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1.
Water Res ; 168: 115211, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669780

RESUMO

It has been long desired but challenging to forward the advanced treatment of wastewater from empirical trials towards scientific design due to the lack of molecular insight into the pollutants of concern. Herein, we first established a systematic methodology to identify the ligands of Ni(II)-complexes in an electroless nickel (EN) plating effluent. The presence of N-containing groups in the ligands of most Ni(II)-complexes was verified by time-aligned ICP-MS and ESI-HRMS, implying the suitability of autocatalytic ozonation for efficient decomplexation. Thereby, a combined process was proposed on the basis of ozonation to achieve over 83% decomplexation of Ni(II) (initially at 0.36 mg/L), followed by selective Ni(II) sequestration for resource recovery. Combinational LC-MS systems revealed the ozonation-induced fragmentation or elimination of most Ni(II)-complexes as well as the structural change of the residual complexed molecules. The released free Ni(II) was further sequestrated by a nanocomposite of hydrated Zr(IV) oxide confined in a polymeric cation exchanger (nHZO@PCE). The fixed-bed working capacity of nHZO@PCE (∼550 BV) for the ozonated EN plating effluent was over 18 times that of the cation exchanger host (∼30 BV) at the breakthrough point of 0.10 mg Ni/L. More attractively, five adsorption-regeneration cycles demonstrated the great potential of the hybrid adsorbent for sustainable utilization. This study is believed to shed new light on how to design rational processes for advanced treatment of real wastewater based on molecular identification.


Assuntos
Nanocompostos , Poluentes Químicos da Água , Adsorção , Níquel , Águas Residuárias
2.
Curr Pharm Des ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31692429

RESUMO

Coronary artery disease is a complex disease caused by the combination of environmental factors and genetic factors. It is one of the leading causes of death and disability in the world. The research on CAD genetic mechanism has been paid close attention. In recent years, Genome-wide association study (GWAS) has developed rapidly around the world. Medical researchers around the world have successfully discovered a series of CAD genetic susceptibility genes or susceptible loci using medical research strategies, pushing CAD research to a New stage. This paper briefly summarizes the important progress made by GWAS for CAD in the world in recent years, and then analyzes the challenges faced by GWAS at this stage and the development trend of future research, so as to promote the transformation of genetic research results to clinical practice and provide guidance for further exploration of the genetic mechanism of CHD.

3.
Drug Chem Toxicol ; : 1-9, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31665930

RESUMO

Orlistat is an FDA-approved over-the-counter drug to treat obesity through the inhibition of lipase activity. Macrophages, which express high levels of lipoprotein lipase (LPL), are important phagocytes in the innate immune system. Our previous studies indicated that environmentally relevant concentrations of arsenite (As+3) could inhibit the major immune functions of macrophages. As the down-regulation of LPL is known to increase the expression of ABCA1, the cholesterol exporter demonstrated to be related to the resistance of arsenic toxicity. We examined if orlistat could reverse the inhibitive effects of As+3 on macrophage functions. The results showed that 50 µM orlistat reversed As+3-induced suppressions on phagocytosis, NO production and cytokine secretion in THP-1 derived macrophages. The expression of ABCA1 was significantly increased by orlistat in As+3 co-treated macrophages, which was associated with decreased intracellular As+3 levels. Collectively, these results indicated that orlistat could reverse the suppressive effects induced by As+3 in macrophages through the increased expression of ABCA1, which has the potential to be developed as a therapeutic agent for arsenic-induced immunosuppression.

