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1.
Front Pharmacol ; 15: 1359632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606171

RESUMO

Camellia oleifera is a medicine food homology plant widely cultivated in the Yangtze River Basin and southern China due to its camellia oil. Camellia oleifera bud and fruit exist simultaneously, and its bud is largely discarded as waste. However, C. oleifera bud has been used in traditional Chinese medicine to treat a variety of ailments. Thus, the purpose of this study was to identify the chemical components of C. oleifera bud ethanol extract (EE) and first evaluate its anticancer effects in non-small cell lung cancer A549 cells. Based on UHPLC-Q-Orbitrap-MS analysis, seventy components were identified. For anticancer activity, C. oleifera bud EE had remarkable cytotoxic effect on non-small cell lung cancer A549 (IC50: 57.53 ± 1.54 µg/mL) and NCI-H1299 (IC50: 131.67 ± 4.32 µg/mL) cells, while showed lower cytotoxicity on non-cancerous MRC-5 (IC50 > 320 µg/mL) and L929 (IC50: 179.84 ± 1.08 µg/mL) cells. It dramatically inhibited the proliferation of A549 cells by inducing cell cycle arrest at the G1 phase. Additionally, it induced apoptosis in A549 cells through a mitochondria-mediated pathway, which decreased mitochondrial membrane potential, upregulated Bax, activated caspase 9 and caspase 3, and resulted in PARP cleavage. Wound healing and transwell invasion assays demonstrated that C. oleifera bud EE inhibited the migration and invasion of A549 cells in a dose-dependent manner. The above findings indicated that C. oleifera bud EE revealed notable anticancer effects by inhibiting proliferation, inducing apoptosis, and suppressing migration and invasion of A549 cells. Hence, C. oleifera bud ethanol extract could serve as a new source of natural anticancer drugs.

2.
BMB Rep ; 57(2): 123, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38416114

RESUMO

[Retraction to: BMB Rep. 2022 June 30; 55(6): 299-304.] Retraction: "Inhibition of ClC-5 suppresses proliferation and induces apoptosis in cholangiocarcinoma cells through the Wnt/ß-catenin signaling pathway," by Zhe Shi, Liyuan Zhou, Yan Zhou, Xiaoyan Jia, Xiangjun Yu, Xiaohong An and Yanzhen Han, BMB Rep. 2022; 55(6) 299-304: The above article, published online on 30 June 2022 in BMB Reports https://doi.org/10.5483/ BMBRep.2022.55.6.044), has been retracted by agreement between the authors and the journal's Editor in Chief. The authors unable to replicate certain results presented in the article and have therefore made the difficult decision to withdraw it. Editorial Board, BMB Reports.

3.
Cereb Cortex ; 34(1)2024 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-37997466

RESUMO

Blood proteins are emerging as potential biomarkers for mild traumatic brain injury (mTBI). Molecular pathology of mTBI underscores the critical roles of neuronal injury, neuroinflammation, and vascular health in disease progression. However, the temporal profile of blood biomarkers associated with the aforementioned molecular pathology after CT-negative mTBI, their diagnostic and prognostic potential, and their utility in monitoring white matter integrity and progressive brain atrophy remain unclear. Thus, we investigated serum biomarkers and neuroimaging in a longitudinal cohort, including 103 CT-negative mTBI patients and 66 matched healthy controls (HCs). Angiogenic biomarker vascular endothelial growth factor (VEGF) exhibited the highest area under the curve of 0.88 in identifying patients from HCs. Inflammatory biomarker interleukin-1ß and neuronal cell body injury biomarker ubiquitin carboxyl-terminal hydrolase L1 were elevated in acute-stage patients and associated with deterioration of cognitive function from acute-stage to 6-12 mo post-injury period. Notably, axonal injury biomarker neurofilament light (NfL) was elevated in acute-stage patients, with higher levels associated with impaired white matter integrity in acute-stage and progressive gray and white matter atrophy from 3- to 6-12 mo post-injury period. Collectively, our findings emphasized the potential clinical value of serum biomarkers, particularly NfL and VEGF, in diagnosing mTBI and monitoring disease progression.


