01, 95% CI 0.84-1.20, P = 0.950) and the Asian subgroup (HR 1.13, 95% CI 0.97-1.33, P = 0.110). Occurrence of febrile neutropenia was significantly higher in FOLFIRINOX at both ethnic subgroups; however, that of peripheral neuropathy was significantly higher only in GNP of the Asian subgroup. Therefore, pharmacoethnicity might be a factor worth considering when deciding on a frontline chemotherapeutic regimen although the overall survival was not significantly different between FOLFIRINOX and GNP for metastatic PCs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etnicidade/estatística & dados numéricos , Neoplasias Pancreáticas/tratamento farmacológico , Albuminas/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Metástase Neoplásica , Oxaliplatina/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/etnologia , Neoplasias Pancreáticas/patologia , Resultado do Tratamento , Gencitabina
16.
Pharmaceutics ; 13(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34452191

RESUMO

Hepatitis A virus (HAV), the causative pathogen of hepatitis A, induces severe acute liver injuries in humans and is a serious public health concern worldwide. However, appropriate therapeutics have not yet been developed. The enzyme heme oxygenase-1 (HO-1) exerts antiviral activities in cells infected with several viruses including hepatitis B and C viruses. In this study, we demonstrated for the first time the suppression of virus replication by HO-1 in cells infected with HAV. Hemin (HO-1 inducer) induced HO-1 mRNA and protein expression, as expected, and below 50 mM, dose-dependently reduced the viral RNA and proteins in the HAV-infected cells without cytotoxicity. Additionally, HO-1 protein overexpression using a protein expression vector suppressed HAV replication. Although ZnPP-9, an HO-1 inhibitor, did not affect HAV replication, it significantly inhibited hemin-induced antiviral activity in HAV-infected cells. Additionally, FeCl3, CORM-3, biliverdin, and the HO-1 inducers andrographolide and CoPP inhibited HAV replication in the HAV-infected cells; andrographolide and CoPP exhibited a dose-dependent effect. In conclusion, these results suggest that HO-1 effectively suppresses HAV infection in vitro, and its enzymatic products appear to exert antiviral activity. We expect that these results could contribute to the development of a new antiviral drug for HAV.

17.
Virus Res ; 296: 198342, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607185

RESUMO

Interferon-lambda (IFN-λ) is a type-III IFN and is considered a candidate of antiviral therapeutics. Although the antiviral effects of IFN-λ have been investigated in several studies, it has not been clinically approved as an antiviral agent. In this study, an adenoviral vector expression system employing a tetracycline-operator system was developed to control the expression of canine IFN-λ3. The antiviral effects of canine IFN-λ3 were determined in Madin-Darby canine kidney cells and canine tracheal epithelial cells. After transducing each cell line with recombinant adenovirus containing canine interferon lambda3 gene (Ad-caIFNλ3), the mRNA-expression of interferon-stimulated genes Mx1, ISG15, and OAS1 increased significantly (P < 0.05). The replication of canine influenza virus (CIV) was significantly suppressed in Ad-caIFNλ3-infected cells. These results indicate that the newly constructed adenoviral vector system could express canine IFN-λ3, which could subsequently inhibit CIV replication in two canine cell lines. These data imply that the recombinant Ad-caIFNλ3 can potentially be used to treat canine influenza and other viral diseases.


Assuntos
Influenza Humana , Orthomyxoviridae , Animais , Antivirais/farmacologia , Cães , Humanos , Interferons/genética , Células Madin Darby de Rim Canino , Orthomyxoviridae/genética , Replicação Viral
18.
Gels ; 6(2)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429228

RESUMO

Two pyrene derivatives having the perylenediimide (1) or the alky chain (2) in the middle of molecules were synthesized. Co-assembled supramolecular gels were prepared at different molar ratios of 0.2, 0.5, and 0.8 equiv. of 2 to 1. By SEM observation, the morphology of co-assembled supramolecular gels changed from spherical nanoparticles to three-dimensional network nanofibers as the ratio of 2 increased. In addition, the pyrene-excimer emission of co-assembled gels increased with increasing concentration of 2, and was stronger when compared with the condition without 1 or 2, indicating the formation of pyrene interaction between 1 and 2. In addition, the sol-gel transition was found to be reversible over repeated measurement by tube inversion method. The rheological properties of co-assembled supramolecular gels were also improved by increasing the ratio of 2, due to the increased nanoscale flexibility of supramolecular packing by introducing alkyl chain groups through heterogeneous pyrene interaction. These findings suggest that macroscale mechanical strength of co-assembled supramolecular gel was strongly influenced by nanoscale flexibility of the supramolecular packing.

19.
Angew Chem Int Ed Engl ; 58(34): 11709-11714, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31243839

RESUMO

We demonstrated the morphology transformation of co-assemblies based on terpyridine-based ligands (1R and 1S) possessing R- or S-alanine analogues and their platinum(II) complex (2R-Pt and 2S-Pt). The right-handed helical ribbon of the co-assembly formed with 0.5 equivalents of 2R-Pt to 1R was converted into the left-handed helical ribbon with 0.6 equivalents of 2R-Pt. The left-handed helical ribbon structure of the co-assembly became a tubular structure in the presence of 0.8-1.0 equivalents of 2R-Pt. The morphology transformation via helical inversion at the supramolecular level was due to an orientation change of the amide groups caused by non-covalent Pt⋅⋅⋅Pt interactions between the terpyridine of 2R-Pt and that of 2R-Pt. This study provides insights into controlling the morphology of the transformation of helical ribbons into tubular structures through helicity inversion in co-assembled supramolecular nanostructures based on platinum(II) complexes.

20.
Korean J Food Sci Anim Resour ; 35(1): 35-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26761798

RESUMO

Super- and sub-critical water treatments have been of interest as novel methods for protein hydrolysis. In the present study, we studied the effect of sub-critical water (Sub-H2O, 300℃, 80 bar) treatment as well as super-critical water (Super-H2O, 400℃, 280 bar) treatment on the physicochemical properties of porcine skin (PS), which has abundant collagen. Porcine skin was subjected to pre-thermal treatment by immersion in water at 70℃, and then treated with sub- or super-critical water. Physicochemical properties of the hydrolysates, such as molecular weight distribution, free amino acid content, amino acid profile, pH, color, and water content were determined. For the molecular weight distribution analysis, 1 kDa hydrolyzed porcine skin (H-PS) was produced by Super-H2O or Sub-H2O treatment. The free amino acid content was 57.18 mM and 30.13 mM after Sub-H2O and Super-H2O treatment, respectively. Determination of amino acid profile revealed that the content of Glu (22.5%) and Pro (30%) was higher after Super-H2O treatment than after Sub-H2O treatment, whereas the content of Gly (28%) and Ala (13.1%) was higher after Sub-H2O treatment. Super-H2O or Sub-H2O treatment affected the pH of PS, which changed from 7.29 (Raw) to 9.22 (after Sub-H2O treatment) and 9.49 (after Super-H2O treatment). Taken together, these results showed that Sub-H2O treatment was slightly more effective for hydrolysis than Super-H2O was. However, both Sub-H2O and Super-H2O treatments were effective processing methods for hydrolysis of PS collagen in a short time and can be regarded as a green chemistry technology.

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