Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.977
Filtrar
1.
Front Cell Neurosci ; 16: 971100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072565

RESUMO

This study aimed to explore the mechanism underlying cognitive dysfunction mediated by the lateral hypothalamic area (LHA) in a hypothalamic-hippocampal circuit in rats with lesion-induced hypothalamic obesity (HO). The HO model was established by electrically lesioning the hypothalamic nuclei. The open field (OP) test, Morris water maze (MWM), novel object recognition (NOR), and novel object location memory (NLM) tests were used to evaluate changes in cognition due to alterations in the hypothalamic-hippocampal circuit. Western blotting, immunohistochemical staining, and cholera toxin subunit B conjugated with Alexa Fluor 488 (CTB488) reverse tracer technology were used to determine synaptophysin (SYN), postsynaptic density protein 95 (PSD95), ionized calcium binding adaptor molecule 1 (Iba1), neuronal nuclear protein (NeuN), and Caspase3 expression levels and the hypothalamic-hippocampal circuit. In HO rats, severe obesity was associated with cognitive dysfunction after the lesion of the hypothalamus. Furthermore, neuronal apoptosis and activated microglia in the downstream of the lesion area (the LHA) induced microglial infiltration into the intact hippocampus via the LHA-hippocampal circuit, and the synapses engulfment in the hippocampus may be the underlying mechanism by which the remodeled microglial mediates memory impairments in HO rats. The HO rats exhibited microglial infiltration and synapse loss into the hippocampus from the lesioned LHA via the hypothalamic-hippocampal circuit. The underlying mechanisms of memory function may be related to the circuit.

2.
Pathol Oncol Res ; 28: 1610504, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061144

RESUMO

Objectives: This study aimed to identify a molecular marker associated with the prognosis of non-small-cell lung cancer (NSCLC). Materials and Methods: The RNA sequencing data and clinical information of NSCLC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The weighted gene co-expression network analysis (WGCNA) was used to identify the co-expression gene modules and differentially expressed genes (DEGs) by comparing gene expression between NSCLC tumor tissues and normal tissues. Subsequently, the functional enrichment analysis of the DEGs was performed. Kaplan-Meier survival analysis and the GEPIA2 online tool were performed to investigate the relationship between the expression of these genes of interest and the survival of NSCLC patients, and to validate one most survival-relevent hub gene, as well as validated the hub gene using independent datasets from the GEO database. Further analysis was carried out to characterize the relationship between the hub gene and tumor immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and other known biomarkers of lung cancer. The related genes were screened by analyzing the protein-protein interaction (PPI) network and the survival model was constructed. GEPIA2 was applied in the potential analysis of pan-cancer biomarker of hub gene. Results: 57 hub genes were found to be involved in intercellular connectivity from the 779 identified differentially co-expressed genes. Myeloid-associated differentiation marker (MYADM) was strongly associated with overall survival (OS) and disease-free survival (DFS) of NSCLC patients, and high MYADM expression was associated with poor prognosis. Thus, MYADM was identified as a risk factor. Additionally, MYADM was validated as a survival risk factor in NSCLC patients in two independent datasets. Further analysis showed that MYADM was nagetively associated with TMB, and was positively correlated with macrophages, neutrophils, and dendritic cells, suggesting its role in regulating tumor immunity. The MYADM expression differed across many types of cancer and had the potential to serve as a pan-cancer marker. Conclusion: MYADM is an independent prognostic factor for NSCLC patients, which can predict the progression of cancer and play a role in the tumor immune cell infiltration in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígenos de Diferenciação , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Prognóstico
3.
Clin Genet ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071563

RESUMO

Hereditary spherocytosis (HS) is a prevalent inherited hemolytic disorder primarily reported in Caucasians. Recently, next-generation sequencing (NGS) techniques have shown tremendous potential in the diagnosis of HS. HS commonly originates from variants in ANK1, SPTB, SLC4A1, SPTA1, and EPB42. This review is focused on thirteen previous clinical studies on genotype-phenotype correlation, which might promote the role of causative variants in the diagnosis and prognosis of HS. Most studies were focused on the pediatric population and Asian countries. The occurrence of novel variants was common in each cohort, and variants with a high frequency of causative genes were demonstrated. In conclusion, patients with variants in SPTA1 and SLC4A1 were reported to have more severe and milder anemia, respectively. ANK1 and SPTB are the most common variants in patients with HS, and no significant difference in phenotypes was observed between patients with variants in ANK1 vs SPTB. The types and locations of variants might influence the phenotype of each genotype, whereas the roles of concomitant pathogenic genes and the source of variants deserve further investigation.

