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1.
Molecules ; 26(1)2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401561

RESUMO

E. coli O157:H7 is a pathogenic bacterium producing verotoxins that could lead to serious complications such as hemolytic uremia syndrome. Fast detection of such pathogens is important. For rapid detection, aptamers are quickly gaining traction as alternative biorecognition molecules besides conventional antibodies. Several DNA aptamers have been selected for E. coli O157:H7. Nonetheless, there has not been a comparative study of the binding characteristics of these aptamers. In this work, we present a comprehensive analysis of binding characteristics including binding affinity (Kd) and binding capacity (Bmax) of DNA-based aptamers for E. coli O157:H7 using qPCR. Our results show that aptamer E18R has the highest binding capacity to E. coli 157:H7 and the highest specificity over non-pathogenic E. coli strains K12 and DH5α. Our study also finds that the common biotin-tag modification at 5' end typically changes the binding capacity significantly. For most of the selected aptamers, the binding capacity after a biotin-tag modification decreases. There exists a discrepancy in the binding capability between the selected aptamer and the aptamer used for detection. Our study also shows that a lower concentration of Mg2+ ions in the binding buffer leads to a decrease in the binding capacity of E17F and E18R, while it does not affect the binding capacity of S1 and EcoR1.

2.
Int Urol Nephrol ; 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-33386583

RESUMO

PURPOSE: To investigate the effect of detrusor underactivity on the efficacy of TURP in patients with benign prostate obstruction. METHODS: A retrospective study of 350 patients with benign prostate obstruction who underwent TURP was carried out. Different degrees of bladder outlet obstruction were grouped by the bladder outlet obstruction index. ROC curves were used to calculate the optimal cut-off point for the bladder contractility index used to divide the DU patients into mild DU and severe DU patients. The effect of DU on the efficacy of TURP in benign prostate obstruction patients was studied by comparing the subjective and objective parameters preoperatively and 3 months postoperatively between severe DU, mild DU and non-DU benign prostate obstruction patients in two obstruction groups (20 ≤ BOOI < 40 and BOOI ≥ 40). RESULTS: According to the ROC curve, the optimal cut-off point for the bladder contractility index was 82; thus, 69 patients were considered mild DU patients (82 ≤ BCI < 100), 67 patients were considered severe DU patients (BCI < 82), and 214 patients were considered non-DU patients (BCI ≥ 100). Both the postoperative subjective and objective parameters of the non-DU, mild DU and severe DU patients significantly improved in two obstruction groups. However, in the 20 ≤ BOOI < 40 group, the successful improvement rates for the IPSS, IPSS-S, IPSS-V, QoL and fQmax in the severe DU patients were only 38.2%, 38.2%, 44.1%, 41.2% and 38.2%, respectively. CONCLUSION: Patients with varying degrees of benign prostate obstruction can benefit from TURP, but for patients with severe DU in the 20 ≤ BOOI < 40 group, TURP should be considered only after deliberation.

3.
Chem Asian J ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427391

RESUMO

Mitochondrial pH is an important factor associated with cellular metabolism and pathological states. Thus, sensitively monitoring its minor change was essential. However, it was challengeable due to the lack of suitable probes. Here, a mitochondria-targeted probe ( NIR-OH-1 ) was synthesized. Based on the protonation/deprotonation of the hydroxy group and the assistance help of carboxyl group on NIR-OH-1 molecular structure, a dramatic NIR activated signal was generated for sensing pH. Probe NIR-OH-1 display ed a good photo-stability, reversibility, and could detect pH change without interference by other biologically active species. Importantly, NIR-OH-1 had an appropriate p K a value (7.77) and tiny acid-base transition range, which was allowed to map the small pH changes of cellular mitochondrial. Moreover, NIR-OH-1 was also successfully applied in real-time monitoring mitochondrial pH-related pathological events in living cells under different stimulation, demonstrating the prospect of its clinical application in accurate mitochondrial pH detection under related physiological and pathological conditions.

