Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 713
Filtrar
1.
World Neurosurg ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33647489

RESUMO

BACKGROUND: Carbamazepine (CBZ) is the first-line therapy for Trigeminal Neuralgia (TGN), and Microvascular Decompression (MVD) is considered as an effective surgical treatment for TGN. But the effect of preoperative CBZ treatment for MVD outcome is not clear. METHODS: A total of 63 patients with classical TGN underwent MVD at the First Affiliated Hospital of Zhengzhou University, PR China, from 2013 to 2019. The data was collected through telephone follow-up and electronic medical records in April 2020, the short-term surgical outcome and the long-term follow-up data were estimated by univariate and multivariate analysis. RESULTS: The multivariate analysis result indicated that preoperative CBZ treatment history was not a significant predictor for short-term outcomes of Microvascular Decompression (P>0.05). The multivariate analysis result for the long-term outcome of MVD indicated that the medication history of preoperative CBZ treatment could predict its postoperative recurrence (P<0.05). CONCLUSION: For patients with classical TGN, a longer preoperative medication history of CBZ treatment had no significant effect on the short-term surgery outcome, but had a poor long-term outcome following MVD.

2.
Nucl Med Biol ; 96-97: 9-18, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33647803

RESUMO

INTRODUCTION: Vesicular monoamine transporter 2 (VMAT2) has been associated with the risk of PD. Genetic reduction of VMAT2 level is reported to increase the vulnerability for dopaminergic neurodegeneration. In this study, by using in vivo microPET imaging with a VMAT2 radioligand [18F]fluoropropyl-(+)-dihydrotetrabenazine ([18F]FP-(+)-DTBZ), we investigated the enhanced role of inhibiting VMAT2 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced loss of dopaminergic neurons. METHODS: The (+)-α-dihydrotetrabenazine ((+)-DTBZ, an inhibitor of VMAT2, 5 mg/kg), or MPTP (low dose (ld): 10 mg/kg, high dose (hd): 30 mg/kg) or both of them were intraperitoneally injected into C57BL/6 mice for 5 or 10 consecutive days. MicroPET imaging with [18F]FP-(+)-DTBZ was performed to test the dopaminergic neuronal integrity. [18F]FP-(+)-DTBZ uptake in striatum was quantified as standardized uptake value (SUV). The pathological changes in the striata and substantia nigra were confirmed by measuring the DA contents and immunohistochemical staining of tyrosine hydroxylase (TH). RESULTS: In vivo imaging results showed that the striatal SUVs of both DTBZ&MPTPld and MPTPhd groups were substantially declined compared to the baseline. Moreover, the striatal uptakes of [18F]FP-(+)-DTBZ in DTBZ&MPTPld and MPTPhd groups were obviously lower than the control, DTBZ group and MPTPld group. Notably, the decrease of the striatal uptake in the DTBZ&MPTPld/10d group was more serious than the DTBZ&MPTPld/5d group and comparable to the MPTPhd group. Consistently, the ratios of DA metabolites to DA in DTBZ&MPTPld/10d and MPTPhd mice were significantly increased. The correlation analysis showed that SUVs were highly correlated to the striatal dopaminergic fiber density and TH-positive dopaminergic neuron number in the substantia nigra. CONCLUSIONS: MicroPET brain imaging with [18F]FP-(+)-DTBZ noninvasively revealed that (+)-DTBZ co-administration significantly aggravated the neurotoxicity of MPTP to dopaminergic neurons, suggesting that inhibition of VMAT2 may be related to the pathogenesis of PD and tracing VMAT2 activity with PET imaging is of potential value in monitoring PD progression.

