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1.
Biomed Environ Sci ; 35(6): 504-517, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35882410

RESUMO

Objective: The hippocampus is thought to be a vulnerable target of microwave exposure. The aim of the present study was to investigate whether 20-hydroxyecdysone (20E) acted as a fate regulator of adult rat hippocampal neural stem cells (NSCs). Furthermore, we investigated if 20E attenuated high power microwave (HMP) radiation-induced learning and memory deficits. Methods: Sixty male Sprague-Dawley rats were randomly divided into three groups: normal controls, radiation treated, and radiation+20E treated. Rats in the radiation and radiation+20E treatment groups were exposed to HPM radiation from a microwave emission system. The learning and memory abilities of the rats were assessed using the Morris water maze test. Primary adult rat hippocampal NSCs were isolated in vitro and cultured to evaluate their proliferation and differentiation. In addition, hematoxylin & eosin staining, western blotting, and immunofluorescence were used to detect changes in the rat brain and the proliferation and differentiation of the adult rat hippocampal NSCs after HPM radiation exposure. Results: The results showed that 20E induced neuronal differentiation of adult hippocampal NSCs from HPM radiation-exposed rats via the Wnt3a/ß-catenin signaling pathway in vitro. Furthermore, 20E facilitated neurogenesis in the subgranular zone of the rat brain following HPM radiation exposure. Administration of 20E attenuated learning and memory deficits in HPM radiation-exposed rats and frizzled-related protein (FRZB) reduced the 20E-induced nuclear translocation of ß-catenin, while FRZB treatment also reversed 20E-induced neuronal differentiation of NSCs in vitro. Conclusion: These results suggested that 20E was a fate regulator of adult rat hippocampal NSCs, where it played a role in attenuating HPM radiation-induced learning and memory deficits.


Assuntos
Células-Tronco Neurais , beta Catenina , Animais , Proliferação de Células , Ecdisterona/metabolismo , Ecdisterona/farmacologia , Hipocampo/metabolismo , Masculino , Transtornos da Memória , Micro-Ondas , Células-Tronco Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , beta Catenina/metabolismo
2.
J Appl Microbiol ; 2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35870153

RESUMO

AIMS: Phenazines, such as phenazine-1-carboxylic acid (PCA), phenazine-1-carboxamide (PCN), 2-hydroxyphenazine-1-carboxylic acid (2-OH-PCA), 2-hydroxyphenazine (2-OH-PHZ), are a class of secondary metabolites secreted by plant-beneficial Pseudomonas. Ps. chlororaphis GP72 utilizes glycerol to synthesize PCA, 2-OH-PCA and 2-OH-PHZ, exhibiting broad-spectrum antifungal activity. Previous studies showed that the addition of dithiothreitol (DTT) could increase the phenazines production in Ps. chlororaphis GP72AN. However, the mechanism of high yield of phenazine by adding DTT is still unclear. METHODS AND RESULTS: In this study, untargeted and targeted metabolomic analysis were adopted to determine the content of metabolites. The results showed that the addition of DTT to GP72AN affected the content of metabolites of central carbon metabolism, shikimate pathway and phenazine competitive pathway. Transcriptome analysis was conducted to investigate the changed cellular process, and the result indicated that the addition of DTT affected the expression of genes involved in phenazine biosynthetic cluster and genes involved in phenazine competitive pathway, driving more carbon flux into phenazine biosynthetic pathway. Furthermore, genes involved in antioxidative stress, phosphate transport system and mexGHI-opmD efflux pump were also affected by adding DTT. CONCLUSION: This study demonstrated that the addition of DTT altered the expression of genes related to phenazine biosynthesis, resulting in the change of metabolites involved in central carbon metabolism, shikimate pathway and phenazine competitive pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: This work expands the understanding of high yield of phenazine by the addition of DTT and provides several targets for increasing phenazine production.