4.
Medicine (Baltimore) ; 99(51): e23807, 2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33371157

RESUMO

BACKGROUND: Chronic insomnia (CI) can lead to cognitive dysfunction and bring great pain to patients' life. There is no effective intervention for cognitive dysfunction caused by CI. Shenmen (HT7) is the first choice for insomnia treatment. However, the effect and mechanism of this acupoint on cognitive function after insomnia is not clear. Therefore, the purpose of this study is to explore whether magnetic stimulation of HT7 can improve cognitive impairment of CI by regulating prefrontal lobe and its mechanism. METHODS/DESIGN: This is a randomized controlled clinical trial. Seventy-two subjects aged 18 to 65 years old with primary insomnia and more than 3 months were randomly divided into 2 groups according to the ratio of 1:1, and 36 healthy controls were included. The control group was given sleep hygiene and cognitive therapy in behavioral cognitive therapy technology, while the experimental group was given the behavioral cognitive therapy technology intervention and magnetic stimulation of HT7 acupoint for 30 times (2 times / d, 5 times / wk for 20 days), while the healthy control group had no intervention measures. Before treatment and 20 days after treatment, we evaluated the working memory (1-back test), episodic memory (Complex Figure Test), and problem-solving ability (Hanoi tower test) processed by prefrontal lobe to explore the effect of magnetic stimulation on cognitive function of CI and its possible mechanism. At the same time, insomnia severity index was used to evaluate sleep state, Becker depression scale was used to evaluate depression, and Beck anxiety scale was used to evaluate anxiety. Chi-squared test or rank sum test was used to collect the data of patients. If P value is less than or equal to .05, the difference will be considered statistically significant. CONCLUSION: This study explored the effect and mechanism of magnetic stimulation of Shenmen (HT7) on cognitive function of CI, and confirmed that magnetic stimulation of HT7 can be used as an alternative therapy to improve cognitive impairment of CI. TRIAL REGISTRATION NUMBER: ChiCTR2000034280.

5.
Environ Res ; 193: 110521, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33279492

RESUMO

Meteorological parameters are the critical factors of affecting respiratory infectious disease such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS) and influenza, however, the effect of meteorological parameters on coronavirus disease 2019 (COVID-19) remains controversial. This study investigated the effects of meteorological factors on daily new cases of COVID-19 in 127 countries, as of August 31 2020. The log-linear generalized additive model (GAM) was used to analyze the effect of meteorological variables on daily new cases of COVID-19. Our findings revealed that temperature, relative humidity, and wind speed are nonlinearly correlated with daily new cases, and they may be negatively correlated with the daily new cases of COVID-19 over 127 countries when temperature, relative humidity and wind speed were below 20°C, 70% and 7 m/s respectively. Temperature(>20°C) was positively correlated with daily new cases. Wind speed (when>7 m/s) and relative humidity (>70%) was not statistically associated with transmission of COVID-19. The results of this research will be a useful supplement to help healthcare policymakers in the Belt and Road countries, the Centers for Disease Control (CDC) and the World Health Organization (WHO) to develop strategies to combat COVID-19.

6.
Curr Mol Med ; 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272176

RESUMO

Male fertility is closely related to the normal function of the hypothalamic-pituitary-testicular axis. The testis is an important male reproductive organ that secretes androgen and produces sperm through spermatogenesis. Spermatogenesis refers to the process by which spermatogonial stem cells (SSCs) produce highly differentiated spermatozoa and is divided into three stages: mitosis, meiosis and spermiogenesis. Spermatogenesis requires SSCs to strike a proper balance between self-renewal and differentiation and the commitment of spermatocytes to meiosis, which involves many molecules and signalling pathways. Abnormal gene expression or signal transduction in the hypothalamus and pituitary, but particularly in the testis, may lead to spermatogenic disorders and male infertility. The phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in many stages of male reproduction, including the regulation of the hypothalamus-pituitary-gonad (HPG) axis during spermatogenesis, the proliferation and differentiation of spermatogonia and somatic cells, and the regulation of sperm autophagy and testicular endocrine function in the presence of environmental pollutants, particularly endocrine-disrupting chemicals (EDCs). In the PI3K/AKT/mTOR signalling pathway, mTOR is considered the central integrator of several signals, regulating metabolism, cell growth and proliferation. In particular, mTOR plays an important role in the maintenance and differentiation of SSCs, as well as in regulating the redox balance and metabolic activity of Sertoli cells, which play an important role in nutritional support during spermatogenesis.

