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1.
Front Mol Neurosci ; 15: 887426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493324

RESUMO

Objective: High-frequency repetitive transcranial magnetic stimulation (rTMS) induces analgesic effects in both experimental pain and clinical pain conditions. However, whether rTMS can modulate sensory and pain thresholds on sensory fibers is still unclear. Here, we compared the effects of three rTMS paradigms on sensory and pain thresholds conducted by different sensory fibers (Aß, Aδ, and C fibers) with sham stimulation and investigate the potential brain activation using functional near-infrared spectroscopy (fNIRS). Methods: Forty right-handed healthy subjects were randomly allocated into one of four groups. Each subject received one session rTMS [prolonged continuous theta-burst stimulation (pcTBS), intermittent theta-burst stimulation (iTBS), 10 Hz rTMS or sham]. Current perception threshold (CPT), pain tolerance threshold (PTT), and fNIRS were measured at baseline, immediately after stimulation, and 1 h after stimulation, respectively. Results: Significant differences between treatments were observed for changes for CPT 2,000 Hz between baseline and 1 h after rTMS (F = 6.551, P < 0.001): pcTBS versus sham (P = 0.004) and pcTBS versus 10 Hz rTMS (P = 0.007). There were significant difference in average HbO µm in the right frontopolar cortex (FPC) [channel 23: P = 0.030 (pcTBS versus sham: P = 0.036)], left dorsolateral prefrontal cortex (DLPFC) [channel 7: P = 0.006 (pcTBS versus sham: P = 0.004)], left FPC [channel 17: P = 0.014 (pcTBS versus sham: P = 0.046), channel 22: P = 0.004 (pcTBS versus sham: P = 0.004)] comparing four group in 1 h after stimulation in PTT 2000 Hz (Aß-fiber). Conclusion: Prolonged continuous theta-burst stimulation can regulate sensitivity on Aß fibers. In addition, single-session pcTBS placed on left M1 can increase the excitability of DLPFC and FPC, indicating the interaction between M1 and prefrontal cortex may be a potential mechanism of analgesic effect of rTMS. Studies in patients with central post-stroke pain are required to confirm the potential clinical applications of pcTBS.

2.
Front Pharmacol ; 13: 863750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35517787

RESUMO

Background: Although many genes related to epithelial-mesenchymal transition (EMT) have been explored in hepatocellular carcinoma (HCC), their prognostic significance still needs further analysis. Methods: Differentially expressed EMT-related genes were obtained through the integrated analysis of 4 Gene expression omnibus (GEO) datasets. The univariate Cox regression and Lasso Cox regression models are utilized to determine the EMT-related gene signature. Based on the results of multivariate Cox regression, a predictive nomogram is established. Time-dependent ROC curve and calibration curve are used to show the distinguishing ability and consistency of the nomogram. Finally, we explored the correlation between EMT risk score and immune immunity. Results: We identified a nine EMT-related gene signature to predict the survival outcome of HCC patients. Based on the EMT risk score's median, HCC patients in each dataset were divided into high and low-risk groups. The survival outcomes of HCC patients in the high-risk group were significantly worse than those in the low-risk group. The prediction nomogram based on the EMT risk score has better distinguishing ability and consistency. High EMT risk score was related to immune infiltration. Conclusion: The nomogram based on the EMT risk score can reliably predict the survival outcome of HCC patients, thereby providing benefits for medical decisions.