3.
Clin Transl Med ; 12(6): e947, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35735103

RESUMO

BACKGROUND: Accumulation of evidence suggests that the gut microbiome, its specific metabolites, and differentially expressed proteins (DEPs) are related to non-small cell lung cancer (NSCLC) pathogenesis. We now report the influences of the gut microbiota, metabolites, and DEPs on the mediation of NSCLC's chronic inflammation and immune dysregulation. METHODS: We conducted 16S ribosomal RNA sequencing for the gut microbiome in healthy volunteers and NSCLC patients. Liquid chromatography-mass spectrometry (LC-MS) analysis was employed to explore differences between metabolites and DEPs in serum samples. Additionally, LC-MS-based metabolomic analysis was conducted in 40 NSCLC tissues and 40 adjacent tissues. The omics data were separately analysed and integrated by using Spearman's correlation coefficient. Then, faecal microbiota transplantation (FMT) assay was used to assess the effects of the gut microbiome and specific metabolites in mice. RESULTS: Faecal microbiome analysis revealed gut microflora dysbiosis in NSCLC patients with Prevotella, Gemmiger, and Roseburia significantly upregulated at the genus level. Then, we identified that nervonic acid/all-trans-retinoic acid level was negatively related to Prevotella. Additionally, a total of core 8 DEPs were selected in the proteome analysis, which mainly participated in the production of IL-8 and NF-κB pathways. CRP, LBP, and CD14 were identified as potential biomarkers for NSCLC. Transplantation of faecal microbiota from patients with NSCLC or Prevotella copri-colonized recipient in mice resulted in inflammation and immune dysregulation. In turn, nervonic acid/all-trans-retinoic acid treatment improved the phenotype of C57BL/6 mice bearing P. copri-treated Lewis lung cancer (LLC). CONCLUSIONS: Overall, these results pointed out that P. copri-nervonic acid/all-trans-retinoic acid axis may contribute to the pathogenesis of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Microbiota , Animais , Bactérias/genética , Humanos , Inflamação , Metaboloma , Camundongos , Camundongos Endogâmicos C57BL , Proteoma/farmacologia , Tretinoína/farmacologia
4.
mBio ; 13(2): e0364421, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35254135

RESUMO

Plant colonization by phytopathogens is a very complex process in which numerous factors are involved. Upon infection by phytopathogens, plants produce salicylic acid (SA) that triggers gene expression within the plant to counter the invading pathogens. The present study demonstrated that SA signal also directly acts on the quorum-sensing (QS) system of the invading pathogen Xanthomonas campestris pv. campestris to affect its virulence by inducing turnover of the diffusible signaling factor (DSF) family QS signal. First, Xanthomonas campestris pv. campestris infection induces SA biosynthesis in the cabbage host plant. SA cannot be degraded by Xanthomonas campestris pv. campestris during culturing. Exogenous addition of SA or endogenous production of SA induces DSF signal turnover during late growth phase of Xanthomonas campestris pv. campestris in XYS medium that mimics plant vascular environments. Further, the DSF turnover gene rpfB is required for SA induction of DSF turnover. However, SA does not affect the expression of rpfB and DSF biosynthesis gene rpfF at the transcriptional level. SA induction of DSF turnover only occurs under acidic conditions in XYS medium. Furthermore, addition of SA to XYS medium significantly increased both culture and cytoplasmic pH. Increased cytoplasmic pH induced DSF turnover in a rpfB-dependent manner. In vitro RpfB-dependent DSF turnover activity increased when pH increased from 6 to 8. SA exposure did not affect the RpfB-dependent DSF turnover in vitro. Finally, SA-treated Xanthomonas campestris pv. campestris strain exhibited enhanced virulence when inoculated on cabbage. These results provide new insight into the roles of SA in host plants and the molecular interactions between Xanthomonas campestris pv. campestris and cruciferous plants. IMPORTANCE SA is a phenolic acid plant hormone that plays an essential role in plant defenses against biotrophic and semibiotrophic pathogens. Substantial progress has been made in understanding the pivotal role of SA in plant immunity. However, the roles of SA in inhibiting invading plant pathogens and the associated underlying molecular mechanisms are not yet fully understood. The present study demonstrated that the SA signal directly acts on the quorum-sensing (QS) system of the invading pathogen Xanthomonas campestris pv. campestris to affect its virulence by inducing turnover of the DSF family QS signal via a pH-dependent manner. These findings provide new insight into the roles of SA and expand our understanding of the molecular interactions between pathogens and plant hosts.


