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1.
World J Surg Oncol ; 20(1): 390, 2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36482360

RESUMEN

BACKGROUND: Cystic angiomatosis is a rare benign disease manifesting as multiple lytic and sclerotic bone lesions, described as the proliferation of vascular and lymphatic channels lined by a single layer of endothelial cells. However, the potential pathogenetic mechanism of the disease still remains unknown. Here, we reported a case of cystic angiomatosis with multifocal bone lesion evaluated by whole exome sequencing. CASE DESCRIPTION: In this presentation, we reported a case of an 11-year-old boy with pain in his chest. Computed tomography (CT) revealed the multiple lytic of the bone in the ribs, clavicle, vertebra thoracalis, skull, mandibula, shoulder blade, etc. The blood test showed ALP to be 393U/L and VEGF to be 287.26 pg/ml. The patient was performed with an open biopsy in the ribs and was diagnosed with cystic angiomatosis. Besides, the whole exome sequencing reported the single-nucleotide substitutions in the coding region of BRIP1, CHEK2, GRM4, and MUC16. Then, the upregulated genes involved CASC15, CENPF, ABCA13, ALK, BLM, and FGFR3. CONCLUSIONS: In this article, we report a rare case of cystic angiomatosis in a child with abnormal VEGF and ALP reported by peripheral blood examination. The whole exome sequencing could provide the reference for the potential molecular mechanism in the diagnosis and treatment of cystic angiomatosis.


Asunto(s)
Células Endoteliales , Factor A de Crecimiento Endotelial Vascular , Niño , Humanos , Factor A de Crecimiento Endotelial Vascular/genética
2.
J Craniofac Surg ; 33(4): e365-e368, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34694764

RESUMEN

RATIONALE: Non-missile penetrating injuries caused by foreign bodies, such as knives or sharp wood, are infrequent. We report a 49-year-old male suffering from severe craniocervical penetrating injury by a steel bar was successfully treated by surgery. CHIEF COMPLAINT: The male patient was a 49-year-old builder. Although working on the construction site, an approximately 60 cm steel bar penetrated the patient's brain vertically through the left top of the head presenting with unconsciousness and intermittent irritability. DIAGNOSIS: Computed tomography of the head showed the entrance and exit of the skull damaged by the steel bar. Three-dimensional reconstruction showed that the steel bar entered the skull from the posterior left coronal suture and penetrated the ipsilateral occipital bone, about 5 cm into the neck soft tissue. INTERVENTION: We successfully performed the operation and removed the steel bar. OUTCOMES: The patient was followed up for 5 years; muscle strength returned to normal. LESSONS: Penetrating injuries caused by steel bars are rare, which always cause severe intracranial injury combined with peripheral tissue injury, by sharing our experience in the treatment of this rare case, we hope to provide a reference for similar injuries in the future.


Asunto(s)
Traumatismos Craneocerebrales , Cuerpos Extraños , Traumatismos Penetrantes de la Cabeza , Heridas Penetrantes , Traumatismos Craneocerebrales/etiología , Cuerpos Extraños/complicaciones , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Traumatismos Penetrantes de la Cabeza/diagnóstico por imagen , Traumatismos Penetrantes de la Cabeza/cirugía , Humanos , Masculino , Persona de Mediana Edad , Acero , Tomografía Computarizada por Rayos X/métodos , Heridas Penetrantes/complicaciones , Heridas Penetrantes/diagnóstico por imagen , Heridas Penetrantes/cirugía
3.
Mar Drugs ; 17(12)2019 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-31835446

RESUMEN

Active polysaccharides as safe and natural polymers against bacterial diarrhea have been reconsidered as an alternative to antibiotics. This work investigated the inhibiting effect of depolymerized sulfated galactans from Eucheuma serra and Gracilaria verrucosa on the growth and adhesion of diarrheagenic enterotoxigenic Escherichia coli (ETEC) K88. Results showed that the sulfated polysaccharides with molecular weight distribution ≤20.0 kDa exhibited antibacterial activity against ETEC K88. A structure-activity study revealed that the anti-ETEC K88 activity of sulfated polysaccharides is strictly determined by their molecular weight distribution, sulfate group content, and monosaccharide composition. In addition, the promoted nucleic acid release and the fluorescence quenching of membrane proteins were observed after the treatment with selected polysaccharides. Scanning electron microscopy further confirmed that the depolymerized sulfated galactans can effectively inhibit ETEC K88 adhesion. In conclusion, depolymerized sulfated galactans exhibited an inhibitory effect on the growth and adhesion of ETEC K88.


