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1.
Sci Rep ; 11(1): 22807, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815476

RESUMO

Apical-basal cell polarity and lumen formation are essential features of many epithelial tissues, which are disrupted in diseases like cancer. Here, we describe a proteomics-based screen to identify proteins involved in lumen formation in three-dimensional spheroid cultures. We established a suspension-based culture method suitable for generating polarized cysts in sufficient quantities for proteomic analysis. Using this approach, we identified several known and unknown proteins proximally associated with PAR6B, an apical protein involved in lumen formation. Functional analyses of candidates identified PARD3B (a homolog of PARD3), RALB, and HRNR as regulators of lumen formation. We also identified PTPN14 as a component of the Par-complex that is required for fidelity of apical-basal polarity. Cells transformed with KRASG12V exhibit lumen collapse/filling concomitant with disruption of the Par-complex and down-regulation of PTPN14. Enforced expression of PTPN14 maintained the lumen and restricted the transformed phenotype in KRASG12V-expressing cells. This represents an applicable approach to explore protein-protein interactions in three-dimensional culture and to identify proteins important for lumen maintenance in normal and oncogene-expressing cells.

2.
Front Med (Lausanne) ; 8: 734812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631751

RESUMO

Background: The aim of this study was to determine the effect of Facebook remote live-streaming-guided exercise on the functional fitness of community-dwelling older adults. Method: This study used a non-randomized controlled design with single-blinding (outcome assessors). Older adults (mean age = 70.36 ± 4.51 years) were assigned to either the experimental group (n = 39) or the control group (n = 34). The experimental group participated in a 75-min Facebook remote live-streaming-guided exercise routine twice a week for 8 weeks at home, whereas the control group maintained their original lifestyle without any intervention. Functional fitness was assessed using the Senior Fitness Test, which assessed upper and lower limb flexibility and muscle strength, cardiorespiratory fitness, and balance. The test was administered before and after the intervention. Results: The results revealed that an 8-week Facebook remote live-streaming-guided exercise intervention increased lower limb flexibility and muscle strength and cardiorespiratory fitness in community-dwelling older adults. Conclusion: The current findings suggest that a home-based exercise program using the Facebook platform may be a feasible method to broadly improve the functional fitness of community-dwelling older adults.

3.
Cell Death Discov ; 7(1): 275, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608124

RESUMO

Apoptosis induced by doxorubicin, bortezomib, or paclitaxel, targeting DNA, 26S proteasome, and microtubules respectively, was assessed in two osteosarcoma cells, p53 wild-type U2OS and p53-null MG63 cells. Doxorubicin-induced apoptosis only occurred in U2OS, not in MG63. In contrast, bortezomib and paclitaxel could drive U2OS or MG63 toward apoptosis effectively, suggesting that apoptosis induced by bortezomib or paclitaxel is p53-independent. The expressions of Bcl2 family members such as Bcl2, Bcl-xl, and Puma could be seen in U2OS and MG63 cells with or without doxorubicin, bortezomib, or paclitaxel treatment. In contrast, another member, Bim, only could be observed in U2OS, not in MG63, under the same conditions. Bim knockdown did not affect the doxorubicin-induced apoptosis in U2OS, suggested that a BH3-only protein other than Bim might participate in apoptosis induced by doxorubicin. Using a BH3-mimetic, ABT-263, to inhibit Bcl2 or Bcl-xl produced a limited apoptotic response in U2OS and MG63 cells, suggesting that this BH3-mimetic cannot activate the Bax/Bak pathway efficiently. Significantly, ABT-263 enhanced doxorubicin- and bortezomib-induced apoptosis synergistically in U2OS and MG63 cells. These results implied that the severe cellular stress caused by doxorubicin or bortezomib might be mediated through a dual process to control apoptosis. Respectively, doxorubicin or bortezomib activates a BH3-only protein in one way and corresponding unknown factors in another way to affect mitochondrial outer membrane permeability, resulting in apoptosis. The combination of doxorubicin with ABT-263 could produce synergistic apoptosis in MG63 cells, which lack p53, suggesting that p53 has no role in doxorubicin-induced apoptosis in osteosarcoma. In addition, ABT-263 enhanced paclitaxel to induce moderate levels of apoptosis.

