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1.
Sci Rep ; 9(1): 11248, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375755

RESUMO

Psychiatric disorders are highly heterogeneous syndromes often explained by underlying and internalized personality disorder(PD) traits that are affected by externalized childhood trauma experiences(CTE). The present study investigated the differential subtype model by examining the association between PD traits and CTE in a clinical sample with transdiagnostic psychopathology. Outpatients(n = 2090) presenting for psychiatric treatment completed self-reported measures of PD traits(Personality Diagnostic Questionnaire) and the childhood adversity(Child Trauma Questionnaire). Canonical variates were generated by canonical correlation analysis(CCA) and then used for hierarchical cluster analysis to produce subtypes. A support vector machine(SVM) model was used and validated using a linear kernel to assess the utility of the extracted subtypes of outpatients in clinical diagnosis classifications. The CCA determined two linear combinations: emotional abuse related dissociality PD traits(antisocial and paranoid PD) and emotional neglect related sociality PD traits(schizoid, passive-aggressive, depressive, histrionic, and avoidant PD). A cluster analysis revealed three subtypes defined by distinct and relatively homogeneous patterns along two dimensions, and comprising 17.5%(cluster-1, n = 365), 34.8%(cluster-2, n = 727), and 47.8%(cluster-3, n = 998) of the sample, each with distinctive features of PD traits and CTE. These subtypes suggest more distinct PD trait correlates of CTE manifestations than were captured by clinical phenomenological diagnostic definitions. Our results highlight important subtypes of psychiatric patients that highlight PD traits and CTE that transcend current diagnostic boundaries. The three different subtypes reflect significant differences in PD and CTE characteristics and lend support to efforts to develop PD and childhood trauma targeted psychotherapy that extends to clinical diagnosis-based interventions.

2.
Nutr Cancer ; : 1-27, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31267795

RESUMO

Background: Rhus chinensis Mill is a traditional Chinese medicine (TCM) mostly used to treat several cancer types. Although previous studies have found that certain ingredients of R. chinensis such as flavonoids can inhibit tumor cell proliferation [e.g. colorectal cancer (CRC)], systematic research on the mechanism underlying anticancer effect of active compounds like triterpenoids (TER) is lacking. Study Design: Herein, the concept of "network pharmacology primarily based on active compounds" was applied to explore the anticancer mechanisms of TER extract from R. chinensis. In this regard, potential targets and pathways of glycolysis and glutaminolysis form the basis for the anti-CRC effect of triterpenoids. Network pharmacology was used to predict several key proteins in the metabolic pathways, which were further verified via western blot and metabolomics methods. Results: Our results showed that the total TER in R. chinensis remarkably inhibited the proliferation and apoptosis of SW620 cells. The top 4 compounds of TER (viz., betulinic acid-BTA, betulonic acid-BTOA, betulin-BT, and semialactic acid-SA) were confirmed through the detection of UPLC-MS and analysis of cell proliferation assays. Mechanistically, this study revealed that TER plays an anti-CRC role through key targets, such as ENO1, ALDOA, PFKFB3, PKM2, and LDHA, as well as key glycolytic and glutaminolytic pathways. Conclusion: Collectively, these results have provided new insights into the mechanism underlying anti-CRC effect of triterpenoids extract obtained from R. chinensis, mainly through combination of compositional quantitative analysis, network pharmacology, and experimental verification.

3.
BMC Psychiatry ; 19(1): 212, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277613

RESUMO

BACKGROUND: Narcissistic personality disorder (NPD) has never been applied in Chinese clinical practice, and the distribution of NPD in the clinical population of China is largely unknown. The current study uses two-stage clinic-based screening to investigate the frequency and clinical features of NPD in a Chinese help-seeking sample. METHODS: A total of 1402 consecutive outpatients ages 18-60 were recruited during their visit to the Shanghai Mental Health Center and screened with the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+) and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis II (SCID-II). The structured clinical interview was administered to estimate the rate of NPD and the frequency of each disorder criterion. RESULTS: The frequency estimate of NPD in the total sample was 4.0%. Among the 56 outpatients who met the criteria for NPD, there were more males than females, and many had a better educational background. The SCID-II interviews revealed high frequencies of diagnostic criterion 1 ("exaggerated sense of self-importance. NPD likely overlaps with Histrionic PD, Borderline PD, and Paranoid PD. This two stage screening method can enhance detection of Chinese NPD patients in clinical settings. CONCLUSIONS: Narcissism pathology is not rare in the Chinese psychiatric community when using the DSM-IV NPD criteria. Existing evidence suggests, at least indirectly, that there are important benefits of NPD diagnosis in psychiatric practice.