4.
Anim Cells Syst (Seoul) ; 26(4): 192-202, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046029

RESUMO

Excessive mechanical traction damages the levator ani muscle (LAM), increasing the incidence of pelvic floor dysfunction (PFD). In this study, we explored the effects of oxidized nicotinamide adenine dinucleotide (NAD+) on the damage to both muscle cells and LAM tissue induced by mechanical stress (MS) at the cellular and animal levels. The cell damage model was established using a four-point bending system. The LAM damage model was established using vaginal distention and traction. Exogenous addition of PJ34, an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), and the nicotinamide mononucleotide (NMN) precursor of NAD+ increased NAD+ levels. ATP content and mitochondrial membrane potential were measured to assess mitochondrial function. NAD+ levels, cell viability, and PARP-1 activity were detected using commercial kits. DNA damage in cells was detected with immunofluorescence staining, and LAM damage was detected with tissue TUNEL staining. PARP-1 activity and DNA damage of LAM were detected by immunohistochemistry. A small amount of DNA damage and PARP-1 activation did not affect NAD+ levels, while excessive DNA damage and PARP-1 activation led to an imbalance of NAD+ homeostasis. Furthermore, increasing NAD+ levels in vivo and in vitro could rescue mitochondrial dysfunction and damage to both muscle cells and LAM tissue induced by MS. In conclusion, MS can induce damage to both C2C12 cells and LAM tissue. Restoring NAD+ homeostasis can rescue this damage by improving mitochondrial function.

6.
J Natl Compr Canc Netw ; 20(9): 1013-1021.e3, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075387

RESUMO

BACKGROUND: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. METHODS: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. RESULTS: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (P<.001). Daily NRS from day 1 to day 6 and patient satisfaction scores on day 3 and day 6 were worse in arm B. Median equivalent-morphine consumption increase was significantly lower in A1 (P=.024) among the 3 arms. No severe adverse event occurred in any arm. CONCLUSIONS: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.


Assuntos
Dor Irruptiva , Dor do Câncer , Neoplasias , Analgesia Controlada pelo Paciente , Analgésicos Opioides , Dor Irruptiva/tratamento farmacológico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/etiologia , Humanos , Hidromorfona/efeitos adversos , Morfina/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Medição da Dor
7.
Neurocrit Care ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36114315