Asunto(s)
Antibacterianos/farmacología , Escherichia coli Enterotoxigénica/efectos de los fármacos , Galactanos/farmacología , Rhodophyta/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Diarrea/tratamiento farmacológico , Galactanos/química , Galactanos/aislamiento & purificación , Gracilaria/química , Microscopía Electrónica de Rastreo , Peso Molecular , Polímeros/química , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Relación Estructura-Actividad , Sulfatos/química
4.
Appl Microbiol Biotechnol ; 100(9): 3841-51, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26971495

RESUMEN

Poly(ß-L-malic acid) is one natural biopolymer that has the outstanding features of biocompatibility, biodegradability, water solubility, and non-immunogenicity, and it is easily chemically modified. So poly(ß-L-malic acid) (PMLA) and its derivatives may have a great potential application as a novel drug delivery system and in the production of advanced biomaterials which have attracted so much research attention. The fungi of Aureobasidium spp. have been discovered to be the most suitable candidates for PMLA production in large quantities which satisfy the demand of either research or industry. In this review, we will give an overall summary about the PMLA produced by Aureobasidium spp. based on related research in the last decades and the elaboration of this PMLA producer will also be accomplished. More importantly, the latest proceedings will be specified and some suggestions to the elucidation of a PMLA biosynthesis pathway which remains undefined up to date will be proposed. Finally, through this review, the further exploitation for the application of PMLA from Aureobasidium spp. can be emphasized and promoted.


Asunto(s)
Ascomicetos/genética , Ascomicetos/metabolismo , Vías Biosintéticas/genética , Malatos/metabolismo , Polímeros/metabolismo
5.
Crit Rev Microbiol ; 41(2): 228-37, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25168340

RESUMEN

The genus Aureobasidium spp. have been divided into three species, A. pullulans. A. leucospermi and A. proteae, and A. pullulans has been known to have five varieties. However, after analysis of many strains of this yeast isolated from different environments, they do not belong to any of the three species or the five varieties. Although pullulan produced by A. pullulans has been widely used in different fields in industry and different strains of this yeast has been known to produce poly(ß-L-malic acid) (PMA), heavy oils and ß-1,3-glucan, it is still unknown how the black yeast synthesizes and secretes the extracellular polymers at molecular level. In this review article, new biosynthetic pathways of pullulan, PMA and heavy oils, the enzymes and their genes related to their biosynthesis and regulation are proposed. Furthermore, some enzymes and their genes related to pullulan biosynthesis in A. pullulans have been characterized. But it is completely unknown how pullulan is secreted and how PMA, heavy oils and ß-1,3-glucan are synthesized and secreted. Therefore, there is much work to be done about taxonomy and biosynthesis, secretion and regulation of pullulan, PMA, heavy oils and ß-1,3-glucan at molecular levels in Aureobasidium spp.


Asunto(s)
Ascomicetos/clasificación , Ascomicetos/metabolismo , Biopolímeros/metabolismo , Regulación Fúngica de la Expresión Génica , Ascomicetos/genética , Vías Biosintéticas/genética
6.
Microb Cell Fact ; 14: 115, 2015 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-26249335

