RESUMEN
Stabilization of a G-quadruplex (G4) in the promotor of the c-MYC proto-oncogene leads to inhibition of gene expression, and it thus represents a potentially attractive new strategy for cancer treatment. However, most G4 stabilizers show little selectivity among the many G4s present in the cellular complement of DNA and RNA. Intriguingly, a crescent-shaped cell-penetrating thiazole peptide, TH3, preferentially stabilizes the c-MYC G4 over other promotor G4s, but the mechanisms leading to this selective binding remain obscure. To investigate these mechanisms at the atomic level, we performed an in silico comparative investigation of the binding of TH3 and its analogue TH1 to the G4s from the promotors of c-MYC, c-KIT1, c-KIT2, and BCL2. Molecular docking and molecular dynamics simulations, combined with in-depth analyses of non-covalent interactions and bulk and per-nucleotide binding free energies, revealed that both TH3 and TH1 can induce the formation of a sandwich-like framework through stacking with both the top and bottom G-tetrads of the c-MYC G4 and the adjacent terminal capping nucleotides. This framework produces enhanced binding affinities for c-MYC G4 relative to other promotor G4s, with TH3 exhibiting an outstanding binding priority. Van der Waals interactions were identified to be the key factor in complex formation in all cases. Collectively, our findings fully agree with available experimental data. Therefore, the identified mechanisms leading to specific binding of TH3 towards c-MYC G4 provide valuable information to guide the development of new selective G4 stabilizers.
Asunto(s)
Genes myc , Simulación del Acoplamiento Molecular , Péptidos/farmacología , Tiazoles/farmacologíaRESUMEN
Quantified inflammatory biomarkers are effective clinical strategy for correct and reasonable drug treatment. In the study, a triple lateral flow immunoassay (triple LFIA) had firstly been developed for specific and simultaneous detection of three pivotal inflammatory biomarkers (PCT, CRP and SAA) via biotin-streptavidin-phycoerythrin signal amplification system in one strip. The developed triple LFIA adopted phycoerythrin (PE) as chromophore to eliminate auto-fluorescence interference from plasma biomolecules and anti-PE mAb as single control line to reduce the nonspecific adsorption, which featured particular advantages in high sensitivity and specificity in a large range of analyte concentrations with the LODs of 0.106 ng/mL for PCT, 0.345 µg/mL for CRP and 3.112 µg/mL SAA, respectively. And the linear quantitative detection ranges were from 0.106 to 100 ng/mL, from 0.345 to 200 µg/mL, and from 3.112 to 200 µg/mL, respectively. Compared to commercial chemiluminescence immunoassay method, the correlations for tested PCT, CRP and SAA in 108 clinical samples were 0.989, 0.987 and 0.988, respectively. In summary, we had proposed a rapid and accurate plasma detection to measure inflammation factors, which facilitated the clinical value to achieve precise treatment.
Asunto(s)
Biotina , Ficoeritrina , Biomarcadores , Inmunoensayo/métodos , Límite de Detección , EstreptavidinaRESUMEN
The purpose of this study was to evaluate the therapeutic effects of artificial dermis combined with autologous split-thickness skin grafting (STSG) compared with autologous intermediate-thickness skin grafting (ITSG) alone in severely burned patients. Fifty-six severely burned patients admitted to our hospital from December 2017 to January 2019 were enrolled and evenly grouped according to the random number table method [AD-STSG group: 28 patients, receiving the treatment of artificial dermis (AD) combined with autologous STSG; ITSG group: 28 patients, receiving autologous ITSG treatment alone]. The healing time and Vancouver Scar Scale (VSS) score of the donor area and graft area, survival rate and infection status of the autologous skin, psychological status (determined by Self-rating Anxiety Scale and Self-rating Depression Scale), and the activity of functional parts of all enrolled patients were included in the evaluation. General items of patients in AD-STSG group and ITSG group, including age, sex, and degree of burn, were all comparable. A significantly shortened healing time of donor skin in AD-STSG group was observed when compared with ITSG group (P < .05) while the recipient skin healed in the same tendency between the two groups. In addition, 21 days after the operation, AD-STSG group presented with significantly higher survival rate of graft skin than ITSG group (P < .05) while same infection status was observed in the two groups. Significantly lower VSS scores were found in AD-STSG group than that in ITSG group 3-, 6- and 10-months after operation (P < .05). Statistical difference regarding psychological status of patients from two groups was unobservable before operation while significantly lower Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were found in AD-STSG group than that in ITSG group 3-, 6- and 10-months after operation (P < .05). Also, AD-STSG group presented improved mobility of functional part than that in ITSG group 10-months after operation without statistical difference (P = .051). Artificial dermis combined with autologous split-thickness skin grafting showed better therapeutic outcomes for the treatment of severely burned patients than autologous intermediate-thickness skin grafting in terms of graft healing time, scar formation, psychological recovery, and perhaps in functional reconstruction.
