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1.
Neural Regen Res ; 17(1): 210-216, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100458

RESUMO

In Alzheimer's disease and ischemic stroke, intranasal insulin can act as a neuroprotective agent. However, whether intranasal insulin has a neuroprotective effect in intracerebral hemorrhage and its potential mechanisms remain poorly understood. In this study, a mouse model of autologous blood-induced intracerebral hemorrhage was treated with 0.5, 1, or 2 IU insulin via intranasal delivery, twice per day, until 24 or 72 hours after surgery. Compared with saline treatment, 1 IU intranasal insulin treatment significantly reduced hematoma volume and brain edema after cerebral hemorrhage, decreased blood-brain barrier permeability and neuronal degeneration damage, reduced neurobehavioral deficits, and improved the survival rate of mice. Expression levels of p-AKT and p-GSK3ß were significantly increased in the perihematoma tissues after intranasal insulin therapy. Our findings suggest that intranasal insulin therapy can protect the neurological function of mice after intracerebral hemorrhage through the AKT/GSK3ß signaling pathway. The study was approved by the Ethics Committee of the North Sichuan Medical College of China (approval No. NSMC(A)2019(01)) on January 7, 2019.

2.
Neuro Oncol ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34918118

RESUMO

BACKGROUND: Elucidating the mechanism by which biallelic inactivation evolved could provide a mechanistic understanding for NF2 tumorigenesis and also a rationale for clinical management. METHODS: A cohort of 60 NF2 patients was recruited. Next-generation sequencing of tumor and paired control samples was used to explore how NF2 mutations evolve in determining the clinical phenotypes. RESULTS: Total 60 blood samples (one from each patient) and 61 (from 35 patients) NF2 associated tumors were collected. Next-generation sequencing of the blood samples detected "first hit" NF2 mutation in 35/60 donors (58.3%), 82.9% of which (29/35) bear heterozygous germline mutations, and 17.1% (6/35) of which are mosaics with variable allelic frequency (VAF). Whilst a number of NF2 patients were found without germline mutation, most (57/61, 93.4%) NF2 associated tumors were identified with NF2 somatic mutation. We calculated the correlation between the onset latency of mosaic and germline NF2 allele carriers with the mosaicism VAF. The mosaicism VAF is negatively and linearly correlated to clinical symptom onset latency (R2 0.3677, P=0.00351), suggesting biallelic inactivation probability is a linear function of 'first hit' prevalence in the body. The second NF2 somatic mutation occurrence time positively correlates with the onset of clinical symptom (R2=0.4151, P=0.02633), suggesting tumor growth is linearly proportional to the time after biallelic inactivation. CONCLUSIONS: Our results suggested that biallelic inactivation of NF2 evolved through neutral drift and pre-existing first hit NF2 allele determines certain aspects of the clinical symptom. Genetic diagnosis should be included in the diagnostic criteria and treatment consideration of NF2.

3.
Magn Reson Chem ; 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34969169

RESUMO

Currently the existence of a gut-bone axis receives massive attention, and while sound premises and indirect proofs exist for the gut-bone axis concept, few studies have provided actual data linking the gut and bone physically. This study aimed to exploit the versatile nature of nuclear magnetic resonance (NMR) to link NMR relaxometry data on bone mineralization with NMR spectroscopic profiling of gut metabolites. For this purpose, sample material was obtained from a 6-week intervention study with ovariectomized (OVX) rats (n=49) fed with 7 different diets varying in calcium content (0.2-6.0 mg/Kg) and prebiotic fiber content (0-5.0 % w/w). This design ensured a span in i) calcium available for bone mineralization and ii) metabolic activity in the gut. After termination of the intervention, longitudinal (T1 ), transverse (T2 ) relaxation as well as mechanical bone strength were measured on the excised femur bones. A PLS model with high predictability (Q2 =0.86, R2 =0.997) was demonstrated between T2 decay curves and femur mechanical strength. Correlations were established between bone T2 populations and gut short-chain fatty acids. In conclusion, the present dual NMR approach showed strong correlation between T2 relaxation and mechanical strength of the bone, and when metabolic activity in the gut was modulated by inulin, the potential existence of a gut-bone axis was demonstrated.