3.
J Hazard Mater ; 414: 125391, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33652221

RESUMO

Exposure to bisphenol A (BPA) is considered to be associated with the increased incidence of breast cancer. As a widespread replacement of BPA, the effect of bisphenol S (BPS) on breast tumor programming has not been studied. We reported that BPS exposure significantly promoted proliferation and deterioration of breast tumor by nonmonotonic dose response. The mechanisms were investigated by molecular biology and mass spectrometry-based lipidomics, proteomics and imaging. BPS exposure induced the spatially intratumor heterogeneity of morphology-driven lipids and proteins. The more significant proliferation resulted from BPS-10 (10 µg/kg body weight /day) exposure was evidenced by the variations of spatial distribution of lipids related to ceramide-sphingomyelin signaling pathway, proteins related to chromosomal stability and cell proliferation in central necrotic regions of breast tumor. In contrast, the BPS-100 exposure obviously accelerated deterioration of breast tumor by the variations of spatial distribution of proteins that were associated with the stability of nucleic acid structure in peripheral neoplastic regions. Accordingly, dysregulation of metabolism and protein function as well as DNA methylation and hypoxic tumor microenvironment could be applied to predict the possibility of tumorigenesis, proliferation and metastasis that might be caused by other bisphenol analogs.

4.
J Ren Nutr ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33642191

RESUMO

OBJECTIVES: During the past few decades, phosphorus intake has dramatically increased along with higher protein intake and overuse of inorganic phosphate additives worldwide. The detrimental effects of overconsumption of phosphorus are well recognized for patients with chronic kidney disease (CKD), and dietary phosphorus restriction was recommended for these patients. However, the effects of dietary phosphorus restriction in healthy people have not been fully studied. METHODS: In this open-label crossover study, healthy adult men (n = 12) consumed normal phosphorus diet (NPD, 1,500 mg/d) for five days. After a 10-day washout period, healthy adults took low phosphorus diet (LPD, 500 mg/d) for another five days. On the fifth day of each intervention, blood, urine and saliva samples were collected at ten time points, and fecal specimens were collected for bacterial taxa identification. RESULTS: We found that 24-h mean levels of serum phosphate (Pi), urinary Pi, serum parathyroid hormone and fibroblast growth factor 23 decreased, while serum calcium (Ca) and 1,25-dihydroxy vitamin D increased significantly under LPD compared with those under NPD. Dietary phosphorus intake did not change salivary Pi, urinary Ca, salivary Ca and magnesium (Mg) metabolism. Compared with NPD, LPD increased the relative abundance of beneficial microbes including Bacteroidetes, Ruminococcaceae and Lachnospiraceae, indicating that multiple bacterial metabolic pathways have been shifted. CONCLUSIONS: Full-scale data of dietary phosphorus restriction on Pi, Ca and Mg metabolism in healthy male adults are provided. More importantly, for the first time, dietary phosphorus restriction was found to reshape the intestinal microbiome, which provides information for benefits of dietary phosphorus restriction in healthy people, and potential clues for treating patients with CKD.

5.
Poult Sci ; 100(2): 973-981, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518151

RESUMO

It is known that nutrition and immunity are connected, but the mechanism is not very clear. Endogenous retroviruses (ERV) account for 8 to 10% of the human and mouse genomes and play an important role in some biological processes of animals. Recent studies indicate that the activation of ERV can affect the expression of the immunity- or inflammation-related genes, and the activities of ERV are subjected to regulation of many factors including nutritional factors. Therefore, we hypothesize that nutritional status can affect the expression of the immunity- or inflammation-related genes via ERV. To verify this hypothesis, the nutritional status of animals was altered by fasting or overfeeding, and the expression of intact ERV (ERVK18P, ERVK25P) and immunity- or inflammation-related genes (DDX41, IFIH1, IFNG, IRF7, STAT3) in the liver was determined by quantitative PCR, followed by overexpressing ERVK25P in goose primary hepatocytes and determining the expression of the immunity- or inflammation-related genes. The data showed that compared with the control group (no fasting), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the fasted chickens but decreased in the liver of the fasted geese. Moreover, compared with the control group (routinely fed), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the overfed geese. In addition, overexpression of ERVK25P in goose primary hepatocytes can induce the expression of the immunity- or inflammation-related genes. In conclusion, these findings suggest that ERV mediate the effects of fasting and overfeeding on the expression of the immunity- or inflammation-related genes, the mediation varied with poultry species, and ERV and the immunity- or inflammation-related genes may be involved in the development of goose fatty liver. This study provides a potential mechanism for the connection between nutrition and immunity.