4.
Toxicol Appl Pharmacol ; 372: 47-56, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981666

RESUMO

As one of the most prevalent contaminants in animal and human food, the deleterious effects of trichothecene mycotoxin deoxynivalenol (DON) warrant extensive investigation. Here, to assess the effects of DON exposure to the populations of gut microbiota, four-weeks-old mice were exposed to different doses (1.0 and 5.0 mg/kg) of DON every two days for 14 days. The contents of the cecum were then collected for DNA extraction and metagenomic shotgun sequencing, in order to detect alterations of the gut microbiota. We found that the average body weight and daily gain in the high dose DON treated group decreased. Metagenomic analysis demonstrated that the relative abundance of Firmicutes in the low and Bacteroidetes in the high dose groups increased compared to that in the untreated control group. Moreover, using gene calling and functional annotation, we found that large numbers of biosynthesis and degradation dependent populations were altered. As a result, metabolism pathways including sphingolipid, protein digestion/absorption, and lipoic acid pathways in the high dose DON exposed group dramatically fluctuated in comparison to the control and low dose groups. In addition, metagenomic binning identified ten microbiota genome drafts, with high levels of completeness, that further explain the DON-induced intestinal toxicity. Our findings suggested that DON exposure significantly impacted the microbiota community in the mouse, causing biosynthesis and degradation damage and metabolism pathway disorders.

5.
Psychiatry ; : 1-11, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31017559

RESUMO

OBJECTIVE: Multiple and overlapping diagnoses of personality disorders (PDs) have been a major obstacle in clinical practice and research. This study aims to investigate the comorbidity of PDs in a sample of a high-risk clinical population. We propose a diagnostic model to address this critical issue. METHODS: The sample population included 982 PD patients. The PD diagnoses were concluded based on self-reported and face-to-face interviews. To address the issue of overlapping PD diagnoses, we defined the criteria for clinically distinguishing principal and subordinate PDs, and determined the frequency of each condition. RESULTS: Diagnostic overlap among PDs was quite common across all categories. Of all 982 PD patients, 436 (44.4%) met the criteria for more than one PD. In terms of specific PD diagnoses, the comorbidity rate of each PD was nearly 47.1-74.7%. The principal and subordinate PDs were distinguished accordingly. Avoidant, obsessive-compulsive, and borderline PD remain the most prevalent types of principal PD in this clinical population. CONCLUSIONS: The principal/subordinate model may be one strategy of resolving the issue of PD comorbidity in Chinese clinical settings.

6.
J Cell Physiol ; 234(10): 17023-17049, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30888065

RESUMO

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.

7.
J Cataract Refract Surg ; 45(6): 766-777, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30876782

RESUMO

PURPOSE: To assess the regional changes in corneal shape after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) in patients with different myopia extents. SETTING: Eye Hospital, Wenzhou Medical University, Wenzhou, China. DESIGN: Retrospective case series. METHODS: A retrospective study of myopic eyes treated with FS-LASIK was conducted to assess the shape changes within different corneal regions after surgery. Corneal curvature was measured in the central region (0 mm to 3.0 mm diameter), pericentral region (3.0 mm to 6.0 mm diameter) and peripheral region (6.0 mm to 9.0 mm diameter) preoperatively and from 1 week to 6 months postoperatively. RESULTS: The study comprised 608 myopic eyes. During the 6-month follow-up, the anterior cornea became steeper in the central and pericentral regions, but flatter in the peripheral region (P < .01), representing a partial, gradual, yet significant reversal of the immediate change in corneal shape after laser ablation. In contrast, the posterior surface experienced significantly less change than the anterior surface, with the cornea becoming slightly flatter (P < .01) in the central region at 1 week postoperatively, and steeper elsewhere (P < .05), and then remaining stable during the rest of the follow-up. On the other hand, the anterior astigmatism had significant decreases in the central region (P < .01) and slight increases in the peripheral region (P < .01) 1 week postoperatively, and that remained stable over the follow-up period. In contrast, there were little or non-significant changes in the posterior astigmatism throughout the follow-up (P > .05). CONCLUSIONS: Postoperative corneal shape changes were different in different regions. There were shape changes in individual corneal regions during the 6-month follow-up period that represented reverse trends; however, the changes were much smaller than the short-term changes observed 1 week after surgery.

