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1.
Plant Dis ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506908

RESUMO

Lotus (Nelumbo nucifera Gaertn.) is a widely cultivated plant in China, and the fruit lotus variety has a high economic value attributed to the exquisite flavor of its fresh seeds. During the summer of 2023, an unidentified blight was observed affecting lotus seedpods in Jiande City, Zhejiang province, with approximately 65% of seedpods impacted in a 130-hectare area. The initial symptoms included dark purple spots on the lotus seedpod surface, which gradually expanded over time. After 5 to 7 days, the entire seedpod turned black, withering, and rendering the lotus seeds inedible. To identify the causal agent, tissues from symptomatic seedpods were excised and disinfected in 75% ethanol for 60 s, and washed twice in sterile distilled water. The disinfected symptomatic tissues (5 × 5 mm) were plated on potato dextrose agar (PDA), incubated at 25 ℃, transferred hyphal tips to obtain pure isolates after 3 days. Fungal colonies exhibiting Botryosphaeriaceae morphology were isolated from 33% of the samples (n = 15). Pure cultures were grown on PDA for both morphological and molecular identification. The colonies displayed a white aerial mycelium, turning olivaceous grey after 7 days. Pycnidia were produced within 3 weeks on PDA with added sterilized healthy lotus seedpod pieces on the surface. Conidia were hyaline, unicellular, ellipsoidal, 12.65 to 20.72 × 3.92 to 9.38 µm in size (mean 16.67 × 6.24 µm, n = 100). To determine the fungal species, genomic DNA was extracted from one representative isolate (ZJUP1112-1), to amplify four gene loci through polymerase chain reactions (PCR): rDNA internal transcribed spacer (ITS) with primers ITS1/ITS4, rDNA large subunit (LSU) with LR0R/LR5, the translation elongation factor 1-alpha gene (tef1) with EF1-728F/EF1-986R, and ß-tubulin gene (tub2) with Bt2a/Bt2b. The PCR products were Sanger sequenced in Zhejiang Shangya biotechnology co., LTD, and the resulting sequences were assembled and deposited in GenBank (ITS: OR740546; LSU: OR740547; tef1: OR776996; tub2: OR776997). BLAST searches indicated the highest nucleotide sequence identity with the reference strains of Neofusicoccum parvum CMW 9081 (ITS: 98.8%, AY236943; LSU: 100%, AY928045; tef1: 99.6%, AY236888; tub2: 99.3%, AY236917). Multi-locus phylogenetic analyses revealed that isolate ZJUP1112-1 formed a highly supported clade with N. parvum. Pathogenicity tests were performed on healthy lotus seedpods using mycelial plugs (5 mm diameter) from actively growing colonies of ZJUP1112-1 that were placed onto the front and side of the seedpods (6 each). Controls received PDA plugs. Treated seedpods were wrapped with parafilm and incubated at 25 ℃ and the experiment was repeated three times. After 5 days, dark purple lesions were observed on the inoculated seedpods, whereas controls remained symptomless. The same isolate was recovered from the margin of resulting lesions and confirmed by morphology, thus fulfilling Koch's postulates. N. parvum is a polyphagous pathogen causing blights and fruit rot on multiple economically important fruit crops, such as cacao (Puig et al. 2019), walnut (Chen et al. 2019), pistachio (Lopez-Moral et al. 2020), chestnut (Seddaiu et al. 2021), blueberry (Spetik et al. 2023) and mango (Polizzi et al. 2022), among others. To the best of our knowledge, this is the first report of N. parvum causing seedpod blight on lotus seedpods in China, which contributes to a better understanding of the pathogens affecting this plant species in China.

