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1.
J Cell Physiol ; 236(2): 889-899, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33020901

RESUMO

Long intergenic noncoding RNAs (lincRNAs) play a vital role in the occurrence and progression of cancer. The mechanism of lincRNAs in colorectal cancer (CRC) has not been fully elucidated. In this context, an integrated comparative long noncoding RNA (lncRNA) microarray technology was used to determine the expression profile of lncRNAs in CRC. The roles of LINC00908 are unclear. We found that LINC00908 was significantly upregulated in CRC. Inhibition of LINC00908 resulted in reduced cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, cyclin-dependent kinase 4, and phosphorylated retinoblastoma. Moreover, inhibition of LINC00908-induced apoptosis through the intrinsic apoptosis signaling pathway, as shown by the activation of caspase-9 and caspase-3. Mechanistically, miR-143-3p directly bound to LINC00908. miR-143-3p expression was negatively correlated with LINC00908 expression in CRC tissue. Functional experiments revealed opposing roles for miR-143-3p and LINC00908, suggesting that LINC00908 negatively regulates miR-143-3p. Mechanistically, miR-143-3p directly targets LINC00908. The KLF5 inhibitor ML264 affected proliferation and apoptosis, indicating that LINC00908 may act as a competing endogenous RNA to facilitate the expression of the miR-143-3p target gene KLF5. Thus, LINC00908 has an important proliferative and antiapoptotic role in CRC by regulating the cell cycle and intrinsic apoptosis. LINC00908 could be a potential biomarker and a new therapeutic target for CRC.

2.
Med Sci Monit ; 26: e926215, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33168797

RESUMO

BACKGROUND Superb microvascular imaging (SMI) is a new blood flow imaging technique used to evaluate microvascular blood flow. This study evaluated whether SMI was superior to color Doppler flow imaging (CDFI) for evaluating placental microcirculation. MATERIAL AND METHODS This prospective study included pregnant women in their third trimester who were evaluated at General Hospital of Hebei Province from February to June 2017. The distribution of vascular patterns, including pulsatility index (PI), resistance index (RI), S/D, time average velocity (TAV), and vessels per unit area, were evaluated by SMI and CDFI. RESULTS This study evaluated 110 pregnant women of mean age 29.53 years. SMI and CDFI yielded statistically significant differences in PI (0.76 vs. 0.62), RI (0.71 vs. 0.47), S/D (2.23 vs. 1.71), TAV (14.35 vs. 22.45), and vessels per unit area (0.26 vs. 0.05) (P<0.001 each). The weight of the pregnant women correlated positively with RI (P=0.048) and negatively with vessels per unit area (P=0.040) as determined by SMI. Weeks of gestation correlated negatively correlated with PI (P=0.008), RI (P=0.004), S/D (P=0.015), and vessels per unit area (P=0.014) by CDFI, and positively with RI (P<0.001) and S/D (P=0.001) by SMI. The results of stratified comparisons of CDFI and SMI based on age, weight, and gestational weeks were consistent overall. CONCLUSIONS SMI, which has a higher rate of placental vascularity, a clearer display of capillaries, a greater sensitivity to low flow, and an advantage in displaying microcirculation of the placenta, can serve as a new and effective method of evaluating placental blood flow.

3.
J Biomed Nanotechnol ; 16(6): 789-809, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33187577

RESUMO

Biomaterial implants and medical devices have been utilized extensively in medical treatment with the development of modern medicine, especially in orthopaedics and stomatology. Along with their applications, biomaterial-associated infections (BAIs) have grown to be one of the main postoperative complications. Antimicrobial coating strategies have been reported to effectively inhibit bacterial adhesion and proliferation on implant surface, extending their lifespan. In this review, the most topical antimicrobial coating designs have been chosen from literature studies. Their antimicrobial mechanisms and antimicrobial activity assessments in literature studies have been presented and compared. Based on their active ingredients, antimicrobial coatings are categories into (i) inorganic agents, including Ag, Cu, ZnO, MoS2 and nitride compound; (ii) organic agents including antibiotic, antimicrobial peptides, polymer, essential oils etc. The review has provided various and detailed options of antimicrobial coating designs for consulting according to their specific application. It is noted that the research of antimicrobial coatings is mostly in vitro and in vivo animal models study. It is thus in need for more preclinical or clinical studies, especially finding the direct connection between the utilization of antimicrobial coated implants and the reduction in BAIs incidence. Furthermore, future antimicrobial coating designs shall respect also biocompatibility, functionality, and durability apart from their antimicrobial activity.


