RESUMO
Auxin plays important roles throughout plant growth and development. However, the mechanisms of auxin regulation of plant structure are poorly understood. In this study, we identified a transcription factor (TF) of the BARLEY B RECOMBINANT/BASIC PENTACYSTEINE (BBR/BPC) family in apple (Malus × domestica), MdBPC2. It was highly expressed in dwarfing rootstocks, and it negatively regulated auxin biosynthesis. Overexpression of MdBPC2 in apple decreased plant height, altered leaf morphology, and inhibited root system development. These phenotypes were due to reduced auxin levels and were restored reversed after exogenous indole acetic acid (IAA) treatment. Silencing of MdBPC2 alone had no obvious phenotypic effect, while silencing both Class I and Class II BPCs in apple significantly increased auxin content in plants. Biochemical analysis demonstrated that MdBPC2 directly bound to the GAGA-rich element in the promoters of the auxin synthesis genes MdYUC2a and MdYUC6b, inhibiting their transcription and reducing auxin accumulation in MdBPC2 overexpression lines. Further studies established that MdBPC2 interacted with the polycomb group (PcG) protein LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) to inhibit MdYUC2a and MdYUC6b expression via methylation of histone 3 lysine 27 (H3K27me3). Silencing MdLHP1 reversed the negative effect of MdBPC2 on auxin accumulation. Our results reveal a dwarfing mechanism in perennial woody plants involving control of auxin biosynthesis by a BPC transcription factor, suggesting its use for genetic improvement of apple rootstock.
Assuntos
Malus , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Malus/genética , Malus/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Fenótipo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismoRESUMO
Purpose: This study systematically assesses the correlation between asymptomatic endometrial thickening after the age of 50 and the risk of endometrial cancer (EC). Methods: A comprehensive search was conducted using the Cochrane Library, Web of Science, PubMed, ProQuest, and Chinese biomedical literature databases Wanfang, Weipu, and CNG until August 2022. The included literature was analyzed using RevMan 5.3 software to explore heterogeneity in each study. Results: Five studies were finally included. The assessment of odds ratio (OR) heterogeneity between women with endometrial thickening and the risk of EC showed P = .18, I2=95%, indicating significant heterogeneity. A random-effects model was applied for meta-analysis, revealing a result of 0.96, 95% CI (0.92, 1.02), P = .18, indicating no statistical significance between the two groups (P > .05). The funnel plot demonstrated asymmetry, suggesting evident publication bias. Conclusion: There is no consistent correlation between asymptomatic endometrial thickening and the occurrence of EC in individuals over 50 years of age.
RESUMO
Dysfunction of Tumour Suppressor Genes (TSGs) is a common feature in carcinogenesis. Epigenetic abnormalities including DNA hypermethylation or aberrant histone modifications in promoter regions have been described for interpreting TSG inactivation. However, in many instances, how TSGs are silenced in tumours are largely unknown. Given that miRNA with low expression in tumours is another recognized signature, we hypothesize that low expression of miRNA may reduce the activity of TSG related enhancers and further lead to inactivation of TSG during cancer development. Here, we reported that low expression of miRNA in cancer as a recognized signature leads to loss of function of TSGs in breast cancer. In 157 paired breast cancer and adjacent normal samples, tumour suppressor gene GPER1 and miR-339 are both downregulated in Luminal A/B and Triple Negative Breast Cancer subtypes. Mechanistic investigations revealed that miR-339 upregulates GPER1 expression in breast cancer cells by switching on the GPER1 enhancer, which can be blocked by enhancer deletion through the CRISPR/Cas9 system. Collectively, our findings reveal novel mechanistic insights into TSG dysfunction in cancer development, and provide evidence that reactivation of TSG by enhancer switching may be a promising alternative strategy for clinical breast cancer treatment.
Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , MicroRNAs/genética , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/genética , Proteínas Supressoras de Tumor/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Elementos Facilitadores Genéticos/genética , Epigenômica , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Humanos , Regiões Promotoras Genéticas/genética , RNA Neoplásico/genética , Sequências Reguladoras de Ácido Nucleico/genéticaRESUMO
RNA binding proteins (RBPs) play pivotal roles in breast cancer (BC) development. As an RBP, Processing of precursor 7 (POP7) is one of the subunits of RNase P and RNase MRP, however, its exact function and mechanism in BC remain unknown. Here, we showed that expression of POP7 was frequently increased in BC cells and in primary breast tumors. Upregulated POP7 significantly promoted BC cell proliferation in vitro and primary tumor growth in vivo. POP7 also increased cell migration, invasion in vitro, and lung metastasis in vivo. Through RNA immunoprecipitation coupled with sequencing (RIP-seq), we found that POP7 bound preferentially to intron regions and POP7-binding peak associated genes were mainly enriched in cancer-related pathways. Furthermore, POP7 regulated Interleukin Enhancer Binding Factor 3 (ILF3) expression through influencing its mRNA stability. Knockdown of ILF3 significantly impaired the increased malignant potential of POP7-overexpressing cells, suggesting that POP7 enhances BC progression through regulating ILF3 expression. Collectively, our findings provide the first evidence for the important role of POP7 and its regulation of ILF3 in promoting BC progression.
Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Proteínas do Fator Nuclear 90 , Ribonuclease P , Feminino , Humanos , Neoplasias da Mama/genética , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Proteínas do Fator Nuclear 90/genética , Estabilidade de RNA/genética , Autoantígenos/genética , Ribonuclease P/genéticaRESUMO
Papillary thyroid cancer (PTC) is a common tumor malignancy of the endocrine system worldwide. Recently, circular RNAs (circRNAs) have been reported to participate in diverse pathological processes, especially in tumorigenesis. However, the functional role and mechanism of circRNA pleckstrin and Sec7 domain containing 3 (circ-PSD3) in PTC are still unclear. In this study, qRT-PCR results showed that circ-PSD3 was significantly upregulated in PTC tissues and cell lines. Meanwhile, circ-PSD3 overexpression was positively associated with larger tumor size, TNM stage, and lymph node metastasis. Knockdown of circ-PSD3 suppressed the proliferation and invasion of PTC cells. Besides, circ-PSD3 interacted with miR-7-5p to reduce its expression, and methyltransferase like 7B (METTL7B) was verified as a target gene of miR-7-5p. Functionally, inhibition of circ-PSD3 impeded PTC cell proliferation and invasion via targeting miR-7-5p to downregulate METTL7B expression. Taken together, silencing of circ-PSD3 hampered the proliferation and invasion of PTC cells via upregulating the inhibitory effect of miR-7-5p on METTL7B expression. Therefore, circ-PSD3 could be a potential diagnostic biomarker or molecular treatment target for PTC.
Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Proteínas de Transporte , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
PURPOSE: In this study, we sought to explore the function of seven important enzymes (MSMO1, EBP, HMGCS1, IDI2, DHCR7, FDFT1, and SQLE) involved in cholesterol biosynthesis especially SQLE in PDAC therapy. METHODS AND RESULTS: The TCGA and Oncomine dataset were used to explore the expression of the seven enzymes in normal and cancerous pancreatic individual, and their anti-proliferation efficiency against PDAC cells was measured by cell viability assay. Expression level and prognostic values of SQLE were evaluated by western blot and Kaplan-Meier analysis. The influence of SQLE knockdown by shRNA in PDAC cells was assessed by transwell, colony formation and cell cycle analysis. RNA-seq and GSEA were utilized to investigate the potential mechanisms. The synergistic effect of SQLE inhibitor, terbinafine, combined with six chemotherapeutic drugs in PDAC cells was tested by CCK-8 method. We demonstrated