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1.
Fetal Pediatr Pathol ; : 1-10, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202960

RESUMO

Background: 6-Pyruvoyl-tetrahydropterin synthase (PTS) is the key enzyme in BH4 synthesis. PTS deficiency is classified as severe type and mild type, and the prognosis and treatment differ for these types. Distinguishing between two types in the early stage is difficult. Reference to reported cases is needed for interpretation of the correlation between genotype and prognosis. Case report: We report a full-term female newborn with mild PTS deficiency. On the day 21 after birth, the phenylalanine level was 859.6 mmol/L (reference range: 30-117 mmol/L). After 1 year of observation, the patient was found to be in a healthy condition without treatment. Conclusions: Although the phenylalanine level is high in mild PTS deficiency patients after birth, some of them may have few symptoms with no treatment. We review 19 cases and find 8 mutations of PTS that may be associated with mild PTS deficiency.

2.
Cell Rep ; 30(12): 4152-4164.e6, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209475

RESUMO

Histone methyl groups can be removed by demethylases. Although LSD1 and JmjC domain-containing proteins have been identified as histone demethylases, enzymes for many histone methylation states or sites are still unknown. Here, we perform a screening of a cDNA library containing 2,500 nuclear proteins and identify hHR23A as a histone H4K20 demethylase. Overexpression of hHR23A reduces the levels of H4K20me1/2/3 in cells. In vitro, hHR23A specifically demethylates H4K20me1/2/3 and generates formaldehyde. The enzymatic activity requires Fe(II) and α-ketoglutarate as cofactors and the UBA domains of hHR23A. hHR23B, a protein homologous to hHR23A, also demethylates H4K20me1/2/3 in vitro and in vivo. We further demonstrate that hHR23A/B activate the transcription of coding genes by demethylating H4K20me1 and the transcription of repetitive elements by demethylating H4K20me3. Nuclear magnetic resonance (NMR) analyses demonstrate that an HxxxE motif in the UBA1 domain is crucial for iron binding and demethylase activity. Thus, we identify two hHR23 proteins as histone demethylases.

3.
Acta Pharmacol Sin ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32210356

RESUMO

Mitophagy is a degradative pathway that mediates the degradation of the entire mitochondria, and defects in this process are implicated in many diseases including cancer. In mammals, mitophagy is mediated by BNIP3L (also known as NIX) that is a dual regulator of mitochondrial turnover and programmed cell death pathways. Acute myeloid leukemia (AML) cells with deficiency of BNIP3L are more sensitive to mitochondria-targeting drugs. But small molecular inhibitors for BNIP3L are currently not available. Some immunomodulatory drugs (IMiDs) have been proved by FDA for hematologic malignancies, however, the underlining molecular mechanisms are still elusive, which hindered the applications of BNIP3L inhibition for AML treatment. In this study we carried out MS-based quantitative proteomics analysis to identify the potential neosubstrates of a novel thalidomide derivative CC-885 in A549 cells. In total, we quantified 5029 proteins with 36 downregulated in CRBN+/+ cell after CC-885 administration. Bioinformatic analysis showed that macromitophagy pathway was enriched in the negative pathway after CC-885 treatment. We further found that CC-885 caused both dose- and time-dependent degradation of BNIP3L in CRBN+/+, but not CRBN-/- cell. Thus, our data uncover a novel role of CC-885 in the regulation of mitophagy by targeting BNIP3L for CRL4CRBN E3 ligase-dependent ubiquitination and degradation, suggesting that CC-885 could be used as a selective BNIP3L degradator for the further investigation. Furthermore, we demonstrated that CC-885 could enhance AML cell sensitivity to the mitochondria-targeting drug rotenone, suggesting that combining CC-885 and mitochondria-targeting drugs may be a therapeutic strategy for AML patients.

