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1.
Neural Regen Res ; 16(8): 1453-1459, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33433458

RESUMO

Brain-derived neurotrophic factor (BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The mRNA expression levels of BDNF and its processing enzymes and receptors (Furin, matrix metallopeptidase 9, tissue-type plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury; however, the expression levels of these mRNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia (approval No. U12-18) on July 30, 2018.

2.
Compr Rev Food Sci Food Saf ; 20(1): 1075-1100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33443809

RESUMO

In recent years, starch-based nanoparticles have attracted great interest due to their small size, good biocompatibility, and environmental friendliness, as well as their potential applications in foods, drug delivery carriers, and biodegradable edible films. Compared with nonstarch polysaccharides, starch can be enzymatically hydrolyzed into glucose in vivo, so it can be used as an enzyme-responsive carrier. The recent research progress of starch-based nanoparticles, including starch nanoparticles, starch nanospheres, starch micelles, starch vesicles, starch nanogels, and starch nanofibers, are reviewed in this paper. The main focus is on their responsiveness, digestibility, toxicity, interactions with other components, and applications. Starch-based nanoparticles are nontoxic and responsive to pH, temperature, light, and other stimuli. It can interact with proteins, antioxidants, and lipids through electrostatic interactions and hydrogen bonding interactions. Starch-based nanoparticles have a wide range of applications, including enhancing the mechanical properties of films and gels, stabilizing emulsions, as a fluorescent indicator, a catalyst, and a nanocarrier to control the release of active ingredients and drugs.

3.
Int J Biol Macromol ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278451

RESUMO

Recently, amylose-lipid complexes have attracted widespread attention because of their various applications. However, DBS complexed with fatty acids of different carbon chain length are rarely studied. This study aimed to probe the complexation of DBS with saturated fatty acids having different carbon chain lengths (C6-C18). The results revealed that DBS was able to form V-type complexes with all the fatty acids considered. Compared to DBS, the relative crystallinity of the complexes increased 2-3 times. DBS with lauric acid and myristic acid formed three types V-type complexes (type I, type IIa, and type IIb). The complexing index followed the order of hexanoic acid > octanoic acid > capric acid > lauric acid > myristic acid > palmitic acid > stearic acid. Furthermore, lauric acid and myristic acid formed complexes with DBS more easily compared with other fatty acids.

4.
Front Cell Dev Biol ; 8: 529544, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262982

RESUMO

Neonatal hypoxic ischemic encephalopathy (HIE) due to birth asphyxia is common and causes severe neurological deficits, without any effective therapies currently available. Neuronal death is an important driving factors of neurological disorders after HIE, but the regulatory mechanisms are still uncertain. Long non-coding RNA (lncRNA) or ceRNA network act as a significant regulator in neuroregeneration and neuronal apoptosis, thus owning a great potential as therapeutic targets in HIE. Here, we found a new lncRNA, is the most functional in targeting the Igfbp3 gene in HIE, which enriched in the cell growth and cell apoptosis processes. In addition, luciferase reporter assay showed competitive regulatory binding sites to the target gene Igfbp3 between TCONS00044054 (Vi4) and miR-185-5p. The change in blood miR-185-5p and Igfbp3 expression is further confirmed in patients with brain ischemia. Moreover, Vi4 overexpression and miR-185-5p knock-out promote the neuron survival and neurite growth, and suppress the cell apoptosis, then further improve the motor and cognitive deficits in rats with HIE, while Igfbp3 interfering got the opposite results. Together, Vi4-miR-185-5p-Igfbp3 regulatory network plays an important role in neuron survival and cell apoptosis and further promote the neuro-functional recovery from HIE, therefore is a likely a drug target for HIE therapy.

5.
J Mol Neurosci ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165740

RESUMO

A Correction to this paper has been published: https://doi.org/10.1007/s12031-020-01741-2.