that downregulation of those enzymes especially SQLE significantly suppressed PDAC cells survival. SQLE was upregulated in PDAC cell lines, and the elevated level of SQLE was correlated with poor prognosis in pancreatic cancer samples. SQLE knockdown could significantly inhibit the proliferation and migration of PDAC cells. Cell cycle was blocked in S phase after SQLE silencing. Mechanistically, GSEA analysis with RNA-seq data revealed that SQLE silencing negatively mediated mTORC1 and TNFα/NF-κB signaling pathways. Besides, SQLE inhibitor terbinafine enhanced chemotherapeutic sensitivity of the six compounds. CONCLUSIONS: This study demonstrated that SQLE was a novel target for PDAC therapy. The synergism role of SQLE inhibition and chemotherapy may be potential therapeutic strategy for pancreatic cancer treatment.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Terbinafina , Neoplasias PancreáticasRESUMO
The authors describe a fluorometric strategy for the determination of dopamine (DA). It is based on the use of aptamer-functionalized MoS2 quantum dots (QDs) and MoS2 nanosheets (NSs). The QDs and NSs were extensively characterized with regard to their physical and chemical properties using methods such as TEM, XRD, FT-IR, EDX and molecular spectroscopies. The aptamer against dopamine was labeled with QDs acting as the energy donor in an energy transfer system, while the NSs serve as the energy acceptor. Under the optimal conditions, the fluorescence (FL) intensity (best measured at excitation/emission peaks of 315/412 nm) increases with increasing DA concentration in the range from 0.1 nM to 1000 nM, with a lower detection limit of 45 pM. The method was successfully applied to the determination of DA in complex matrices. In our perception, the method has a wide scope in that it may be extended to other biomolecules for which respective aptamer are available. The QDs show excellent optical properties, good stability, low cytotoxicity, and may also be applied to fluorometric imaging of live cells. Graphical abstract A "turn-on" fluorometric aptasensor for the determination of dopamine (DA) was established based on aptamer-functionalized molybdenum disulfide quantum dots (MoS2 QDs) and MoS2 nanosheets. This assay exhibits high selectivity and sensitivity with a detection limit as low as 45 pM.
Assuntos
Aptâmeros de Nucleotídeos/química , DNA/química , Dissulfetos/química , Dopamina/análise , Transferência Ressonante de Energia de Fluorescência/métodos , Molibdênio/química , Pontos Quânticos/química , Sequência de Bases , Técnicas Biossensoriais/métodos , Dissulfetos/toxicidade , Células HeLa , Humanos , Limite de Detecção , Molibdênio/toxicidade , Pontos Quânticos/toxicidadeRESUMO
Breast cancer is one of the most common malignant diseases in women. Triple-negative breast cancer (TNBC) shows higher aggressiveness and recurrence rates than other subtypes, and there are no effective targets or tailored treatments for TNBC patients. Thus, finding effective prognostic markers for TNBC could help clinicians in their ability to care for their patients. We used tissue microarrays (TMAs) to detect microRNA-493 (miR-493) expression in breast cancer samples. A miRCURY LNA detection probe specific for miR-493 was used in in situ hybridization assays. Staining results were reviewed by two independent pathologists and classified as high or low expression of miR-493. Kaplan-Meier survival plots and multivariate Cox analysis were carried out to clarify the relationship between miR-493 and survival. In the Kaplan-Meier analysis, patients with high miR-493 expression had better disease-free survival than patients with low miR-493 expression. After adjusting for common clinicopathological factors in breast cancer, the expression level of miR-493 was still a significant prognostic factor in breast cancer. Further subtype analysis revealed that miR-493 expression levels were only significantly prognostic in TNBC patients. These results were validated in the Molecular Taxonomy of Breast Cancer International Consortium database for overall survival. We proved the prognostic role of miR-493 in TNBC by using one of the largest breast cancer TMAs available and validated it in a large public RNA sequencing database.