3.
Neuron ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35550066

RESUMO

Colorectal cancer stem cells (CSCs) contribute to colorectal tumorigenesis and metastasis. Colorectal CSCs reside within specialized niches and harbor self-renewal and differentiation capacities. However, the niche regulations of CSCs remain unclear. Here, we show that intestinal nerve cells are required for CSC self-renewal and colorectal tumorigenesis. Enteric serotonergic neurons produce 5-hydroxytryptamine (5-HT) to function as a modulator of CSC self-renewal. 5-HT receptors HTR1B/1D/1F are highly expressed in colorectal CSCs and engage with 5-HT to initiate Wnt/ß-catenin signaling. Mechanistically, colorectal cancer (CRC)-enriched microbiota metabolite isovalerate suppresses the enrichment of the NuRD complex onto Tph2 promoter to initiate Tph2 expression, leading to 5-HT production. 5-HT signaling is correlated with CRC severity. Blocking 5-HT signaling in mice not only inhibits the self-renewal of colorectal CSCs but also displays therapeutic efficacy against CRC tumors. Our findings reveal a cross talk between intestinal neurons and tumor cells that serves as an additional layer for CSC regulation.

4.
Front Oncol ; 12: 878482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574398

RESUMO

Objective: This study was to explore the difference and significance of parietal pleura invasion and rib invasion in pathological T classification with non-small cell lung cancer. Methods: A total of 8681 patients after lung resection were selected to perform analyses. Multivariable Cox analysis was used to identify the mortality differences in patients between parietal pleura invasion and rib invasion. Eligible patients with chest wall invasion were re-categorized according to the prognosis. Cancer-specific survival curves for different pathological T (pT) classifications were presented. Results: There were 466 patients considered parietal pleura invasion, and 237 patients served as rib invasion. Cases with rib invasion had poorer survival than those with the invasion of parietal pleura (adjusted hazard ratio [HR]= 1.627, P =0.004). In the cohort for parietal pleura invasion, patients with tumor size ≤5cm reached more satisfactory survival outcomes than patients with tumor size >5cm (unadjusted HR =1.598, P =0.006). However, there was no predictive difference in the cohort of rib invasion. The results of the multivariable analysis revealed that the mortality with parietal pleura invasion plus tumor size ≤5cm were similar to patients with classification pT3 (P =0.761), and patients for parietal pleura invasion plus tumor size >5cm and pT4 had no stratified survival outcome (P =0.809). Patients identified as rib invasion had a poorer prognosis than patients for pT4 (P =0.037). Conclusions: Rib invasion has a poorer prognosis than pT4. Patients with parietal pleura invasion and tumor size with 5.1-7.0cm could be appropriately up-classified from pT3 to pT4.

5.
Anim Biotechnol ; : 1-8, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507751

RESUMO

The early weaning and starter feeding have significant effects on lamb growth and digestive tract development. However, it is not clear whether the expression of IGF-1/IGF-1R genes could be affected by feeding starter and weaning. Therefore, a total of 102 Hu male neonatal lambs were randomly divided into 3 groups: fed with starter at 42d + weaned at 56d (group A), fed with starter at 7d + weaned at 28d (group B) and fed with starter at 7d + weaned at 56d (group C), to explore the effects of starter feeding and weaning age on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of Hu sheep. The results showed that IGF-I and IGF-IR genes were expressed extensively in various tissues of lambs, the expression of IGF-I was significantly higher in liver (p < 0.01), while the expression of IGF-IR was higher in rumen among gastrointestinal tissues. The mRNA level of IGF-I of group C was strikingly higher than that of group A at 28, 70, and 84d (p < 0.01) in liver, respectively. Rumen mRNA level of IGF-IR of group C was prominently higher than that of group A at 70d and 84d (p < 0.05), respectively. However, IGF-IR expression of group A was higher than that of group C at 14 and 42d (p < 0.05). The mRNA level of IGF-I of group B was significantly higher than that of group C at 42, 56, 70, and 84d (p < 0.01) in liver, while IGF-IR expression of group B was higher than that of group C at 70d (p < 0.01). In conclusion, early weaning and starter feeding affected liver IGF-I mRNA and rumen IGF-IR mRNA expression.