6.
Biomed Res Int ; 2020: 9786428, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33102601

RESUMO

Background: Colorectal cancer (CRC) is an underlying deadly malignancy with poor prognosis, lacking effective therapies currently available to improve the prognosis. C18H17NO6 (AUCAN), a kind of dibenzofuran extracted from a special plant in Yunnan Province (China), is identified as a natural anticancer agent exerting strong inhibitory activities on various cancers. Our study was committed to investigating the potency of AUCAN against colorectal cancers and further exploring the potential mechanisms via proteomic analysis. Methods: Cell Counting Kit-8 assay and immunofluorescence staining were used to investigate the effect of AUCAN on the viability and proliferation of HCT-116 cells and RKO cells. The apoptosis of HCT-116 and RKO cells after AUCAN administration was determined by the flow cytometry test. The effects of AUCAN on invasion and migration of tumor cells were investigated by the colony formation assay, wound healing test, and Transwell invasion test. Meanwhile, the energy metabolism and growth of tumor tissues after AUCAN administration with 10 mg/kg and 20 mg/kg were examined by PET-CT in vivo. The side effects of AUCAN treatment were also evaluated through blood routine and liver function examination. RKO cell proliferation and apoptosis in vivo were further determined by hematoxylin and eosin staining, TUNEL staining, and immunohistochemistry. Furthermore, the differentially expressed proteins (DEPs) involved in AUCAN treatment were determined by proteomic analysis followed by functional clustering analysis. Results: The results showed that AUCAN suppressed the migratory abilities and enhanced apoptosis of HCT-116 and RKO cell lines. Meanwhile, AUCAN treatment dramatically depressed the growth and volume of colorectal tumors in nude mice and suppressed the survival of RKO cells in tumor tissues without any side effects on the blood routine and liver function. In addition, twenty-four upregulated and forty-two downregulated proteins were identified. Additionally, functional clustering analysis concealed enriched biological processes, cellular components, molecular functions, and related pathways of these proteins involved in cellular metabolic. Finally, the protein-protein interaction analysis revealed the regulatory connection among these DEPs. Conclusions: Taken together, AUCAN exerted its significant antitumor effect without side effects in the blood routine and liver function and the underlying mechanisms were preliminarily investigated by proteomic analysis.

7.
J Pain Res ; 13: 2673-2684, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116809

RESUMO

Purpose: To investigate the impact of body mass index (BMI) on the analgesic effects and adverse reactions of patient-controlled intravenous analgesia (PCIA). Methods: From 2017 to 2018, 390 patients undergoing open gastrointestinal surgery were reviewed at West China Hospital, Sichuan University. All used PCIA of sufentanil combined with dexmedetomidine and flurbiprofen axetil. According to their BMIs, they were placed into six groups: group A (BMI < 18.5kg/m2, 29), group B (18.5kg/m2 ≤ BMI< 22kg/m2, 124), group C (22kg/m2 ≤ BMI < 24kg/m2, 99), group D (24kg/m2 ≤ BMI < 26kg/m2, 69), group E (26kg/m2 ≤ BMI < 28kg/m2, 46) and group F (BMI ≥28kg/m2, 23). Main data of the perioperative use of analgesics, postoperative visual analogue score (VAS), and adverse reactions were collected. Results: Twenty-four hours (h) after surgery, patients in group A had a higher resting VAS than the other groups, especially B (pA-B = 0.011). VAS of patients during activity in group B was lower than those in group C 48 h after surgery (p = 0.013). Compared with groups B to F, group A had a significantly lower incidence of hypertension (p = 0.012) and a significantly higher incidence of vomiting 24 h after surgery (p = 0.009). Binary logistic analysis found that higher age was a risk factor for vomiting 24 h after surgery (OR 1.158, p = 0.045). Conclusion: Using the same PCIA, patients with BMIs of less than 18.5 kg/m2 had worse analgesia on the first day after surgery and were more likely to vomit. Postoperative analgesia and related experiences in patients with BMIs of less than 18.5 kg/m2 need to be improved.