6.
Plant Dis ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33529072

RESUMO

Litchi (Litchi chinensis Sonn.) is an indigenous tropical and subtropical fruit in Southern China with an attractive appearance, delicious taste, and good nutritional value (Jiang et al. 2003). In March 2020, brown rots were observed on nearly ripe litchi fruits (cv. Guihuaxiang) in an orchard of Lingshui county, Hainan province of China (18.615877° N, 109.948871° E). About 5% fruits were symptomatic in the field, and the disease caused postharvest losses during storage. The initial infected fruits had no obvious symptoms on the outer pericarp surfaces, but appeared irregular, brown to black-brown lesions in the inner pericarps around the pedicels. Then lesions expanded and became brown rots. Small tissues (4 mm × 4 mm) of fruit pericarps were cut from symptomatic fruits, surface-sterilized in 1% sodium hypochlorite for 3 min, rinsed in sterilized water three times, plated on potato dextrose agar (PDA) and incubated at 28℃ in the darkness. Morphologically similar colonies were isolated from 85% of 20 samples after 4 days of incubation. Ten isolates were purified using a single-spore isolation method. The isolates grown on PDA had abundant, fluffy, whitish to yellowish aerial mycelia, and the reverse side of the Petri dish was pale brown. Morphological characteristics of conidia were further determined on carnation leaf-piece agar (CLA) (Leslie et al. 2006). Macroconidia were straight to slightly curved, 3- to 5-septates with a foot-shaped basal cell, tapered at the apex, 2.70 to 4.43 µm × 18.63 to 37.58 µm (3.56 ± 0.36 × 28.68 ± 4.34 µm) (n = 100). Microconidia were fusoid to ovoid, 0- to 1-septate, 2.10 to 3.57 µm × 8.18 to 18.20 µm (2.88 ± 0.34 × 11.71 ± 1.97 µm) (n = 100). Chlamydospores on hyphae singly or in chains were globose, subglobose, or ellipsoidal. Based on cultural features and morphological characteristics, the fungus was identified as a Fusarium species (Leslie et al. 2006). To further confirm the pathogen, DNA was extracted from the 7-day-old aerial mycelia of three isolates (LZ-1, LZ-3, and LZ-5) following Chohan et al. (2019). The sequences of the internal transcribed spacer region of rDNA (ITS), translation elongation factor-1 alpha (tef1) gene, and histone H3 (his3) gene were partially amplified using primers ITS1/ITS4, EF1-728F/EF1-986R, and CYLH3F/CYLH3R, respectively (Funnell-Harris et al. 2017). The nucleotide sequences were deposited in GenBank (ITS: 515 bp, MW029882, 533 bp, MW092186, and 465 bp, MW092187; tef1: 292 bp, MW034437, 262 bp, MW159143, and 292 bp, MW159141; his3: 489 bp, MW034438, 477 bp, MW159142, and 474 bp, MW159140). The ITS, tef1, and his3 genes showed 99-100% similarity with the ITS (MH979697), tef1 (MH979698), and his3 (MH979696) genes, respectively of Fusarium incarnatum (TG0520) from muskmelon fruit. The phylogenetic analysis of the tef1 and his3 gene sequences showed that the three isolates clustered with F. incarnatum. Pathogenicity tests were conducted by spraying conidial suspension (1×106 conidia/ml) on wounded young fruits in the orchid. Negative controls were sprayed with sterilized water. Fruits were bagged with polythene bags for 24 hours and then unbagged for 10 days. Each treatment had 30 fruits. The inoculated fruits developed symptoms similar to those observed in the orchard and showed light brown lesions on the outer pericarp surfaces and irregular, brown to black-brown lesions in the inner pericarps, while the fruits of negative control remained symptomless. The same fungus was successfully recovered from symptomatic fruits, and thus, the test for the Koch's postulates was completed. F. semitectum (synonym: F. incarnatum) (Saha et al. 2005), F. oxysporum (Bashar et al. 2012), and F. moniliforme (Rashid et al. 2015) have been previously reported as pathogens causing litchi fruit rots in India and Bangladesh. To our knowledge, this is the first report of Fusarium incarnatum causing litchi fruit rot in China.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33608303