Assuntos
Concussão Encefálica , Humanos , Concussão Encefálica/diagnóstico por imagem , Fator A de Crescimento do Endotélio Vascular , Proteínas de Neurofilamentos , Progressão da Doença , Biomarcadores , Atrofia/patologia , Tomografia Computadorizada por Raios X , Encéfalo/diagnóstico por imagem , Encéfalo/patologia
5.
Int Immunopharmacol ; 115: 109732, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37724958

RESUMO

BACKGROUND: Failures in invasive extravillous trophoblasts (EVTs) migration into the maternal uterus have been noticed in preeclampsia (PE). Human umbilical cord mesenchymal stem cell (hUCMSC)-derived extracellular vesicles (EVs) have been highlighted for the role as a potential therapeutic method in PE. This study intends to investigate the mechanistic basis of hUCMSCs-derived EVs loaded with bioinformatically identified TFCP2 in the activities of EVTs of PE. METHODS: Primary human EVTs were exposed to hypoxic/reoxygenation (H/R) to mimic the environment encountered in PE. The in vivo PE-like phenotypes were induced in mice by reduced uterine perfusion pressure (RUPP) surgery. CCK-8, Transwell and flow cytometry assays were performed to detect proliferation, migration, invasion and apoptosis of H/R-exposed EVTs. More importantly, EVs were extracted from hUCMSCs and transduced with ectopically expressed TFCP2, followed by co-culture with EVTs. RESULTS: TFCP2 was found to be down-regulated in the preeclamptic placental tissues and in H/R-exposed EVTs. hUCMSCs-EVs loaded with TFCP2 activated the Wnt/ß-catenin pathway, thereby promoting the proliferative, migratory, and invasive potential of EVTs. Furthermore, overexpression of TFCP2 alleviated PE-like phenotypes in mice, which was associated with activated Wnt/ß-catenin pathway. CONCLUSION: From our data we conclude that hUCMSCs-EVs overexpressing TFCP2 may be instrumental for the therapeutic targeting and clinical management of PE.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Animais , Camundongos , beta Catenina , Pré-Eclâmpsia/terapia , Placenta , Fatores de Transcrição , Hipóxia , Fatores Imunológicos , Proteínas de Ligação a DNA
6.
Anal Chim Acta ; 1275: 341567, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37524461

RESUMO

Whole-cell bacteria imprinted polymer-based sensors still face challenges in the form of the difficulty of removing the template entirely, low affinity, and poor sensitivity. To further improve their performance, it is pivotal to modulate the morphology and chemical properties of imprintied polymer by taking advantage of doping engineering. Here we introduced D-tartaric acid (D-TA) as a dopant and employed pyrrole as a functional monomer to construct D-TA/polypyrrole (PPy)-based bacteria imprinted polymer (DPBIP) sensor for Vibrio parahaemolyticus (VP) detection. It is demonstrated that D-TA doping can synergistically accelerate the removal of template bacteria from imprinted polymers (1.5 h), improve bacteria affinity of imprinted sites (the recognition time of 30 min), and enhance the sensitivity of DPBIP sensor (a detection limit of 19 CFU mL-1). The DPBIP sensor had a linear range of 102∼106 CFU mL-1 and exhibited high selectivity and good repeatability. Moreover, a recovery of 94.8%-105.3% was achieved in drinking water and oyster samples. Therefore, small functional molecules doping opens a new avenue to engineering BIP-based sensors with high performance, holding potential applications in securing food safety.