Assuntos
Anti-Infecciosos , Materiais Revestidos Biocompatíveis , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Aderência Bacteriana , Próteses e Implantes
4.
PLoS One ; 15(11): e0241494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33152001

RESUMO

OBJECTIVE: Full endoscopic lumbar discectomy (FELD) for lumbar disc herniation (LDH) has become popular in recent years. Previous studies have proven the efficacy, but few have discussed the possible risk factors of poor outcome. In this study, we reviewed patients who underwent FELD at Changhua Christian Hospital in the past 10 years and sought to identify factors associated with poor surgical outcomes and re-operations. METHODS: We retrospectively reviewed records from mid-2009 to mid-2018. Patients had undergone FELD and follow-up for ≥1 year were included. Factors included in the outcome evaluations were age, sex, surgical time, body mass index, surgical methods, disc herniation type, extension of herniation, degree of canal compromised, disc degenerative grade, smoking and alcohol use, surgical lumbar level, symptom duration, Oswestry low back disability index, and visual analog scale score. We had evolved from inside-out methods to outside-in methods after 2016, thus, we included this factor in the analysis. The primary outcomes of interest were poor/fair MacNab score and re-operation. RESULTS: From mid-2009 to mid-2018, 521 patients met our criteria and were analyzed. The median follow-up was 1685 days (range, 523-3923 days). Thirty-one (6.0%) patients had poor surgical outcomes (fair/poor MacNab score) and 45 (8.6%) patients required re-operation. Prolapsed herniated disc (P < 0.001), higher disc degenerative grade (P = 0.047), higher lumbar level (P = 0.026), longer preoperative symptoms (P < 0.001), and surgery before 2017 (outside-in technique, P = 0.020) were significant factors associated with poor outcomes in univariate analyses. In multivariate analyses, prolapsed herniated disc (P < 0.001), higher disc degenerative grade (P = 0.030), and higher lumbar level (P = 0.046) were statistically significant. The most common adverse symptom was numbness. Factors possibly associated with higher re-operation rate were older age (P = 0.045), alcohol use (P = 0.073) and higher lumbar level (P = 0.069). Only alcohol use showed statistically significant re-operation rates in multivariate analyses (P = 0.035). CONCLUSIONS: For treating LDH by FELD, we concluded that prolapsed disc, higher disc degenerative grade, higher lumbar level, and longer preoperative symptom duration were possibly associated with unsatisfactory surgical outcomes (poor/fair MacNab score). The outside-in technique might be superior to the inside-out technique. Older age and alcohol use might be associated with a higher re-operation rate.

