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Here, we report on a case of human infection with the H3N8 avian influenza virus. The patient had multiple myeloma and died of severe infection. Genome analysis showed multiple gene mutations and reassortments without mammalian-adaptive mutations. This suggests that avian influenza (A/H3N8) virus infection could be lethal for immunocompromised persons.
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Subtipo H3N8 del Virus de la Influenza A , Gripe Humana , Humanos , China , Subtipo H3N8 del Virus de la Influenza A/genéticaRESUMEN
BACKGROUND: Peutz-Jeghers syndrome (PJS), a rare dominantly inherited disease, is primarily characterized by hamartomatous polyps and melanotic macules as well as by an increased risk of cancer. The current study aimed to identify the pathogenic gene and pathogenic mechanism of a proband with PJS, thereby offering precise prevention and treatment strategies for PJS. METHODS: A detailed clinical examination was performed of the proband diagnosed with PJS and her family members. In addition, peripheral venous blood was collected from the family members to extract genomic DNA. The pathogenic genes of the proband were identified using whole-exome sequencing, and the candidate pathogenic variants were verified via Sanger sequencing. Meanwhile, co-segregation tests were performed among six family members. Finally, reverse transcription-polymerase chain reaction (RT-PCR) was performed to assess transcript variants in the peripheral blood cells of patients and non-related healthy controls. RESULTS: Genetic testing revealed a rare splicing variant c.921-1G > C in STK11 in the proband and in her sister and nephew, and the variant co-segregated among the affected family members and nonrelated healthy controls. The proband phenotypically presented with a rare gastric-type adenocarcinoma of the cervix. RT-PCR revealed that the STK11 c.921-1G > C variant could produce two transcripts. Of note, 40 base pairs were deleted in the aberrant transcript between exons 3 and 4, resulting in a frameshift variant and premature termination of the amino acid in exon 6 and ultimately leading to the loss of its functional domain in the STK11 protein. Finally, RT-PCR showed that compared with healthy controls, STK11 mRNA expression level was < 50% in patients. CONCLUSION: The present study results indicated that the rare splicing variant c.921-1G > C in intron 7 of STK11 may be a pathogenic variant in patients with PJS. However, this variant (in intron 7) may not produce abnormal transcripts (deletion of 40 base pairs between exons 3 and 4), and PJS may be attributed to the decrease in STK11 expression. Therefore, this study emphasized the importance of genetic counseling, pre-symptomatic monitoring, and early complication management in PJS.
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Intrones , Linaje , Síndrome de Peutz-Jeghers , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quinasas de la Proteína-Quinasa Activada por el AMP , Pueblos del Este de Asia , Secuenciación del Exoma , Intrones/genética , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/patología , Síndrome de Peutz-Jeghers/complicaciones , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Empalme del ARNRESUMEN
BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This condition is characterized by germline variants in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2. In this study, we analyzed the molecular defects and clinical manifestations of two families affected with CRC and proposed appropriate individual preventive strategies for all carriers of the variant. METHODS: We recruited two families diagnosed with CRC and combined their family history and immunohistochemical results to analyze the variants of probands and those of other family members by using whole exome sequencing. Subsequently, gene variants in each family were screened by comparing them with the variants available in the public database. Sanger sequencing was performed to verify the variant sites. An online platform ( https://www.uniprot.org ) was used to analyze the functional domains of mutant proteins. RESULTS: A novel frameshift variant (NM_001281492, c.1129_1130del, p.R377fs) in MSH6 and a known deleterious variant (NM_000249.4:c.1731G > A, p.S577S) in MLH1 were identified in the two families with CRC. Using bioinformatics tools, we noted that the frameshift variant reduced the number of amino acids in the MSH6 protein from 1230 to 383, thereby leading to no MSH6 protein expression. The silent variant caused splicing defects and was strongly associated with LS. 5-Fluorouracil-based adjuvant chemotherapy is not recommended for patients with LS. CONCLUSIONS: The novel frameshift variant (MSH6, c.1129_1130del, p.R377fs) is likely pathogenic to LS, and the variant (MLH1, c.1731G > A, p.S577S) has been further confirmed to be pathogenic to LS. Our findings underscore the significance of genetic testing for LS and recommend that genetic consultation and regular follow-ups be conducted to guide individualized treatment for cancer-afflicted families, especially those with a deficiency in MMR expression.
