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Long non-coding RNA (lncRNA) is a type of non-coding RNA with the more than 200 nucleotides. Several lncRNAs have been identified as the potential targets for cancer therapy. LncRNA00067110 is one of the differentially expressed genes in the transcriptome profiles of melanoma B16-F10 cells compared to normal mice melanocytes. To investigate whether lncRNA00067110 regulates the proliferation, apoptosis and melanogenesis of B16-F10 cells, the calcium-binding tyrosine phosphorylation regulated protein (Cabyr) target gene was predicted by LncTar and verified by dual luciferase activities. The regulating function of lncRNA00067110 was investigated by the analysis of transcriptome profiles and to detect the proliferation, apoptosis and melanin production of B16-F10 cells transfected by the overexpression plasmids of lncRNA00067110. The results showed that the relationship of lncRNA00067110 targeting Cabyr, the mRNA and protein levels of proliferation (MEK/ERK/MNK/CREB) and melanogenesis-related genes (TYR family and CREB) were significantly down-regulated, while the mRNA and protein levels of apoptosis-related genes (AKT and Bcl-2) were up-regulated in B16-F10 cells with lncRNA00067110 overexpression. The transcriptome profile of B16-F10 cells with lncRNA00067110 overexpression showed that 17 genes were differentially expressed, among which Cabyr was up-regulated. Furthermore, the effect of lncRNA00067110 on the phenotypes of cell proliferation and apoptosis were verified. The results suggested that lncRNA00067110 might be a novel target for the treatment of melanoma by targeting Cabyr, which regulate the expression of related genes to inhibit the proliferation and melanogenesis, as well as to induce the apoptosis of B16-F10 cells.
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Diabetic retinopathy (DR) is one of the main cause of severe visual impairment in diabetic patients. Most of the existing treatments are aimed at patients with intermediate and advanced stages of vision impairment, and are invasive treatments with limited effects. Therefore, it is urgent for non-invasive new therapies and new targets to prevent the risk of DR or delay the progress of DR. Early optimization of metabolic therapies, which are strict control of blood glucose, blood pressure and blood lipid in the early stage of diabetes, may prevent or improve potential and reversible microangiopathy, however, there is still a lack of comprehensive and effective drug targeted therapy and unified clinical application standards. Therefore, this study summarizes the application of new hypoglycemic drugs and some antihypertensive and lipid-lowering drugs in the prevention and treatment of DR in recent years, in order to provide some reference for the clinical early prevention and treatment of this disease.
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The TMEM106B protein is a type-II transmembrane protein, which localizes in the endosome and lysosome of dendrites in primary neurons. TMEM106B is essential for maintaining and branching of dendrites, and thus regulates retrograde lysosomal trafficking of dendrites in primary neurons. Mammalian melanocytes are derived from neural cells, while melanosomes are originated from early endosome. However, the function of TMEM106B protein in melanocytes and its potential molecular mechanism in melanogenesis still remain unknown. Recently it was reported that transcription factor EB (TFEB) was the regulator of lysosome synthesis and TMEM106B protein overexpression promoted TFEB translocation into the nucleus. However, MITF (microphthalmia-associated transcription factor) and TFEB regulate each other in melanoma cells in vitro. Here in, plasmid containing gene for TMEM106B overexpression was transfected into melanocytes to investigate the regulation of TMEM106B on melanogenesis. The results showed that TMEM106B protein was localized in the cytoplasm of melanocytes. Compared with the negative control (NC), the mRNA levels of cyclic AMP-responsive element-binding protein (CREB) and MITF, especially CREB, were significantly increased in melanocytes with TMEM106B overexpression P< 0. 001). Western blot analysis showed that the expression of phosphorylated MAP kinase (p-ERK) was apparently increased (P<0.001) and resulted in the up-regulation of melanogenic regulatory proteins, including MITF, tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1) and 2 (TYRP2). Masson-Fontana method showed that TMEM106B influenced the production of melanin in melanocytes. The spectrophotometry assay indicated that the amount of total melanin (ASM) (P<0. 001) and eumelanin (EM) (P<0. 05) were increased in alpaca melanocytes transfected with TMEM106B, while pheomelanin (PM) (P<0. 001) was decreased. These results demonstrated that TMEM106B played a vital role in melanogenesis in melanocytes by regulating ERK/CREB signaling pathway.