Assuntos
Brassica , Xanthomonas campestris , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Concentração de Íons de Hidrogênio , Percepção de Quorum/genética , Ácido Salicílico/metabolismo , Xanthomonas campestris/genética
5.
J Clin Oncol ; 40(15): 1681-1692, 2022 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-35263150

RESUMO

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/uso terapêutico , Quimiorradioterapia/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Neoplasias Retais/patologia
6.
Front Genet ; 13: 861096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35350239

RESUMO

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.

7.
Front Neurosci ; 16: 820106, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185459

RESUMO

Alcohol use disorders (AUD) is characterized by persistent or intermittent alcohol cravings and compulsive drinking. The functional changes in the central nervous system (CNS) after alcohol consumption are alcohol-associated cognitive impairment and mood disorders, which are major health issues reported in AUDs. Studies have shown that transferring the intestinal microbiota from AUDs patients to germ-free animals causes learning and memory dysfunction, depression and anxiety-like behavior, indicating the vital role of intestinal microbiota in development of neuropsychiatric disorders in AUD. Intestinal flora composition of AUD patients are significantly different from normal people, suggesting that intestinal flora imbalance orchestrate the development of neuropsychiatric disorders in AUD. Studies suggests that gut microbiome links bidirectional signaling network of the enteric nervous system (ENS) to central nervous system (CNS), forming gut-microbe-brain axis (brain-gut axis). In this review, we discussed pathogenesis and possible treatment of AUD-induced cognitive deficits, anxiety, and depression disorders. Further, we described the mechanism of intestinal flora imbalance and dysfunction of hippocampus-amygdala-frontal cortex (gut-limbic circuit system dysfunction). Therefore, we postulate therapeutic interventions of gut-brain axis as novel strategies for treatment of AUD-induced neuropsychiatric disorders.

8.
Signal Transduct Target Ther ; 7(1): 38, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35145057

RESUMO

Small interfering RNA (siRNA) constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B. A novel ionizable lipidoid nanoparticle (RBP131) and a state-of-the-art lyophilization technology were developed in this study, enabling to deliver siRNA targeting apolipoprotein B (APOB) into the hepatocytes with an ED50 of 0.05 mg/kg after intravenous injection. In addition, according to the requirements of Investigational New Drug (IND) application, a potent siRNA targeting hepatitis B virus (HBV) was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008. Efficacy investigations in transient and transgenic mouse models revealed that the expressions of viral RNAs and antigens (HBsAg and HBeAg), as well as viral DNA, were repressed, dose-dependently and time-dependently at multilog decreasing amplitude, in both circulation and liver tissue. In contrast, entecavir (ETV), the first-line clinically-employed nucleoside analog drug, barely recused the antigen expression, although it triggered as high as 3.50 log reduction of viral DNA, in line with clinical observations. Moreover, the toxicity profiles suggested satisfactory safety outcomes with ten times the therapeutic window. Therefore, this study provides an effective nucleic acid delivery system and a promising RNAi agent for the treatment of hepatitis B.


Assuntos
Regulação Viral da Expressão Gênica/efeitos dos fármacos , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Hepatite B , RNA Interferente Pequeno , Células Hep G2 , Hepatite B/tratamento farmacológico , Hepatite B/genética , Hepatite B/metabolismo , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/biossíntese , Antígenos E da Hepatite B/genética , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia
9.
Mol Neurobiol ; 59(1): 35-46, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34618330

RESUMO

We recently reported that intraperitoneal injection of 7,8-dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor-mimicking small compound, could attenuate alcohol-related behaviors in a two-bottle choice ethanol consumption procedure (IA2BC) in rats via tropomyosin receptor kinase B in the ventral tegmental area (VTA), which is closely related to alcohol use disorder. However, the detailed mechanisms underlying the regulation of 7,8-DHF on alcohol drinking behavior remain elusive. In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72 h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibited alcohol intake, whereas application of S-Nitroso-N-acetyl-DL-penicillamine (SNAP, the NO donor) in the VTA further enhanced alcohol consumption in IA2BC rats. Interestingly, either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (a sGC inhibitor) or KT5823 [a selective protein kinase G (PKG) inhibitor] blocked NO's enhancing effect on ethanol intake. Intraperitoneal injection of 7,8-DHF reduced the overexpression of NO; SNAP microinjected into the VTA reversed the inhibitory effects of 7,8-DHF on alcohol consumption. Our findings suggest that NO-cGMP-PKG might be involved in regulation of 7,8-DHF on alcohol consumption in IA2BC rats.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Flavonas/farmacologia , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Área Tegmentar Ventral/efeitos dos fármacos , Animais , GMP Cíclico/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Área Tegmentar Ventral/metabolismo
10.
Int J Gen Med ; 14: 9419-9431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34908869