4.
Zool Res ; 41(2): 188-193, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32135580

RESUMO

A new species of the genus Amolops, Amolops tuanjieensis sp. nov., is described from Yunnan, China. The new species can be distinguished by the following characters: dorsolateral folds present; dorsal and ventral surfaces smooth; top of head and dorsum brown-red with irregular gray and dark spots; flank green; side of head black, from tip of snout, diffusing posteriorly to axilla, continuing as black streak below edge of dorsolateral fold; SVL 39.5-40.4 mm in males, 56.8-60.7 mm in females; tympanum distinct; supratympanic fold indistinct; vomerine teeth in two oblique rows between choanae, closer to each other than choanae; vocal sacs present; nuptial pads present; outer metatarsal tubercle absent, supernumerary tubercles absent; all fingertips expanded into discs; limbs dorsally brown with dark brown bars and irregular dark brown blotches.

6.
Sci Adv ; 6(6): eaaz2736, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32128386

RESUMO

Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca2+ channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of mdx mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca2+ channels may represent a promising approach to treat DMD and related muscle diseases.

7.
J Transl Med ; 18(1): 106, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111248

RESUMO

BACKGROUND: Thiazide diuretics reduce the risk of recurrent kidney calculi in patients with kidney calculi or hypercalciuria. However, whether thiazide diuretics can definitely prevent recurrent kidney calculi remains unclear. We aimed to evaluate the effect and safety of thiazide diuretics on recurrent kidney calculi. METHODS: The PubMed, Cochrane Library, and EMBASE databases were systematically searched using the keywords thiazide diuretics and kidney calculi to identify randomized controlled trials (RCTs). The primary outcome was the incidence of recurrent kidney calculi, and the secondary outcome was the 24-h urinary calcium level. The pooled risk ratio (RR), risk difference (RD), standardized mean difference (SMD), and 95% confidence interval (CI) were calculated. The evidence quality was graded using the GRADE criteria, and recommendations for recurrent kidney calculus prevention using thiazide diuretics were reassessed. RESULTS: Eight RCTs involving 571 patients were included. The pooled RR for the incidence of kidney calculi in the thiazide diuretic groups was 0.44 (95% CI 0.33-0.58, P < 0.0001) compared to that in the placebo and untreated groups; the pooled RD was - 0.23 (95% CI - 0.30 to - 0.16, P < 0.0001). The pooled SMD for the 24-h urinary calcium level was - 18.59 (95% CI - 25.11 to - 12.08, P < 0.0001). The thiazide diuretic groups had a high incidence of adverse reactions and low tolerance. The evidence quality for decrease in kidney calculus incidence using thiazide diuretics was low, while that for the 24-h urinary calcium level decrease among those with recurrent kidney calculi was moderate, and that for the decrease in kidney calculus incidence using short-acting and long-acting thiazide diuretics was low. The overall strength of recommendation for prevention of recurrent renal calculi using thiazide diuretics was not recommended. The subgroup and sensitivity analysis findings were robust. CONCLUSIONS: Long-term use of thiazide diuretics reduces the incidence of recurrent renal calculi and 24-h urinary calcium level. However, the benefits are insufficient, and the evidence quality is low. Considering the adverse effects, poor patient compliance, and economic burden of long-term medication, their use in preventing recurrent kidney calculi is not recommended.