RESUMEN

BACKGROUND: Polymalic acid (PMA) has many applications in food and medical industries. However, so far it has not been commercially produced by fermentation. Therefore, it is very important how to develop an economical process for a large scale production of PMA by one step fermentation. RESULTS: After over 200 strains of Aureobasidium spp. isolated from the mangrove systems in the South of China were screened for their ability to produce Ca(2+)-polymalate (PMA), it was found that Aureobasidium pullulans var. pullulans MCW strain among them could produce high level of Ca(2+)-PMA. The medium containing only 140.0 g/L glucose, 65.0 g/L CaCO3 and 7.5 g/L corn steep liquor was found to be the most suitable for Ca(2+)-PMA production. Then, 121.3 g/L of Ca(2+)-PMA was produced by A. pullulans var. pullulans MCW strain within 120 h at flask level. During 10-L batch fermentation, 152.52 g/L of Ca(2+)-PMA in the culture and 8.6 g/L of cell dry weight were obtained within 96 h, leaving 4.5 g/L of reducing sugar in the fermented medium. After purification of the Ca(2+)-PMA from the culture and acid hydrolysis of the purified Ca(2+)-PMA, HPLC analysis showed that A. pullulans var. pullulans MCW strain produced only one main component of Ca(2+)-PMA and the hydrolysate of the purified Ca(2+)-PMA was mainly composed of L-malic acid. Mw (the apparent molecular weight) of the purified PMA was 2.054 × 10(5) (g/moL) and the purified PMA was estimated to be composed of 1784 L-malic acids. CONCLUSIONS: It was found that A. pullulans var. pullulans MCW strain obtained in this study could yield 152.52 g/L of Ca(2+)-PMA within the short time, the produced PMA had the highest molecular weight and the medium for production of Ca(2+)- PMA by this yeast was very simple.


Asunto(s)
Ascomicetos/metabolismo , Calcio/metabolismo , Glucanos/biosíntesis , Malatos/metabolismo , Polímeros/metabolismo , Reactores Biológicos/microbiología , Medios de Cultivo/metabolismo , Glucanos/química , Peso Molecular
7.
Biomacromolecules ; 15(11): 4260-71, 2014 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-25287757

RESUMEN

A fully biobased and supertough thermoplastic vulcanizate (TPV) consisting of polylactide (PLA) and a biobased vulcanized unsaturated aliphatic polyester elastomer (UPE) was fabricated via peroxide-induced dynamic vulcanization. Interfacial compatibilization between PLA and UPE took place during dynamic vulcanization, which was confirmed by gel measurement and NMR analysis. After vulcanization, the TPV exhibited a quasi cocontinuous morphology with vulcanized UPE compactly dispersed in PLA matrix, which was different from the pristine PLA/UPE blend, exhibiting typically phase-separated morphology with unvulcanized UPE droplets discretely dispersed in matrix. The TPV showed significantly improved tensile and impact toughness with values up to about 99.3 MJ/m(3) and 586.6 J/m, respectively, compared to those of 3.2 MJ/m(3) and 16.8 J/m for neat PLA, respectively. The toughening mechanisms under tensile and impact tests were investigated and deduced as massive shear yielding of the PLA matrix triggered by internal cavitation of VUPE. The fully biobased supertough PLA vulcanizate could serve as a promising alternative to traditional commodity plastics.


Asunto(s)
Materiales Biocompatibles/química , Plásticos Biodegradables/química , Peróxidos/química , Poliésteres/química , Elastómeros/química
8.
Neural Regen Res ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38993126

RESUMEN

ABSTRACT: The oral cavity is a complex physiological community encompassing a wide range of microorganisms. Dysbiosis of oral microbiota can lead to various oral infectious diseases, such as periodontitis and tooth decay, and even affect systemic health, including brain aging and neurodegenerative diseases. Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration, indicating potential avenues for intervention strategies. In this review, we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases, and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration. We also highlight advances in therapeutic development grounded in the realm of oral microbes, with the goal of advancing brain health and promoting healthy aging.