Assuntos
MicroRNAs/biossíntese , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Biomarcadores Tumorais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias de Mama Triplo Negativas/mortalidadeRESUMO
BACKGROUND/AIMS: Food antigens are thought to play a vital role in the initiation and perpetuation of Crohn's disease (CD). The main purpose of this study was to evaluate the potential association of serum food specific IgG antibodies and small bowel (SB) inflammation in CD patients. METHODS: We conducted a prospective observational study with 96 CD patients. Demographic, disease-related data and inflammatory parameters were collected. Serum food IgG antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Capsule endoscopy was performed to detect SB inflammation quantified by the Lewis Score. RESULTS: Seventy-eight of (81.3%) CD patients were detected positive for at least one food-specific antibody. The five most prevalent food antibodies in CD patients were tomato, egg, corn, rice, and soybean. Patients with SB inflammation had a higher positive rate of food IgG antibodies (P = 0.010) and more IgG-positive food items (P = 0.010) than those without. Specifically, patients with SB inflammation were more likely to have positive food-specific IgG against egg (P = 0.014), corn (P = 0.014), and wheat (P = 0.048). Additionally, the number of positive food IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation (P = 0.015 and P = 0.013, respectively). CONCLUSION: Our study confirmed that CD patients with SB inflammation had a higher positive rate of food IgG antibodies and more IgG-positive food items. The number of food positive IgGs ≥ 3 and elevated ESR were independently associated with concurrent SB inflammation.
Assuntos
Doença de Crohn , Humanos , Antígenos , Doença de Crohn/complicações , Alimentos , Imunoglobulina G , Inflamação , Estudos ProspectivosRESUMO
Autism is a widespread neurodevelopmental disorder. Although the research on autism spectrum disorders has been increasing in the past decade, there is still no specific answer to its mechanism of action and treatment. As a pro-inflammatory microRNA, miR-301a is abnormally expressed in various psychiatric diseases including autism. Here, we show that miR-301a deletion and inhibition exhibited two distinct abnormal behavioral phenotypes in mice. We observed that miR-301a deletion in mice impaired learning/memory, and enhanced anxiety. On the contrary, miR-301a inhibition effectively reduced the maternal immune activation (MIA)-induced autism-like behaviors in mice. We further demonstrated that miR-301a bound to the 3'UTR region of the SOCS3, and that inhibition of miR-301a led to the upregulation of SOCS3 in hippocampus. The last result in the reduction of the inflammatory response by inhibiting phosphorylation of AKT and STAT3, and the expression level of IL-17A in poly(I:C)-induced autism-like features in mice. The obtained data revealed the miR-301a as a critical participant in partial behavior phenotypes, which may exhibit a divergent role between gene knockout and knockdown. Our findings ascertain that miR-301a negatively regulates SOCS3 in MIA-induced autism in mice and could present a new therapeutic target for ameliorating the behavioral abnormalities of autism.
RESUMO
OBJECTIVE: To investigate the survival benefit of preoperative bone scan in asymptomatic patients with early-stage non-small cell lung cancer (NSCLC). METHODS: This retrospective study included patients with radical resection for stage T1N0M0 NSCLC between March 2013 and December 2018. During postoperative follow-up, we monitored patient survival and the development of bone metastasis. We compared overall survival, bone metastasis-free survival, and recurrence-free survival in patients with or without preoperative bone scan. Propensity score matching and inverse probability of treatment weighting were used to minimize election bias. RESULTS: A total of 868 patients (58.19 ± 9.69 years; 415 men) were included in the study. Of 87.7% (761 of 868) underwent preoperative bone scan. In the multivariable analyses, bone scan did not improve overall survival (hazard ratio [HR] 1.49; 95% confidence intervals [CI] 0.91-2.42; p = 0.113), bone metastasis-free survival (HR 1.18; 95% CI 0.73-1.90; p = 0.551), and recurrence-free survival (HR 0.89; 95% CI 0.58-1.39; p = 0.618). Similar results were obtained after propensity score matching (overall survival [HR 1.28; 95% CI 0.74-2.23; p = 0.379], bone metastasis-free survival [HR 1.00; 95% CI 0.58-1.72; p = 0.997], and recurrence-free survival [HR 0.76; 95% CI 0.46-1.24; p = 0.270]) and inverse probability of treatment weighting. CONCLUSION: There were no significant differences in overall survival, bone metastasis-free survival, and recurrence-free survival between asymptomatic patients with clinical stage IA NSCLC with or without preoperative bone scan.