5.
JMIR Public Health Surveill ; 6(4): e21963, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33151157

RESUMO

BACKGROUND: Instagram is a popular social networking platform for users to upload pictures sharing their experiences. Instagram has been widely used by vaping companies and stores to promote electronic cigarettes (e-cigarettes), as well as by public health entities to communicate the risks of e-cigarette use (vaping) to the public. OBJECTIVE: We aimed to characterize current vaping-related content on Instagram through descriptive analyses. METHODS: From Instagram, 42,951 posts were collected using vaping-related hashtags in November 2019. The posts were grouped as (1) pro-vaping, (2) vaping warning, (3) neutral to vaping, and (4) not related to vaping based on the attitudes to vaping expressed within the posts. From these Instagram posts and the corresponding 18,786 unique Instagram user accounts, 200 pro-vaping and 200 vaping-warning posts as well as 200 pro-vaping and 200 vaping-warning user accounts were randomly selected for hand coding. Furthermore, follower counts and media counts of the Instagram user accounts as well as the "like" counts and hashtags of the posts were compared between pro-vaping and vaping-warning groups. RESULTS: There were more posts in the pro-vaping group (41,412 posts) than there were in the vaping-warning group (1539 posts). The majority of pro-vaping images were product display images (163/200, 81.5%), and the most popular image type in vaping-warning posts was educational (95/200, 47.5%). The highest proportion of pro-vaping user account type was vaping store (110/189, 58.1%), and the store account type had the highest mean number of posts (10.33 posts/account). The top 3 vaping-warning user account types were personal (79/155, 51%), vaping-warning community (37/155, 23.9%), and community (35/155, 22.6%), of which the vaping-warning community had the highest mean number of posts (3.68 posts/account). Pro-vaping user accounts had more followers (median 850) and media (median 232) than vaping-warning user accounts had (follower count: median 191; media count: 92). Pro-vaping posts had more "likes" (median 22) and hashtags (mean 20.39) than vaping-warning posts had ("like" count: median 12; hashtags: mean 7.16). CONCLUSIONS: Instagram is dominated by pro-vaping content, and pro-vaping posts and user accounts seem to have more user engagement than vaping-warning accounts have. These results highlight the importance of regulating e-cigarette posts on social media and the urgency of identifying effective communication content and message delivery methods with the public about the health effects of e-cigarettes to ameliorate the epidemic of vaping in youth.

6.
Int J Psychophysiol ; 158: 380-388, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171138

RESUMO

BACKGROUND: Neurofeedback training aims to develop awareness and control of psychological states in order to self-regulate brain activity and while used widely therapeutically, important questions remain unanswered. Central to these aims is an assumed association between the live EEG-based feedback and the subjective experience of a psychological state. To date, there is little evidence to support this relationship. Previous studies examining the association between an EEG index and subjective experience have explored only the presence or absence of the state, or merely assumed state variations. The current study aims to examine this association by considering how different levels of a psychological state (i.e., attention) are reflected in EEG coherence. METHODS: Our approach aims to allow comparisons of EEG coherence between psychological states (attention vs. rest), and also within subjectively-rated levels of a psychological state (attention) through a purpose-designed questionnaire. Thirty healthy adult participants performed a resting eyes-open (REO) and attention modulation task, while 28 channels of EEG were recorded. Levels within the psychological state were subjectively-attested by participants on a trial-by-trial basis. RESULTS: The main analyses examined the effect of subjectively-rated attention levels (SRALs) on EEG coherence, with results suggesting that high and low SRALs may be represented by: 1) different levels of alpha and theta coherence at anterior and posterior electrodes of the frontal lobe bilaterally, and 2) different levels of alpha coherence between central and parietal lobes, also bilaterally. DISCUSSION: These findings provide partial, preliminary evidence for EEG correlates of SRALs. These findings may have implications for understanding underlying mechanisms of NFT, which is an underdeveloped area.

7.
Langmuir ; 36(46): 13981-13988, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33175536

RESUMO

Peptides with a sequence of Nap-Ix-GPLGLAG-R4-NH2 (x = 2, 4, and 6, shorted as I2R4, I4R4, and I6R4) were used as capping agents for the synthesis of zeolitic imidazolate framework-8 (ZIF-8) in water. Peptide addition can significantly inhibit the growth of ZIF-8 crystals. The shape and size of ZIF-8 crystals was related closely to the number of isoleucine (Ile, I) residues as well as concentration of the peptide. The shape of ZIF-8 crystals changes from rhomboid dodecahedron to truncated rhombic dodecahedron to cube with the decreasing number of isoleucine residues from six to two. At a peptide concentration of 1.0 mM, the morphology of ZIF-8 crystals was cubic, truncated rhombic dodecahedron, and typical rhombic dodecahedron in the cases of I2R4, I4R4, and I6R4, respectively. Also, the particle size can be regulated from ca. 1.7 µm to <100 nm by controlling the peptide concentration from 0 to 2.0 mM. This work develops a simple and green method for the synthesis of ZIF-8 crystals with controllable shape and size in water, which shows high potential for biomedical and biological applications.

8.
Biomed Environ Sci ; 33(10): 750-759, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33228834

RESUMO

Objective: To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong. Methods: A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls. Results: Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant. Conclusion: The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.