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Neoplasias Colorrectales Hereditarias sin Poliposis , Síndromes Neoplásicos Hereditarios , Humanos , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Reparación de la Incompatibilidad de ADN/genética , Mutación de Línea Germinal , Proteínas de Unión al ADN/genética , China/epidemiología , Homólogo 1 de la Proteína MutL/genética , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismoRESUMEN
Although bacteriophage-based biosensors hold promise for detecting Staphylococcus aureus in food products in a timely, simple, and sensitive manner, the associated targeting mechanism of the biosensors remains unclear. Herein, a colourimetric biosensor SapYZU11@ZnFe2O4, based on a broad-spectrum S. aureus lytic phage SapYZU11 and a ZnFe2O4 nanozyme, was constructed, and its capacity to detect viable S. aureus in food was evaluated. Characterisation of SapYZU11@ZnFe2O4 revealed its effective immobilisation, outstanding biological activity, and peroxidase-like capability. The peroxidase activity of SapYZU11@ZnFe2O4 significantly decreased after the addition of S. aureus, potentially due to blockage of the nanozyme active sites. Moreover, SapYZU11@ZnFe2O4 can detect S. aureus from various sources and S. aureus isolates that phage SapYZU11 could not lyse. This may be facilitated by the adsorption of the special receptor-binding proteins on the phage tail fibre and wall teichoic acid receptors of S. aureus. Besides, SapYZU11@ZnFe2O4 exhibited remarkable sensitivity and specificity when employing colourimetric techniques to rapidly determine viable S. aureus counts in food samples, with a detection limit of 0.87 × 102 CFU/mL. Thus, SapYZU11@ZnFe2O4 has broad application prospects for the detection of viable S. aureus cells on food substrates.
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Técnicas Biosensibles , Colorimetría , Contaminación de Alimentos , Microbiología de Alimentos , Staphylococcus aureus , Staphylococcus aureus/aislamiento & purificación , Técnicas Biosensibles/métodos , Colorimetría/métodos , Contaminación de Alimentos/análisis , Fagos de Staphylococcus , Límite de DetecciónRESUMEN
BACKGROUND: Real-world evidence on inactivated COVID-19 vaccines against the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2 is limited, leaving an important gap in the evidence base about inactivated COVID-19 vaccines for use by immunization programs. OBJECTIVE: To estimate inactivated vaccine effectiveness (VE) against the B.1.617.2 variant. DESIGN: Retrospective cohort study. SETTING: The study was based on the first outbreak of the B.1.617.2 variant in mainland China that was discovered and traced in Guangdong in May and June 2021. PARTICIPANTS: 10 805 adult case patients with laboratory-confirmed infection and close contacts. MEASUREMENTS: Participants were categorized as unvaccinated, partially vaccinated (1 dose), and fully vaccinated (2 doses). We estimated VE against the primary outcome of pneumonia and the secondary outcomes of infections, symptomatic infections, and severe or critical illness associated with the B.1.617.2 variant. RESULTS: Results are reported in the order of outcome severity. Of 10 805 participants, 1.3% contracted infections, 1.2% developed symptomatic infections, 1.1% had pneumonia, and 0.2% had severe or critical illness. The adjusted VEs of full vaccination were 51.8% (95% CI, 20.3% to 83.2%) against infection, 60.4% (CI, 31.8% to 88.9%) against symptomatic infection, and 78.4% (CI, 56.9% to 99.9%) against pneumonia. Also, full vaccination was 100% (CI, 98.4% to 100.0%) effective against severe or critical illness. By contrast, the adjusted VEs of partial vaccination against infection, symptomatic infection, and pneumonia were 10.7% (CI, -41.2% to 62.6%), 6.8% (CI, -47.4% to 61.0%), and 11.6% (CI, -42.6% to 65.8%), respectively. LIMITATION: Observational study with possible unmeasured confounders; insufficient data to do reliable subgroup analyses by age and vaccine brand. CONCLUSION: Full vaccination with inactivated vaccines is effective against the B.1.617.2 variant. Effort should be made to ensure full vaccination of target populations. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China and Key-Area Research and Development Program of Guangdong Province.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Estudios de Cohortes , Enfermedad Crítica , Humanos , Estudios Retrospectivos , SARS-CoV-2/genética , Vacunas de Productos InactivadosRESUMEN