RESUMO

OBJECTIVE: To evaluate radiologic and clinical inflammatory activity in women with MS during pregnancy and postpartum. METHODS: We performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the University of California, San Francisco MS Center between 2005 and 2018. Proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions (primary outcome) and annualized relapse rate (ARR; secondary) were compared before and after pregnancy. RESULTS: We identified 155 pregnancies in 119 women (median Expanded Disability Status Scale [EDSS] 2.0). For the 146 live birth pregnancies, prepregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p = 0.017) and increased in the 3 months postpartum (ARR 0.61, p = 0.012); and 16% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 53% had new T2 and/or Gd+ lesions postpartum compared with 32% prepregnancy (p < 0.001). Postpartum clinical relapses were associated with Gd+ lesions (p < 0.001). However, even for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 31%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio = 0.3, 95% confidence interval 0.1-0.9) were observed for relapses. CONCLUSIONS: Building on previous reports of increased relapse rate in the first 3 months postpartum, we report a significant association between inflammation on MRI and this clinical activity. We also detected postpartum radiologic activity in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.

8.
Food Chem Toxicol ; 150: 112071, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33609594

RESUMO

In this work, a one-step fluorometric strategy based on nanometal surface energy transfer (NSET) between carbon dots (CDs) and gold nanoparticles (AuNPs) was developed for facile detection of Staphylococcus aureus (S. aureus). The fluorescence of CDs was quenched up to 63.5% by AuNPs due to nucleic acid hybridization in the presence of linker DNA, which contained the complementary sequences of S. aureus-specific aptamer, and the fluorescence signal was in the "off" state. Upon aptamer addition, the CDs was released from linker DNA through the strong competitiveness of aptamer, leading to the notable fluorescence recovered. Once S. aureus is introduced, aptamer preferentially bind to the bacterial surface and cannot hybridize with complementary sequences in the linker DNA, resulting in the fluorescence signal with "off" state. Based on these findings, the performance and reliability of the fluorescence-based assay were evaluated. Compared to direct hybridization of complementary DNA on the surface of CDs and AuNPs, our sensing strategy has enhanced detection limit (10 cfu⋅mL-1) and improved linear range (10 to 106 cfu⋅mL-1) for S. aureus. Therefore, our proposed enzyme-free and label-free strategy may become a promising method for ease of operation, sensitive and selective S. aureus detection.

9.
Mol Immunol ; 133: 77-85, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33636432

RESUMO

Tripartite motif-containing 9 (TRIM9) has been demonstrated to exert important roles in regulation of innate immune signaling. In this study, a novel TRIM9 homolog was identified from Penaeus monodon (named PmTRIM9). The open reading frame (ORF) of PmTRIM9 was 2064 bp, which encoding a 687-amino-acid polypeptide. Following Vibrio parahaemolyticus challenge, the expression levels of PmTRIM9 mRNA were significantly down-regulated in tested tissues. RNA interference and recombinant protein injection experiments were performed to explore the function of PmTRIM9, and the results showed it could facilitate V. parahaemolyticus replication and lead P. monodon more vulnerable to V. parahaemolyticus challenge. The dual-luciferase reporter assay showed that PmTRIM9 possessed the ability to inhibit the promoter activity in HEK293 T cells. Silencing of PmTRIM9 could increase the expression of the major NF-κB transcription factor, PmRelish. Further studies showed that knockdown of PmRelish promoted the V. parahaemolyticus infection and decreased the expression of specific antimicrobial peptides (AMPs), including PmCRU5, PmCRU7, PmALF6, PmALF3, PmLYZ and PmPEN5. However, knockdown of PmTRIM9 increased expression levels of the same AMPs, but except for PmCRU5, indicating that PmTRIM9 may negatively regulate the PmRelish-mediated expression of AMPs. All these results suggest that PmTRIM9 was involved in facilitating V. parahaemolyticus infection by inhibition of Relish pathway in P. monodon.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33543825

