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1.
Plant Physiol ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983053

RESUMO

Light affects many physiological and developmental processes of plants by regulating the expression and activity of light responsive proteins. Among them, phytochrome interacting factors (PIFs) play pivotal roles in the regulation of anthocyanin accumulation and hypocotyl growth. However, the molecular mechanism is not well understood, especially in woody plants, such as apple (Malus × domestica). In this study, we identified a light responsive PIF protein, MdPIF7, in apple and investigated the molecular mechanism of its regulation of anthocyanin biosynthesis and hypocotyl growth. We found that overexpression of MdPIF7 decreased anthocyanin accumulation in transgenic apple materials and promoted hypocotyl elongation in ectopically expressed Arabidopsis (Arabidopsis thaliana). Further investigation showed that MdPIF7 functioned by interacting with B-box 23 (MdBBX23), a positive regulator of anthocyanin biosynthesis in apple and hypocotyl growth inhibition in ectopically expressed Arabidopsis, and attenuating the transcriptional activation of MdBBX23 on LONG HYPOCOTYL 5 (MdHY5). In addition, MdPIF7 interacted with basic region leucine zipper 44 (MdbZIP44) and ethylene response factor 38 (MdERF38), two positive regulators of anthocyanin biosynthesis, and it negatively regulated MdbZIP44- and MdERF38-promoted anthocyanin accumulation by interfering with the interaction between MdbZIP44/MdERF38 and MdMYB1. Taken together, our results reveal that MdPIF7 regulates anthocyanin biosynthesis in apple and hypocotyl growth in ectopically expressed Arabidopsis through MdPIF7-MdBBX23-MdHY5 and MdPIF7-MdbZIP44/MdERF38-MdMYB1 modules. Our findings enrich the functional studies of PIF proteins and provide insights into the molecular mechanism of PIF-mediated anthocyanin biosynthesis and hypocotyl growth.

3.
Cell Death Dis ; 13(1): 41, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013118

RESUMO

Despite the great advances in target therapy, lung cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in various cancers; however, the pathological roles and clinical implication in lung cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients' tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung cancer treatment.

4.
Support Care Cancer ; 30(1): 875-885, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34392426

RESUMO

OBJECTIVES: To clarify the influence of hemoglobin on cancer cachexia and to determine whether hemoglobin affects the prognosis or quality of life of patients with cancer cachexia and whether these effects are caused by an interaction between hemoglobin and other factors. MATERIAL AND METHODS: This study was a multicenter cohort of 2715 patients with cancer cachexia diagnosed from June 2012 to December 2019. The primary outcomes and measures were overall survival (OS) time and all-cause mortality. The association between hemoglobin and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided p-value. Optimal stratification was used to determine the threshold value. We also evaluated the cross-classification of hemoglobin and each variable with survival. RESULTS: Among the 2715 participants diagnosed with cancer cachexia, 1592 (58.6%) were male, and the mean (SD) age was 58.8 (11.7) years. The optimal cutoff point for hemoglobin as a predictor of cancer cachexia mortality was 140 g/L for males and 101 g/L for females in our research. The decrease in hemoglobin was positively correlated with all-cause mortality. These associations were consistent across cancer subtypes. In the multivariable analysis, after adjusting for sex, age, TNM stage, tumor type, radiotherapy, chemotherapy, Karnofsky performance status score, and other factors, patients diagnosed with cancer cachexia who had low hemoglobin levels were more likely to have a worse prognosis (HR 2.40; 95% CI, 1.12-1.51). CONCLUSION: Our results suggested that the proposed hemoglobin cutoff point would be valuable for prognostic prediction in patients with cancer cachexia, especially for long-term prognosis.