Assuntos
Impressão Molecular , Vibrio parahaemolyticus , Polímeros/química , Pirróis/química , Limite de Detecção , Técnicas Eletroquímicas
7.
J Ethnopharmacol ; 301: 115846, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36280015

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hedychium flavum, an ornamental, edible, and medicinal plant, is extensively cultivated as a source of aromatic essential oils (EO). Its flower is a traditional Chinese medicine for treating inflammation-related diseases like indigestion, diarrhea, and stomach pain. In particular, H. flavum flower EO has been used in cosmetics and as an aromatic stomachic to treat chronic gastritis in China. AIM OF THE STUDY: This research aimed to analyze H. flavum flower EO's chemical composition and explore its anti-inflammatory activities and related mechanisms in vitro and in vivo. MATERIALS AND METHODS: EO's chemical composition was determined by GC-FID/MS analysis. For in vitro test, the anti-inflammatory activity of EO was demonstrated by measuring the LPS-induced release of NO, PGE2, IL-1ß, TNF-α, and IL-6 in RAW264.7 macrophages, and then its related mechanisms were explored using qRT-PCR, western blot, and immunofluorescent staining analysis. Next, EO's in vivo anti-inflammatory potential was further evaluated using a xylene-induced ear edema model, in which ear swelling and TNF-α, IL-6, and IL-1ß levels in serum and tissue were examined. RESULTS: The main components of EO were ß-pinene (20.2%), α-pinene (9.3%), α-phellandrene (8.3%), 1,8-cineole (7.1%), E-nerolidol (5.4%), limonene (4.4%), borneol (4.1%), and ß-caryophyllene (3.7%). For the anti-inflammatory activities in vitro, EO dramatically reduced the LPS-stimulated NO and PGE2 release by suppressing the mRNA and protein expression of iNOS and COX-2. Meanwhile, it remarkably decreased IL-6, TNF-α, and IL-1ß production by inhibiting their mRNA levels. Related mechanism studies indicated that it not only inhibited IκBα phosphorylation and degradation, leading to blockade of NF-κB nuclear transfer but also suppressed MAPKs (ERK, p38, and JNK) phosphorylation in LPS-stimulated RAW264.7 cells. Further in vivo assay showed that EO ameliorated xylene-induced ear edema in mice and reduced TNF-α, IL-6, and IL-1ß levels in serum and tissue. CONCLUSIONS: H. flavum EO exerted significant anti-inflammatory activity in vivo and in vitro, and its mechanism of action is related to the inhibition of MAPK and NF-κB activation. Thus, H. flavum EO could be considered a novel and promising anti-inflammatory agent and possess high potential for utilization in the pharmaceutical field.


Assuntos
Óleos Voláteis , Zingiberaceae , Animais , Camundongos , Anti-Inflamatórios , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Flores/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Células RAW 264.7 , RNA Mensageiro , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Xilenos , Zingiberaceae/metabolismo
9.
Pharmaceuticals (Basel) ; 15(9)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36145290

RESUMO

Alpinia galanga is widely cultivated for its essential oil (EO), which has been used in cosmetics and perfumes. Previous studies of A. galanga focussed mostly on the rhizome but seldom on the flower. Therefore, this study was designed to identify the chemical composition of A. galanga flower EO and firstly estimate its antioxidant, antibacterial, enzyme inhibitory, and anticancer activities. According to the results of the gas chromatography with flame ionization or mass selective detection (GC-FID/MS) analysis, the most abundant component of the EO was farnesene (64.3%), followed by farnesyl acetate (3.6%), aceteugenol (3.2%), eugenol (3.1%), E-nerolidol (2.9%), decyl acetate (2.4%), octyl acetate (2.0%), sesquirosefuran (1.9%), (E)-ß-farnesene (1.7%), and germacrene D (1.5%). For the bioactivities, the EO exhibited moderate DPPH and ABTS radical scavenging effects with IC50 values of 138.62 ± 3.07 µg/mL and 40.48 ± 0.49 µg/mL, respectively. Moreover, the EO showed strong-to-moderate antibacterial activities with various diameter of inhibition zone (DIZ) (8.79−14.32 mm), minimal inhibitory concentration (MIC) (3.13−6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25−12.50 mg/mL) values against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris. Interestingly, the EO possessed remarkable α-glucosidase inhibition (IC50 = 0.16 ± 0.03 mg/mL), which was equivalent to that of the positive control acarbose (IC50 = 0.15 ± 0.01 mg/mL) (p > 0.05). It showed moderate tyrosinase inhibition (IC50 = 0.62 ± 0.09 mg/mL) and weak inhibitory activity on acetylcholinesterase (AChE) (IC50 = 2.49 ± 0.24 mg/mL) and butyrylcholinesterase (BChE) (IC50 = 10.14 ± 0.59 mg/mL). Furthermore, the EO exhibited considerable selective cytotoxicity to K562 cells (IC50 = 41.55 ± 2.28 µg/mL) and lower cytotoxicity to non-cancerous L929 cells (IC50 = 120.54 ± 8.37 µg/mL), and it induced K562 cell apoptosis in a dose-dependent manner. Hence, A. galanga flower EO could be regarded as a bioactive natural product with great application potential in the pharmaceutical field.