8.
Medicine (Baltimore) ; 99(8): e19034, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080077

RESUMO

BACKGROUND: Previous studies showed conflicting results for associations between vitamin D and prediabetes. The study aimed to make a systematic review and meta-analysis for the association between vitamin D and prediabetes. METHODS: We searched for articles identifying associations between vitamin D and prediabetes published in English until July 2019 in following databases (PubMed, Web of Science, EMBASE, Medline, Google Scholar, and Cochrane databases). Finally, we conducted these analyses (heterogeneities examination, meta-regression analyses, sensitivity analysis, and publication bias examination) using STATA 12.0 software (Stata Corporation, College Station, TX, USA). Q test and I were applied to examine heterogeneities between studies. RESULTS: Twelve studies were finally included in the present study. The study included 4 studies to explore the association between serum levels of 25-hydroxy (OH) vitamin D and risks of prediabetes (including 3094 participants). Additionally, the present study included 8 studies (including 865 individuals with prediabetes treated with vitamin D supplementation and 715 patients treated with placebo) to assess differences in therapeutic effects between individuals with prediabetes treated with vitamin D supplementation and those treated with placebo. The present study showed no significant associations between low serum levels of 25(OH) vitamin D and high risk of prediabetes. Additionally, the study showed no significant differences in changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) between individuals with prediabetes treated with vitamin D and those patients given placebo, whereas meta-analysis showed significantly greater changes in 2-hour oral glucose tolerance test (2HPG) in individuals with prediabetes treated with vitamin D, compared with individuals with prediabetes treated with placebo. CONCLUSION: The study supported that low serum levels of 25(OH) vitamin D increased the risk of prediabetes. In addition, vitamin D supplementation improves impaired glucose tolerance in prediabetes. However, more large-scale clinical trials are essential to explore the association between vitamin D and prediabetes.


Assuntos
Estado Pré-Diabético/sangue , Estado Pré-Diabético/tratamento farmacológico , Vitamina D/sangue , Vitaminas/sangue , Glicemia/efeitos dos fármacos , Jejum/sangue , Intolerância à Glucose/tratamento farmacológico , Teste de Tolerância a Glucose/métodos , Hemoglobina A Glicada/análise , Humanos , Resistência à Insulina/fisiologia , Placebos/administração & dosagem , Fatores de Risco , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico
9.
Dev Comp Immunol ; 107: 103637, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32035081

RESUMO

As a member of the genus Cyprinivirus in the family Alloherpesviridae, Cyprinid herpesvirus 2 (CyHV-2) has caused great economic loss in the aquaculture industry, mainly in C. auratus gibelio and goldfish. However, the molecular mechanisms underlying the pathogenicity of CyHV-2 remain elusive. In this study, high-throughput sequencing technology was employed to explore the miRNA expression profiles of C. auratus gibelio (GiCF) caudal fin cells in response to Cyprinid Herpesvirus-2 (CyHV-2) infection. A total of 631 novel miRNAs and 409 known miRNAs were identified. The expression levels of 7 miRNAs were found as significantly modulated (5 down-regulation and 2 up-regulation; P < 0.01, |logFC|>1, TPM>10) in CyHV-2 infected cells. 7 miRNA and their potential mRNA targets were validated by Real-time PCR (qRT-PCR), respectively. Targets prediction and functional analysis of these 7 miRNAs revealed significant enrichment for several signaling pathways, including PPAR, p53 and FoxO pathways. These studies provided more valuable basis for further study on the roles of miRNAs in CyHV-2 replication and pathogenesis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32057232

RESUMO

Layered lithium-rich transition-metal oxides (LRMs) have been considered as the most promising next-generation cathode materials for lithium-ion batteries. However, capacity fading, poor rate performance, and large voltage decays during cycles hinder their commercial application. Herein, a spinel membrane (SM) was first in situ constructed on the surface of the octahedral single crystal Li1.22Mn0.55Ni0.115Co0.115O2 (O-LRM) to form the O-LRM@SM composite with superior structural stability. The synergetic effects between the single crystal and spinel membrane are the origins of the enhancement of performance. On the one hand, the single crystal avoids the generation of inactive Li2MnO3-like phase domains, which is the main reason for capacity fading. On the other hand, the spinel membrane not only prevents the side reactions between the electrolyte and cathode materials but also increases the diffusion kinetics of lithium ions and inhibits the phase transformation on the electrode surface. Based on the beneficial structure, the O-LRM@SM electrode delivers a high discharge specific capacity and energy density (245.6 mA h g-1 and 852.1 W h kg-1 at 0.5 C), low voltage decay (0.38 V for 200 cycle), excellent rate performance, and cycle stability.

