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1.
Ann Hum Genet ; 88(2): 126-137, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37846608

RESUMEN

INTRODUCTION: Prostate cancer is one of the most common cancer types in males and rs12621278:A > G has been suggested to be associated with this disease by previous genome-wide association studies. One thousand genomes project data analysis indicated that rs12621278:A > G is within two long-core haplotypes. However, the origin, causal variant(s), and molecular function of these haplotypes were remaining unclear. MATERIALS AND METHODS: Population genetics analysis and functional genomics work was performed for this locus. RESULTS: Phylogeny analysis verified that the rare haplotype is derived from Neanderthal introgression. Genome annotation suggested that three genetic variants in the core haplotypes, rs116108611:G > A, rs139972066:AAAAAAAA > AAAAAAAAA, and rs3835124:ATTTATT > ATT, are located in functional regions. Luciferase assay indicated that rs139972066:AAAAAAAA > AAAAAAAAA and rs116108611:G > A are not able to alter ITGA6 (integrin alpha 6) and ITGA6 antisense RNA 1 expression, respectively. In contrast, rs3835124:ATTTATT > ATT can significantly influence PDK1 (pyruvate dehydrogenase kinase 1) expression, which was verified by expression quantitative trait locus analysis. This genetic variant can alter transcription factor cut like homeobox 1 interaction efficiency. The introgressed haplotype was observed to be subject to positive selection in East Asian populations. The molecular function of the haplotype suggested that Neanderthal should be with lower PDK1 expression and further different energy homeostasis from modern human. CONCLUSION: This study provided new insight into the contribution of Neanderthal introgression to human phenotypes.


Asunto(s)
Hombre de Neandertal , Neoplasias , Humanos , Animales , Hombre de Neandertal/genética , Estudio de Asociación del Genoma Completo , Genética de Población , Filogenia , Haplotipos , Genoma Humano , Neoplasias/genética
2.
Bull Entomol Res ; 114(2): 281-292, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38602247

RESUMEN

Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.


Asunto(s)
Proteínas de Insectos , Larva , Mariposas Nocturnas , Animales , Mariposas Nocturnas/inmunología , Mariposas Nocturnas/genética , Mariposas Nocturnas/microbiología , Mariposas Nocturnas/crecimiento & desarrollo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Larva/crecimiento & desarrollo , Larva/microbiología , Bacillus thuringiensis , Beauveria/fisiología , Péptidos Antimicrobianos/genética , Pupa/crecimiento & desarrollo , Interferencia de ARN
3.
Connect Tissue Res ; 64(3): 274-284, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36537662

RESUMEN

AIM: Emerging data have demonstrated that low-grade inflammation in osteoarthritis, a long-held degenerative disease. The inflamed synovium produces various cytokines that induce cartilage destruction and joint pain. A previous study showed that teriparatide, an FDA approved anti-osteoporotic drug, may enhance cartilage repair. Our study focuses on its role in OA synovitis. MATERIALS AND METHODS: Primary mouse articular chondrocytes were used to determine the most potent cytokines involved in OA inflammation and cartilage destruction. A destabilization of the medial meniscus mouse model was established to investigate the effect of teriparatide in OA, particularly, on synovial inflammation and cartilage degradation. RESULTS: In vitro experiments showed that TNF-α was the most potent inducer of cartilage matrix-degrading enzymes, and that teriparatide antagonized the TNF-α of effect. Consistently, articular cartilage samples from TNF-α transgenic mice contained more MMP-13 positive chondrocytes than those from wild type mice. In addition, more type II collagen was cleaved in human OA cartilage than in normal cartilage samples. CONCLUSIONS: Teriparatide can prevent synovitis and cartilage degradation by suppressing TNF-α mediated MMP-13 overexpression. Together with its chondroregenerative capability, teriparatide may be the first effective disease modifying osteoarthritis drug.