2.
Nat Commun ; 14(1): 7659, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38036535

RESUMO

Many of the Alzheimer's disease (AD) risk genes are specifically expressed in microglia and astrocytes, but how and when the genetic risk localizing to these cell types contributes to AD pathophysiology remains unclear. Here, we derive cell-type-specific AD polygenic risk scores (ADPRS) from two extensively characterized datasets and uncover the impact of cell-type-specific genetic risk on AD endophenotypes. In an autopsy dataset spanning all stages of AD (n = 1457), the astrocytic ADPRS affected diffuse and neuritic plaques (amyloid-ß), while microglial ADPRS affected neuritic plaques, microglial activation, neurofibrillary tangles (tau), and cognitive decline. In an independent neuroimaging dataset of cognitively unimpaired elderly (n = 2921), astrocytic ADPRS was associated with amyloid-ß, and microglial ADPRS was associated with amyloid-ß and tau, connecting cell-type-specific genetic risk with AD pathology even before symptom onset. Together, our study provides human genetic evidence implicating multiple glial cell types in AD pathophysiology, starting from the preclinical stage.


Assuntos
Doença de Alzheimer , Humanos , Idoso , Doença de Alzheimer/metabolismo , Placa Amiloide/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Emaranhados Neurofibrilares/genética , Emaranhados Neurofibrilares/metabolismo , Fatores de Risco
3.
Clin Med Insights Oncol ; 17: 11795549231203142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905234

RESUMO

Background: The influence of the breast as the primary site on the outcome of diffuse large B-cell lymphoma (DLBCL) and further changes in therapeutic strategies remain unclear. We aimed to compare the outcomes between primary breast and non-breast DLBCL and analyze the genetic profiles of some of the study cohorts using next-generation sequencing. Methods: This matched-pair study reviewed the medical records of 19 patients with stage I and II primary breast DLBCL diagnosed between January 2005 and December 2021 on the basis of the Wiseman and Liao criteria, and we used 1:4 propensity score matching to identify patients with non-breast DLBCL as the control group. The overall response rate, progression-free survival (PFS), and overall survival (OS) were the outcome measures. Results: Patients with primary breast and non-breast DLBCL had a 5-year PFS of 72.6% and 86.9%, respectively (P = .206). These 2 groups also had comparable 5-year OS (86.9% vs 87.8%; P = .772). The breast as the primary site was not associated with inferior PFS (hazard ratio [HR]: 2.14; 95% CI: 0.66-6.96; P = .206) and OS (HR: 1.26; 95% CI: 0.27-5.93; P = .772). Conclusion: Patients with primary breast DLBCL and those with non-breast DLBCL had comparable PFS and OS under rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens. Further investigations of the mutation profile, its clinical impact, potential central nervous system relapse, and prognosis of primary breast DLBCL are required.

4.
medRxiv ; 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37333223

RESUMO

Alzheimer's disease (AD) heritability is enriched in glial genes, but how and when cell-type-specific genetic risk contributes to AD remains unclear. Here, we derive cell-type-specific AD polygenic risk scores (ADPRS) from two extensively characterized datasets. In an autopsy dataset spanning all stages of AD (n=1,457), astrocytic (Ast) ADPRS was associated with both diffuse and neuritic Aß plaques, while microglial (Mic) ADPRS was associated with neuritic Aß plaques, microglial activation, tau, and cognitive decline. Causal modeling analyses further clarified these relationships. In an independent neuroimaging dataset of cognitively unimpaired elderly (n=2,921), Ast-ADPRS were associated with Aß, and Mic-ADPRS was associated with Aß and tau, showing a consistent pattern with the autopsy dataset. Oligodendrocytic and excitatory neuronal ADPRSs were associated with tau, but only in the autopsy dataset including symptomatic AD cases. Together, our study provides human genetic evidence implicating multiple glial cell types in AD pathophysiology, starting from the preclinical stage.