4.
Int J Gen Med ; 14: 3961-3969, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349545

RESUMO

Objective: The aim of the present study was to explore related clinical pregnancy outcome factors in intrauterine insemination (IUI). Materials and Methods: The clinical data of 3984 IUI cycles in 1862 couples experiencing infertility who attended the Reproductive Center of Binzhou Medical University Hospital between July 2006 and July 2017 were retrospectively analyzed. Female and male patient age, endometrial thickness (EMT), the post-wash total motile sperm count (PTMC), artificial insemination timing, insemination frequency, and ovarian stimulation protocols were compared between the study's pregnant group and non-pregnant group in order to explore any correlation. Results: There were statistically significant differences in female and male age, EMT, artificial insemination timing, insemination frequency, and ovarian stimulation protocols between the two groups (p < 0.05). The clinical pregnancy rate was significantly higher in ovarian stimulation cycles than in natural cycles (21.2% and 11.6%, respectively; p < 0.01), the clinical pregnancy rate was significantly higher in double IUI than in single IUI (17.8% and 12.1%, respectively; p < 0.01), and EMT was significantly greater in the pregnant group than in the control group (p < 0.05). However, the differences in clinical pregnancy rates among the PTMC groups were not statistically significant (14.8%, 14.4%, 17.3%, and 17.3%, respectively; p > 0.05). Conclusion: The results of the present study demonstrate that the clinical IUI pregnancy rate is correlated with the factors of female age, male age, EMT, artificial insemination timing, insemination frequency, and ovarian stimulation protocols; the ovarian stimulation protocol can noticeably improve the patient pregnancy outcome. Furthermore, compared with single IUI, double IUI can significantly increase the clinical pregnancy rate.

5.
Ther Adv Drug Saf ; 12: 20420986211027096, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349976

RESUMO

Objectives: The aim of this study was to conduct a meta-analysis to assess the clinical safety of ceftolozane-tazobactam for the treatment of acute bacterial infections in adult patients. Methods: The PubMed, Embase, and Cochrane databases were searched from their inception until May 2020 for relevant randomized controlled trials (RCTs). Only RCTs evaluating the risk of adverse events (AEs) for ceftolozane-tazobactam and comparative treatments for acute bacterial infections in adult patients were included. Results: Overall, four RCTs including a total of 2924 patients (1475 in the ceftolozane-tazobactam group and 1449 in the control group) were included in the meta-analysis. The rate of treatment-emergent AEs was 51.3% (748/1458) in the ceftolozane-tazobactam group, which was comparable to the control group, 49.9% [714/1430; odd's ratio (OR), 1.06; 95% confidence interval (CI), 0.91-1.25; I 2 = 0%]. In addition, no difference was observed between the ceftolozane-tazobactam and control groups in terms of the risk of serious AEs (OR, 1.22; 95% CI, 0.93-1.61; I 2 = 15.5%) and the risk of discontinuing the study drug due to AEs (OR, 0.85; 95% CI, 0.55-1.33; I 2 = 0%). The rate of all-cause mortality did not significantly differ between the ceftolozane-tazobactam and control groups (OR, 1.11; 95% CI, 0.82-1.50; I 2 = 0%). The only exception was the risk of Clostridiodes difficile (C. difficile) colitis, where ceftolozane-tazobactam treatment was associated with a significantly higher risk compared with the control group [0.72% (10/1376) versus 0.14% (2/1391), OR, 3.84; 95% CI, 1.23-11.97; I 2 = 0%]. Conclusion: Ceftolozane-tazobactam treatment is as tolerable as comparative treatment options for acute bacterial infections in adult patients, however it has an increased risk of C. difficile infection. As a novel broad-spectrum antibiotic, ceftolozane-tazobactam could be a safe therapeutic option for use in common clinical practice. Plain language summary: The safety of ceftolozane-tazobactam (an antibiotics) for the treatment of acute bacterial infections Objective(s): Ceftolozane-tazobactam is an effective antibiotic for the treatment of acute bacterial infections. This study conducts a meta-analysis to assess the clinical safety (side effects) of ceftolozane-tazobactam for the treatment of acute bacterial infections in adult patients compared with other drugs. Methods: We extracted data from four randomized controlled trials, including a total of 2924 patients (1475 in the ceftolozane-tazobactam group and 1449 in the control group). Results: The rate of treatment related adverse events (AEs) was similar in the ceftolozane-tazobactam group (51.3%) and control group (49.9%). There was also no difference in risk of serious adverse events, the risk of discontinuing the study drug due to AEs, and all-cause mortality. The only exception was the risk of Clostridiodes difficile colitis (a cause of antibiotic-associated diarrhea), where ceftolozane-tazobactam treatment was associated with a significantly higher risk compared with the control group. Conclusion: In conclusion, as a novel broad-spectrum antibiotic, ceftolozane-tazobactam could be a safe therapeutic option for use in clinical practice.