10.
BMB Rep ; 55(6): 299-304, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35651328

RESUMO

Chloride channel-5 (ClC-5), an important branch of the ClC family, is involved in the regulation of the proliferation and cell-fate of a variety of cells, including tumor cells. However, its function in cholangiocarcinoma (CCA) cells remains enigmatic. Here, we discovered that ClC-5 was up-regulated in CCA tissues and CCA cell lines, while ClC-5 silencing inhibited CCA cell proliferation and induced apoptosis. Further mechanism studies revealed that ClC-5 inhibition could inhibit Wnt/ß-catenin signaling activity and further activate the mitochondria apoptotic pathway in CCA cells. Furthermore, rescuing Wnt/ß-catenin signaling activation eliminated the anti-tumor function of ClC-5 knockdown. Together, our research findings illustrated that ClC-5 inhibition plays an anti-tumor role in CCA cells via inhibiting the activity of the Wnt/ß-catenin pathway, which in turn activates the mitochondrial apoptotic pathway. [BMB Reports 2022; 55(6): 299-304].


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Apoptose , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Proliferação de Células , Canais de Cloreto/metabolismo , Colangiocarcinoma/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo
11.
Food Sci Nutr ; 10(5): 1481-1493, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35592301

RESUMO

Grass carp (Ctenopharyngodon idellus) is one of the three most cultivated freshwater fish around the world, but it is mainly consumed afresh, so only a small part of them are processed into salted fish or snack food. This research was performed to prepare and screen antioxidant peptides from grass carp muscle to promote its high-value utilization. The parameters of double-enzyme two-step hydrolysis were optimized, the peptides with the highest ABTS.+ scavenging ability were enriched and identified by Sephadex G-25 and LC-Q-Orbitrap-MS/MS. The synergistic-antagonistic effect among identified peptides was also investigated. The optimized conditions were hydrolyzed with protamex (10,000 U/g) at pH 8.0, 50°C for 3 h, followed by hydrolysis with alcalase (6,000 U/g) at pH 9.0, 50 °C for 2 h, and the protein-liquid ratio was 4%. The hydrolysates were further fractionated to obtain five fractions, in which fraction 3 (F3) exhibited the strongest ABTS.+ and O 2 · - scavenging ability with the IC50 values of 0.11 and 0.47 mg/ml, respectively. Twelve novel antioxidant peptides were identified, in which VAGW possessed the highest activity (139.77 µmol GSH/g). Significantly synergistic effects were observed on the two and three peptides' combination among VAGW, APPAMW, LFGY, FYYGK, and LLLYK, while the C-terminal tryptophan (Trp) played an important role in the synergism. This study found that grass carp muscle hydrolysates can be potential natural antioxidants in functional products. The synergistic effects among peptides may provide a perspective for the combined application of peptides.