9.
Heliyon ; 10(11): e32237, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38933984

RESUMEN

Background: The botulinum toxin is an extremely potent substance that impacts the nervous system. There has been a rise in cases of medical poisoning associated with it, particularly in the field of plastic and aesthetic procedures, in recent years. Case description: A 51-year-old woman underwent a facial wrinkle reduction procedure with an unauthorized injection of 100 U of botulinum toxin at an unlicensed medical facility six days prior to hospitalization. Over time, her toxicity symptoms intensified, impacting her respiratory muscles, and she did not receive antitoxin treatment. She was concurrently diagnosed with a COVID-19 infection during this period. Nonetheless, she experienced a full recovery 86 days after the injection. Conclusion: Currently, there is no effective antidote for botulism. Nevertheless, the timely administration of antitoxin can contribute to reducing the duration of the illness, alleviating symptoms, and preventing its recurrence. It is essential to recognize that individual responses may vary, and in this instance, the absence of antitoxin treatment did not significantly prolong the course of the disease. Accurate diagnosis of medical poisoning can be based on injection history and clinical symptoms. Early indications like fatigue and dry mouth warrant particular attention, emphasizing the importance of immediate medical intervention. To address emergencies, the Center for Disease Control (CDC) should maintain an accessible supply of antitoxin. Patients with severe poisoning should be hospitalized until their respiratory muscle strength is fully restored.

10.
Protein Cell ; 15(8): 612-632, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38577810

RESUMEN

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.


Asunto(s)
Envejecimiento , Encía , Transcriptoma , Proteínas Señalizadoras YAP , Encía/metabolismo , Encía/patología , Animales , Humanos , Envejecimiento/genética , Envejecimiento/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Queratinocitos/metabolismo , Células Epiteliales/metabolismo , Masculino
11.
Sci Total Environ ; 926: 172125, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38565353

RESUMEN

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.


Asunto(s)
Toxinas Marinas , Mytilus , Animales , Toxinas Marinas/toxicidad , Microplásticos/metabolismo , Plásticos/metabolismo , Mytilus/metabolismo , Mariscos
12.
Protein Expr Purif ; 88(1): 85-92, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23246713

RESUMEN

The xylan binding domain (XBD) and linker sequences (LS) from thermostable and thermophilic Thermomonospora fusca xylanase A (TfxA) was fused to the carboxyl-terminus of a family 11 hybrid xylanase ATx. The constructed chimera (ATxX) was successfully expressed in Pichia pastoris, partially purified to homogeneity, and then characterized in detail. After 96-h 0.25% methanol induction, the xylanase and cellulose activity of ATxX from pPATxX1 transformant culture medium supernatant were 452.1 U/mg and 19.3 U/mg, respectively. SDS-PAGE analysis revealed that the molecular mass of ATxX was about 33.01 kDa. 3.7% ATxX was bound after incubation with 1% microcrystal cellulose at 25 °C for 3 h, while the ATx did not show cellulose binding-hydrolyzing ability. These results suggested that ATx obtained cellulose binding and hydrolyzing ability by fusing with XBD and LS. Enzymatic studies showed that the temperature and pH optimum of the ATxX xylanase activity were 60 °C and pH 5.0, respectively, which were the same as that of ATx. The temperature and pH optimum of the ATxX cellulase activity were 60 °C and pH 6.0, respectively. The major hydrolytic products released by ATxX from birchwood xylan were xylotriose and xylohexaose. Xylooligosaccharides from xylobiose to xylohexaose could be hydrolyzed by ATxX. Mode of action analysis showed that the chimeric ATxX was an endo-acting enzyme. The XBD and LS plays an important role in the binding and hydrolyzing of xylanase to insoluble substrates.


Asunto(s)
Actinomycetales/enzimología , Endo-1,4-beta Xilanasas/genética , Endo-1,4-beta Xilanasas/aislamiento & purificación , Proteínas Recombinantes de Fusión/aislamiento & purificación , Celulosa/química , Endo-1,4-beta Xilanasas/biosíntesis , Endo-1,4-beta Xilanasas/química , Concentración de Iones de Hidrógeno , Pichia , Unión Proteica , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Xilanos/química , Xilanos/metabolismo
13.
Appl Microbiol Biotechnol ; 97(20): 8931-9, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23948724