10.
J Hazard Mater ; : 124565, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33229257

RESUMO

Two-dimensional transition metal carbide and nitride are promising energy storage materials. However, the aggregation and rearrangement of two-dimensional nanosheets limit their electrochemical performance. In this paper, a novel hierarchical porous "skin/skeleton"-like MXene/biomass derived carbon fibers (MXene/CF) heterostructure is prepared by one-step pyrolysis, which efficiently weakens the stacking of MXene nanosheets. Moreover, MXene/CF has a well-defined hierarchical porous structure, thereby facilitating electrolyte penetration and providing efficient and stable channels for rapid diffusion/transfer of ions to the electrode and producing functional MXene-based electrodes. When MXene/CF heterostructure is applied as a self-supporting electrode for supercapacitors, the electrode has high volumetric capacitance of 7.14 F cm-3, good rate characteristics (63.9% from 0.5 to 100 A g-1), and excellent cyclic stability (99.8% after 5000 cycles). In addition, all solid-state symmetric supercapacitors based on MXene/CF electrodes are also assembled, which not only exhibits high capacitance and rate performance, but also has good flexibility and long durability. The device still maintains structural integrity and steady capacitance even after 2500 cycles at different bending angles. This work is expecting to guide the design of the next generation of flexible, portable and highly integrated supercapacitors with high capacity and rate performance to further meet the requirements of sustainable development.

11.
World J Gastroenterol ; 26(40): 6295-6303, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33177801

RESUMO

BACKGROUND: Ethylmalonic encephalopathy (EE) is a rare autosomal recessive metabolic disorder caused by impaired mitochondrial sulfur dioxygenase. Due to poor therapeutic effect of current conventional treatments, progressive psychomotor regression and neurological impairment usually contribute to early death in the first decade of life. Liver transplantation (LT) is emerging as a novel therapeutic option for EE; however, worldwide experience is still limited. CASE SUMMARY: An 18-mo-old patient with the diagnosis of EE received a living donor liver transplant in our institution, which, to our knowledge, is the first case in Asian-Pacific countries. During 20 mo of follow-up, the longitudinal metabolic evaluations revealed a wild fluctuation in urinary EMA levels, still far beyond the normal range. Urinary 2-methylsuccinic acid levels gradually restored to normal, whereas the concentrations of urinary isobutyrylglycine and plasma C4- and C5-acylcarnitines fluctuated markedly and still remained above the reference limits. Only mild amelioration of petechiae and ecchymosis was observed, and no dramatic reversion of chronic mucoid diarrhea and orthostatic acrocyanosis occurred. Although brain magnetic resonance imaging suggested a certain improvement in basal ganglia lesions, the patient still presented developmental delay and neurologic disability. CONCLUSION: LT may bring about a partial but not complete cure to EE. Given its definite role in defending against the devastating natural progression of EE, LT should still be considered for patients with EE in the absence of other superior therapeutic options. Early establishment of diagnosis and initiation of conventional treatment pre-transplant, timely LT, and continuous administration of metabolism-correcting medications post-transplant may be helpful in minimizing the neurologic impairment and maximizing the therapeutic value of LT in EE.

12.
J Med Internet Res ; 22(11): e18998, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180022

RESUMO

BACKGROUND: As human society enters an era of vast and easily accessible social media, a growing number of people are exploiting the internet to search and exchange medical information. Because internet search data could reflect population interest in particular health topics, they provide a new way of understanding health concerns regarding noncommunicable diseases (NCDs) and the role they play in their prevention. OBJECTIVE: We aimed to explore the association of internet search data for NCDs with published disease incidence and mortality rates in the United States and to grasp the health concerns toward NCDs. METHODS: We tracked NCDs by examining the correlations among the incidence rates, mortality rates, and internet searches in the United States from 2004 to 2017, and we established forecast models based on the relationship between the disease rates and internet searches. RESULTS: Incidence and mortality rates of 29 diseases in the United States were statistically significantly correlated with the relative search volumes (RSVs) of their search terms (P<.05). From the perspective of the goodness of fit of the multiple regression prediction models, the results were closest to 1 for diabetes mellitus, stroke, atrial fibrillation and flutter, Hodgkin lymphoma, and testicular cancer; the coefficients of determination of their linear regression models for predicting incidence were 80%, 88%, 96%, 80%, and 78%, respectively. Meanwhile, the coefficient of determination of their linear regression models for predicting mortality was 82%, 62%, 94%, 78%, and 62%, respectively. CONCLUSIONS: An advanced understanding of search behaviors could augment traditional epidemiologic surveillance and could be used as a reference to aid in disease prediction and prevention.