Asunto(s)
Quemaduras , Trasplante de Piel/métodos , Piel Artificial , Adulto , Quemaduras/cirugía , Dermis , Femenino , Humanos , Masculino , Estudios ProspectivosRESUMEN
Three new nardosinane-type sesquiterpenoids linardosinenes A-C (1-3) and four new neolemnane-type sesquiterpenoids lineolemnenes A-D (4-7), together with the related known compound 4-acetoxy-2,8-neolemnadien-5-one (8), were isolated from the Xisha soft coral Litophyton nigrum. The structures of these new compounds were elucidated by comprehensive analyses of spectroscopic data, in association withmodified Mosher's method and ECD calculations for configurational assignments and the absolute configuration of8was determined by X-ray diffraction analysis for the first time. Structurally uncommon nornardosinane and seconeolemnane skeletons for compounds 1 and 7, respectively, are rare carbon frameworks in naturally occurring sesquiterpenoids. The absolute configurations of 1, 7, and 8 were determined by modified Mosher's method, TDDFT ECD approach, and X-ray diffraction analysis, respectively. This is the first chemical study of L. nigrum and the first report of nornardosinane, seconeolemnane and related sesquiterpenoids from the genus Litophyton. The isolates 1-7 were evaluated for their cytotoxicity against THP-1, SNU-398, HT-29, Capan-1 and A549 cell lines and inhibitory activities against PTP1B, BRD4, HDAC1 and HDAC6 protein kinases. The results indicated that compounds 2-5 inhibited proliferation of human cancer cells. However, none of them were potent inhibitors of protein kinases.
Asunto(s)
Antozoos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Humanos , Modelos Moleculares , Neoplasias/tratamiento farmacológicoRESUMEN
A novel marine actinomycete, designated LHW63021T, was isolated from a marine sponge, genus Craniella, collected in the South China Sea. A polyphasic approach was applied to characterize the taxonomic position of this strain. The strain was found to have scarce aerial mycelia that differentiated into spore chains. The cell-wall hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid. Glucose, galactose, mannose and madurose were found in the whole-cell hydrolysates. The dominant polar lipids were phosphatidylinositol and diphosphatidylglycerol. MK-9(H6) and MK-9(H8) were the predominant menaquinones. The major fatty acids were iso-C16â:â0, iso-C18â:â0, 10-methyl C17â:â0 and C18â:â1 ω9c. The DNA G+C content based on the draft genome sequence was 72.0 mol%. 16S rRNA gene sequence analysis indicated that strain LHW63021T was a member of the genus Actinomadura and had the highest similarity to Actinomadura echinospora DSM 43163T (97.3â%). Phylogenetic trees supported their close relationship. The average nucleotide identity and digital DNA-DNA hybridization values between the whole genome sequences of strain LHW63021T and A. echinospora DSM 43163T were 79.13 and 23.20â%, respectively. The evidence from the polyphasic study shows that strain LHW63021T represents a novel species of the genus Actinomadura, for which the name Actinomadura craniellae sp. nov. is proposed. The type strain is LHW63021T (=DSM 106125T=CCTCC AA 2018015T).