RESUMO

BACKGROUND: Whether insulin resistance underlies deep venous thrombosis (DVT) development in patients with severe traumatic brain injury (TBI) is unclear. In this study, the association between plasma insulin levels and DVT was analyzed in patients with severe TBI. METHODS: A prospective observational study of 73 patients measured insulin, glucose, glucagon-like peptide 1 (GLP-1), inflammatory factors, and hematological profiles within four preset times during the first 14 days after TBI. Ultrasonic surveillance of DVT was tracked. Two-way analysis of variance was used to determine the factors that discriminated between patients with and without DVT or with and without insulin therapy. Partial correlations of insulin level with all the variables were conducted separately in patients with DVT or patients without DVT. Factors associated with DVT were analyzed by multivariable logistic regression. Neurological outcomes 6 months after TBI were assessed. RESULTS: Among patients with a mean (± standard deviation) age of 53 (± 16 years), DVT developed in 20 patients (27%) on median 10.4 days (range 4-22), with higher Acute Physiology and Chronic Health Evaluation II scores but similar Sequential Organ Failure Assessment scores and TBI severity. Patients with DVT were more likely to receive insulin therapy than patients without DVT (60% vs. 28%; P = 0.012); hence, they had higher 14-day insulin levels. However, insulin levels were comparable between patients with DVT and patients without DVT in the subgroups of patients with insulin therapy (n = 27) and patients without insulin therapy (n = 46). The platelet profile significantly discriminated between patients with and without DVT. Surprisingly, none of the coagulation profiles, blood cell counts, or inflammatory mediators differed between the two groups. Patients with insulin therapy had significantly higher insulin (P = 0.006), glucose (P < 0.001), and GLP-1 (P = 0.01) levels and were more likely to develop DVT (60% vs. 15%; P < 0.001) along with concomitant platelet depletion. Insulin levels correlated with glucose, GLP-1 levels, and platelet count exclusively in patients without DVT. Conversely, in patients with DVT, insulin correlated negatively with GLP-1 levels (P = 0.016). Age (P = 0.01) and elevated insulin levels at days 4-7 (P = 0.04) were independently associated with DVT. Patients with insulin therapy also showed worse Glasgow Outcome Scale scores (P = 0.001). CONCLUSIONS: Elevated insulin levels in the first 14 days after TBI may indicate insulin resistance, which is associated with platelet hyperactivity, and thus increasing the risk of DVT.

9.
Hematology ; 27(1): 977-986, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36053135

RESUMO

OBJECTIVES: Multiple myeloma (MM) is an incurable plasma cell malignancy associated with poor survival. Novel therapeutic drugs are urgently needed to improve MM therapy and patient outcomes. This study aimed to investigate the effect of formosanin C (FC), a Chinese medicine monomer, on MM in vitro and disclose the underlying molecular mechanism. METHODS: The effect of FC on the viability, proliferation, apoptosis, and autophagy of MM cell lines (NCI-H929 and ARP1) was studied through CCK-8, colony formation, flow cytometry, GFP-LC3, and western blotting assays, respectively. A pharmacological approach and network pharmacology technology were implemented to explore the potential mechanisms of the action of FC on MM cells. RESULTS: FC efficiently suppressed the viability and colony-forming capacity, but promoted the number of autophagic vacuoles with GFP-LC3 localization and the percentage of apoptotic cells in MM cells. Additionally, FC significantly increased the levels of the autophagy-related proteins LC3-Ⅱ and Beclin 1, as well as the apoptosis-related proteins Bax and cleaved caspase-3, but blocked the expression of the proapoptotic protein Bcl-2 in the cells; these effects were reversed by an inhibitor of autophagy, 3-methyladenine. What's more, we found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was involved in the FC-mediated inhibition of MM. Pharmacological inhibition of this pathway dramatically relieved FC-triggered excessive expression of autophagy-related proteins and rescued MM cells from FC-induced apoptosis. CONCLUSION: Our findings indicate that FC exhibits an anti-MM effect by activating cell autophagy through the PI3K/AKT/mTOR signaling pathway.


Assuntos
Mieloma Múltiplo , Proteínas Proto-Oncogênicas c-akt , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteínas Relacionadas à Autofagia/farmacologia , Linhagem Celular Tumoral , Diosgenina/análogos & derivados , Humanos , Mieloma Múltiplo/tratamento farmacológico , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
10.
ACS Appl Mater Interfaces ; 14(37): 42113-42122, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36074742