6.
J Oncol ; 2022: 1763778, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444698

RESUMO

Programmed cell death 1 ligand 1 (PD-L1) has been approved as predictive biomarker for non-small-cell lung cancer (NSCLC) patients treated with PD-(L)1 blockade therapy. The clinical/genomic features associated with PD-L1 are not well studied. Genomic profiling of tumor biopsies from 883 Chinese NSCLC patients was performed by targeted next-generation sequencing. Immunohistochemical analysis was conducted to evaluate PD-L1 expression levels using antibodies Dako 22C3 and 28-8, respectively. Our study showed distinct correlation between PD-L1 expression and clinical/genomic characteristics when using different PD-L1 antibodies and in different histological subtypes including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), respectively. PD-L1 high expression (22C3) was associated with male and lymph node metastasis only in ADC patients. Furthermore, mutations of TP53 and KRAS, KIF5B-RET fusion, copy number gains of PD-L1 and PD-L2, and arm-level amplifications of chr.12p were significantly associated with PD-L1 positive status in ADC patients. For SCC patients, the gain of EGFR and MDM2 and loss of PTPRD were negatively associated with PD-L1 expression. We also compared our results with other studies and found conflicting results presumably because of the multiplicity of antibody clones and platforms, the difference of cutoffs for assigning PD-L1 expression levels, and the variation in study populations. Our study can help to understand the utility and validity of PD-L1 as biomarker of response to immune checkpoint inhibitors.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35445551

RESUMO

Interspecies transmission of influenza A virus (IAV) between pigs and people represents a threat to both animal and public health. To better understand the risks of influenza transmission at the human-animal interface, we evaluated 1) the rate of IAV detection in swine farmworkers before and after work during two human influenza seasons, 2) assessed risk factors associated with IAV detection in farmworkers and 3) characterized the genetic sequences of IAV detected in both workers and pigs. Of 58 workers providing nasal passage samples during 8-week periods during the 2017/18 and 2018/19 influenza seasons, 33 (57%) tested positive by rRT-PCR at least once. Sixteen (27%) workers tested positive before work and 24 (41%) after work. At the sample level, 58 of 1,785 nasal swabs (3.2%) tested rRT-PCR positive, of which 20 of 898 (2.2%) were collected prior to work and 38 of 887 (4.3%) after work. Although farmworkers were more likely to test positive at the end of the working day (OR = 1.98, 95% CI 1.14-3.41), there were no influenza-like illness (ILI) symptoms, or other risk indicators, associated with IAV detection before or after reporting to work. Direct whole-genome sequencing from samples obtained from worker nasal passages indicated evidence of infection of a worker with pandemic 2009 H1N1 of human-origin IAV (H1-pdm 1A 3.3.2) when reporting to work, and exposure of several workers to a swine-origin IAV (H1-alpha 1A 1.1) circulating in the pigs on the farm where they were employed. Our study provides evidence of 1) risk of IAV transmission between pigs and people, 2) pandemic H1N1 IAV infected workers reporting to work and 3) workers exposed to swine harbouring swine-origin IAV in their nasal passages temporarily. Overall, our results emphasize the need to implement surveillance and transmission preventive protocols at the pig/human interface.

8.
Front Pharmacol ; 13: 854851, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431958

RESUMO

Objective: The purpose of this study was to establish an N6-methylandenosine (m6A)-related long non-coding RNA (lncRNA) signature to predict the prognosis of hepatocellular carcinoma (HCC). Methods: Pearson correlation analysis was used to identify m6A-related lncRNAs. We then performed univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct an m6A-related lncRNA signature. Based on the cutoff value of the risk score determined by the X-title software, we divided the HCC patients into high -and low-risk groups. A time-dependent ROC curve was used to evaluate the predictive value of the model. Finally, we constructed a nomogram based on the m6A-related lncRNA signature. Results: ZEB1-AS1, MIR210HG, BACE1-AS, and SNHG3 were identified to comprise an m6A-related lncRNA signature. These four lncRNAs were upregulated in HCC tissues compared to normal tissues. The prognosis of patients with HCC in the low-risk group was significantly longer than that in the high-risk group. The M6A-related lncRNA signature was significantly associated with clinicopathological features and was established as a risk factor for the prognosis of patients with HCC. The nomogram based on the m6A-related lncRNA signature had a good distinguishing ability and consistency. Conclusion: We identified an m6A-related lncRNA signature and constructed a nomogram model to evaluate the prognosis of patients with HCC.