RESUMO

PURPOSE: This study aimed to identify novel methylation-regulated genes as diagnostic biomarkers and therapeutic targets for hepatoblastoma (HB). MATERIALS AND METHODS: The DNA methylation data of 19 HB tumor samples and 10 normal liver samples from the GSE78732 dataset and gene expression profiling data of 53 HB tumor samples and 14 normal liver samples from the GSE131329 dataset and 31 HB tumor samples and 32 normal liver samples from the GSE133039 dataset were downloaded form the Gene Expression Omnibus database. Next, differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified. Venn diagrams were used to identify methylation-regulated genes. The VarElect online tool was selected to identify key methylation-regulated genes, and a protein-protein interaction (PPI) network was constructed to show the interactions among key methylation-regulated genes and DEGs. Finally, Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to investigate the potential regulatory mechanisms of key methylation-regulated genes. RESULTS: A total of 457 DMGs and 1597 DEGs were identified between the HB and normal liver samples. After DMGs and DEGs overlapping, 22 hypomethylated and upregulated genes and 19 hypermethylated and downregulated genes in HB were screened. Survival analysis revealed that 13 methylation-regulated genes were associated with the prognosis of liver cancer. Moreover, SPP1, UHRF1, and HEY1 were selected as the key DNA methylation-regulated genes. The PPI network revealed that all of them could affect TP53, while both UHRF1 and HEY1 could influence BMP4. Enrichment analysis suggested that the DEGs were involved in TP53-related pathways, including the cell cycle and p53 signaling pathway. Finally, SPP1, UHRF1, and HEY1 were hypomethylated and upregulated in the HB samples compared with those in the normal liver samples. CONCLUSION: SPP1, UHRE1, and HEY1 may play important roles in HB and be used as biomarkers for its diagnosis and treatment.

11.
Asian J Androl ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34806654

RESUMO

To explore the relationship between genetic polymorphisms of metabolic enzymes such as CYP1A1, CYP2D6, GSTM1, GSTT1, and GSTP1 and idiopathic male infertility. By observing the efficacy of antioxidants in the treatment of idiopathic male infertility, the effect of metabolic enzyme gene polymorphisms on antioxidant therapy in patients with idiopathic male infertility was prospectively studied. This case-control study included 310 men with idiopathic infertility and 170 healthy controls. The cytochrome P450 1A1 (CYP1A1), cytochrome P450 2D6 (CYP2D6), glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) genotypes in peripheral blood samples were analyzed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). The idiopathic male infertility group was treated with vitamin C, vitamin E, and coenzyme Q10 for 3 months and followed up for 6 months. GSTM1(-), GSTT1(-), and GSTM1/T1(-/-) in the idiopathic male infertility groups were more common than those in the control group. The sperm concentration, motility, viability, mitochondrial membrane potential (MMP), and seminal plasma total antioxidant capacity (T-AOC) level in patients with GSTM1(-), GSTT1(-), and GSTM1/T1(-/-) were lower than those in wild-type carriers, and the sperm DNA fragmentation index (DFI), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and malondialdehyde (MDA) and nitric oxide (NO) levels were higher. Therefore, oxidative damage may play an important role in the occurrence and development of idiopathic male infertility, but antioxidant therapy is not effective in male infertility patients with GSTM1 and GSTT1 gene deletions.