5.
Int Immunopharmacol ; 112: 109204, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36067651

RESUMO

Amomum longiligulare polysaccharide 1 (ALP1) was extracted from Amomum longiligulare T.L. Wu fruits and the poly (lactic-co-glycolic acid) nanoparticle enveloping ALP1 (ALPP) showed a good promoting effect on the activation of macrophages in our previous study. To further understand the immunomodulatory property of ALPP, the effect of ALPP on T lymphocytes and dendritic cells was investigated in the present study. The proliferation rates of chicken T lymphocytes and chicken bone marrow dendritic cells (chBM-DCs) that were treated with ALP1 or ALPP were determined by using MTT method. Meanwhile, the relative mRNA levels of cytokines from T lymphocytes and surface molecules of chBM-DCs were determined by using qRT-PCR method. In addition, the drug uptake capacity of chBM-DCs was also tested. As a result, the promoting effect on the proliferation of T lymphocytes and the Th1-type immune response of ALPP was better than that of ALP1. In addition, ALPP was much more effectively swallowed by chBM-DCs so that its promoting effect on the proliferation and maturation of chBM-DCs was higher than that of ALP1. To conclude, ALPP had a stronger immunomodulatory activity than ALP1, and showed the potential to become a new type of immune booster.


Assuntos
Amomum , Nanopartículas , Linfócitos T , Células Dendríticas , Polissacarídeos/farmacologia , Citocinas , RNA Mensageiro
6.
Hum Vaccin Immunother ; 17(12): 5546-5557, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34520322

RESUMO

Immunotherapy for cancer has attracted considerable attention. As one of the immunotherapeutics, tumor vaccines exert great potential for cancer immunotherapy. The most important components in tumor vaccines are antigens and adjuvants, which determine the therapeutic safety and efficacy, respectively. After decades of research, many types of adjuvants have been developed. Although these adjuvants can induce strong and long-lasting immune responses in tumor immunity, they also cause more severe toxic side effects and are therefore not suitable for use in humans. With the development of innate immunity research, pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are receiving more attention in vaccine design. However, whether they have the potential to become new adjuvants remains to be elucidated. The purpose of this review is to provide newideas for the research and development of new adjuvants by discussing the mechanisms and related functions of PAMPs and DAMPs.


Assuntos
Vacinas Anticâncer , Neoplasias , Vacinas , Adjuvantes Imunológicos/farmacologia , Humanos , Imunidade Inata , Neoplasias/terapia , Moléculas com Motivos Associados a Patógenos
7.
Mol Immunol ; 139: 184-192, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34560414

RESUMO

Metastatic renal carcinoma is a kind of tumor with high degree of malignancy, but there are no effective treatment methods and strategies at present. In this study, we designed a folate-grafted PEI600-CyD (H1) nanoparticle-mediated DNA vaccine containing an adjuvant of high mobility group box 1 protein (HMGB1) and a tumor-specific antigen of B7H3 (CD276) for renal carcinoma therapy. Mice bearing subcutaneous human B7H3 (hB7H3)-Renca tumor were immunized with H1-pHMGB1/pB7H3, H1-pB7H3, H1-pHMGB1, or Mock vaccine. Compared to other control groups, the growth of the tumor was significantly inhibited in H1-pHMGB1/pB7H3 vaccine group. The increased proportion and mature of CD11c+ DCs were observed in the spleen of H1-pHMGB1/pB7H3 treated mice. Likewise, HMGB1 promoted B7H3 vaccine to induce tumor-specific CD8+ T cell proliferation and CTL responses. Beyond that, H1-pHMGB1/pB7H3 vaccine strengthened the induction of functional CD8+ T cells. With the depletion of CD8+ T cells, the anti-tumor effect of H1-pHMGB1/pB7H3 also disappeared, indicating that CD8+ T cells are the key factor of the anti-tumor activity of the vaccine. So, to sum up, H1-pHMGB1/pB7H3 vaccine could achieve the desired anti-tumor effect by enhancing the response of tumor-specific functional CD8+ T cell responses. H1 nanoparticle-based vaccines may have great potential and prospect in the treatment of primary solid tumors.