Asunto(s)
Actinobacteria/clasificación , Filogenia , Poríferos/microbiología , Actinobacteria/aislamiento & purificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , Pared Celular/química , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A novel marine actinomycete, designated LHW63014T, isolated from a marine sponge, Craniella species, collected in the South China Sea, was examined using a polyphasic approach. The 16S rRNA gene sequence of strain LHW63014T showed highest similarities to Jishengella endophytica 202201T (98.9â%), Micromonospora olivasterospora DSM 43868T (98.7â%), Micromonospora maris AB-18-032T (98.6â%) and Micromonospora gifhornensis DSM 44337T (98.6â%). Phylogenetic analyses of the family Micromonosporaceae based on the 16S rRNA and gyrB gene sequences indicated that strain LHW63014T and J. endophytica 202201T located within the genus Micromonospora. Morphological and chemotaxonomic characteristics confirmed their affiliation to the genus Micromonospora. Based on phenotypic characteristics, phylogenetic data and digital DNA-DNA hybridization results, strain LHW63014T could be distinguished from its closest taxa, representing a novel species of the genus Micromonospora, for which the name Micromonospora craniellae sp. nov., is proposed, with the type strain LHW63014T (=DSM 106193T=CCTCC AA 2018012T). It is also proposed that J. endophytica be transferred to genus Micromonospora as Micromonospora endophytica comb. nov. (type strain 202201T =CGMCC 4.5597T=DSM 45430T).
Asunto(s)
Micromonospora/clasificación , Filogenia , Poríferos/microbiología , Animales , Técnicas de Tipificación Bacteriana , China , ADN Bacteriano/genética , Genes Bacterianos , Micromonospora/aislamiento & purificación , Micromonosporaceae/clasificación , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
Two marine actinomycete strains, LHW50302T and LHW51701T, were isolated from marine sponges collected in Sansha, Hainan Province, China. The morphological, chemotaxonomic and phylogenetic characteristics were consistent with their classification in the genus Streptomyces. The strains formed hooked and looped chains of arthrospores with smooth surfaces. The cell-wall hydrolysates of the strains contained ll-diaminopimelic acid as the diagnostic diamino acid. MK-9(H8) was the predominant menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Major fatty acids of the strains were iso-C16â:â0, anteiso-C15â:â0 and anteiso-C17â:â0. The 16S rRNA gene sequences indicated that the strains clustered together with Streptomyces albus CGMCC 4.1640T and Streptomyces qinglanensis CGMCC 4.6825T. Multilocus sequence analysis (MLSA) confirmed their relationship. Genome relatedness in forms of average nucleotide identity, digital DNA-DNA hybridization value and MLSA evolutionary distance between each of the strains and its closest relatives showed that they belonged to distinct species. On the basis of these results, strains LHW50302T and LHW51701T belong to two novel species in the genus Streptomyces, for which the names Streptomyces reniochalinae sp. nov. (type strain LHW50302T=CCTCC AA 2018013T=DSM 106194T) and Streptomyces diacarni sp. nov. (type strain LHW51701T=CCTCC AA 2018017T=DSM 106126T) are proposed, respectively.
Asunto(s)
Filogenia , Poríferos/microbiología , Streptomyces/clasificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Tipificación de Secuencias Multilocus , Hibridación de Ácido Nucleico , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Streptomyces/genética , Streptomyces/aislamiento & purificación , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A novel aerobic, spore-forming, marine actinomycete, designated strain LHW63015T, was isolated from a Craniella marine sponge collected in the South China Sea. The strain formed extensively branched substrate and aerial mycelia which carried long and crooked spore chains composed of ridged spores and spherical pseudosporangia. Strain LHW63015T contained meso-diaminopimelic acid as the diagnostic diamino acid. Glucose, ribose, mannose, galactose and madurose occured in whole-cell hydrolysates. The predominant polar lipids were hydroxyl-phosphatidylethanolamine, phosphoglycolipid and ninhydrin-positive phosphoglycolipid. MK-10(H4) and MK-10(H6) were the predominant menaquinones. The major fatty acids were 10-methyl C17â:â0 and C17â:â1ω8c. The G+C content of the genomic DNA was 70.8 mol%. In phylogenetic analysis based on 16S rRNA gene sequences, strain LHW63015T fell within the family Streptosporangiaceae and formed a distinct monophyletic lineage adjacent to the genus Sphaerisporangium, and shared the highest 16S rRNA gene sequence similarity of 96.2â% with Sphaerisporangium album YIM 48782T. On the basis of the polyphasic evidence, a novel genus and species of the family Streptosporangiaceae, for which the name Spongiactinospora rosea gen. nov., sp. nov., is proposed, with the type strain LHW63015T (=DSM 106635T=CCTCC AA 2018019T).