Lilii Bulbus is a commonly used Chinese herbal medicine with both medicinal and edible values, while the market products usually has the problem of sulfur fumigation. Therefore, the quality and safety of Lilii Bulbus products deserve attention. In this study, ultra-high performance liquid chromatography-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to analyze the differential components of Lilii Bulbus before and after sulfur fumigation. We identified ten markers generated after sulfur fumigation, summarized their mass fragmentation and transformation patterns, and verified the structures of phenylacrylic acid markers of sulfur fumigation. At the same time, the cytotoxicity of the aqueous extracts of Lilii Bulbus before and after sulfur fumigation was evaluated. The results showed that in the concentration range of 0-800 mg·L~(-1), the aqueous extract of Lilii Bulbus after sulfur fumigation had no significant effect on the viability of human liver LO2 cells, human renal proximal tubular HK-2 cells, and rat adrenal pheochromocytoma PC-12 cells. Moreover, the viability of the cells exposed to the aqueous extract of Lilii Bulbus before and after sulfur fumigation showed no significant difference. This study identified phenylacrylic acid and furostanol saponins as markers of sulfur-fumigated Lilii Bulbus for the first time, and made clear that proper sulfur fumigation of Lilii Bulbus would not produce cytotoxicity, providing a theoretical basis for the rapid identification and quality and safety control of sulfur-fumigated Lilii Bulbus.
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Fumigación , Espectrometría de Masas en Tándem , Humanos , Animales , Ratas , Cromatografía Líquida de Alta Presión , Células Epiteliales , AzufreRESUMEN
Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.
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Bombyx , Morus , Animales , Morus/química , Ácido Clorogénico/análisis , Cromatografía de Gases y Espectrometría de Masas , Cromatografía Líquida de Alta Presión/métodos , Hojas de la Planta/químicaRESUMEN
OBJECTIVES: Subarachnoid hemorrhage (SAH) is a subtype of stroke, and early brain injury (EBI) is a contributor to its unfavorable outcome. microRNA (miRNA) is abundantly expressed in the brain and participates in brain injury. This study investigated the effect of miR-452-3p on EBI after SAH. METHODS: The murine model of SAH was established. miR-452-3p expression was detected 48 h after the model establishment. Neurobehavioral function, blood-brain barrier permeability, brain water content, neuronal apoptosis, and inflammatory factors were evaluated. The cell model of SAH was induced by oxygen hemoglobin. Apoptosis rate, lactate dehydrogenase, and reactive oxygen species were detected. The targeting relationship between miR-452-3p and histone deacetylase 3 (HDAC3) was verified. The acetylation of p65 and the binding of HDAC3 to p65 were detected. The inhibitory protein of the nuclear factor κB pathway (IκBα) was detected. Suberoylanilide hydroxamic acid was injected into the SAH mice treated with miR-452-3p inhibitor. RESULTS: SAH mice showed upregulated miR-452-3p expression; reduced the neurological score; increased blood-brain barrier permeability, brain water content, and neuronal apoptosis; elevated pro-inflammatory factors; and reduced anti-inflammatory factors. SAH increased the apoptosis rate, lactate dehydrogenase release, and reactive oxygen species levels in oxygen-hemoglobin-treated neuron cells. Inhibition of miR-452-3p reversed the above trends. miR-452-3p targeted HDAC3. SAH upregulated p65 acetylation. miR-452-3p inhibitor promoted the binding of HDAC3 to p65, decreased p65 acetylation, and upregulated IκBα. Suberoylanilide hydroxamic acid reversed the protective effect of miR-452-3p inhibitor on SAH mice and aggravated brain injury. CONCLUSIONS: miR-452-3p targeted HDAC3 to inhibit the deacetylation of p65 and activate the nuclear factor κB pathway, thus aggravating EBI after SAH.