8.
Int J Biol Macromol ; 163: 2048-2059, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961176

RESUMO

In this work, we aimed to investigate the effect of the combination of starch nanoparticles (SNPs) and Tween 80 (TW) on the stability of oil-in-water emulsions. The emulsions prepared under different SNPs/TW ratios and different oil fraction values were characterized by means of photography, optical microscopy, laser particle size analysis, rheological measurement, quartz crystal microbalance analysis, and confocal laser scanning microscopy. At an oil fraction value of 0.4, the emulsions with a 3: 1 ratio of SNPs (1.5%, w/v) to TW (0.5%, w/v) exhibited excellent storage stability over a long period of 30 d, which was significantly better than the 2% TW stabilized emulsion and the 2% SNPs stabilized emulsion. Compared with the SNPs stable emulsions, the presence of TW decreased the emulsion droplets size, which was beneficial to reduce the aggregation of droplets. Emulsions co-stabilized by SNPs and TW can maintain good performance under harsh conditions. The results of quartz crystal microbalance analysis and isothermal titration calorimetry revealed non-covalent interactions between SNPs and TW. The results showed that SNPs and TW co-existed at the oil-water interface and improved the performance of the emulsion.

9.
Carbohydr Polym ; 246: 116586, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32747246

RESUMO

Chitosan hydrogels fabricated by covalent crosslinking exhibit tough mechanical properties and chemical stability. In this paper, debranched starch (DBS) is oxidized to dialdehyde debranched starch (DADBS), which is used as a new type of a crosslinking agent to prepare hydrogels. Chitosan hydrogels with excellent properties are prepared by dynamic Schiff-base crosslinking between the aldehyde groups in DADBS and the amino groups in chitosan. Hence, chitosan hydrogels exhibit a rapid gelation ability, with a gelation time of less than 30 s, and their storage modulus increases with the gelation time. By adjusting the molar ratio of the amino group of chitosan to the aldehyde group of DADBS and the reaction temperature, the hydrogels exhibit tunable elasticity and mechanical properties. Notably, scanning electron microscopy revealed the presence of 100-200 nm microgels in the hydrogel network, which could exert a strengthening effect on the mechanical properties of the hydrogels. In addition, chitosan hydrogels exhibit a rapid self-healing ability and remarkable fluorescence properties; also, they can be 3D printed in different shapes. Overall, the DADBS cross-linked chitosan hydrogels demonstrate potential applications in food, medicine, agriculture, and materials.

10.
Int J Biol Macromol ; 163: 1557-1564, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32784021

RESUMO

The rapid fabrication of starch gels with excellent mechanical properties still presents a challenge. This study aimed to develop a simple alcohol soaking method to fabricate strong starch gels in a short time. The mechanical properties, crystallization behaviors, and structural characteristics of starch gels were investigated by rheological testing, texture profile analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and low-field nuclear magnetic resonance (LF-NMR). The mechanical strength of the starch gel increased from 170.21 g to 666.16 g. The gelation time of starch gel decreased from 12 h (traditional retrogradation) to 2 h. DSC indicated that the enthalpy of starch gel increased from 0.88 J/g to 2.90 J/g. XRD analysis showed that the crystallinity of starch gel increased from 3.8% to 8.9% after alcohol soaking. Alcohol dehydrated the starch gels system, so that amylopectins were arranged to form more crystals. This new simple approach, alcohol soaking to form strong starch gels, can expand the applications of starch in food, agriculture, and textiles.

11.
Brain Res ; 1748: 147070, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32827549

RESUMO

Hypoxic-ischemic encephalopathy (HIE) results in high neonatal mortality and severe neurological impairments, and its underlying molecular mechanism underwent extensive investigations. Long non-coding RNA (lncRNA) is considered to be an important regulator on brain development and many neurological diseases. Currently, little is known about the role of Vof-16 (lncRNA) in HIE. We detected the relative expression level of Vof-16 in the cortex and hippocampus of hypoxic-ischemic (HI) models whose successful establishment was verified by TTC staining. Then, Vof-16 knockout rats were generated using the CRISPR/Cas engineering technology to search the specific function of the Vof-16 through a series of behavioral evaluations including Neurological severity scores (NSS), Y-maze test, Morris water maze (MWW) test, open field test, and Rotarod test. The results demonstrated the expression of Vof-16 was substantially up-regulated in the cortex and hippocampus of rats with HI injury. Importantly, Vof-16 knockout facilitated the recovery from long-term HI induced nerve damage and neurobehavioral dysfunctions. In conclusion, this study suggests Vof-16 knockout is a promising treatment target for neonatal HIE.