9.
Cell Res ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428874

RESUMO

Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored. Here, we investigated the dynamic changes in nucleosome occupancy and positioning in pronucleus-stage zygotes using ultra low-input MNase-seq. We observed distinct features of inheritance and reconstruction of nucleosome positioning in both paternal and maternal genomes. Genome-wide de novo nucleosome occupancy in the paternal genome was observed as early as 1 h after the injection of sperm into ooplasm. The nucleosome positioning pattern was continually rebuilt to form nucleosome-depleted regions (NDRs) at promoters and transcription factor (TF) binding sites with differential dynamics in paternal and maternal genomes. NDRs formed more quickly on the promoters of genes involved in zygotic genome activation (ZGA), and this formation is closely linked to histone acetylation, but not transcription elongation or DNA replication. Importantly, we found that NDR establishment on the binding motifs of specific TFs might be associated with their potential pioneer functions in ZGA. Further investigations suggested that the predicted factors MLX and RFX1 played important roles in regulating minor and major ZGA, respectively. Our data not only elucidate the nucleosome positioning dynamics in both male and female pronuclei following fertilization, but also provide an efficient method for identifying key transcription regulators during development.

10.
Front Mol Neurosci ; 15: 835012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359568

RESUMO

Globally, traumatic brain injury (TBI) is an acute clinical event and an important cause of death and long-term disability. However, the underlying mechanism of the pathophysiological has not been fully elucidated and the lack of effective treatment a huge burden to individuals, families, and society. Several studies have shown that long non-coding RNAs (lncRNAs) might play a crucial role in TBI; they are abundant in the central nervous system (CNS) and participate in a variety of pathophysiological processes, including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis, and neurogenesis. Some lncRNAs modulate multiple therapeutic targets after TBI, including inflammation, thus, these lncRNAs have tremendous therapeutic potential for TBI, as they are promising biomarkers for TBI diagnosis, treatment, and prognosis prediction. This review discusses the differential expression of different lncRNAs in brain tissue during TBI, which is likely related to the physiological and pathological processes involved in TBI. These findings may provide new targets for further scientific research on the molecular mechanisms of TBI and potential therapeutic interventions.

11.
Front Immunol ; 13: 844036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359983

RESUMO

Background and Objectives: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is considered an immune-mediated heterogeneous disease that involves both cellular and humoral immunity. The advent of the new concept of node-paranodopathy in recent years has boosted the identification of more antibody-positive CIDP variants patients. Cases of Caspr1 autoantibodies are the least common. Here, we reported two patients with Caspr1 autoantibodies and summarized their clinical features and treatment responses. Methods: Do statistical analyses on the clinical manifestations and laboratory examinations obtained from two patients identified in this study, and eight patients with anti-Caspr1 antibodies reported in previous research. And based on the developed scoring standard, draw the radar charts and line graphs. Results: Similar to other studies, the two patients we mentioned had a subacute and severe onset, distal phenotype, sensory ataxia, and severe pain. Differently, they had severe pain accompanying cold sense and coarse tremor in both hands, which may be a typical symptom for the anti-Caspr1 positive patient in south China. And we drew the line and radar graph for two China patients based on five aspects, muscle strength, sensory nerve, cranial nerve, laboratory tests, and NCS examinations. The two visual data charts offered new complementary means for the diagnostic assessment of CIDP variants. Conclusion: Pain with cold sense, coarse tremor in hands, and CSF protein levels greater than 3g/L may be the source of the distinct symptoms observed in patients with anti-Caspr1 autoantibodies in south China.


Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Autoanticorpos , Humanos , Dor , Fenótipo , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Tremor
12.
J Cell Mol Med ; 26(10): 2935-2946, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35388602

RESUMO

The aim of this study was to identify potential biomarkers of TB in blood and determine their function in Mtb-infected macrophages. First of all, WGCNA was used to analyse 9451 genes with significant changes in TB patients' whole blood. The 220 interferon-γ-related genes were identified, and then 30 key genes were screened using Cytoscape. Then, the AUC values of key genes were calculated to further narrow the gene range. Finally, we identified 9 genes from GSE19444. ROC analysis showed that SAMD9L, among 9 genes, had a high diagnostic value (AUC = 0.925) and a differential diagnostic value (AUC>0.865). To further narrow down the range of DEGs, the top 10 hub-connecting genes were screened from monocytes (GSE19443). Finally, we obtained 4 genes (SAMD9L, GBP1, GBP5 and STAT1) by intersections of genes from monocytes and whole blood. Among them, it was found that the function of SAMD9L was unknown after data review, so this paper studied this gene. Our results showed that SAMD9L is up-regulated and suppresses cell necrosis, and might be regulated by TLR2 and HIF-1α during Mtb infection. In addition, miR-181b-5p is significantly up-regulated in the peripheral blood plasma of tuberculosis patients, which has a high diagnostic value (AUC = 0.969).

13.
Sci Total Environ ; 836: 155472, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35472359

RESUMO

Studies have documented the significant effect of various factors on hydrological drought events. However, few studies have quantified drought's development and recovery process under environmental changes. This study focused on identifying hydrological drought's development and recovery characteristics and their potential causes in a typical semi-arid area. The Standardized Streamflow Index (SSI) was used as a metric for hydrological droughts, while the run theory was applied to identify the development and recovery processes of droughts. Changes in observed (human disturbed scenario) and simulated (natural scenario) droughts by employing the SWAT (Soil and Water Assessment Tool) model were also investigated from 1970 to 2016. The "simulated-observed" approach was used to assess the impacts of human regulations on hydrological drought development and recovery characteristics. Results showed that hydrological droughts occurred mainly during 1980-1990 and 2000-2016. In the natural condition, drought duration and intensity were higher, while lower severity in the drought recovery stage than development stage was observed. The drainage characteristics of the basin played the most critical role in the development and recovery characteristics of drought, which were also influenced by climatic conditions. Human activities had exacerbated recent natural hydrological drought. When considering the contribution of human activities, the reservoir operation was the dominant anthropic factor affected the development and recovery process of drought in the study area. Under the effects of reservoir regulation, long-duration hydrological droughts became rare. Moreover, the recovery ability of drought had been weakened. The effects of the reservoir were progressively crucial gradually. Although the water got from the river by the reservoir had been reduced, the negative impact on aggravating drought remains stronger than the reservoir was initially constructed. The results of our study will help improve the optimal management of reservoirs in semi-arid areas and enhance drought early warning and forecasting system.

14.
Front Endocrinol (Lausanne) ; 13: 800135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295993

RESUMO

Objective: A Rathke's cleft cyst (RCC) is a common, benign, cystic disease that often leads to hypophyseal dysfunction or head symptoms. The relationship between RCCs and pituitary gland function is not clear. We therefore carried out a study to examine this relationship in greater detail. Methods: The study was a retrospective, cohort design in patients diagnosed with a RCC between January 2019 to July 2021 at the First Affiliated Hospital of Zhengzhou University, China. Results: A total of 221 patients were enrolled and then divided into study cohorts according to the diameter of the RCC, clinical manifestations, and surgical treatment received. The majority of patients were symptomatic (143/221), including 83 cases of dizziness and headache, 9 of vision loss and visual field defect, and 2 of diabetes insipidus. 52 cases had abnormal pituitary function, with 8 cases interestingly showing high adrenocorticotropic-hormone (ACTH) and cortisone levels, while 8 juvenile cases had developed central precocious puberty. Patients with larger RCCs were more likely to present with headaches and dizziness, with subjects who suffered from these symptoms having high ACTH and cortisone levels. Conclusion: Although the size of a RCC is not an important factor influencing hypopituitary function, we consider that endocrine evaluation should be carried out in all patients with a RCC.


