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1.
Chemosphere ; 262: 128045, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182117

RESUMO

The vulnerability to environmental insults is heightened at early stages of development. However, the neurotoxic potential of bisphenol A (BPA) and bisphenol S (BPS) at developmental windows remains unclear. To investigate the mechanisms mediating the developmental neurotoxicity, zebrafish embryos were treated with 0.01, 0.03, 0.01, 0.3, 1 µM BPA/BPS. Also, we used Tg(HuC:GFP) zebrafish to investigate whether BPA/BPS could induce neuron development. The reduction in body length, and increased heart rate were significant in 0.3 and 1 µM BPA/BPS groups. The green fluorescence protein (GFP) intensity increased at 72 hpf and 120 hpf in Tg(HuC:GFP) larvae which was consistent with the increased mRNA expression of elval3 following BPS treatments, an indication of the plausible effect of BPS on embryonic neuron development. Additionally, BPA/BPS treatments elicited hyperactivity and reduced static time in zebrafish larvae, suggesting behavioral alterations. Moreover, qRT-PCR results showed that BPA and BPS could interfere with the normal expression of development-related genes vegfa, wnt8a, and mstn1 at the developmental stages. The expression of neurodevelopment-related genes (ngn1, elavl3, gfap, α1-tubulin, mbp, and gap43) were significantly upregulated in BPA and BPS treatments, except for the remarkable downregulation of mbp and gfap elicited by BPA at 48 (0.03 µM) and 120 hpf (0.3 µM) respectively; ngn1 at 48 hpf for 0.1 µM BPS. Overall, our results highlighted that embryonic exposure to low concentrations of BPA/BPS could be deleterious to the central nervous system development and elicit behavioral abnormalities in zebrafish at developmental stages.

2.
Biomed Res Int ; 2020: 8765028, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33150182

RESUMO

Immunotherapy, especially based on chimeric antigen receptor (CAR) T cells, has achieved prominent success in the treatment of hematological malignancies. However, approximately 30-50% of patients will have disease relapse following remission after receiving CD19-targeting CAR-T cells, with failure of maintaining a long-term effect. Mechanisms underlying CAR-T therapy inefficiency consist of loss or modulation of target antigen and CAR-T cell poor persistence which mostly results from T cell exhaustion. The unique features and restoration strategies of exhausted T cells (Tex) have been well described in solid tumors. However, the overview associated with CAR-T cell exhaustion is relatively rare in hematological malignancies. In this review, we summarize the characteristics, cellular, and molecular mechanisms of Tex cells as well as approaches to reverse CAR-T cell exhaustion in hematological malignancies, providing novel strategies for immunotherapies.

3.
Pharm Res ; 37(12): 247, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216236

RESUMO

PURPOSE: KRAS is the most frequently mutated gene in human cancers, and ~ 90% of pancreatic cancers exhibit KRAS mutations. Despite the well-known role of KRAS in malignancies, directly inhibiting KRAS is challenging. METHODS: In this study, we successfully synthesized apolipoprotein E3-based liposomes for the co-delivery of gemcitabine (GEM) and a small interfering RNA targeting KRAS (KRAS-siRNA) to improve the efficacy of pancreatic cancer treatment. RESULTS: Apolipoprotein E3 self-assembly on the liposome surface led to a substantial increase in its internalization in PANC1 human pancreatic cancer cells. KRAS-siRNA led to downregulated KRAS protein expression and KRAS-dependent carcinogenic pathways, resulting in the inhibition of cell proliferation, cell cycle arrest, increased apoptosis, and suppression of tumor progression. The combination of KRAS-siRNA and GEM induced a synergistic improvement in cell apoptosis and significantly lower cell viability compared with single-agent therapy. The low IC50 value of A3-SGLP might be attributed to potentiation of the anticancer effect of GEM by siRNA-mediated silencing of KRAS mutations, thereby inducing synergistic effects on cancer cells. CONCLUSION: A3-SGLP led to a marked decrease in the overall tumor burden and did not show any signs of toxicity. Therefore, the combination of KRAS-siRNA and GEM holds great potential for the treatment of pancreatic cancer.