12.
Front Cell Dev Biol ; 8: 577, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793586

RESUMO

Spinal cord injury (SCI) is a fatal disease that can cause severe disability. Cortical reorganization subserved the recovery of spontaneous function after SCI, although the potential molecular mechanism in this remote control is largely unknown. Therefore, using proteomics analysis, RNA interference/overexpression, and CRISPR/Cas9 in vivo and in vitro, we analyzed how the molecular network functions in neurological improvement, especially in the recovery of motor function after spinal cord transection (SCT) via the remote regulation of cerebral cortex. We discovered that the overexpression of pyridoxal kinase (PDXK) in the motor cortex enhanced neuronal growth and survival and improved locomotor function in the hindlimb. In addition, PDXK was confirmed as a target of miR-339 but not miR-124. MiR-339 knockout (KO) significantly increased the neurite outgrowth and decreased cell apoptosis in cortical neurons. Moreover, miR-339 KO rats exhibited functional recovery indicated by improved Basso, Beattie, and Bresnehan (BBB) score. Furthermore, bioinformatics prediction showed that PDXK was associated with GAP43, a crucial molecule related to neurite growth and functional improvement. The current research therefore confirmed that miR-339 targeting PDXK facilitated neurological recovery in the motor cortex of SCT rats, and the underlying mechanism was associated with regulating GAP43 in the remote cortex of rats subjected to SCT. These findings may uncover a new understanding of remoting cortex control following SCI and provide a new therapeutic strategy for the recovery of SCI in future clinical trials.

13.
J Agric Food Chem ; 68(37): 10174-10183, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32816465

RESUMO

Nanoparticles (NPs) can form a protein corona (PC) with proteins in biological fluids. We examined whether starch nanoparticles (SNPs) form a PC and interact with digestive enzymes in simulated gastric and intestinal fluids. We investigated the adsorption of pepsin and trypsin on unmodified, carboxyl-, and amino-modified SNPs (SNPs, COOH-SNPs, and NH2-SNPs, respectively). Quartz crystal microbalance data showed that a tight and irreversible pepsin corona formed on the NH2-SNPs, pepsin had little or no binding to the SNPs and COOH-SNPs, and trypsin had weak binding to all three kinds of NPs. Dynamic light scattering data showed that pepsin significantly increased the size of the NH2-SNPs from 120 ± 2.6 to 203 ± 12.2 nm and decreased their surface potential from 23.2 ± 1.0 to 12.7 ± 0.2 mV. NH2-SNPs could induce the fluorescence quenching of pepsin and change its secondary structures without affecting its activity.

14.
Brain Behav ; 10(8): e01696, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32525289

RESUMO

INTRODUCTION: Neonatal hypoxia-ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive. METHODS: We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen-glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL-1ß was examined in bFGF knockdown condition. IL-1ß knockout (KO) rats were generated using CRISPR/Cas9-mediated technologies. We used an accepted rat model of HI, to assess the effect of IL-1ß deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level. RESULTS: We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin-1ß (IL-1ß). IL-1ß was up-regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD-mediated pathways. We found HI resulted in up-regulation of IL-1ß mRNA in cortex and hippocampus. IL-1ß KO rats markedly attenuated the impairment of long-term learning and memory induced by HI. Meanwhile, IL-1ß-/- (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine/threonine protein kinase (AKT1) mRNA and protein expression was significantly up-regulated in IL-1ß KO rats. CONCLUSIONS: We showed that IL-1ß-mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.

