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1.
Front Pharmacol ; 12: 730241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721022

RESUMO

G-749 is an FLT3 kinase inhibitor that was originally developed as a treatment for acute myeloid leukemia. Some FLT3 kinase inhibitors are dual kinase inhibitors that inhibit the TAM (Tyro3, Axl, Mer) receptor tyrosine kinase family and are used to treat solid cancers such as non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). AXL promotes metastasis, suppression of immune response, and drug resistance in NSCLC and TNBC. G-749, a potential TAM receptor tyrosine kinase inhibitor, and its derivative SKI-G-801, effectively inhibits the phosphorylation of AXL at nanomolar concentration (IC50 = 20 nM). This study aimed to investigate the anticancer effects of G-749 targeting the TAM receptor tyrosine kinase in colon cancer. Here, we demonstrate the potential of G-749 to effectively inhibit tumorigenesis by degrading TYRO3 via regulated intramembrane proteolysis both in vitro and in vivo. In addition, we demonstrated that G-749 inhibits the signaling pathway associated with cell proliferation in colon cancer cell lines HCT15 and SW620, as well as tumor xenograft mouse models. We propose G-749 as a new therapeutic agent for the treatment of colon cancer caused by abnormal TYRO3 expression or activity.

2.
Retina ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34743130

RESUMO

PURPOSE: To investigate the correlation of foveal photoreceptor integrity with the vessel density (VD) of the retina and choriocapillaris using swept-source optical coherence tomography (OCT) angiography (OCTA) in eyes with diabetic retinopathy (DR). METHODS: We retrospectively reviewed subjects having eyes with DR, who underwent OCTA using swept-source OCT (DRI OCT Triton; Topcon). We analyzed the area of the foveal avascular zone (FAZ) and VDs of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris. The length of the lateral extent of ellipsoid zone (EZ) disruption, central subfield thickness, and subfoveal choroidal thickness were measured. Furthermore, we analyzed factors that were closely associated with the length of EZ disruption. RESULTS: A total of 159 eyes with DR and 30 healthy control eyes were included in this study. In all eyes, the lengths of EZ disruption were positively correlated with the FAZ area (P=0.009). However, they were negatively correlated with the parafoveal VD of the SCP (P=0.049), the foveal VD of DCP (P=0.003), and that of the choriocapillaris (P=0.036). CONCLUSIONS: The size of the FAZ and ischemia at the DCP may play an important role in maintaining foveal photoreceptor integrity in eyes with DR. Considering OCTA artifacts, such as projection and shadowing, future studies are required to reveal the correlation between EZ disruption and the VD of the choriocapillaris.

3.
Phytomedicine ; 93: 153811, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735908

RESUMO

BACKGROUND: The immune-enhancing effects of red Platycodon grandiflorus root extract (RPGE) has been reported in vitro and in vivo, but there are few studies on humans. Therefore, this study aimed to investigate the efficacy and safety of RPGE in enhancing immune function in healthy subjects. SUBJECTS AND METHODS: An 8-week randomized, double-blind, parallel, placebo-controlled clinical trial was conducted at the Gachon University Gil Medical Center, Incheon, South Korea. A total of 100 adults aged 20-75 years with white blood cell counts of 3000-10,000 cell/µL were randomly divided into two groups (RPGE group, 50 and placebo group, 50) using a computer-generated random list with a 1:1 allocation ratio. The subjects consumed RPGE (2 times/day, 2 tablets/time, 375 mg RPGE powder/tablet) or placebo for 8 weeks. All test foods for the human study were coded and administered under double-blind conditions. The primary outcome was a change in the NK cell activity after 8 weeks of treatment compared to the baseline. RESULTS: Among 100 subjects enrolled for the study, 87 completed the study. NK cell activity (p = 0.005) and IFN-γ level (p = 0.003) of the RPGE group (n = 41) were higher than those of the placebo group (n = 46). The findings of the safety assessment revealed absence of clinically significant changes in any test and serious adverse events throughout the study. CONCLUSION: In conclusion, these results demonstrate the efficacy and safety of RPGE, suggesting it to be a beneficial agent for enhancing immune function in humans. TRIAL REGISTRATION: CRIS Registration Number KCT0005945, https://cris.nih.go.kr.