4.
Sci Rep ; 10(1): 20310, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219232

RESUMO

This study aims to investigate optimization of the basal-top-dressing nitrogen ratio for improving winter wheat grain yield, nitrogen use efficiency, water use efficiency and physiological parameters under supplemental irrigation. A water-saving irrigation (SI) regime was established and sufficient irrigation (UI) was used as a control condition. The split-nitrogen regimes used were based on a identical total nitrogen application rate of 240 kg ha-1 but were split in four different proportions between sowing and the jointing stage; i.e. 10:0 (N1), 7:3 (N2), 5:5 (N3) and 3:7 (N4). Compared with the N1, N2 and N4 treatments, N3 treatment increased grain yield, nitrogen and water use efficiencies by 5.27-17.75%, 5.68-18.78% and 5.65-31.02%, respectively, in both years. The yield advantage obtained with the optimized split-nitrogen fertilizer application may be attributable to greater flag leaf photosynthetic capacity and grain-filling capacity. Furthermore, the N3 treatment maintained the highest nitrogen and water use efficiencies. Moreover, we observed that water use efficiency of SI compared with UI increased by 9.75% in 2016 and 10.79% in 2017, respectively. It can be concluded that SI along with a 5:5 basal-top-dressing nitrogen ratio should be considered as an optimal fertigation strategy for both high grain yield and efficiency in winter wheat.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33220929

RESUMO

Dysfunction of long noncoding RNA (lncRNA) is associated with tumorigenesis of various malignancies, including glioma. Previously, lncRNA ARRDC1 antisense RNA 1(ARRDC1-AS1) has been reported to be dysregulated in several tumors. However, the roles of ARRDC1-AS1 in glioma have not been investigated. In this study, we firstly reported that ARRDC1-AS1 expression was distinctly increased in both glioma specimens and cell lines, and high ARRDC1-AS1 expression was associated with advanced clinical progression and poor prognosis of glioma patients. Additionally, STAT1 could activate the transcription of ARRDC1-AS1. Functional studies revealed that knockdown of ARRDC1-AS1 suppressed the proliferation, migration and invasion of glioma cells. Mechanisms exploration indicated ARRDC1-AS1 served as a sponge of miR-432-5p to upregulate PRMT5 expressions. Rescue experiments indicated that knockdown of miR-432-5p reversed the inhibiting effects of ARRDC1-AS1 knockdown on glioma cells. Overall, our findings highlighted the importance of STAT1/ARRDC1-AS1/miR-432-5p/PRMT5 axis in glioma progression and offered novel strategies for glioma treatments.

6.
Ann Hepatol ; : 100290, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221398

RESUMO

Pediatric acute liver failure (PALF) due to mushroom poisoning is a rare and life-threatening disease. There is no specific treatment. Plasma exchange (PE) is often used as a bridge to the regeneration of the liver or transplantation. However, PE is limited due to an inadequate plasma supply and transfusion-related risks. The double plasma molecular adsorption system (DPMAS) can adsorb toxins, including bilirubin and inflammatory mediators. However, the DPMAS cannot improve coagulation disorders. Combining PE and the DPMAS could compensate for the shortcomings of the two techniques. A previous study showed that the combination might be more effective than using PE or the DPMAS alone in patients with mild acute-on-chronic liver failure. To the best of our knowledge, few studies combined PE and the DPMAS for the treatment of PALF due to mushroom poisoning. Here, we specifically describe our experience with PE and the DPMAS in PALF. In conclusion, our study shows that the DPMAS and PE are safe and effective in reducing the bilirubin level and improving blood coagulation in PALF due to mushroom poisoning as a bridge to transplantation or recovery.