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Lesiones Encefálicas , MicroARNs , Hemorragia Subaracnoidea , Animales , Antiinflamatorios/farmacología , Apoptosis , Lesiones Encefálicas/metabolismo , Histona Desacetilasas , Lactato Deshidrogenasas/metabolismo , Ratones , MicroARNs/farmacología , MicroARNs/uso terapéutico , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , FN-kappa B/farmacología , FN-kappa B/uso terapéutico , Oxígeno , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Hemorragia Subaracnoidea/tratamiento farmacológico , Vorinostat/farmacología , Vorinostat/uso terapéutico , Agua/farmacologíaRESUMEN
Some studies have demonstrated that precipitation is an important risk factor of dengue epidemics. However, current studies mostly focused on a single precipitation variable, and few studies focused on the impact of precipitation patterns on dengue epidemics. This study aims to explore optimal precipitation patterns for dengue epidemics. Weekly dengue case counts and meteorological data from 2006 to 2018 in Guangzhou of China were collected. A generalized additive model with Poisson distribution was used to investigate the association between precipitation patterns and dengue. Precipitation patterns were defined as the combinations of three weekly precipitation variables: accumulative precipitation (Pre_A), the number of days with light or moderate precipitation (Pre_LMD), and the coefficient of precipitation variation (Pre_CV). We explored to identify optimal precipitation patterns for dengue epidemics. With a lead time of 10 weeks, minimum temperature, relative humidity, Pre_A, and Pre_LMD were positively associated with dengue, while Pre_CV was negatively associated with dengue. A precipitation pattern with Pre_A of 20.67-55.50 mm per week, Pre_LMD of 3-4 days per week, and Pre_CV less than 1.41 per week might be an optimal precipitation pattern for dengue epidemics in Guangzhou. The finding may be used for climate-smart early warning and decision-making of dengue prevention and control.
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Dengue , Epidemias , China/epidemiología , Clima , Dengue/epidemiología , Humanos , Incidencia , Distribución de Poisson , TemperaturaRESUMEN
Based on the systematic retrieval and the reported components of Sojae Semen Nigrum and Sojae Semen Praeparatum, this study conducted in-depth analysis of conversion of components in the fermentation process, and discussed types and possible mec-hanisms of conversion of chemical components, so as to provide the basis for studying technology, medicinal ingredients and quality standards. According to the analysis, there is a certain degree of conversion of nutrients(like protein, sugar, lipid), bioactive substances(like isoflavones, saponins, γ-aminobutyric acid) and other substances(like nucleosides, melanoids, biamines, etc) in the process of fermentation.
