RESUMO
Pancreatic adenocarcinoma is a highly lethal malignant gastrointestinal tumor. Sparstolonin B is an isocoumarin whose anticancer activity has recently received increasing attention. This study aimed to investigate Sparstolonin B's potential antitumor effect on pancreatic adenocarcinoma. The effect of Sparstolonin B on pancreatic cancer target genes and molecular mechanism was predicted via network pharmacology; Sparstolonin B significantly decreased Panc-1 and SW1990 cell viability and effectively suppressed the proliferation, migration, and invasion of pancreatic cancer cells as shown by CCK-8, colony formation, and Transwell assays. Flow cytometry showed that it induced cell cycle arrest and apoptosis. Sparstolonin B also upregulated Bax levels but decreased those of MMP2 and Bcl-2, downregulated IκBα expression, and upregulated p65 and IκBα phosphorylation; however, it had no effect on total NF-κB p65 levels. The NF-κB pathway inhibitor QNZ reversed these effects. The treatment group (26 µmol/L) had reduced graft volume and weight and fewer Ki-67-positive cells than the control group. Therefore, Sparstolonin B can inhibit the growth and induce the apoptosis of pancreatic cancer cells via the NF-κB signaling pathway and may be a potential novel drug for pancreatic cancer treatment.
Assuntos
Adenocarcinoma , Compostos Heterocíclicos de 4 ou mais Anéis , NF-kappa B , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Proteínas I-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Neoplasias PancreáticasRESUMO
OBJECTIVES: Transauricular vagal nerve stimulation (taVNS) at 40 Hz attenuates hippocampal amyloid load in 6-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, but it is unclear whether 40-Hz taVNS can improve cognition in these mice. Moreover, the underlying mechanisms are still unclear. MATERIALS AND METHODS: 6-month-old C57BL/6 (wild type [WT]) and APP/PS1 mice were subjected to 40-Hz taVNS. Novel Object Recognition and the Morris Water Maze were used to evaluate cognition. Hippocampal amyloid-ß (Aß)1-40, Aß1-42, pro-interleukin (IL)-1ß, and pro-IL-18 were measured using enzyme-linked immunosorbent assays. Hippocampal Aß42, purinergic 2X7 receptor (P2X7R), nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, IL-1ß, and IL-18 expression were evaluated by western blotting. Histologic assessments including immunofluorescence, immunohistochemistry, Nissl staining, and Congo red staining were used to assess microglial phagocytosis, neuroprotective effects, and Aß plaque load. RESULTS: 40-Hz taVNS improved spatial memory and learning in 6-month-old APP/PS1 mice but did not affect recognition memory. There were no effects on the cognitive behaviors of 6-month-old WT mice. taVNS at 40 Hz modulated microglia; significantly decreased levels of Aß1-40, Aß1-42, pro-IL-1ß, and pro-IL-18; inhibited Aß42, P2X7R, NLRP3, Caspase-1, IL-1ß, and IL-18 expression; reduced Aß deposits; and had neuroprotective effects in the hippocampus of 6-month-old APP/PS1 mice. These changes were not observed in 6-month-old WT mice. CONCLUSION: Our results show that 40-Hz taVNS inhibits the hippocampal P2X7R/NLRP3/Caspase-1 signaling and improves spatial learning and memory in 6-month-old APP/PS1 mice.
Assuntos
Fármacos Neuroprotetores , Estimulação do Nervo Vago , Camundongos , Animais , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Interleucina-18/farmacologia , Aprendizagem Espacial , Presenilina-1/genética , Presenilina-1/metabolismo , Presenilina-1/farmacologia , Caspase 1/metabolismo , Caspase 1/farmacologia , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Camundongos Transgênicos , Hipocampo/metabolismoRESUMO
In this paper, a microscale high-frequency ultrasonic transducer was prepared by combining traditional planar ultrasonic phased-array technology and micro processing technology. The piezoelectric ceramic material PZT was used as the functional material of the transducer. The number of the arrays was 72, the width of each array was 50 µm, the pitch of each array was 70 µm, and the length of each array was 3 mm. The PZT chip was finely ground to a thickness of 130 µm and could reach a frequency of 10 MHz. The experimental platform of micron-scale precision was set up for a beam-forming lateral sound field test and imaging experiment to validate the theoretical analysis. The echo imaging test showed that a mold with a feature size of about 400 µm could be imaged well.