13.
Cell Rep ; 33(6): 108369, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33176141

RESUMO

Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. Whether Casp3-AMPAR interaction is involved in the maintenance of peripheral hypersensitivity after nerve injury remained unknown. Here, we show that nerve injury suppresses long-term depression (LTD) and downregulates Casp3 in the anterior cingulate cortex (ACC). Interfering with interactions between Casp3 and AMPAR subunits or reducing Casp3 activity in the ACC suppresses LTD induction and causes peripheral hypersensitivity. Overexpression of Casp3 restores LTD and reduces peripheral hypersensitivity after nerve injury. We reveal how Casp3 is involved in the maintenance of peripheral hypersensitivity. Our findings suggest that restoration of LTD via Casp3 provides a therapeutic strategy for neuropathic pain management.

14.
Chin Med J (Engl) ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33177395

RESUMO

OBJECTIVES: Lipid abnormalities are prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and contribute to increasing risk of cardiovascular events. This study aims to investigate the incidence of dyslipidemia and its risk factors in PLWH after receiving different first-line free antiretroviral regimens. METHODS: PLWH who sought care at the Third People's Hospital of Shenzhen from January 2014 to December 2018 were included, and the baseline characteristics and clinical data during the follow-up were collected, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The risk factors of dyslipidemia after antiretroviral therapy were analyzed with the generalized estimating equation model. RESULTS: Among the 7623 PLWH included, the mean levels of TC, HDL-C and LDL-C were 4.23 ±â€Š0.85 mmol/L, 1.27 ±â€Š0.29 mmol/L and 2.54 ±â€Š0.65 mmol/L, respectively, and the median TG was 1.17 (IQR: 0.85-1.68) mmol/L. Compared with that in PLWH receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + ritonavir-boosted lopinavir (LPV/r), zidovudine (AZT) + 3TC + efavirenz (EFV), and AZT + 3TC + LPV/r, the incidence of dyslipidemia was lower in PLWH receiving TDF + 3TC + EFV. In multivariate analysis, we found that the risks of elevations of TG, TC, and LDL-C were higher with TDF + 3TC + LPV/r (TG: odds ratio [OR] = 2.82, 95% confidence interval (CI): 2.55-3.11, P < 0.001; TC: OR = 1.24, 95% CI: 1.14-1.35, P < 0.001; LDL: OR = 1.06, 95% CI: 1.00-1.12, P = 0.041), AZT + 3TC + EFV (TG: OR = 1.41, 95% CI: 1.28-1.55, P < 0.001; TC: OR = 1.43, 95% CI: 1.31-1.56, P < 0.001; LDL: OR = 1.18, 95% CI: 1.12-1.25, P < 0.001), and AZT + 3TC + LPV/r (TG: OR = 3.08, 95% CI: 2.65-3.59, P < 0.001; TC: OR = 2.40, 95% CI: 1.96-2.94, P < 0.001; LDL: OR = 1.52, 95% CI: 1.37-1.69, P < 0.001) than with TDF + 3TC + EFV, while treatment with TDF + 3TC + LPV/r was less likely to restore HDL-C levels compared with TDF + 3TC + EFV (OR = 0.95, 95% CI: 0.92-0.97, P < 0.001). In addition to antiretroviral regimens, antiretroviral therapy duration, older age, overweight, obesity and other traditional factors were also important risk factors for dyslipidemia. CONCLUSION: The incidence of dyslipidemia varies with different antiretroviral regimens, with TDF + 3TC + EFV having lower risk for dyslipidemia than the other first-line free antiretroviral regimens in China.