Assuntos
Antígenos B7/imunologia , Vacinas Anticâncer/farmacologia , Carcinoma de Células Renais/imunologia , Proteína HMGB1/imunologia , Neoplasias Renais/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Vacinas de DNA/imunologia
8.
Int Immunopharmacol ; 99: 108053, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435578

RESUMO

Amomum longiligulare polysaccharides 1 (ALP1) was a glucosan that possessed an immune enhancement ability. However, disadvantages including short biological half-life hindered the application of ALP1. To solve these shortcomings, ALP1 was successfully prepared to nanoparticles (ALPP) with poly (lactic-co-glycolic acid) in the present study. And the optimal preparation conditions were developed by using the response surface method with a Box-Behnken design. The results showed that the encapsulation efficiency of ALPP reached a high level (79.88%) when the volume ratio of the water phase to the organic phase was 1:7, the volume ratio of the primary emulsion to the external water phase was 1:7, and the concentration of F68 was 0.7%. ALPP showed a controlled and sustained release. Meanwhile, the scanning electron microscope results showed that ALPP was a kind of nanoparticles with a diameter of 389.77 nm. In addition, the activating effect of ALPP on macrophages was studied. The results indicated that ALPP showed a better activity on promoting the RAW264.7 cells' activities and polarizing RAW264.7 cells into both M1 type and M2 type macrophages, compared to ALP1.


Assuntos
Amomum/química , Nanopartículas/química , Preparações de Plantas/imunologia , Preparações de Plantas/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/imunologia , Polissacarídeos/farmacologia , Animais , Frutas/química , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Nanopartículas/metabolismo , Tamanho da Partícula , Fagocitose/efeitos dos fármacos , Preparações de Plantas/química , Preparações de Plantas/isolamento & purificação , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7
9.
Int J Biol Macromol ; 183: 1574-1584, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34044027

RESUMO

The aim of this study is to explore the characterization of Amomum longiligulare T.L. Wu fruits polysaccharide (ALP) and their immune enhancement effects. Two homogeneous polysaccharides (ALP1 and ALP2) were isolated from the fruits. The structural characterization results showed that ALP1 (26.10 kDa) and ALP2 (64.10 kDa) were both mainly composed of glucose. Furthermore, ALP1 was consisted of (1,2)-α-D-Glcp, (1,2,3)-α-D-Glcp and T-α-D-Glcp, while ALP2 was consisted of T-α-D-Glcp, (1,3)-α-D-Glcp and (1,3,6)-α-D-Glcp. Afterwards, the immune enhancement effects of two polysaccharides were evaluated by determining their effects on immunogenicities of infectious bursal disease virus (IBDV) VP2 protein. Chickens were immunized with IBDV VP2 protein accompanied with ALP1/ALP2. And the results indicated both ALP1 and ALP2 promoted the weights and bursa of fabricius indexes of chickens. In addition, both two polysaccharides increased specific IBDV antibody levels, while ALP1 possessed higher immune enhancement ability and was expected to be an adjuvant for IBDV VP2 protein.


Assuntos
Amomum/química , Glucose/química , Vírus da Doença Infecciosa da Bursa/imunologia , Polissacarídeos/administração & dosagem , Proteínas Estruturais Virais/administração & dosagem , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais/metabolismo , Sequência de Carboidratos , Galinhas , Imunização , Peso Molecular , Extratos Vegetais/química , Polissacarídeos/química , Polissacarídeos/imunologia , Proteínas Estruturais Virais/imunologia
10.
Int Immunopharmacol ; 97: 107708, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33915496

RESUMO

Polysaccharides are important components of Alpiniae oxyphyllae fructus that have been shown to exhibit significant immunomodulatory activity in our previous study. However, whether and how A. oxyphyllae fructus polysaccharides (AOFP) affect macrophages has not been determined. To further study the immunomodulatory activity of AOFP, the effect of AOFP on RAW264.7 cell activation was investigated in the present work. The results showed that AOFP2 significantly increased the phagocytic activity of RAW264.7 macrophages. AOFP2 promoted the secretion of TNF-α, IL-6, IL-10, TGF-ß, NO and iNOS and enhanced the Th2-type immune response via its activation effect on macrophages. Additionally, the structure of AOFP2 was characterized in the present study, as the structural features of polysaccharides determine their biological activities. AOFP2 was only composed of glucose, exhibiting an average molecular weight of 44.3 kDa. Furthermore, the infrared spectroscopy, methylation and nuclear magnetic resonance results indicated that AOFP2 consisted of â†’ 4)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1 â†’ and T-α-Glcp.