RESUMO
Dickeya species are soft rot disease-causing bacterial plant pathogens and an emerging agricultural threat in Europe. Environmental modulation of gene expression is critical for Dickeya dadantii pathogenesis. While the bacterium uses various environmental cues to distinguish between its habitats, an intricate transcriptional control system coordinating the expression of virulence genes ensures efficient infection. Understanding of this behaviour requires a detailed knowledge of expression patterns under a wide range of environmental conditions, which is currently lacking. To obtain a comprehensive picture of this adaptive response, we devised a strategy to examine the D. dadantii transcriptome in a series of 32 infection-relevant conditions encountered in the hosts. We propose a temporal map of the bacterial response to various stress conditions and show that D. dadantii elicits complex genetic behaviour combining common stress-response genes with distinct sets of genes specifically induced under each particular stress. Comparison of our dataset with an in planta expression profile reveals the combined impact of stress factors and enables us to predict the major stress confronting D. dadantii at a particular stage of infection. We provide a comprehensive catalog of D. dadantii genomic responses to environmentally relevant stimuli, thus facilitating future studies of this important plant pathogen.
Assuntos
Proteínas de Bactérias/genética , Enterobacteriaceae/genética , Regulação Bacteriana da Expressão Gênica , Doenças das Plantas/microbiologia , Plantas/microbiologia , Proteínas de Bactérias/metabolismo , Enterobacteriaceae/metabolismo , Enterobacteriaceae/patogenicidade , Europa (Continente) , Genômica , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo (TXL) is one of the most common traditional Chinese medicines and plays a vital role in treating atherosclerosis (AS). Endothelial cell (EC) pyroptosis plays a crucial role in the development of AS. Previous research revealed the inhibitory function of TXL in EC apoptosis and autophagy. However, whether TXL can inhibit the pyroptosis of ECs has not been determined. AIM OF THE STUDY: To explore the influence of TXL on EC pyroptosis and determine its underlying mechanism of action in AS. MATERIALS AND METHODS: The TXL components were determined by ultra-performance liquid chromatography coupled with a photodiode array detector. We used ApoE-/- mice to establish a disease model of AS. After treatment with TXL, we recorded pathological changes in the mice and performed immunofluorescence staining of mice aortas. We also measured protein and gene levels to explore the influence of TXL on pyroptosis in vivo. The model was established by stimulating mouse aortic endothelial cells (MAECs) with oxidized low-density lipoprotein (ox-LDL) and analyzing the effect of TXL on pyroptosis by Western blotting (WB), real-time PCR (RT-PCR), and flow cytometry (FCM). We also investigated the impact of TXL on reactive oxygen species (ROS) by FCM and WB. RESULTS: Ten major components of TXL were detected. The vivo results showed that TXL inhibited the development of AS and decreased EC pyroptosis, the activation of caspase-1, and the release of inflammatory cytokines. The vitro experiments showed that TXL significantly reduced the extent of injury to MAECs by oxidized LDL (ox-LDL). TXL reversed the high expression of gasdermin D and other proteins induced by ox-LDL and had a significant synergistic effect with the caspase-1 inhibitor VX-765. We also confirmed that TXL decreased the accumulation of ROS and the expression levels of its essential regulatory proteins Cox2 and iNOS. When ROS accumulation was reduced, EC pyroptotic damage was reduced accordingly. CONCLUSION: Our results indicated that TXL inhibited EC pyroptosis in AS. Reducing the accumulation of ROS may be the essential mechanism of AS inhibition by TXL.