Assuntos
Caquexia , Neoplasias , Caquexia/epidemiologia , Caquexia/etiologia , Estudos de Coortes , Feminino , Hemoglobinas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Prognóstico , Qualidade de Vida , Estudos Retrospectivos
5.
Orthop Surg ; 13(8): 2417-2422, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34734478

RESUMO

OBJECTIVE: To investigate the biomechanical and elution properties of meropenem-loaded bone cement. METHODS: Bone cement (Palacos LV) with 5% (2 g/4 0g), 10% (4 g/40 g), and 15% (6 g/40 g) meropenem; 5% (2 g/40 g) and 10% (4 g/40 g) vancomycin; and blank bone cement were prepared in a total of six groups named A2, A4, A6, B2, B4, and A0 (antibiotic-free). 36 cylinder specimens (6-mm diameter and 12-mm height) of all six groups were molded for a compression test. After the compression test, because of mechanical properties below the ISO standard requirements, groups B2, B4 were not subjected to a bending test. So a total of 24 rectangular strip specimens (10-mm width, 75-mm length, and 3.3-mm thickness) for groups A2, A4, A6 and A0 were molded for the bending test. Between-group differences of compressive strength, bending strength and bending modulus were analyzed. The meropenem standard was prepared as a series of standard solutions to calculate the standard curve. At a constant temperature of 37 °C, separately, meropenem-loaded bone cement cylinder specimens (12 mm in diameter and 17 mm in length) of A2, A4 and A6 were serially immersed in saline solution without stirring. The eluent drug concentration at 24, 48, 72 h and 6, 12, 24 days was measured and the drug concentration-time curve of meropenem was constructed. RESULTS: With the exception of groups B2 and B4, all cements compressive strength values were well above the minimum requirement of the ISO 5833 standard (70 MPa). The compressive strength and bending strength values of group A4 were higher than those of group A0 (P < 0.05), but no difference was found between the A0, A2 and A6 groups (P > 0.05). There were no intergroup differences of bending modulus between the A0, A2, A4 and A6 groups (P > 0.05). A standard curve of meropenem was obtained and a regression equation was constructed: Y = 15.0265 X + 13.5218, r = 1.00. At 37 °C, the release of meropenem was rapid during the first 48 h for all A2, A4, A6 samples, and subsequent release continued to decrease. CONCLUSION: When adding up to 15% (6 g/40 g) meropenem to the bone cement, the biomechanical properties were not reduced, and bone cement with 10% (4 g/40 g) meropenem had the best performance. At a constant temperature of 37°C, meropenem can be released from bone cement for up to 24 days.

6.
J Inflamm Res ; 14: 5527-5540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737602

RESUMO

Background: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality. Patients and Methods: This multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria. Results: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590-2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups. Conclusion: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

7.
ACS Omega ; 6(44): 29820-29829, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34778655

RESUMO

Strain engineering can effectively improve the energy band degeneracy of two-dimensional transition metal dichalcogenides so that they exhibit good thermoelectric properties under strain. In this work, we have studied the phonon, electronic, thermal, and thermoelectric properties of 1T-phase monolayer HfS2 with biaxial strain based on first-principles calculations combined with Boltzmann equations. At 0% strain, the results show that the lattice thermal conductivity of monolayer HfS2 is 5.01 W m-1 K-1 and the electronic thermal conductivities of n-type and p-type doped monolayer HfS2 are 2.94 and 0.39 W m-1 K-1, respectively, when the doping concentration is around 5 × 1012 cm-2. The power factors of the n-type and p-type doped monolayer HfS2 are different, 29.4 and 1.6 mW mK-2, respectively. Finally, the maximum ZT value of the n-type monolayer HfS2 is 1.09, which is higher than 0.09 of the p-type monolayer HfS2. Under biaxial strain, for n-type HfS2, the lattice thermal conductivity, the electronic thermal conductivity, and the power factor are 1.55 W m-1 K-1, 1.44 W m-1 K-1, and 22.9 mW mK-2 at 6% strain, respectively. Based on the above factor, the ZT value reaches its maximum of 2.29 at 6% strain. For p-type HfS2, the lattice thermal conductivity and the electronic thermal conductivity are 1.12 and 1.53 W m-1 K-1 at 7% strain, respectively. Moreover, the power factor is greatly improved to 29.5 mW mK-2. Finally, the maximum ZT value of the p-type monolayer HfS2 is 3.35 at 7% strain. It is obvious that strain can greatly improve the thermoelectric performance of monolayer HfS2, especially for p-type HfS2. We hope that the research results can provide data references for future experimental exploration.