Assuntos
Platycodon , Método Duplo-Cego , Humanos , Imunidade , Extratos Vegetais/farmacologia , República da Coreia , Resultado do Tratamento
4.
Sci Rep ; 11(1): 21556, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732810

RESUMO

The purpose of this study was to investigate whether sex differences in visceral fat volume and glucose uptake measured by positron emission tomography/computed tomography (PET/CT) in abdominal visceral fat can stratify overall survival (OS) in patients with colorectal cancer (CRC). We retrospectively enrolled 293 patients diagnosed with CRC who underwent PET/CT before surgical resection. Fluorodeoxyglucose uptake of visceral adipose tissue (VAT-SUV) and subcutaneous adiposity tissue (SAT-SUV) were measured using PET/CT. The relative VAT (rVAT) was defined as the visceral fat volume normalized to the total volume of fat (VAT plus SAT). We defined sex-specific cutoff values for VAT-SUV, SAT-SUV, and rVAT. Univariate and multivariate analyses using Cox proportional hazard regression analysis were performed to identify the independent prognostic factors. The study population comprised 181 men and 112 women. The rVAT (0.40 vs. 0.29, p < 0.001) and VAT-SUV (0.55 vs. 0.48, p = 0.007) were significantly greater in men than in women. High rVAT (than low rVAT) and high VAT-SUV (than low VAT-SUV) showed a worse prognosis in male and female patients, respectively. Multivariate analysis indicated that the combination of rVAT and VAT-SUV was an independent prognostic factor for predicting OS in both male and female patients. The combination of rVAT and VAT-SUV could differentiate the patients with the best survival outcome from the other three individual groups in female patients, but not in males. Glucose uptake and relative volume of visceral fat may provide a new risk stratification for patients with CRC, especially female patients.

5.
Cancer Med ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643052

RESUMO

BACKGROUND: Although skeletal muscle index (SMI) and radiodensity (SMD) are well-known prognostic factors, the clinical impact of the integrated measure, known as skeletal muscle gauge (SMG), has been limited in patients with colorectal cancer (CRC). PATIENTS AND METHODS: A total of 727 and 268 patients with CRC at two tertiary centers were included and allocated into the training and test sets, respectively. Preoperative slice computed tomography images of the third lumbar area were evaluated for SMI and SMD. SMG was calculated as SMI × SMD and expressed as an arbitrary unit (AU). The optimal cutoff SMG value was determined to maximize the overall survival (OS) difference between the groups with respect to sex in the training set. The multivariate Cox proportional hazard model evaluated the association of its clinical significance. RESULTS: With regard to SMG, 1640 and 1523 AU were identified as cutoff values for males and females, respectively. The patients with low SMG values showed significantly worse 5-year OS than those with high SMG values in the two datasets (both p < 0.001). In the multivariate analysis, low SMG was identified as an independent poor prognostic factor of OS in the training set (hazard ratio 2.18, 95% confidence interval 1.43-3.32, p < 0.001) and test set (hazard ratio 1.79, 95% confidence interval 1.07-3.00, p = 0.025), whereas SMI and SMD were not. CONCLUSION: SMG acts synergistically to improve its prognostic predictive accuracy as compared with SMI or SMD alone in patients with CRC. Additional research is warranted to define its significance in different ethnic groups.