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Glycine max , Isoflavonas , Cromatografía Líquida de Alta Presión , Fermentación , Isoflavonas/análisis , Semen/químicaRESUMEN
OBJECTIVE: To compare the severity of psychological distress between patients with epilepsy and healthy controls during the COVID-19 outbreak in southwest China, as well as identify potential risk factors of severe psychological distress among patients with epilepsy. METHODS: This cross-sectional case-control study examined a consecutive sample of patients older than 15 years treated at the epilepsy center of West China Hospital between February 1 and February 29, 2020. As controls, sex- and age-matched healthy visitors of inpatients (unrelated to the patients) were also enrolled during the same period. Data on demographics and attention paid to COVID-19 were collected by online questionnaire, data on epilepsy features were collected from electronic medical records, and psychological distress was evaluated using the 6-item Kessler Psychological Distress Scale (K-6). Potential risk factors of severe psychological distress were identified using multivariate logistic regression. RESULTS: The 252 patients and 252 controls in this study were similar along all demographic variables except family income. Patients with epilepsy showed significantly higher K-6 scores than healthy controls and spent significantly more time following the COVID-19 outbreak (both P < .001). Univariate analyses associated both diagnosis of drug-resistant epilepsy and time spent paying attention to COVID-19 with severe psychological distress (defined as K-6 score >12; both P ≤ .001). Multivariate logistic regression identified two independent predictors of severe psychological distress: time spent paying attention to COVID-19 (odds ratio [OR] = 1.172, 95% confidence interval [CI] = 1.073-1.280) and diagnosis of drug-resistant epilepsy (OR = 0.283, 95% CI = 0.128-0.623). SIGNIFICANCE: During public health outbreaks, clinicians and caregivers should focus not only on seizure control but also on mental health of patients with epilepsy, especially those with drug-resistant epilepsy. K-6 scores > 12 indicate severe psychological distress. This may mean, for example, encouraging patients to engage in other activities instead of excessively following media coverage of the outbreak.
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Ansiedad/epidemiología , Infecciones por Coronavirus , Depresión/epidemiología , Epilepsia/epidemiología , Pandemias , Neumonía Viral , Distrés Psicológico , Adolescente , Adulto , Ansiedad/psicología , Atención , Betacoronavirus , COVID-19 , Estudios de Casos y Controles , China/epidemiología , Estudios Transversales , Depresión/psicología , Brotes de Enfermedades , Epilepsia Refractaria/epidemiología , Femenino , Humanos , Masculino , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto JovenRESUMEN
The present study included 658 hospitalized patients with confirmed COVID-19. Forty-two (6.4%) out of 658 patients presented with ketosis on admission with no obvious fever or diarrhoea. They had a median (interquartile range [IQR]) age of 47.0 (38.0-70.3) years, and 16 (38.1%) were men. Patients with ketosis were younger (median age 47.0 vs. 58.0 years; P = 0.003) and had a greater prevalence of fatigue (31.0% vs. 10.6%; P < 0.001), diabetes (35.7% vs. 18.5%; P = 0.007) and digestive disorders (31.0% vs. 12.0%; P < 0.001). They had a longer median (IQR) length of hospital stay (19.0 [12.8-33.3] vs. 16.0 [10.0-24.0] days; P < 0.001) and a higher mortality rate (21.4% vs. 8.9%; P = 0.017). Three (20.0%) out of the 15 patients with diabetic ketosis developed acidosis, five patients (26.7%) with diabetic ketosis died, and one of these (25.0%) presented with acidosis. Two (7.4%) and four (14.3%) of the 27 non-diabetic ketotic patients developed severe acidosis and died, respectively, and one (25.0%) of these presented with acidosis. This suggests that COVID-19 infection caused ketosis or ketoacidosis, and induced diabetic ketoacidosis for those with diabetes. Ketosis increased the length of hospital stay and mortality. Meanwhile, diabetes increased the length of hospital stay for patients with ketosis but had no effect on their mortality.