8.
Gene ; 696: 40-46, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30772519

RESUMO

Copy number variation (CNV), as an important component of genomic structural variation (SV), plays essential roles in phenotypic variability, disease susceptibility and species evolution. To investigate whether critical CNVs exist in dairy goats with differing fecundity, we performed genome-wide sequencing of two populations of Laoshan dairy goats with large differences in litter size. After reference genome aligning, CNV calling, and annotation, we screened identified CNVs in the high-fecundity (HF) and low-fecundity (LF) groups to identify discrepant CNVs and their distribution within the genome. Prolactin-related protein 1 and 6 (PRP1 and PRP6), important factors regulating reproductive processes, were demonstrated to be duplicated in the HF group. In summary, based on the differences in CNVs between goats with differing litter sizes, it suggests CNVs may contribute to litter size in Laoshan dairy goats.


Assuntos
Variações do Número de Cópias de DNA/genética , Fertilidade/genética , Cabras/genética , Tamanho da Ninhada de Vivíparos/genética , Característica Quantitativa Herdável , Animais , Feminino , Gado/genética , Anotação de Sequência Molecular , Gravidez , Sequenciamento Completo do Genoma
9.
J Ethnopharmacol ; 235: 255-267, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30772482

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Studies have shown that the etiology and pathogenesis of colorectal cancer are closely related to the tumor microenvironment, and the cancer tissue is still in the state of "energy deficit" and has to promote energy generation through high glycolysis. Rhus chinensis Mill is a Chinese herbal medicine used to treat various types of solid tumors in China. Colorectal cancer (CRC) is a heterogeneous disease group caused by abnormal changes in glucose metabolism resulted in lactic acid production, which remodels acidosis. AIM OF THE STUDY: Although previous studies have shown that the active compounds of Rhus chinensis Mill. can inhibit the proliferation of tumor cells, whether its triterpenoids could effectively regulate glycolysis involved in CRC have not been systematically investigated. MATERIALS AND METHODS: In this study, the extraction of triterpenoids extract from Rhus chinensis Mill. was obtained, and cell viability assay, the percentage of apoptosis for CRC cells were counted, and matrigel invasion assay and production of lactic acid and glucose uptake assay was determined. we further examined the expression of the key glycolytic enzymes and acid-sending ion channel (ASIC) family members of SW620 cells, and some key proteins in the glycolytic pathway were further verified. RESULTS: Notably, triterpenoids (TER) of Rhus chinensis Mill. showed effective anti-proliferative activity and significantly altered protein levels associated with CRC cell survival and glycolysis metabolism. TER could down-regulate the expression of ASIC2, in CRC SW620 cell line. Most importantly, the levels of ASIC2 and calcineurin/nuclear factor of activated T cells (NFAT) were also down-regulated by TER. Furthermore, inhibition of activated the ASIC2-mediated calcineurin/NFAT1 pathway and target gene transcript expression of MMP-2 and MMP-9 in parallel to reduce, and resulted in the reduced invasion ability by TER treatment. CONCLUSION: The potential pathways and targets that involved in glycolysis to excert the anti-CRC effects of main compounds in triterpenoids of Rhus chinensis Mill. were predicted by network pharmacology methods. Our findings thus provided rational evidence that inhibition of the ASIC2-induced calcineurin/NFAT pathway by triterpenoids in Rhus chinensis Mill. profoundly suppressed cell growth and invasion in CRC, which target alternative glycolysis in colorectal tumor cells, may be a useful adjuvant therapy in the treatment of colorectal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Rhus/química , Triterpenos/farmacologia , Canais Iônicos Sensíveis a Ácido/metabolismo , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Calcineurina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Regulação para Baixo/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa/métodos , Fatores de Transcrição NFATC/metabolismo , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Triterpenos/isolamento & purificação , Microambiente Tumoral
10.
J Cell Physiol ; 234(8): 14339-14350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30633354