Assuntos
Aterosclerose , Células Endoteliais , Camundongos , Animais , Piroptose , Caspase 1/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Aterosclerose/metabolismoRESUMO
Head and neck cancer is a malignant tumour with a high mortality rate characterized by late diagnosis, high recurrence and metastasis rates, and poor prognosis. Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer. Various factors are involved in the occurrence and development of HNSCC, including external inflammatory stimuli and oncogenic viral infections. In recent years, studies on the regulation of cell death have provided new insights into the biology and therapeutic response of HNSCC, such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and recently the newly discovered cuproptosis. We explored how various cell deaths act as a unique defence mechanism against cancer emergence and how they can be exploited to inhibit tumorigenesis and progression, thus introducing regulatory cell death (RCD) as a novel strategy for tumour therapy. In contrast to accidental cell death, RCD is controlled by specific signal transduction pathways, including TP53 signalling, KRAS signalling, NOTCH signalling, hypoxia signalling, and metabolic reprogramming. In this review, we describe the molecular mechanisms of nonapoptotic RCD and its relationship to HNSCC and discuss the crosstalk between relevant signalling pathways in HNSCC cells. We also highlight novel approaches to tumour elimination through RCD.
RESUMO
Neurological diseases are complex diseases affecting the brain and spinal cord, with numerous etiologies and pathogenesis not yet fully elucidated. Tripterygium wilfordii Hook. F. (TWHF) is a traditional Chinese medicine with a long history of medicinal use in China and is widely used to treat autoimmune and inflammatory diseases such as systemic lupus erythematosus and rheumatoid arthritis. With the rapid development of modern technology, the two main bioactive components of TWHF, triptolide and celastrol, have been found to have anti-inflammatory, immunosuppressive and anti-tumor effects and can be used in the treatment of a variety of diseases, including neurological diseases. In this paper, we summarize the preclinical studies of triptolide and celastrol in neurological diseases such as neurodegenerative diseases, brain and spinal cord injury, and epilepsy. In addition, we review the mechanisms of action of triptolide and celastrol in neurological diseases, their toxicity, related derivatives, and nanotechnology-based carrier system.
RESUMO
Dickeya dadantii is a phytopathogenic bacterium that causes soft rot in a wide range of plant hosts worldwide and a model organism for studying virulence gene regulation. The present study provides a comprehensive and annotated transcriptomic map of D. dadantii obtained by a computational method combining five independent transcriptomic data sets: (i) paired-end RNA sequencing (RNA-seq) data for a precise reconstruction of the RNA landscape; (ii) DNA microarray data providing transcriptional responses to a broad variety of environmental conditions; (iii) long-read Nanopore native RNA-seq data for isoform-level transcriptome validation and determination of transcription termination sites; (iv) differential RNA sequencing (dRNA-seq) data for the precise mapping of transcription start sites; (v) in planta DNA microarray data for a comparison of gene expression profiles between in vitro experiments and the early stages of plant infection. Our results show that transcription units sometimes coincide with predicted operons but are generally longer, most of them comprising internal promoters and terminators that generate alternative transcripts of variable gene composition. We characterize the occurrence of transcriptional read-through at terminators, which might play a basal regulation role and explain the extent of transcription beyond the scale of operons. We finally highlight the presence of noncontiguous operons and excludons in the D. dadantii genome, novel genomic arrangements that might contribute to the basal coordination of transcription. The highlighted transcriptional organization may allow D. dadantii to finely adjust its gene expression program for a rapid adaptation to fast-changing environments. IMPORTANCE This is the first transcriptomic map of a Dickeya species. It may therefore significantly contribute to further progress in the field of phytopathogenicity. It is also one of the first reported applications of long-read Nanopore native RNA-seq in prokaryotes. Our findings yield insights into basal rules of coordination of transcription that might be valid for other bacteria and may raise interest in the field of microbiology in general. In particular, we demonstrate that gene expression is coordinated at the scale of transcription units rather than operons, which are larger functional genomic units capable of generating transcripts with variable gene composition for a fine-tuning of gene expression in response to environmental changes. In line with recent studies, our findings indicate that the canonical operon model is insufficient to explain the complexity of bacterial transcriptomes.