Assuntos
Carcinoma de Células Renais , Cistos do Sistema Nervoso Central , Cortisona , Neoplasias Renais , Doenças da Hipófise , Neoplasias Hipofisárias , Hormônio Adrenocorticotrópico , Cistos do Sistema Nervoso Central/complicações , Tontura , Feminino , Humanos , Masculino , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Hipófise , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos
15.
Neurochem Res ; 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35266084

RESUMO

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients. However, the effects and mechanism of autophagy after TBI remain unclear. This study aimed to investigate whether tetrandrine could ameliorate TBI through autophagy to reduce ferroptosis. A mice model for TBI was implemented. Behavioral and histomorphological experiments were performed to evaluate outcomes of the mice. The ferroptosis levels was detected by Perls staining. Enzyme-linked immunosorbent assay (ELISA) was applied to detect malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels in the brain tissue. Western blot test was performed to detect Beclin 1, light chain 3 (LC3) II/I, p62, GPX4, SCL7A11, and ferritin heavy chain 1 (FTH1) levels, and the expression of LC3B, Beclin 1, GPX4, and FTH1 in the brain tissue was detected by immunofluorescence (IF). The behavioral and histomorphological results demonstrated that tetrandrine improved the neurological function and cerebral edema on days 1, 3, and 7 after TBI. The ELISA results suggested that tetrandrine reduced the MDA concentration and increased GSH concentration on days 1, 3, and 7 after TBI. IF staining and Perls staining reflected that tetrandrine promoted autophagy and inhibited ferroptosis on days 1, 3, and 7 after TBI, respectively. Tetrandrine further improved the neurological function, cerebral edema, autophagy, and ferroptosis on days 1, 3, and 7 after TBI after adding the autophagy inducer rapamycin. The effect of TET in alleviating TBI increased with the increase of time and dose. Tetrandrine ameliorated TBI by regulating autophagy to reduce ferroptosis, providing a new therapeutic strategy for TBI.

16.
Mol Ther Nucleic Acids ; 27: 718-732, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35317282

RESUMO

Drug discovery from plants usually focuses on small molecules rather than such biological macromolecules as RNAs. Although plant transfer RNA (tRNA)-derived fragment (tRF) has been associated with the developmental and defense mechanisms in plants, its regulatory role in mammals remains unclear. By employing a novel reverse small interfering RNA (siRNA) screening strategy, we show that a tRF mimic (antisense derived from the 5' end of tRNAHis(GUG) of Chinese yew) exhibits comparable anti-cancer activity with that of taxol on ovarian cancer A2780 cells, with a 16-fold lower dosage than that of taxol. A dual-luciferase reporter assay revealed that tRF-T11 directly targets the 3' UTR of oncogene TRPA1 mRNA. Furthermore, an Argonaute-RNA immunoprecipitation (AGO-RIP) assay demonstrated that tRF-T11 can interact with AGO2 to suppress TRPA1 via an RNAi pathway. This study uncovers a new role of plant-derived tRFs in regulating endogenous genes. This holds great promise for exploiting novel RNA drugs derived from nature and sheds light on the discovery of unknown molecular targets of therapeutics.