15.
Int J Biol Macromol ; 161: 481-491, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32534085

RESUMO

Starch nanoparticles are promising candidates for the delivery of active compounds or drugs. The purpose of this study was to prepare nanoparticles from debranched starch using an ionic gelation method. Negatively charged carboxymethyl debranched starch (CMDBS) was obtained by modification of debranched starch (DBS). The zeta potential value of CMDBS with a degree of substitution of 0.81 was approximately -26 mV. The starch nanoparticles formed from 2 mg mL-1 CMDBS and cationized DBS (CDBS) had particle sizes of 50 to 100 nm, as determined by transmission electron spectroscopy, and most nanoparticles were spherical in shape. Measurements with a quartz crystal microbalance with dissipation monitoring confirmed a successful adsorption interaction between the negatively charged CMDBS and positively charged CDBS. Epigallocatechin gallate (EGCG) was successfully incorporated into the nanoparticles with the highest encapsulation efficiency of 84.4%, and the resulting nanoparticles showed controlled release of EGCG into simulated gastric and intestinal fluids.

16.
Brain Res Bull ; 162: 218-230, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32579902

RESUMO

Neonatal hypoxic-ischemic encephalopathy (HIE) is major cause of neonatal death or long-term neurodevelopmental disabilities, which becomes a major practical problem currently in clinic. Whereas, its pathophysiology and underlying molecular mechanism is not clear. MicroRNAs are involved in the normal growth and development of neuronal cells. Herein, the objective of this research was to examine the roles of miR-410-3p in neurological deficits, neuronal injury and neuron apoptosis after hypoxic-ischemic and to explore its associated mechanisms. We established the hypoxic-ischemic brain damage (HIBD) model and oxygen glucose deprivation (OGD) model. Zea-longa score and TTC staining were used to detect the acute cerebral dysfunction after HIBD. QPCR verification exhibited notable downregulation of miR-410-3p expression at 24 h in rats after HIBD as well as that in PC12, SY5Y cells and primary cortical neurons post OGD. To further determine the function of miR-410-3p, lentivirus-mediated overexpression virus was applied in vivo and in vitro. Behavioral tests, including Morris water maze, open field test, Y maze test, neurological severity score and rotating rod test, were performed to evaluate long-term behavioral changes of rats at 1 month post HIBD. The results showed that the number of cells together with the axonal length were reduced post OGD. While the increase of cells number and the axonal length was measured after upregulating miR-410-3p. Meanwhile, miR-410-3p overexpression inhibited neuron apoptosis and enhanced neuronal survival. In addition, long-term motor and cognitive functions were remarkably recovered in HIBD rats with miR-410-3p overexpression. Together, miR-410-3p exerts a critical role in protecting neuronal growth as well as promoting motor and cognitive function recovery in neonatal rats subjected to HIBD. The current study therefore provides critical insights to develop the activator of miR-410-3p for the clinical treatment of HIBD in future clinic trial.

17.
BMC Neurosci ; 21(1): 18, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349668

RESUMO

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) represents as a major cause of neonatal morbidity and mortality. However, the underlying molecular mechanisms in brain damage are still not fully elucidated. This study was conducted to determine the specific potential molecular mechanism in the hypoxic-ischemic induced cerebral injury. METHODS: Here, hypoxic-ischemic (HI) animal models were established and primary cortical neurons were subjected to oxygen-glucose deprivation (OGD) to mimic HIE model in vivo and in vitro. The HI-induced neurological injury was evaluated by Zea-longa scores, Triphenyte-trazoliumchloride (TTC) staining the Terminal Deoxynucleotidyl Transferased Utp Nick End Labeling (TUNEL) and immunofluorescent staining. Then the expression of Cytochrome c oxidase subunit 5a (COX5A) was determined by immunohistochemistry, western blotting (WB) and quantitative real time Polymerase Chain Reaction (qRT-PCR) techniques. Moreover, HSV-mediated COX5A over-expression virus was transducted into OGD neurons to explore the role of COX5A in vitro, and the underlying mechanism was predicted by GeneMANIA, then verified by WB and qRT-PCR. RESULTS: HI induced a severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats, in corresponding to the decrease on the expression of COX5A in both sides of the brain. What's more, COX5A over-expression significantly promoted the neuronal survival, reduced the apoptosis rate, and markedly increased the neurites length after OGD. Moreover, Triosephosephate isomerase (TPI) was predicted as physical interactions with COX5A, and COX5A over-expression largely increased the expressional level of TPI. CONCLUSIONS: The present findings suggest that COX5A plays an important role in promoting neurological recovery after HI, and this process is related to TPI up-regulation.

