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1.
J Endod ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31623908

RESUMO

INTRODUCTION: Cyclophilin A (CypA) is a cytosolic protein involved in multiple biological functions, such as inflammation, tissue remodeling, tumorigenesis, and vascular diseases. Human periapical lesions are induced by bacterial infections. However, the expression of CypA in human periapical lesions remains unclear. This study aimed to investigate the presence of CypA in human periapical lesions and the possible association of CypA with angiogenesis, inflammatory cell infiltration, and alveolar bone degradation during inflammatory development. METHODS: Fifty-eight human periapical tissues, including periapical granulomas (PGs, n = 28), radicular cysts (RCs, n = 24), and healthy control tissues (control group, n = 6) were collected. Samples were fixed and analyzed. CypA expression was detected and analyzed by immunohistochemistry in different cross sections. Double immunofluorescence was assessed to colocalize CypA with CD34, CypA with matrix metalloproteinase 9 (MMP-9), and CD147 with MMP-9. RESULTS: CypA was significantly overexpressed in the RC and PG groups compared with the control group (P < .05), but the difference between the RC and PG groups was insignificant (P > .05). CypA-positive cells were mainly lymphocytes, endothelial cells, epithelial cells, and plasma cells. The double-labeling analysis of CypA with CD34 suggested that CypA expression was associated with angiogenesis during periapical lesions. MMP-9 colocalized with both CypA and CD147 indicated that CypA may colocalize with CD147 and may be associated with the degradation of soft and hard tissues around human periapical lesions. CONCLUSIONS: CypA may be involved in the development of periapical lesions with an increase in inflammatory cell infiltration, angiogenesis acceleration, and alveolar bone degradation.

2.
Anesthesiology ; 131(5): 1125-1147, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567367

RESUMO

BACKGROUND: Cancer pain is a pervasive clinical symptom impairing life quality. Vascular endothelial growth factor A has been well studied in tumor angiogenesis and is recognized as a therapeutic target for anti-cancer treatment. This study tested the hypothesis that vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 contribute to bone cancer pain regulation associated with spinal central sensitization. METHODS: This study was performed on female rats using a metastatic breast cancer bone pain model. Nociceptive behaviors were evaluated by mechanical allodynia, thermal hyperalgesia, spontaneous pain, and CatWalk gait analysis. Expression levels were measured by real-time quantitative polymerase chain reaction, western blot, and immunofluorescence analysis. Excitatory synaptic transmission was detected by whole-cell patch-clamp recordings. The primary outcome was the effect of pharmacologic intervention of spinal vascular endothelial growth factor A/vascular endothelial growth factor receptor 2-signaling on bone cancer pain behaviors. RESULTS: The mRNA and protein expression of vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 were upregulated in tumor-bearing rats. Spinal blocking vascular endothelial growth factor A or vascular endothelial growth factor receptor 2 significantly attenuated tumor-induced mechanical allodynia (mean ± SD: vascular endothelial growth factor A, 7.6 ± 2.6 g vs. 5.3 ± 3.3 g; vascular endothelial growth factor receptor 2, 7.8 ± 3.0 g vs. 5.2 ± 3.4 g; n = 6; P < 0.0001) and thermal hyperalgesia (mean ± SD: vascular endothelial growth factor A, 9.0 ± 2.4 s vs. 7.4 ± 2.7 s; vascular endothelial growth factor receptor 2, 9.3 ± 2.5 s vs. 7.5 ± 3.1 s; n = 6; P < 0.0001), as well as spontaneous pain and abnormal gaits. Exogenous vascular endothelial growth factor A enhanced excitatory synaptic transmission in a vascular endothelial growth factor receptor 2-dependent manner, and spinal injection of exogenous vascular endothelial growth factor A was sufficient to cause pain hypersensitivity via vascular endothelial growth factor receptor 2-mediated activation of protein kinase C and Src family kinase in naïve rats. Moreover, spinal blocking vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 pathways suppressed protein kinase C-mediated N-methyl-D-aspartate receptor activation and Src family kinase-mediated proinflammatory cytokine production. CONCLUSIONS: Vascular endothelial growth factor A/vascular endothelial growth factor receptor 2 contributes to central sensitization and bone cancer pain via activation of neuronal protein kinase C and microglial Src family kinase pathways in the spinal cord.