12.
Pathogens ; 10(11)2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34832636

RESUMO

Giardia duodenalis is a flagellated zoonotic parasite that can infect various animals and humans, causing economic losses in husbandry and detriments to public health. Although it has been reported in pigs worldwide, there are few reports on the prevalence and assemblages of G. duodenalis infection in pigs in China. In this study, the 396 pig fecal samples were randomly collected from seven farms in Zhejiang, Guangdong and Yunnan provinces in southern China, and were examined by means of the nested PCR amplification of ß-giardin (bg), glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) for the detection of G. duodenalis. Overall, 21 fecal samples were positive for G. duodenalis, with a prevalence of 5.3%. Three risk factors are associated with G. duodenalis infection, namely, region, age and gender. Moreover, 13, six and two samples were successfully amplified at the bg, gdh and tpi gene loci, respectively. Three assemblages of G. duodenalis were identified, including assemblage E (n = 17), assemblage A (n = 3) and assemblage B (n = 1). Assemblage E was the dominating genotype and was distributed in three provinces. These assemblages of G. duodenalis have also been found in human beings, non-human primates, sheep, goats and cattle, which further reveals that farmed pigs pose a potential threat to public health.

13.
Inorg Chem ; 60(23): 18307-18313, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34797066

RESUMO

Introducing transition metals into the intercluster linkers has been considered an important strategy for the rapid development of metal chalcogenide supertetrahedral (Tn) cluster-based open frameworks with excellent properties. However, using this strategy for achieving the structure and property tunability in the cluster-based framework of Tn (n ≥ 5) is still a great challenge. Herein, we report on three new sulfide and oxosulfide open frameworks of T5 clusters, i.e., T5-ZnMnInOS ([In30Zn5Mn4O2S58]12-), T5-MnInOS ([In34Mn5O2S58]8-), and T5-MnInS ([In28Mn6S54]12-). Interestingly, transition metals Zn and Mn are successfully introduced into T5-ZnMnInOS and T5-MnInOS via the consolidation of corner-shared Zn2OS2 and Mn2OS2 units, respectively. Under the photoexcitation of UV light, three compounds can emit bright-orange-red light closely associated with the Mn2+ ions, and the compounds containing M2OS2 units exhibit better photoluminescence (PL) lifetimes. Variable-temperature PL spectra demonstrate that the introduced M2OS2 units are favorable for weakening the deformation of the skeleton structure and decreasing the red shifts of the emission peaks at low temperatures. Moreover, the experimental results exhibit that the three compounds are wide-band-gap semiconductors and that the photogenerated electron separation efficiency can be doubly increased because the intercluster linkers are fixed by the M2OS2 units. This work paves a new way for enriching the content and distribution types of transition-metal sites in the supertetrahedral cluster-based metal chalcogenide open frameworks.

14.
J Immunol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799425

RESUMO

The proinflammatory cytokine IL-1ß is a crucial mediator of inflammatory responses. IL-1ß-induced signaling is finely regulated by various mechanisms, and its imbalance is involved in a variety of diseases. In this study, we identified FAM177A1, a protein of unknown function, as a negative regulator of IL-1ß-induced signaling in human cells. Overexpression of FAM177A1 inhibited IL-1ß-triggered activation of NF-κB and transcription of inflammatory genes, whereas knockdown of FAM177A1 showed the opposite effects. Mechanistically, FAM177A1 competitively bound to the E3 ubiquitin ligase TRAF6 and impaired its interaction with the E2-conjugating enzyme Ubc13; therefore, it inhibited TRAF6-mediated polyubiquitination and recruitment of downstream signaling molecules. These findings reveal a function of FAM177A1 and promote our understanding of the regulatory mechanisms of IL-1ß-induced inflammatory responses.

15.
World J Clin Cases ; 9(30): 8985-8998, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34786382

RESUMO

BACKGROUND: Myopia, as one of the common ocular diseases, often occurs in adolescence. In addition to the harm from itself, it may also lead to serious complications. Thus, prevention and control of myopia are attracting more and more attention. Previous research revealed that single-focal glasses and orthokeratology lenses (OK lenses) played an important part in slowing down myopia and preventing high myopia. AIM: To compare the clinical effects of OK lenses and frame glasses against the increase of diopter in adolescent myopia and further explore the mechanism of the OK lens. METHODS: Changes in diopter and axial length were collected among 70 adolescent myopia patients (124 eyes) wearing OK lenses for 1 year (group A) and 59 adolescent myopia patients (113 eyes) wearing frame glasses (group B). Refractive states of their retina were inspected through multispectral refraction topography. The obtained hyperopic defocus was analyzed for the mechanism of OK lenses on slowing down the increase of myopic diopter by delaying the increase of ocular axis length and reducing the near hyperopia defocus. RESULTS: Teenagers in groups A and B were divided into low myopia (0D - -3.00 D) and moderate myopia (-3.25D - -6.00 D), without statistical differences among gender and age. After 1-year treatment, the increase of diopter and axis length and changes of retinal hyperopic defocus amount of group A were significantly less than those of group B. According to the multiple linear analysis, the retinal defocus in the upper, lower, nasal, and temporal directions had almost the same effect on the total defocus. The amount of peripheral retinal defocus (15°-53°) in group A was significantly lower than that in group B. CONCLUSION: Multispectral refraction topography is progressive and instructive in clinical prevention and control of myopia.