Asunto(s)
Cartílago Articular , Osteoartritis , Sinovitis , Humanos , Ratones , Animales , Teriparatido/farmacología , Teriparatido/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Cartílago/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Condrocitos/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/metabolismo , Modelos Animales de Enfermedad , Sinovitis/tratamiento farmacológico , Ratones Transgénicos , Citocinas/metabolismo , Cartílago Articular/metabolismo
4.
Bull Entomol Res ; 113(6): 756-766, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37730215

RESUMEN

Kazal-type serine protease inhibitors (KaSPI) play important roles in insect growth, development, digestion, metabolism and immune defence. In this study, based on the transcriptome of Mythimna separata, the cDNA sequence of MsKaSPI with Kazal domain was uploaded to GenBank (MN931651). Spatial and temporal expression analysis showed that MsKaSPI was expressed at different developmental stages and different tissues, and it was induced by 20-hydroxyecdysone in third-instar larvae of M. separata. After 24 h infection by Beauveria bassiana, the expression level of MsKaSPI and the corresponding MsKaSPI content were significantly up-regulated, being 6.42-fold and 1.91-fold to the control group, respectively, while the activities of serine protease, trypsin and chymotrypsin were inhibited. After RNA interference interfered with MsKaSPI for 6 h, the expression decreased by 73.44%, the corresponding content of MsKaSPI protein decreased by 55.66% after 12 h, and the activities of serine protease and trypsin were significantly enhanced. Meanwhile, both the larval and pupal stages of M. separata were prolonged, the weights were reduced and the number of eggs per female decreased by 181. Beauveria bassiana infection also increased the mortality of MsKaSPI-silenced M. separata by 18.96%. These prove MsKaSPI can not only result in slow growth and low fecundity of M. separata by regulating the activity of related protease, but also participate in the resistance to pathogenic fungi by regulating the serine protease inhibitor content and the activities of related serine protease.


Asunto(s)
Antifúngicos , Mariposas Nocturnas , Femenino , Animales , Antifúngicos/farmacología , Inhibidores de Serinpeptidasas Tipo Kazal/farmacología , Tripsina , Mariposas Nocturnas/genética , Larva
5.
J Asian Nat Prod Res ; 25(10): 983-991, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37010919

RESUMEN

Homoisoflavone contains 16 carbon atoms in the skeleton. The homoisoflavonoid skeleton from natural products can be roughly divided into 13 kinds, among which 5 kinds of common skeletons contain a large amount of compounds and 8 kinds of abnormal skeletons comprise a small amount of compounds. In this article, the structure identification experience of homoisoflavonoids found in Caesalpinia mimosoides was used as references and an efficient 1H NMR spectroscopic method for identifying homoisoflavonoid structure has been established. Using the chemical shift differences of H-2, 3, 4 and 9, the common natural homoisoflavonoids can be quickly and conveniently determined.


Asunto(s)
Caesalpinia , Isoflavonas , Espectroscopía de Protones por Resonancia Magnética , Isoflavonas/química , Espectroscopía de Resonancia Magnética , Imagen por Resonancia Magnética , Estructura Molecular , Caesalpinia/química
6.
Am J Respir Cell Mol Biol ; 66(3): 283-292, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34851809

RESUMEN

Asthma is a common, complex disease with apparent genetic predispositions, and previous genome-wide association studies suggest that rs1295686 within the IL13 (IL-13) gene is significantly associated with asthma. Analysis of the data provided by the 1,000 Genomes Project indicated an additional four SNPs in nearly complete linkage disequilibrium with rs1295686 in White people. However, the causal SNPs and the associated mechanism remain unclear. To investigate this issue, functional genomics approaches were utilized to analyze the functions of these SNPs. Dual-luciferase assays indicated that the functional SNP is not rs1295686 but a haplotype consisting of three other SNPs: rs1295685, rs848, and rs847. Through chromosome conformation capture, it was found that the enhancer containing the three functional SNPs interacts with the promoter of TH2LCRR (T helper type 2 locus control region associated RNA), a recently identified long noncoding RNA. RNA-seq data analysis indicated that TH2LCRR expression is significantly increased in patients with asthma and is dependent on the genotype at this locus, indicating that TH2LCRR is a novel susceptibility gene for asthma and that these SNPs confer asthma risk by regulating TH2LCRR expression. By chromatin immunoprecipitation, the related transcription factors that bind in the region surrounding these three SNPs were identified, and their interactions were investigated by functional genomics approaches. Our effort identified a novel mechanism through which genetic variations at this locus could influence asthma susceptibility.