Assuntos
Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Ósseas/secundário , Neoplasias Ósseas/diagnóstico por imagem , Prognóstico , Idoso , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologiaRESUMO
OBJECTIVE: To explore the effect of traditional Chinese and western medicine on the levels of inflammatory cytokines in the peripheral blood of patients with lupus nephritis (LN). METHODS: A total of 80 patients with LN admitted to the hospital from August 2016 to August 2017 were retrospectively analyzed. They were equally separated into an experimental group and a control group by the different types of medications. The control group was treated with western medicine, and the experimental group was treated with the combination of traditional Chinese and western medicines. The therapeutic effects were compared. RESULTS: The levels of IL-6, IL-18 and TNF-α in the experimental group after treatment were (5.47±1.66) pg/ml, (31.66±3.87) pg/ml, and (9.28±3.06) pg/ml, respectively, which were significantly lower than (13.71±3.86) pg/ml, (68.47±4.26) pg/ml, and (22.17±6.54) pg/ml before treatment. The difference was statistically significant (t1 = 12.403, t2 = 40.450, t3 = 11.291, all P<0.001). In the control group after treatment, the levels of IL-6, IL-18 and TNF-α were (12.68±1.32) pg/ml, (68.22±3.42) pg/ml, and (19.78±5.57) pg/ml, respectively. The difference in control and experimental groups was statistically significant (t1 = 21.501, t2 = 44.771, t3 = 10.449, P<0.001). The total effective rate was 95.00% (38/40) in the experimental group and 80.00% (32/40) in control group, (X2 = 4.114, P<0.001). There SLEDAI scores of the experimental group were much lower than control after 8 and 12 weeks of treatment (t1 = 8.186, t2 = 20.776, P<0.001). Moreover, the liver and kidney Yin deficiency symptoms in both groups were significantly improved after treatment (P<0.01). CONCLUSION: The combined treatment of traditional Chinese and western medicine can successfully prevent the secretion of serum IL-6, IL-18 and TNF-α, control the development of disease, boost the therapeutic outcome, and alleviate the immune injury of the body.
RESUMO
Traffic accidents occur frequently in urban underground road diverging and merging areas due to the limited vision and complex traffic. Well-designed traffic visual guidance is one of the effective measures to alleviate the traffic safety problems in the diverging and merging areas of urban underground roads. In this study, four different integrated traffic guidance schemes (including signs, marking lines and sidewall guidance) were proposed and their effects on drivers' behaviour were investigated through driving simulator experiments and questionnaire survey. To investigate the influence of different schemes, eight variables about driving behaviour and guidance efficiency were assessed for analysis. Finally, a fuzzy comprehensive evaluation model based on analytic hierarchy process (FCE + AHP) was constructed to evaluate the effect of guidance schemes. Vehicle running state, driver operation behaviour and guidance efficiency were mainly considered. The guidance evaluation results obtained by the model were consistent with the conclusions of the driver subjective questionnaire. The results show that reasonable setting of white dotted lines and colour guidance can help drivers find exits quickly and improve driving stability. However, excessive combination of traffic guidance leads to information overload and produces the opposite effect. This study can provide a generic framework for the design and evaluation of traffic guidance facilities of urban underground roads.
Assuntos
Acidentes de Trânsito , Condução de Veículo , Humanos , Acidentes de Trânsito/prevenção & controle , Inquéritos e QuestionáriosRESUMO
Fuzhuan brick tea (FBT) is a post-fermented dark tea preferred by consumers for its excellent hypolipidemic activity, and theabrownin (TB) is the main bioactive composition in FBT. This work explored the structural and hypolipidemic properties of TB derived from Pingwu FBT, and investigated whether it exerted hypolipidemic activity by inhibiting intestinal lipid absorption. Structural characterization revealed that TB was an amorphous polymerized phenolic compound rich in hydroxyl and carboxyl groups with good thermostability. In vivo, TB and its fractions with different molecular weights (TB-LT3k, TB-3-10k, TB-10-30k, TB-30-100k, TB-GT100k) significantly reduced the lipid levels of hyperlipidemia zebrafish (P < 0.05). Moreover, TB attenuated hyperlipidemia by inhibiting intestinal lipid absorption, as TB effectively bound to bile acids, inhibited enzymatic activity of pancreatic lipase and cholesterol esterase, influenced micelle formation, and decreased micellar cholesterol solubility. Results facilitated research on TB and offered support for its feasibility as a natural alternative to prevent hyperlipidemia.