7.
Micron ; 140: 102976, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33221524

RESUMO

The Asian larch bark beetle, Ips subelongatus, is a severe pest of larches in Northeastern China. The gustatory and olfactory systems of I. subelongatus play important roles in host location, mating, and feeding. In this study, we examined the types, distributions, and abundances of various sensilla associated with the mouthparts and antennae of I. subelongatus using scanning electron microscopy (SEM). On the mouthparts, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-3), sensilla basiconica (S.b.1-2), sensilla twig basiconica (S.tb.1-3), and sensilla placodea (S.p). S.t.3 are the most abundant sensilla subtype on the mouthparts in both sexes, while S.b.1 are the least abundant. Most sensilla on the mouthparts are located on the maxillae and labium, and the apex of each maxillary and labial palp carry the same sensilla subtypes (S.b.2 and S.tb.1-3). However, the total number of sensilla on the apex of each maxillary palp is higher than that on the labial palp. On the antennae, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-2), sensilla basiconica (S.b.1-3), Böhm bristles (B.b), and sensilla coeloconica (S.co). Antennal sensilla are mostly situated on the anterior surface of the antennal club, particularly on the two dense sensory bands. S.b.1 are the most abundant sensilla subtype on the antennae in both sexes, while S.t.1 are the least abundant. No sexual dimorphism in sensilla type or distribution on the mouthparts or antennae is observed between the sexes of I. subelongatus. However, S.t.3 (on mouthparts) and S.c.1 (on antennae) were significantly more abundant in males than in females, while more S.t.1 (on mouthparts) were observed in females than in males. Finally, the putative functions of each kind of sensilla with respect to their fine structures, distributions, and abundances on the mouthparts and antennae are discussed.

8.
BMC Med Genet ; 21(1): 230, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225895

RESUMO

BACKGROUND: Retinoblastoma is a rare intraocular malignancy and typically initiated by inactivating biallelic mutations of RB1 gene. Each year, ~ 8000 children worldwide are diagnosed for retinoblastoma. In high-income countries, patient survival is over 95% while low-income countries is ~ 30%.If disease is diagnosed early and treated in centers specializing in retinoblastoma, the survival might exceed 95% and many eyes could be safely treated and support a lifetime of good vision. In China, approximate 1100 newly diagnosed cases are expected annually and 28 hospitals covering 25 provinces established centers classified by expertise and resources for better treatment options and follow-up. Comparing with other province of eastern China, Yunnan province is remote geographically. This might result that healthcare staff have low awareness of the role of genetic testing in management and screening in families. METHODS: The patients with retinoblastoma were selected in Yunnan. DNA from blood was used for targeted gene sequencing. Then, an in-house bioinformatics pipeline was done to detect both single nucleotide variants and small insertions/deletions. The pathogenic mutations were identified and further confirmed by conventional methods and cosegregation in families. RESULTS: Using our approach, targeted next generation sequencing was used to detect the mutation of these 12 probands. Bioinformatic predictions showed that nine mutations were found in our study and four were novel pathogenic variants in these nine mutations. CONCLUSIONS: It's the first report to describe RB1 mutations in Yunnan children with retinoblastoma. This study would improve role of genetic testing for management and family screening.

9.
Chem Soc Rev ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226395

RESUMO

Microporous framework membranes such as metal-organic framework (MOF) membranes and covalent organic framework (COF) membranes are constructed by the controlled growth of small building blocks with large porosity and permanent well-defined micropore structures, which can overcome the ubiquitous tradeoff between membrane permeability and selectivity; they hold great promise for the enormous challenging separations in energy and environment fields. Therefore, microporous framework membranes are endowed with great expectations as next-generation membranes, and have evolved into a booming research field. Numerous novel membrane materials, versatile manipulation strategies of membrane structures, and fascinating applications have erupted in the last five years. First, this review summarizes and categorizes the microporous framework membranes with pore sizes lower than 2 nm based on their chemistry: inorganic microporous framework membranes, organic-inorganic microporous framework membranes, and organic microporous framework membranes, where the chemistry, fabrications, and differences among these membranes have been highlighted. Special attention is paid to the membrane structures and their corresponding modifications, including pore architecture, intercrystalline grain boundary, as well as their diverse control strategies. Then, the separation mechanisms of membranes are covered, such as diffusion-selectivity separation, adsorption-selectivity separation, and synergetic adsorption-diffusion-selectivity separation. Meanwhile, intricate membrane design to realize synergistic separation and some emerging mechanisms are highlighted. Finally, the applications of microporous framework membranes for precise gas separation, liquid molecule separation, and ion sieving are summarized. The remaining challenges and future perspectives in this field are discussed. This timely review may provide genuine guidance on the manipulation of membrane structures and inspire creative designs of novel membranes, promoting the sustainable development and steadily increasing prosperity of this field.