7.
Ultrasound Med Biol ; 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33328131

RESUMO

Thyroid carcinoma is one of the most common endocrine diseases globally, and the incidence has been on the rise in recent years. Ultrasound imaging is the primary clinical method for early thyroid nodule diagnosis. Regions of interest (ROIs) of nodules in ultrasound images are difficult to detect because of their irregular shape nand vague margins. Accurate real-time thyroid nodule detection can provide ROIs for subsequent nodule diagnosis automatically, avoid variabilities between the subjective interpretations and inter-observer effectively and alleviate the workloads of medical practitioners. The aim of this study was to present a reliable, real-time detection method based on the Faster R-CNN (region-based convolutional network) framework for accurate and fast detection of thyroid nodules in ultrasound images. Our study proposed a faster and more accurate thyroid nodule detection method based on the Faster R-CNN framework by adding three strategies: feature pyramid, spatial remapping and anchor-box redesign. Specifically, the network takes raw ultrasound images as inputs and generates boxes with positions and the possibilities that these boxes contain thyroid nodules. The proposed method could locate and detect target nodules accurately with a mean average precision of 92.79% with more than 9000 patient images. In addition, the detection rate has accelerated to >16 frames per second, four times faster than that of the initial network. Therefore, it can meet the requirements of clinical application. The performance of the fivefold cross-validation was also accurate and robust. The proposed automatic thyroid nodule detection method yields better performance in accuracy and detection speed, which indicates the potential value of our method in assisting clinical ultrasound image interpretation.

8.
J Nat Prod ; 83(11): 3372-3380, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33180497

RESUMO

The effects of l-tryptophan supplementation on secondary metabolite production in the marine-derived fungus Fusarium sp. L1 were investigated by culturing the fungus in GPY medium with and without the amino acid. HPLC analysis of the products showed distinct metabolite profiles between the two cultures. The 1H NMR spectrum of the EtOAc extract of the culture supplemented with l-tryptophan displayed a series of characteristic aromatic proton signals (δH 6.50-8.50) and NH signals (δH 10.50-11.50) that were not observed in those from cultures not supplemented with l-tryptophan. Subsequently, 23 distinct indole alkaloids, including six new compounds, fusaindoterpenes A and B (1 and 2), fusariumindoles A-C (3-5), and (±)-isoalternatine A (6), together with 17 known compounds, were obtained from this culture. Fusaindoterpene A (1) contains a 6/9/6/6/5 heterocyclic system. Their chemical structures were determined by analysis of HRMS, NMR spectroscopy, optical rotation calculation, ECD calculation, and single-crystal X-ray diffraction data. Compounds 2, 9, and 15 displayed inhibitory activity against the Zika virus (ZIKV) in a standard plaque assay with EC50 values of 7.5, 4.2, and 5.0 µM, respectively, while not showing significant cell cytotoxicity against the A549 adenocarcinomic human alveolar basal epithelial cell line.

9.
J Diabetes Complications ; : 107766, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33168395

RESUMO

INTRODUCTION: The epithelial tight junctions of intestine were impaired in murine model of type 2 diabetes mellitus (T2DM). The aim of this work was to investigate the alteration of intestinal barrier in T2DM patients. METHODS: 90 patients with T2DM and 28 healthy controls were recruited. Serum lipopolysaccharide (LPS), Zonulin, and intestinal fatty acid binding protein (IFABP) were measured by ELISA, based on which a derived permeability risk score (PRS) was calculated. Subgroup analyses were conducted based on the glycemic control (HbA1c < 7%, or HbA1c ≥ 7%), the amount of chronic diabetic complications, and the use of aspirin at the time. RESULTS: Serum LPS, Zonulin, and IFABP, and PRS of T2DM group were significantly higher than those of the control group (p < 0.05 for all). Serum LPS and PRS was higher in T2DM patients with poor glycemic control (both p < 0.05). Patients with more chronic complications of diabetes had higher serum LPS and IFABP, and PRS (all p < 0.05). No differences were found in these serum markers between T2DM patients being treated with aspirin or not. CONCLUSIONS: Intestinal barrier function was impaired in T2DM patients. Poor glycemic control and more chronic complications of diabetes were associated with worse intestinal barrier function. Treatment with aspirin did not aggravate the impairment of intestinal barrier in T2DM patients.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33241876

RESUMO

Single-cell and in situ cell-based operation with nanopipette approach offers a possibility to elucidate the intracellular processes and may aid the improvement of therapy efficiency and precision. We present here a photo-responsive hydrogel-nanopipette hybrid system that can achieve single-cell operation with high spatial/temporal resolution and negligible cell-damage. This strategy overcomes long-time obstacles in nanopipette single-cell studies as high electric potential (~1000 mV) or organic solvent is always used during operations, which would inevitably impose disturbance and damage to targeted cells. The light-triggered system promotes a potential-free, non-invasive single-cell injection, resulting in a well-retained cell viability (90% survival rate). Moreover, the photo-driven injection enables a precisely dose-controllable single-cell drug delivery. As a proof-of-concept, significantly reduced lethal doses of doxorubicin (163-217 fg/cell) are demonstrated in corresponding cell lines, indicating a potential precision cell therapy strategy based on the photo-responsive hydrogel-nanopipette system.