Asunto(s)
Asma , Estudio de Asociación del Genoma Completo , ARN/genética , Asma/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas
7.
Molecules ; 27(5)2022 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-35268807

RESUMEN

Oxytropis falcata Bunge is a plant used in traditional Tibetan medicine, with reported anti-inflammatory and antioxidants effects and alleviation of myocardial ischemia reperfusion injury (MIRI). However, the underlying mechanism against MIRI and the phytochemical composition of O. falcata are vague. One fraction named OFF1 with anti-MIRI activity was obtained from O. falcata, and the chemical constituents were identified by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS). The potential targets and signaling pathways involved in the action of O. falcata against MIRI were predicted by network pharmacology analysis, and its molecular mechanism on MIRI was determined by in vitro assays. The results revealed that flavonoids are the dominant constituents of OFF1. A total of 92 flavonoids reported in O. falcata targeted 213 potential MIRI-associated factors, including tumor necrosis factor (TNF), prostaglandin-endoperoxide synthase 2 (PTGS2), and the NF-κB signaling pathway. The in vitro assay on H9c2 cardiomyocytes subjected to hypoxia/reoxygenation injury confirmed that the flavonoids in OFF1 reduced myocardial marker levels, apoptotic rate, and the inflammatory response triggered by oxidative stress. Moreover, OFF1 attenuated MIRI by downregulating the ROS-mediated JNK/p38MAPK/NF-κB pathway. Collectively, these findings provide novel insights into the molecular mechanism of O. falcata in alleviating MIRI, being a potential therapeutic candidate.


Asunto(s)
Daño por Reperfusión Miocárdica , Oxytropis , Flavonoides/farmacología , Flavonoides/uso terapéutico , Daño por Reperfusión Miocárdica/metabolismo , FN-kappa B/metabolismo , Oxytropis/química , Transducción de Señal
8.
Genet Mol Biol ; 45(4): e20210420, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36255267

RESUMEN

Breast cancer is the most common malignant tumor in women. A previous genome-wide association study reports that rs72755295, a SNP locating at intron of EXO1 (exonuclease 1), is associated with breast cancer. Due to the complete linkage disequilibrium between rs72755295 and rs4149909, a nonsynonymous mutation for EXO1, rs4149909 is supposed to be the causal SNP. Since EXO1 is overexpressed in breast carcinoma samples, we hypothesized that the genetic variations in this locus might confer breast cancer risk by regulating EXO1 expression. To substantiate this, a functional genomics study was performed. The dual luciferase assay indicated that G of rs72755295 presents significantly higher relative enhancer activity than A, thus verifying that this SNP can influence gene expression in breast cell. Through chromosome conformation capture it was disclosed that the enhancer containing rs72755295 can interact with the EXO1 promoter. RNA-seq analysis indicated that EXO1 expression is dependent on the rs72755295 genotype. By chromatin immunoprecipitation, the transcription factor PAX6 (paired box 6) was recognized to bind the region spanning rs72755295. In electrophoretic mobility shift assay, G of rs72755295 displays obviously higher binding affinity with nuclear protein than A. Our results indicated that rs72755295 is a cis-regulatory variation for EXO1 and might confer breast cancer risk besides rs4149909.