RESUMO

Low-valence titanium sulfides (LVTS) have metal-like electrical conductivities and a strong polysulfide binding abilities, which are promising anodes for sodium ion batteries with high capacities and long cycle lifes. However, it is difficult for traditional synthesis methods to synthesize LVTS without impurities. The electric field regulation method possesses the advantages of flexibility and high efficiency, achieving accurate control of the metal reduction process by adjusting the electrolysis potential and reaction time. In this work, we synthesized a series of LVTS (TiS and Ti2S) using electric field control methods and investigated their electrochemical behaviors as sodium storage anodes for the first time. Compared with traditional TiS2, LVTS display remarkable Na storage properties under the condition of complete electrochemical conversion at 0.005-3 V. Especially for TiS, it demonstrates a high capacity of 409 mAh g-1 at 1 A g-1 and inspiring cyclic stability over 6000 cycles. The large number of vacancies in the crystal structure can chemically anchor polysulfides and alleviate their dissolution in the electrolyte, resulting in superior long-term cyclic stability. The high intrinsic conductivity of LVTS is in favor of rapid transfer of electrons and promotes the fast conversion of polysulfides to sodium sulfides, thus realizing high reversible capacities. Moreover, with its fast Na+ transport kinetics, the as-prepared TiS demonstrates an impressive rate performance of 321 mAh g-1 at 15 A g-1. Overall, the electric field regulation method is flexible and efficient, which provides a new route for the preparation of high-performance electrode materials. Moreover, nonstoichiometric metal compounds possess abundant active sites and rapid electron transport kinetics, which provide a new choice for promising sodium storage materials in large-scale energy storage applications.

11.
Environ Pollut ; 313: 120147, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36096263

RESUMO

1-bromopropane is a US Environmental Protection Agency-identified significant hazardous air pollutant with concerned adverse respiratory effect. We aimed to investigate the relationship between 1-bromopropane exposure and pulmonary function and the underlying role of oxidative damage, which all remain unknown. Pulmonary function and urinary biomarkers of 1-bromopropane exposure (N-Acetyl-S-(n-propyl)-L-cysteine, BPMA) and oxidative damage to DNA (8-hydroxy-deoxyguanosine, 8-OHdG) and lipid (8-iso-prostaglandin-F2α, 8-iso-PGF2α) were measured for 3259 Chinese urban adults from the Wuhan-Zhuhai cohort. The cross-sectional relationship of BPMA with pulmonary function and the joint relationship of BPMA and 8-OHdG or 8-iso-PGF2α with pulmonary function were investigated by linear mixed models. The mediating roles of 8-OHdG and 8-iso-PGF2α were evaluated by mediation analysis. Additionally, a panel of 138 subjects was randomly convened from the same cohort to evaluate the stability of BPMA repeatedly measured in urine samples collected over consecutive three days and intervals of one, two, and three years, and to estimate the longitudinal relationship of BPMA with pulmonary function change in three years. We found each 3-fold increase in BPMA was cross-sectionally related to FVC and FEV1 reductions by 29.88-mL and 25.67-mL, respectively (all P < 0.05). Joint relationship of BPMA and 8-OHdG rather than 8-iso-PGF2α with reduced pulmonary function was observed. Moreover, 8-OHdG significantly mediated 9.44% of the BPMA-related FVC reduction. Findings from the panel revealed a fair to excellent stability (intraclass correlation coefficient: 0.43-0.79) of BPMA in repeated urines collected over a period of three years. Besides, BPMA was longitudinally related to pulmonary function reduction in three years: compared with subjects with persistently low BPMA level, those with persistently high BPMA level had 79.08-mL/year and 49.80-mL/year declines in FVC and FEV1, respectively (all P < 0.05). Conclusively, 1-bromopropane exposure might impair pulmonary function of urban adult population, and oxidative DNA damage might be a potential mechanism underlying 1-bromopropane impairing pulmonary function especially FVC.

12.
Biosens Bioelectron ; 217: 114682, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36115124

RESUMO

Detecting the concentration of oxidized low-density lipoprotein (Ox-LDL) in whole blood is of great significance for monitoring the development of atherosclerosis. In order to simplify the complex processing steps of blood sample before the detection, an electrochemical sensor based on micromotor technology was designed, which was called magnesium (Mg)-Fe3O4@ prussian blue (PB)@ antibody of Ox-LDL (Ab)@ bovine serum albumin (BSA). The active capture of Ox-LDL in whole blood can be realized by the help of the movement of Mg microsphere with the driving force of H2. Then the captured Ox-LDL was collected on the surface of the magnetic glassy carbon electrode (MGCE) by self-made funnel device, and the content of Ox-LDL was detected by electrochemical workstation in the way of chronoamperometry (i-t). Due to the application of micromotor, the electrochemical sensor proposed in this study had good detection efficiency for Ox-LDL in whole blood with range from 1 × 10-2 µg/mL to 10 µg/mL, and the limit of detection (LOD) towards Ox-LDL was 9.80 × 10-4 µg/mL. The electrochemical sensor based on micromotor technology provides a rapid, effective, and sensitive method for the detection of Ox-LDL in whole blood.