12.
BMC Nephrol ; 23(1): 156, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459121

RESUMO

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a bone-derived factor involved in metabolism, but also a biomarker of kidney disease and cardiovascular pathophysiology. We conducted this cross-sectional observational study to explore relationships between plasma NGAL and thoracic aorta calcification (TAC) in maintenance hemodialysis (MHD) patients with and without diabetes. METHODS: Plasma NGAL was measured by ELISA, TAC was evaluated via computed tomography scan using a 3D quantification method or chest radiography aortic arch calcification score. Spearman correlation, Logistic regression and Partial correlation analysis were used to describe the correlations between NGAL and TAC. RESULTS: Plasma NGAL levels were lower in MHD patients with diabetes compared to those without diabetes (49.33(42.37, 55.48) vs 56.78(44.37, 674.13) ng/mL, P = 0.026). In MHD patients without diabetes, lg (NGAL) was positively correlated with ARC value(R = 0.612, P = 0.003) analyzed by Spearman correlation; for partial correlation analysis, lg (NGAL) was positively correlated with ARC value, after adjusting for age and sex (R = 0.550, P = 0.015), adjusting for age, sex and CHD (R = 0.565, P = 0.015), adjusting for age, sex, CHD and Alb (R = 0.536, P = 0.027), or adjusting for age, sex, CHD, Alb, and dialyzer membrane (polysulfone) (R = 0.590, P = 0.016); however, when adjusting for age, sex, CHD, Alb and Ca, the correlation between lg (NGAL) and ARC value disappeared. Positive correlation were found between NGAL and Ca (R = 0.644, P < 0.001), Ca and ACR (R = 0.534, P = 0.013) in Spearman coefficient analysis. CONCLUSION: There were positive correlations among plasma NGAL, serum Ca and ARC in MHD patients without diabetes; which suggests that NGAL is possibly a participant in cardiovascular calcification, in non-diabetic MHD.


Assuntos
Aorta Torácica , Doenças da Aorta , Calcinose , Falência Renal Crônica , Lipocalina-2 , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/sangue , Doenças da Aorta/complicações , Doenças da Aorta/patologia , Biomarcadores , Calcinose/sangue , Calcinose/complicações , Estudos Transversais , Complicações do Diabetes , Diabetes Mellitus , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Lipocalina-2/sangue , Diálise Renal
13.
Can J Physiol Pharmacol ; 100(7): 584-593, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35413227

RESUMO

Chemotherapy is one of the most important strategies in the treatment of cancer; however, chemoresistance restricts the effect of chemotherapy. Growing reports suggest that chloride channel-3 (ClC-3) is involved in regulating the sensitivity of multiple chemotherapeutic agents in the chemotherapy of various tumours, while its role in the chemotherapy of cholangiocarcinoma (CCA) is still poorly understood. Herein, we observed that ClC-3 was highly expressed in CCA chemoresistant tissues and CCA cisplatin-resistant cells QBC939/DDP, and the sensitivities of QBC939 and QBC939/DDP cells to cisplatin were all increased after inhibition of ClC-3. Further mechanism exploration revealed that ClC-3 knockdown reduced the level of autophagy. Furthermore, in both QBC939 and QBC939/DDP cells, the autophagy agonist rapamycin eliminated the increased cisplatin sensitivity of ClC-3 knockdown without affecting ClC-3 expression. Collectively, all the findings demonstrate that ClC-3 knockdown increases cisplatin-induced cell death in CCA cells though inhibiting autophagy, regardless of the occurrence of cisplatin resistance. In addition, our results also suggest that targeted inhibition of ClC-3 may be a potential strategy for chemosensitization in CCA chemotherapy.


Assuntos
Antineoplásicos , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Antineoplásicos/farmacologia , Apoptose , Autofagia , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Canais de Cloreto , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Cisplatino/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos
14.
Am J Nephrol ; 53(2-3): 129-138, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35272286