4.
Expert Rev Mol Diagn ; : 1-9, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34904499

RESUMO

BACKGROUND: Signal sequence receptor subunit delta (SSR4) gene is reported to encode the translocon-associated protein δ and related with the human immune regulation. However, the expression of SSR4 in colon adenocarcinoma (COAD) and its correlation with clinical treatment remains unclear. RESEARCH DESIGN AND METHODS: SSR4 mRNA expression level and its relationship with tumor infiltrating lymphocytes (TILs) in COAD were evaluated through several databases. Furthermore, the study collected 238 cases of COAD tissue samples to detect the association of SSR4 protein expression level in TILs with clinical pathological information, and the prognosis of COAD. RESULTS: SSR4 mRNA was significantly highly expressed in COAD tissues and significantly correlated with several types of TILs in COAD. Moreover, SSR4 highly expressed in many types of TILs, especially highly expressed in plasma cell from COAD patients with advanced TNM stage. High SSR4 protein expression in TILs was associated with lymph node metastasis, distant metastasis, American Joint Committee on Cancer (AJCC) staging, and Response Evaluation Criteria in Solid Tumors (RECIST) efficacy. COAD patients with high SSR4 expression in TILs had better overall survival. CONCLUSIONS: In conclusion, high SSR4 mRNA and protein expression in TILs can be used as a prognostic biomarker for predicting better overall survival and treatment efficacy in COAD patients.

5.
Adv Mater ; : e2104786, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34837249

RESUMO

Aiming to overcome both the structural and commercial limitations of flexible thermoelectric power generators (F-TEGs), we designed an efficient room-temperature aqueous selenization reaction that could be completed in air within less than 1 min, to directly fabricate thin ß-Ag2 Se films consisting of perfectly crystalline and large columnar grains with both in-plane randomness and out-of-plane [201] preferred orientation. A high power factor (PF) of 2590 ± 414 µW m-1 K-2 and a figure-of-merit (zT) of 1.2 ± 0.42 were obtained from the sample with a thickness of ∼1 µm. The maximum output power density (MOPD) of the best 4-leg TEG sample reached up to 27.6 ± 1.95 and 124 ± 8.78 W·m-2 at room temperature with 30 K and 60 K temperature differences, respectively, which may be used in future flexible TE devices. This article is protected by copyright. All rights reserved.

6.
Epilepsy Res ; 178: 106817, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34837825

RESUMO

Epilepsy is a high incidence neurological disease, and its repeated attacks cause serious physical and psychological damage to the patient. Differentially expressed in normal and neoplastic cells (DENN) domain containing 5B (DENND5B) is a lipoprotein binding protein that mediates synaptic vesicle transport and regulates neuroplasticity and lipid metabolism. Nevertheless, the effect of DENND5B on seizures remains unclear. We aimed to investigate the association of DENND5B with epilepsy, detect its expression and distribution in the nervous system, and explore its role in epileptogenesis through western blot, immunofluorescence staining, and behavioral studies. In this experiment, two C57BL/6 mice models, which induced seizures by pentylenetetrazole and kainic acid, were established. We observed that the expression of DENND5B was reduced in the brains of patients with temporal lobe epilepsy, and its expression was also similarly decreased in both chronic epileptic mice. The findings strongly suggest that DENND5B may be associated with epileptic seizures. Results of immunofluorescence showed that DENND5B was mainly expressed in the hippocampal region and co-located with neurons but not with astrocytes. Next, we used lentivirus to induce both lentiviral vector-mediated overexpression and knockdown of DENND5B in mice to test the change of susceptibility and severity of seizures in the two chronic seizure models. Knockdown of DENND5B was found to promote epileptic seizures, increase chronic spontaneous recurrent epileptic seizures and epileptic discharge, and reduce the incubation period. However, overexpression of DENND5B showed the opposite effect. These results suggest that DENND5B overexpression decreased the behavioral phenotype of epileptic seizures, but DENND5B downregulation had the opposite effect. In summary, our findings suggest that DENND5B can regulate epileptic seizures and may provide a new target for antiepileptic therapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34725556

RESUMO

The neuroinflammatory pathway regulated by nuclear factor kappa-B (NF-κB) plays an important role in the occurrence, development, and prognosis of poststroke depression (PSD). The regulatory effect of the traditional Chinese medicine compound Xingnao Jieyu decoction (XNJY) on the NF-κB pathway of PSD is still unclear. This study aimed to observe the effect of XNJY on PSD and explore the molecular mechanism of its intervention in the NF-κB pathway. Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress were used to establish a PSD rat model. Body mass measurement, behavioral testing, Nissl staining, ELISA, and Western blot were also performed. XNJY and fluoxetine hydrochloride (Flu) treatment of PSD model rats showed significant antidepressant effects. XNJY and Flu treatment could reduce cortical and hippocampal neuronal damage. XNJY reduced inflammation and restored the levels of IL-4, IL-10, and BDNF. In addition, XNJY showed a significant regulatory effect on the NF-κB pathway and the expression of synapse-related proteins PSD-95 and SYN. These results showed that XNJY could significantly reduce the depressive symptoms of PSD rats, and this reduction may be related to the regulation of the NF-κB signaling pathway to improve neuroinflammation and synaptic function.