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Dickkopf-3 (DKK3) , as a critical inhibitor of the Wnt/p-catenin signaling pathway, may he involved in melanogenesis.In the current study, we investigated the effects of DKK3 on melanogenesis in melanocytes of alpaca.Overexpression of DKK3 in alpaca melanocytes, the expression of Wntl, Lefl , Myc and the major target genes termed microphthalmia-associated transcription factor (M1TF) and its downstream genes, including tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and tyrosinase- related protein 2 (TYRP2) were significantly decreased at both mRNA and protein levels (P<0.05); total alkali melanin, pheomelanin and eumelanin were decreased by 80.30%, 72.17% and 64.60% (P <0.05), respectively.In contrast, in the melanocytes transfected with siRNA-DKK3 (a small interference RNA targeting DKK3) , the expression of Wntl, Lefl, Myc, MITF, TYR, TYRPl and TYRP2 were significantly increased at both mRNA and protein levels (P<0.05) ; total alkali melanin, pheomelanin and eumelanin were significantly increased by 1.65 folds, 1.25 folds and 1.21 folds (P< 0.05) , respectively.These results indicate that DKK3 regulates melanogenesis in alpaca melanocytes via the Wnt/p-catenin signaling pathway and down-regulates MITF.
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Although many microRNAs (miRNAs) are known to function as regulators of coat color and melanogenesis, the underlying molecular mechanisms of miR-100-5p governing melanogenesis were not completely known.The goal of this study was to determine the effect of miR-l()()-5p on melanogenesis in alpaca melanocytes.Fibroblast growth factor 21 (FGF21) is a predicted target gene of miR-100-5p and the luciferase reporter assay demonstrated that miR-100-5p regulates FGF21 by binding to its 3' untranslated region (3'UTR).In this study, alpaca melanocytes were transfected with miR-100-5p, inhibitor and negative control plasmid.Results showed that miR-100-5p overexpression significantly decreased mRNA and protein expression of FGF2\.Meanwhile, the ERK signal pathway was inhibited, with subsequent up-regulation of microphthalmia-associated transcription factor (MITF) , tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2), which increased melanin production.The results suggest that miR-100-5p may regulate melanogenesis by targeting FGF21 via extracellular regulated MAP kinase (ERK) signaling pathway.
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Objective To provide reference for medical and health services and forensic expertise, the causes and manners of death of psychiatric patients were analyzed retrospectively. Methods A total of 105 autopsy cases of psychiatric patients accepted and settled by Institute of Forensic Science of Criminal Investigation Police University of China from 2004 to 2019 were collected. The cases were divided into four groups: disease death, suicidal death, accidental death and homicidal death. The common causes of death of each group were statistically analyzed and the differences in age, disease duration, body mass index (BMI) and gender among the groups were assessed. Results Of the 105 cases, 60 were male and 45 were female, the course of psychosis was (12.9±10.4) years, the age of the deceased was (51.3±11.4) years, and 61.0% was schizophrenic. There were 50 cases (47.6%) in the disease death group, in which the psychiatric patients were the oldest and had the longest course of psychosis and lowest BMI. Pulmonary thromboembolism, respiratory infections, and cardiogenic disease were the most common causes of death in the group. There were 26 accidental deaths (24.8%), among which traffic accidents were the most common cause of death. There were 15 homicidal deaths (14.3%), all of which were male, with craniocerebral injury being the most common cause of death. There were 14 suicidal deaths (13.3%). In suicidal death group, the age of the deceased was the youngest, the course of psychosis was the shortest and falling from the height was the most common way to commit suicide. Conclusion Understanding the common causes of death of psychiatric patients may contribute to developing measures to reduce the mortality rate of the population. It is necessary to investigate the age, course of psychosis and gender of the deceased when assessing the manner of death.
