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1.
Front Pharmacol ; 15: 1415265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39323630

RESUMO

Epimedium Folium has been extensively utilized for medicinal purposes in China for a significant period. This review undertakes a comprehensive examination of literature pertaining to Epimedium and its metabolites over the past decade, drawing from databases such as PubMed. Through meticulous organization and synthesis of pertinent research findings, including disease models, pharmacological effects, and related aspects, this narrative review sheds light on the principal pharmacological activities and associated mechanisms of Epimedium in safeguarding the reproductive system, promoting bone health, mitigating inflammation, and combating tumors and viral infections. Consequently, this review contributes to a more profound comprehension of the recent advances in Epimedium research.

2.
Carbohydr Res ; 542: 109205, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38981321

RESUMO

There has been a sudden increase in viral diseases, such as coronavirus disease 2019 (COVID-19), causing significant harm to human and animal well-being, as well as economic development. Medicinal herbs, with a history of thousands of years in clinical use, contain versatile polysaccharides as one of their primary compounds. This review offers an overview of the antiviral effects of polysaccharides from medicinal herbs on viruses in humans, poultry, swine and aquaculture in recent years. The mechanism of these antiviral polysaccharides, involved in hindering various stages of the viral life cycle thereby blocking virus infection, is summarized. The review also explores other underlying mechanisms of antiviral effects, such as enhancing the immune response, regulating inflammatory reactions, balancing gut flora, reducing oxidative stress, and suppressing apoptosis through various corresponding signaling pathways. The structure-function relationships discussed in this article also aid in understanding the antiviral mechanism of natural polysaccharides, indicating the need for more in-depth research and analysis. Natural polysaccharides from medicinal herbs have emerged as valuable resources in the fight against viral infections, exhibiting high effectiveness. This review emphasizes the promising role of polysaccharides from medicinal herbs as potential candidates for blocking viral infections in humans and animals.


Assuntos
Antivirais , Plantas Medicinais , Polissacarídeos , Antivirais/farmacologia , Antivirais/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Humanos , Plantas Medicinais/química , Animais , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
3.
Life Sci ; 352: 122877, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38942358

RESUMO

AIMS: The study evaluated the antiviral effect of Verapamil against respiratory syncytial virus (RSV) and investigated its underlying mechanism. MATERIALS AND METHODS: RSV-infected BALB/c mice were treated with Verapamil. Body weight, survival rates, viral load, lung damage, inflammatory factors, and the expression of RSV fusion (F) protein were analyzed. In cellular studies, intracellular Ca2+ and viral titers were measured in the presence of Verapamil, Calcium Chloride, and EGTA. A time-of-addition assay assessed the antiviral effect of Verapamil. KEY FINDINGS: Mice infected with RSV and treated with Verapamil exhibited a significant decrease in weight loss, an increase in survival rates, and reductions in viral titers, RSV F protein expression, inflammatory responses, and lung tissue injury. Verapamil reduced intracellular calcium levels, which correlated with reduced viral titers. The addition of calcium chloride reversed the anti-viral effects mediated by Verapamil, while EGTA potentiated them. The antiviral activity of Verapamil was observed during the early phase of RSV infection, likely by blocking Ca2+ channels and inhibiting virus replication. SIGNIFICANCE: Verapamil effectively inhibits RSV infection by blocking calcium channels and reducing intracellular calcium levels, thereby impeding viral replication. Thus, Verapamil shows promise as a treatment for RSV.


Assuntos
Antivirais , Cálcio , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial , Verapamil , Verapamil/farmacologia , Animais , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Infecções por Vírus Respiratório Sincicial/metabolismo , Cálcio/metabolismo , Camundongos , Antivirais/farmacologia , Feminino , Replicação Viral/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Humanos , Carga Viral/efeitos dos fármacos , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Pulmão/virologia , Pulmão/metabolismo , Pulmão/efeitos dos fármacos
4.
Antiviral Res ; 226: 105880, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38608838

RESUMO

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.