4.
Mol Ther Nucleic Acids ; 18: 627-637, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31689617

RESUMO

Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31671051

RESUMO

A Gram-strain positive, mycelium-forming actinomycete, YIM 121212T, was isolated from an alkaline soil sample collected in Yunnan province, PR China. Classification using a polyphasic approach indicated that YIM 121212T represents a member of the genus Prauserella, and is closely related to Prauserella coralliicola SCSIO 11529T (99.31 %), Prauserella endophytica SP28S-3T (99.17 %), Prauserella soli 12-833T (97.43 %), Prauserella oleivorans RIPIT (97.03 %), Prauserella marina MS498T (96.74 %), Prauserella rugosa DSM 43194T (96.54 %) and Prauserella muralis 05-Be-005T (95.92 %). Average nucleotide identity values (ANI) of YIM 121212T to P. coralliicola DSM 45821T and P. endophytica CGMCC 4.7182T were 93.1 and 92.8 %, respectively, which were lower than the threshold of 95 %. The digital DNA-DNA hybridization (dDDH) values between YIM 121212T and these two species were 50.8 and 49.9 %, respectively and thus were also well below the cut off value (>70 %) for species delineation. The DNA G+C content of YIM 121212T is 70.8 mol%. Major fatty acids are iso-C16 : 0, iso-C16 : 1H, C16 : 1ω7c/iso-C15 : 0 2OH, C17 : 1ω6c, and C17 : 1ω8c. The predominant menaquinone is MK-9(H4). The polar lipid profile consists of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylmethylethanolamine (PME), phosphatidylinositol (PI), and phosphatidylinositol mannoside (PIM). The draft genomes were further analyzed for the presence of secondary metabolite biosynthesis (SMB) gene clusters. On the basis of the above observations, YIM121212T can be distinguished from closely related species belonging to the genus Prauserella. Thus, YIM121212T represents a novel species of the genus Prauserella, for which the name Prauserella flavalba sp. nov. is proposed. The type strain is YIM121212T (=CCTCC AA 2013011T=DSM 45973T).

6.
PLoS One ; 14(10): e0224597, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31648273

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0173755.].

7.
J Basic Microbiol ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31617947

RESUMO

Limited information is available on the performance of plant growth-promoting inoculants or bioproducts under different soil nutritional or fertility conditions. Consequently, the objective of this study was to evaluate the effects of a commercially available Bacillus-containing bioproduct, Microlife Abundance, at concentrations of 5.5 and 6.5 log cfu/ml on early growth, fertilizer use-efficiency, and fruit yield of bell pepper (Capsicum annuum L.) under two different soil fertility conditions (25% and 100% recommended N rates). Two pot experiments were conducted with bell pepper: (a) a 4-week-long early growth test with inoculant treatments applied once at transplanting; and (b) a 13-week-long yield test with inoculant treatments applied at transplanting and again at first blossom-set. Results from the early growth test indicated that at both N fertilization levels, applying Abundance once at transplanting at 6.5 log cfu/ml rather than 5.5 log cfu/ml significantly increased root dry weight, total root length, root volume, root surface area, and total length of very fine roots compared with the noninoculated control by 20%, 13%, 17%, 15%, and 12%, respectively. In contrast to the early growth, results from the yield test showed that only at the 100% recommended N rate, applying Abundance twice at both concentrations significantly enhanced N fertilizer use-efficiency and marketable yield of bell pepper over the noninoculated control by 34% (5.5 log cfu/ml) and 30% (6.5 log cfu/ml). Therefore, the efficacy of the Bacillus-containing bioproduct Abundance in enhancing fertilizer use-efficiency and marketable yield of bell pepper varied between soil nutritional conditions, but the early growth promotion effect of Abundance did not. Our results also demonstrate that selected microbial-based bioproducts, like Abundance, can be compatible with chemical fertilizers to enhance fertilizer use-efficiency and crop yields, but cannot be used as complete substitutes for chemical fertilizers.