6.
J Transl Med ; 19(1): 355, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404433

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking. METHODS: Fourteen cytokines and chemokines mRNA were detected in urinary extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ. RESULTS: The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model. CONCLUSIONS: Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.


Assuntos
Quimiocina CCL21 , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Vesículas Extracelulares , Animais , Aquaporina 2 , Biomarcadores , Quimiocina CCL21/genética , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/genética , Humanos , RNA Mensageiro/genética , Ratos
7.
Nat Commun ; 12(1): 4697, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349123

RESUMO

Polarized epithelial cells can organize into complex structures with a characteristic central lumen. Lumen formation requires that cells coordinately orient their polarity axis so that the basolateral domain is on the outside and apical domain inside epithelial structures. Here we show that the transmembrane aminopeptidase, CD13, is a key determinant of epithelial polarity orientation. CD13 localizes to the apical membrane and associates with an apical complex with Par6. CD13-deficient cells display inverted polarity in which apical proteins are retained on the outer cell periphery and fail to accumulate at an intercellular apical initiation site. Here we show that CD13 is required to couple apical protein cargo to Rab11-endosomes and for capture of endosomes at the apical initiation site. This role in polarity utilizes the short intracellular domain but is independent of CD13 peptidase activity.


Assuntos
Antígenos CD13/metabolismo , Polaridade Celular , Células Epiteliais/citologia , Epitélio/crescimento & desenvolvimento , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antígenos CD13/química , Antígenos CD13/genética , Células CACO-2 , Membrana Celular/metabolismo , Endocitose , Endossomos/metabolismo , Células Epiteliais/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Domínios Proteicos , Proteínas rab de Ligação ao GTP/metabolismo
8.
Cancer Lett ; 520: 160-171, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265398

RESUMO

Nuclear translocation regulated by phosphorylation is a key step in providing activated mitogen-activated protein kinases (MAPKs) access to their nuclear targets; however, the mechanisms linking MAPK-induced nuclear translocation and target gene expression mediating oncologic activity remain obscure. Here, we show that the MAPK extracellular signal-regulated kinase (ERK) 1, but not ERK2, phosphorylated intestine-specific homeobox (ISX), leading to its nuclear translocation and downstream oncogenic signaling. Mechanistically, ERK1 phosphorylated serine 183 of ISX, facilitating its nuclear translocation and downstream target gene expression. In contrast, dominant-negative ERK1 expression in hepatoma cells inhibited the nuclear translocation of ISX and the expression of downstream genes involved in cell proliferation, malignant transformation, and epithelial-mesenchymal transition in vitro and in vivo. An activating mutation in ISX (S183D) exhibited a constitutive nuclear localization and resistance to sorafenib. Additionally, in 576 paired clinical hepatocellular carcinoma (HCC) samples and adjacent normal tissues, ERK1 and ISX were co-expressed in a tumor-specific manner at mRNA and protein levels, while their mRNA levels showed significant correlation with survival duration, tumor size, number, and stage. These results highlight the significance of ERK1/ISX signaling in HCC progression and its potential as a prognostic and therapeutic target in HCC.