Assuntos
Hiperlipidemias , Doenças Metabólicas , Animais , Chá/química , Peixe-Zebra , Hiperlipidemias/tratamento farmacológico , Digestão , LipídeosRESUMO
Objective: To evaluate the clinical efficacy of Gandakang tablets plus methylprednisolone in patients with systemic lupus erythematosus (SLE). Methods: From February 2015 to February 2019, 60 eligible patients with SLE were recruited and assigned via the random number table method at a ratio of 1 : 1 to receive either methylprednisolone (control group) or Gandakang tablets plus methylprednisolone (observation group). The primary endpoint was clinical efficacy, and the secondary endpoints included Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, immunoglobulin (Ig), inflammatory factor levels, and adverse events. Results: Gandakang tablets plus methylprednisolone were associated with a significantly higher treatment efficacy versus methylprednisolone alone (P < 0.05). Gandakang tablets plus methylprednisolone resulted in significantly lower SLEDAI scores and lower levels of IgG, IgM, IgA, tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-6 (IL-6) versus single medication of methylprednisolone (P < 0.05). The two groups showed a similar incidence of adverse events (P > 0.05). Patients given Gandakang tablets plus methylprednisolone had higher mental health, emotional role, physical role, social functioning, and bodily pain scores versus those receiving the monotherapy of methylprednisolone (P < 0.05). Conclusion: Gandakang tablets plus methylprednisolone is effective in the treatment of SLE by enhancing the patients' immunity, mitigating the inflammatory response, eliminating negative emotions, and improving their quality of life.
RESUMO
Purpose: This study was conducted to characterize the expression level of peripheral blood toll-like receptors 9 (TLR9), nuclear factor kappa-B protein 65 (NF-κB p65), and myeloid differentiation factor88 (MyD88) of active systemic lupus erythematosus (SLE) and analyse their clinical significance. Methods: The prospective cohort study enrolled 30 active SLE patients (SG1 group), 30 stable SLE patients (SG2 group), and 20 healthy individuals (RG group) in the First Affiliated Hospital of Hainan Medical University between January 2018 and June 2020. All SLE patients were treated with methylprednisolone tablets. Quantitative polymerase chain reaction (qPCR) was used to determine the levels of TLR9, MyD88, and NF-κB p65 in the peripheral blood mononuclear cell (PBMC). ELISA was adopted for the determination of serum interleukin (IL-6) and tumor necrosis factor-α (TNF-α). Results: Patients in SG1 showed the highest mRNA levels of TLR9, MyD88, and NF-κB p65, followed by SG2, and then RG. SG1 had the highest serum levels of IL-6 and TNF-α, followed by SG2 and RG. The level of TLR9 was positively correlated with the SLE disease activity index (SLEDAI) and negatively correlated with complement component 3 (C3) and complement component 4 (C4). MyD88 and NF-κB p65 were positively correlated with SLEDAI. Conclusion: Compared with a healthy status, SLE induces an increase in TLR9, MyD88, NF-κB p65, IL-6, and TNF-α levels, and the activation of the TLR9-MyD88-NF-κB p65 signal path was associated with the pathogenesis of SLE.
RESUMO
OBJECTIVE: To investigate the prevalence of off-label aspirin indications and the level of scientific support for off-label indications of aspirin in gynaecology and obstetrics outpatients. DESIGN: A retrospective cross-sectional study. SETTING: Two tertiary hospitals (a general hospital and a women and children's specialised hospital) in Xiamen, a city located on the southeastern coast of China. PARTICIPANTS: A total of 4257 prescriptions were included for 2091 female patients aged >18 who visited the gynaecology and obstetrics outpatient clinics and received aspirin treatment. OUTCOME MEASURES: The primary measure of this study was the proportion of off-label indications and of off-label indications supported by strong scientific evidence. Evidence from clinical guidelines and Micromedex is shown using descriptive statements. On-label indications of drugs in the same class as aspirin were also referred to for off-label aspirin use without strong evidence support. RESULTS: All indications of aspirin on outpatient prescriptions were determined as off-label use in this study. The most frequent off-label indication was recurrent miscarriage (2244 prescriptions, 52.71%). Totally, 30.94% of the prescriptions were supported by strong evidence for indications, including recurrent miscarriage with antiphospholipid syndrome and prophylaxis for pre-eclampsia. No drugs in the same class as aspirin had on-label indications for off-label aspirin use without strong evidence support. CONCLUSIONS: This study demonstrated that all indications of aspirin used in gynaecology and obstetrics outpatients at the two tertiary hospitals were off-label and not always supported by strong evidence, implicating that physicians should be cautious when issuing off-label prescriptions. More original clinical research on off-label aspirin use is needed to provide reference for routine clinical practice.