10.
Mol Cell Proteomics ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203746

RESUMO

Hirschsprung disease (HSCR) is a heterogeneous group of neurocristopathy characterized by the absence of the enteric ganglia along a variable length of the intestine. Genetic defects play a major role in the pathogenesis of HSCR while family studies of pathogenic variants in all the known genes (loci) only demonstrate incomplete penetrance and variable expressivity for unknown reasons. Here, we applied large-scale, quantitative proteomics of human colon tissues from 21 patients using iTRAQ method followed by bioinformatics analysis. Selected findings were confirmed by parallel reaction monitoring (PRM) verification. At last the interesting differentially expressed proteins were confirmed by western blot. A total of 5341 proteins in human colon tissues were identified. Among them, 664 proteins with >1.2-fold difference were identified in 6 groups: groups A1 and A2 pooled protein from the ganglionic and aganglionic colon of male, long-segment HSCR patients (L-HSCR, n=7); groups B1 and B2 pooled protein from the ganglionic and aganglionic colon of male, short-segment HSCR patients (S-HSCR, n=7); and groups C1 and C2 pooled protein from the ganglionic and aganglionic colon of female, S-HSCR patients (n=7). Based on these analyses, 49 proteins from 5 pathways were selected for PRM verification, including ribosome, endocytosis, spliceosome, oxidative phosphorylation and cell adhesion. The downregulation of three neuron projection development genes ARF4, KIF5B and RAB8A in the aganglionic part of the colon were verified in 15 paired colon samples using WB. The findings of this study will shed new light on the pathogenesis of HSCR and facilitate the development of therapeutic targets.

11.
Small ; : e2004679, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206474

RESUMO

The encapsulation of specific nanoentities into hollow nanomaterials derived from metal organic frameworks has attracted continuous and growing research attentions owing to their unique structural properties and unusual synergistic functions. Herein, using the phase transformation of uniform rhombi dodecahedron ZIF-67, hollow nano-shell with a well-defined morphology is successfully prepared. Particularly, the iron-oxygen complex, that is formed by the interaction between TCPP-Fe/Cu (TCPP = tetrakis(4-carboxyphenyl)-porphyrin) and oxygen, can be acted as an ideal proton acceptor for practical organic reactions. Considering the unique adaptability of hollow ZIFs (named HZ) to the transformation of encapsulated TCPP-Fe/Cu bimetallic catalytic active sites, a heterogeneous catalyst (defined as HZ@TCPP-Fe/Cu) through morphology-controlled thermal transformation and rear assemble processes is designed and constructed. Under heterogeneous conditions, HZ@TCPP-Fe/Cu serves as a multifunctional molecular selector to promote the oxidative dehydrogenation of different aromatic hydrazide derivatives with high selectivity toward primary carbon among primary, secondary, and tertiary carbons that are unachievable by other traditional homogeneous catalysts. The high catalytic activity, selectivity, and recyclability of the catalyst proposed here are attractive advantages for an alternative route to the environmentally benign transformation of aromatic hydrazides to aromatic azobenzene.