9.
Zhen Ci Yan Jiu ; 46(6): 480-5, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34190451

RESUMO

For a long time, Chinese medicine has attached great importance to "pulse diagnosis for patients before acupuncture treatment", which emphasizes the close relationship between pulse diagnosis and acupuncture. Pulse diagnosis information is closely related to acupuncture research and runs through the whole process of diagnosis and treatment. However, the lack of repeatable and quantifiable real-time detection means of pulse diagnosis information has affected the application of pulse diagnosis in acupuncture research. Photo plethysmo graphy (PPG) technology has the advantages of convenient acquisition, low price, non-invasive, easy to use and so on. Under the guidance of TCM diagnosis theory, this paper discussed the principle and characteristics of fingertip volumetric pulse wave, studied its relationship with Cunkou pulse diagnosis, developed a new fingertip blood volumetric pulse wave measuring instrument, explored the acquisition and measurement methods of volumetric pulse wave signal, and proposed the relationship between the measuring instrument and acupuncture research. It can provide basic tools and data analysis and support for acupuncture research.


Assuntos
Terapia por Acupuntura , Moxibustão , Frequência Cardíaca , Humanos , Medicina Tradicional Chinesa
10.
Cancer Med ; 10(16): 5545-5556, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34173348

RESUMO

Epigenetic regulation is important for cancer tumor metastasis and progression, including lung and liver cancer. However, the mechanism of epigenetic regulation in liver cancer leaves much to be discussed. According to a previous study, p300/CBP-associated factor (PCAF) mediated epithelial-mesenchymal transition (EMT) and promotes cancer metastasis by recruiting intestine-specific homeobox (ISX) and bromodomain-containing protein 4 (BRD4) in lung cancer. To figure out whether the three genes are also expressed in patients with hepatocellular carcinoma (HCC) or not, and their correlation with patients' outcome, BRD4, PCAF, and ISX messenger RNA (mRNA) expression levels in 377 patients with HCC were investigated using quantitative polymerase chain reaction and confocal fluorescence imaging. The correlation of the gene expression (PCAF, ISX, and BRD4) in liver cancer is also being investigated. Here, we show that the mRNA expression of PCAF, BRD4, and ISX in 377 paired specimens from patients with HCC, and the adjacent normal tissues exhibited a tumor-specific expression pattern, highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. The results show that ISX and BRD4 can potentially be a target for improving the survival rate.

11.
Arch Public Health ; 79(1): 108, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34144712

RESUMO

BACKGROUND: Falls among older adults are a serious public health problem. Many studies indicate that positive functional fitness performance decreases the risk of falls. A limited amount of previous study has investigated the association between broad functional fitness and the fall risk. This study examines the associations between functional fitness and the risk of falling among community-dwelling older adults. METHODS: Three waves of cross-sectional data were collected from 2017 to 2019 in Taipei City, Taiwan. Six hundred sixty-five participants aged ≥65 years were randomly recruited from 12 districts of Taipei. Eight functional fitness tests (i.e., back scratch, chair-sit and-reach, 8-ft up-and-go, 30-s sit-to-stand, 30-s arm curl, 30-s single-leg stance, 2-min step, and hand grip strength tests) were performed to record the physical performance of older subjects. A Chinese version of the fall-risk questionnaire (FRQ) was used to calculate the fall risk scores. Linear regression and logistic regression were utilized to estimate the relationships of each functional fitness and fall risk. RESULT: The results showed that 37.45% of older adults had a high risk of falling. It was found for each functional fitness that performance was linearly associated with the risk of falling. Moreover, older adults with low-performance levels in all functional fitness except back-scratching were more likely to have a higher risk of falling. CONCLUSIONS: Our study indicated that functional fitness performance appears to provide valid predictive guidance for reducing the risk of falling among the older population.