13.
Front Immunol ; 13: 930103, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090987

RESUMO

Objective: To address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy. Methods: Studies were conducted in asthmatic patients and macrophage-specific Mbd2 knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with Mbd2 siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model. Results: Asthmatic patients and mice challenged with OVA exhibited upregulated MBD2 expression in macrophages, especially in alternatively activated (M2) macrophages. In particular, macrophage-specific knockout of Mbd2 protected mice from OVA-induced allergic airway inflammation and suppressed the M2 program. Notably, intratracheal administration of liposomes carrying Mbd2 siRNA decreased the expression of Mbd2 and prevented OVA-induced allergic airway inflammation in mice, as indicated by the attenuated airway inflammation and mucus production. Conclusions: The above data indicate that Mbd2 implicates in the pathogenesis of asthma predominantly by regulating the polarization of M2 macrophages, which supports that Mbd2 could be a viable target for treatment of asthma in clinical settings.


Assuntos
Asma , Lipossomos , Animais , Asma/induzido quimicamente , Asma/genética , Asma/prevenção & controle , Proteínas de Ligação a DNA/genética , Inflamação/induzido quimicamente , Inflamação/genética , Lipossomos/uso terapêutico , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Ovalbumina/efeitos adversos , RNA Interferente Pequeno/uso terapêutico
14.
Artigo em Inglês | MEDLINE | ID: mdl-36094079

RESUMO

Acetaminophen (APAP)-induced liver injury (AILI) is a common liver disease in clinical practice. Only one clinically approved drug, N-acetylcysteine (NAC), for the treatment of AILI is available in clinics, but novel treatment strategies are still needed due to the complicated pathological changes of AILI and the side effects of NAC. Here, we found that astaxanthin (ASX) can prevent AILI through the Nrf2/HO-1 pathway. After treatment with ASX, there was a positive activation of the Nrf2/HO-1 pathway in AILI models both in vivo and in vitro accompanied by enhanced autophagy and reduced ferroptosis. In APAP-challenged L02 liver cells, ASX reduced autophagy and enhanced apoptosis of the cells. Furthermore, we developed ASX-loaded hollow mesoporous silica nanoparticles (HMSN@ASX) to improve the aqueous solubility of ASX and targeted delivery of ASX to the liver and then significantly improve the therapeutic effects. Taken together, we found that ASX can protect against AILI by activating the Nrf2/HO-1 pathway, which mainly affects oxidative stress, autophagy, and ferroptosis processes, and the HMSN@ASX nanosystem can target the liver to enhance the treatment efficiency of AILI.

15.
Anal Chim Acta ; 1227: 340311, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36089321

RESUMO

Since pesticide residues in food have attracted increasing concern worldwide, it is crucial to develop rapid and sensitive analytical methods to detect pesticide residues and ensure food safety. In this work, via the biotin-streptavidin (SA) recognition system, we constructed a magnetic relaxation switching (MRS) immunosensor for sensitive detection of chlorpyrifos (CPF). With a competitive immunoassay mode, H2O2 and Fe2+ were firstly optimized as the reaction substrates. Wherein, horseradish peroxidase (HRP) acted as enzyme label to catalyze H2O2 and mediated the conversion of Fe2+/Fe3+. By introducing Fe2+/Fe3+ interconversion as MRS signal output, CPF was detected by the immunoreaction induced variations of the transverse relaxation time (ΔT2). The proposed MRS immunosensor exhibited a detection linear range from 0.01 to 1000 ng mL-1 (R2 = 0.9916), with the limit of detection (LOD) of 6 pg mL-1 (3S/M, n = 3). As a proof-of-concept, CPF was easily detected among five different pesticides at a low concentration level (0.1 ng mL-1), as well as in real samples (apple, tea, and lettuce) with recoveries of 80.70-115.30%. Besides, the sensor can realize one step of "separation and detection" towards CPF with the aid of magnetic nanoparticles, which demonstrate its promising potential for pesticide residue detection in food samples and environment.