12.
Insects ; 11(11)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187256

RESUMO

Chitin synthase 1 (CHS1) is an essential gene regulating chitin during different developmental stages of arthropods. In the current study, we explored for the first time the role of CHS1 gene regulation in the citrus red mite, Panonychus citri (McGregor) (Acari: Tetranychidae), by silencing its expression using (RNA interference) RNAi-based strategies. The results reveal that P. citri tested in different developmental stages, including larvae, protonymphs, deutonymphs, and adults fed on sweet orange leaves dipped in various concentrations (200, 400, 600, and 800 ng/µL) of dsRNA-PcCHS1, resulted in a continuous reduction in their gene expression, and the extent of transcript knockdown was positively correlated with the concentration of dsRNA. Concentration-mortality response assays revealed a mortality of more than 50% among all the studied developmental stages, except for adulthood. Furthermore, the target gene dsRNA-PcCHS1 treatment of larvae, protonymphs, deutonymphs, and females at a treatment rate of 800 ng/mL of dsRNA significantly decreased the egg-laying rates by 48.50%, 43.79%, 54%, and 39%, respectively, and the hatching rates were also considerably reduced by 64.70%, 70%, 64%, and 52.90%, respectively. Moreover, using the leaf dip method, we found that the RNA interference effectively reduced the PcCHS1 transcript levels by 42.50% and 42.06% in the eggs and adults, respectively. The results of this study demonstrate that the RNAi of PcCHS1 can dramatically reduce the survival and fecundity of P. citri, but the dsRNA concentrations and developmental stages can significantly influence the RNAi effects. These findings indicate the potential utility of the PcCHS1 gene in causing developmental irregularities, which could aid in the development of effective and novel RNAi-based strategies for controlling P. citri.

13.
Emerg Microbes Infect ; 9(1): 2368-2378, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33151135

RESUMO

Managing recovered COVID-19 patients with recurrent-positive SARS-CoV-2 RNA test results is challenging. We performed a population-based observational study to characterize the viral RNA level and serum antibody responses in recurrent-positive patients and evaluate their viral transmission risk. Of 479 recovered COVID-19 patients, 93 (19%) recurrent-positive patients were identified, characterized by younger age, with a median discharge-to-recurrent-positive length of 8 days. After readmission, recurrent-positive patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in recurrent-positive patients ranged from 1.8 to 5.7 log10 copies/mL (median: 3.2), which was significantly lower than the corresponding values at disease onset. There are generally no significant differences in antibody levels between recurrent-positive and non-recurrent-positive patients, or in recurrent-positive patients over time (before, during, or after recurrent-positive detection). Virus isolation of nine representative specimens returned negative results. Whole genome sequencing of six specimens yielded only genomic fragments. 96 close contacts and 1,200 candidate contacts of 23 recurrent-positive patients showed no clinical symptoms; their viral RNA (1,296/1,296) and antibody (20/20) tests were negative. After full recovery (no longer/never recurrent-positive), 60% (98/162) patients had neutralizing antibody titers of ≥1:32. Our findings suggested that an intermittent, non-stable excretion of low-level viral RNA may result in recurrent-positive occurrence, rather than re-infection. Recurrent-positive patients pose a low transmission risk, a relatively relaxed management of recovered COVID-19 patients is recommended.

14.
Biosci Rep ; 40(11)2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33135729

RESUMO

BACKGROUND: Ovarian cancer causes high mortality rate worldwide, and despite numerous attempts, the outcome for patients with ovarian cancer are still not well improved. Microarray-based gene expressional analysis provides with valuable information for discriminating functional genes in ovarian cancer development and progression. However, due to the differences in experimental design, the results varied significantly across individual datasets. METHODS: In the present study, the data of gene expression in ovarian cancer were downloaded from Gene Expression Omnibus (GEO) and 16 studies were included. A meta-analysis based gene expression analysis was performed to identify differentially expressed genes (DEGs). The most differentially expressed genes in our meta-analysis were selected for gene expression and gene function validation. RESULTS: A total of 972 DEGs with P-value < 0.001 were identified in ovarian cancer, including 541 up-regulated genes and 431 down-regulated genes, among which 92 additional DEGs were found as gained DEGs. Top five up- and down-regulated genes were selected for the validation of gene expression profiling. Among these genes, up-regulated CD24 molecule (CD24), SRY (sex determining region Y)-box transcription factor 17 (SOX17), WFDC2, epithelial cell adhesion molecule (EPCAM), innate immunity activator (INAVA), and down-regulated aldehyde oxidase 1 (AOX1) were revealed to be with consistent expressional patterns in clinical patient samples of ovarian cancer. Gene functional analysis demonstrated that up-regulated WFDC2 and INAVA promoted ovarian cancer cell migration, WFDC2 enhanced cell proliferation, while down-regulated AOX1 was functional in inducing cell apoptosis of ovarian cancer. CONCLUSION: Our study shed light on the molecular mechanisms underlying the development of ovarian cancer, and facilitated the understanding of novel diagnostic and therapeutic targets in ovarian cancer.