9.
IUBMB Life ; 73(1): 146-158, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33249722

RESUMEN

Activating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene-delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum-derived exosomes from OA mice as the gene-delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury-induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham-Exo and OA-Exo, respectively. ATF4-overexpressing OA-Exo (ATF4-OA-Exo) was developed by introducing ATF4 mRNA into OA-Exo via electroporation. Four weeks after surgery, OA mice received intra-articular injections of sham-Exo, OA-Exo, and ATF4-OA-Exo, respectively. The results showed that intra-articular injection of ATF4-OA-Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra-articular injection of ATF4-OA-Exo. Further in vitro assays revealed that ATF4-OA-Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF-α- or tunicamycin-treated chondrocytes. Together, ATF4-modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.


Asunto(s)
Factor de Transcripción Activador 4/metabolismo , Autofagia , Cartílago Articular/citología , Condrocitos/citología , Exosomas/trasplante , Osteoartritis/prevención & control , Factor de Transcripción Activador 4/genética , Animales , Exosomas/genética , Exosomas/metabolismo , Femenino , Ratones , Ratones Endogámicos C57BL , Osteoartritis/metabolismo , Osteoartritis/patología
10.
PLoS Biol ; 16(6): e2004880, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29879109

RESUMEN

N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase-like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here, we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout (cKO) mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of newborn cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion-induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum.


Asunto(s)
Adenosina/análogos & derivados , Cerebelo/embriología , Metiltransferasas/metabolismo , ARN Mensajero/genética , Adenosina/metabolismo , Empalme Alternativo/genética , Animales , Apoptosis/genética , Células Cultivadas , Cerebelo/anomalías , Cerebelo/patología , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Regulación de la Expresión Génica/genética , Metilación , Metiltransferasas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , Malformaciones del Sistema Nervioso/genética , Malformaciones del Sistema Nervioso/patología , Estabilidad del ARN/genética , ARN Mensajero/metabolismo
11.
J Gastroenterol Hepatol ; 36(5): 1291-1299, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33091955

RESUMEN

BACKGROUND AND AIM: It has been reported that serum quantification of anti-HBc (qAnti-HBc) could predict antiviral response in chronic hepatitis B (CHB) patients, while its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) remains unclear. Its implication in HBV-ACLF was evaluated in this study. METHODS: Baseline serum qAnti-HBc levels were retrospectively detected in HBV-ACLF and CHB patients using recently developed double-sandwich immunoassay. The association of qAnti-HBc level with clinical outcomes was evaluated by multiple logistic regression. Nomogram was adopted to formulate an algorithm incorporating qAnti-HBc for the prediction of survival in HBV-ACLF. The post-hospitalization of HBV-ACLF patients were followed-up for 1 year. RESULTS: Eighty-eight HBV-ACLF as training set, 80 HBV-ACLF as validation set and 216 CHB cases were included. Serum qAnti-HBc level was significantly higher in HBV-ACLF (4.95 ± 0.54 log10  IU/mL) than CHB patients (4.47 ± 0.84 log10  IU/mL) (P < 0.01). Among HBV-ACLF cases, both in training and validation set, patients with poor outcomes had lower qAnti-HBc level. Area under receiver operating characteristic curve of the novel qAnti-HBc inclusive model was 0.82, superior to 0.73 from model for end-stage liver disease scores (P = 0.018), which was confirmed in validation set. During follow-up, the qAnti-HBc level declined at month 3 and month 6, then plateaued at 3.84 log10  IU/mL. CONCLUSIONS: Serum qAnti-HBc level was associated with disease severity and might be served as a novel biomarker in the prediction of HBV-ACLF clinical outcomes. The underlying immunological mechanism warrants further investigation.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/etiología , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/diagnóstico , Adulto , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Índice de Severidad de la Enfermedad
12.
Bioorg Chem ; 107: 104628, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33461038

RESUMEN

Most of Euphorbiaceae plants are considered as folk medicinal plants because of their various pharmacological effects. However, there are eight Leptopus genus plants which belong to Euphorbiaceae have never be investigated. Thus, four Leptopus genus plants were collected to study their chemical constituents and pharmacological activities. In the present work, the cytotoxicities of the extracts of four Leptopus genus plants were evaluated before phytochemical experiments. And nine new phenylpropanoid-conjugated pentacyclic triterpenoids, along with twenty-two known compounds were isolated from the whole plants of Leptopus lolonum. The structures of these new compounds were unequivocally elucidated by HRESIMS and 1D/2D NMR data. All triterpenoids were screened for their cytotoxicities against four cancer cell lines including HepG2, MCF-7, A549 and HeLa. Among these isolates, the triterpenoid with a phenylpropanoid unit showed increasing cytotoxicity on cancer cells, which suggested the importance of the phenylpropanoid moiety.