11.
Ear Nose Throat J ; : 145561320976405, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236644

RESUMO

Sigmoid sinus thrombophlebitis is a severe and potentially fatal intracranial complication of acute otitis media and middle ear cholesteatoma. Early administration of broad-spectrum antibiotics and immediate radical mastoidectomy are the recommended standard treatments; however anticoagulant therapy is always an option worthy of clinical consideration. Here, we report a case of middle ear cholesteatoma complicated with sigmoid sinus thrombophlebitis in a patient who received anticoagulant therapy for 1 year before the operation because of the coronavirus disease 2019 pandemic.

12.
Front Pharmacol ; 11: 580073, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224034

RESUMO

A lismatis Rhizoma (zexie), an herb used in traditional Chinese medicine, exhibits hypolipemic, anti-inflammation and anti-atherosclerotic activities. Alisol A is one of the main active ingredients in Alismatis Rhizoma extract. In this study, we investigate the role of alisol A in anti-atherosclerosis (AS). Our study demonstrated that alisol A can effectively inhibit the formation of arterial plaques and blocked the progression of AS in ApoE-/- mice fed with high-fat diet and significantly reduced the expression of inflammatory cytokins in aorta, including ICAM-1, IL-6, and MMP-9. In addition, we found that alisol A increased the expression of PPARα and PPARδ proteins in HepG2 cells and in liver tissue from ApoE-/- mice. Alisol A activated the AMPK/SIRT1 signaling pathway and NF-κB inhibitor IκBα in HepG2 cells. Our results suggested that alisol A is a multi-targeted agent that exerts anti-atherosclerotic action by regulating lipid metabolism and inhibiting inflammatory cytokine production. Therefore, alisol could be a promising lead compound to develop drugs for the treatment of AS.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33224259

RESUMO

Rosanortriterpenes A-B (RTA and RTB), two nortriterpenoids, are characteristic constituents in the fruits of Rosa laevigata var. leiocapus. However, pharmacological studies on these compounds are still scarce. In the present study, we aim to investigate the anti-inflammatory mechanisms associated with the effects of RTA-B in RAW264.7 macrophages and LO2 cells by detecting cell viabilities, nitric oxide (NO) production, tumour necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) production. Simultaneously, the anti-inflammatory action mechanisms of these two compounds were illustrated through western blot assay. Besides, the antihepatic fibrosis activities of these compounds have also been explored. The results demonstrated that RTA and RTB inhibited the production of NO, TNF-α, and IL-6 and suppressed liver fibrosis. RTA and RTB treatment also greatly inhibited the activation of NF-kappaB (NF-κB) pathway. Our study confirmed the promising anti-inflammatory and anti-liver fibrosis actions of RTA-B, suggesting that they might be developed as alternative and promising drugs for the treatment of hepatic inflammatory and fibrotic diseases.

14.
Int J Biol Sci ; 16(16): 3221-3230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162827

RESUMO

Growth factor receptor-bound protein 7 (GRB7) has been found closely related to the occurrence and development of various tumors, but its function in bladder cancer has not yet been elucidated. The study is aiming at investigating the expression and function of GRB7 in bladder cancer. The Cancer Genome Atlas (TCGA) database was selected to analyze mRNA levels of GRB7 in bladder cancer. RT-qPCR and Western blot were conducted to detect the expression of GRB7 in normal bladder epithelial cells, seven bladder cancer cell lines and eight pairs of malignant/nonmalignant bladder tissues. The role of GRB7 in tumor proliferation and tumorigenesis was explored by establishing stable cells, in vitro cell experiments and in vivo xenograft models. The molecular regulation mechanism of GRB7 in bladder cancer was investigated by treatment with AKT inhibitor. GRB7 mRNA was upregulated in bladder cancer samples compared with that in normal tissue samples. Overexpressing GRB7 significantly promoted the proliferation and tumorigenesis of bladder cancer. However, silencing GRB7 played the retarding part. GRB7 promoted G1/S transition by activating the AKT pathway. Our results indicate that GRB7 plays an important role in promoting proliferation and tumorigenesis of bladder cancer.