15.
Eur J Med Chem ; : 112988, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33189438

RESUMO

The molecular chaperone heat shock protein 90 (Hsp90) is a promising target for cancer therapy. Natural product aconitine is a potential Hsp90 inhibitor reported in our previous work. In this study, we designed and synthesized a series of 2-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-azabicyclo[3.2.1]octan-3-one derivatives as potent Hsp90 inhibitors by simplifying and modifying aconitine scaffold. Among these compounds, 14t exhibited an excellent antiproliferative activity against LoVo cells with an IC50 value of 0.02 µM and a significant Hsp90α inhibitory activity with an IC50 value of 0.71 nM. Molecular docking studies provided a rational binding model of 14t in complex with Hsp90α. The following cell cycle and apoptosis assays revealed that compound 14t could arrest cell cycle at G1/S phase and induce cell apoptosis via up-regulation of bax and cleaved-caspase 3 protein expressions while inhibiting the expressions of bcl-2. Moreover, 14t could inhibit cell migration in LoVo and SW620 cell lines. Consistent with in vitro results, 14t significantly repressed tumor growth in the SW620 xenograft mouse model.

16.
Adv Mater ; : e2005625, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33191506

RESUMO

Suspended single-hole transistors (SHTs) can also serve as nanoelectromechanical resonators, providing an ideal platform for investigating interactions between mechanical vibrations and charge carriers. Demonstrating such a device in silicon (Si) is of particular interest, due to the strong piezoresistive effect of Si and potential applications in Si-based quantum computation. Here, a suspended Si SHT also acting as a nanoelectromechanical beam resonator is demonstrated. The resonant frequency and zero-point motion of the device are ≈3 GHz and 0.2 pm, respectively, reaching the best level among similar devices demonstrated with Si-containing materials. The mechanical vibration is transduced to electrical readout by the SHT. The signal transduction mechanism is dominated by the piezoresistive effect. A giant apparent effective piezoresistive gauge factor with strong correlation to single-hole tunneling is extracted in this device. The results show the great potential of the device in interfacing charge carriers with mechanical vibrations, as well as investigating potential quantum behavior of the vibration phonon mode.

17.
Theranostics ; 10(26): 11892-11907, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204318

RESUMO

Background: There is an urgent need for the detection of aggressive prostate cancer. Glycoproteins play essential roles in cancer development, while urine is a noninvasive and easily obtainable biological fluid that contains secretory glycoproteins from the urogenital system. Therefore, here we aimed to identify urinary glycoproteins that are capable of differentiating aggressive from non-aggressive prostate cancer. Methods: Quantitative mass spectrometry data of glycopeptides from a discovery cohort comprised of 74 aggressive (Gleason score ≥8) and 68 non-aggressive (Gleason score = 6) prostate cancer urine specimens were acquired via a data independent acquisition approach. The glycopeptides showing distinct expression profiles in aggressive relative to non-aggressive prostate cancer were further evaluated for their performance in distinguishing the two groups either individually or in combination with others using repeated 5-fold cross validation with logistic regression to build predictive models. Predictive models showing good performance from the discovery cohort were further evaluated using a validation cohort. Results: Among the 20 candidate glycoproteins, urinary ACPP outperformed the other candidates. Urinary ACPP can also serve as an adjunct to serum PSA to further improve the discrimination power for aggressive prostate cancer (AUC= 0.82, 95% confidence interval 0.75 to 0.89). A three-signature panel including urinary ACPP, urinary CLU, and serum PSA displayed the ability to distinguish aggressive prostate cancer from non-aggressive prostate cancer with an AUC of 0.86 (95% confidence interval 0.8 to 0.92). Another three-signature panel containing urinary ACPP, urinary LOX, and serum PSA also demonstrated its ability in recognizing aggressive prostate cancer (AUC=0.82, 95% confidence interval 0.75 to 0.9). Moreover, consistent performance was observed from each panel when evaluated using a validation cohort. Conclusion: We have identified glycopeptides of urinary glycoproteins associated with aggressive prostate cancer using a quantitative mass spectrometry-based glycoproteomic approach and demonstrated their potential to serve as noninvasive urinary glycoprotein biomarkers worthy of further validation by a multi-center study.