Assuntos
Antivirais , Micelas , Infecções por Vírus Respiratório Sincicial , Animais , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Camundongos , Antivirais/administração & dosagem , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Administração por Inalação , Fenóis/uso terapêutico , Fenóis/administração & dosagem , Fenóis/farmacologia , Fenóis/química , Pulmão/virologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Feminino , Houttuynia/química , Linhagem Celular
5.
Molecules ; 28(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38067601

RESUMO

Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis. Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds.


Assuntos
Lignanas , Adenosina Trifosfatases , Anti-Inflamatórios/farmacologia , Lactonas , Lignanas/farmacologia , Lignanas/química
6.
J Biomol Struct Dyn ; : 1-11, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38116950

RESUMO

SARS-CoV-2 viral infection is regulated by the host cell receptors ACE2 and TMPRSS2, and therefore the effect of various natural and synthetic compounds on these receptors has recently been the subject of investigations. Cyclodextrins, naturally occurring polysaccharides derived from starch, are soluble in water and have a hydrophobic cavity at their center enabling them to accommodate small molecules and utilize them as carriers in the food, supplements, and pharmaceutical industries to improve the solubility, stability, and bioavailability of target compounds. In the current study, computational molecular simulations were used to investigate the ability of α-, ß- and γ-Cyclodextrins on human cell surface receptors. Cell-based experimental approaches, including expression analyses at mRNA and protein levels and virus replication, were used to assess the effect on receptor expression and virus infection, respectively. We found that none of the three CDs could dock effectively to human cell surface receptor ACE2 and viral protease Mpro (essential for virus replication). On the other hand, α- and ß-CD showed strong and stable interactions with TMPRSS2, and the expression of both ACE2 and TMPRSS2 was downregulated at the mRNA and protein levels in cyclodextrin (CD)-treated cells. A cell-based virus replication assay showed ∼20% inhibition by ß- and γ-CD. Taken together, the study suggested that (i) downregulation of expression of host cell receptors may not be sufficient to inhibit virus infection (ii) activity of the receptors and virus protein Mpro may play a critical and clinically relevant role, and hence (iii) newly emerging anti-Covid-19 compounds warrant multimodal functional analyses.Communicated by Ramaswamy H. Sarma.

7.
J Microorg Control ; 28(3): 83-92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37866900

RESUMO

Norovirus (NoV)is a major causative virus of viral gastroenteritis and requires a general disinfection method because it is resistant to common disinfectants such as ethanol and chlorhexidine. This study aimed to find natural extracts as candidates for versatile disinfectant ingredients. The antiviral effect of natural extracts against NoV can be evaluated using the feline calicivirus (FCV)-inactivation test and NoV virus-like particle (NoV-VLP)-binding inhibition test. In this study, screening of natural extracts with anti- NoV effects was performed using these two methods. Of the 63 natural extracts examined, 14 were found to have high FCV-inactivation and NoV-VLP-binding inhibitory effects. In addition, we evaluated the NoV-VLPbinding inhibitory effect of grape seed extract(GSE)containing proanthocyanidins under multiple concentration conditions and treatment times and determined that the binding inhibitory effect of GSE was concentration- and time-dependent. Electron microscopy showed that GSE-treated NoV-VLPs aggregated, distorted, and swelled, suggesting that GSE directly interacts with NoV particles. The results suggest that some natural extracts containing GSE can be used as components of disinfectants against NoV.


Assuntos
Desinfetantes , Extrato de Sementes de Uva , Norovirus , Proantocianidinas , Animais , Gatos , Extrato de Sementes de Uva/farmacologia , Desinfetantes/farmacologia , Desinfecção , Proantocianidinas/farmacologia
8.
Antivir Ther ; 28(5): 13596535231207499, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37846668