6.
Antioxidants (Basel) ; 10(10)2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34679767

RESUMO

Sarcopenic obesity is a combination of sarcopenia and obesity. Although several herbal extracts showed improvement on sarcopenia and obesity, respectively, there are few studies on sarcopenic obesity. Lonicera caerulea (honeysuckle berry, HB) can ameliorate metabolic disorders including obesity. However, its effects on sarcopenic obesity have not been reported yet. Thus, the aim of this study was to investigate whether HB extract might have any beneficial effects on sarcopenic obesity in high-fat diet-induced mice. Forty-eight mice were classified into six groups and treated for eight weeks: (1) NC, normal diet control; (2) HC, high-fat diet control; (3) PC, high-fat diet with orlistat; (4) HB100, high-fat diet with HB extract at 100 mg/kg; (5) HB200, high-fat diet with HB extract at 200 mg/kg; and (6) HB400, high-fat diet with HB extract at 400 mg/kg. Body weight, fat accumulation, muscle mass, muscle strength, and mRNA expression of muscle atrophy were monitored. Compared with the HC group, HB administration showed anti-obesity properties. It reduced body weight gain and modulated serum biochemical parameters and tissue antioxidant enzymes. HB also increased muscle strength and muscle mass of hind legs. In addition, it decreased mRNA expression levels of Atrogin1 and MuRF1 as markers of muscle atrophy but increased PGC1α and SIRT1 as markers of muscle growth. These results suggest that HB might be effective in preventing sarcopenia associated with obesity.

7.
Ann Coloproctol ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34657410

RESUMO

Purpose: This study aimed to investigate the clinicopathologic features and survival in patients with both breast cancer (BrC) and colorectal cancer (CRC). Methods: Between 1996 and 2019, patients who were diagnosed with both BrC and CRC were evaluated retrospectively. Patients with distant metastasis, palliative resection, and previous cancer histories except for BrCs or CRCs were excluded. Altogether, 105 patients were divided into the B=C group (n=21), B-first group (n=40), and C-first group (n=44) according to the definition of synchronous and metachronous cancers. The clinicopathologic features and overall survival were evaluated. Results: TNM stages and histologic types were comparable among the 3 groups (P=0.434). The interval of diagnosis was 67.1±40.4 and 59.3±47.2 months in the B- and C-first groups, respectively. The incidence of adjuvant chemotherapy in the B-first group was 57.5%, which was higher than the B=C and C-first groups (P<0.001). The estrogen receptor, progesterone receptor, Ki-67, and HER-2 molecular markers were not significantly different among the groups. The overall survival of the B-first group showed lower survival rates than the C-first group (P=0.039). In the logistic regression, HER-2 status (hazard ratio [HR], 11.9; P=0.032) and lymph node metastasis of CRC (HR, 5.8; P=0.036) were prognostic factors affecting overall survival. Conclusion: B-first group had poorer survival outcomes than the C-first group in patients with the metachronous BrC and CRC. HER2 positivity and CRC lymph node metastasis may be prognostic factors that affect overall survival in these patients. The findings support that a colorectal cancer screening program should be included during BrC surveillance.

8.
Ann Surg Oncol ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665362

RESUMO

BACKGROUND: Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS). However, MMC has a side effect of myelosuppression. This study aimed to evaluate the clinical manifestations and impact of MMC-induced neutropenia after CRS and HIPEC in colorectal cancer patients. METHODS: A total of 124 colorectal cancer patients who underwent CRS with HIPEC between March 2015 and January 2019 were evaluated. Patients with malignancies of non-colorectal origin, hospital stay longer than 60 days, peritoneal cancer index > 30, and complete cytoreduction score > 2 were excluded. MMC 35 mg/m2 was administered for 90 min at 41-43 °C. The patients were divided into three groups: no neutropenia, mild neutropenia (grade 1-2), and severe neutropenia (grade 3-4). RESULTS: In total, mild and severe neutropenia occurred in 30 (24.2%) and 48 (38.7%) patients, respectively. Age and body surface area were significantly different among the neutropenia groups. Severe neutropenia developed significantly earlier than mild neutropenia (6.9 days vs. 10.4 days, p < 0.001) and also lasted significantly longer (4.6 days vs. 2.5 days, p = 0.005). The rate of major postoperative complications was significantly higher in the severe neutropenia group than in the no and mild neutropenia groups (8.3% vs. 6.7% vs. 6.5%, p = 0.015) CONCLUSIONS: Severe neutropenia starts earlier and lasts longer than mild neutropenia after CRS and HIPEC using an MMC triple method. The higher rate of major postoperative complications in patients with severe neutropenia highlights the importance of postoperative management during the neutropenia period.