RESUMEN

After over 100 strains of Aureobasidium spp isolated from mangrove system were screened for their ability to produce poly(ß-malic acid) (PMA), it was found that Aureobasidium sp. P6 strain among them could produce high level of Ca(2+)-PMA. Fourteen percent glucose and 6.5 % CaCO3 in the medium were the most suitable for Ca(2+)-PMA production. Then, 100.7 g/l of Ca(2+)-PMA was produced using Aureobasidium sp. P6 strain within 168 h at flask level. During 10-l batch fermentation, when the medium contained 12.0 % glucose, 98.7 g/l of Ca(2+)-PMA in the culture and 14.7 g/l of cell dry weight were obtained within 156 h, leaving 0.34 % reducing sugar in the fermented medium. When glucose concentration in the fermentation medium was 14.0 %, 118.3 g/l of Ca(2+)-PMA in the culture and 16.4 g/l of cell dry weight were obtained within 168 h, leaving 0.4 % reducing sugar in the fermented medium. After purification of Ca(2+)-PMA from the culture and acid hydrolysis of the pure Ca(2+)-PMA, analysis of HPLC showed that Aureobasidium sp. P6 strain only produced two main components of Ca(2+)-PMA and minor amount of calcium malate and that the hydrolysate of PMA was mainly composed of calcium malate. This is the first time to report that the novel yeast strain Aureobasidium sp. P6 strain isolated from the mangrove systems can produce such high amount of Ca(2+)-PMA.


Asunto(s)
Glucosa/metabolismo , Malatos/metabolismo , Polímeros/metabolismo , Árboles/microbiología , Levaduras/aislamiento & purificación , Levaduras/metabolismo , China , Medios de Cultivo/metabolismo , Fermentación , Datos de Secuencia Molecular , Filogenia , Humedales , Levaduras/clasificación , Levaduras/genética
14.
Zootaxa ; 5380(5): 401-445, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38221300

RESUMEN

The genus Conicera Meigen from China is revised. 35 species are recorded, of which 19 are new to science: C. obtusifinis sp. nov., C. petalina sp. nov., C. maculifemoris sp. nov., C. forcipis sp. nov., C. ancoraria sp. nov., C. angusta sp. nov., C. tortuosa sp. nov., C. dentisparsa sp. nov., C. convallis sp. nov., C. chayuensis sp. nov., C. triangularis sp. nov., C. margiflucta sp. nov., C. securiclata sp. nov., C. palmata sp. nov., C. marginata sp. nov., C. denticulata sp. nov., C. microspinulosa sp. nov., C. grandicaudata sp. nov. and C. obtusidentis sp. nov. 5 species are recorded for the first time in China: C. gracilis Michailovskaya, C. pacifica Michailovskaya, C. similis (Haliday), C. tibialis Schmitz and C. schnittmanni Schmitz. All known species are redescribed and illustrated. A key to species from China is presented.


Asunto(s)
Dípteros , Animales , China , Distribución Animal
15.
Environ Pollut ; 316(Pt 1): 120544, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36334776

RESUMEN

The toxicity of microplastics (MPs) to marine microalgae has raised much concern. However, research at metabolic level is quite limited. In this study, the physiological and metabolic effects of polystyrene (PS) and aged polystyrene (A-PS) MPs on Dunaliella salina were investigated. Both PS and A-PS inhibited the growth of microalgae, but promoted the pigment synthesis in algal cells. The oxidative stress analysis indicated that PS and A-PS induced high production of reactive oxygen species (ROS), and caused oxidative damage to algal cells. Particularly, the highest ROS level in PS and A-PS groups were 1.70- and 2.24-fold of that in the control group, respectively. Untargeted metabolomics analysis indicated that PS and A-PS significantly increased the differential metabolites. Compared with the control group, the significant upregulation of glycerophospholipids metabolites illustrated that severe membrane lipid peroxidation occurred in the MPs groups. Metabolic pathways analysis showed that PS and A-PS perturbed the amino acid-related metabolic pathways. In particular, the amino acid biosynthesis and ATP-binding cassette (ABC) transporter pathways were significantly upregulated, thus promoting nitrogen storage and transmembrane transport in Dunaliella salina. Transmembrane transport requires a large amount of ATP; as a result, algal cell division is inhibited. In addition, A-PS stimulated more active glutathione metabolism than PS. These results enrich the understanding of the toxicity of PS MPs to microalgae at the metabolic level, and are helpful for further assessing the ecological impacts of MPs on microalgae.