RESUMO

INTRODUCTION: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is highly specific for primary membranous nephropathy (PMN). Here, we compare the diagnostic value of different circulating PLA2R-Ab cutoff titers in multicenter cohorts, with particular focus on determining the optimal cutoff value for Chinese patients. METHODS: In total, 288 patients with PMN and 301 with other nephropathies were recruited retrospectively from five hospitals in China between September 2011 and October 2018. PLA2R-Ab in serum obtained at renal biopsy was determined by enzyme-linked immunosorbent assay. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve of PLA2R-Ab in diagnosing PMN were assessed. Diagnostic efficiency was evaluated by internal validation. RESULTS: The sensitivity, specificity, PPV, NPV, and Youden index for PMN diagnosis were 71%, 90%, 88%, 75%, and 0.61 at the cutoff of 3.8 RU/mL; 74%, 86%, 84%, 76%, and 0.60 at 2.7 RU/mL; 68%, 92%, 90%, 73%, and 0.60 at 5.2 RU/mL; 64%, 95%, 93%, 72%, and 0.59 at 9.0 RU/mL; 57%, 96%, 94%, 68%, and 0.54 at 14.0 RU/mL; 51%, 97%, 95%, 66%, and 0.49 at 20.0 RU/mL; 47%, 98%, 96%, 64%, and 0.45 at 40.0 RU/mL, respectively. The area under the ROC curve was 0.83. CONCLUSION: By comprehensively considering specificity and sensitivity, we show that 3.8 RU/mL is the optimal cutoff of PLA2R-Ab in Chinese PMN patients, with a sensitivity of 71% and a specificity of 90%. The cutoff values were 5.2 RU/mL and 9.0 RU/mL when the diagnostic specificity was increased to 92% and 95%, respectively.


Assuntos
Glomerulonefrite Membranosa , Autoanticorpos , Ensaio de Imunoadsorção Enzimática , Humanos , Curva ROC , Receptores da Fosfolipase A2 , Estudos Retrospectivos
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 43-48, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35123602

RESUMO

OBJECTIVE: To explore the effect of age on the time of neutropenia after initial induction therapy for newly diagnosed acute myeloid leukemia (AML) patients. METHODS: Data of 18-65 years old AML patients treated in our hospital from Junuary 2015 to July 2020 were retrospectively analyzed. The clinical characteristics, time of neutropenia after initial induction treatment, early responses, and related influencing factors for the time of neutropenia were analyzed and compared between 18-40 years old group and 41-65 years old group. RESULTS: There were 112 patients enrolled in this study, including 66 (58.9%) males, and their median age was 46 years old. Compared with 18-40 years old group, the incidence of FLT3-ITD gene mutation increased (P=0.039) but core binding factor (CBF) decreased (P=0.003) significantly in 41-65 years old group. The incidence of neutropenia was 97.3%, and the average time was (18.70±1.192) days. The time of neutropenia was (21.43±1.736) days in 41-65 years old group, which was longer than (14.91±1.356) days in 18-40 years old group (P=0.006). The time of neutropenia in CBF positive group was shorter than that in negative group (P=0.012), as well as in patients with remission (CR+CRi) (≤ 2 courses) than those with non-remission (NR) (P=0.024), while in high-risk group was longer than that in low-risk group (P=0.040). Multivariate analysis showed that age, FLT3-ITD gene mutation positive, and non-remission (NR) after two courses of treatment were independent risk factors for the time of neutropenia. CONCLUSION: In non-elderly patients with newly diagnosed AML, age is an influencing factor for the time of neutropenia. Key words  ;


Assuntos
Leucemia Mieloide Aguda , Neutropenia , Adolescente , Adulto , Idoso , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms
16.
J Bone Miner Metab ; 39(6): 1058-1065, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34392464