8.
Theor Appl Genet ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34766198

RESUMO

KEY MESSAGE: Map-based cloning was used to identify the BrWAX2 gene, which was involved in the cuticular wax biosynthesis. The malfunction of BrWAX2 together with other reduced expression of genes in alkane-forming pathway caused the glossy phenotype. Cuticular wax covering the outer plant surface plays various roles in protecting against biotic and abiotic stresses. Wax-less mutant shows glossy in stem and leaf surface and plays important roles in enriching Chinese cabbage germplasm resources for breeding brilliant green varieties. However, genes responsible for the glossy trait in Chinese cabbage are rarely reported. In this study, we identified a glossy Chinese cabbage line Y1211-1. Genetic analysis indicated that the glossy trait in Y1211-1 was controlled by a single recessive locus, BrWAX2 (Brassica rapa WAX 2). Using bulked segregant sequencing (BSA-Seq) and kompetitive allele-specific PCR (KASP) assays, BrWAX2 was fine-mapped to an interval of 100.78 kb. Functional annotation analysis, expression analysis, and sequence variation analysis revealed that Bra032670, homologous to CER1 in Arabidopsis, was the most likely candidate gene for BrWAX2. The gene Bra032670 was absent in glossy mutant. Cuticular wax composition analysis and RNA-Seq analysis suggested that the absence of BrWAX2 together with the decreased expression of other genes in alkane-forming pathway reduced the wax amount and caused the glossy phenotype. Furthermore, we developed and validated the functional marker BrWAX2-sp for BrWAX2. Overall, these results provide insight into the molecular mechanism underlying cuticular wax biosynthesis and reveal valuable information for marker-assisted selection (MAS) breeding in Chinese cabbage.

10.
Front Oncol ; 11: 710423, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692487

RESUMO

Background: Colorectal cancer (CRC) is one of the most common malignancies throughout the world, with high rates of morbidity and mortality. Previous studies reported that serum creatinine (Scr) concentrations were associated with overall survival (OS) in cancer patients, but little is known about the association between Scr and OS in patients with CRC. This study investigated the relationship between Scr concentrations and OS in patients with CRC and examined possible effect modifiers. Methods: A retrospective cohort, including 1,733 patients with CRC, was established from a multi-center clinical study. Patients were divided into low (<71 µmol/L in men or <59 µmol/L in women), normal (71-104 µmol/L in men or 59-85 µmol/L in women) and high (>104 µmol/L in men or >85 µmol/L in women) Scr groups. Cox regression analysis was used to examine association between Scr concentrations and OS. Stratified (subgroup) analyses were used to examine men and women separately. Interaction tests were used to evaluate associations between each variable and OS, as well as possible interactions of these variables with Scr levels. Cross-classified analyses were used only in men. Results: Patients with low [hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.19-1.72; P < 0.001] or high (HR = 1.89, 95% CI = 1.36-2.63; P < 0.001) Scr level had a significantly lower OS than patients with normal Scr levels. Significant interactions with Scr concentrations were observed for body mass index (P for interaction = 0.019) in men. Conclusion: Low or high Scr concentration is associated with significantly lower OS in patients with CRC. Future study is warranted to investigate the underlying mechanism.