Asunto(s)
Actinobacteria/citología , Filogenia , Poríferos/microbiología , Actinobacteria/aislamiento & purificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Grasos/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/químicaRESUMEN
A novel actinobacterium, designated LHW52908T, was isolated from a marine sponge, Leucettachagosensis, collected in the South China Sea. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain LHW52908T was member of the family Geodermatophilaceae, with highest similarities to Geodermatophilus obscurus DSM 43160T (97.7â%), Geodermatophilus siccatus CF6T (97.6â%) and Geodermatophiluschilensis B12T (97.5â%). Multilocus sequence analysis confirmed that the strain should be a member of genus Geodermatophilus. Chemotaxonomic characteristics confirmed the genus-level affiliation of strain LHW52908T. Based on phylogenetic data, average nucleotide identity and digital DNA-DNA hybridization results, strain LHW52908T could be distinguished from its closest neighbours, representing a novel species of the genus Geodermatophilus, for which the name Geodermatophilusmarinus sp. nov. is proposed, with the type strain LHW52908T (=DSM 106570T=CCTCC AA 2018014T).
Asunto(s)
Actinobacteria/clasificación , Filogenia , Poríferos/microbiología , Actinobacteria/aislamiento & purificación , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Tipificación de Secuencias Multilocus , Hibridación de Ácido Nucleico , Océanos y Mares , Fosfolípidos/química , Pigmentación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
The objective of this study was to investigate the antibacterial effects of cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) and its principal constituent cinnamaldehyde against Porphyromonas gingivalis and to elucidate the antibacterial mechanism. GC-MS analysis showed that cinnamaldehyde was the major constituent in CBEO (57.97%). The minimum inhibition concentrations (MICs) of CBEO and cinnamaldehyde were 6.25⯵g/mL and 2.5⯵M for P. gingivalis, respectively. Nucleic acid and protein leakage was observed with increasing concentrations of CBEO and cinnamaldehyde. Additionally, propidium iodide uptake assays revealed CBEO and cinnamaldehyde at 1â¯×â¯MIC impaired P. gingivalis membrane integrity by enhancing cell permeability. Morphological changes in P. gingivalis cells were observed by scanning electron microscopy, which indicated cell membrane destruction. To further determine the anti-biofilm effect, relative biofilm formation and established biofilms were examined, which demonstrated that both CBEO and cinnamaldehyde at sub-MIC levels inhibited P. gingivalis biofilm formation by 74.5% and 67.3% separately, but only CBEO slightly decreased established biofilms by 33.5% at 4â¯×â¯MIC. These results suggest the potential of CBEO as a natural antimicrobial agent against periodontal disease. Furthermore, cinnamaldehyde was confirmed to be the antibacterial substance of CBEO with inhibitory action against P. gingivalis.
Asunto(s)
Acroleína/análogos & derivados , Antibacterianos/farmacología , Cinnamomum zeylanicum/química , Aceites Volátiles/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Acroleína/aislamiento & purificación , Acroleína/farmacología , Antibacterianos/aislamiento & purificación , Membrana Celular/efectos de los fármacos , Membrana Celular/fisiología , Cromatografía de Gases y Espectrometría de Masas , Humanos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Aceites Volátiles/aislamiento & purificación , Permeabilidad/efectos de los fármacos , Corteza de la Planta/química , Porphyromonas gingivalis/ultraestructuraRESUMEN
The pentacyclic triterpenoid corosolic acid was metabolized by Cunninghamella echinulata CGMCC 3.2000 to its C-24 aldehyde group metabolite and five other hydroxylated metabolites: madasiatic acid (2), 2α, 3ß, 7ß-trihydroxyurs-12-en-28-oic acid (3), 2α, 3ß, 15α-trihydroxyurs-12-en-28-oic acid (4), 2α, 3ß, 6ß, 7ß-tetrahydroxyurs-12-en-28-oic acid (5), 2α, 3ß, 7ß, 15α-tetrahydroxyurs-12-en-28-oic acid (6), and 2α, 3ß,7ß-trihydroxy-24-al-urs-12-en-28-oic acid (7); compounds 3, 5, and 7 were new compounds. The α-glucosidase inhibitory effects of the metabolites were also evaluated.