Assuntos
Técnicas Biossensoriais , Clorpirifos , Resíduos de Praguicidas , Técnicas Biossensoriais/métodos , Peróxido de Hidrogênio , Imunoensaio/métodos , Fenômenos Magnéticos
16.
Environ Pollut ; 310: 119898, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35940488

RESUMO

As a polycyclic aromatic hydrocarbon, environmental exposure to phenanthrene is widespread worldwide. The potential effects and mechanism of phenanthrene exposure on fasting plasma glucose (FPG) have not been well determined. In this study, we aim to explore the effects of phenanthrene exposure and AMER3 variants on fasting plasma glucose (FPG) through a longitudinal epidemiological study. Repeated measurements of five urinary hydroxyphenanthrene (OHPh) for 5739 participants with 7083 observations from the Wuhan-Zhuhai cohort were performed to analyze the relationships between total OHPh (ΣOHPh) and FPG using linear mixed models and restricted cubic spline functions. Then, we genotyped 2777 participants (4104 observations) using the Infinium OmniZhongHua-8 BeadChip and included all 14 single nucleotide polymorphisms (SNPs) within the AMER3 gene to analyze the interaction of the AMER3 on the relationship between ΣOHPh and FPG. We observed a U-shaped relationship between ΣOHPh and FPG, and the turning point of ΣOHPh was 2.512 µg/mmol Cr. When lower than the turning point, ΣOHPh was negatively associated with FPG, while higher than the turning point, ΣOHPh was positively associated with FPG. Furthermore, we observed interactions (Pint <0.05) between two common variants (rs72854995 and rs72854999) of the AMER3 and ΣOHPh on FPG change: the U-shaped relationship was still observed in the GG genotype groups but not in the allele A carriers. Our results suggested that the AMER3 gene can modify the U-shaped relationship between phenanthrenes exposure and FPG, which showed a new gene-environment interaction and will provide a new perspective on the relationship between phenanthrene exposure and FPG.


Assuntos
Jejum , Hidrocarbonetos Policíclicos Aromáticos , Glicemia , Exposição Ambiental , Interação Gene-Ambiente , Humanos
17.
Front Nutr ; 9: 965180, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990348

RESUMO

Mounting evidence suggested that high loading intensity of exercise might be detrimental to human health, especially the gastrointestinal tract. Pterostilbene (PTE), derived from grapes and blueberries, might reach a high concentration of intestinal contents. Our study aimed to evaluate PTE's ability to prevent the loss of intestinal epithelial barrier in high loading intensity of exercise. The exercise model was established by the forced running of mice. An effective HPLC-UV method was developed to quantify PTE concentration in intestinal content. The mRNA changes were detected by quantitative polymerase chain reaction (qPCR). The structure of intestinal flora was analyzed by 16S rRNA sequencing. The PTE (100 mg/kg/d) could significantly attenuate exercise-induced intestinal epithelial barrier loss. Moreover, the HPLC-UV assay showed that the PTE concentration of intestinal content could last 12 h. Furthermore, the exercise increased the abundance of Alistipes, which was related to lipopolysaccharide (LPS) production but could not be reversed by PTE intervention. Besides, cell experiments showed that PTE could promote the expression of intestinal epithelial tight junction (TJ) molecules in vitro. In conclusion, PTE has a significant interest in preventing exercise-induced intestinal damage.