3.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117662, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31654845

RESUMO

Exploring the protein-nanomaterials interactions is the topic of high relevance for the future applications of new nanomaterials in biological system. Herein, the binding mechanism of bovine serum albumin(BSA) and bovine hemoglobin(BHB) with two-dimensional black phosphorus nanosheets (BP NSs) was reported. Muti-spectral results showed that the combination of BP NPs with protein resulted in the fluorescence quenching of BSA and BHB and induced the extension of the protein peptide chain by van der Waals forces, hydrophobic forces, and electron-transfer forces. Both BSA and BHB retain their structure in α-helix form. The induced circular dichroism (ICD) spectral results showed that the presence of BP NPs partly destroyed the binding domain of BHB with bilirubin and altered the tertiary structure of BHB by BP NPs binding.

4.
Br J Pharmacol ; 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655022

RESUMO

Background And Purpose Growing evidence indicates targeting mitochondrial dynamics and biogenesis could accelerate recovery from renal ischemia-reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Transcription factor forkhead box O1 (FOXO1) is a key regulator of mitochondrial homeostasis and plays a pathologic role in the progression of renal disease. Experimental Approach A mouse model of renal I/R injury and a hypoxia/reoxygenation (H/R) injury model for human renal tubular epithelial cells (HK2s) were used. Key Results I/R injury up-regulated renal expression of FOXO1, and treatment with FOXO1-selective inhibitor AS1842856 prior to I/R injury decreased serum urea nitrogen, serum creatinine and the tubular damage score after injury. Post-I/R injury AS1842856 treatment could also ameliorate renal function and improve the survival rate of mice following injury. AS1842856 administration reduced mitochondrial mediated apoptosis, suppressed the overproduction of mitochondrial reactive oxygen species (mtROS) and accelerated recovery of ATP both in vivo and in vitro. Additionally, FOXO1 inhibition improved mitochondrial biogenesis and suppressed mitophagy. Expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, was down-regulated in both I/R and H/R injury, which could be abrogated by FOXO1 inhibition. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that FOXO1 inhibited PGC-1α transcription by competing with CREB for its binding to transcriptional coactivators CREBBP/EP300 (CBP/P300). Conclusion And Implications These findings suggested that FOXO1 was critical to maintain mitochondrial function in renal tubular epithelial cells and FOXO1 may serve as a therapeutic target for pharmacologic intervention in renal.

5.
Chem Commun (Camb) ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31650997

RESUMO

We fabricated a robust porous copper oxide nanobelt coating on copper foam by a facile oxidation-dehydration reaction, which is firstly reported as a low-cost pure copper-based urea oxidization catalyst. This catalyst has enriched electrochemically active surface area, abudant nanopores and micropores for gas and electrolyte diffusion, and high conductivity from copper foam for electron transfer and herein shows superior UOR performance, outperforming noble metal catalysts or most of the as-reported nonprecious metal UOR catalysts especially at high current density.

6.
J Pain ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494272

RESUMO

Orofacial pain is characterized by its easy spread to adjacent areas, thus presenting with primary hyperalgesia (hypersensitivity at the site of injury) and secondary hyperalgesia (extraterritorial hypersensitivity outside the injured zone). However, the mechanisms behind the secondary hyperalgesia are poorly understood. In the present study, we used a mouse model of partial transection of the infraorbital nerve (pT-ION) to study whether calcium channel subunit α2δ1 (Cavα2δ1) and its downstream signaling contributes to the development of secondary hyperalgesia in the orofacial area. pT-ION caused primary (V2 skin) and secondary (V3 skin) hyperalgesia, which was reversed by the Cavα2δ1 antagonist gabapentin and by the expression of Cavα2δ1-targeting interfering RNA in trigeminal ganglion (TG)-V3 neurons. pT-ION induced increased expression of PKC and TRPA1, which was reversed by Cavα2δ1-targeting interfering RNA, and PKC inhibition reversed the upregulation of TRPA1 and gap junction (GJ) proteins induced by pT-ION. Cavα2δ1 overexpression in TG-V2 neurons induced the upregulation of PKC, TRPA1, and the GJ proteins in the TG and trigeminal subnucleus caudalis and induced hypersensitivity in the V3 skin area, which was reversed by TRPA1, GJ, or PKC blockade. Thus, we conclude that Cavα2δ1 contributes to the development of secondary hyperalgesia through its downstream PKC-TRPA1/GJ signaling pathways. PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia. This suggests that inhibitors of Cavα2δ1, TRPA1, or GJs might be effective treatments for nerve injury-induced spreading of orofacial pain.