RESUMO

BACKGROUND: Avian infectious bronchitis virus (IBV), a coronavirus, causes a huge economic loss to the poultry industry. Andrographolide (APL) is a compound with a variety of pharmacological properties, including antiviral and anti-inflammatory effects. In this study, APL was evaluated for antiviral activity by its anti-apoptotic, anti-pyroptosis, and anti-inflammatory effects. METHODS: The cytotoxicity of APL was determined by the MTT method. We investigated the therapeutic impact of APL on IBV through a plate assay. We explored that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation in HD11 cells by RT-qPCR and immunofluorescence. Also, it was verified in the clinical chicken embryo trial. RESULTS: We found that APL down-regulated apoptosis-related genes Caspase-3, Caspase-8, Caspase-9, Bax, Bid, and Bak, down-regulated pyroptosis gene DFNA5, and down-regulated inflammation-related genes (NF-κB, NLRP3, iNOS, TNF-α, and IL-1ß). In addition, APL reduced the reactive oxygen species (ROS) production in cells. Finally, clinical trials showed that APL inhibited IBV-induced apoptosis, pyroptosis, and inflammation, as well as reduced the mortality and malformation of chicken embryos. CONCLUSIONS: In this study, we delved into the antiviral properties of APL in the context of chicken macrophage (HD11) infection with IBV. Our findings confirm that andrographolide effectively inhibits apoptosis, pyroptosis, and inflammation by IBV infection. Furthermore, this inhibition was verified on chicken embryos in vivo. This inhibition suggests a substantial potential for APL as a therapeutic agent to mitigate the harmful effects of IBV on host cells.


Assuntos
Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Animais , Embrião de Galinha , Piroptose , Galinhas , Apoptose/genética , Inflamação/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Anti-Inflamatórios/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/veterinária
9.
Toxicon ; 234: 107278, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37683701

RESUMO

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.

10.
J Nat Med ; 77(4): 677-687, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37488321

RESUMO

Type I and III interferons (IFNs) both serve as pivotal components of the host antiviral innate immune system. Although they exert similar antiviral effects, type I IFNs can also activate neutrophil inflammation, a function not born by type III IFNs. Baicalin, the main bioactive component of Scutellariae radix, has been shown to exert therapeutic effects on viral diseases due to its anti-viral, anti-inflammatory and immunomulatory activities. There is uncertainty, however, on the association between the antiviral effects of baicalin and the modulation of anti-viral IFNs production and the immunological effects of type I IFNs. Here, a Poly (I:C)-stimulated A549 cell line was established to mimic a viral infection model. Our results demonstrated that baicalin could elevate the expression of type I and III IFNs and their receptors in Poly (I:C)-stimulated A549 cells. Moreover, the potential regulation effects of baicalin for type I IFN-induced neutrophil inflammation was further explored. Results showed that baicalin diminished the production of the pro-inflammatory cytokines (IL-1ß, IL-6, IL-17 and TNF-α), ROS, and neutrophil extracellular traps and suppressed chemotaxis. Collectively, all these data indicated that baicalin had a dual role on IFNs production and effects: (1) Baicalin was able to elevate the expression of type I and III IFNs and their receptors, (2) and it alleviated type I IFN-mediated neutrophil inflammatory response. This meant that baicalin has the potential to act as an eximious immunomodulator, exerting antiviral effects and reducing inflammation.


Assuntos
Antivirais , Interferon Tipo I , Humanos , Antivirais/farmacologia , Neutrófilos/metabolismo , Interferon Tipo I/metabolismo , Inflamação/tratamento farmacológico
11.
Fish Shellfish Immunol ; 138: 108826, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201732