9.
Cancer Res Treat ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34665954

RESUMO

Purpose: The clinical significance of body mass index (BMI) on long-term outcomes has not been extensively investigated in Asian patients with colorectal cancer (CRC). This study aims to describe the association between BMI and survival, plus providing BMI cut-off value for predicting prognosis in CRC patients. Materials and Methods: A total of 1,182 patients who had undergone surgery for stage I-III CRC from June 2004 to February 2014 were included. BMI was categorized into four groups based on the recommendation for Asian ethnicity. The optimal BMI cut-off value was determined to maximize overall survival (OS) difference. Results: In multivariable analysis, underweight BMI was significantly associated with poor OS (hazard ratio [HR] = 2.38, 95% confidence interval [CI] = 1.55-3.71, p<0.001) and obese BMI was associated with better OS (HR = 0.72, 95% CI = 0.53-0.97, p=0.036) compared with the normal BMI. Overweight and obese BMI were associated with better recurrence-free survival (RFS) (HR = 0.64, 95% CI = 0.42-0.99, p=0.046; HR = 0.58, 95% CI = 0.38-0.89, p=0.014, respectively) compared with the normal BMI group. BMI cut-off value was 20.44 kg/m2. Adding the BMI cut-off value to cancer staging could increase discriminatory performance in terms of integrated area under the curve and Harrell's concordance index. Conclusion: Compared to normal BMI, underweight BMI was associated with poor survival whereas obese BMI was associated with better survival. BMI cut-off value of 20.44 kg/m2 is a useful discriminator in Asian patients with CRC.

10.
Clin Nutr ; 40(11): 5631-5638, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34662848

RESUMO

BACKGROUND: Although different body composition including fat adiposity has known to be associated with survival in patients with colorectal cancer (CRC), the clinical significance was inconsistent. We investigated prognostic impact of visceral and subcutaneous fat adiposity in patients with CRC after surgical resection. MATERIAL AND METHODS: This retrospective single center study included 987 stage I-III CRC patients (583 males, and 404 females) who underwent surgical resection between March 2005 and April 2014. Preoperative diagnostic computed tomography images were used to quantify visceral fat area (VFA) and subcutaneous fat area (SFA). The sex-specific optimal cut-off value for body fat composition was defined using the X-tile program. The Cox proportional hazards model was used to determine the correlation fat composition and disease-free survival (DFS). Harrell's concordance index (C-index) and integrated area under curve (iAUC) were used to evaluate the predictive ability of cut-derived stratification. RESULTS: In univariate analysis, high SFA (≥141.73 cm2 in males and ≥168.71 cm2 in females) and high VFA (≥174.38 cm2 in male and ≥83.65 cm2 in female) were identified as significant prognostic factors for better DFS (p = .001 and p = .003 respectively). However, multivariate analysis revealed that high SFA independently predicted longer DFS (HR 0.505; 95% CI 0.266-0.957; p = .036) whereas, high VFA did not (HR 0.656; 95% CI 0.402-1.071; p = .092). Combining stage and SFA-cutoff showed better discriminatory performance than the model using stage solitary with respect to C-index (0.667; 95% CI 0.623-6.711; p = .0098) and iAUC (0.601; 95% CI 0.556-0.620). CONCLUSION: High SFA was correlated with better DFS in patients with CRC. Subcutaneous fat can have additive predictive capability when incorporated into clinical decision-making.