Assuntos
Ginecologia , Obstetrícia , Idoso , Aspirina/uso terapêutico , Criança , China , Estudos Transversais , Feminino , Humanos , Uso Off-Label , Pacientes Ambulatoriais , Padrões de Prática Médica , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
Gypsum (calcium sulfate dihydrate, CaSO4 ·2H2O) is commonly applied to improve soil quality and nutrient supply. Previous studies also suggested it is a cost-effective soil amendment in alleviating cadmium (Cd) toxicity and accumulation in plants. The aim of this study was to investigate how this is achieved. We used pak choi as our research material because it is a popular vegetable in Asia, and as a leafy vegetable, it accumulates higher Cd level than other types of vegetable. Under Cd stress, application of CaSO4 promoted pak choi seedling growth, decreased the oxidative stress in roots, reduced Cd accumulation, and enhanced the photosynthesis in shoots. We revealed the inhibition of Cd2+ absorption by CaSO4 is largely due to the competition between Ca2+ and Cd2+ for ion channels or transporter. Moreover, under Cd stress, CaSO4 facilitated the sulphate assimilation, increased the biosynthesis of phytochelatins, and activated the expression of transporters for vacuolar sequestration. Together, CaSO4 could benefit plant growth and enhance Cd tolerance by suppressing Cd root uptake and lowering the Cd content in cytoplasm.
Assuntos
Plântula , Poluentes do Solo , Cádmio/análise , Cádmio/toxicidade , Sulfato de Cálcio , Raízes de Plantas/química , Plântula/química , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidadeRESUMO
OBJECTIVES: Small cell lung cancer (SCLC) is notorious for aggressive malignancy without effective treatment, and most patients eventually develop tumor progression with a poor prognosis. There is an urgent need for discovering novel antitumor agents or therapeutic strategies for SCLC. MATERIALS AND METHODS: We performed a screening method based on CCK-8 assay to screen 640 natural compounds for SCLC. The effects of Sanguinarine chloride on SCLC cell proliferation, colony formation, cell cycle, apoptosis, migration and invasion were determined. RNA-seq and bioinformatics analysis was performed to investigate the anti-SCLC mechanism of Sanguinarine chloride. Publicly available datasets and samples were analyzed to investigate the expression level of CDKN1A and its clinical significance. Loss of functional cancer cell models were constructed by shRNA-mediated silencing. Quantitative RT-PCR and Western blot were used to measure gene and protein expression. Immunohistochemistry staining was performed to detect the expression of CDKN1A, Ki67, and Cleaved caspase 3 in xenograft tissues. RESULTS: We identified Sanguinarine chloride as a potential inhibitor of SCLC, which inhibited cell proliferation, colony formation, cell cycle, cell migration and invasion, and promoted apoptosis of SCLC cells. Sanguinarine chloride played an important role in anti-SCLC by upregulating the expression of CDKN1A. Furthermore, Sanguinarine chloride in combination with panobinostat, or THZ1, or gemcitabine, or (+)-JQ-1 increased the anti-SCLC effect compared with either agent alone treatment. CONCLUSIONS: Our findings identified Sanguinarine chloride as a potential inhibitor of SCLC by upregulating the expression of CDKN1A. Sanguinarine chloride in combination with chemotherapy compounds exhibited strong synergism anti-SCLC properties, which could be further clinically explored for the treatment of SCLC.