12.
Sci Total Environ ; 718: 137242, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32105927

RESUMO

Accurate identification of nitrate (NO3-) sources is critical to address the issue of groundwater pollution. The nitrogen (N) isotopic enrichment factor (ɛp/s) is an important parameter to explain the N cycle and determine the proportional contribution of NO3- sources. Considering the isotopic fractionation effects in N transformation processes, this study quantitatively analyzed the NO3- sources in groundwater using stable isotopes (δ15N-NO3- and δ18O-NO3-) and the Bayesian isotope mixing model (SIAR). For the first time, the ɛp/s values (0.0‰, -8.7‰, -8.7‰, and 14.7‰) of atmospheric deposition (AD), soil nitrogen (SN), chemical fertilizers (CF), and manure and sewage (M&S) were calculated to determine the NO3- source apportionment in groundwater. It was proved that the isotopic fractionation effect could produce a more accurate NO3- source apportionment. We also found that the NO3- source contributions were closely related to the cropping system. In the vegetable cultivation area, CF (54.32%) and SN (37.75%) were the dominant NO3- source, while in the grain cultivation area, NO3- pollution was largely influenced by SN (33.67%), CF (33.27%), and M&S (30.16%). According to this study, the isotope fractionation is strongly recommended for NO3- source apportionment in groundwater system.

13.
Eur J Radiol ; 124: 108858, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035370

RESUMO

PURPOSE: To verify the feasibility of synthetic MRI in quantitative evaluation of lumbar intervertebral disk (IVD) degeneration, as compared to the conventional CarrPurcell-Meiboom-Gill (CPMG) T2 mapping approach. METHODS: Twenty-four patients with chronic low back pain participated in this study. Patients underwent routine lumbar MRI, CPMG T2 mapping, and synthetic MRI (MAGiC) acquisition. The degree of IVD degeneration was derived from T2-weighted images according to the Pfirrmann classification. The correlation between two T2 measurements was assessed by Pearson correlation and Bland-Altman analysis. Statistical differences of quantitative values obtained from MAGiC data across different degeneration grades were quantified by one-way ANOVA. ROC curves were used to test the sensitivity and specificity of CPMG and MAGiC T2 measurements for assessing Pfirrmann grading. RESULTS: T2 values obtained from CPMG and MAGiC data exhibited strong positive correlation (r = 0.962, p < 0.01). Significant negative correlations were found between quantitative values (p < 0.05) and the Pfirrmann grading. Quantitative values show significant difference across Pfirrmann grading groups (one-way ANOVA, p < 0.001). Additionally, post-hoc tests show significant differences of T1 and T2 between adjacent groups among grades I-IV (p < 0.05), while the significant differences of PD were only observed between adjacent groups among grades II-IV (p < 0.05). There is no significant difference between AUCs of T2 values obtained from CPMG and MAGiC data in differentiating grade I/ II, grade II/ III and grade III/IV. CONCLUSIONS: The synthetic MRI may be used to provide quantitative biomarkers for assessing the level of lumbar intervertebral disc degeneration.

14.
J Cell Biochem ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32056279

RESUMO

Angiogenesis and vasculogenic mimicry (VM) are the main causes of tumor metastasis and recurrence. In this study, we investigated the antiangiogenesis and anti-VM formation of a novel microtubule depolymerizing agent, DHPAC, as well as combretastatin A4 (CA4, a combretastatin derivate) in non-small-cell lung cancer (NSCLC), subsequently elucidating the underlying mechanisms. In human umbilical vein endothelial cells (HUVECs), DHPAC could enter cells and inhibit proliferation, migration, and angiogenesis in the presence and absence of conditioned medium from H1299 cells. Interestingly, the inhibition was enhanced under the stimulation of the conditioned medium. Under hypoxia or normoxia, DHPAC suppressed signal transducer and activator of transcription 3 phosphorylation and reduced vascular endothelial growth factor (VEGF) expression and secretion from HUVECs, thus impeding the activation of the downstream signal transduction pathway of VEGF/VEGFR2. However, JNK inhibitors reversed the inhibitory effect of DHPAC on the angiogenesis, suggesting that DHPAC regulated angiogenesis through activating JNK. In H1299 cells, DHPAC could inhibit proliferation, migration, invasion, and the formation of VM. In addition, DHPAC inhibited the phosphorylation of FAK and AKT and decreased the expressions of VEGF, matrix metalloproteinase 2 (MMP2), MMP9 and Laminin 5, suggesting that DHPAC inhibited VM formation via the FAK/AKT signaling pathway. In addition, CA4 showed a similar effect as DHPAC against angiogenesis and VM formation. These new findings support the use of microtubule destabilizing agents as a promising strategy for cancer therapy.