RESUMO

Herpesviral hematopoietic necrosis disease causes by cyprinid herpesvirus 2 (CyHV-2) infection is a high mortality disease that leads to great economic damage to gibel carp, Carassius auratus gibelio aquaculture. In this study, an attenuated strain of CyHV-2 G-RP7 was achieved by subculture on RyuF-2 cells derived from the fin of Ryukin-variety goldfish and GiCF cells derived from fin of gibel carp. As the attenuated vaccine candidate, there are no clinical symptoms of gibel carp that immersion or intraperitoneal injection with G-RP7 strain. The protection rates of G-PR7 to gibel carp by immersion and intraperitoneal injection were 92% and 100%, respectively. In the test for virulence reversion, the candidate was propagated through gibel carp six times by intraperitoneal injection with kidney and spleen homogenate of the inoculated fish. During in vivo passages in gibel carp, no abnormality and mortality of the inoculated fish were observed, and the virus DNA copies maintain a low level from the first passage to the sixth passage. The dynamic of virus DNA in each tissue of G-RP7 vaccination fish increased within 1, 3, and 5 days post-immunization, and subsequently decreased and stabilized within 7 and 14 days. In addition, the increase of anti-virus antibody titer was detected both immersion and injection immunization fish 21 days after vaccination by ELISA. These results demonstrated that G-RP7 can be a promising live attenuated vaccine candidate against the disease.


Assuntos
Doenças dos Peixes , Infecções por Herpesviridae , Herpesviridae , Animais , Carpa Dourada , Vacinas Atenuadas , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Vírus de DNA/genética , Necrose , DNA Viral
12.
Antibodies (Basel) ; 12(2)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37218902

RESUMO

To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.

13.
Microbiol Immunol ; 67(7): 334-344, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37248051

RESUMO

We first investigated the interactions between several algae-derived lectins and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We created lectin columns using high-mannose (HM)-type glycan-specific lectins OAA and KAA-1 or core fucose-specific lectin hypninA-2 and conducted binding experiments with SARS-CoV-2. The results showed that these lectins were capable of binding to the virus. Furthermore, when examining the neutralization ability of nine different lectins, it was found that KAA-1, ESA-2, and hypninA-2 were effective in neutralizing SARS-CoV-2. In competitive inhibition experiments with glycoproteins, neutralization was confirmed to occur through HM-type or core fucose-type glycans. However, neutralization was not observed with other lectins, such as OAA. This trend of KAA-1 and ESA-2 having the neutralizing ability and OAA not having it was also similar to influenza viruses. Electron microscopy observations revealed that KAA-1 and hypninA-2 strongly aggregated SARS-CoV-2 particles, while OAA showed a low degree of aggregation. It is believed that the neutralization of SARS-CoV-2 involves multiple factors, such as glycan attachment sites on the S protein, the size of lectins, and their propensity to aggregate, which cause inhibition of receptor binding or aggregation of virus particles. This study demonstrated that several algae-derived lectins could neutralize SARS-CoV-2 and that lectin columns can effectively recover and concentrate the virus.


Assuntos
COVID-19 , Orthomyxoviridae , Humanos , SARS-CoV-2/metabolismo , Manose/metabolismo , Fucose , Lectinas/farmacologia , Lectinas de Ligação a Manose/metabolismo , Lectinas de Ligação a Manose/farmacologia , Polissacarídeos/metabolismo
14.
Virol J ; 20(1): 79, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37101205