RESUMO

From the previous research, it has been supported that activin A (ActA) is conducive to ovarian development in vitro. In the present paper, with the aim to identify the molecular pathways through which ActA can influence processes of the fetal and early postnatal oogenesis, we analyzed the transcriptome of embryonic ovaries (12.5 days postcoitum) in vitro cultured with or without ActA for 6 days, as well as the produced oocytes for 28 days, and further compared the gene expression profile with their in vivo counterparts. With the confirmation of designed test, we found that the addition of ActA to the ovary culture tended, generally, to align oocyte gene expression to the in vivo condition, in particular of a number of genes involved in meiosis and epigenetic modifications of histones. In particular, we identified DNA recombination during the oocyte meiotic prophase I and lysine trimethylation of the histone H3K27 during the oocyte growth phase as molecular pathways modulated by ActA.

11.
Proteomics ; : e1800271, 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30515942

RESUMO

We artificially infected Sprague Dawley (SD) rats and Kunming (KM) mice with type II Toxoplasma gondii (T. gondii) strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. We aimed to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, we established a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) to identify differentially expressed proteins (DEPs) in the rats' and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) was upregulated and the tight junction (TJ) pathway showed a disorder. We presumed that T. gondii-stimulated C3 disrupts the TJ of the blood-brain barrier (BBB) in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space. This article is protected by copyright. All rights reserved.

12.
Aging (Albany NY) ; 10(12): 4175-4187, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30591620

RESUMO

Di (2-ethylhexyl) phthalate (DEHP), an estrogen-like compound that is a ubiquitous environmental contaminant, has been reported to adversely affect human and mammalian reproduction. Many studies have found that exposure to DEHP during pregnancy perturbs female germ cell meiosis and is detrimental to oogenesis. Previous studies have demonstrated that melatonin (MLT) is beneficial to reproductive endocrinology, oogenesis, and embryonic development as the ability to antioxidative and antiapoptotic. However, whether the meiotic defect of germ cells exposed to DEHP could be rescued by MLT is not clear. Here, we cultured 12.5 days post coitum (dpc) fetal mouse ovaries for 6 days, exposed them to 100 µM DEHP with or without 1 µM MLT in vitro.. The results showed that DEHP exposure induced the abnormal formation of DNA double-strand breaks (DSBs), and inhibited the repair of DSBs during meiotic recombination. In addition, we found defective oocytes were prone to undergo apoptosis. Notably, this defect could be remarkably ameliorated by the addition of MLT via a reduction of the levels of reactive oxygen species and an inhibition of apoptosis. In conclusion, our data revealed that MLT had a protective action against the meiotic deterioration of fetal oocytes induced by DEHP in the mouse in vitro.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30419454

RESUMO

The present study focuses on the biodegradation of triphenylmethane dye crystal violet (CV) by Cedecea davisae. The degradation of CV was evaluated via ultraviolet absorbance at 254 nm (UV254) and chemical oxygen demand (COD) removal, and the kinetics was used to evaluate the degradation efficiency. Intermediate products were analyzed via UV-vis spectroscopy (UV), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC). Results showed that C. davisae was able to decolorize the CV, and the maximum decolorization ratio reached 97%. COD reduction was observed after decolorization, with average removal rates of >90% after 48 h. Moreover, 50% of UV254 can be removed after 14 h. The removal efficiency of CV by C. davisae followed first- and second-order reaction kinetics at temperature ranged from 20 °C to 40 °C and pH 4.0 to 6.0, respectively. By using UV, the peak representing the CV disappeared 14 h after CV decolorization, and the degradation of aromatic and naphthalene rings was attributed to the formation of a new metabolite. The FTIR spectra of metabolites showed that a new functional group of OH, CH, CH2, CH3, NH, CN, CN, or CO was produced. The chromatograms of HPLC recorded at 589 nm at retention time decreased and were not detected following incubation for 8 h by C. davisae.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30415361