Asunto(s)
Cunninghamella/metabolismo , Inhibidores de Glicósido Hidrolasas/farmacología , Hipoglucemiantes/farmacología , Triterpenos/farmacología , Biotransformación , Diabetes Mellitus/tratamiento farmacológico , Inhibidores de Glicósido Hidrolasas/química , Hipoglucemiantes/química , Estructura Molecular , Estereoisomerismo , Triterpenos/química , alfa-Glucosidasas/efectos de los fármacos , alfa-Glucosidasas/metabolismoRESUMEN
The pentacyclic triterpenoid hederagenin (1) was subjected to biotransformation by Cunninghamella echinulate CGMCC 3.2000, Mucor subtilissimus CGMCC 3.2454 and Pseudomonas oleovorans CGMCC 1.1641. Three metabolites were obtained. On the basis of nuclear magnetic resonance and high-resolution mass spectral analyses, their structures were characterized as 3ß, 23-dihydroxyolean-12-en-28-oic acid 28-O-ß-D-glucopyranosyl ester (2), 3ß, 15α, 23-trihydroxyolean-12-en-28-oic acid (3), 1ß, 3ß, 23-trihydroxyolean-12-en-28-oic acid (4), and metabolite (3) was a new compound. This was the first report on the biotransformation of hederagenin.
Asunto(s)
Cunninghamella/metabolismo , Mucor/metabolismo , Ácido Oleanólico/análogos & derivados , Pseudomonas oleovorans/metabolismo , Biotransformación , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Saponinas/químicaRESUMEN
CONTEXT: Melanin plays an important role in preventing skin photoageing by blocking ultraviolet B (UVB). However, East Asian women prefer light and fair skin, therefore they want to keep their skin from photoageing and at the same time reduce the melanin in their skin. Chrysin is a kind of natural flavonoid with luxurious biological activities, which has a very promising effect on achieving this goal. OBJECTIVE: To elucidate the effects and mechanisms of chrysin on photoageing and melanogenesis. MATERIALS AND METHODS: Human dermal fibroblasts (HDF) and B16 murine melanoma cells were incubated with chrysin (0-25 µM) for 48 h. Anti-photoageing activity was examined in HDF by assessment of synthesis/degradation of collagen I, antioxidative and antisenescent activities through ELISA and colorimetric method. Anti-melanogenesis activity was tested by assessment of melanin, tyrosinase (TYR), melanogenic proteins inhibition activities in B16 cells using colorimetric and ELISA method. RESULTS: Chrysin increased collagen I secretion (50-121.54% at 6.25-25 µM) and chrysin showed anti-photoageing activity by decreasing the degradation of collagen I, repairing oxidation damage and reducing the rate of HDF senescence. Furthermore, chrysin exhibited inhibitory activities with 3.00-20.35% reduction of melanin content at 6.25-25 µM, and inhibited melanin synthesis through the inhibition of TYR activity and the suppression of melanogenic proteins (TYR, TYR-related protein-1/2 and microphthalmia-associated transcription factor) expressions. DISCUSSION AND CONCLUSION: Chrysin may have potential for developing a functional cosmetic agent because of its anti-photoageing and anti-melanogenesis activities.
Asunto(s)
Flavonoides/farmacología , Melaninas/biosíntesis , Envejecimiento de la Piel/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Colágeno/metabolismo , Glutatión/metabolismo , Humanos , Ratones , Monofenol Monooxigenasa/metabolismoRESUMEN
MAP30 (Momordica Antiviral Protein 30 Kd), a single-stranded type-I ribosome inactivating protein, possesses versatile biological activities including anti-tumor abilities. However, the low efficiency penetrating into tumor cells hampers the tumoricidal effect of MAP30. This paper describes MAP30 fused with a human-derived cell penetrating peptide HBD which overcome the low uptake efficiency by tumor cells and exhibits higher anti-tumor bioactivity. MAP30 gene was cloned from the genomic DNA of Momordica charantia and the recombinant plasmid pET28b-MAP30-HBD was established and transferred into Escherichia coli BL21 (DE3). The recombinant MAP30-HBD protein (rMAP30-HBD) was expressed in a soluble form after being induced by 0.5mM IPTG for 14h at 15°C. The recombinant protein was purified to greater than 95% purity with Ni-NTA affinity chromatography. The rMAP30-HBD protein not only has topological inactivation and protein translation inhibition activity but also showed significant improvements in cytotoxic activity compared to that of the rMAP30 protein without HBD in the tested tumor cell lines, and induced higher apoptosis rates in HeLa cells analyzed by Annexin V-FITC with FACS. This paper demonstrated a new method for improving MAP30 protein anti-tumor activity and might have potential applications in cancer therapy area.