8.
Invest Ophthalmol Vis Sci ; 60(13): 4346-4359, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626691

RESUMO

Purpose: Glaucoma is a neurodegenerative eye disease characterized by gradually impaired visual field and irreversible blindness due to retinal ganglion cell (RGC) loss. Our previous studies have confirmed that hydrogen sulfide (H2S) takes part in the glaucomatous process and contributes to RGC protection. The present study aimed to further investigate the role of extracellular signal-regulated kinase 1/2 (ERK 1/2) pathway underlying the impact of H2S, to better understand the mechanism through which H2S exerts neuroprotection in glaucoma. Methods: An established rat glaucoma model was used and 168 rats were qualified to undergo sodium hydrosulfide (NaHS, a H2S donor)/PD98059 (an ERK inhibitor) treatment. Then the survival and apoptosis of RGC were evaluated through retrograde labeling and TUNEL staining, along with activity evaluations of ERK 1/2 pathway, intrinsic apoptotic pathway, glial activation, nuclear factor kappa B (NF-κB) pathway, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, autophagy, and TNF-α production through immunohistochemistry, Western blotting, and ELISA. Results: The study demonstrated that NaHS suppressed ERK 1/2 pathway activity similarly to PD98059 in retinas of experimental glaucoma rats, while PD98059 also similarly suppressed glial activation, NF-κB pathway, NADPH oxidase, and TNF-α production. However, PD98059 did not affect RGC survival, apoptotic regulation, or autophagy as NaHS did. Conclusions: Our study indicated that inhibition of ERK 1/2 pathway might partly contribute to the neuroprotection by H2S in experimental glaucoma; however, it was insufficient to initiate the therapeutic effect on its own.

9.
Sensors (Basel) ; 19(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540299

RESUMO

In this paper, three-dimensional (3-D) multiple-input multiple-output (MIMO) radar accurate localization and imaging method with motion parameter estimation is proposed for targets with complex motions. To characterize the target accurately, a multi-dimensional signal model is established including the parameters on target 3-D position, translation velocity, and rotating angular velocity. For simplicity, the signal model is transformed into three-joint two-dimensional (2-D) parametric models by analyzing the motion characteristics. Then a gridless method based on atomic norm optimization is proposed to improve precision and simultaneously avoid basis mismatch in traditional compressive sensing (CS) techniques. Once the covariance matrix is obtained by solving the corresponding semi-definite program (SDP), estimating signal parameters via rotational invariance techniques (ESPRIT) can be used to estimate the positions, then motion parameters can be obtained by Least Square (LS) method, accordingly. Afterwards, pairing correction is carried out to remove registration errors by setting judgment conditions according to resolution performance analysis, to improve the accuracy. In this way, high-precision imaging can be realized without a spectral search process, and any slight changes of target posture can be detected accurately. Simulation results show that proposed method can realize accurate localization and imaging with motion parameter estimated efficiently.

10.
Theranostics ; 9(20): 5755-5768, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534517

RESUMO

Severe multidrug resistance (MDR) often develops in the process of chemotherapy for most small molecule anticancer drugs, which results in clinical chemotherapy failures. Methods: Here, a nanodrug is constructed through the self-assembly of amphiphilic drug-inhibitor conjugates (ADIC) containing a redox-responsive linkage for reversing the multidrug resistance (MDR) in cancer treatment. Specifically, hydrophilic anticancer irinotecan (Ir) and hydrophobic P-gp protein inhibitor quinine (Qu) are linked by a redox responsive bridge for overcoming MDR of tumors. Results: Ir-ss-Qu is able to self-assemble into nanoparticles (NPs) in water and shows the longer blood retention half-life compared with that of free Ir or Qu, which facilitates drug accumulation in tumor site. After endocytosis of Ir-ss-Qu NPs by drug-resistant tumor cells, the disulfide bond in the linkage between Ir and Qu is cleaved rapidly induced by glutathione (GSH) to release anticancer drug Ir and inhibitor Qu synchronously. The released Qu can markedly reduce the expression of P-gp in drug-resistant tumor cells and inhibits P-gp to pump Ir out of the cells. The increased concentration of intracellular Ir can effectively improve the therapeutic efficacy. Conclusions: Such redox-responsive Ir-ss-Qu NPs, as a drug delivery system, exhibit very high cytotoxicity and the most effective inhibitory to the growth of drug-resistant breast cancer compared with that of free therapeutic agents in vitro and in vivo.