RESUMO

This study determined the subcellular distribution, chemical forms, and effects of metal homeostasis of excess Cd in Cladophora rupestris. Biosorption data were analyzed with Langmuir and Freundlich adsorption models and kinetic equations. Results showed that C. rupestris can accumulate Cd. Cd mainly localized in the cell wall and debris (42.8-68.2%) of C. rupestris, followed by the soluble fraction (22.1-38.4%) observed in C. rupestris. A large quantity of Cd ions existed as insoluble CdHPO4 complexed with organic acids, Cd(H2PO4)2, Cd-phosphate complexes (FHAC) (43.2-56.0%), and pectate and protein-integrated Cd (FNaCl) (30.8-43.2%). The adsorption data were well fitted by the Freundlich model (R2 = 0.933) and could be described by the pseudo-second-order reaction rate (R2 = 0.997) and Elovich (R2 = 0.972) equations. Related parameters indicated that Cd adsorption by C. rupestris is a heterogeneous diffusion. Cd promoted Ca and Zn uptake by C. rupestris. Cu, Fe, Mn, and Mg adsorption was promoted by low Cd concentrations and inhibited by high Cd concentrations. Results suggested that cell wall sequestration, vacuolar compartmentalization, and chemical morphological transformation are important mechanisms of Cd stress tolerance by C. rupestris. This study suggests that C. rupestris has bioremediation potential of Cd.

15.
Sensors (Basel) ; 18(11)2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30400669

RESUMO

FlexRay is a next-generation in-vehicle communication protocol which works in real time with flexibility. The most common applications in FlexRay are high bandwidth. X-by-wire applications, such as brake by wire and throttle by wire. However, there is no mechanism which can prevent transient faults in the application layer of FlexRay. If a transient fault occurs during driving, this would be very dangerous; therefore, we propose a fast reliability scheduling algorithm (FRSA) to improve the communication reliability of FlexRay. The proposed method reduces the probability of transient faults in one clock cycle by using a retransmission mechanism to recover the transient errors, and further improves computational complexity using the lookup table method to ensure system reliability. In this paper, we analyze a related literature to establish the system reliability constraints needed to evaluate the necessary time and slot usage, and the proposed cost function is used to evaluate the performance and efficiency when the number of messages is increased. Experimental results show that the proposed FRSA reduces execution time by an average 70.76% and cost by an average 13.33% more than the other existing methods. This method can be useful to others, especially regarding research about periodic time-triggered communication systems.

16.
Inorg Chem ; 57(21): 13128-13136, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30351070

RESUMO

Open-framework chalcogenides with ion-exchange capacity are promising materials for removing hazardous heavy-metal ions and for capturing radioactive Cs+. However, research on the exchange mechanism is limited, especially for the framework chalcogenides that have multiple bridging anions. Generally, open-framework chalcogenides that have multiple bridging anions at the window or wall of the channels are rigid during the ion-exchange process. We show here that microporous sulfides with µ3-S2- (where µ3 = triple bridging mode) at the windows exhibit framework flexibility upon ion exchange. Three new microporous sulfides Na4Cu8Ge3S12·2H2O (1), Na3(Hen)Cu8Sn3S12 (where en = ethylenediamine) (2) and (dap)2(Hdap)4Cu8Ge3S18 (where dap = 1,2-diaminopropane) (3) were synthesized under solvothermal conditions. Compounds 1 and 2 contain a copper-rich framework composed of icosahedral [Cu8S12]16- units linked via monomeric GeS44- or SnS44- tetrahedral units, whereas compound 3 features an expanded framework composed of icosahedral [Cu8S12]16- units interconnected with dimeric Ge2S64- units. These compounds exhibit unusual ion-exchange properties. Specifically, the frameworks of 1 and 2 (with µ3-S at the small windows) show "breathing action" upon ion exchange of K+ or Rb+, which have relative large sizes, and compound 3 exhibits framework flexibility upon Cs+ ion exchange with both space group and channels changed.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30360743