15.
ACS Synth Biol ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179507

RESUMO

Protein dimerization systems controlled by red light with increased tissue penetration depth are a highly needed tool for clinical applications such as cell and gene therapies. However, mammalian applications of existing red light-induced dimerization systems are hampered by limitations of their two components: a photosensory protein (or photoreceptor) which often requires a mammalian exogenous chromophore and a naturally occurring photoreceptor binding protein typically having a complex structure and nonideal binding properties. Here, we introduce an efficient, generalizable method (COMBINES-LID) for creating highly specific, reversible light-induced heterodimerization systems independent of any existing binders to a photoreceptor. It involves a two-step binder screen (phage display and yeast two-hybrid) of a combinatorial nanobody library to obtain binders that selectively engage a light-activated form of a photoswitchable protein or domain not the dark form. Proof-of-principle was provided by engineering nanobody-based, red light-induced dimerization (nanoReD) systems comprising a truncated bacterial phytochrome sensory module using a mammalian endogenous chromophore, biliverdin, and light-form specific nanobodies. Selected nanoReD systems were biochemically characterized, exhibiting low dark activity and high induction specificity, and further demonstrated for the reversible control of protein translocation and activation of gene expression in mice. Overall, COMBINES-LID opens new opportunities for creating genetically encoded actuators for the optical manipulation of biological processes.

16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(4): 330-335, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-33167093

RESUMO

OBJECTIVE: To investigate the effects of a novel polyamine metabolism enzyme inhibitor SI-4650 on autophagy and apoptosis of colon cancer CT-26 cells as well as their correlation. METHODS: CT-26 cells treated with 40, 80 µmol·L-1 SI-4650 alone or in combination with 3-MA were used as experimental group. CT-26 cells treated with 0 µmol·L-1 SI-4650 alone or in combination with 3-MA were used as control group. Chemiluminescence was used to analyze the effect of SI-4650 on spermine oxidase (SMO) and acetylpolyamine oxidase(APAO) activity. High performance liquid chromatography (HPLC) was performed to detect cellular polyamine content.The CCK8 method was used to detect the inhibitory effect of SI-4650 on proliferation of CT-26 cells. PI single-staining/flow cytometry (FCM) were used to analyze cell cycle. Western blot were used to analyze autophagy. Apoptosis was analyzed by PI/FITC-Annexin V double staining, JC-1 fluorescent probe and Fluo-3 AM calcium ion fluorescent probe combined with flow cytometry and Western blot. RESULTS: CCK8 assay showed that 24-,48-,72-hours treated with SI-4650 all could inhibit the proliferative activity of CT-26 cells in a dose- and time-dependent manner (P<0.01) . The inhibition rate was 36.98% and 46.91% in 40 µmol·L-1 SI-4650 group and 80 µmol·L-1 SI-4650 group respectively. SI-4650 could significantly inhibit the activities of SMO and APAO interfere with polyamine metabolism and reduce the content of total polyamine in CT-26 cells (P<0.01). SI-4650 could block CT-26 cells in G0/G1 phase, significantly reduce the number of cells in S phase(P<0.01), and lead to a significant increase in the contents of autophagy-related Beclin-1, LC3-II in CT-26 cells(P<0.01); At the same time, the concentration of calcium in CT-26 cells was increased, the mitochondrial membrane potential was decreased, the expressions of c-PARP and Bax were increased, the content of Bcl-2 was decreased, and the number of apoptotic cells was increased. After SI-4650 combined with autophagy inhibitor 3-MA treatment of CT-26 cells, the level of autophagy, the apoptosis-related protein, mitochondrial membrane potential and calcium ion concentration were decreased, and the number of apoptotic cells was decreased. CONCLUSION: SI-4650 has the pharmacological activity of killing colon cancer CT-26 cells, and its mechanism may be related to the interference of polyamine metabolism and induction of cell apoptosis and autophagy. In this process, autophagy is inhibited to block apoptosis, autophagy and apoptosis combined to kill tumor cells.