18.
Stem Cell Res Ther ; 11(1): 155, 2020 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299503

RESUMO

BACKGROUND: The limited neuronal differentiation of the endogenous or grafted neural stem cells (NSCs) after brain injury hampers the clinic usage of NSCs. Panax notoginseng saponins (PNS) were extensively used for their clinical value, such as in controlling blood pressure, blood glucose, and inhibiting neuronal apoptosis and enhancing neuronal protection, but whether or not it exerts an effect in promoting neuronal differentiation of the endogenous NSCs is completely unclear and the potential underlying mechanism requires further exploration. METHODS: Firstly, we determined whether PNS could successfully induce NSCs to differentiate to neurons under the serum condition. Mass spectrometry and quantitative polymerase chain reaction (Q-PCR) were then performed to screen the differentially expressed proteins (genes) between the PNS + serum and serum control group, upon which dihydropyrimidinase-like 2 (DPYSL2), a possible candidate, was then selected for the subsequent research. To further investigate the actual role of DPYSL2 in the NSC differentiation, DPYSL2-expressing lentivirus was employed to obtain DPYSL2 overexpression in NSCs. DPYSL2-knockout rats were constructed to study its effects on hippocampal neural stem cells. Immunofluorescent staining was performed to identify the differentiation direction of NSCs after 7 days from DPYSL2 transfection, as well as those from DPYSL2-knockout rats. RESULTS: Seven differentially expressed protein spots were detected by PD Quest, and DPYSL2 was found as one of the key factors of NSC differentiation in a PNS-treated condition. The results of immunostaining further showed that mainly Tuj1 and GFAP-positive cells increased in the DPYSL2-overexpressed group, while both were depressed in the hippocampal NSCs in the DPYSL2-knockout rat. CONCLUSIONS: The present study revealed that the differentiation direction of NSCs could be enhanced through PNS administration, and the DPYSL2 is a key regulator in promoting NSC differentiation. These results not only emphasized the effect of PNS but also indicated DPYSL2 could be a novel target to enhance the NSC differentiation in future clinical trials.

19.
Chin Med ; 15: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226478

RESUMO

Background: Colorectal cancer, one of the most common digestive tumors with high mortality and morbidity worldwide, currently lacks effective therapies available to improve the prognosis. This study was aimed to investigate the potency of Scutellarin against colorectal cancers, and explore the related mechanism via genomic and proteomic analysis. Methods: Cell counting kit-8 assay was employed to detect the viability of HCT-116 and RKO cell lines treated with Scutellarin. The apoptosis of HCT-116 and RKO cells after Scutellarin administration was determined by TUNEL staining and Caspase 3/7 activity. Cell cycle was detected by flow cytometry analysis. The wound healing and transwell invasion test detected the role of Scutellarin in migration and invasion of HCT-116 and RKO cells. Meanwhile, the energy metabolism and growth of tumor tissues in vivo at day 28 were observed by PET-CT after Scutellarin administration with 50 mg/kg, 100 mg/kg and 300 mg/kg into 4-week-old nude mice. Blood routine and liver functions were also detected to evaluate the side effect of Scutellarin. Furthermore, the disease and function classifications which the differentially expressed genes and proteins involved after Scutellarin treatment were determined by genomic and proteomic analysis respectively. Results: The Scutellarin inhibited the migration and increased apoptosis of HCT-116 and RKO cell lines. Besides, Scutellarin treatment substantially decreased the growth and volume of colorectal tumors in nude mice without side effects on the blood routine and liver function. The differentially expressed genes in RKO cells after Scutellarin administration were mainly enriched in cell death and survival, organismal injury and abnormalities, and cancer. In addition, forty-seven upregulated and twenty-nine downregulated proteins were identified. Functional clustering analysis exhibited enriched biological processes, cellular components, molecular functions and related pathways of these proteins in cellular metabolic. Then protein-protein interactions analysis showed the regulatory relationship among these differentially expressed proteins. Conclusions: Taken together, the present findings revealed that Scutellarin exerted significant antitumor effect with no side effects in the blood and liver by regulating various important molecules in tumor proliferation, apoptosis and metastasis.

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