Assuntos
Alpinia/química , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/química , Polissacarídeos/farmacologia , Animais , Fatores Imunológicos/química , Camundongos , Peso Molecular , Polissacarídeos/química , Células RAW 264.7
11.
Antibiotics (Basel) ; 10(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572268

RESUMO

(1) Background: Elizabethkingia spp. is an emerging nosocomial pathogen which causes mostly blood stream infection and nosocomial pneumonia. Among Elizabethkingia species, Elizabethkingia anophelis is the major pathogen, but misidentification as Elizabethkingia meningoseptica is a common problem. Elizabethkingia also possesses broad antibiotic resistance, resulting in high morbidity and mortality of the infection. The aim of our study was to review Elizabethkingia intra-abdominal infections and investigate resistance mechanisms against TMP/SMX in Elizabethkingia anophelis by whole genome sequencing. (2) Methods: We retrospectively searched records of patients with Elizabethkingia intra-abdominal infection between 1990 and 2019. We also conducted whole genome sequencing for a TMP/SMX-resistant Elizabethkingia anophelis to identify possible mechanisms of resistance. (3) Results: We identified a total of nine cases of Elizabethkingia intra-abdominal infection in a review of the literature, including our own case. The cases included three biliary tract infections, three CAPD-related infection, two with infected ascites, and two postoperation infections. Host factor, indwelling-catheter, and previous invasive procedure, including surgery, play important roles in Elizabethkingia infection. Removal of the catheter is crucial for successful treatment. Genomic analysis revealed accumulated mutations leading to TMP/SMX-resistance in folP. (4) Conclusions: Patients with underlying disease and indwelling catheter are more susceptible to Elizabethkingia intra-abdominal infection, and successful treatment requires removal of the catheter. The emerging resistance to TMP/SMX may be related to accumulated mutations in folP.

12.
J Am Med Inform Assoc ; 28(3): 533-540, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33215194

RESUMO

OBJECTIVE: Tuberculosis is the leading cause of death from a single infectious agent. The emergence of antimicrobial resistant Mycobacterium tuberculosis strains makes the problem more severe. Pyrazinamide (PZA) is an important component for short-course treatment regimens and first- and second-line treatment regimens. This research aims for fast diagnosis of M. tuberculosis resistance to PZA and identification of genetic features causing resistance. MATERIALS AND METHODS: We use clinically collected genomic data of M. tuberculosis that are resistant or susceptible to PZA. A machine learning platform is built to diagnose PZA resistance using the whole genome sequence data, and to identify resistance genes and mutations. The platform consists of a deep convolutional neural network (DCNN) model for resistance diagnosis and a support vector machine (SVM) model as a surrogate to identify resistance genes and mutations. RESULTS: The DCNN model achieves a PZA resistance diagnosis accuracy of 93%. Each prediction takes less than a second. The SVM has revealed 2 novel genes, embB and gyrA, besides the well-known pncA gene, and 9 mutations that harbor PZA resistance. DISCUSSION: The DCNN and SVM machine learning platform, if used together with the real-time genome sequencing machines, could allow for rapid PZA diagnosis, allowing for critical time to ensure good patient outcomes, and preventing outbreaks of deadly infections. Furthermore, identifying pertinent resistance genes and mutations will help researchers better understand the biological mechanisms behind resistance. CONCLUSIONS: Machine learning can be used to achieve high-accuracy resistance prediction, and identify genes and mutations causing the resistance.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Aprendizado de Máquina , Mycobacterium tuberculosis/genética , Redes Neurais de Computação , Pirazinamida/farmacologia , Máquina de Vetores de Suporte , Tuberculose/microbiologia , Antituberculosos/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/uso terapêutico , Tuberculose/tratamento farmacológico
13.
Int Immunopharmacol ; 86: 106708, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32570039