11.
Front Oncol ; 11: 707705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568033

RESUMO

Background: Recently, albumin-globulin ratio (AGR), a serological indicator that reflects nutritional status and systemic inflammatory, has been reported to be associated with the prognosis of various cancers. However, there is currently no research report on its relationship with cancer cachexia. Objectives: This study aimed to explore the prognostic value of AGR in patients with cancer cachexia through a multicenter retrospective analysis. Methods: We recruited 2,364 patients with cancer cachexia and randomly divided the patients into training and validation cohorts at a ratio of 7:3. The optimal stratification method was used to determine the optimal cutoff value of AGR. The survival curve was evaluated by the Kaplan-Meier method. Cox regression proportional-hazards model was used to determine independent prognostic factors in patients with cancer cachexia. The time-dependent receiver operating characteristic curve was used to compare the prognostic performance of different malnutrition evaluation tools. Results: The optimal cutoff value of AGR is 1.24 in patients with cancer cachexia. Increasing AGR was associated with survival in a dose-response manner with a forward L-shape. Compared with the high AGR group, the low AGR group had a shorter overall survival; and there was consistency in training and validation cohorts. In the stratified analysis of TNM stage, AGR has good prognostic distinguishing ability for advanced patients. Multivariate survival analysis determined that low AGR was an independent risk factor affecting all-cause mortality in patients with cancer cachexia. In addition, compared with other malnutrition evaluation tools, AGR could effectively stratify the prognosis of patients with cancer cachexia. Conclusion: AGR was an independent prognostic factor affecting patients with cancer cachexia, especially in advanced patients. Compared with other malnutrition evaluation tools, AGR can effectively stratify the prognosis of patients with cancer cachexia.

12.
Cancer Manag Res ; 13: 6775-6783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512017

RESUMO

Purpose: Serum albumin can indicate the onset of cancer cachexia, provide information about a patient's nutritional status, and serve as a biomarker for the prognosis of patients with cancer cachexia. However, the relationship between serum albumin levels and mortality in patients with cancer cachexia remains unclear. We aimed to examine the association of albumin and total protein with 1-year mortality in patients with cancer cachexia. Patients and Methods: We conducted a nested case-control study using data from a multicenter cancer clinical survey from 2013 to 2018. In total, 266 patients with cancer cachexia who survived for <1 year and 266 patients who survived for ≥1 year were included in this study. The participants were matched by age, sex, tumor type, tumor stage, and hospital site. The crude and adjusted risks of 1-year survival were estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression, with or without adjustment for covariates. Results: Logistic regression analysis revealed a significantly negative linear association between albumin level and 1-year mortality in patients with cancer cachexia (p < 0.001). An L-shaped relationship existed between total protein and 1-year mortality, with a turning point at 70.4 g/L. When albumin was divided into quartiles, Q3 (OR: 0.40; 95% CI: 0.24, 0.68; p < 0.001) and Q4 (OR: 0.33; 95% CI: 0.19, 0.55; p < 0.001) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. When total protein was divided into quartiles, Q2 (OR: 0.38; 95% CI: 0.23, 0.64; p < 0.001), Q3 (OR: 0.57; 95% CI: 0.33, 0.96; p = 0.035), and Q4 (OR: 0.43; 95% CI: 0.25, 0.72; p = 0.002) were associated with higher 1-year survival than Q1 among patients with cancer cachexia. Conclusion: Serum albumin and total protein may predict 1-year survival. Future clinical studies should lead to a more comprehensive understanding of the effects of serum protein levels in patients with cancer cachexia.

13.
J Enzyme Inhib Med Chem ; 36(1): 2104-2117, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34579614

RESUMO

Tyrosinase (TYR) inhibitors are in great demand in the food, cosmetic and medical industrials due to their important roles. Therefore, the discovery of high-quality TYR inhibitors is always pursued. Natural products as one of the most important sources of bioactive compounds discovery have been increasingly used for TYR inhibitors screening. However, due to their complex compositions, it is still a great challenge to rapid screening and identification of biologically active components from them. In recent years, with the help of separation technologies and the affinity and intrinsic activity of target enzymes, two advanced approaches including affinity screening and inhibition profiling showed great promises for a successful screening of bioactive compounds from natural sources. This review summarises the recent progress of separation-based methods for TYR inhibitors screening, with an emphasis on the principle, application, advantage, and drawback of each method along with perspectives in the future development of these screening techniques and screened hit compounds.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34585849