Assuntos
Enterobacteriaceae , Regulação Bacteriana da Expressão Gênica , Bactérias , Dickeya , Enterobacteriaceae/metabolismoRESUMO
Radiofrequency (RF) catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF), but ablation lesions will result in swelling and hematoma of local surrounding tissue, triggering inflammatory cell infiltration and increased release of inflammatory cytokines. Some studies have shown that the inflammatory response may be related to the early occurrence of AF. The most direct way to inhibit perioperative inflammation is to use anti-inflammatory drugs such as glucocorticoids. Here, we prepared polylactic-co-glycolic acid (PLGA) nanoparticles loaded with budesonide (BUD) and delivered them through irrigation of saline during the onset of ablation. Local high temperature promoted local rupture of PLGA nanoparticles, releasing BUD, and produced a timely and effective local myocardial anti-inflammatory effect, resulting in the reduction of acute hematoma and inflammatory cell infiltration and the enhancement of ablation effect. Nanoparticles would also infiltrate into the local myocardium and gradually release BUD ingredients to produce a continuous anti-inflammatory effect in the next few days. This resulted in a decrease in the level of inflammatory cytokine IL-6 and an increase of anti-inflammatory cytokine IL-10. This study explored an extraordinary drug delivery strategy to reduce ablation-related inflammation, which may prevent early recurrence of AF.
RESUMO
The Qingchangligan formula (QCLGF) is a traditional Chinese medicine that has significant clinical potential for patients with acute liver failure (ALF). However, the experimental evidence of the effect of QCLGF on ALF and the associated mechanisms remain elusive. We aimed to evaluate the function of QCLGF in ALF and the underlying mechanism. ALF was induced in rats by intraperitoneal injection of D-GalN (1100 mg/kg). The Qingchangligan formula was administered to the rats (6.725 g/kg · d) for 5 days, and the model group and the control group were given the same amount of physiological saline. Then 16S rRNA gene sequencing, high performance gas chromatography-mass spectrometry (GC-MS), and RNA-seq analysis were performed on the samples. The levels of ALT and AST in the ALF rats were abnormal (5322.08 ± 566.27 U/L and 7655.95 ± 1238.08 U/L, respectively) compared with the normal control (98.98 ± 6.90 U/L and 99.63 ± 10.94 U/L, respectively). The levels of ALT and AST in the QCLGF rats (2997.67 ± 469.24 U/L and 4158.40 ± 596.07 U/L, respectively) were closer the normal control group. Liver HE staining showed that the degree of liver damage in the QCLGF rats was lighter than that in the ALF rats. The overall structure of the gut microbiota after ALF was significantly altered, including Proteobacteria, Blautia, Romboutsia, Parabacteroides, UCG-008, Parasutterella, Ruminococcus, norank_f:Lachnospiraceae, the Eubacterium_xylanophilum_group, Oscillibacter, and Eisenbergiella. QCLGF balanced the structure and abundance of intestinal flora. The levels of D(+)galactose, isopropyl beta-D-1-thiogalactopyranoside and D-mannitol were lighter in the plasma of the ALF rats than in the normal control rats, but there were significantly elevated levels of those metabolites in the QCLGF rats. The gene expression changed significantly in the ALF rats. QCLGF regulated the expression of THBS1 and the KEGG pathways of carbohydrate metabolism, lipid metabolism, signal transduction, the immune system, and infectious disease: bacterial. QCLGF may alleviating intestinal flora disorder, regulating galactose metabolism and downregulating the expression of THBS1 to alleviate D-GalN induced acute liver failure.
Assuntos
Microbioma Gastrointestinal , Falência Hepática Aguda , Animais , Metabolismo dos Carboidratos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Galactose , Humanos , Fígado/metabolismo , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/metabolismo , RNA Ribossômico 16S/genética , RatosRESUMO
BACKGROUND: The method to evaluate the efficacy of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors has become a big concern for researchers with its widely application. Pseudoprogressive disease (PPD) makes this process more difficult, which means that the tumor progressed at the initial evaluation, but re-evaluation after continued treatment suggested that the treatment was effective. However, PPD has not attracted enough attention of clinical doctors. This article is to systematically evaluate the incidence of PPD associated with PD-1/PD-L1 inhibitors with meta-analysis, to provide guidance for the recognition and management of PPD. METHODS: The databases of PubMed, EMBase, Cochrane Library were retrieved from the earliest collection date of the databases until Dec 5, 2019. The search terms of "pseudoprogressive disease, anti-PD-1, anti-PD-L1, PD-1/PD-L1 inhibitor, etc" were used for logistic combination search. Published studies on PPD caused by PD-1/PD-L1 inhibitors were included. Meta-analysis was performed with Stata 15.1. Subgroup analysis was performed according to the study population, tumor type, and evaluation criteria for efficacy. RESULTS: Seven researches, including 1458 patients were taken into the study. Meta-analysis showed that the overall incidence of PPD was 3.70% (95% confidence interval [CI]: 2.70%, 4.90%). Subgroup analysis showed that the incidence of PPD was 3.30% (95% CI: 1.90%, 5.90%) in non-small cell lung cancer patients and 5.10% (95% CI: 2.30%, 11.6%) in melanoma patients. There was no statistically significant difference between East and West populations and among various efficacy evaluation criteria. CONCLUSION: The incidence of PPD related to PD-1/PD-L1 inhibitors is not high, but the evaluation criteria has not yet been unified. Close monitoring, careful identification and proper application should be carried out in the clinic, and full management of the treatment with PD-1/PD-L1 inhibitors should be well done.