RESUMO

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen, characterized by its genetic and antigenic variation. The PRRSV vaccine is widely used, however, the unsatisfied heterologic protection and the risk of reverse virulence raise the requirement to find some new anti-PRRSV strategies for disease control. Tylvalosin tartrate is used to inhibit PRRSV in the field non-specifically, however, the mechanism is still less known. METHODS: The antiviral effects of Tylvalosin tartrates from three producers were evaluated in a cell inoculation model. Their safety and efficacy concentrations, and effecting stage during PRRSV infection were analyzed. And, the Tylvalosin tartrates regulated genes and pathways which are potentially related to the anti-viral effect were further explored by using transcriptomics analysis. Last, the transcription level of six anti-virus-related DEGs was selected to confirm by qPCR, and the expression level of HMOX1, a reported anti-PRRSV gene, was proved by western blot. RESULTS: The safety concentrations of Tylvalosin tartrates from three different producers were 40 µg/mL (Tyl A, Tyl B, and Tyl C) in MARC-145 cells and 20 µg/mL (Tyl A) or 40 µg/mL (Tyl B and Tyl C) in primary pulmonary alveolar macrophages (PAMs) respectively. Tylvalosin tartrate can inhibit PRRSV proliferation in a dose-dependent manner, causing more than 90% proliferation reduction at 40 µg/mL. But it shows no virucidal effect, and only achieves the antiviral effect via long-term action on the cells during the PRRSV proliferation. Furthermore, GO terms and KEGG pathway analysis was carried out based on the RNA sequencing and transcriptomic data. It was found that the Tylvalosin tartrates can regulate the signal transduction, proteolysis, and oxidation-reduction process, as well as some pathways such as protein digestion and absorption, PI3K-Akt signaling, FoxO signaling, and Ferroptosis pathways, which might relate to PRRSV proliferation or host innate immune response, but further studies still need to confirm it. Among them, six antivirus-related genes HMOX1, ATF3, FTH1, FTL, NR4A1, and CDKN1A were identified to be regulated by Tylvalosin tartrate, and the increased expression level of HMOX1 was further confirmed by western blot. CONCLUSIONS: Tylvalosin tartrate can inhibit PRRSV proliferation in vitro in a dose-dependent manner. The identified DEGs and pathways in transcriptomic data will provide valuable clues for further exploring the host cell restriction factors or anti-PRRSV target.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Antivirais/farmacologia , Antivirais/metabolismo , Tartaratos/metabolismo , Tartaratos/farmacologia , Transcriptoma , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Macrófagos Alveolares , Replicação Viral
15.
Front Immunol ; 14: 1129705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895557

RESUMO

COVID-19 pandemic continues to spread throughout the world with an urgent demand for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a bacterial vector COVID-19 vaccine (aPA-RBD) that carries the gene for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Live-attenuated strains of Pseudomonas aeruginosa (aPA) were constructed which express the recombinant RBD and effectively deliver RBD protein into various antigen presenting cells through bacterial type 3 secretion system (T3SS) in vitro. In mice, two-dose of intranasal aPA-RBD vaccinations elicited the development of RBD-specific serum IgG and IgM. Importantly, the sera from the immunized mice were able to neutralize host cell infections by SARS-CoV-2 pseudovirus as well as the authentic virus variants potently. T-cell responses of immunized mice were assessed by enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) assays. aPA-RBD vaccinations can elicit RBD-specific CD4+and CD8+T cell responses. T3SS-based RBD intracellular delivery heightens the efficiency of antigen presentation and enables the aPA-RBD vaccine to elicit CD8+T cell response. Thus, aPA vector has the potential as an inexpensive, readily manufactured, and respiratory tract vaccination route vaccine platform for other pathogens.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Animais , Humanos , Camundongos , Sistemas de Secreção Tipo III , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2
16.
Antiviral Res ; 212: 105579, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36907442

RESUMO

Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus in the family Coronaviridae, causes acute diarrhea and/or vomiting, dehydration, and high mortality in neonatal piglets. It has caused huge economic losses to animal husbandry worldwide. Current commercial PEDV vaccines do not provide enough protection against variant and evolved virus strains. No specific drugs are available to treat PEDV infection. The development of more effective therapeutic anti-PEDV agents is urgently needed. Our previous study suggested that porcine milk small extracellular vesicles (sEV) facilitate intestinal tract development and prevent lipopolysaccharide-induced intestinal injury. However, the effects of milk sEV during viral infection remain unclear. Our study found that porcine milk sEV, which was isolated and purified by differential ultracentrifugation, could inhibit PEDV replication in IPEC-J2 and Vero cells. Simultaneously, we constructed a PEDV infection model for piglet intestinal organoids and found that milk sEV also inhibited PEDV infection. Subsequently, in vivo experiments showed that milk sEV pre-feeding exerted robust protection of piglets from PEDV-induced diarrhea and mortality. Strikingly, we found that the miRNAs extracted from milk sEV inhibited PEDV infection. miRNA-seq, bioinformatics analysis, and experimental verification demonstrated that miR-let-7e and miR-27b, which were identified in milk sEV targeted PEDV N and host HMGB1, suppressed viral replication. Taken together, we revealed the biological function of milk sEV in resisting PEDV infection and proved its cargo miRNAs, miR-let-7e and miR-27b, possess antiviral functions. This study is the first description of the novel function of porcine milk sEV in regulating PEDV infection. It provides a better understanding of milk sEV resistance to coronavirus infection, warranting further studies to develop sEV as an attractive antiviral.