12.
Antonie Van Leeuwenhoek ; 114(7): 933-945, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33864545

RESUMO

A nitrogen-fixing isolate of facultatively anaerobic, marine bacterium, designated strain NFV-1T, was recovered from the lagoon sediment of Dongsha Island, Taiwan. It was a Gram-negative rod which exhibited motility with monotrichous flagellation in broth cultures. The strain required NaCl for growth and grew optimally at about 25-35 °C, 3% NaCl and pH 7-8. It grew aerobically and could achieve anaerobic growth by fermenting D-glucose or other carbohydrates as substrates. NH4Cl could serve as a sole nitrogen source for growth aerobically and anaerobically, whereas growth with N2 as the sole nitrogen source was observed only under anaerobic conditions. Cellular fatty acids were predominated by C16:1 ω7c, C16:0, and C18:1 ω7c. The major polar lipids consisted of phosphatidylethanolamine and phosphatidylserine. Strain NFV-1T had a DNA G + C content of 42.5 mol%, as evaluated according to the chromosomal DNA sequencing data. Analyses of sequence similarities and phylogeny based on the 16S rRNA genes, together with the housekeeping genes, gyrB, ftsZ, mreB, topA and gapA, indicated that the strain formed a distinct species-level lineage in the genus Vibrio of the family Vibrionaceae. These phylogenetic data and those from genomic and phenotypic characterisations support the establishment of a novel Vibrio species, for which the name Vibrio nitrifigilis sp. nov. (type strain NFV-1T = BCRC 81211T = JCM 33628T) is proposed.


Assuntos
Nitrogênio , Vibrio , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/análise , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vibrio/genética
13.
Autophagy ; : 1-16, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853474

RESUMO

We propose that beyond its role in WNT secretion, WLS/GPR177 (wntless, WNT ligand secretion mediator) acts as an essential regulator controlling protein glycosylation, endoplasmic reticulum (ER) homeostasis, and dendritic cell (DC)-mediated immunity. WLS deficiency in bone marrow-derived DCs (BMDCs) resulted in poor growth and an inability to mount cytokine and T-cell responses in vitro, phenotypes that were irreversible by the addition of exogenous WNTs. In fact, WLS was discovered to integrate a protein complex in N-glycan-dependent and WLS domain-selective manners, comprising ER stress sensors and lectin chaperones. WLS deficiency in BMDCs led to increased ER stress response and macroautophagy/autophagy, decreased calcium efflux from the ER, and the loss of CALR (calreticulin)-CANX (calnexin) cycle, and hence protein hypo-glycosylation. Consequently, DC-specific wls-null mice were unable to develop both Th1-, Th2- and Th17-associated responses in the respective autoimmune and allergic disease models. These results suggest that WLS is a critical chaperone in maintaining ER homeostasis, glycoprotein quality control and calcium dynamics in DCs.Abbreviations: ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; ATG16L1: autophagy related 16 like 1; ATP2A1/SERCA1: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1; BALF: bronchoalveolar lavage fluid; BFA: brefeldin A; BMDC: bone marrow-derived dendritic cell; CALR: calreticulin; CANX: calnexin; CCL2/MCP-1: C-C motif chemokine ligand 2; CNS: central nervous system; CT: C-terminal domain; DTT: dithiothreitol; DNAJB9/ERDJ4: DnaJ heat shock protein family (Hsp40) member B9; EAE: experimental autoimmune encephalomyelitis; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; GFP: green fluorescent protein; HSPA5/GRP78/BiP: heat shock protein A5; IFNA: interferon alpha; IFNAR1: interferon alpha and beta receptor subunit 1; IFNB: interferon beta; IFNG/INFγ: interferon gamma; IFNGR2: interferon gamma receptor 2; IL6: interleukin 6; IL10: interleukin 10; IL12A: interleukin 12A; IL23A: interleukin 23 subunit alpha; ITGAX/CD11c: integrin subunit alpha X; ITPR1/InsP3R1: inositol 1,4,5-trisphosphate receptor type 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; OVA: ovalbumin; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PLF: predicted lipocalin fold; PPP1R15A/GADD34: protein phosphatase 1 regulatory subunit 15A; RYR1/RyanR1: ryanodine receptor 1, skeletal muscle; SD: signal domain; TGFB/TGF-ß: transforming growth factor beta family; Th1: T helper cell type 1; Th17: T helper cell type 17; TM: tunicamycin; TNF/TNF-α: tumor necrosis factor; UPR: unfolded protein response; WLS/wntless: WNT ligand secretion mediator.