RESUMO

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. METHODS: This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut-off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC. RESULTS: In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow-up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient-years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244-2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC. CONCLUSIONS: For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34337882

RESUMO

BACKGROUND: Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil-to-lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters. METHODS: This is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all-cause mortality. The association between NLR and all-cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two-sided P-value. Optimal stratification was used to solve threshold points. We also evaluated the cross-classification of NLR for each variable of survival. RESULTS: Of the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow-up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%-32.0%), resulting in a rate of 226.07 events per 1000 patient-years. An increase in NLR had an inverted L-shaped dose-response association with all-cause mortality. The optimal cut-off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33-1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ-C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy. CONCLUSIONS: The baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

16.
Immunity ; 54(9): 2042-2056.e8, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34407391

RESUMO

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.


Assuntos
Quimiocina CCL1/metabolismo , Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Miofibroblastos/metabolismo , Fosfoproteínas/metabolismo , Fibrose Pulmonar/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Diferenciação Celular/fisiologia , Fibroblastos/patologia , Humanos , Camundongos , Miofibroblastos/patologia , Fibrose Pulmonar/patologia , Transdução de Sinais/fisiologia
17.
Front Nutr ; 8: 714051, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422885

RESUMO

Background: Fat-free mass (FFM) depletion can be masked by a stable body weight or weight gain in the presence of a normal or high body mass index (BMI). This study investigated the prognostic value of low fat-free mass index (FFMI) in cancer patients with normal or high BMI. Methods: This multicenter retrospective cohort study included 1,602 cancer patients with normal/high BMI. The association of FFMI with patients' overall survival (OS) was analyzed by the Kaplan-Meier method and a Cox model. Results: In this analysis, there were 974 (60.8%) females and 628 (39.2%) males. Low FFMI was associated with worse OS when compared with those patients with normal FFMI. After multivariate adjustment, low FFMI was demonstrated to be an independent unfavorable prognostic factor (HR: 1.69; 95% CI: 1.28, 2.23; P < 0.001) in cancer patients with normal/high BMI. For specific tumor type, low FFMI was found to be associated with worse prognosis in patients with lung cancer, breast cancer and upper gastrointestinal cancer. In subgroup analysis, the association of low FFMI with worse survival was significantly modified by weight loss (P for interaction = 0.012), and those patients with concurrent low FFMI and weight loss showed the worst prognosis (HR: 3.53; 95% CI: 2.04, 6.11; P < 0.001). Conclusion: Low FFMI was associated with worse prognosis in cancer patients with normal/high BMI. This study highlights the usefulness of FFMI for prognostic estimation in these patients.

18.
Histol Histopathol ; : 18358, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269397

RESUMO

BACKGROUND: Herein, we aimed to determine whether DAPK1 and its post-transcriptional regulator miR-361 were implicated in high glucose (HG)-induced podocyte injury and renal damage in db/db mice. MATERIALS AND METHODS: Podocytes were incubated with normal glucose (NG; 5 mM) or HG (30 mM). Podocyte apoptosis was evaluated using TUNEL staining. Lentiviral-delivered specific short hairpin RNA (shRNA) was designed to silence DAPK1 expression in podocytes. miR-361 agomir was administrated by tail intravenous injection in db/db diabetic mice to investigate the renoprotection of miR-361 in vivo. RESULTS: Exposure of podocytes to HG led to a significant increase in DAPK1 mRNA and protein levels and a decrease in miR-361 expression levels. Knockdown of DAPK1 attenuated HG-triggered growth inhibition, apoptosis, DNA damage and cell membrane damage in podocytes. Mechanically, DAPK1 was a direct target of miR-361. Transfection with miR-361 mimics into podocytes resulted in a significant decrease in the DAPK1 protein expression level. In addition, HG-induced the up-regulation of the DAPK1 protein expression level in podocytes was restrained by miR-361 mimics transfection. Intriguingly, overexpression of DAPK1 in HG-stimulated podocytes muted miR-361-mediated cytoprotection, including anti-apoptosis, resistance to DNA and membrane damage. In vivo, overexpression of miR-361 protected against hyperglycemia-induced podocyte loss, tubular atrophy and interstitial fibrosis in the kidney of db/db mice. Moreover, overexpression of miR-361 inhibited the protein expression of DAPK1 in the kidney of db/db mice. CONCLUSION: Our research presented a novel mechanism of HG-induced podocyte damage or renal lesion, supporting the miR-361/DAPK1 signaling pathway that could be used as a potential therapeutic target for the treatment of DN.