Asunto(s)
Antineoplásicos Fitogénicos/química , Malpighiales/química , Propanoles/química , Triterpenos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Espectroscopía de Resonancia Magnética , Malpighiales/metabolismo , Conformación Molecular , Extractos Vegetales/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Plantas Medicinales/química , Plantas Medicinales/metabolismo , Relación Estructura-Actividad , Triterpenos/aislamiento & purificación , Triterpenos/farmacología
13.
Bioorg Chem ; 111: 104886, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33836342

RESUMEN

Our present and previous phytochemical investigations on Leptopus lolonum have resulted in the isolation of almost 30 phenylpropanoid-conjugated pentacyclic triterpenoids (PCPTs). During the continuous study on PCPTs, this kind of triterpenoid ester is considered as a natural product with low toxicity because of it's widely distribution in natural plants and edible fruits including kiwi fruit, durian, jujube, pawpaw, apple and pear. In the present work, we report the isolation, structural elucidation and cytotoxic evaluation of four new PCPTs (1-4) which obtained from L. lolonum. In addition, the possible biosynthesis pathway for 28-norlupane triterpenoid and potent effect of phenylpropanoid moiety for increasing the cytotxic effect of triterpenoids were also discussed. Among these compounds, compound 1 exhibited the highest cytotoxic effect on HepG2 cells with IC50 value of 11.87 µM. Further flow cytometry and western blot analysis demonstrated that 1 caused G1 cell cycle arrest by up-regulated the expression of phosphorylated p53 protein in HepG2 cells and induced cell apoptosis via MAPK and Akt pathways. These results emphasized the potential of PCPTs as lead compounds for developing anti-cancer drugs.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Malpighiales/química , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales/química , Propanoles/química , Propanoles/aislamiento & purificación , Propanoles/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología
14.
Acta Pharmacol Sin ; 42(10): 1714-1722, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33469196

RESUMEN

Lung cancer is one of the leading causes of cancer-related death worldwide. Various therapeutic failed in the effective treatment of the lung cancer due to their limited accumulation and exposure in tumors. In order to promote the chemotherapeutics delivery to lung tumor, we introduced chitosan oligosaccharide (CSO) modification on the liposomes. CSO conjugated Pluronic P123 polymers with different CSO grafting amounts, called as CP50 and CP20, were synthesized and used to prepare CSO modified liposomes (CP50-LSs and CP20-LSs). CP50-LSs and CP20-LSs displayed significantly enhanced cellular uptake in A549 cells in vitro as well as superior tumor accumulation in vivo compared with non-CSO modified liposomes (P-LSs). This phenomenon was related to the increased affinity between CSO modified liposomes and tumor cells following massive adsorption of collagen, which was highly expressed in lung tumors. In the A549 tumor-bearing mouse model, intravenous injection of paclitaxel (PTX)-loaded CP50-LSs every 3 days for 21 days resulted in optimal antitumor therapeutic performance with an inhibition rate of 86.4%. These results reveal that CSO modification provides promising applicability for nanomedicine design in the lung cancer treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Quitosano/química , Portadores de Fármacos/química , Liposomas/química , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Células A549 , Animales , Antineoplásicos/química , Quitosano/metabolismo , Portadores de Fármacos/metabolismo , Liberación de Fármacos , Humanos , Liposomas/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Oligosacáridos/química , Oligosacáridos/metabolismo , Paclitaxel/química
15.
Nanomedicine ; 33: 102362, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33476765

RESUMEN

Stroke is one of the most serious problems that seriously affect people's health and brings huge economic burden to society. The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In recent years, nano drug delivery system has developed rapidly and applied to treat ischemic stroke. Here, we report the synthesis and functionalization of monodisperse hollow structured MnO2 (H-MnO2). The highly monodisperse H-MnO2 with uniform morphology was obtained by in situ growing MnO2 on solid silica nanoparticles and subsequently removing the silica core. After successive modification of poly ethylene glycol(PEG), we further verified their protective effect on ischemic stroke in our study.