RESUMO

Polysaccharide is the main active component of okra (Abelmoschus esculentus L.) and it can effectively stimulate the activation of macrophages. However, the immune regulatory mechanism is still not clear. Therefore, the present study aimed to reveal the possible mechanism by investigating the effect of okra polysaccharide-2 (RPS-2) on Toll-like receptor (TLR) 2/4-mediated signal transduction pathways in RAW264.7 murine macrophage cells. In order to confirm whether RPS-2 stimulated macrophages activation via TLR2 or TLR4, RAW264.7 murine macrophage cells were pretreated with TLR2/4 inhibitors for 1 h before RPS-2 treatment, and then the NO, IL-10, TNF-α levels were tested. The results indicated that both TLR2 and TLR4 were the keys of immune regulatory effect of RPS-2. Afterwards, the effect of RPS-2 on NF-κB and MAPKs signaling pathways were studied by western blot analysis. It showed RPS-2 induced the phosphorylation of p65, IκBα, p38, ERK1/2 and JNK. At the same time, the specific inhibitors reduced these phosphorylation levels as well as NO, IL-10 and TNF-α amounts. In a word, RPS-2 activated macrophages by NF-κB and MAPKs signal transduction pathways.


Assuntos
Abelmoschus/química , Polissacarídeos/imunologia , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Proteínas I-kappa B/metabolismo , Interleucina-10/metabolismo , Janus Quinases/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Subunidade p50 de NF-kappa B/efeitos dos fármacos , Óxido Nítrico/metabolismo , Fagocitose/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Polissacarídeos/metabolismo , Células RAW 264.7 , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/antagonistas & inibidores , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
J Ethnopharmacol ; 259: 113009, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32450234

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The dry overground parts of Pogostemon cablin (Blanco) Benth. is widely used in China as a traditional Chinese medicine for the treatment of diarrhea, vomiting, nausea and fever. Polysaccharide is an important component of Pogostemon cablin (Blanco) Benth. but has not been studied. Pogostemon cablin (Blanco) Benth. is used to treat porcine epidemic diarrhea. But it is not known whether Pogostemon cablin polysaccharides (PCPs) has the antiviral activities against porcine epidemic diarrhea virus (PEDV). AIM OF THE STUDY: The purpose of present study is to investigate the structural characterization and the anti-PEDV activities of PCPs. MATERIALS AND METHODS: PCPs were prepared by water extraction and alcohol precipitation method and purified with DEAE-52 cellulose column and Sephadex G-100 column. Then, the structural characterization of the polysaccharides including the infrared spectrum, molecular weight and monosaccharide composition were analyzed. Afterwards, the antiviral effect of PCPs against PEDV on IPEC-J2 cells was studied by MTT method and real-time PCR method. Additionally, the effects of PCPs on PEDV adsorption, penetration and replication were analyzed by real-time PCR method. Furthermore, we also investigate whether the anti-oxidative effects of PCPs were important to the anti-PEDV activities. RESULTS: Four polysaccharides were obtained and named as PCP1.1 (31.3 kDa), PCP1.2 (3.5 kDa), PCP2.1 (9.1 kDa) and PCP2.2 (8.3 kDa). PCP1.1, PCP1.2 and PCP2.1 were composed of fucose, arabinose, galactose, glucose, mannose, galacturonic acid and glucuronic acid; and PCP2.2 was composed of arabinose, galactose, glucose, galacturonic acid and glucuronic acid. All PCPs showed anti-PEDV activities. PCP1.1 and PCP1.2 inhibited PEDV replication, while PCP2.1 and PCP2.2 inhibited PEDV penetration and replication. All PCPs showed anti-oxidative effects, which were important to the anti-PEDV activities. CONCLUSIONS: The treatment effect of Pogostemon cablin (Blanco) Benth. on porcine epidemic diarrhea might be related to the anti-PEDV effect of PCPs. Furthermore, the anti-oxidative effects of PCPs play important roles in their antiviral activities against PEDV.