RESUMO

Colorectal cancer is a heterogeneous group of diseases that result from the accumulation of different sets of genomic alterations, together with epigenomic alterations, and it is influenced by tumor-host interactions, leading to tumor cell growth and glycolytic imbalances. This review summarizes recent findings that involve multiple signaling molecules and downstream genes in the dysregulated glycolytic pathway. This paper further discusses the role of the dysregulated glycolytic pathway in the tumor initiation, progression and the concomitant systemic immunosuppression commonly observed in colorectal cancer patients. Moreover, the relationship between colorectal cancer cells and T cells, especially CD8+ T cells, is discussed, while different aspects of metabolic pathway regulation in cancer cell proliferation are comprehensively defined. Furthermore, this study elaborates on metabolism in colorectal cancer, specifically key metabolic modulators together with regulators, glycolytic enzymes, and glucose deprivation induced by tumor cells and how they inhibit T-cell glycolysis and immunogenic functions. Moreover, metabolic pathways that are integral to T cell function, differentiation, and activation are described. Selective metabolic inhibitors or immune-modulation agents targeting these pathways may be clinically useful to increase effector T cell responses for colorectal cancer treatment. However, there is a need to identify specific antigens using a cancer patient-personalized approach and combination strategies with other therapeutic agents to effectively target tumor metabolic pathways.

18.
J Cell Biochem ; 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30362665

RESUMO

Alterations in cellular energy metabolism play critical roles in colorectal cancer (CRC). These alterations, which correlate to KRAS mutations, have been identified as energy metabolism signatures. This review summarizes the relationship between colorectal tumors associated with mutated KRAS and energy metabolism, especially for the deregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review will concentrate on the role of metabolic genes, factors and signaling pathways, which are coupled with the primary energy source connected with the KRAS mutation that induces metabolic alterations. Strategies for targeting energy metabolism in mutated KRAS CRC are also introduced. In conclusion, deregulated energy metabolism has a close relationship with KRAS mutations in colorectal tumors. Therefore, selective inhibitors, agents against metabolic targets or KRAS signaling, may be clinically useful for colorectal tumor treatment through a patient-personalized approach.

19.
J Cell Physiol ; 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30341899

RESUMO

Alterations in cellular energy metabolism play a critical role in colorectal cancer (CRC), which has been identified as the definition of consensus molecular subtypes (CMSs), and CMS3 tumors exhibit energy metabolism signatures along with Kirsten rat sarcoma viral oncogene homolog (KRAS)-activating mutations. This review summarizes the relationship between CMS3 tumors associated with mutated KRAS and energy metabolism in CRC, especially for the dysregulated energy metabolism that affects tumor cell proliferation, invasion, and migration. Furthermore, this review concentrates on the role of metabolic genes and factors and signaling pathways, which coupled with a primary energy source connected with the CMS3 associated with mutated KRAS, induce metabolic alterations. The strategies to target energy metabolism for the metabolic alterations in mutated KRAS CRC are also introduced. In conclusion, dysregulated energy metabolism has a close relationship with mutated KRAS in CMS3 tumors. Therefore, selective inhibitors or agents against metabolic targets or KRAS signaling may be clinically useful for CMS3 tumor treatment through a personalized approach for patients with cancer.

20.
Curr Eye Res ; : 1-6, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30273056

RESUMO

PURPOSE: To assess the effects of prostaglandin F2α analogues travoprost on the biomechanical behavior of ex-vivo rabbit cornea. MATERIALS AND METHODS: 18 Japanese white rabbits were included in the study. The left eye (treated group, Tr) of each rabbit was preserved for 10 days in storage medium Eusol-C solution with 1:10 travoprost diluent, while the contralateral eye (control group, Co) was preserved in a similar but travoprost-free medium. Strips of corneal tissue were dissected and tested under cyclic load conditions with up to 0.1 N uniaxial tension force. The resulting load-elongation data were used to derive the stress-strain behavior and the tangent modulus (Et) of the tissue. Differences in Et between the treated (Et-Tr) and control group (Et-Co) were assessed statistically to determine the biomechanical effects of travoprost on the cornea. RESULTS: Central corneal thickness (CCT) in the two groups was similar before (P = 0.073) and remained similar after storage (P = 0.303) although it became significantly thicker in both groups after preservation (P < 0.01). Compared with the control group, the travoprost treated corneas exhibited lower Et values but the differences reduced and became insignificant with rises in stress to which the tissue was subjected (1 - Et-Tr/Et-Co = -11.7 ± 41.8%, P < 0.05 at 10 kPa stress; -9.2 ± 36.1%, P > 0.05 at 20 kPa; -7.3 ± 35.4%, P > 0.05 at 30 kPa). CONCLUSIONS: Significant reductions in corneal stiffness, that are associated with the use of travoprost, were observed experimentally under low applied stresses. This stiffness-reduction effect should be considered in clinical management, especially in primary open angle glaucoma treatment.

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