15.
Materials (Basel) ; 13(22)2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182692

RESUMO

The asphalt mastic-aggregate interface plays an essential role in determining the service performance of asphalt mixtures. The objective of this paper was to investigate the adhesion behaviors and mechanism between asphalt mastic and aggregate based on molecular dynamic (MD) simulations. First, the asphalt mastic model considering the actual mass ratio of filler to asphalt (F/A) condition was established and validated in terms of thermodynamic properties. Second, the molecular arrangement characteristics of polar components on the aggregate substrate were analyzed by radial distribution function (RDF), relative concentration (RC), and mean square displacement (MSD). Third, the interfacial adhesion ability between asphalt and aggregate was quantitively evaluated based on the work of adhesion. Finally, the coupling effect of moisture and temperature on interfacial adhesion behaviors was investigated to explore the adhesion failure characteristics of the asphalt-aggregate interface. The results demonstrate that the thermodynamic properties could be employed to validate the reliability of the asphalt mastic model. The self-aggregation degree of polar components in base asphalt could be significantly increased with the addition of silica particles, exhibiting a change of configuration from "parallel arrangement" into "stack distribution" due to the high polarity of silica particles. The polar components in asphalt mastic exhibit a more uniform distribution state and lower mobility capability than base asphalt owing to the adsorption effect of silica particles. Silica particles with amounts of residual charges could significantly increase the electrostatic energy of the asphalt mastic-aggregate interface, contributing to an improvement of the adhesion between asphalt mastic and aggregate. The increase of temperature enhances the work of adhesion of the asphalt mastic-aggregate interface, which is opposite to that of the base asphalt-aggregate interface. The asphalt mastic exhibits a greater sensitivity to interfacial moisture damage than base asphalt. The findings would provide insights into a better understanding on the micro adhesion mechanism of the asphalt mastic-aggregate interface.

16.
Complement Ther Med ; 54: 102579, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33183675

RESUMO

OBJECTIVE: Although many studies have attempted to unravel the relationship between vitamin D deficiency and the incidence of VTE, the results remained inconsistent. To address this discrepancy, we performed a systematic review and meta-analysis to precisely disentangle the relationship between serum vitamin D levels and VTE risk. METHODS: The Web of Science, Scopus, PubMed/Medline, Embase, and Google Scholar databases were searched for all available observational studies that reported the risk of venous thromboembolism (VTE) based on serum vitamin D levels categories. The search was performed up to March 2020. RESULTS: Seven studies were included. The overall analysis showed a significantly increased risk of VTE in subjects with low levels of serum vitamin D compared with those with normal vitamin D levels (RR = 1.34; 95% CI: 1.07-1.69; P = 0.011). In a sensitivity analysis, we did not observe a significant effect of any individual study on the combined effect sizes. Nevertheless, significant heterogeneity was present among the studies (Cochrane Q test, p = 0.018, I2 = 61%). In the stratified analysis, low vitamin D levels were positively associated with an increased risk of VTE in prospective population-based studies (RR = 1.31; 95% CI: 1.06-1.61; P = 0.010) and in subjects below 60 years old (RR = 1.28; 95% CI: 1.07-1.54; P = 0.060). CONCLUSION: our systematic review and meta-analysis showed that a low serum vitamin D level was indeed associated with an increased risk of VTE.

17.
Sci Total Environ ; : 143377, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33198994

RESUMO

The production of fluorescent dissolved organic matter (FDOM) by phytoplankton and its subsequent degradation, both of which occur constantly under diurnal-day time sunlight and by night time dark-microbial respiration processes in the upper layer of surface waters, influence markedly several biogeochemical processes and functions in aquatic environments and can be feasibly related to global warming (GW). In this work sunlight-mediated high-temperature was shown to accelerate the production of FDOM, but also its complete disappearance over a 24-h diurnal period in July at the highest air and water temperatures (respectively, 41.1 and 33.5 °C), differently from lower temperature months. Extracellular polymeric substances (EPS), an early-state DOM, were produced by phytoplankton in July in the early morning (6:00-9:00), then they were degraded into four FDOM components over midday (10:00-15:00), which was followed by simultaneous production and almost complete degradation of FDOM with reformation of EPS during the night (2:00-6:00). Such transformations occurred simultaneously with the fluctuating production of nutrients, dissolved organic carbon (DOC), dissolved organic nitrogen (DON) and the two isotopes (δ15N and δ18O) of NO3-. It was estimated that complete degradation of FDOM in July was associated with mineralization of approximately 15% of the initial DOC, which showed a nighttime minimum (00:00) in comparison to a maximum at 13:00. FDOM identified by excitation-emission matrix spectroscopy combined with parallel factor analysis consisted of EPS, autochthonous humic-like substances (AHLS) of C- and M-types, a combined form of C- and M-types of AHLS, protein-like substances (PLS), newly-released PLS, tryptophan-like substances, tyrosine-like substances (TYLS), a combined form of TYLS and phenylalanine-like substances (PALS), and their degradation products. Finally, stepwise degradation and production processes are synthesized in a pathway for FDOM components production and their subsequent transformation under different diurnal temperature conditions, which provided a broader paradigm for future impacts on GW-mediated DOM dynamics in lake water.