RESUMO

INTRODUCTION: Neutrophil gelatinase-associated lipocalin (NGAL) is not only a biomarker of kidney injury but also a bone-derived factor involved in metabolism. We aimed to explore relationships between plasma NGAL and chronic kidney disease-mineral bone disorder (CKD-MBD) parameters in maintenance hemodialysis (MHD) patients. MATERIALS AND METHODS: First, a cross sectional observational study, including 105 MHD patients, was conducted to explore relationships between plasma NGAL levels and CKD-MBD parameters. Second, impact of parathyroidectomy and auto-transplantation (PTX + AT) on plasma NGAL was investigated in 12 MHD patients with severe secondary hyperparathyroidism (SHPT). RESULTS: According to Spearman correlation analysis, plasma NGAL levels were positively correlated with female (r = 0.243, P = 0.012), vintage (r = 0.290, P = 0.003), Klotho (r = 0.234, P = 0.016), calcium(Ca) (r = 0.332, P = 0.001), alkaline phosphatase (ALP) (r = 0.401, P < 0.001) and intact parathyroid hormone (iPTH) (r = 0.256, P = 0.008); while inversely correlated with albumin(Alb) (r = - 0.201, P = 0.039). After adjusting for age, sex, vintage, Alb and all parameters of CKD-MBD(Ca, P, lg(ALP), lg(iPTH), Klotho and fibroblast growth factor 23(FGF23)), lg(NGAL) were positively correlated with Ca (r = 0.481, P < 0.001), P (r = 0.336, P = 0.037), lg(ALP) (r = 0.646, P < 0.001) in Partial correlation analysis; further multiple linear regression analysis showed same positive associations between lg(NGAL) and Ca (ß = 0.330, P = 0.002), P (ß = 0.218, P = 0.037), lg(ALP) (ß = 0.671, P < 0.001). During the 4-7 days after PTX + AT, plasma NGAL decreased from 715.84 (578.73, 988.14) to 688.42 (660.00, 760.26) ng/mL (P = 0.071), Klotho increased from 496.45 (341.73, 848.30) to 1138.25 (593.87, 2009.27) pg/mL (P = 0.099). CONCLUSION: Plasma NGAL levels were positively associated with ALP in MHD patients; and downtrends were shown after PTX + AT in patients with severe SHPT. These findings suggest that NGAL is a participant in CKD-MBD under MHD condition.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica , Lipocalina-2/sangue , Insuficiência Renal Crônica , Biomarcadores , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
17.
Am J Hum Genet ; 108(1): 163-175, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33357406

RESUMO

The lack of functional evidence for the majority of missense variants limits their clinical interpretability and poses a key barrier to the broad utility of carrier screening. In Lynch syndrome (LS), one of the most highly prevalent cancer syndromes, nearly 90% of clinically observed missense variants are deemed "variants of uncertain significance" (VUS). To systematically resolve their functional status, we performed a massively parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factor MSH2. The resulting functional effect map is substantially complete, covering 94% of the 17,746 possible variants, and is highly concordant (96%) with existing functional data and expert clinicians' interpretations. The large majority (89%) of missense variants were functionally neutral, perhaps unexpectedly in light of its evolutionary conservation. These data provide ready-to-use functional evidence to resolve the ∼1,300 extant missense VUSs in MSH2 and may facilitate the prospective classification of newly discovered variants in the clinic.


Assuntos
Predisposição Genética para Doença/genética , Proteína 2 Homóloga a MutS/genética , Mutação de Sentido Incorreto/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Células HEK293 , Humanos
18.
Fish Shellfish Immunol ; 90: 264-273, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054356

RESUMO

We investigated the effects of icariin (ICA) on growth performance, antioxidant capacity and non-specific immunity in Chinese mitten crab (Eriocheir sinensis). A total of 200 healthy crabs (average weight: 33.58 ±â€¯0.05 g) were randomly assigned to four treatments with five replicates, each with ten individuals per pool. There were four dietary treatments: the control group (fed with the basal diet), the ICA 50 group, the ICA100 group, and the ICA 200 group (fed with the basal diet supplemented with 50, 100, and 200 mg/kg ICA, respectively). These diets were provided for 8 weeks. Results indicated that ICA100 crabs had higher weight gain (WG), specific growth rate (SGR) and survival rate (SR) than the controls. Protein carbonyl content (PCC) and malondialdehyde (MDA) concentrations in the haemolymph and hepatopancreas of ICA100 crabs were significantly lower than in the control group, while the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were significantly higher. The activities of PO, LZM, ACP and AKP were significantly enhanced with ICA supplementation at 50 and 100 mg/kg, yet decreased subsequently at 200 mg/kg. Furthermore, supplementation of 100 mg/kg ICA up-regulated the mRNA expression of prophenoloxidase (proPO), catalase (CAT), mitochondrial manganese superoxide dismutase (mtMnSOD), thioredoxin-1 (Trx1) and peroxiredoxin 6 (Prx6), while the mRNA expression of toll like receptors (TLRs), NF-κB-like transcription factor Relish and lipopolysaccharide-induced TNF-α factor (LITAF) were down-regulated in the hepatopancreas (P < 0.05). These findings indicate that dietary ICA supplementation at an optimum dose of 100 mg/kg may be effective in improving growth performance, antioxidant capability and non-specific immunity of Chinese mitten crab.