11.
Tumori ; : 300891619871103, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478461

RESUMO

BACKGROUND: An integral and well-functioning vascular system is essential for tumor progression and chemotherapy infusion. However, the lumen integrity of the microvessels and its significance in prognosis has not been studied. In this study, we found that the proportion of collapsed microvessels is suggested to be a novel biomarker for predicting prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, immunohistochemical CD31 staining was performed to identify the microvessels in tumor specimens. Proportions of collapsed vessels were estimated in CD31-stained tumor specimens from 100 patients with NSCLC. The correlation between collapsed microvessel proportion and survival time were evaluated by univariate and multivariate analysis. RESULTS: Data from 99 patients were analyzed and a wide range of collapse-microvessel fraction was observed in 96 patients (1.4%-70%). Elevated collapse proportion (⩾6.5%) indicated poor overall survival in both univariate analysis (p = 0.042) and multivariate analysis (p = 0.014). CONCLUSIONS: Elevated proportion of collapsed microvessels indicted poor survival outcome in patients with NSCLC.

12.
Forensic Sci Int ; 302: 109922, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31442682

RESUMO

Diatom examinations have been widely used to perform drowning diagnosis in forensic practice. However, current methods for recognizing diatoms, which use light or electron microscopy, are time-consuming and laborious and often result in false positive or negative decisions. In this study, we demonstrated an artificial intelligence (AI)-based system to automatically identify diatoms in conjunction with a classical chemical digestion approach. By employing transfer learning and data augmentation methods, we trained convolutional neural network (CNN) models on thousands or tens of thousands of tiles from digital whole-slide images of diatom smears. The results showed that the trained model identified the regions containing diatoms in the tiles. In an independent test, where the slide samples were collected in forensic casework, the best CNN model demonstrated a performance competitive with those of 5 forensic pathologists with experience in diatom quantification. This pilot study paves the way for future intelligent diatom examinations; many efficient diatom extraction methods could be incorporated into our automated system.

13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 36(4): 541-547, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31441253

RESUMO

Stereo-electroencephalography (SEEG) is widely used to record the electrical activity of patients' brain in clinical. The SEEG-based epileptogenic network can better describe the origin and the spreading of seizures, which makes it an important measure to localize epileptogenic zone (EZ). SEEG data from six patients with refractory epilepsy are used in this study. Five of them are with temporal lobe epilepsy, and the other is with extratemporal lobe epilepsy. The node outflow (out-degree) and inflow (in-degree) of information are calculated in each node of epileptic network, and the overlay between selected nodes and resected nodes is analyzed. In this study, SEEG data is transformed to bipolar montage, and then the epileptic network is established by using independent effective coherence (iCoh) method. The SEEG segments at onset, middle and termination of seizures in Delta, Theta, Alpha, Beta, and Gamma rhythms are used respectively. Finally, the K-means clustering algorithm is applied on the node values of out-degree and in-degree respectively. The nodes in the cluster with high value are compared with the resected regions. The final results show that the accuracy of selected nodes in resected region in the Delta, Alpha and Beta rhythm are 0.90, 0.88 and 0.89 based on out-degree values in temporal lobe epilepsy patients respectively, while the in-degree values cannot differentiate them. In contrast, the out-degree values are higher outside the temporal lobe in the patient with extratemporal lobe epilepsy. Based on the out-degree feature in low-frequency epileptic network, this study provides a potential quantitative measure for identifying patients with temporal lobe epilepsy in clinical.


Assuntos
Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico , Ondas Encefálicas , Humanos
14.
Infect Dis Poverty ; 8(1): 70, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409377