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autopsia , Causas de Morte , Medicina Legal , Estudos Retrospectivos , SuicídioRESUMO
Objective To retrospectively analyze the characteristics of the traumatic rupture of intracranial internal carotid artery in order to provide reference for forensic expertise examination and identification. Methods A total of 11 autopsy cases of traumatic rupture of intracranial internal carotid artery were collected. The gender, age, cause of injury, blood loss on the scene, location of internal carotid artery rupture, hardening degree of the rupture of the wall, brain injury, blood ethanol content and cause of death were also recorded. Results All 11 cases died on the scene, of which 7 died from traffic accidents, 2 falls from height and 2 from bare handed injuries. None of the 11 victims suffered serious head and body surface injury. The internal carotid artery rupture in the 9 cases of traffic injury and fall from height injury occurred in the cavernous segment. In all these cases, there were transverse fractures of the middle cranial fossa with the carotid sulcus involved, and minor intracranial hemorrhage and brain contusion. In 2 cases of bare handed injuries, internal carotid artery rupture occurred in the ophthalmic artery segment, accompanied by fatal intracranial hemorrhage and diffuse axonal injury, but no skull fracture. All 11 cases showed full-thickness rupture of the vessel wall, and the long axis of the wounds was perpendicular to those of the artery. Conclusion The incidence of intracranial internal carotid artery rupture in high-energy trauma events such as traffic accidents and high falls deserves attention. Injuries of the cavernous segment or ophthalmic segment might be more common. The main injury mechanism of intracranial internal carotid artery rupture might be that the blood vessels were pulled and the bone fragments caused damage.
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Humanos , Acidentes de Trânsito , Artéria Carótida Interna/diagnóstico por imagem , Estudos Retrospectivos , Ruptura , Fraturas CranianasRESUMO
The microbiome in neonates is affected by many factors such as mode of birth and feeding pattern, and homeostasis or disorder of microbiome is associated with various neonatal diseases. Preterm infants have a gestational age of <37 weeks at birth, with immature development and different colonization of bacteria from full-term infants. The research on the characteristics of microbiome and their association with diseases in preterm infants can provide new ideas for the treatment of neonatal diseases. This article reviews the characteristics of intrauterine microbiome, dermal microbiome, oral microbiome, stomach microbiome, intestinal microbiome, and environmental microbiome and their association with common diseases in preterm infants.
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Humanos , Lactente , Recém-Nascido , Bactérias , Idade Gestacional , Recém-Nascido Prematuro , MicrobiotaRESUMO
AIM: To investigate whether Toll-like receptor 4 ( TLR4 ) and Nod-like receptor protein 3 (NLRP3) inflammasome were involved in contrast medium (CM)-induced inflammation and injury in renal tubular epithe-lial cells.METHODS: Iopromide was used to injure NRK-52E cells in the study.The cell viability was measured by CCK-8 assay.The protein levels of TLR4, NLRP3, apoptosis-associated speckle-like protein (ASC), caspase-1 and cleaved caspase-3 were determined by Western blot .The releases of interleukin ( IL )-1βand IL-18 were detected by ELISA .The apoptotic rate was evaluated by Hoechst staining , and mitochondrial membrane potential ( MMP) was analyzed by JC-1 staining.siRNA was transfected into the NRK-52E cells to silence NLRP3 expression.RESULTS:CM decreased the viability of NRK-52E cells (P<0.05).CM also elevated the protein levels of cleaved caspase-3, TLR4, NLRP3, IL-1βand IL-18 (P<0.05).Silencing NLRP3 attenuated CM-induced releases of inflammatory cytokines .Moreover, treat-ment with TLR4 inhibitor TAK-242 or knockdown of NLRP3 by siRNA transfection both attenuated cell apoptosis and loss of MMP caused by CM .CONCLUSION:TLR4/NLRP3 inflammasome takes part in the pathogenesis of CM-induced acute kidney injury , and mediates CM-induced injury and inflammation in renal tubular epithelial cells .