17.
Life Sci ; 296: 120439, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35235851

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world. The clinical benefit of anti-angiogenic strategy as a single drug is limited. Some studies showed that the combination of anti-angiogenic therapy and chemotherapy exhibited synergistic effect and reduced the side effects of chemotherapy drugs. We investigated the combined effects of these two types of drugs in gastric cancer cells in vitro and in vivo. METHODS: cell viability, migration, invasion, and apoptosis were evaluated by CCK-8, wound-healing, transwell, and Annexin V-FITC/PI assay, respectively. In vivo anti-cancer efficacy was tested for the cell proliferation and metastasis in cell line derived tumor xenograft (CDX) model and patient derived tumor xenografted (PDX) model based on Tg (fli-1: EGFP) zebrafish embryos; RESULTS: In the cell experiments, the combination of the two types of drugs could inhibit the proliferation and metastasis of gastric cancer cells and promote apoptosis through VEGFR-2/AKT/ERK1/2 signal. In the zebrafish CDX (zCDX) model and zebrafish PDX (zPDX) model, the combination of the two treatment also showed a synergistic effect in inhibiting gastric cancer cell metastasis and cell proliferation. CONCLUSIONS: Apatinib/ramucirumab targeted therapy combined with docetaxel or 5-fluorouracil (5-FU) may serve as an effective treatment strategy for patients with advanced gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Animais Geneticamente Modificados , Anticorpos Monoclonais Humanizados/administração & dosagem , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Docetaxel/administração & dosagem , Embrião não Mamífero , Fluoruracila/administração & dosagem , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/administração & dosagem , Neoplasias Gástricas/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra/embriologia , Peixe-Zebra/genética
18.
Macromol Rapid Commun ; : e2100899, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247010

RESUMO

The molecular diversity of aggregation-induced emission remains a challenge due to the limitation of conventional synthesis methods. Here, a series of novel neutral and cationic conjugated polymers composed of various ratios of tetraarylethylene (TAE) containing a bridged oxygen (O) and fluorene (F) units is designed and synthesized via the geminal cross-coupling (GCC) of 1,1-dibromoolefins. The incorporation of TAE segments into the conjugated backbone of polyfluorene produces pronounced aggregation-induced ratiometric fluorescence, i.e., aggregation-induced emission (AIE) at 520-600 nm and grows synergistically with aggregations-caused quenching (ACQ) at 400-450 nm. The content of fluorene unit in the polymer backbones determines the intensity of the initial fluorescence in the blue light region. The huge distinction (about 150 nm) in dual emission wavelengths caused by the environment change makes these conjugated polyelectrolytes particularly suitable for ratiometric fluorescence sensing. Based on electrostatic interaction mechanism, the gradual addition of heparin into the cationic conjugated polymers aqueous solutions can induce dual-color fluorescence changes with a detection limit of 9 × 10-9 m. This work exhibits the great facility of using GCC reaction to synthesis the conjugated TAE polymers with superior AIE properties and special functions.

19.
Parasitology ; 149(2): 218-233, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35234601

RESUMO

Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.


Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Esquistossomose , Animais , Bovinos , China/epidemiologia , Humanos , Estudos Longitudinais , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Schistosoma japonicum/genética , Esquistossomose/epidemiologia , Esquistossomose Japônica/epidemiologia , Esquistossomose Japônica/veterinária , Caramujos
20.
Anat Rec (Hoboken) ; 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35238492

RESUMO

Poststroke thalamic pain (PSTP) is one of the most common sequelae following stroke. Analgesics, antidepressants, anticonvulsants, and surgical treatment are conventional treatment methods of PSTP, but these methods have limited efficacy, cost more, and cause a likelihood of adverse reactions. Clinical studies have shown that acupuncture has a significant analgesic effect on PSTP without obvious side effects. But, there is a lack of high-quality evidence concerning its effectiveness and safety to support its use. Therefore, this study aimed to evaluate the clinical efficacy and safety of acupuncture versus Western medicine for the treatment of PSTP to provide evidence to support clinical PSTP treatment. Searches were conducted to identify randomized controlled trials investigating the use of acupuncture for PSTP across six databases, including PubMed, the Cochrane Library, EMBASE, the China National Knowledge Infrastructure, Wan Fang Database, and the Chinese Scientific Journal Database VIP. RevMan 5.3 software was used for the meta-analysis. The results showed that compared with Western medicine, acupuncture had a higher total effective rate for the treatment of PSTP, reduced visual analog scale scores, increased beta-endorphin content, and decreased incidence of adverse reactions. However, the sample sizes of the included studies were insufficient, and the quality of the articles was relatively poor. In future studies, the clinical study design should be standardized and the sample size should be expanded to validate these results.

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