7.
J Neurosci ; 39(44): 8705-8716, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31548235

RESUMO

The characteristics of a network are determined by parameters that describe the intrinsic properties of the component neurons and their synapses. Degeneracy occurs when more than one set of parameters produces the same (or very similar) output. It is not clear whether network degeneracy impacts network function or is simply a reflection of the fact that, although it is important for a network to be able to generate a particular output, it is not important how this is achieved. We address this issue in the feeding network of the mollusc Aplysia In this system, there are two stimulation paradigms that generate egestive motor programs: repetition priming and positive biasing. We demonstrate that circuit parameters differ in the 2 cases (e.g., egestive repetition priming requires activity in an interneuron, B20, which is not essential for positive biasing). We show that degeneracy has consequences for task switching. If egestive repetition priming is immediately followed by stimulation of an ingestive input to the feeding central pattern generator, the first few cycles of activity are egestive (not ingestive). In this situation, there is a task switch cost. This "cost" is in part due to the potentiating effect of egestive repetition priming on B20. In contrast, there is no switch cost after positive biasing. Stimulation of the ingestive central pattern generator input immediately triggers ingestive activity. Our results indicate that the mechanisms used to pattern activity can impact network function in that they can determine how readily a network can switch from one configuration to another.SIGNIFICANCE STATEMENT A particular pattern of neural activity can be generated by more than one set of circuit parameters. How or whether this impacts network function is unclear. We address this issue in the feeding network of Aplysia and demonstrate that degeneracy in network function can have consequences for task switching. Namely, we show that, when egestive activity is generated via one set of circuit modifications, an immediate switch to ingestive activity is not possible. In contrast, rapid transitions to ingestive activity are possible if egestive activity is generated via a different set of circuit modifications.

8.
Genomics Proteomics Bioinformatics ; 17(3): 229-247, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31494266

RESUMO

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

9.
ACS Appl Mater Interfaces ; 11(39): 35738-35745, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31464414

RESUMO

Graphdiyne (GDY), a new type of carbon material with an electron-rich conjugated structure, has been investigated as a separator coating layer to enhance the electrochemical performance of lithium-sulfur (Li-S) battery. Acetylenic bond (-C≡C-C≡C-) and benzene ring in the GDY coating layer are experimentally verified to reversibly attract the soluble lithium polysulfides by chemical adsorption during cycling. Meanwhile, the shuttle effect of soluble polysulfides is further physically restricted by the GDY coating layer due to the evenly distributed pores (5.42 Å) and a consistent interlayer spacing (3.65 Å) of GDY. Moreover, GDY is a conducting carbon skeleton with high Li+ mobility that can improve the rate performance. Hence, Li-S battery with an as-prepared GDY coating layer shows excellent electrochemical performances including superior specific capacity, excellent rate performance, and low capacity attenuation rate. The high initial discharge capacity of 1648.5 mA h g-1 at 0.1C and 819.5 mA h g-1 even at a high rate of 2C is achieved by this novel separator. The initial capacity of 1112.9 mA h g-1 at 0.5C is retained to 816.7 mA h g-1 after 200 cycles with a low attenuation rate of 0.13% per cycle. Compared with other coated separators, these results show that the GDY coating layer endows the separator with superior electrochemical performances for Li-S battery.