RESUMO

BACKGROUND: Most species of Triatominae live exclusively in Latin America. However, one species, Triatoma rubrofasciata, has been recorded in the Americas as well as in various port areas in Africa and Asia. An increasing number of T. rubrofasciata have been reported in southern China in recent years. However, the origin of this invasive insect vector in China remains unknown, therefore, accurate identification and phylogenetic analysis of the bugs are urgently needed. METHODS: A total of seven triatomine insect specimens were found and collected from Maoming City, Guangdong Province, China (GDMM) and Zhangzhou City, Fujian Province, China (FJZZ), respectively. The obtained insect vector specimens were observed under a dissecting microscope for morphological classification and then the genomic DNA was extracted, and the 16S ribosomal RNA (rRNA), 28S rRNA as well as cytochrome oxidase subunit I (COI) genes of the species were amplified and sequenced. Subsequently, molecular phylogenetic analyses based on multiple alignments of the above genes were conducted in order to identify the species and determine the phylogenetic origin approximation accurately. RESULTS: The triatomine insects collected from GDMM and FJZZ were identified as Triatoma rubrofasciata using morphological and genetic analyses. All of the Chinese T. rubrofasciata captured in FJZZ, GDMM and other localities in southern China, together with a Vietnamese and Brazilian strain, formed a new, cohesive clade. T. rubrofasciata in GDMM and FJZZ are likely derived from strains found in Vietnam or Brazil. CONCLUSIONS: To the best of our knowledge, this is the first record of the invasive insect T. rubrofasciata, which is likely derived from strains native to Vietnam or Brazil, in both Maoming City, Guangdong Province and Zhangzhou City, Fujian Province of China. A comparison of the DNA sequences of the 16 s rRNA, 28 s rRNA and COI genes confirmed the specific identification of T. rubrofasciata, and its potential origin in China is based on the phylogenetic analyses undertaken in this study. More targeted interventions and improved entomological surveillance are urgently needed to control the spread of this haematophagous insect in China.

15.
Circ Res ; 125(7): 707-719, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412728

RESUMO

RATIONALE: PGC1α (peroxisome proliferator-activated receptor gamma coactivator 1α) represents an attractive target interfering bioenergetics and mitochondrial homeostasis, yet multiple attempts have failed to upregulate PGC1α expression as a therapy, for instance, causing cardiomyopathy. OBJECTIVE: To determine whether a fine-tuning of PGC1α expression is essential for cardiac homeostasis in a context-dependent manner. METHODS AND RESULTS: Moderate cardiac-specific PGC1α overexpression through a ROSA26 locus knock-in strategy was utilized in WT (wild type) mice and in G3Terc-/- (third generation of telomerase deficient; hereafter as G3) mouse model, respectively. Ultrastructure, mitochondrial stress, echocardiographic, and a variety of biological approaches were applied to assess mitochondrial physiology and cardiac function. While WT mice showed a relatively consistent PGC1α expression from 3 to 12 months old, age-matched G3 mice exhibited declined PGC1α expression and compromised mitochondrial function. Cardiac-specific overexpression of PGC1α (PGC1αOE) promoted mitochondrial and cardiac function in 3-month-old WT mice but accelerated cardiac aging and significantly shortened life span in 12-month-old WT mice because of increased mitochondrial damage and reactive oxygen species insult. In contrast, cardiac-specific PGC1α knock in in G3 (G3 PGC1αOE) mice restored mitochondrial homeostasis and attenuated senescence-associated secretory phenotypes, thereby preserving cardiac performance with age and extending health span. Mechanistically, age-dependent defect in mitophagy is associated with accumulation of damaged mitochondria that leads to cardiac impairment and premature death in 12-month-old WT PGC1αOE mice. In the context of telomere dysfunction, PGC1α induction replenished energy supply through restoring the compromised mitochondrial biogenesis and thus is beneficial to old G3 heart. CONCLUSIONS: Fine-tuning the expression of PGC1α is crucial for the cardiac homeostasis because the balance between mitochondrial biogenesis and clearance is vital for regulating mitochondrial function and homeostasis. These results reinforce the importance of carefully evaluating the PGC1α-boosting strategies in a context-dependent manner to facilitate clinical translation of novel cardioprotective therapies.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31372922

RESUMO

Many attempts have been made to estimate the post-mortem interval (PMI) using bioanalytical methods based on multiple biological samples. Cartilage tissues could be used as an alternative for this purpose because their rate of degradation is slower than that of other soft tissue or biofluid samples. In this study, we applied Fourier transform infrared (FTIR) spectroscopy to acquire bioinformation from human annular cartilages within 30 days post-mortem. Principal component analysis (PCA) showed that sex and causes of death have almost no impact on the overall spectral variations caused by post-mortem changes. With pre-processing approaches, several predicted models were established using a conventional machine learning method, known as the partial least square (PLS) regression. The best model achieved a satisfactory prediction with a low error of 1.49 days using the second derivative transform of 3-point smoothing and extended multiplicative scatter correction (EMSC), and the spectral regions from proteins and carbohydrates contributed greatly to the PMI prediction. This study demonstrates the feasibility of cartilage-based FTIR analysis for PMI estimation. Further work will introduce advanced algorithms for more accurate and precise PMI prediction.