17.
Biomed Chromatogr ; : e5022, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169403

RESUMO

PURPOSE: To develop an ultra-high performance liquid chromatography (UPLC) method to quantify lacosamide (LCM), oxcarbazepine (OXC) and lamotrigine (LTG) in children with epilepsy in China. METHODS: Phenytoin sodium was used as the internal standard (IS). The mobile phase contained ammonium dihydrogen phosphate solution (10 mmol/L, pH = 4.0) and methanol (55:45, v/v). The flow rate, injection volume, column temperature, and detection wavelength were 0.2 mL/min, 2 µL, 30 °C and 240 nm, respectively. RESULTS: The method was linear within 0.5 - 40, 2.5 - 80 and 2.5 - 40 µg·mL-1 for LCM, MHD and LTG, respectively (r2 ≥ 0.998). The intra - and inter - day precision as measured by the RSD values were between 1.36 - 4.50%, 0.54 - 1.91% and 0.58 - 1.56%. Recovery ranged from 96.58 to 106.22%. All serum samples could be maintained for up to 3 h at ambient temperature, 24 h at 4°C, 30 days at -30°C, and after successive freeze-thaw cycles (24 h per cycle) in the absence of significant degradation. CONCLUSIONS: We have developed and validated a novel UPLC method that can quantify LCM, MHD and LTG in human serum in Xinjiang, China.

18.
Int J Clin Pract ; : e13843, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33222369

RESUMO

OBJECTIVE: The purpose of this study was to analyze the clinical and pathological characteristics, treatments and outcomes of post-transplant lymphoproliferative disorder (PTLD) in pediatric liver transplant recipients. METHOD: A retrospective analysis of records from nine pediatric liver transplant recipients with PTLD who were treated at our Liver Transplant Center over the period from Jun 2013 to Aug 2018. RESULT: Of these nine patients, seven received liver transplantation in our center and the remaining two patients at other hospitals. The overall incidence of PTLD in pediatric liver transplant recipients in our center was 1.4% (7/485). The median onset of PTLD after liver transplantation was 11 months. Three cases were classified as infectious mononucleosis PTLD, one case was plasmacytic hyperplasia PTLD, one case was polymorphic PTLD and two cases were Burkitt lymphoma. One case showed diffuse large B cell lymphoma and one was classical Hodgkin lymphoma-like PTLD. These patients presented with different clinical manifestations including fever, anemia, diarrhea, hypoproteinemia,enlargement of lymph nodes, hepatosplenomegaly, jaundice, bowel obstruction and even intestinal perforation. Nine patients were positive for EBV-DNA in serum. After diagnosis, immunosuppressants were reduced or discontinued in all cases. Eight patients received anti-CD20 monoclonal antibody (Rituximab) therapy, four cases were treated with a combination of chemotherapy (R-CHOP, ABVD, COPP/ABV) and one case was combined with radiotherapy. Two cases received surgical treatment due to bowel obstruction. Eight of these patients achieved a complete remission and remained healthy when assessed at the time of final follow-up. One patient died as a result of PTLD progression. CONCLUSION: PTLD is one of the most serious and fatal complications after liver transplantation. The definitive diagnosis requires histopathology. Treatment varies and basically includes immunosuppression reduction, anti-CD20 antibody, surgery, radiotherapy and chemotherapy.

19.
Mol Cancer ; 19(1): 164, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225938

RESUMO

BACKGROUND: Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive. METHODS: qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed. RESULTS: Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1). CONCLUSIONS: Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment.

20.
J Med Chem ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226226

RESUMO

The discovery of a pan-genotypic hepatitis C virus (HCV) NS3/4A protease inhibitor based on a P1-P3 macrocyclic tripeptide motif is described. The all-carbon tether linking the P1-P3 subsites of 21 is functionalized with alkyl substituents, which are shown to effectively modulate both potency and absorption, distribution, metabolism, and excretion (ADME) properties. The CF3Boc-group that caps the P3 amino moiety was discovered to be an essential contributor to metabolic stability, while positioning a methyl group at the C1 position of the P1' cyclopropyl ring enhanced plasma trough values following oral administration to rats. The C7-fluoro, C6-CD3O substitution pattern of the P2* isoquinoline heterocycle of 21 was essential to securing the targeted potency, pharmacokinetic (PK), and toxicological profiles. The C6-CD3O redirected metabolism away from a problematic pathway, thereby circumventing the time-dependent cytochrome P (CYP) 450 inhibition observed with the C6-CH3O prototype.

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