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COVID-19/complicaciones , Cetoacidosis Diabética/etiología , Cetosis/etiología , Adulto , Anciano , COVID-19/epidemiología , COVID-19/metabolismo , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/patología , Progresión de la Enfermedad , Femenino , Humanos , Cetosis/epidemiología , Cetosis/patología , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Pandemias , Prevalencia , Estudios Retrospectivos , SARS-CoV-2/fisiología , Índice de Severidad de la EnfermedadRESUMEN
The purpose of this article is to study the degradation of chemical compositions after the silkworm excrement being expelled from the silkworm, and to determine its main metabolic compositions and their changing relationships. This research is based on UPLC-Q-TOF-MS technology. Based on the systematic analysis of the main chemical compositions contained in silkworm excrement, the principal compositions analysis(PCA) and partial least squares discriminant analysis(OPLS-DA) on commercial silkworm excrement and fresh silkworm excrement were analyzed for differences. The S-plot chart of OPLS-DA was used to select and identify the chemical compositions that contributed significantly to the difference. At the same time, the relative peak areas of the different compositions were extracted by Masslynx to obtain the relative content of different compositions in fresh silkworm excrement. The results showed that there was a significant difference in the chemical compositions between fresh silkworm excrement and commercial silkworm excrement. The difference compositions were mainly flavonoid glycosides and Diels-Alder type composition, and two types of compounds are degradated during the storage of silkworm sand. In this study, the chemical compositions of fresh silkworm excrement were systematically identified and analyzed for the first time by mass spectrometry, and it was found that some chemical compositions of silkworm excrement were degradated with time during storage.
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Bombyx , Medicamentos Herbarios Chinos , Animales , Cromatografía Líquida de Alta Presión , Análisis Discriminante , Espectrometría de MasasRESUMEN
This study aimed to develop novel temperature-sensitive liposomes loading paclitaxel (PTX-TSL) and evaluate them in vitro to improve the delivery efficiency and targeting of PTX. K237 peptide was conjugated to the terminal NHS of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)-(DSPE-PEG-NHS), and K237-modified PTX-TSL (K237-PTX-TSL) was prepared using a film dispersion method. K237-TSL encapsulation with calcein was synthesized and used to determine the cellular uptake of TSL. The morphology of K237-PTX-TSL was observed using a transmission electron microscope. The particle size and potential were measured using a laser particle size analyzer. The phase transition temperature was detected using the differential scanning calorimetry. The Cell Counting Kit-8 assay and flow cytometry were used to evaluate the effects of K237-PTX-TSL on the proliferation and cell cycle of cell lines SKOV-3 and human umbilical vein endothelial cell (HUVEC). The encapsulation efficiency of K237-PTX-TSL was 94.23% ± 0.76%. The particle diameter was 88.3 ± 4.7 nm. K237-PTX-TSL showed a fast release profile at 42 °C, while it was stable at 37 °C. PTX-TSL combined with hyperthermia significantly inhibited the cell proliferation of SKOV-3 cells and HUVECs due to increased cell arrest in the G2/M phase. The half-minimal inhibitory concentration value of K237-PTX-TSL on SKOV-3 cells and HUVECs was 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L, respectively, which were significantly lower than those with PTX-TSL (p < 0.01). K237 modification could increase the targeting efficiency of TSL to cancer cells and vascular endothelial cells, thus resulting in higher cytotoxicities compared with PTX-TSL, which might be a potential formulation for targeting cancer therapy.