10.
Int J Nanomedicine ; 14: 5017-5032, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371944

RESUMO

Background: Epigallocatechin gallate (EGCG), the major anti-inflammatory compound in green tea, has been shown to suppress osteoclast (OC) differentiation. However, the low aqueous solubility of EGCG always leads to poor bioavailability, adverse effects, and several drawbacks for clinical applications. Purpose: In this study, we synthesized EGCG-capped gold nanoparticles (EGCG-GNPs) to solve the drawbacks for clinical uses of EGCG in bone destruction disorders by direct reduction of HAuCl4 in EGCG aqueous solution. Methods and Results: The obtained EGCG-GNPs were negatively charged and spherical. Theoretical calculation results suggested that EGCG was released from GNPs in an acidic environment. Cellular uptake study showed an obviously large amount of intracellular EGCG-GNPs without cytotoxicity. EGCG-GNPs exhibited better effects in reducing intracellular reactive oxygen species levels than free EGCG. A more dramatic anti-osteoclastogenic effect induced by EGCG-GNPs than free EGCG was observed in lipopolysaccharide (LPS)-stimulated bone marrow macrophages, including decreased formation of TRAP-positive multinuclear cells and actin rings. Meanwhile, EGCG-GNPs not only suppressed the mRNA expression of genetic markers of OC differentiation but also inhibited MAPK signaling pathways. Furthermore, we confirmed that EGCG-GNPs greatly reversed bone resorption in the LPS-induced calvarial bone erosion model in vivo, which was more effective than applying free EGCG, specifically in inhibiting the number of OCs, improving bone density, and preventing bone loss. Conclusion: EGCG-GNPs showed better anti-osteoclastogenic effect than free EGCG in vitro and in vivo, indicating their potential in anti-bone resorption treatment strategy.


Assuntos
Catequina/análogos & derivados , Ouro/farmacologia , Nanopartículas Metálicas/química , Osteogênese/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Reabsorção Óssea/patologia , Catequina/farmacologia , Morte Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Ligantes , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Nanopartículas Metálicas/ultraestrutura , Camundongos Endogâmicos BALB C , Modelos Biológicos , Ligante RANK/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Crânio/patologia , Transcrição Genética/efeitos dos fármacos
11.
Int Immunol ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412363

RESUMO

B cell novel protein 1 (BCNP1) has recently been identified as a new B cell receptor (BCR) signaling molecule but its physiological function remains unknown. Here we demonstrate that mice deficient in BCNP1 exhibit impaired B cell maturation and a reduction of B-1a cells. BCNP1-deficient spleen B cells show enhanced survival, proliferation and Ca2+ influx in response to BCR crosslinking as compared with WT spleen B cells. Consistently, mutant B cells show elevated phosphorylation of SYK, B cell linker protein (BLNK) and PLCγ2 upon BCR crosslinking. In vivo, BCNP1-deficient mice exhibit enhanced humoral immune responses to T-independent and -dependent antigens. Moreover, aged mutant mice contain elevated levels of serum IgM and IgG3 antibodies and exhibit polyclonal and monoclonal B cell expansion in lymphoid organs. These results reveal distinct roles for BCNP1 in B cell development, activation and homeostasis.

12.
Urol Oncol ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31466813

RESUMO

OBJECTIVE: Docetaxel has been shown to be an effective chemotherapy agent when combined with androgen deprivation therapy for hormone sensitive metastatic prostate cancer (CaP). Since very high risk CaP has a high rate of occult metastatic disease and early recurrence, we hypothesize that patients with very high risk locally advanced CaP may benefit from docetaxel-based neoadjuvant chemohormonal therapy (NCHT). Thus, we conducted a retrospective study to identify the outcome of these patients treated with NCHT followed by radical prostatectomy (RP). PATIENTS AND METHODS: We retrospectively analyzed data from 177 consecutive patients who had very high risk locally advanced CaP between March 2014 and July 2017. Patients received 3 different therapies: (i) 60 men in NCHT group, (ii) 73 men in neoadjuvant hormonal therapy (NHT) group, and (iii) 44 men received immediate RP without neoadjuvant therapy (No-NT group). Surgical outcomes were analyzed and survival differences were compared by the Kaplan-Meier method. RESULTS: The NCHT group had statistically significant higher preoperative Prostate-Specific Antigen (PSA) (P < 0.002), higher Gleason score (P < 0.002), and more advanced clinical stage (P < 0.001) than other groups. After RP, 81% (42/52) of patients in NCHT group, 73% (51/70) of patients in NHT group, and 48% (21/44) of patients in No-NT group achieved an undetectable PSA (P < 0.001). A total of 14% (6/42) patients achieving a postoperative undetectable PSA experienced biochemical recurrence in the NCHT group, with median biochemical progression-free survival (bPFS) time of 19 months; 47% (24/51) experienced biochemical recurrence in the NHT group, with median bPFS time of 13 months; 81% (17/21) experienced biochemical recurrence in the No-NT group, with median bPFS time of 9 months (P < 0.001). The median follow-up time of 3 groups was 12.5 months in the NCHT group, 18.3 months in the NHT group, and 22.8 months in the No-NT group (P = 0.01). CONCLUSION: Despite having poorer prognostic factors, the NCHT group had better bPFS time after surgery compared to NHT and No-NT groups. Randomized controlled investigations are needed to validate these results and further follow-up is required for survival endpoints.