RESUMO

Single-atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. SAE has recently been demonstrated high potential in tumor therapy by altering cellular redox balance. Here, we constructed a PEGylated manganese-based SAE (Mn/PSAE) by coordination of single-atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H 2 O 2 to -OH through a Fenton-like reaction; it also promotes the decomposition of H 2 O 2 to O 2 and continuously catalyzes the conversion of O 2 to cytotoxic -O 2 - via oxidase-like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. In addition, the prominent photo-thermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.

11.
J Orthop Surg Res ; 16(1): 128, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568152

RESUMO

BACKGROUND: Whether vastus medialis obliquus atrophy exists in patients with patellofemoral pain syndrome and whether the amount of atrophy differs between the vastus medialis obliquus and vastus lateralis muscles remain unknown. MATERIALS: From June 2016 to March 2019, 61 patients with patellofemoral pain syndrome were retrospectively included in the study group, and an age-, sex-, and body mass index-matched cohort of 61 patients with normal knees was randomly selected as the control group. All enrolled subjects had undergone CT scans in the supine position. The cross-sectional areas of the vastus medialis obliquus and the vastus lateralis muscle in the sections 0, 5, 10, 15, and 20 mm above the upper pole of the patella were measured, and the vastus medialis obliquus/vastus lateralis muscle area ratio was evaluated. RESULTS: In the study group, the vastus medialis obliquus areas and the vastus lateralis muscle areas in the sections that were 0, 5, 10, 15, and 20 mm above the upper pole of the patella were significantly smaller than the respective areas in the control group (P < 0.05). The vastus medialis obliquus/vastus lateralis muscle area ratio was significantly smaller at the upper pole of the patella (the section 0 mm above the upper pole of the patella) than the corresponding ratio in the control group (P < 0.05). No significant difference was noted between the two groups in the sections 5, 10, 15, and 20 mm above the upper pole of the patella (P > 0.05). CONCLUSION: In patients with patellofemoral pain syndrome, vastus medialis obliquus and vastus lateralis muscle atrophy existed in sections 0-20 mm above the upper pole of the patella, compared with normal controls, and atrophy of the vastus medialis obliquus was more evident than that of the vastus lateralis muscle at the upper pole of the patella. These findings support the rationale for the use of general quadriceps exercise combined with vastus medialis obliquus strengthening exercise as part of the rehabilitation programme for the patients with patellofemoral pain syndrome.

12.
J Med Chem ; 64(4): 2010-2023, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33543615

RESUMO

Hsp90 is a new promising target for cancer treatment. Many inhibitors have been discovered as therapeutic agents, and some have passed Phase I and II. However, no one is approved by FDA yet. Novel and druggable Hsp90 inhibitors are still demanding. Here, we report a new way to discover high potent Hsp90 inhibitors as antinasopharyngeal carcinoma agents through assembling fragments. With chemotyping analysis, we extract seven chemotypes from 3482 known Hsp90 inhibitors, screen 500 fragments that are compatible with the chemotypes, and confirm 15 anti-Hsp90 fragments. Click chemistry is employed to construct 172 molecules and synthesize 21 compounds among them. The best inhibitor 3d was further optimized and resulted in more potent 4f (IC50 = 0.16 µM). In vitro and in vivo experiments confirmed that 4f is a promising agent against nasopharyngeal carcinoma. This study may provide a strategy in discovering new ligands against targets without well-understood structures.