11.
Mol Ther Oncolytics ; 23: 138-150, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34703882

RESUMO

CD200 is known as an immune checkpoint molecule that inhibits innate immune cell activation. Using a head and neck squamous cell carcinoma (HNSCC) model, we sought to determine whether localized delivery of adenovirus-expressing sCD200R1-Ig, the soluble extracellular domain of CD200R1, enhances antitumor immunity. Mouse-derived bone marrow cells and M1/M2-like macrophages were cocultured with tumor cells and analyzed for macrophage polarization. As an in vivo model, C57BL/6 mice were subcutaneously injected with MEER/CD200High cells, CD200-overexpressing mouse HNSCC cells. Adenovirus-expressing sCD200R1-Ig (Ad5sCD200R1) was designed, and its effect was tested. Components in the tumor-immune microenvironment (TIME) were quantified using flow cytometry. CD200 promoted tumor growth and induced the expression of immune-related genes, especially macrophage colony-stimulating factor (M-CSF). Interestingly, CD200 induced M2-like polarization both in vitro and in vivo. Consequently, CD200 recruited more regulatory T (Treg) cells and fewer CD8+ effector T cells. These effects were effectively abolished by local injection of Ad5sCD200R1. These protumor effects of CD200 were driven through the ß-catenin/NF-κB/M-CSF axis. CD200 upregulated PD-L1, and the combined targeting of CD200 and PD-1 thus showed synergy. The immune checkpoint CD200 upregulated immune-related genes through ß-catenin signaling, reprogrammed the TIME, and exerted protumor effects. Ad5sCD200R1 injection could be an effective targeted strategy to enhance antitumor immunoediting.

13.
Front Nutr ; 8: 644406, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568400

RESUMO

Lemon (Citrus limon Burm. f.) is one of the most widely produced and consumed fruits in the world. The seeds of lemon are generally discarded as waste. The purpose of this study was to investigate the quality characteristics and antioxidant potential of lemon seed oil obtained by four extraction methods (roasted-pressing at 170°C, RP-170; roasted-pressing at 100°C, RP-100; cold-pressing, CP; and supercritical fluid, SF). No significant differences in the viscosity, density, and refractive index were observed in the oil obtained from different methods. In the case of Hunter's value, L (lightness) and b (yellowness) values of SF were higher than those of the others. The oil obtained by the CP method exhibited higher levels of Ca (252.17 mg/kg), Cu (2.38 mg/kg), K (225.98 mg/kg), and Mo (0.47 mg/kg) than that of other methods. The highest contents of total phenols (165.90 mg/mL) and flavonoids (21.69 mg/mL) were significantly high in oil obtained by the SF method. Oleic and linoleic acids consisted of principal fatty acids, which were significantly higher in oil obtained by RP-170. Higher amounts of volatile flavor compounds, such as γ-terpinene, sabinene, and limonene, were observed in CP compared to those observed for the other methods. This study elucidates the effects of different methods of oil extraction on the composition of lemon seed oil and highlights potential applications of these benefits in the food, cosmetic, pharmaceutical, and/or fragrance industries.

14.
Medicina (Kaunas) ; 57(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34577876

RESUMO

Background and Objectives: Hyperuricemia is associated with several comorbidities. The association between uric acid (UA) and pulmonary function is still a controversial issue. This study evaluated the gender-specific association of serum UA and pulmonary function. Materials and Methods: A total of 3177 (weighted n = 19,770,902) participants aged 40 years or older were selected from the 2016 Korean National Health and Nutrition Examination Survey and included. Results: Female participants with hyperuricemia were older than participants with normouricemia. Body mass index (BMI), mean arterial pressure (MAP), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) were significantly associated with UA levels in both males and females. Hyperuricemia and increase in UA quartile were significantly associated with decreased forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in females after adjustment for age, income, region, education, marital status, alcohol consumption, smoking, BMI, MAP, HbA1c, and eGFR. There was no significant association between UA levels and lung function in males. After additional adjustment for respiratory disease including pulmonary tuberculosis, asthma, and lung cancer, the association between hyperuricemia and decreased FEV1 and FVC in females was revealed. Conclusions: Hyperuricemia was associated with decreased FVE1 and FVC in the female general population.