16.
J Cosmet Dermatol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648670

RESUMO

BACKGROUND: Salvianolic acid B (SAB) is one of the main active ingredients of Salvia Miltiorrhiza. It has significant skin anti-aging, whitening, and sun protection properties. AIMS: The study aimed at studying the mechanism underlying the effect of salvianolic acid Bon collagen synthesis, which has good anti-aging efficacy and modulates microcirculation. METHODS: This study employed available public databases, bioinformatics methodologies, and the inverse docking approach to explore the effectiveness of SAB in the regulating collagen synthesis, and then used an human dermal fibroblast (HDF)- Human dermal microvascular endothelial cell (HDMEC) in vitro model to validate the predicted mechanism of SAB in influencing collagen synthesis. RESULTS: The results showed that NO production in SAB-treated HDMEC-conditioned medium was increased compared to that in control media, and the same tendency was also observed for growth factor production. SAB also upregulated HDMEC cellular eNOS and VEGF. When SAB-treated HDMEC conditioned medium was transferred to HDFs, the expression of collagen I, collagen III, and elastin in HDFs was upregulated and MMP-1 was downregulated. CONCLUSIONS: The results show that SAB regulates collagen through the HDMEC-HDF pathway. Furthermore, the mechanisms might be closely related to the microcirculation factors NO and VEGF.

17.
Synth Syst Biotechnol ; 6(4): 262-271, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34584994

RESUMO

Histone-like nucleoid-structuring (H-NS) proteins are key regulators in gene expression silencing and in nucleoid compaction. The H-NS family member proteins MvaU in Pseudomonas aeruginosa are thought to bind the same AT-rich regions of chromosomes and function to coordinate the control of a common set of genes. Here, we explored the molecular mechanism by which MvaU controls PCA biosynthesis in P. aeruginosa PA1201. We present evidence suggesting that MvaU is self-regulated. Deletion of mvaU significantly increased PCA production, and PCA production sharply decreased when mvaU was over-expressed. MvaU transcriptionally repressed phz2 cluster expression and consequently reduced PCA biosynthesis. ß-galactosidase assays confirmed that base pairing near the -35 box is required when MvaU regulates PCA production in PA1201. Electrophoretic mobility shift assays (EMSA) and additional point mutation analysis demonstrated that MvaU directly bound to an AT-rich motif within the promoter of the phz2 cluster. Chromatin immunoprecipitation (ChIP) analysis also indicated that MvaU directly bound to the P5 region of the phz2 cluster promoter. MvaU repression of PCA biosynthesis was independent of QscR and OxyR in PA1201 and neither PCA or H2O2 were the environmental signals that induced mvaU expression. These findings detail a new MvaU-dependent regulatory pathway of PCA biosynthesis in PA1201 and provide a foundation to increase PCA fermentation titer by genetic engineering.