Asunto(s)
Antineoplásicos , Péptidos de Penetración Celular , Neoplasias/tratamiento farmacológico , Proteínas Inactivadoras de Ribosomas Tipo 2 , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Péptidos de Penetración Celular/biosíntesis , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/genética , Péptidos de Penetración Celular/aislamiento & purificación , Péptidos de Penetración Celular/farmacología , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/farmacología , Proteínas Inactivadoras de Ribosomas Tipo 2/biosíntesis , Proteínas Inactivadoras de Ribosomas Tipo 2/química , Proteínas Inactivadoras de Ribosomas Tipo 2/genética , Proteínas Inactivadoras de Ribosomas Tipo 2/aislamiento & purificación , Proteínas Inactivadoras de Ribosomas Tipo 2/farmacologíaRESUMEN
BACKGROUND: Cerebral infarction is a local or extensive necrosis of brain tissue. Subsequently, the corresponding neurological deficits appear. The incidence of cerebrovascular diseases in China is increasing gradually. After the onset of cerebrovascular disease, the most common sequelae include movement disorders, language disorders, and cognitive dysfunction. AIM: To investigate the effect of early refined nursing program on the prognosis of middle-aged and elderly patients with cerebral infarction combined with cognitive dysfunction. METHODS: A retrospective study was conducted to divide 60 patients with cerebral infarction and cognitive impairment into an experimental group (n = 32) and a control group (n = 28). The experimental group received early intensive care every day, and the control group received daily routine care. The scores of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT), as well as the latency and amplitude of the event-related potential P300, were used as main indicators to evaluate changes in cognitive function, and changes in BDNF, TGF-ß, and GDNF expression were used as secondary indicators. RESULTS: Both groups experienced notable enhancements in MMSE scores, with the experimental group demonstrating higher scores than the control group (experimental: 28.75 ± 2.31; control: 25.84 ± 2.87). Moreover, reductions in TMT-A and TMT-B scores were observed in both groups (experimental: TMT-A 52.36 ± 6.18, TMT-B 98.47 ± 10.23; control: TMT-A 61.48 ± 7.92, TMT-B 112.63 ± 12.55), with the experimental group displaying lower scores. P300 Latency decreased (experimental: 270.63 ms ± 14.28 ms; control: 285.72 ms ± 16.45 ms), while amplitude increased (experimental: 7.82 µV ± 1.05 µV; control: 6.35 µV ± 0.98 µV) significantly in both groups, with superior outcomes in the experimental cohort. Additionally, the levels of the growth factors BDNF, TGF-ß1, and GDNF surged (experimental: BDNF 48.37 ng/mL ± 5.62 ng/mL, TGF-ß1 52.14 pg/mL ± 4.28 pg/mL, GDNF 34.76 ng/mL ± 3.89 ng/mL; control: BDNF 42.58 ng/mL ± 4.73 ng/mL, TGF-ß1 46.23 pg/mL ± 3.94 pg/mL, GDNF 30.25 ng/mL ± 2.98 ng/mL) in both groups, with higher levels in the experimental group. CONCLUSION: For middle-aged and elderly patients with cerebral infarction and cognitive dysfunction, early refined nursing can significantly improve their cognitive function and prognosis.
RESUMEN
Parkinson's disease (PD), the second most common neurodegenerative disorder, is linked to α-synuclein (α-Syn) aggregation. Despite no specific drug being available for its treatment, curcumin, from the spice turmeric, shows promise. However, its application in PD is limited by a lack of understanding of its anti-amyloidogenic mechanisms. In this study, we first reconstructed the liquid-liquid phase separation (LLPS) of α-Syn in vitro under different conditions, which may be an initial step in entraining the pathogenic aggregation. Subsequently, we evaluated the effects of curcumin on the formation of droplets, oligomers, and aggregated fibers during the LLPS of α-synuclein, as well as its impact on the toxicity of aggregated α-synuclein to cultured cells. Importantly, we found that curcumin can inhibit amyloid formation by inhibiting the occurrence of LLPS and the subsequent formation of oligomers of α-Syn in the early stages of aggregation. Finally, the molecular dynamic simulations of interactions between α-Syn decamer fibrils and curcumin showed that van der Waal's interactions make the largest contribution to the anti-aggregation effect of curcumin. These results may help to clarify the mechanism by which curcumin inhibits the formation of α-Syn aggregates during the development of PD.