18.
Nat Prod Res ; : 1-7, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33131334

RESUMO

Two new compounds (1 and 2), belonging to C-20 oxygenated ent-kauranes-type diterpenoids, were identified from the aerial parts of Isodon serra. Their structures were elucidated by extensive analysis of HRESI-MS and NMR spectroscopic data. Both these two compounds possess a common 7,20-epoxy-ent-kauranes skeleton with a hydroxyl group rarely occurring at C-13. Compounds 1 and 2 were evaluated for their cytotoxic activity against Hela-60 and HepG2 as well as the antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli.

19.
Pain Res Manag ; 2020: 7104392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014214

RESUMO

Background: Protein kinase C (PKC), nuclear factor-kappa B p65 (NF-κB p65), and P2X3 receptor (P2X3R) play significant roles in the sensitization and transduction of nociceptive signals, which are considered as potential targets for the treatment of neuropathic pain. However, the mechanisms and relationships among them have not been clearly clarified. Methods: 80 rats were randomized and divided into 10 groups (n = 8). Sciatic chronic constriction injury (CCI) rats were intrathecally administered with bisindolylmaleimide I (GF109203X), a PKC-selective antagonist once a day, or pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor twice a day. Sham-operated rats were intrathecally administered with saline. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were evaluated in all the groups before CCI operation (baseline) and on the 1st, 3rd, 7th, 10th, and 14th day after CCI operation. Protein levels of p-PKCα, p-NF-κB p65, and P2X3R were analyzed in the CCI ipsilateral L4-6 dorsal root ganglions (DRGs). Results: Intrathecal injection of GF109203X or PDTC alleviated the TWL and MWT in the following 2 weeks after CCI surgery. The protein levels of p-PKCα, p-NF-κB p65, and P2X3R in the ipsilateral DRGs significantly increased after CCI operation, which could be partly reversed by intrathecal administration of GF109203X or PDTC. Conclusion: The upregulation of p-PKCα, p-NF-κB p65, and P2X3R expression in the DRGs of CCI rats was involved in the occurrence and development of neuropathic pain. Phosphorylated PKCα and phosphorylated NF-κB p65 regulated with each other. Phosphorylated NF-κB p65 and PKCα have a mutual regulation relationship with P2X3R, respectively, while the specific regulatory mechanism needs further research.

20.
J Clin Biochem Nutr ; 67(2): 146-152, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33041511

RESUMO

Our study was to understand the autophagy induce by different ratios and concentrations of LA/DHA on Raw264.7 cell, and then to investigate the effect of Raw264.7 autophagy on the clearance of Staphylococcus aureus. Raw264.7 cells was treated by LA/DHA in different concentrations (50/100 µmol/L) and ratios (4:1, 6:1, 8:1, 1:4, 1:6 and 1:8) for 6/12/24 h, cell viability assay was assessed by Cell Counting Kit-8, LC3B, p62, P-mTOR, P-Akt, P-PI3K and BECN 1 were detected by the Western blot. LA/DHA could induce autophagy of Raw264.7 cells through the PI3K-Akt-mTOR signaling pathway, the strong effect on autophagy by the concentration is 100 µmol/L, the ratio is 6:1 of LA/DHA, and the treatment time is 24 h. Compared with the images in the control group obtained by merging red and green fluorescence channels, the treatment of LA, DHA in a ratio of 6:1 at a concentration of 100 µmol/L for 24 h significantly lead to a substantial number of autophagosomes (yellow) as well as autolysosomes (red), enhancing autophagy flux. Autophagy induce by LA/DHA can devour and damage intracellular and extracellular Staphylococcus aureus. These results indicate that LA/DHA cloud induce autophagy and enhance the phagocytosis and killing ability of macrophages to intracellular parasitic bacteria.

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