15.
Cell Mol Neurobiol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060857

RESUMO

Natural bioactive compounds have increasingly proved to be promising in evidence- or target-directed treatment or modification of a spectrum of diseases including cerebral ischemic stroke. Hydroxysafflor yellow A (HSYA), a major active component of the safflower plant, has drawn more interests in recent year for its multiple pharmacological actions in the treatment of cerebrovascular and cardiovascular diseases. Although the Janus kinase signaling, such as JAK2/STAT3 pathway, has been implicated in the modulation of the disease, the inhibition or activation of the pathway that contributed to the neuronal prevention from ischemic damages remains controversial. In this study, a series of experiments were performed to examine the dose- and therapeutic time window-related pharmacological efficacies of HSYA with emphasis on the HSYA-modulated interaction of JAK2/STAT3 and SOCS3 signaling in the MCAO rats. We found that HSYA treatment significantly rescued the neurological and functional deficits in a dose-dependent manner in the MCAO rats within 3 h after ischemia. HSYA treatment with a dosage of 8 mg/kg or higher markedly downregulated the expression of the JAK2-mediated signaling that was activated in response to ischemic insult, while it also promoted the expression of SOCS3 coordinately. In the subsequent experiments with the use of the JAK2 inhibitor WP1066, we found that the treatment of WP1066 alone or combination of WP1066/HSYA all exhibited inhibitory effects on JAK2-mediated signaling, while there was no influence on the SOCS3 activity of corresponding efficacious data in the MCAO rats, suggesting that excessive activation of JAK2/STAT3 might be necessary for HSYA to provoke SOCS3-negative feedback signaling. Taking together, our study demonstrates that HSYA might modulate the crosstalk between JAK2/STAT3 and SOCS3 signaling pathways that eventually contributed to its therapeutic roles against cerebral ischemic stroke.

16.
Aging Cell ; 19(2): e13096, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31944526

RESUMO

Necroptosis is crucially involved in severe cardiac pathological conditions. However, whether necroptosis contributes to age-related intolerance to ischemia/reperfusion (I/R) injury remains elusive. In addition, metformin as a potential anti-aging related injury drug, how it interacts with myocardial necroptosis is not yet clear. Male C57BL/6 mice at 3-4- (young) and 22-24 months of age (aged) and RIPK3-deficient (Ripk3-/- ) mice were used to investigate aging-related I/R injury in vivo. Metformin (125 µg/kg, i.p.), necrostatin-1 (3.5 mg/kg), and adenovirus vector encoding p62-shRNAs (Ad-sh-p62) were used to treat aging mice. I/R-induced myocardial necroptosis was exaggerated in aged mice, which correlated with autophagy defects characterized by p62 accumulation in aged hearts or aged human myocardium. Functionally, blocking autophagic flux promoted H/R-evoked cardiomyocyte necroptosis in vitro. We further revealed that p62 forms a complex with RIP1-RIP3 (necrosome) and promotes the binding of RIP1 and RIP3. In mice, necrostatin-1 treatment (a RIP1 inhibitor), RIP3 deficiency, and cardiac p62 knockdown in vivo demonstrated that p62-RIP1-RIP3-dependent myocardial necroptosis contributes to aging-related myocardial vulnerability to I/R injury. Notably, metformin treatment disrupted p62-RIP1-RIP3 complexes and effectively repressed I/R-induced necroptosis in aged hearts, ultimately reducing mortality in this model. These findings highlight previously unknown mechanisms of aging-related myocardial ischemic vulnerability: p62-necrosome-dependent necroptosis. Metformin acts as a cardioprotective agent that inhibits this unfavorable chain mechanism of aging-related I/R susceptibility.