Asunto(s)
Chlorophyceae , Microalgas , Contaminantes Químicos del Agua , Microplásticos/toxicidad , Poliestirenos/metabolismo , Plásticos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Chlorophyceae/metabolismo , Aminoácidos/metabolismo , Adenosina Trifosfato/metabolismo , Contaminantes Químicos del Agua/metabolismo
16.
Biosens Bioelectron ; 234: 115363, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37146537

RESUMEN

As an efficient patient management tool of precision medicine, decentralized therapeutic drug monitoring (TDM) provides new vision for therapy adherence and health management of schizophrenia in a convenient manner. To dispense with psychologically burdensome blood sampling and to achieve real-time, noninvasive, and continual circulating tracking of drugs with narrow therapeutic window, we study the temporal metabolism of clozapine, an antipsychotic with severe side effect, in rat saliva by a wireless, integrated and patient-friendly smart lollipop sensing system. Highly sensitive and efficient sensing performance with acceptable anti-biofouling property was realized based on the synergistic effect of electrodeposited reduced graphene oxide and ionic liquids in pretreatment-free saliva with low detection limit and good accuracy cross-validated with conventional method. On this basis, continual salivary drug levels with distinctive pharmacokinetics were found in different routes of drug administration. Pilot experiment reveals a strong correlation between blood and saliva clozapine and a positive relationship between drug dosage and salivary drug level, indicating potential applications presented by noninvasive saliva analysis towards patient-centered and personalized pharmacotherapy and adherence management via proposed smart lollipop system.


Asunto(s)
Técnicas Biosensibles , Clozapina , Esquizofrenia , Animales , Ratas , Clozapina/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Monitoreo de Drogas/métodos , Saliva/metabolismo , Administración del Tratamiento Farmacológico , Técnicas Biosensibles/métodos
17.
Cell Death Differ ; 29(4): 861-873, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34974534

RESUMEN

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin-remodeling enzyme involved in DNA damage response and gene transcription, and its dysregulation has been linked with Charcot-Marie-Tooth disease, neurodevelopmental disorder, and cancer. Despite its functional importance, how MORC2 is regulated remains enigmatic. Here, we report that MORC2 is O-GlcNAcylated by O-GlcNAc transferase (OGT) at threonine 556. Mutation of this site or pharmacological inhibition of OGT impairs MORC2-mediated breast cancer cell migration and invasion in vitro and lung colonization in vivo. Moreover, transforming growth factor-ß1 (TGF-ß1) induces MORC2 O-GlcNAcylation through enhancing the stability of glutamine-fructose-6-phosphate aminotransferase (GFAT), the rate-limiting enzyme for producing the sugar donor for OGT. O-GlcNAcylated MORC2 is required for transcriptional activation of TGF-ß1 target genes connective tissue growth factor (CTGF) and snail family transcriptional repressor 1 (SNAIL). In support of these observations, knockdown of GFAT, SNAIL or CTGF compromises TGF-ß1-induced, MORC2 O-GlcNAcylation-mediated breast cancer cell migration and invasion. Clinically, high expression of OGT, MORC2, SNAIL, and CTGF in breast tumors is associated with poor patient prognosis. Collectively, these findings uncover a previously unrecognized mechanistic role for MORC2 O-GlcNAcylation in breast cancer progression and provide evidence for targeting MORC2-dependent breast cancer through blocking its O-GlcNAcylation.


Asunto(s)
Neoplasias de la Mama , Factor de Crecimiento Transformador beta1 , Neoplasias de la Mama/patología , Femenino , Humanos , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismo , Treonina , Factores de Transcripción/genética
18.
Polymers (Basel) ; 13(13)2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-34209099