13.
Food Chem Toxicol ; 149: 112035, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33548372

RESUMO

Food safety problems attributed to foodborne pathogenic bacteria seriously endanger human health and cause substantial economic losses. Novel assays for rapid and sensitive identification of foodborne pathogenic bacteria are highly desired. In this study, a multicolor sensing system has been established for simultaneous determination of four foodborne bacteria by exploiting oxidase mimicking activity of aptamer-functionalized manganese dioxide-coated ferriferrous oxide (apt-Fe3O4/MnO2) nanocomposites and oxTMB etching of gold nanorods (AuNRs). Apt-Fe3O4/MnO2 nanocomposites were used as capture probes to recognize and capture specific bacteria. The captured bacteria blocked the catalytic sites of the magnetic conjugate, which inhibited the catalyzation of oxTMB and further reduced the etching of AuNRs. Consequently, the longitudinal shift of AuNRs decreased linearly with the increase of the concentration of bacteria ranging from 10 to 106 CFU mL-1. Instrumental detection limits for S. aureus, L. monocytogenes, E. coli O157:H7 and V. parahaemolyticus reached down to 1.3 CFU mL-1, 1.2 CFU mL-1, 1.3 CFU mL-1 and 1.4 CFU mL-1, respectively. And their visual detection limit was as low as 10 CFU mL-1. The whole detection process only needs 40 min, suggesting that this method is promising in on-site detection of bacteria.

14.
Age Ageing ; 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33492360

RESUMO

OBJECTIVE: we aimed to investigate the association of smoking cessation with risk of all-cause mortality amongst oldest old people (aged ≥ 80 years). DESIGN: this was a prospective cohort study. SETTING: the Chinese Longitudinal Healthy Longevity Survey, implemented in 23 provinces of China. PARTICIPANTS: a total of 28,643 community-dwelling oldest old people (mean age, 92.9 ± 7.5 years) were included. METHODS: in this community-based cohort study, Cox proportional hazards models were used to examine the association of smoking cessation with risk of all-cause mortality. RESULTS: during 136,585 person-years of follow-up from baseline to 1 September 2014, compared with never smokers, hazard ratios and 95% confidence intervals for all-cause mortality were 1.06 (1.02-1.10) for current smokers, 1.23 (1.09-1.39) for transient quitters (≤1 consecutive years since smoking cessation), 1.22 (1.12-1.32) for recent quitters (2-6 consecutive years since smoking cessation) and 1.11 (1.02-1.22) for long-term quitters (>6 consecutive years since smoking cessation). Cox models with penalised splines revealed an increased risk of all-cause mortality after smoking cessation; the highest mortality risk was observed within 2-4 years after smoking cessation and the risk gradually decreased with duration of smoking cessation. We further conducted subgroup analyses and sensitivity analyses to reduce the impact of reverse causation. CONCLUSIONS: smoking is harmful to health in all populations. Our study findings indicated smoking cessation in late life to be associated with increased risk of all-cause mortality amongst oldest old people who have smoked for a long time.

15.
Pharmacol Res ; : 105436, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33497804

RESUMO

Type 2 diabetes (T2D) is a public health problem with a rising incidence worldwide. In this study, a potential new biomarker for T2D and mechanisms underlying the hypoglycemic effects of Enteromorpha prolifera oligosaccharide were investigated. Tandem mass tag labeling with LC-MS/MS was used to identify the differentially expressed proteins (DEPs) between the jejunum of diabetic rats and control rats. Correlations between glycometabolic parameters and DEPs were revealed by a network analysis. The expression levels of target genes in key metabolic pathways were further evaluated to identify candidate biomarkers. Among 6810 total proteins, approximately 88 % were quantified, of which 148 DEPs with a fold change of <0.83 or>1.2 and a corrected p-value of <0.05 were identified. A KEGG enrichment analysis indicated that the hypoglycaemic effects of E. prolifera oligosaccharide involved the PI3K/AKT and extracellular matrix receptor interaction signaling pathways. More importantly, Col1a1 was the most significant gene in the extracellular matrix receptor interaction pathway and was linked to hypoglycaemic activity for the first time. Thus, Col1a1 is a novel potential therapeutic target for alleviating T2D.