19.
Front Plant Sci ; 12: 693344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249065

RESUMO

Salicylic acid (SA) has been proven to be a multifunctional signaling molecule that participates in the response of plants to abiotic stresses. In this study, we used cold-sensitive cucumber and cold-tolerant pumpkin as experimental materials to examine the roles of SA in root-shoot communication responses to aerial or/and root-zone chilling stress in own-root and hetero-root grafted cucumber and pumpkin plants. The results showed that pumpkin (Cm) rootstock enhanced the chilling tolerance of grafted cucumber, as evidenced by the observed lower levels of electrolyte leakage (EL), malondialdehyde (MDA), and higher photosynthetic rate (Pn) and gene expression of Rubisco activase (RCA). However, cucumber (Cs) rootstock decreased the chilling tolerance of grafted pumpkins. Cs/Cm plants showed an increase in the mRNA expression of C-repeat-binding factor (CBF1), an inducer of CBF expression (ICE1), and cold-responsive (COR47) genes and CBF1 protein levels in leaves under 5/25 and 5/5°C stresses, or in roots under 25/5 and 5/5°C stresses, respectively, compared with the Cs/Cs. Chilling stress increased the endogenous SA content and the activity of phenylalanine ammonia-lyase (PAL), and the increase in SA content and activity of PAL in Cs/Cm plants was much higher than in Cs/Cs plants. Transcription profiling analysis revealed the key genes of SA biosynthesis, PAL, ICS, and SABP2 were upregulated, while SAMT, the key gene of SA degradation, was downregulated in Cs/Cm leaves, compared with Cs/Cs leaves under chilling stress. The accumulation of SA in the Cs/Cm leaves was mainly attributed to an increase in SA biosynthesis in leaves and that in transport from roots under aerial and root-zone chilling stress, respectively. In addition, exogenous SA significantly upregulated the expression level of cold-responsive (COR) genes, enhanced actual photochemical efficiency (Φ PSII), maximum photochemical efficiency (F v/F m), and Pn, while decreased EL, MDA, and CI in grafted cucumber. These results suggest that SA is involved in rootstock-scion communication and grafting-induced chilling tolerance by upregulating the expression of COR genes in cucumber plants under chilling stress.

20.
Eur J Pharmacol ; 908: 174346, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34270985

RESUMO

Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Gefitinib, an inhibitor of EGFR tyrosine kinase, is highly effective in treating NSCLC patients with activating EGFR mutations (L858R or Ex19del). However, despite excellent disease control with gefitinib therapy, innate resistance and inevitable acquired resistance represent immense challenges in NSCLC therapy. Gefitinib potently induces cytoprotective autophagy, which has been implied to contribute to both innate and acquired resistance to gefitinib in NSCLC cells. Currently, abrogation of autophagy is considered a promising strategy for NSCLC therapy. In the present study, YC-1, an inhibitor of HIF-1α, was first found to significantly inhibit the autophagy induced by gefitinib by disrupting the fusion of autophagosomes and lysosomes and thereby enhancing the proapoptotic effect of gefitinib in gefitinib-resistant NSCLC cells. Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.

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