17.
J Forensic Leg Med ; 66: 167-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326692

RESUMO

OBJECTIVE: To determine the history of malpractice literature using forensic science based on a bibliometric and graph theory. METHODS: Documented data were retrieved from the Web of Science Core Collection of Clarivate Analytics on February 22, 2019. We selected articles for the years 1975-2018 from among documents concerning malpractice in the "Medicine, Legal" section and the Science Citation Index Expanded and the Social Sciences Citation Index. Descriptive statistics and co-occurrence analyses were performed using Microsoft Excel 2016, Gephi 0.9.2, and VOSviewer 1.6.10 software. RESULTS: In all, 379 papers and 3160 citing articles were retrieved. The most active publication year was 2013. Relative growth rate showed no malpractice explosion during the study period. Full articles comprised 83.11% of all papers. There were marked differences between the number of publications during the first 21 years and the last 23 years. More studies were published in the United States than in other countries and regions, but malpractice research has diminished during the most recent 3 years. Journal of Law, Medicine and Ethics contributed the most to the field, with 51 documents. The journal with the highest impact factor, however, was Forensic Science International: Genetics. B. Madea topped the list of authors with the highest number of documents. Three clusters were identified, led by authors C. Terranova, B. Madea, and T.A. Brennan, respectively. The malpractice topics that received the most attention were malpractice claims, the types of malpractice, and the causes of medical malpractice. Our study of the citing papers also provided interesting results. CONCLUSION: This bibliometric analysis indicated that studying the field of medical malpractice was poor during 1975-2018. United States was the most prolific country, and B. Madea published more documents in the field. The studies in Medicine, Legal mostly focused on the claims, appraisement methods, and causes of medical malpractice. In the future, forensic scientists should pay more attention to medical malpractice.


Assuntos
Bibliometria , Ciências Forenses , Imperícia , Editoração/estatística & dados numéricos , Humanos
18.
FASEB J ; 33(9): 9828-9841, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31291555

RESUMO

Identification of anti-osteoclastogenic agents is important for the treatment of bone loss diseases that feature excessive osteoclast (OC) activity and bone resorption. Tranylcypromine (TCP), an irreversible inhibitor of monoamine oxidase (MAO), has been used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders. TCP has been discovered to exert anabolic effect on osteoblasts, and MAO-A has also been verified as an important mediator in prostate cancer cells to accelerate osteoclastogenesis. In current study, we were focused on TCP and MAO-A effects on osteoclastogenesis. As illustrated by tartrate-resistant acid phosphatase staining, TCP was capable of inhibiting osteoclastogenesis induced by receptor activators of the NF-κB ligand (RANKL) in bone marrow-derived macrophage cells without any cytotoxicity. It was also shown to effectively suppress bone resorption of OCs. The subsequent study revealed that TCP inhibited osteoclastogenesis-related genes in a time-dependent manner through protein kinase B (AKT)-mediated mechanism followed by the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-c-fos pathway. And TCP could overcome the osteoclastogenic effects of AKT activator SC79. In addition, our results indicated that the expression and catalytic activity of MAO-A were up-regulated by RANKL stimulation and down-regulated by TCP in vitro and in vivo. Furthermore, the effects of MAO-A knockdown on OC differentiation indicated that MAO-A played an important role in osteoclastogenesis in vitro and might contribute to the inhibitory effects of TCP. And AKT, NFATc1, and c-fos were involved in the MAO-A pathway. Notably, our in vivo study reflected that TCPs were capable of restoring the bone loss in LPS-induced calvaria osteolysis and estrogen deficiency-induced osteoporosis models. Thus, our current work provided a potential option for the treatment of bone loss diseases and highlighted the important role of MAO-A in osteoclastogenesis as well.-Liu, Z., Yang, K., Yan, X., Wang, T., Jiang, T., Zhou, Q., Qi, J., Qian, N., Zhou, H., Chen, B., Huang, P., Guo, L., Zhang, X., Xu, X., Jiang, M., Deng, L. The effects of tranylcypromine on osteoclastogenesis in vitro and in vivo.