17.
Sci Rep ; 10(1): 1256, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988387

RESUMO

Wnt signalling mediates complex cell-cellinteractions during development and proliferation. Annexin A8 (AnxA8), a calcium-dependent phospholipid-binding protein, and canonical Wnt signalling mechanisms have both been implicated in retinal pigment epithelial (RPE) cell differentiation. The aim here was to examine the possibility of cross-talk between AnxA8 and Wnt signalling, as both are down-regulated upon fenretinide (FR)-mediated RPE transdifferentiation. AnxA8 suppression in RPE cells via siRNA or administration of FR induced neuronal-like cell transdifferentiation and reduced expression of Wnt-related genes, as measured by real-time PCR and western blotting. AnxA8 gene expression, on the other hand, remained unaltered upon manipulating Wnt signalling, suggesting Wnt-related genes to be downstream effectors of AnxA8. Co-immunoprecipitation revealed an interaction between AnxA8 and ß-catenin, which was reduced in the presence of activated TGF-ß1. TGF-ß1 signalling also reversed the AnxA8 loss-induced cell morphology changes, and induced ß-catenin translocation and GSK-3ß phosphorylation in the absence of AnxA8. Ectopic over-expression of AnxA8 led to an increase in active ß-catenin and GSK-3ß phosphorylation. These data demonstrate an important role for AnxA8 as a regulator of Wnt signalling and a determinant of RPE phenotype, with implications for regenerative medicine approaches that utilise stem cell-derived RPE cells to treat conditions such as age-related macular degeneration.

18.
Epilepsy Behav ; 103(Pt A): 106858, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899164

RESUMO

In this study, we aimed to detect longitudinal alterations in local spontaneous brain activity and functional connectivity (FC) of the default mode network (DMN) in patients with temporal lobe epilepsy (TLE) over a two-year follow-up. We used amplitude of low-frequency fluctuation (ALFF) analysis and independent component analysis (ICA) to explore differences in local spontaneous brain activity and FC strength. In total, 33 participants (16 patients with TLE and 17 age- and gender-matched healthy controls (HCs)) were recruited in this study. All participants performed the Attention Network Test (ANT) for evaluation of the executive control function. Compared with healthy patients at baseline, patients with TLE at follow-up exhibited increased ALFF values in the left medial frontal gyrus, as well as reduced FC values in the left inferior parietal gyrus (IPG) within the DMN. Patients with TLE revealed executive dysfunction, but no progressive deterioration was observed during follow-up. This study revealed the abnormal distribution of ALFF values and Rs-FC changes over a two-year follow-up period in TLE, both of which demonstrated different reorganization trajectories and loss of efficiency.