Asunto(s)
Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Compuestos de Manganeso/química , Sistema de Administración de Fármacos con Nanopartículas/química , Óxidos/química , Polietilenglicoles/química , Dióxido de Silicio/química , Animales , Apoptosis/efectos de los fármacos , Conducta Animal , Modelos Animales de Enfermedad , Liberación de Fármacos , Humanos , Masculino , Prueba del Laberinto Acuático de Morris , Sistema de Administración de Fármacos con Nanopartículas/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas/efectos adversos , Ratas , Ratas Sprague-Dawley , Propiedades de Superficie
16.
J Environ Manage ; 278(Pt 2): 111573, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33137687

RESUMEN

This study investigated impacts of silver nanoparticles (AgNPs) on nitrogen removal within constructed wetlands (CWs) with different flow directions. The obtained results showed that addition of AgNPs at 0.5 and 2 mg/L significantly inhibited NH4+-N removal, resulting from lower abundances of functional genes (amoA and nxrA) within CWs. And higher abundances of amoA and nxrA genes at 0.5 mg/L were observed in downward flow CW, leading to better NH4+-N removal, compared to upward flow CW. Besides, nitrifying genes amoA and nxrA in upward flow CW at 2.0 mg/L exhibited higher than downward flow CW, explaining better NH4+-N removal in upward flow CW. 0.5 mg/L AgNPs significantly declined NO3--N and TN removal, resulted from decreasing abundances of nirK, nirS and nosZ. In contrast, abundances of nirK, nirS and nosZ genes had slightly lower or higher than before adding AgNPs in upward flow CW, leading to lower NO3--N and TN effluent concentrations. High throughput sequencing also indicated the changes of functional bacterial community after exposing to AgNPs.


Asunto(s)
Nanopartículas del Metal , Humedales , Desnitrificación , Nitrógeno/análisis , Plata , Eliminación de Residuos Líquidos , Aguas Residuales
17.
Pharmazie ; 76(2): 55-60, 2021 02 25.
Artículo en Inglés | MEDLINE | ID: mdl-33714280

RESUMEN

Ferulic acid, a hydroxyl derivative extracted from plants, is abundant in free state in seeds and leaves, or covalently linked with cell wall polysaccharides, lignin and different polymers. It has various pharmacological activities, including antioxidant and anti-inflammatory effects, regulates immunity, protects the cardiovascular system, and contributes to the prevention of tumors and diabetes. The protective effect on cardiovascular system is the most valuable one in view of clinical application. Here, we are reviewing the research progress concerning the pharmacological effects of ferulic acid and its derivatives on cardiovascular diseases in the past five years, mainly focusing on mechanisms of action and clinical application. This should provide guidance for clinical applications of ferulic acid and its derivatives in the treatment of cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Ácidos Cumáricos/farmacología , Animales , Humanos , Extractos Vegetales , Plantas/química
18.
Pak J Med Sci ; 37(3): 740-745, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34104158