18.
BMC Cancer ; 22(1): 859, 2022 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-35933338

RESUMO

BACKGROUND: The KMT2A gene, formerly named the MLL gene, is rearranged (KMT2Ar) in 70-75% of infants, 5-6% of children and 10-15% of adult patients with B cell acute lymphoblastic leukemia (B-ALL). The outcome after chemotherapy of pediatric cases remains poor, and only a few studies have investigated the clinical and laboratory features, treatment response and prognosis in Chinese populations. METHODS: A total of 48 B-ALL children with KMT2Ar were enrolled in the study, and clinical and laboratory data were collected and analyzed by age group. The relationship between prognosis and traditional risk factors and treatment response was investigated for these patients who received chemotherapy. RESULTS: The 48 enrolled patients included 28 males and 20 females; 18 (37.50%) or 30 (62.50%) patients were an age of < 12 m (infant B-ALL) or of > 12 m at onset. An initial WBC count of 300 × 109/L was detected in 7 (14.58%) patients; testicular leukemia (TL) or central nervous system involvement was found in 5 (10.41%) or 3 (6.25%) patients, respectively. Statistical differences were not found in the age groups of sex or initial WBC count, whereas TL was more common in the infant group (P < 0.05). 11q23 was detected in 18 patients; KMT2Ar was detected in 46 (95.83%) or 45 (93.75%) patients by FISH or multiplex RT-PCR technology, respectively; RNA-seq data were obtained for 18 patients, and 3 patients with uncommon KMT2Ar were identified. KMT2A-AFF1, KMT2A-MLLT3 and KMT2A-MLLT1 were the most common transcripts. Statistical differences were not found in treatment response by age groups, including dexamethasone induction, bone marrow (BM) smear status and minimal residual disease (MRD) level at different time points (TP), treatment-related mortality (TRM), or complete remission (CR) rate (P > 0.05); MRD levels monitored by FCM or PCR were unequal at the same TP. Four patients died of treatment, and TRM was 8.33%; 40 patients achieved CR, and the CR rate for the cohort was 83.33%. Seven patients quit, 15 patients relapsed, and the 5 yr cumulative relapse rate was 59.16 ± 9.16%; the 5 yr prospective EFS (pEFS) for patients who were included or excluded from the TRM group was 36.86 ± 8.48% or 40.84 ± 9.16%, respectively. Multivariate analysis for prognosis and hazard ratio was performed for 37 patients without TRM and revealed that an initial WBC count of > 300 × 109/L and a positive level of FCM-MRD were strongly related to a poor outcome for B-ALL patients with KMT2Ar (P < 0.05).


Assuntos
Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Feminino , Humanos , Masculino , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Estudos Prospectivos , Indução de Remissão
20.
Front Aging Neurosci ; 14: 926485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912073

RESUMO

Small extracellular vesicles (sEVs) mediate cell-cell communication by transferring their cargo biological materials into recipient cells. Diabetes mellitus (DM) induces cerebral vascular dysfunction and neurogenesis impairment, which are associated with cognitive decline and an increased risk of developing dementia. Whether the sEVs are involved in DM-induced cerebral vascular disease, is unknown. Therefore, we studied sEVs derived from cerebral endothelial cells (CEC-sEVs) of aged DM rats (DM-CEC-sEVs) and found that DM-CEC-sEVs robustly inhibited neural stem cell (NSC) generation of new neuroblasts and damaged cerebral endothelial function. Treatment of aged DM-rats with CEC-sEVs derived from adult healthy normal rats (N-CEC-sEVs) ameliorated cognitive deficits and improved cerebral vascular function and enhanced neurogenesis. Intravenously administered N-CEC-sEVs crossed the blood brain barrier and were internalized by neural stem cells in the neurogenic region, which were associated with augmentation of miR-1 and -146a and reduction of myeloid differentiation primary response gene 88 and thrombospondin 1 proteins. In addition, uptake of N-CEC-sEVs by the recipient cells was mediated by clathrin and caveolin dependent endocytosis signaling pathways. The present study provides ex vivo and in vivo evidence that DM-CEC-sEVs induce cerebral vascular dysfunction and neurogenesis impairment and that N-CEC-sEVs have a therapeutic effect on improvement of cognitive function by ameliorating dysfunction of cerebral vessels and increasing neurogenesis in aged DM rats, respectively.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...