13.
Int J Biol Macromol ; 139: 521-530, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377297

RESUMO

Chitosan-1-(mercaptomethyl)-cyclopropane acetic acid (CS-MCA) copolymer was synthesized by amino linkage. The obtained copolymer was characterized by FTIR, 1H NMR, XRD, TGA and SEM. Porous and reticulate morphologies were found on the CS-MCA surface. The effects of pH on the rheological properties of CS-MCA were investigated. On the one hand, the apparent viscosity of CS-MCA indicated a shear-thinning behavior. The graft of MCA enhanced the moduli and the maximum elastic properties were observed at pH = 7.00. The addition of dithiothreitol reduced the viscosity and modulus of CS-MCA hydrogel, and the gelation time, temperature and frequency were obtained in dynamic oscillatory tests. The antibacterial effect of CS-MCA against E. coli was investigated for the inhibition zone and bacterial growth curve. These results showed that CS-MCA had better antibacterial ability than chitosan without modification. Therefore, the rheological behavior and functional activities can be applied for the hydrocolloid gels in food and pharmaceutical applications.

14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 734-736, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302924

RESUMO

OBJECTIVE: To explore the molecular basis for a blood donor with an ABO subtype. METHODS: The proband and his family members were subjected to serological analysis. Their genotypes were determined by real-time PCR and sequencing of the coding regions of ABO gene. RESULTS: The proband was determined as an ABw subtype. By sequencing analysis, the proband was typed as A102/BW03. Compared with ABO*B.01, the proband was found to harbor a 721C>T variant (ABO*BW.03 allele) in exon 7 of the ABO gene, which caused substitution of Arginine at position 241 by Tryptophan resulting in a ABW phenotype. The blood type of the proband's sister was similar to that of the proband. The maternal serological pattern was B type, and the result of sequencing suggested that the genotype fit with B101/Bw03. CONCLUSION: The 721C>T in the exon 7 of the ABO glycosyltransferase gene probably underlies the Bw03 phenotype. The ABO*Bw.03 variant of the proband and his sister were inherited from their mother.


Assuntos
Sistema do Grupo Sanguíneo ABO/genética , Substituição de Aminoácidos , Feminino , Genótipo , Humanos , Masculino , Linhagem , Sequenciamento Completo do Exoma
15.
J Vis Exp ; (148)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31259888

RESUMO

Methods based on homologous recombination to modify genes have significantly furthered biological research. Genetically engineered mouse models (GEMMs) are a rigorous method for studying mammalian development and disease. Our laboratory has developed several GEMMs of prostate cancer (PCa) that lack expression of one or multiple tumor suppressor genes using the site-specific Cre-loxP recombinase system and a prostate-specific promoter. In this article, we describe our method for necropsy of these PCa GEMMs, primarily focusing on dissection of mouse prostate tumors. New methods developed over the last decade have facilitated the culture of epithelial-derived cells to model organ systems in vitro in three dimensions. We also detail a 3D cell culture method to generate tumor organoids from mouse PCa GEMMs. Pre-clinical cancer research has been dominated by 2D cell culture and cell line-derived or patient-derived xenograft models. These methods lack tumor microenvironment, a limitation of using these techniques in pre-clinical studies. GEMMs are more physiologically-relevant for understanding tumorigenesis and cancer progression. Tumor organoid culture is an in vitro model system that recapitulates tumor architecture and cell lineage characteristics. In addition, 3D cell culture methods allow for growth of normal cells for comparison to tumor cell cultures, rarely possible using 2D cell culture techniques. In combination, use of GEMMs and 3D cell culture in pre-clinical studies has the potential to improve our understanding of cancer biology.