RESUMEN

OBJECTIVES: To observe the clinical value of 3D printing technology assisted surgery combined with early postoperative comprehensive rehabilitation in elderly patients with intertrochanteric fractures. METHODS: Sixty elderly patients with intertrochanteric fractures of the femur who were treated in our hospital from January 2018 to January 2020 were selected and randomly divided into two groups. In the experimental group, 3D printing technology assisted surgery combined with early postoperative comprehensive rehabilitation was used for treatment. While in the control group, traditional open reduction and dynamic hip screw internal fixation combined with postoperative conventional treatment was utilized. The duration of surgery, intraoperative blood loss, postoperative hospital stay, weight bearing time, fracture healing time and other surgical indicators were recorded respectively, and hip joint function recovery was evaluated prior to and 2 weeks after surgery. All patients were followed up for six months to observe the occurrence of complications within half a year, including deep vein thrombosis, incision infection, avascular necrosis of femoral head, hip joint stiffness, delayed fracture healing, etc. Subsequently, the differences in postoperative complications between the two groups were compared and analyzed. RESULTS: The operation time, blood loss, postoperative hospital stay, weight bearing time and fracture healing time of the experimental group were better than those of the control group, and the difference was statistically significant (p<0.05). After treatment, the hip joint function of the experimental group was significantly improved compared with the control group, with a statistically significant difference(p=0.03). The incidence of operative complications in the experimental group was 10% (3/30) within six months postoperatively, significantly lower than the 33% (10/30) in the control group, with statistical significance (p=0.03). CONCLUSION: 3D printing with early rehab proved to be effective treatment in our study. Such a combined treatment has the advantages of precise operative reduction, fast postoperative recovery, and certain safety and effectiveness.

19.
J Clin Microbiol ; 58(9)2020 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-32554476

RESUMEN

Hepatitis B virus (HBV) RNA may independently predict virological and serological response. This study aimed to compare dynamic changes in serum HBV RNA levels and HBV quasispecies evolution patterns between entecavir and pegylated-interferon mono-treatment in chronic hepatitis B patients and to determine the clinical significance during treatment. TaqMan real-time PCR was used for quantitative analysis. HBV RNA levels were retrospectively determined in serial serum samples from 178 chronic hepatitis B patients who received either entecavir or pegylated-interferon treatment. Both serum HBV DNA and RNA quasispecies were analyzed via next-generation sequencing. Receiver operating characteristics (ROC) analysis was performed to evaluate the prediction value of individual biomarkers for hepatitis B e antigen (HBeAg) seroconversion. Patients who received pegylated-interferon treatment showed stronger declines in HBV RNA levels than did those who received entecavir treatment. Serum HBV RNA levels were lower in patients with subsequent HBeAg seroconversion. At baseline, the level of HBV RNA was better than other indicators in predicting HBeAg seroconversion. Moreover, the predictive value of serum HBV RNA levels was better in the entecavir group. Baseline HBV RNA exhibited a significantly higher genetic diversity than HBV DNA and had a significant decline after 4 weeks of entecavir treatment. Higher baseline genetic diversity may result in a better outcome in pegylated-interferon-treated patients. Serum HBV RNA levels showed different decline kinetics, and HBV RNA quasispecies showed different evolution patterns in entecavir and pegylated-interferon mono-treatment. Taken together, serum HBV RNA may serve as a promising biomarker of HBeAg seroconversion in patients during antiviral treatment.


Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica , Antivirales/uso terapéutico , ADN Viral/genética , Guanina/análogos & derivados , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Polietilenglicoles/uso terapéutico , Cuasiespecies , ARN , Proteínas Recombinantes , Estudios Retrospectivos , Resultado del Tratamiento , Carga Viral
20.
Opt Express ; 28(13): 18713-18727, 2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32672166

RESUMEN

Based on our previously proposed modified Monte Carlo method, which is efficient to simulate the time-dependent polarized radiative transfer problem in an atmosphere-ocean model with a reflective/refractive interface, we further investigate the square pulse effect on the polarized radiative transfer in an atmosphere-ocean model. A short square pulse, with a duration of nanoseconds, is assumed to be incident at the top of the atmosphere. The polarized signals varying with time and directions are presented for the locations just above and below the atmosphere-water interface and at the bottom of the ocean, and effects of the incidence and disappearance of the external pulse on the Stokes vector components are analyzed. Results in this paper present the general distribution of square-pulse induced polarized signals and they are important for signal analysis in the field of remote sensing using nanosecond pulses.

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