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Antineoplásicos Fitogénicos/administración & dosificación , Liposomas , Oligopéptidos , Paclitaxel/administración & dosificación , Animales , Línea Celular , Humanos , Liposomas/química , Fosfatidiletanolaminas , Polietilenglicoles , Temperatura de TransiciónRESUMEN
BACKGROUND/AIMS: This study aimed to investigate the effects of the VR-10 TSP-1 synthetic polypeptide on cytokines and the proliferation and migration of endothelial cells, as well as exploring a new method for anti-ocular neoangiogenesis. METHODS: We measured the proliferation of RF/6A cells by an MTT assay and investigated the migration of RF/6A cells by a Transwell chamber assay. We examined the mRNA transcript levels of TGF-ß2, VEGF, PEDF, Bcl-2 and FasL in RF/6A cells by RT-PCR and evaluated the expression of Fas and caspase-3 proteins in RF/6A cells by western blot analysis. RESULTS: 1. TSP-1 (1 µg/ml) and synthetic peptide VR-10 (0.1 µg/ml, 1 µg/ml and 10 µg/ml) inhibited the proliferation of RF/6A cells in a time and dose-dependent way. 2. TSP-1 and synthetic peptide VR-10 could inhibit the migration of RF/6A cells in a Transwell chamber (P < 0.001). It was demonstrated that 10 µg/ml synthetic peptide VR-10 had the strongest effect. 3. The expression of TGF-ß2 mRNA in RF/6A cells increased after treatment with 1 µg/ml TSP-1 (P < 0.0001). However, there was no significant difference between the synthetic peptide VR-10 and the control group (P > 0.05). Expression of PEDF mRNA in RF/6A cells was increased after treatment with 1 µg/ml TSP-1 and synthetic peptide VR-10. We demonstrated that 10 µg/ml synthetic peptide VR-10 had the strongest effect (P < 0.001). There were significant differences between groups (P < 0.001). Expression of TGF-ß2 mRNA in RF/6A cells increased after treatment with 1 µg/ml TSP-1 (P = 0.000). There was no significant difference between the synthetic peptide VR-10 and the control group (P > 0.05). PEDF mRNA expression in RF/6A cells decreased after 1 µg/ml TSP-1 and synthetic peptide VR-10 therapy, among which 10 µg/ml synthetic peptide VR-10 demonstrated the strongest effect (P < 0.001). There were significant differences between groups (P < 0.001), except for the 1 µg/ml synthetic peptide VR-10 and 1 µg/ml synthetic peptide VR-10 groups (P = 0.615). 4. Compared with the control group, FasL mRNA expression was significantly increased in the 10 µg/ml synthetic peptide VR-10 treatment group; however, Bcl-2 mRNA expression was decreased. 5. Western blotting showed that RF/6A cells in the control group mainly expressed the 32 kD procaspase-3 forms. For the 10 µg/ml synthetic peptide, VR-10 treatment group, it showed decreased expression of procaspase-3 (32 kD) and concomitant increased expression of its shorter pro apoptotic forms (20 kD). Compared with the control group, Fas protein expression significantly increased in the 10 µg/ml synthetic peptide VR-10 treatment group. CONCLUSIONS: Synthetic peptide VR-10 had an inhibitory action on the proliferation and migration of RF/6A cells. VR-10 inhibited angiogenesis by its combined actions, which included up-regulating the expression of an anti-angiogenesis gene, namely, pigment epithelium-derived factor (PEDF), down-regulating the expression of the pro-angiogenic vascular endothelial growth factor (VEGF), and mediated endothelial cell apoptosis.
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Proliferación Celular/efectos de los fármacos , Péptidos/farmacología , Trombospondina 1/farmacología , Animales , Caspasa 3/metabolismo , Línea Celular , Movimiento Celular/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Proteínas del Ojo/genética , Proteínas del Ojo/metabolismo , Proteína Ligando Fas/genética , Proteína Ligando Fas/metabolismo , Macaca mulatta , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Péptidos/síntesis química , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Retina/citología , Serpinas/genética , Serpinas/metabolismo , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Epimedii Folium has a long history in China as a common traditional Chinese medicine. Key factors of Epimedii Folium quality were summarized based on ancient literatures, Chinese Pharmacopoeias and modern research in different period of history. The main reason for unqualified Epimedii Folium is unstable icariin. Therefore, it's suggested that: the precondition of the quality control of epimedium is to find the proper quality marker. It's suggested that the medicinal parts should be reverted to "dry whole plant overground" to solve Epimedium resource shortage problem. In addition, it is necessary to strengthen the standardized cultivation, so as to ensure germplasm, production area, and producing method to guarantee the quality of Epimedium Folium. In the drying method, it is recommended to change "dry in the sun or shade" to "dry", namely dry in the sun, shade or drier, in order to provide a new method to improve the quality control and quality standard of Epimedii Folium.