8.
Am J Transl Res ; 13(8): 8787-8803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539995

RESUMO

A stable, human sporadic vestibular schwannoma cell line is not currently available. By using a lentivirus-mediated transfection from a 41-year-old sporadic vestibular schwannoma patient, primary schwannoma cells were obtained, cultured and immortalized using the hHERT gene. The NF2 gene of the resulting JEI-001 cell line contains a specific Exon 5 mutation. The schwannoma cell origin of this cell line was confirmed using STR techniques and immunocytochemistry. A comparison between the primary tumor tissue and JEI-001 revealed a common mutation of the NF2 gene, which indicated that the JEI-001 cell line had retained most of its original tumor characteristics. The JEI-001 cell line was found to be non-tumorigenic in nude mice, but certain growth features had been altered, resulting in changes such as independence from the Schwann cell growth factors and a higher proliferation rate. This was the first known study to establish cell lines immortalized from human sporadic vestibular schwannoma that had different characteristics from that of HEI-193. This is a novel model system that can be used for the study of NF2 gene functions, in order to elaborate on the biological features of sporadic vestibular schwannoma, even including familial NF2 tumors, and to further explore the molecular pathogenesis and develop new adjuvant therapies.

9.
Am J Transl Res ; 13(8): 9586-9592, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540082

RESUMO

PURPOSE: To explore the effect of Etoricoxib on serum miR-214 expression level and inflammatory reaction in patients with knee osteoarthritis. METHODS: 96 patients with knee osteoarthritis admitted to our hospital (January 2019 to January 2020) were selected. 48 patients in the control group received Celecoxib and 48 patients in the observation group received Etoricoxib. The treatment effect, knee function, inflammatory factor level, immune function, and serum miR-214 expression level of the two groups were compared. 6 months after treatment, the incidence of complications (deformities, deep infections and severe pain) between the two groups was compared. RESULTS: (1) The observation group had a higher total effective rate (93.75%) in comparison to the control group (72.92%) (P<0.05). (2) Before treatment, the serum miR-214 expression level of the two groups was basically the same (P>0.05). After treatment, the serum miR-214 expression level of the two groups decreased significantly, with a more marked decrease in the observation group (P<0.05). (3) Before treatment, the levels of IL-1ß, TNF-α, and hs-CRP were not statistically different in the two groups (P>0.05). After treatment, IL-1ß, TNF-α, and hs-CRP in both groups decreased, and the decrease in the observation group was significantly greater (P<0.05). (4) Before treatment, the levels of CD3+CD8+ and CD3+ were basically the same in both groups (P>0.05). After treatment, the levels of CD3+CD8+ and CD3+ in the two groups increased, and for the observation group, were significantly greater P<0.05. (5) The Lysholm score was higher in the observation group than it was in the control group (inter-group effect: F = 58.070, P<0.001), and the Lysholm score of both groups tended to increase with time (time effect: F = 145.900, P<0.001). Grouping and time showed an interactive effect (interactive effect: F = 8.646, P<0.001). 6 months after treatment, observation group showed a lower complication rate when compared to the control groupt (P<0.05). CONCLUSION: Etoricoxib has a strong effect on patients with knee osteoarthritis. It can significantly reduce the expression of serum miR-214 and the level of inflammatory factors, and is worthy of clinical application.