Assuntos
Antivirais/farmacologia , Mucosa Intestinal/virologia , Extratos Vegetais/farmacologia , Pogostemon , Polissacarídeos/farmacologia , Vírus da Diarreia Epidêmica Suína/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antivirais/isolamento & purificação , Linhagem Celular , Mucosa Intestinal/metabolismo , Estrutura Molecular , Peso Molecular , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Pogostemon/química , Polissacarídeos/isolamento & purificação , Vírus da Diarreia Epidêmica Suína/patogenicidade , Relação Estrutura-Atividade , Sus scrofa
15.
J Microbiol Immunol Infect ; 53(3): 481-484, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32111449
16.
PLoS Biol ; 17(3): e2007097, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30883547

RESUMO

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.


Assuntos
Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Memória/fisiologia , Receptores de Serotonina/metabolismo , Ácido 3-Hidroxibutírico/sangue , Animais , Western Blotting , Corticosterona/sangue , Eletrofisiologia , Teste de Tolerância a Glucose , Hipocampo/citologia , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Receptores de Serotonina/genética , Serotonina/sangue , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
17.
Nephron ; 139(2): 172-180, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29672315

RESUMO

BACKGROUND/AIMS: To investigate the downregulation of microRNA (miR)-10b in clear cell renal cell carcinoma (ccRCC) and its mechanistic involvement in tumourigenesis. METHODS: The relative expression of miR-10b in ccRCC samples were determined by real-time PCR. Exogenous expression and knockdown of endogenous miR-10b were performed by transfection with indicated plasmids into 786-0 cells. Cell proliferation was evaluated using Cell Counting Kit-8 assay. Cell apoptosis was analyzed by Annexin V/propidium iodide staining. MAPK pathway activation was detected by western blotting with indicated antibodies. RESULTS: We confirmed the downregulation of miR-10b in ccRCC tumour. The forced expression of miR-10b inhibited cell proliferation in 786-0 cells. Moreover, miR-10b stimulated apoptosis in 786-0 cells, which was abrogated by specific miR-10b inhibitor. We further elucidated that the apoptosis induction was mediated by the JNK pathway activation. We consolidated this observation by combinational treatment with JNK specific inhibitor, which was shown to completely impede miR-10b elicited apoptosis. CONCLUSION: We suggested a tumour suppressor function of miR-10b in tumourigenesis of ccRCC via proliferation suppression and apoptosis induction, and the latter was mediated by the JNK pathway activation.


Assuntos
Apoptose/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , MAP Quinase Quinase 4/metabolismo , MicroRNAs/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Humanos , MicroRNAs/genética
18.
FEBS Open Bio ; 7(8): 1078-1084, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28781948

RESUMO

Hyperacidity in the stomach is known to promote the progression of gastric cancer. The plant-derived chemotherapeutic curcumin is used to treat gastric cancer. The objective of this study was to investigate whether curcumin regulates gastrin-mediated acid secretion in suppressing gastric cancer. Gastric cancer cells were treated with 25 µm curcumin, followed by Annexin V/propidium iodide double-staining assay to evaluate cell apoptosis. Western blot analysis was used to analyze caspase-3 expression in response to curcumin treatment. Gastrin levels in culture medium were also monitored. Mice bearing gastric cancers were treated with curcumin, followed by analysis of tumor caspase-3 expression, gastric acid pH, and gastric secretion in serum. Curcumin prominently inhibited gastric cancer cell proliferation and promoted cell apoptosis. Caspase-3 was upregulated by curcumin treatment. Curcumin also reduced gastrin secretion. Curcumin dramatically inhibited tumor growth, increased gastric pH, and reduced gastric secretion. In gastric cancer, curcumin suppresses gastrin-mediated acid secretion, which inhibits gastric cancer progression.