Assuntos
Pulmão , Ácido Úrico , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Inquéritos Nutricionais , República da Coreia/epidemiologia
15.
J Inflamm Res ; 14: 4457-4466, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522115

RESUMO

Background: Recent data suggest that alterations in the neutrophil-to-lymphocyte ratio (NLR) in the perioperative periods can serve as prognostic factors. However, research on the clinical impact has been limited and even discordant in patients with colorectal cancer (CRC). Patients and Methods: The optimal cut-off value of preoperative NLR (NLR-pre), postoperative NLR (NLR-post), and its change (NLR-delta) were determined to maximize differences in overall survival (OS) between groups. Patients were categorized into four groups (NLR-trend) as follows: G1, low NLR-pre and NLR-post; G2, low NLR-pre and high NLR-post; G3, high NLR-pre and low NLR-post; and G4, high NLR-pre and NLR-post. Discriminatory performance was compared using integrated AUC (iAUC) between all indicators. Results: A total of 576 patients diagnosed with stage I-IV CRC were included. The cut-off points were determined as 2.33 for NLR-pre, 2.06 for NLR-post, and -1.08 for NLR-delta. Subgroup dichotomization using NLR-pre, NLR-post, NLR-delta and NLR-trend were all identified as significant prognostic factors by univariate analysis. However, NLR-trend was only remained as an independent prognostic factor in the multivariate analysis. The iAUC of the NLR-trend was superior to that of NLR-pre (bootstrap iAUC mean difference=0.036; 95% CI 0.013-0.073), NLR-post (bootstrap iAUC mean difference=0.045; 95% CI 0.019-0.081) and NLR-delta (bootstrap iAUC mean difference=0.061; 95% CI 0.025-0.104). Conclusion: Risk stratification and combining of preoperative and postoperative NLR (NLR-trend) can improve prognostic discrimination compared with single measurements or simple changes in NLR in patients with CRC.

16.
Nanotoxicology ; 15(8): 1087-1101, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34469701

RESUMO

In our previous study, 20 nm-sized amorphous silica nanoparticles (20-SiNPs), but not 50 nm-sized amorphous silica nanoparticles (50-SiNPs), induced pulmonary inflammatory response in rats exposed repeatedly for 14 days (12.5, 25, and 50 µg/time, total six times). In this study, we tried to clarify the causes of different responses induced by both SiNPs using mice (12.5, 25, and 50 µg/lung) and mouse alveolar macrophage cells. When exposed to alveolar macrophage cells for 24 h, both SiNPs decreased cell viability and enhanced ROS generation compared to controls. The 20- and 50-SiNPs also formed giant and autophagosome-like vacuoles in the cytoplasm, respectively. Structural damage of organelles was more pronounced in 20-SiNPs-treated cells than in 50-SiNPs-treated cells, and an increased mitochondrial membrane potential and mitochondrial calcium accumulation were observed only in the 20-SiNPs-treated cells. Additionally, a single intratracheal instillation of both sizes of SiNPs to mice clearly elevated the relative proportion of neutrophils and inhibited differentiation of macrophages and expression of an adhesion molecule. Meanwhile, interestingly, the total number of pulmonary cells and the levels of pro-inflammatory mediators more notably increased in the lungs of mice exposed to 20-SiNPs compared to 50-SiNPs. Given that accumulation of giant vacuoles and dilation of the ER and mitochondria are key indicators of paraptosis, we suggest that 20-SiNPs-induced pulmonary inflammation may be associated with paraptosis of alveolar macrophages.