10.
Microbiol Spectr ; 9(1): e0026121, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34346744

RESUMO

The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time platform. Fourteen samples were extracted from sputum, nasopharyngeal swabs, or stool, which in total produced 283,655 high-quality circular consensus sequences. We observed a stable quasispecies structure that one master mutant (mean abundance ∼0.70), followed by numerous minor mutants (mean abundance ∼1.21 × 10-3). Under high selective pressure, minor mutants may obtain a fitness advantage and become the master ones. The later predominant substitution D614G existed in the minor mutants of more than one early patient. An epidemic variant had a possibility to be independently originated from multiple hosts. The mutant spectrums covered ∼85% amino acid variations of public genomes (GISAID; frequency ≥ 0.1) and likely provided an advantage mutation pool for the current/future epidemic variants. Notably, 32 of 35 collected antibody escape substitutions were preexistent in the early quasispecies. Virus populations in different tissues/organs revealed potentially independent replications. The quasispecies complexity of sputum samples was significantly lower than that of nasopharyngeal swabs (P = 0.02). Evolution analysis revealed that three continuous S2 domains (HR1, CH, and CD) had undergone a positive selection. Cell fusion-related domains may play a crucial role in adapting to the intrahost immune system. Our findings suggested that future epidemiologic investigations and clinical interventions should consider the quasispecies information that has missed by routine single consensus genome. IMPORTANCE RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene.


Assuntos
Epidemias , Mutação , Quase-Espécies , SARS-CoV-2/classificação , SARS-CoV-2/genética , Adulto , Idoso , Sequência de Bases , COVID-19/virologia , Criança , Feminino , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/genética
11.
ACS Omega ; 6(29): 18566-18575, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34337197

RESUMO

In this work, zeolitic imidazolate frameworks (ZIF-8) and carboxylated carbon nanotubes (CNTs) were compounded to prepare a kebab-like one-dimensional linear composite, ZIF-8@CNTs. The mixed-matrix membrane (MMM) for separating carbon dioxide is prepared by embedding it into the polymer matrix Pebax-1657. The results indicated the successful synthesis of the ZIF-8@CNT composite. The combination of ZIF-8 and carboxylated CNTs avoided the aggregation of ZIF-8 in the polymer, increased the free volume of the MMM, and enhanced the CO2 adsorption performance and CO2/N2 separation performance. In addition, the interaction between CNTs and ZIF-8 provided a fast transport channel for CO2 molecules and improved the mechanical properties of the MMM. The 5 wt % ZIF-8@CNT MMM showed the best separation performance with a CO2 permeability of 225.5 Barrer and a CO2/N2 selectivity of 48.9, which exceeded the Robeson upper limit in 2008. The combination of high permeability and selectivity made Pebax/ZIF-8@CNT MMMs promising for industrial CO2 separation applications.

12.
Phys Chem Chem Phys ; 23(31): 16469-16487, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34338709

RESUMO

Cu-based thin films are ideal absorbing layer materials for new-generation thin-film solar cells, which have many advantages, such as environment-friendly components, abundant raw materials, low cost, simple manufacturing process, strong anti-interference, radiation resistance, high light absorption coefficient and suitable band gap. Copper indium gallium selenide (CIGS) thin-film solar cells, which have the highest photoelectric conversion efficiency (23.35%) among the various Cu-based materials, have been intensively investigated and exploited. To promote the progress of Cu-based thin-film solar cells, the rational design of efficient materials and devices and the in-depth understanding of their photophysical mechanisms are not only urgently required, but also have plenty of room for research. Accordingly, herein, we firstly define the concept of "Cu-based materials", and further present a comprehensive review on the materials (design and fabrication), devices (assembly and performances), and charge carrier dynamics of Cu-based thin-film semiconductor materials, including perovskites, oxides, chalcogenides (binary, ternary, quaternary and quinary) and perovskite-like iodides. In addition, the current challenges and prospects in this topic are critically concluded. Particularly, this review may help researchers focused on investigating thin-film solar cells.

13.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34389675

RESUMO

To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor ß (ERß) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERß. ERß is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERß+ TNBC patient-derived xenografts in mice and found that the ERß agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERß is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERß functionless on genes involved in proliferation and inflammation.

14.
BMC Endocr Disord ; 21(1): 148, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238277

RESUMO

BACKGROUND: Recent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD. METHODS: A total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. RESULTS: There was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P = 0.014) and allele frequency of rs744877 (P = 0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR = 0.79, 95%CI 0.66-0.95; P = 0.013) and an additive model (OR = 0.77, 95%CI 0.64-0.94, P = 0.008), and was also observed after adjusted age and gender under a dominant model (OR = 0.78, 95%CI 0.65-0.95; P = 0.011) and an additive model (OR = 0.76, 95%CI 0.63-0.93, P = 0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR = 0.84, 95%CI 0.71-0.98, P = 0.027), a dominant model (OR = 0.74, 95%CI 0.60-0.91; P = 0.005), and an additive model (OR = 0.72, 95%CI 0.58-0.90, P = 0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis. CONCLUSION: This is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.