RESUMEN
Five new anthranilic acid derivatives, penipacids A-E (1-5), together with one known analogue (6), which was previously synthesized, were characterized from the ethyl acetate extract of the marine sediment-derived fungus Penicillium paneum SD-44. Their structures were elucidated mainly by extensive NMR spectroscopic and mass spectrometric analysis. The cytotoxicity and antimicrobial activity of the isolated compounds were evaluated. Compounds 1, and 5 exhibited inhibitory activity against human colon cancer RKO cell line, while compound 6 displayed cytotoxic activity against Hela cell line.
Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Penicillium/química , ortoaminobenzoatos/farmacología , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Sedimentos Geológicos , Células HeLa , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/química , Ácido Micofenólico/aislamiento & purificación , Ácido Micofenólico/farmacología , ortoaminobenzoatos/química , ortoaminobenzoatos/aislamiento & purificaciónRESUMEN
Medical product contamination has become a threatening issue against human health, which is the main reason why protective nonwoven fabrics have gained considerable attention. In the present, there is a soaring number of studies on establishing protection systems with nonwoven composites via needle punch. Meanwhile, the disadvantages of composites, such as poor mechanical performance and texture, impose restrictions. Hence, in this study, an eco-friendly method composed of needling, hot pressing, and lamination is applied to produce water-resistant, windproof, and antimicrobial Tencel/low-melting-point polyester-thermoplastic polyurethane/Triclosan (Tencel/LMPET-TPU/TCL) laminated membranes. Field-emission scanning electron microscope (SEM) images and FTIR show needle-punched Tencel/LMPET membranes successfully coated with TPU/TCL laminated membranes, thereby extensively improving nonwoven membranes in terms of water-resistant, windproof, and antimicrobial attributes. Parameters including needle punch depth, content of LMPET fibers, and concentration of TCL are changed during the production. Specifically, Tencel/LMPET-TPU/TCL-0.1 laminated nonwovens acquire good water resistance (100 kPa), outstanding windproof performance (<0.1 cm3/cm2/s), and good antimicrobial ability against Escherichia coli and Staphylococcus aureus. Made with a green production process that is pollution-free, the proposed products are windproof, water resistant, and antimicrobial, which ensures promising uses in the medical and protective textile fields.
RESUMEN
The hard-healing chronic wounds of diabetics are still one of the most intractable problems in clinical skin injury repair. Wound microenvironments directly affect wound healing speed, but conventional dressings exhibit limited efficacy in regulating the wound microenvironment and facilitating healing. To address this serious issue, we designed a thermo-sensitive drug-controlled hydrogel with wound self-adjusting effects, consisting of a sodium alginate (SA), Antheraeapernyi silk gland protein (ASGP) and poly(N-isopropylacrylamide) (PNIPAM) for a self-adjusting microenvironment, resulting in an intelligent releasing drug which promotes skin regeneration. PNIPAM has a benign temperature-sensitive effect. The contraction, drugs and water molecules expulsion of hydrogel were generated upon surpassing lower critical solution temperatures, which made the hydrogel system have smart drug release properties. The addition of ASGP further improves the biocompatibility and endows the thermo-sensitive drug-controlled hydrogel with adhesion. Additionally, in vitro assays demonstrate that the thermo-sensitive drug-controlled hydrogels have good biocompatibility, including the ability to promote the adhesion and proliferation of human skin fibroblast cells. This work proposes an approach for smart drug-controlled hydrogels with a thermo response to promote wound healing by self-adjusting the wound microenvironment.
RESUMEN
BACKGROUND: Multidrug resistance (MDR) is a major obstacle in the chemotherapeutic treatment of many human cancers. 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) isolated from the buds of Cleistocalyx operculatus (Roxb.) Merr. et Perry (Myrtaceae), was investigated for its reversal effects on cancer cell MDR. RESULTS: A human hepatocellular tumor xenograft model was established with the BEL-7402/5-FU cell line. Combined 5-fluorouracil (5-FU) and DMC (40 mg kg(-1) ) treatment significantly elevated tumor inhibition rate to 72.2%. DMC could also increase 5-FU concentrations in tumor tissues and increase caspase-3 activity. Also, combined therapy resulted in enhanced tumor apoptotic and reduced proliferative activities relative to 5-FU alone. Examining body weight and other signs of unwanted toxicity of the different treatment groups revealed no significant signs of adverse effects. CONCLUSION: All results suggested that DMC reverses 5-FU resistance, with a benign side effects profile.