16.
BMC Neurol ; 21(1): 12, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430805

RESUMO

BACKGROUND: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. METHODS: In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. RESULTS: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language. CONCLUSIONS: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.

17.
J Med Internet Res ; 23(1): e24356, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33470940

RESUMO

BACKGROUND: Cognitive impairment is one of the most debilitating manifestations of multiple sclerosis. Currently, the assessment of cognition relies on a time-consuming and extensive neuropsychological examination, which is only available in some centers. OBJECTIVE: To enable simpler, more accessible cognitive screening, we sought to determine the feasibility and potential assessment sensitivity of an unsupervised, adaptive, video game-based digital therapeutic to assess cognition in multiple sclerosis. METHODS: A total of 100 people with multiple sclerosis (33 with cognitive impairment and 67 without cognitive impairment) and 24 adults without multiple sclerosis were tested with the tablet game (EVO Monitor) and standard measures, including the Brief International Cognitive Assessment for Multiple Sclerosis (which included the Symbol Digit Modalities Test [SDMT]) and Multiple Sclerosis Functional Composite 4 (which included the Timed 25-Foot Walk test). Patients with multiple sclerosis also underwent neurological evaluations and contributed recent structural magnetic resonance imaging scans. Group differences in EVO Monitor performance and the association between EVO Monitor performance and standard measures were investigated. RESULTS: Participants with multiple sclerosis and cognitive impairment showed worse performance in EVO Monitor compared with participants without multiple sclerosis (P=.01) and participants with multiple sclerosis without cognitive impairment (all P<.002). Regression analyses indicated that participants with a lower SDMT score showed lower performance in EVO Monitor (r=0.52, P<.001). Further exploratory analyses revealed associations between performance in EVO Monitor and walking speed (r=-0.45, P<.001) as well as brain volumetric data (left thalamic volume: r=0.47, P<.001; right thalamic volume: r=0.39, P=.002; left rostral middle frontal volume: r=0.28, P=.03; right rostral middle frontal volume: r=0.27, P=.03). CONCLUSIONS: These findings suggest that EVO Monitor, an unsupervised, video game-based digital program integrated with adaptive mechanics, is a clinically valuable approach to measuring cognitive performance in patients with multiple sclerosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03569618; https://clinicaltrials.gov/ct2/show/NCT03569618.

18.
ACS Appl Mater Interfaces ; 13(4): 5574-5582, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33472372

RESUMO

Soft actuators with perception capability are essential for robots to intelligently interact with humans and the environment. However, existing perceptive soft actuators require complex integration and coupling between the discrete functional units to achieve autonomy. Here, we report entirely soft actuators with embodied sensing, actuation, and control at the single-unit level. This is achieved by synergistically harnessing the mechanosensing and electrothermal properties of liquid metal (LM) to actuate the thermally responsive liquid crystal elastomer (LCE). We create multifunctional LM circuits on the LCE surface using a simple and facile methodology based on magnetic printing. The fluidic LM circuit can not only be utilized as a conformable resistive heater but also as a sensory skin to perceive its own deformation. Moreover, the rational design of the LM circuits makes it possible to achieve biomimetic autonomous actuation in response to mechanical stimuli such as pressure or strain. In addition, the intrinsic stretchability of LM allows us to create 3D spring-like actuators via a simple prestretch step, and complex helical motions can be obtained upon mechanical stimulation. This work provides a unique and simple design for autonomous soft robotics with embodied intelligence.