17.
J Clin Med ; 10(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34362167

RESUMO

Early and precise neurological prognostication without self-fulfilling prophecy is challenging in post-cardiac arrest syndrome (PCAS), particularly during the targeted temperature management (TTM) period. This study aimed to investigate the feasibility of vasomotor reactivity (VMR) using transcranial Doppler (TCD) to determine whether final outcomes of patients with comatose PCAS are predicted. This study included patients who had out-of-hospital cardiac arrest in a tertiary referral hospital over 4 years. The eligible criteria included age ≥18 years, successful return of spontaneous circulation, TTM application, and bedside TCD examination within 72 h. Baseline demographics and multimodal prognostic parameters, including imaging findings, electrophysiological studies, and TCD-VMR parameters, were assessed. The final outcome parameter was cerebral performance category scale (CPC) at 1 month. Potential determinants were compared between good (CPC 1-2) and poor (CPC 3-5) outcome groups. The good outcome group (n = 41) (vs. poor (n = 117)) showed a higher VMR value (54.4% ± 33.0% vs. 25.1% ± 35.8%, p < 0.001). The addition of VMR to conventional prognostic parameters significantly improved the prediction power of good outcomes. This study suggests that TCD-VMR is a useful tool at the bedside to evaluate outcomes of patients with comatose PCAS during the TTM.

18.
Toxics ; 9(7)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203397

RESUMO

Although cigarette smoking has been postulated to be a potential risk factor for Alzheimer's disease (AD), the toxic mechanism is still unclear. Additionally, astrocytes have been identified as a potential target, given they play multiple roles in maintaining normal brain function. In this study, we explored the toxic mechanism of whole cigarette smoke condensates (WCSC) using murine astrocytes. Cell proliferation, the percentage of cells in the G2/M phase, and LDH concentrations in the cell supernatants were all reduced in WCSC-treated cells. In addition, oxidative stress was induced, together with shortening of processes, structural damage of organelles, disturbances in mitochondrial function, blockage of autophagic signals, accumulation of amyloid ß precursor protein, and loss of chemotactic functions. Based on these results, we hypothesize that dysfunction of astrocytes may contribute to the occurrence of cigarette-smoking-induced AD.

19.
J Vet Sci ; 22(4): e53, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34170094

RESUMO

BACKGROUND: Canine adipose-derived stem cells (cADSCs) exhibit various differentiation properties and are isolated from the canine subcutaneous fat. Although cADSCs are valuable as tools for research on adipogenic differentiation, studies focusing on adipogenic differentiation methods and the underlying mechanisms are still lacking. OBJECTIVES: In this study, we aimed to establish an optimal method for adipogenic differentiation conditions of cADSCs and evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) and estrogen receptor (ER) signaling in the adipogenic differentiation. METHODS: To induce adipogenic differentiation of cADSCs, 3 different adipogenic medium conditions, MDI, DRI, and MDRI, using 3-isobutyl-1-methylxanthine (M), dexamethasone (D), insulin (I), and rosiglitazone (R) were tested. RESULTS: MDRI, addition of PPARγ agonist rosiglitazone to MDI, was the most significantly facilitated cADSC into adipocyte. GW9662, an antagonist of PPARγ, significantly reduced adipogenic differentiation induced by rosiglitazone. Adipogenic differentiation was also stimulated when 17ß-estradiol was added to MDI and DRI, and this stimulation was inhibited by the ER antagonist ICI182,780. CONCLUSIONS: Taken together, our results suggest that PPARγ and ER signaling are related to the adipogenic differentiation of cADSCs. This study could provide basic information for future research on obesity or anti-obesity mechanisms in dogs.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Cães , Hipoglicemiantes/farmacologia , Rosiglitazona/farmacologia , Células-Tronco/fisiologia , Adipogenia , Animais , Células Cultivadas , Estrogênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , Células-Tronco/efeitos dos fármacos
20.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073834

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid ß-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos/metabolismo , Lipogênese/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores Purinérgicos P2Y2/metabolismo , Acetil-CoA Carboxilase/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Peso Corporal , Antígenos CD36/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Dieta Hiperlipídica , Ácido Graxo Sintases/metabolismo , Insulina/sangue , Resistência à Insulina/fisiologia , Lipase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Obesos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Obesidade/metabolismo , Receptores Purinérgicos P2Y2/deficiência , Receptores Purinérgicos P2Y2/genética , Estearoil-CoA Dessaturase/metabolismo
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