19.
J Ethnopharmacol ; 251: 112548, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917277

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lychee seed, the seed of Litchi chinensis Sonn. is one of the commonly used in traditional Chinese medicine (TCM). It possesses many pharmacological effects such as blood glucose and lipid-lowering effects, liver protection, and antioxidation. Our preliminary studies have proven that an active fraction derived from lychee seed (LSF) can significantly decrease the blood glucose level, inhibit amyloid-ß (Aß) fibril formation and Tau hyperphosphorylation, and improve the cognitive function and behavior of Alzheimer's disease (AD) model rats. AIM OF THE STUDY: The aim of this study was to identify the main active components in LSF that can inhibit the hyperphosphorylation of Tau through improving insulin resistance (IR) in dexamethasone (DXM)-induced HepG2 and HT22 cells. MATERIALS AND METHODS: The isolation was guided by the bioactivity evaluation of the improvement effect of IR in HepG2 and HT22 cells. The mRNA and protein expressions of IRS-1, PI3K, Akt, GSK-3ß, and Tau were measured by RT-PCR, Western blotting, and immunofluorescence methods, respectively. RESULTS: After extraction, isolation, and elucidation using chromatography and spectrum technologies, three polyphenols including catechin, procyanidin A1 and procyanidin A2 were identified from fractions 3, 5, and 9 derived from LSF. These polyphenols inhibit hyperphosphorylated Tau via the up-regulation of IRS-1/PI3K/Akt and down-regulation of GSK-3ß. Molecular docking result further demonstrate that these polyphenols exhibit good binding property with insulin receptor. CONCLUSIONS: catechin, procyanidin A1, and procyanidin A2 are the main components in LSF that inhibit Tau hyperphosphorylation through improving IR via the IRS-1/PI3K/Akt/GSK-3ß pathway. Therefore, the findings in the current study provide novel insight into the anti-AD mechanism of the components in LSF derived from lychee seed, which is valuable for the further development of a novel drug or nutrient supplement for the prevention and treatment of AD.

20.
BMC Psychiatry ; 20(1): 15, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918691

RESUMO

BACKGROUND: We aimed to investigate the effect of early-age (prenatal, infant, and childhood) trauma on adulthood alcohol use disorder. METHODS: A total number of 1534 subjects who were born and live in the city of Tangshan were selected. The subjects were divided into three age groups. General demographic data, conditions of the mothers during pregnancy, and condition of the babies at birth, were collected. The diagnosis of alcohol use disorder was based on Structured Clinical Interviews for DSM-IV Axis Disorders (patient version) (SCID). The childhood trauma questionnaire short form (CTQ-SF) [1] and the Lifetime of Experience Questionnaire (LTE-Q) [2] were used to evaluate stress in childhood and adulthood, respectively. RESULTS: Only male subjects were diagnosed with lifelong alcohol abuse and alcohol dependence. There was no statistically significant difference in the prevalence of lifetime alcohol use disorder (X2 = 4.480, P = 0.345), current alcohol abuse, and current alcohol dependence among the three groups (X2abuse = 2.177, X2depedence = 2.198, P > 0.05). However, higher prevalence of lifetime alcohol use disorders was found in group with higher scores of CTQ (X2 = 9.315, P = 0.009), emotional abuse (X2 = 8.025, P = 0.018), physical abuse (X2 = 20.4080, P < 0.001), but not in the group with higher scores of emotional neglect (X2 = 1.226, P = 0.542), sexual abuse (X2 = 2.779, P = 0.249), physical neglect (X2 = 3.978, P = 0.137), LTE-Q (X2 = 5.415, P = 0.067), and PSQI (X2 = 5.238, P = 0.073). Protective factor for alcohol abuse for men was identified to be heavy drinking (OR = 0.085, 95%CI: 0.011-0.661), and the risk factors for alcohol abuse were identified to be frequent drinking (OR = 2.736, 95%CI: 1.500, 4.988), and consumption of low liquor (OR = 2.563, 95%CI: 1.387, 4.734). Risk factors for alcohol dependence in males were identified to be consumption of low liquor (OR = 5.501, 95%CI: 2.004, 15.103), frequent drinking (OR = 2.680, 95%CI: 1.164, 6.170), and childhood physical abuse (OR = 2.310, 95% CI: 1.026, 5.201). CONCLUSION: Traumatic experience during infant and prenatal periods does not have a strong statistical correlation with alcohol use disorders for male adults. However, subjects with high CTQ scores, experience of emotional abuse and physical abuse show a statistically higher prevalence of lifetime alcohol use disorders. Several risk factors including consumption of low liquor, frequent drinking, and childhood physical abuse contribute to alcohol dependence in male adults.

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