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Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/normas , Epimedium/química , Flavonoides/química , China , Hojas de la Planta/químicaRESUMEN
Salviae Miltiorrhizae Radix et Rhizoma (Danshen) is one of the commonly used bulk medicinal materials in China. It is widely used in clinical practice, and has many pharmacological effects, such as antithromboticï¼antibacterialï¼anti-inflammatoryï¼anti-oxidative and immunomodulatory activities. The quality of Danshen determines the quality of the curative effect. The current wild resources of Danshen gradually decrease, the cultivation area is widely distributed, among them, Shandong, Sichuan, Anhui, Shanxi, Hebei, Henan and other provinces have large acreage for Danshen. However, germplasm, origin, cultivation, harvest, process and other factors have a certain impact on the active ingredients of Danshen, which lead to the quality of Danshen good and bad mixed. This paper is based on the systematic analysis of literature on quality evaluation of Danshen. To provide a new idea for the further research on the quality of Danshen, we summarized the main factors affecting the quality of Salvia miltiorrhiza that of germplasm, origin, cultivation, harvest, process, storage, product specifications and so on.
Asunto(s)
Medicamentos Herbarios Chinos/normas , Salvia miltiorrhiza/química , China , Raíces de Plantas/química , Control de Calidad , Rizoma/químicaRESUMEN
Eighteen novel ciprofloxacin-histone deacetylase inhibitor (HDACi) conjugates were designed and synthesized from suberic acid and ciprofloxacin via esterification and amidation reaction. All conjugates were confirmed by the application of (1)H NMR and HR-MS spectra, their activities against HDACs were evaluated by HDACs assay kit and the anti-tumor activities were evaluated in five cancer cells with CCK-8 assay. The preliminary biological results showed that these conjugates displayed potent activity against HDACs and significant anti-proliferative effect on the cancer cells. Some conjugates exhibited activities better than that of the parent compound ciprofloxacin and drug SAHA. Specifically, compound 12b exhibited the most potent anti-HDAC1 (IC(50) = 0.041 ± 0.005 µmol·L(-1)) and HDAC6 (IC(50) = 0.039 ± 0.006 µmol·L(-1)) activities, and also showed the greatest potency against NCI-H460 (IC(50) = 0.7 ± 0.04 µmol·L(-1)) and A549 (IC(50) = 0.9 ± 0.12 µmol·L(-1)). These results suggest that the histone deacetylase inhibitors have significant anti-tumor activities, which can enhance the anti-tumor activity of quinolones
Asunto(s)
Antineoplásicos/farmacología , Ciprofloxacina/farmacología , Histona Desacetilasa 1/antagonistas & inhibidores , Inhibidores de Histona Desacetilasas/farmacología , Antineoplásicos/síntesis química , Línea Celular Tumoral , Inhibidores de Histona Desacetilasas/síntesis química , Histona Desacetilasas , HumanosRESUMEN
Danshen has a long history in China as a commen traditional Chinese medicine, but many other members of the Salvia family is also used as Danshen in particular regions. The name of Danshen were analyzed according to the color, efficacity and etc. To investigate the real origin of Danshen, the stalk, leaf, flower and radix in chronicle and pictures of ancient literature were deciphered. It showed that in the past dynasties, Salvia miltiorrhiza was the most likely plant used as Danshen. The rigin and quality evaluation of Danshen were also summerized, provided new insight and proof for the development and utilization of Danshen.
Asunto(s)
Medicamentos Herbarios Chinos/historia , Salvia miltiorrhiza , China , Historia Antigua , Medicina Tradicional ChinaRESUMEN
Basically, Dao-di hers are produced in specific area which has a long history, good quality, good medicine, curative effect. However genuine medicinal material area in history is not static, this makes the establishment of genuine medicinal material origin and the in-depth research be very difficult. This paper has profoundly analyzed the origin of different historical periods taking Astragalus membranaceus and Salvia miltiorrhiza as examples, and then summarized the reasons of herbal origin changes from the humanities, social and natural three aspects. This paper provides a basis for establishment and the further research of high-quality genuine producing area.