Assuntos
Infecções por Coronavirus , MicroRNAs , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Chlorocebus aethiops , Animais , Suínos , Células Vero , Vírus da Diarreia Epidêmica Suína/genética , Leite , MicroRNAs/genética , MicroRNAs/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Diarreia/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/tratamento farmacológico , Doenças dos Suínos/prevenção & controle
17.
Biomed Pharmacother ; 161: 114457, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36868016

RESUMO

As the most versatile antigen-presenting cells (APCs), dendritic cells (DCs) function as the cardinal commanders in orchestrating innate and adaptive immunity for either eliciting protective immune responses against canceration and microbial invasion or maintaining immune homeostasis/tolerance. In fact, in physiological or pathological conditions, the diversified migratory patterns and exquisite chemotaxis of DCs, prominently manipulate their biological activities in both secondary lymphoid organs (SLOs) as well as homeostatic/inflammatory peripheral tissues in vivo. Thus, the inherent mechanisms or regulation strategies to modulate the directional migration of DCs even could be regarded as the crucial cartographers of the immune system. Herein, we systemically reviewed the existing mechanistic understandings and regulation measures of trafficking both endogenous DC subtypes and reinfused DCs vaccines towards either SLOs or inflammatory foci (including neoplastic lesions, infections, acute/chronic tissue inflammations, autoimmune diseases and graft sites). Furthermore, we briefly introduced the DCs-participated prophylactic and therapeutic clinical application against disparate diseases, and also provided insights into the future clinical immunotherapies development as well as the vaccines design associated with modulating DCs mobilization modes.


Assuntos
Doenças Autoimunes , Vacinas Anticâncer , Humanos , Células Dendríticas , Quimiotaxia , Doenças Autoimunes/metabolismo , Imunoterapia , Inflamação/metabolismo
18.
Int J Mol Sci ; 24(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36674860

RESUMO

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.


Assuntos
Anti-Infecciosos , Incrustação Biológica , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Bactérias , Propriedades de Superfície
19.
Sustain Cities Soc ; 89: 104326, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36467253

RESUMO

With the global prevalence of COVID-19 disease, the concept of urban resilience against pandemics has drawn the attention of a wide range of researchers, urban planners, and policymakers. This study aims to identify the major dimensions and principles of urban resilience to pandemics through a systematic review focused on lessons learned from the COVID-19 pandemic and comparing different perspectives regarding resilient urban environments to such diseases. Based on the findings, the study proposes a conceptual framework and a series of principles of urban resilience to pandemics, consisting of four spatial levels: housing, neighborhoods, city, and the regional and national scales, and three dimensions of pandemic resilience: pandemic-related health requirements, environmental psychological principles, and general resilience principles. The findings show that resilient cities should be able to implement the pandemic-related health requirements, the psychological principles of the environment to reduce the stresses caused by the pandemic, and the general principles of resilience in the smart city context. This framework provides scholars and policymakers with a comprehensive understanding of resilience on different scales and assists them in making better-informed decisions.

20.
Curr Med Chem ; 30(23): 2672-2689, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36017852

RESUMO

2-Oxazolidinone is well known as a pharmacophore for antibacterial agents represented by two marketed medicines, Linezolid and Tedizolid. On the other hand, there are growing reports on the various biological activities of 2-oxazolidinones beyond antibacterial activities. Therefore, in this review, we provide an overview of the progress of this untraditional area of 2-oxazolidinones in the past 10 years (2011-2021).


Assuntos
Antibacterianos , Oxazolidinonas , Humanos , Oxindóis , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Oxazolidinonas/farmacologia , Linezolida , Testes de Sensibilidade Microbiana
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