14.
Hum Cell ; 34(3): 785-799, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33683656

RESUMO

Club cells are critical in maintaining airway integrity via, in part, secretion of immunomodulatory Club cell 10 kd protein (CC10) and xenobiotic detoxification. Aryl hydrocarbon receptor (AhR) is important in xenobiotic metabolism, but its role in Club cell function is unclear. To this end, an AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ, 10 nM) was found to induce, in a ligand and AhR-dependent manner, endoplasmic reticulum stress, phospholipid remodeling, free fatty acid and triglyceride synthesis, leading to perilipin 2-dependent lipid droplet (LD) biogenesis in a Club cell-like cell line, NL20. The increase in LDs was due, in part, to the blockade of adipose triglyceride lipase to LDs, while perilipin 5 facilitated LDs-mitochondria connection, leading to the breakdown of LDs via mitochondrial ß-oxidation and acetyl-coA generation. In FICZ-treated cells, increased CC10 secretion and its intracellular association with LDs were noted. Administration of low (0.28 ng), medium (1.42 ng), and high (7.10 ng) doses of FICZ in C57BL/6 mice significantly enhanced lipopolysaccharide (LPS, 0.1 µg)-induced airway inflammation, mucin secretion, pro-inflammatory cytokines and CC10 in the bronchoalveolar lavage fluids, as compared to those seen in mice receiving LPS alone, suggesting the importance of AhR signaling in controlling the metabolic homeostasis and functions of Club cells.


Assuntos
Células Epiteliais/metabolismo , Gotículas Lipídicas/metabolismo , Receptores de Hidrocarboneto Arílico/fisiologia , Sistema Respiratório/citologia , Animais , Carbazóis/farmacologia , Linhagem Celular , Humanos , Inativação Metabólica , Ligantes , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Perilipina-1/farmacologia , Transdução de Sinais/fisiologia , Uteroglobina/metabolismo , Xenobióticos/metabolismo
15.
J Int Med Res ; 49(3): 300060521994925, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33729859

RESUMO

OBJECTIVE: To investigate the relationship between peroxisome proliferator-activated receptor gamma (PPARγ) mRNA, serum adiponectin (ADP) and lipids in paediatric patients with Kawasaki disease (KD). METHODS: This prospective study enrolled paediatric patients with KD and grouped them according to the presence or absence of coronary artery lesions (CAL). A group of healthy age-matched children were recruited as the control group. The levels of PPARγ mRNA, serum ADP and lipids were compared between the groups. Receiver operating characteristic (ROC) curve analysis was undertaken to determine if the PPARγ mRNA level could be used as a predictive biomarker of CAL prognosis. RESULTS: The study enrolled 42 patients with KD (18 with CAL [CAL group] and 24 without CAL [NCAL group]) and 20 age-matched controls. PPARγ mRNA levels in patients with KD were significantly higher than those in the controls; but significantly lower in the CAL group than the NCAL group. ROC curve analysis demonstrated that the PPARγ mRNA level provided good predictive accuracy for the prognosis of CAL. There was no association between PPARγ, ADP and lipid levels. CONCLUSION: There was dyslipidaemia in children with KD, but there was no correlation with PPARγ and ADP. PPARγ may be a predictor of CAL in patients with KD with good predictive accuracy.


Assuntos
Síndrome de Linfonodos Mucocutâneos , PPAR gama , Adiponectina/genética , Criança , Vasos Coronários , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/genética , PPAR gama/genética , Estudos Prospectivos
16.
Commun Biol ; 4(1): 371, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742081

RESUMO

Metabolic plasticity enables cancer cells to switch between glycolysis and oxidative phosphorylation to adapt to changing conditions during cancer progression, whereas metabolic dependencies limit plasticity. To understand a role for the architectural environment in these processes we examined metabolic dependencies of cancer cells cultured in flat (2D) and organotypic (3D) environments. Here we show that cancer cells in flat cultures exist in a high energy state (oxidative phosphorylation), are glycolytic, and depend on glucose and glutamine for growth. In contrast, cells in organotypic culture exhibit lower energy and glycolysis, with extensive metabolic plasticity to maintain growth during glucose or amino acid deprivation. Expression of KRASG12V in organotypic cells drives glucose dependence, however cells retain metabolic plasticity to glutamine deprivation. Finally, our data reveal that mechanical properties control metabolic plasticity, which correlates with canonical Wnt signaling. In summary, our work highlights that the architectural and mechanical properties influence cells to permit or restrict metabolic plasticity.