Assuntos
Antígeno B7-H1/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos como Assunto , Progressão da Doença , Humanos , Carga TumoralRESUMO
In order to understand the large-scale distribution of microbial populations simultaneously and their relationship with environmental parameters, flow cytometry was used to analyse samples collected from 46 stations in the coastal waters of Qingdao in spring, 2007. The distribution of virus was significantly and positively correlated with heterotrophic bacteria. Two groups of picophytoplankton (Synechococcus and picoeukaryotes) were detected; however, Prochlorococcus was not found. Picoeukaryotes and nanophytoplankton were abundant in the near-shore waters, whereas Synechococcus was abundant in the off-shore areas. No variation was found in vertical distribution of virus, heterotrophic bacteria, Synechococcus and nanophytoplankton abundances, except picoeukaryotes abundance in the bottom layer was dramatically lower than that in the upper layers. Correlation analyses indicated that the relationship between abiotic variables and heterotrophic bacteria, pico- and nanophytoplankton was closer than that between abiotic variables and virioplankton. Temperature and nutrients were the synchronous factors controlling the growth of heterotrophic bacteria, pico- and nanophytoplankton in the coastal waters of Qingdao in spring. The results suggested that synergistic and antagonistic effects existed among microbial groups.
Assuntos
Bactérias/isolamento & purificação , Biodiversidade , Ecossistema , Eucariotos/isolamento & purificação , Água do Mar/parasitologia , Água do Mar/virologia , Vírus/isolamento & purificação , Bactérias/classificação , China , Eucariotos/classificação , Citometria de Fluxo , Compostos Inorgânicos/análise , Compostos Orgânicos/análise , Água do Mar/microbiologia , Temperatura , Vírus/classificação , Água/químicaRESUMO
Spiroplasma eriocheiris is a causative agent of the tremor disease (TD) of Chinese mitten crab Eriocheir sinensis which is a novel pathogen of aquatic animals found in recent years. A gene, adhesin-like protein (ALP41), of S. eriocheiris from E. sinensis was identified and its characteristics were analyzed in present paper. The role of this pathogen's host-binding protein in promoting immune responses was characterized through analyzing the interaction between S. eriocheiris and E. sinensis. The full-length DNA of ALP41 is 1074 bp and encodes 357 amino acid residues. The theoretical molecular weight and isoelectric point for the ALP41 are 40.94 kDa and 4.79, respectively. Since UGA is read as a tryptophan codon and not as a termination signal in most Mollicute species, the ALP41 gene was site-mutated from TGA to TGG and transcribed in Escherichia coli to full expression; the titer of rabbits anti-ALP41 serum was about 1:6000. A specific immunoreactive band was identified when rabbits anti-S. eriocheiris serum was opposed to the recombinant protein. The ALP41 band was detected using anti-ALP41 serum and the total proteins of S. eriocheiris. Realtime-PCR was used for detection of expression levels of the immune genes in E. sinensis. Among the examined genes, the mRNA expression of anti-lipopolysaccharide factor (ALF), prophenoloxidase (proPO), peroxiredoxin 6 (Prx6) and pacifastin light chain (PLC) in E. sinensis were significantly induced after ALP41 treatment.