16.
BMC Cancer ; 19(1): 676, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288785

RESUMO

BACKGROUND: Chronic lymphocytic leukemia is a malignancy with good prognosis. However, the incidence of secondary tumors increases every year after the diagnosis of chronic lymphotcytic leukemia. One of the induced secondary tumors is prostate cancer. For high-risk prostate cancer in particular, the standard therapy is radical prostatectomy and extended lymphadenectomy, which carries high risks of lymphatic leakage and reduced quality of life. Currently, there has been no study reporting the necessity of extended lymphadenectomy for high-risk prostate cancer in patients with chronic lymphocytic leukemia. CASE PRESENTATION: We reported two cases with concomitant high-risk prostate cancer and chronic lymphocytic leukemia. The first patient was a 60-year-old male diagnosed with synchronous prostate cancer and chronic lymphocytic leukemia. The second patient was a 70-year-old male initially presented with chronic lymphocytic leukemia alone but was then diagnosed with high-risk prostate cancer nine years later. Both patients received neoadjuvant androgen deprivation therapy and robot-assisted radical prostatectomy. The first patient underwent extended lymphadenectomy and developed prolonged postoperative lymphatic cyst. Histology showed chronic lymphocytic leukemia infiltration in resected lymph nodes. Serum prostate-specific antigen levels at one and 13 months post-operation were both 0.01 ng/ml. The second patient received positron emission tomography/computed tomography before androgen deprivation therapy, which showed mild fluorodeoxyglucose-avidity in lymph nodes across the entire body. Lymph node biopsy showed only chronic lymphocytic leukemia. The patient experienced no postoperative complication. Serum prostate-specific antigen levels at one and nine months post-operation were both 0.02 ng/ml. CONCLUSIONS: Extended lymphadenectomy may not be necessary for patients with concomitant high-risk prostate cancer and chronic lymphocytic leukemia, but such patients must undergo thorough preoperative assessment and mindful postoperative follow-up. Positron emission tomography/computed tomography may be valuable in detecting nodal metastases. A lymph node biopsy is necessary for patients with an ambiguous positron emission tomography/computed tomography in the metastatic involvement of lymph node.

17.
Chem Commun (Camb) ; 55(59): 8587-8590, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31276130

RESUMO

A robust porous copper-cobalt-sulfur-oxygen nanowire coating (Cu-Co-S-O NWC) was fabricated for the first time on copper foam using a mild thiosulfate ion redox reaction-driven chemical bath synthesis (CBS) strategy. Cu-Co-S-O NWC has a large ECAS, enriched tunnels for gas and electrolyte diffusion and good electron transfer performance from the highly conductive copper foam substrate, and herein, shows improved overall OER activity, outperforming the precious IrO2 catalyst and almost all the as-reported Cu-based or Co-based catalysts, especially at high current density.

18.
Food Chem ; 297: 125035, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253330

RESUMO

In this study, an electrochemical system was established to detect the branched-chain amino acid aminotransferase (BCAT) activity in lactic acid bacteria (LAB). A nanocomposite of chitosan (CS) with multi-walled carbon nanotubes (MWCNTs) was synthesized, and the composite solution were uniformly spread over the glassy carbon electrode (GCE) surface by drop-casting to fabricate an electrochemical biosensor. The composite was characterized by scanning electron microscopy (SEM) and cyclic voltammetry (TEM). Results indicated that the MWCNTs-CS/GCE electrode exhibited higher stability and sensitivity, compared with the GCE electrode. The linear response for nicotinamide adenine dinucleotide (NADH) was 1.0-9.0 µM and the response limit was 0.12 µM. The system effectively and sensitively detected the BCAT activity by NADH concentration in the LAB culture, comparing with the optical method. The culture condition of LAB was optimized by using this system, evidencing that established method was available to detect the BCAT activity of LAB.