19.
J Low Genit Tract Dis ; 25(1): 22-26, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33347045

RESUMO

OBJECTIVE: The aim of the study was to evaluate the Cobas 4800 Assay and the SeqHPV Assay with self (S) and direct (D) cervical samples in the Chinese Multicenter Screening Trial (CHIMUST). MATERIALS AND METHODS: The CHIMUST is a large population-based multicenter clinical trial, and 10,885 women aged 30-59 years from 15 sites in 7 provinces with no cervical cancer screening for 3 years were eligible. All participating women contributed one self-collected sample (S) and 1 physician-collected endocervical sample (DL). The self-collected sample was first applied to the solid media transport card (SS), and then, the brush placed in 6 mL of ThinPrepSolution (SL). All samples were tested with Cobas 4800 and SeqHPV high-risk HPV assays. Patients human papillomavirus positive (self or direct) were recalled for colposcopy and biopsies. RESULTS: A total of 10,399 women had complete data. The mean age was 43.9 years. A total of 1.4% (142/10,399) had cervical intraepithelial neoplasia (CIN) 2+ and 0.5% (54/10,339) had CIN 3+. In the liquid specimens, the overall HPV infection rates were 10.8% for Cobas and 10.9% for SeqHPV in D sample, and 13.7% for Cobas and 11.6% for SeqHPV in SL sample, respectively. The sensitivity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 95.07%, 95.07%, 94.33%, and 96.48%, respectively. The specificity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 90.38%, 87.35%, 90.21%, and 89.53%, respectively. There were no differences in sensitivity when applying the 2 assays to both self- and directly collected samples in liquid transport media (p > .05). CONCLUSIONS: Both Cobas and SeqHPV screening assays using both self-collected and directly endocervical collected specimens demonstrate similar sensitivity for the detection of CIN 2+ and CIN 3+.

20.
Ecotoxicol Environ Saf ; 209: 111800, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33340955

RESUMO

Cell division cycle 37 (Cdc37) is an important cytoplasmic phosphoprotein, which usually functions as a complex with heat shock protein 90 (Hsp90), to effectively reduce the damage caused by heavy metals, such as cadmium (Cd), in aquatic animals. The high toxicity of Cd in aquatic systems generally has a deleterious effect on healthy farming of shrimps. In the present study, a novel Cdc37 gene from Penaeus monodon was identified and designated as PmCdc37. Following exposure to Cd stress, the expression levels of PmCdc37 were upregulated at the transcriptional level in both the hepatopancreas and hemolymph. RNA interference and recombinant protein injection experiments were carried out to determine the function of PmCdc37 in P. monodon following Cd exposure. To clarify the correlations between PmCdc37 and PmHsp90, the respective recombinant proteins were expressed in vitro, and the ATPase activity of PmHsp90, with or without PmCdc37, was assessed. Moreover, a pull-down assay was conducted to detect the correlation between PmCdc37 and PmHsp90. After analyzing the expression patterns of PmHsp90 following Cd challenge, whether PmHsp90 can promote the ability of PmCdc37 to resist Cd stress or not was investigated. The results showed that formation of a PmHsp90/PmCdc37 complex protected shrimp against Cd stress-induced damage. Moreover, we also confirmed that PmSOD is involved in Cd stress, and that the PmHsp90/PmCdc37 complex can regulate SOD enzymatic activity. PmSOD was involved in decreasing the MDA content in shrimp hemolymph caused by Cd stress. We concluded that during exposure to Cd, the PmHsp90/PmCdc37 complex increases SOD enzyme activity, and in turn decreases the MDA content, thereby protecting shrimp against the damage caused by Cd stress. The present studies contribute to understanding the molecular mechanism underlying resistance to Cd stress in shrimp.


Assuntos
Cádmio/toxicidade , Proteínas de Ciclo Celular/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Penaeidae/fisiologia , Animais , Cádmio/metabolismo , Proteínas de Choque Térmico HSP90/genética , Hemolinfa/metabolismo , Hepatopâncreas/metabolismo , Peroxidação de Lipídeos/fisiologia , Penaeidae/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...