RESUMEN

In recent years, many investigations have been devoted to fused deposition modeling (FDM) of high-performance polymer-polyetheretherketone (PEEK) and carbon-fiber-reinforced PEEK (CF/PEEK) for biomedical and aerospace applications. However, the staircase effect naturally brought about by FDM restricts further applications of 3D-printed PEEK and its composites in high-temperature molds, medical implants, and precision components, which require better or customized surface qualities. Hence, this work aimed to reduce the staircase effect and improve the surface quality of 3D-printed PEEK and CF/PEEK parts by dry milling of the fluctuant exterior surface. The co-dependency between 3D printing parameters (raster angle and layer thickness) and milling parameters (depth of cut, spindle speed, and feed rate per tooth) were investigated through experiments. The difference in removal mechanisms for PEEK and CF/PEEK was revealed. It was confirmed that the smearing effect enhanced the surface quality based on the morphology analysis and the simulation model. Both the raster angle of +45°/-45° and the small layer thickness could improve the surface quality of these 3D-printed polymers after dry milling. A large depth of cut and a large feed rate per tooth were likely to deteriorate the finished polymer surface. The spindle speed could influence the morphologies without significant changes in roughness values. Finally, a demonstration was performed to verify that dry milling of 3D-printed amorphous PEEK and CF/PEEK parts could lead to a high surface quality for critical requirements.

19.
Sci Total Environ ; 797: 149180, 2021 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-34311354

RESUMEN

The toxicity of microplastics to marine organisms has attracted much attention; however, studies of their effects on marine microalgae remain limited. Here, the effects of the single and combined toxicity of polystyrene (PS) and triphenyl phosphate (TPhP) on the cell growth, photosynthesis, and oxidative stress of Chaetoceros meülleri were investigated. PS inhibited growth of the algae cells and caused a dose-dependent effect on oxidative stress. The significantly high production of reactive oxygen species (ROS) induced severe cell membrane damage, as confirmed by high fluorescence polarization. However, there was no obvious decrease in chlorophyll a content, and 80 mg/L of PS significantly promoted chlorophyll a synthesis. The TPhP also inhibited cell growth, except at low concentrations (0.2-0.8 mg/L), which stimulated algae growth over 48 h. Moreover, no obvious decrease in chlorophyll a and maximal photochemical efficiency of PSII was found in the TPhP experimental groups except for 3.2 mg/L TPhP, where the rapid light curves showed a significantly reduced photosynthetic capacity of algae. In addition, TPhP caused high ROS levels at 96 h, resulting in cell membrane damage. Using the additive index and independent action methods, the combined toxic effects of PS and TPhP on the algae were evaluated as antagonistic; however, cell membrane damage caused by high ROS levels was still noticeable. This study has shown the potential toxicity of PS and TPhP to marine microalgae, and provided insights into the combined risk assessment of TPhP and microplastics in the marine environment.


Asunto(s)
Poliestirenos , Contaminantes Químicos del Agua , Clorofila A , Organofosfatos , Estrés Oxidativo , Fotosíntesis , Plásticos , Poliestirenos/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
20.
Water Res ; 207: 117825, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34763279

RESUMEN

Still ∼10% of world's population has no sustainable access to centralized water supply system, causing millions of deaths annually by waterborne diseases. Here, we develop polypyrrole nanowire arrays (PPyNWs)-modified electrodes by polymerization of pyrrole on graphite felt for point-of-use water disinfection via low-voltage electroporation. A flow-through mode is specially applied to alleviate diffusion barrier of pyrrole in the porous graphite felt for uniform PPyNWs growth. The flow-through disinfection device using the optimized PPyNWs electrode achieves above 4-log removal for model virus (MS2) and gram-positive/negative bacteria (E. faecalis and E. coli) at applied voltage of 1.0 V and fluxes below 1000 and 2500 L/m2/h. Electroporation is recognized as the dominant disinfection mechanism by using square-wave alternating voltage of ±1.0 V to eliminate the electrochemical reactions. In-situ sampling experiments reveal that anode acts as the main disinfection function due to its electric field attraction with negatively charged E. coli cells. The live/dead baclight staining experiments indicate an adsorption-desorption process of E. coli cells on anode, and the adsorption-desorption balance determines the disinfection abilities of PPyNWs anode. Under 1.0 V and 2000 L/m2/h, the disinfection device enables above 4-log E. coli removal in tap water within 7-day operation with energy consumption below 20 mJ/L, suggesting its sound application potential for point-of-use water disinfection.


Asunto(s)
Nanocables , Purificación del Agua , Desinfección , Electrodos , Electroporación , Escherichia coli , Polímeros , Pirroles , Agua
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