Assuntos
Proteínas de Bactérias/metabolismo , Técnicas Eletroquímicas/métodos , Lactobacillales/enzimologia , Transaminases/metabolismo , Técnicas Biossensoriais/métodos , Quitosana/química , Eletrodos , Proteínas Musculares/metabolismo , NAD/química , NAD/metabolismo , Nanotubos de Carbono/química
19.
Neuroscience ; 412: 16-28, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125603

RESUMO

The chronic neuropathic pain-associated psychiatric disorders have seriously disturbed the quality of patients' life, such as depression and anxiety. Neuroinflammation in the hippocampus plays an important role in the neuropathic pain-associated depressive and anxiety disorders, but the underlying mechanism has not been thoroughly elucidated to date. The Nod-like receptor protein (NLRP)-1 inflammasome, which controls the production of pro-inflammatory cytokines, was broadly involved in the neuroinflammation-related diseases. In the present study, we show that the NLRP1 inflammasome is significantly activated in the hippocampus of rats subjected to the chronic constriction injury (CCI)-induced neuropathic pain. Inhibiting the product of NLRP1 inflammasome not only attenuated the depression-like behaviors but also suppressed the production of mature IL-1ß in the hippocampus of CCI rats. The double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) has been recently shown to be a pivotal regulator for the activation of inflammasome. In the rats subjected to CCI neuropathic pain, the PKR was simultaneously activated in hippocampus. Functional inhibition of PKR suppressed the NLRP1 inflammasome activation and effectively attenuated the CCI-induced depression-like behaviors. These results indicate that the hippocampal PKR/NLRP1 inflammasome pathway play an important role in the development of the depressive behaviors after chronic neuropathic pain. Thus, interrupting this pathway might provide a novel therapeutic strategy for neuropathic pain-associated depressive disorders.

20.
Neuropharmacology ; 155: 31-43, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103617

RESUMO

Ghrelin is an orexigenic hormone that also plays an important role in mood disorders. Our previous studies demonstrated that ghrelin administration could protect against depression-like behaviors of chronic unpredictable mild stress (CUMS) in rodents. However, the mechanism related to the effect of ghrelin on CUMS mice has yet to be revealed. This article shows that ghrelin (5 nmol/kg/day for 2 weeks, i.p.) decreased depression-like behaviors induced by CUMS and increased hippocampal integrity (neurogenesis and spine density) measured via Ki67, 5-bromo-2-deoxyuridine (BrdU), doublecortin (DCX) labeling and Golgi-cox staining, which were decreased under CUMS. The behavioral phenotypes of Growth hormone secretagogue receptor (Ghsr)-null and wild type (WT) mice were evaluated under no stress condition and after CUMS exposure to determine the effect of Ghsr knockout on the behavioral phenotypes and stress susceptibility of mice. Ghsr-null mice exhibited depression-like behaviors under no stress condition. CUMS induced similar depression- and anxiety-like behavioral manifestations in both Ghsr-null and WT mice. A similar pattern of behavioral changes was observed after hippocampal GHSR knockdown. Additionally, both Ghsr knockout as well as CUMS exhibited deleterious effects on neurogenesis and spine density in the dentate gyrus (DG). Besides, CCK8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay showed that ghrelin has a proliferative effect on primary cultured hippocampal neural stem cells (NSCs) and this proliferation was blocked by D-Lys3-GHRP-6 (DLS, the antagonist of GHSR, 100 µM) pretreatment. Ghrelin-induced proliferation is associated with the inhibition of G1 arrest, and this inhibition was blocked by LY294002 (specific inhibitor of PI3K, 20 µM). Furthermore, the in vivo data displayed that LY294002 (50 nmol, i.c.v.) can significantly block the antidepressant-like action of exogenous ghrelin treatment. All these results suggest that ghrelin/GHSR signaling maintains the integrity of hippocampus and has an inherent neuroprotective effect whether facing stress or not.

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