18.
Oncol Rep ; 46(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34368874

RESUMO

Long noncoding RNA (lncRNA) CDKN2B­antisense RNA 1 (AS1) functions as a tumor oncogene in numerous cancers. However, the roles and mechanism of CDKN2B­AS1 in colorectal cancer (CRC) have not been explored. The present study aimed to investigate whether and how CDKN2B­AS1 contributes to CRC progression. The data revealed that CDKN2B­AS1 expression was upregulated in CRC tissues. Loss­of­function assays demonstrated that CDKN2B­AS1 in CRC modulated cell proliferation and apoptosis, which was mediated by cyclin D1, cyclin­dependent kinase (CDK) 4, p­Rb, caspase­9 and caspase­3. Bioinformatics analysis and luciferase reporter assays indicated direct binding of microRNA (miR)­28­5p to CDKN2B­AS1. Moreover, the results herein revealed that the expression of miR­28­5p was negatively correlated with that of CDKN2B­AS1 in CRC tissue. Moreover, CDKN2B­AS1 acted as a miR­28­5p competing endogenous RNA (ceRNA) to target and regulate the expression of URGCP. These findings indicated that CDKN2B­AS1 plays roles in CRC progression, providing a potential therapeutic target or novel diagnostic biomarker for CRC.


Assuntos
Apoptose/genética , Proliferação de Células/genética , Neoplasias Colorretais/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Caspases/metabolismo , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Regulação para Cima
19.
Arch Microbiol ; 203(9): 5363-5371, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34386827

RESUMO

A novel mycelium-forming actinomycete strain, designated YIM S01255T were isolated from a salt lake. Optimal growth occurred in the presence of 0-5.0% (w/v) NaCl, at pH 7.0-8.0, and at 37 °C. Strain YIM S01255T contained meso-diaminopimelic acid as the diagnostic diamino acid, and glucose, galactose and arabinose as the whole-cell sugars. The major fatty acid (> 5.0%) were iso-C16:0, iso-C16:1H and iso-C15:0. The major menaquinone were MK-9(H4) and MK-8(H4). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylinositolmannoside and phosphatidylinositol. The DNA G + C content was 70.7 mol%. The 16S rRNA gene sequence of the strain showed high similarity to members of genera in the family Pseudonocardiaceae with values less than 95.8%, and most closely related to the genus Amycolatopsis. Both of phylogenetic analysis based on 16S rRNA gene sequences and the up-to-date bacterial genome sequences analysis revealed that strains YIM S01255T and Prauserella shujinwangii XJ46T formed a distinct monophyletic clade and was separated from the other members within the family Pseudonocardiaceae. The average nucleotide identity (ANI) values and digital DNA-DNA hybridization (dDDH) between the two strains were 81.0% and 40.6%, respectively. The distinctive polyphasic evidences differentiated YIM S01255T from members of the family Pseudonocardiaceae, so strain YIM S01255T is considered to represent a novel species of a novel genus of the family Pseudonocardiaceae, for which the name Qaidamihabitans albus gen. nov., sp. nov. is proposed. The type strain of genus Qaidamihabitans is YIM S01255T (= KCTC 49476T = CGMCC 4.7684T). Moreover, Prauserella shujinwangii is also proposed to being transferred into the genus Qaidamihabitans as Qaidamihabitans shujinwangii comb. nov. (type strain XJ46T = CGMCC 4.7125T = JCM 19736T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Actinobacteria , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2
20.
J Cancer Res Ther ; 17(3): 664-670, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269297

RESUMO

OBJECTIVE: The objective of this study was to perform a meta-analysis comparing the efficiency of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy to EGFR TKI treatment alone in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Following keyword queries in databases and identification of randomized control trials for inclusion, hazard ratios (HRs), relative risks (RRs), and associated 95% confidence intervals (95% CIs) were determined. RESULTS: Ten randomized controlled trials involving 1354 participants with NSCLC were evaluated. We found that a combined approach of chemotherapy with EGFR TKIs significantly improved overall survival (OS) compared with EGFR TKI alone in our patient cohort (HR = 0.47, 95% CI = 0.31-0.72). In addition, a higher overall response rate (ORR) was found for patients who received combined treatment compared to chemotherapy alone (RR = 2.17, 95% CI = 1.51-3.12). Furthermore, concomitant use of chemotherapy with TKIs significantly improved the progression-free survival (PFS) when compared to the use of TKIs alone (HR = 0.68, 95% CI = 0.49-0.95). Moreover, there was a higher ORR among patients who received combined treatment as compared to those who were managed using TKIs only (RR=1.17, 95%CI=1.09-1.25). CONCLUSION: Our meta-analysis shows that EGFR TKIs with chemotherapy confer better OS and ORR compared to either treatment alone, similarly, the combined treatment showed better PFS and ORR profiles than the use of TKI alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto
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