15.
Front Bioeng Biotechnol ; 9: 672594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34113606

RESUMO

The prevalence of the two most common neurodegenerative diseases, Parkinson's disease (PD) and Alzheimer's Disease (AD), are expected to rise alongside the progressive aging of society. Both PD and AD are classified as proteinopathies with misfolded proteins α-synuclein, amyloid-ß, and tau. Emerging evidence suggests that these misfolded aggregates are prion-like proteins that induce pathological cell-to-cell spreading, which is a major driver in pathogenesis. Additional factors that can further affect pathology spreading include oxidative stress, mitochondrial damage, inflammation, and cell death. Nanomaterials present advantages over traditional chemical or biological therapeutic approaches at targeting these specific mechanisms. They can have intrinsic properties that lead to a decrease in oxidative stress or an ability to bind and disaggregate fibrils. Additionally, nanomaterials enhance transportation across the blood-brain barrier, are easily functionalized, increase drug half-lives, protect cargo from immune detection, and provide a physical structure that can support cell growth. This review highlights emergent nanomaterials with these advantages that target oxidative stress, the fibrillization process, inflammation, and aid in regenerative medicine for both PD and AD.

16.
Transl Oncol ; 14(8): 101146, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34118692

RESUMO

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Mutational analysis identified 6 out of 14 HNPGLs harboring clinicopathologic SDH gene mutations. The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. The paraganglioma cell line (PGL-626) was established from a sample that harbored a missense SDHB mutation (c.649C > T). Spectrometric analysis using tandem mass tags identified 151 proteins significantly differentially expressed in HNPGLs compared with normal nerves. Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.

17.
J Cardiothorac Surg ; 16(1): 155, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059106

RESUMO

BACKGROUND: This study aimed to investigate the pulmonary ventilation function (PVF) according to different types of rib fractures and pain levels. METHODS: This was a retrospective study of patients with thoracic trauma admitted to our ward from May 1, 2015, to February 1, 2017. Vital capacity (VC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF) were measured on admission. A numerical rating scale (NRS) was used for pain assessment. RESULTS: A total of 118 (85 males and 33 females) were included. The location of rib fractures did not affect the PVF. When the number of rib fractures was ≥5, the PVF was lower than in those with ≤4 fractures (VC: 0.40 vs. 0.47, P = 0.009; FEV1: 0.37 vs. 0.44, P = 0.012; PEF: 0.17 vs. 0.20, P = 0.031). There were no difference in PVF values between rib fractures with multiple locations and those with non-multiple locations (VC: 0.41 vs. 0.43, P = 0.202; FEV1: 0.37 vs. 0.39, P = 0.692; PEF: 0.18 vs. 0.18, P = 0.684). When there were ≥ 5 breakpoints, the PVF parameters were lower than those with ≤4 breakpoints (VC: 0.40 vs. 0.50, P = 0.030; FEV1: 0.37 vs. 0.45, P = 0.022; PEF: 0.18 vs. 0.20, P = 0.013). When the NRS ≥ 7, the PVF values were lower than for those with NRS ≤ 6 (VC: 0.41 vs. 0.50, P = 0.003; FEV1: 0.37 vs. 0.47, P = 0.040; PEF: 0.18 vs. 0.20, P = 0.027). CONCLUSIONS: When the total number of fractured ribs is ≥5, there are ≥5 breakpoints, or NRS is ≥7, the VC, FEV1, and PEF are more affected. TRIAL REGISTRATION: The trial was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, and individual consent for this retrospectively registered analysis was waived.


Assuntos
Dor Musculoesquelética/etiologia , Dor Musculoesquelética/fisiopatologia , Fraturas das Costelas/complicações , Fraturas das Costelas/fisiopatologia , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pico do Fluxo Expiratório , Estudos Retrospectivos , Capacidade Vital , Adulto Jovem
18.
Food Chem ; 361: 130177, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34077883

RESUMO

Carotenoid content in maize sprouts can be increased by NaCl stress, although high NaCl concentrations negatively impact plant growth. The effects of exogenous methyl jasmonate (MeJA) on contents of carotenoid and antioxidant capacity of yellow maize sprouts under NaCl stress were investigated. Our results showed that treatments of NaCl both alone and combined with MeJA enhanced the carotenoid accumulation in maize sprouts. Moreover, the carotenoid biosynthesis related genes showed different expression patterns under addition of MeJA treatment. Additionally, the combined treatment led to significantly higher content of most carotenoids profiles and the addition of MeJA could alleviate the harmful effect caused by NaCl stress. Furthermore, the combined treatment improved antioxidant enzyme activities and radical scavenging capacity. The results implied that MeJA is kind of effective plant growth regulator for enhancing carotenoid accumulation in maize sprouts by up-regulating the expression levels of key genes involved in carotenoid biosynthetic pathway.