19.
Phys Chem Chem Phys ; 18(37): 26254-26261, 2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27711691

RESUMO

Planar heterojunction perovskite solar cells (PHJ-PSCs) constructed with one-step precursor solution spin-coating deposition (OPSSD) usually give an extremely low performance mainly due to the poor morphology and low crystallinity of the perovskite films. In this work, by incorporating a suitable HONH3Cl additive in the perovskite precursor solution, a high quality perovskite film with improved morphology and crystallinity was obtained. The UV-vis measurement of the CH3NH3I solutions without and with HONH3Cl demonstrates that the improved quality of the perovskite film can be easily attributed to a combined effect of N2, I2, H2O and CH3NH3Cl originating from the oxidation of CH3NH3I triggered by the HONH3Cl additive, which can manipulate the crystallization process of the perovskite. Accordingly, the improved performance for the HONH3Cl-induced PHJ-PSCs can also be demonstrated. At the optimized molar ratio of 1 : 1 : 0.1 for PbI2 : CH3NH3I : HONH3Cl, the PHJ-PSCs exhibit an average power conversion efficiency (PCE) of 10.61 ± 0.51%, which is much higher than that of pristine 1 : 1 : 0 based cells without additive (7.21 ± 0.61%), and the best performing HONH3Cl-induced device can yield a PCE as high as 11.12% with a Jsc of 18.42 mA cm-2, Voc of 0.95 V and FF of 0.63. Introducing suitable HONH3Cl as an additive into the perovskite precursor solution is really an effective route to enhance the performance of the PHJ-PSCs via OPSSD.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(4): 467-71, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27113171

RESUMO

OBJECTIVE: To investigate the effect of di-(2-ethylhexyl) phthalate (DEHP) exposure on the growth and development of placenta, uterine natural killer (uNK) cell number and angiogenesis at the maternal-fetal interface in pregnant mice. METHODS: From day 1 of pregnancy, pregnant mice were exposed daily to DEHP by oral gavage at 125, 250, or 500 mg/kg for 13 consecutive days. The uterine and placental tissues were then harvested for HE staining and immunohistochemistry to examine the effect of DEHP exposure on the growth and development of the placenta and angiogenesis and uNK cell number at the maternal-fetal interface. RESULTS: Compared with the control group, the mice exposed to 500 mg/kg DEHP, but not those exposed to 125 and 250 mg/kg, showed significantly reduced number of embryo implantation (P<0.05). DEHP exposure significantly increased the rate of abortion. DEHP exposure at 125, 250, and 500 mg/kg significantly and dose-dependently lowered the placental weight compared with that in the control group (0.0637±0.0133, 0.0587±0.0176, 0.0524±0.0183 g vs 0.0786±0.0143 g, respectively; P<0.01), and significantly reduced the total area of the placenta and area of spongiotrophoblasts. DEHP exposure resulted in a significant reduction in the number of fetal vascular branches, and collapse and atresia of blood vessels. The mice exposed to DEHP at 125, 250, and 500 mg/kg had significantly lowered numbers of uNK cells (83.2±10.3, 60.7±12.4, and 50.4±14.5/HP, respectively) as compared with the control group (105.1±14.2/HP) at the maternal-fetal interface (P<0.01). CONCLUSION: DEHP exposure significantly affects the growth and development of the placenta in mice possibly by suppressing angiogenesis and reducing uNK cell number at the maternal-fetal interface during pregnancy.


Assuntos
Dietilexilftalato/efeitos adversos , Exposição Materna/efeitos adversos , Placenta/efeitos dos fármacos , Placentação/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Implantação do Embrião , Feminino , Sangue Fetal , Células Matadoras Naturais/citologia , Camundongos , Neovascularização Fisiológica , Gravidez
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