Assuntos
Adesinas Bacterianas/imunologia , Braquiúros/imunologia , Braquiúros/microbiologia , Imunidade Inata/imunologia , Spiroplasma/imunologia , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Sequência de Aminoácidos , Animais , Antígenos de Bactérias/imunologia , Sequência de Bases , Regulação Bacteriana da Expressão Gênica , Dados de Sequência Molecular , Spiroplasma/genéticaRESUMO
High mobility group box-1 (HMGB1) plays an important role in various liver injuries. In the case of acute liver injury, it leads to aseptic inflammation and other reactions, and also regulates specific cell death responses in chronic liver injury. HMGB1 has been demonstrated to be a good therapeutic target for treating liver failure. Quercetin (Que), as an antioxidant, is a potential phytochemical with hepatocyte protection and is also considered to be an inhibitor of HMGB1. However, the mechanism of its hepatoprotective effects remains to be characterized. The present study explored whether the hepatoprotective effect of Que antagonizes HMGB1, and subsequent molecular signaling events. Our results indicated that Que protects L02 cells from d-galactosamine (d-GaLN)-induced cellular damage by reducing intracellular reactive oxygen species (ROS) production and apoptotic responses in the mitochondrial pathway. Immunofluorescence and Western blot assays showed that HMGB1 was involved in d-GaLN-induced L02 cell damage. Further research showed that after transfection with HMGB1 short hairpin RNA (shRNA), cell viability was improved, and intracellular ROS production and apoptosis were suppressed. When co-treated with Que, the expression of HMGB1 was decreased significantly, the expression of proteins in the corresponding signal pathway were further reduced, and the production of ROS and apoptosis were further suppressed. Molecular docking also indicated the binding of Que and HMGB1. Taken together, these results indicate that Que significantly improves d-GaLN-induced cellular damage by inhibiting oxidative stress and mitochondrial apoptosis via inhibiting HMGB1.
RESUMO
Background: Dermatologic toxicities are the most common side effects associated with the targeted drugs epidermal growth factor receptor inhibitors (EGFRIs), in which xerosis commonly complicated by pruritus severely disturbs the quality of life. The study has observed the curative effect of Zizao Yangrong granules (ZYG) from Chishui Xuanzhu in the treatment of EGFRIs-related xerosis and pruritus, as well as evaluating the safety of the prescription. Methods: Patients (n = 68) who had xerosis after using EGFRIs were enrolled and then randomly divided into the treatment group and control group, respectively, receiving ZYG and placebo granules combined with vitamin E ointment. The intervention lasted 4 weeks. Changes in xerosis and pruritus were observed, and blood routine examination as well as liver and kidney function are observed as safety indexes. The water content of skin and qualify of life were observed. Results: A total of 66 out of 68 patients finished the study with 34 patients in each group. The effective rates of xerosis among the treatment group and control group were 84.8% and 69.7% after 2 weeks' treatment (P < .05), while they were 84.8% and 75.8% after 4 weeks' treatment (P < .05). The patients in the experimental group had better quality of life than that in the control group (P = .045). Conclusion: ZYG can effectively improve the skin dryness associated with EGFRIs, and significantly improve the quality of life of patients with good safety; however, larger randomized controlled trials are needed to verify these findings.
Assuntos
Preparações Farmacêuticas , Qualidade de Vida , Receptores ErbB , Humanos , Inibidores de Proteínas Quinases , Prurido/induzido quimicamente , Prurido/tratamento farmacológicoRESUMO
A gold microwire mask method is developed for the fabrication of transistors based on single lightly Sb-doped SnO(2) nanowires. Damage of the nanowire's surface can be avoided without any thermal annealing and surface modification, which is very convenient for the fundamental electrical and photoelectric characterization of one-dimensional inorganic nanomaterials. Transport measurements of the individual SnO(2) nanowire devices demonstrate the high-performance n-type field effect transistor characteristics without significant hysteresis in the transfer curves. The current on/off ratio and the subthreshold swing of the nanowire transistors are found to be 10(6) and 240 mV/decade, respectively.
RESUMO
Photothermal therapy, due to its security and effectiveness, has recently become a promising cancer treatment after surgery, radiotherapy, chemotherapy, and biological therapy. In this article, soy protein isolate/reduced graphene oxide (SPI/rGO) nanocomposites are prepared via a simple and green process. That is, GO is reduced in situ and stabilized by SPI, an abundant, low-cost, sustainable natural material, and simultaneously forms SPI/rGO nanocomposites. The resulting SPI/rGO nanocomposites disperse in water very well and exhibit good biocompatibility due to the attachment of SPI to the surface of rGO. Such SPI/rGO nanocomposites demonstrate an excellent photothermal capacity and are able to kill HeLa cells efficiently with near-infrared irradiation (808nm). The results in this work suggest that such a SPI/rGO hybrid material could be a promising candidate for future applications of photothermal therapy.