Assuntos
Adjuvantes Imunológicos/metabolismo , Braquiúros/imunologia , Flavonoides/metabolismo , Imunidade Inata/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Ração Animal/análise , Animais , Antioxidantes , Braquiúros/genética , Braquiúros/crescimento & desenvolvimento , Braquiúros/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Distribuição Aleatória
19.
Medicine (Baltimore) ; 98(16): e15262, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008967

RESUMO

RATIONALE: Fibroma of tendon sheath is a rare entity that is typically attached to the tendon sheath. PATIENT CONCERNS: A 43-year-old man presented with a painful mass in his right wrist, which was initially misdiagnosed as an enchondroma. DIAGNOSIS: Fibroma embedded into carpal bones, which exhibited lytic radiographic features similar to those of enchondroma. Excisional biopsy demonstrated spindle-shaped cells and collagen-like stroma. INTERVENTIONS: The patient underwent lesion resection surgery. OUTCOMES: The patient recovered well and showed no signs of recurrence at 6-month follow-up. LESSONS: This case provides valuable insights for hand surgeons. While radiograph is helpful in multiple diseases, histological examination is indispensable for establishment of final diagnosis.


Assuntos
Neoplasias Ósseas/diagnóstico , Ossos do Carpo/patologia , Condroma/diagnóstico , Fibroma/diagnóstico , Neoplasias de Tecidos Moles/diagnóstico , Tendões , Adulto , Ossos do Carpo/diagnóstico por imagem , Ossos do Carpo/cirurgia , Diagnóstico Diferencial , Erros de Diagnóstico , Fibroma/diagnóstico por imagem , Fibroma/patologia , Fibroma/cirurgia , Humanos , Masculino , Radiografia , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Tendões/diagnóstico por imagem , Tendões/patologia , Tendões/cirurgia
20.
Technol Cancer Res Treat ; 18: 1533033819831989, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30885065

RESUMO

PURPOSE: To analyze and study the short-term therapeutic effects and main adverse effects of 2 Porphyrin photosensitizer-mediated photodynamic therapy for esophageal cancer. METHODS: We apply the hematoporphyrin derivative and hematoporphyrin injection produced by different manufacturers at different periods as photosensitizers in therapy of 79 esophageal cancer cases, with the administration dosage of 5 mg/kg and intravenous drip 24 hours before irradiation. We apply the gold vapor laser and semiconductor laser, respectively, as treatment light source, with the power density of 100 to 300 mW/cm2 and energy density of 100 to 300 J/cm2. After treatment for 1 to 4 sessions, we evaluate the short-term therapeutic effects as complete response, partial response, minor response, or no change, and then make comparative study on therapeutic effects and adverse effects. RESULTS: There were 47 patients in hematoporphyrin derivative group, including 3 (6.4%) patients with complete response, 31 (66.0%) patients with partial response, 10 (21.3%) patients with minor response, and 3 (6.4%) patients with no change. The dysphagia score was reduced from 2.53 (1.16) before treatment to 1.32 (1.20; P < .01) after treatment. There were 32 patients in the hematoporphyrin injection group, including 3 (9.4%) patients with complete response, 19 (59.4%) patients with partial response, 6 (18.8%) patients with minor response, and 4 (12.5%) patients with no change. The dysphagia score was reduced from 2.41 (1.13) before treatment to 1.18 (0.99; P < .01) after treatment. The dysphagia scores of 2 groups after treatment were significantly reduced compared to those before treatment. Both groups did not display serious adverse effect. CONCLUSIONS: Two porphyrin photosensitizers in treatment of esophageal cancer at different clinical stages all had good effect with similar therapeutic effect, mild adverse effect, and good tolerance, which implies it is a preferable palliative therapy means.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/terapia , Hematoporfirinas , Terapia a Laser , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
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