Assuntos
Acetatos/farmacologia , Carotenoides/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Cloreto de Sódio/farmacologia , Zea mays/efeitos dos fármacos , Antioxidantes/metabolismo , Enzimas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Salino , Plântula/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Zea mays/fisiologia
19.
BMC Endocr Disord ; 21(1): 92, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933044

RESUMO

BACKGROUND: The prevalence of diabetes is increasing worldwide. Our study aimed to estimate the changing trends in the prevalence and incidence of diagnosed type 2 diabetes mellitus (T2DM) among Xiamen residents and the floating population using real-world data. METHOD: We used real-world data from the System of Xiamen Citizens Health Information from 2014 to 2019 to estimate the changing trends in the prevalence and incidence of diagnosed T2DM. The System included the diagnosis of diabetes and the prescription of hypoglycemic drugs. Prevalent cases of T2DM were individuals who were diagnosed with T2DM and/or using hypoglycemic drugs. Incident cases were individuals with diagnosed T2DM and/or using hypoglycemic drugs in 2014 or 2019 who had not been diagnosed and/or did not use hypoglycemic drugs in the past. RESULTS: In 2014 and 2019, the prevalence of T2DM in Xiamen was 4.04 and 4.84%, respectively. In 2014 and 2019, the incidence rate of T2DM in Xiamen was 14.1 per 1000 person-year and 15.0 per 1000 person-year, respectively. There was a significant increase in both the prevalence (Prevalence difference: 0.80, 95%CI 0.76-0.83%, P < 0.001) and the incidence of T2DM (Incidence difference: 0.9, 95%CI 0.7-1.1, P < 0.001). in Xiamen. The prevalence and incidence of T2DM in people aged 18-39 increased significantly (P < 0.001), while the prevalence and incidence of T2DM in people aged 40-69 reduced significantly (P < 0.001). CONCLUSIONS: There was a significant increase in the prevalence and incidence of T2DM in Xiamen from 2014 to 2019 especially among those with younger age.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , História do Século XXI , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
20.
Laryngoscope ; 131(9): E2573-E2582, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33956344

RESUMO

OBJECTIVES/HYPOTHESIS: Lipopolysaccharide (LPS), a key component of bacterial endotoxins, activates macrophages and triggers the release of inflammatory cytokines in mammalian tissues. Recent studies have shown that intratympanic injection of LPS simulates acute otitis media (AOM) and results in morphological and functional changes in the inner ear. Here we established an AOM mouse model with LPS to investigate the uptake of ototoxic gentamicin in the inner ear, and elucidated the underlying mechanism by focusing on cochlear inflammation as a result of AOM. STUDY DESIGN: Preclinical rodent animal model. METHODS: Fluorescently tagged gentamicin (GTTR) was systemically administered to mice with AOM. Iba1-positive macrophage morphology and inner ear cytokine profile were evaluated by immunofluorescence technique and a mouse cytokine array kit, respectively. RESULTS: We observed characteristic symptoms of AOM in the LPS-treated ears with elevated hearing thresholds indicating a conductive hearing loss. More importantly, the LPS-induced AOM activated cochlear inflammatory responses, manifested by macrophage infiltration, particularly in the organ of Corti and the spiral ligament, in addition to the up-regulation of proinflammatory cytokines. Meanwhile, GTTR uptake in the stria vascularis and sensory hair cells from all the LPS-treated ears was significantly enhanced at 24, 48, and 72-hour post-treatment, as the most prominent enhancement was observed in the 48-hour group. CONCLUSION: In summary, this study suggests that the pathological cochlea is more susceptible to ototoxic drugs, including aminoglycosides, and justified the clinical concern of aminoglycoside ototoxicity in the AOM treatment. Laryngoscope, 131:E2573-E2582, 2021.


Assuntos
Cóclea/metabolismo , Gentamicinas/farmacocinética , Lipopolissacarídeos/administração & dosagem , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Gentamicinas/toxicidade , Injeção Intratimpânica , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Otite Média/tratamento farmacológico
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