18.
J Ethnopharmacol ; : 113586, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33212178

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus (AS), previously classified as Eleutherococcus senticosus, is one of the most commonly used herbs in the Chinese materia medica. However, there is currently no comprehensive review summarising advances in AS research. AS has been used as a functional food and in various preparations since ancient times, to invigorate the liver and kidneys, replenish vitality, strengthen the bones, stimulate appetite, and improve memory. It is widely used in countries such as China, Korea, Japan, and Russia, for specific pharmacologic effects, although it contains various chemical components that ensure its broad-spectrum effect. Its chemical constituents mainly include glycosides and flavonoids. Over the past several decades, researchers worldwide have conducted systematic investigations on this herb. AS has positive pharmacological effects on the cardiovascular, central nervous, and immune systems. Representative pathways stimulated by AS are related to neuroactive ligand-receptor interactions, cancer, and phosphatidylinositol 3 kinase/protein kinase B signalling. Importantly, AS is safe and exerts no significant adverse effects at normal doses. AIM OF THE STUDY: To provide comprehensive insights into the ethnobotany, medicinal uses, chemical composition, pharmacological activity, and toxicology of AS to aid its future development and utilisation. MATERIALS AND METHODS: Information about AS was collected from various sources, including classic books about Chinese herbal medicine and scientific databases including scientific journals, books, and pharmacopoeia. We discuss the ethnopharmacology of AS from 1965 to 2020 and summarise the knowledge of AS phytochemicals, pharmacological activity, quality control, and toxicology. CONCLUSIONS: From the current literature, we conclude that AS is a promising dietary Chinese herb with various potential applications owing to its multiple therapeutic effects.

20.
J Immunol Res ; 2020: 9465398, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134398

RESUMO

This new decade has started with a global pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), precipitating a worldwide health crisis and economic downturn. Scientists and clinicians have been racing against time to find therapies for COVID-19. Repurposing approved drugs, developing vaccines and employing passive immunization are three major therapeutic approaches to fighting COVID-19. Chicken immunoglobulin Y (IgY) has the potential to be used as neutralizing antibody against respiratory infections, and its advantages include high avidity, low risk of adverse immune responses, and easy local delivery by intranasal administration. In this study, we raised antibody against the spike (S) protein of SARS-CoV-2 in chickens and extracted IgY (called IgY-S) from egg yolk. IgY-S exhibited high immunoreactivity against SARS-CoV-2 S, and by epitope mapping, we found five linear epitopes of IgY-S in SARS-CoV-2 S, two of which are cross-reactive with SARS-CoV S. Notably, epitope SIIAYTMSL, one of the identified epitopes, partially overlaps the S1/S2 cleavage region in SARS-CoV-2 S and is located on the surface of S trimer in 3D structure, close to the S1/S2 cleavage site. Thus, antibody binding at this location could physically block the access of proteolytic enzymes to S1/S2 cleavage site and thereby impede S1/S2 proteolytic cleavage, which is crucial to subsequent virus-cell membrane fusion and viral cell entry. Therefore, the feasibility of using IgY-S or epitope SIIAYTMS-specific IgY as neutralizing antibody for preventing or treating SARS-CoV-2 infection is worth exploring.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/terapia , Mapeamento de Epitopos , Imunoglobulinas/isolamento & purificação , Pneumonia Viral/terapia , Administração Intranasal , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/isolamento & purificação , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/isolamento & purificação , Galinhas , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Estudos de Viabilidade , Humanos , Imunização Passiva/métodos , Imunoglobulinas/administração & dosagem , Imunoglobulinas/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/imunologia
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