Assuntos
Grafite , Hipertermia Induzida/métodos , Nanocompostos/química , Neoplasias/terapia , Fototerapia/métodos , Proteínas de Soja , Grafite/química , Grafite/farmacologia , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas de Soja/química , Proteínas de Soja/farmacologiaRESUMO
UNLABELLED: Recent studies strongly suggest that the gene expression sustaining both normal and pathogenic bacterial growth is governed by the structural dynamics of the chromosome. However, the mechanistic device coordinating the chromosomal configuration with selective expression of the adaptive traits remains largely unknown. We used a holistic approach exploring the inherent relationships between the physicochemical properties of the DNA and the expression of adaptive traits, including virulence factors, in the pathogen Dickeya dadantii (formerly Erwinia chrysanthemi). In the transcriptomes obtained under adverse conditions encountered during bacterial infection, we explored the patterns of chromosomal DNA sequence organization, supercoil dynamics, and gene expression densities, together with the long-range regulatory impacts of the abundant DNA architectural proteins implicated in pathogenicity control. By integrating these data, we identified transient chromosomal domains of coherent gene expression featuring distinct couplings between DNA thermodynamic stability, supercoil dynamics, and virulence traits. IMPORTANCE: We infer that the organization of transient chromosomal domains serving specific functions acts as a fundamental device for versatile adjustment of the pathogen to environmental stress. We believe that the identification of chromosomal "stress-response" domains harboring distinct virulence traits and mediating the cellular adaptive behavior provides a breakthrough in understanding the control mechanisms of bacterial pathogenicity.
Assuntos
DNA Bacteriano/genética , Dickeya chrysanthemi/genética , Dickeya chrysanthemi/patogenicidade , Regulação Bacteriana da Expressão Gênica , Estresse Fisiológico , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cromossomos Bacterianos , DNA Bacteriano/química , DNA Super-Helicoidal , Dickeya chrysanthemi/fisiologia , Genes Bacterianos , Lamiales/microbiologia , Transcriptoma , Virulência , Fatores de Virulência/metabolismoRESUMO
A strategy to prepare doxorubicin-loaded magnetic silk fibroin nanoparticles is presented. The nanoparticles serve as a nanometer-scale drug-delivery system in the chemotherapy of multidrug-resistant cancer under the guidance of a magnetic field. The magnetic tumor-targeting ability broadens the range of biomedical applications of silk fibroin, and the nanoparticle-assisted preparation strategy is useful for the advancement of other biomacromolecule-based materials.
Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Fibroínas/química , Imãs/química , Nanopartículas/química , Animais , Bombyx , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Compostos Férricos/química , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Campos Magnéticos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Eletricidade EstáticaRESUMO
Spiroplasma eriocheiris causes tremor disease (TD) of Chinese mitten crab Eriocheir sinensis, but little is known about the molecular characterization of this pathogen. The present study was undertaken to identify a unique gene of spiroplasma, spiralin-like protein (SLP25) and analyze its character. The full-length DNA of SLP25 is 699 bp encodes a protein of 232 amino acid residues. The theoretical isoelectric point and molecular weight for the SLP25 are 4.50 and 24.67 kDa, respectively. The similarity of SLP25 deduced amino acid sequence, shared with the spiralin from other species, indicated that the gene might be a member of the spiralin family. After cloning the SLP25, the gene was site-mutated from TGA to TGG and transcribed in E. coli to full expression of the recombinant SLP25. Anti-SLP25 serum was prepared by immunization of rabbits. The titer of anti-SLP25 serum was about 1:20000. A SLP25 band was detected by anti-SLP25 antibody using the total proteins of S. eriocheiris. A specific immunoreactive band was detected when anti-S. eriocheiris serum was opposed to the recombinant protein. This finding suggests that SLP25 could be a good antigen for immunodiagnosis of TD of E. sinensis.