Assuntos
Plasticidade Celular , Metabolismo Energético , Células Epiteliais/metabolismo , Neoplasias/metabolismo , Células A549 , Aminoácidos/metabolismo , Células CACO-2 , Técnicas de Cultura de Células , Proliferação de Células , Células Epiteliais/patologia , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Glicólise , Humanos , Células MCF-7 , Metabolômica , Mutação , Neoplasias/genética , Neoplasias/patologia , Fosforilação Oxidativa , Fenótipo , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Tempo , Microambiente Tumoral , Via de Sinalização Wnt
17.
J Inflamm Res ; 14: 299-311, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33574691

RESUMO

Background: Club cells play an important role in maintaining lung homeostasis and aryl hydrocarbon receptor (AhR) is known to be important in xenobiotic metabolism, but its role in regulating club cells is currently unknown. Methods: To this end, mice with club cell-specific AhR deficiency were generated and evaluated in a model of antigen (ovalbumin, OVA)-induced airway inflammation for the number of infiltrating inflammatory cells, the levels of cytokines and CC10 and Notch signaling by standard methods. Results: After OVA sensitization and challenge, Scgb1a1-Cre; Ahrflox/flox mice showed aggravated levels of pulmonary inflammation with increased levels of inflammatory cells and cytokines 1 day after challenge as compared to those seen in their littermate controls, but in contrast to the littermate controls, no significant change in the levels of CC10 and SP-D was noted in Scgb1a1-Cre; Ahrflox/flox mice. Surprisingly, 7 days after the challenge, while, as expected, wild-type mice recovered from acute inflammation, significantly increased lymphocytic infiltration was noted in Scgb1a1-Cre; Ahrflox/flox mice, suggesting their defective mechanism of recovery. Mechanistically, this was due, in part, to the decreased Notch1 signaling and expression of its downstream gene, HES5, while AhR was shown to positively regulate Notch1 expression via its transactivating activity targeting the xenobiotic response element in the promoter region of Notch1 gene. Conclusion: Under the condition of pulmonary inflammation, AhR is critical in controlling lung club cell homeostasis via targeting Notch1 signaling and the generation of anti-inflammatory mediators.

18.
Cell Commun Signal ; 19(1): 9, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33478523

RESUMO

BACKGROUND: To investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors. METHODS: The BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts. RESULTS: LA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate. CONCLUSION: LA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC. Video Abstract.

19.
Cell Prolif ; 54(3): e12980, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33502070

RESUMO

Chronic kidney disease (CKD) is a severe health problem worldwide, and vascular calcification (VC) contributes substantially to the cardiovascular morbidity and high mortality of CKD. CKD is often accompanied by a variety of pathophysiological states, such as inflammation, oxidative stress, hyperglycaemia, hyperparathyroidism and haemodynamic derangement, that can cause injuries to smooth muscle cells (SMCs) and endothelial cells (ECs) to promote VC. Similar to SMCs, whose role has been widely explored in VC, ECs may contribute to VC via osteochondral transdifferentiation, apoptosis, etc. In addition, given their location in the innermost layer of the blood vessel lumen and preferential reception of various pro-calcification stimuli, ECs can pass messages to vascular wall cells and communicate with them. Crosstalk between ECs and SMCs via cytokines through a paracrine mechanism, extracellular vesicles, miRNAs and myoendothelial gap junctions also plays a role in VC. In this review, we emphasize the role of intercellular crosstalk between ECs and SMCs in VC associated with CKD.


Assuntos
Células Endoteliais/metabolismo , Músculo Liso Vascular/metabolismo , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismo , Animais , Calcificação Fisiológica/fisiologia , Células Endoteliais/patologia , Humanos , Miócitos de Músculo Liso/citologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Calcificação Vascular/complicações
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