19.
Oncol Rep ; 42(3): 1017-1034, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322267

RESUMO

The current study aimed to identify the potential clinical significance and molecular mechanisms of kinesin (KIF) family member genes in lung adenocarcinoma (LUAD) using genome­wide RNA sequencing (RNA­seq) datasets derived from The Cancer Genome Atlas (TCGA) database. Clinical parameters and RNA­seq data of patients with LUAD from the TCGA database enabled the assessment of the clinical significance of KIF genes, while the potential mechanisms of their interactions in LUAD were investigated by gene set enrichment analysis (GSEA). A gene signature with potential prognostic value was constructed via a stepwise multivariable Cox analysis. In total, 23 KIF genes were identified to be differentially expressed genes (DEGs) between the LUAD tumor and adjacent non­cancerous tissues. Of these, 8 differentially expressed KIF genes were strongly found to be strongly associated with the overall survival of patients with LUAD. Three of these genes were found to be able to be grouped as a potential prognostic gene signature. Patients with higher risk scores calculated using this gene signature were found to have a markedly higher risk of mortality (adjusted P=0.003; adjusted HR, 1.576; 95% CI, 1.166­2.129). Time­dependent receiver operating characteristic analysis indicated that this prognostic signature was able to accurately predict patient prognosis with an area under curve of 0.636, 0.643,0.665, 0.670 and 0.593 for the 1­, 2­, 3­, 4­ and 5­year survival, respectively. This prognostic gene signature was identified as an independent risk factor for LUAD and was able to more accurately predict prognosis in comparison to other known clinical parameters, as shown via comprehensive survival analysis. GSEA enrichment revealed that that KIF14, KIF18B and KIF20A mediated basic cell physiology through the regulation of the cell cycle, DNA replication, and DNA repair biological processes and pathways. On the whole, the findings of this study identified 23 KIF genes that were DEGs between LUAD tumor and adjacent non­cancerous tissues. In total, 8 of these genes had the potential to function as prognostic and diagnostic biomarkers in patients with LUAD.

20.
Int J Biochem Cell Biol ; 114: 105570, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302227

RESUMO

Skin wound healing is a complex physiological process that maintains the integrity of the skin tissues, involving a variety of distinct cell types and signaling molecules. The specific signaling pathways or extracellular cues that govern the healing processes remain elusive. Microvesicles (MVs) have recently emerged as critical mediators of cell communication by delivery of genetic materials to target cells. In this study, we found the direct delivery of HEKa-MVs expressing miR-21 mimics significantly promoted the healing of skin wound in diabetic rats. In-depth studies showed that MV miR-21 promoted fibroblast migration, differentiation, and contraction, induced a pro-angiogenic process of endothelial cells and mediated a pro-inflammatory response. Mechanically, MV miR-21 might target specific essential effector mRNA in fibroblasts such as MMP-1, MMP-3, TIMP3, and TIMP4 to increase MMPs expression and enzymatic activities. Moreover, MV miR-21 regulated ɑ-SMA and N-cadherin to induce fibroblast-myofibroblast differentiation. MV miR-21 up-regulated the IL-6 and IL-8 expressions and their secretion to amplify the immune response. Furthermore, MV miR-21 down-regulated PTEN and RECK in protein level, and activate MAPK/ERK signaling cascade, thereby promoting fibroblast functions. Thus, our study has provided for the first time the basis for the potential application of HEKa-MVs, and MV miR-21 in particular for wound healing.

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