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Objective To explore the impact of berberine on serum levels of insulin resistance and cytokines in schizophrenia patients treated with risperidone. Methods Sixty-four schizophrenia patients treated with risperidone were randomized to berberine group (n=31) and control group (n=33). The fasting plasma blood glucose (FBG) and fasting insulin (Fins) were detected before and after treatment in two groups. The homeostasis model assessment for insulin resistance (HOMA-IR) was calculated. The serum levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α) were evaluated by enzyme linked immunosorbent assay before and after the treatment. Results Compared with control group and pre-treatment group, the levels of FBG, Fins, HOMA-IR, IL-1β, IL-6 and TNF-α were significantly decreased after treatment in berberine group (P 0.05). There was positive correlation between HOMA-IR and IL-1β, IL-6 and TNF-α in berberine group (r=0.316, 0.351 and 0.401, P 1β, IL-6 and TNF-α levels in schizophrenia patients treated with risperidone. The HOMA-IR level is closely correlated with IL-1β, IL-6 and TNF-αlevels.
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To solve the problem of synthesized magnetic nanoparticles in cancer therapy, a new drug delivery system synthesized from bacteria was used to load cytosine arabinoside (Ara-C). Genipin (GP) and poly-l-glutamic acid (PLGA) were selected as dual cross-linkers. The preparation and characterization of Ara-C-loaded GP-PLGA-modified bacterial magnetosomes (BMs) (ABMs-P), as well as their in vitro antitumor effects, were all investigated. Transmission electron micrographs (TEM) and Fourier transform infrared (FTIR) spectroscopy suggested that Ara-C could be bound to the membrane of BMs modified by GP-PLGA. The diameters of the BMs and ABMs-P were 42.0±8.6 nm and 74.9±8.2 nm, respectively. The zeta potential revealed that the nanoparticles were stable. Moreover, this system exhibited optimal drug-loading properties and long-term release behavior. The optimal encapsulation efficiency and drug-loading were 64.1%±6.6% and 38.9%±2.4%, respectively, and ABMs-P could effectively release 90% Ara-C within 40 days, without the release of an initial burst. In addition, in vitro antitumor experiments elucidated that ABMs-P is cytotoxic to HL-60 cell lines, with an inhibition rate of 95%. The method of coupling drugs on BMs using dual cross-linkers is effective, and our results reveal that this new system has potential applications for drug delivery in the future.
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Antineoplásicos , Citarabina , Portadores de Fármacos/química , Ácido Glutâmico/química , Iridoides/química , Magnetossomos/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citarabina/química , Citarabina/farmacologia , Células HL-60 , HumanosRESUMO
Objective To discuss Buyang-huanwu decoction preventing the formation of lower limb deep vein thrombosis (DVT) after major orthopedic surgery.Methods 60 patients were randomly divided into a treatment group and a control group.The treatment group was treated with oral liquid of Buyang-huanwu,twice a day; while the control group was treated with 5000IU of low molecular heparin through subcutaneous injection,once daily.Prothrombin time (PT),activated partial thromboplatin time (APTT),fibrinogen (FIB),D-dimer,lower limb deep vein color B ultrasonic and the wound flow changes after 48 hours were observed at 1st,7th,and 14th day after medication.Results ①)Comparison on the incidence of DVT:The incidence of DVT in the treatment group was higher than the control group at 7th day after medication,this incidence turn to equal in the two groups at the 14th day after medication,while at the end of therapy,the incidence of DVT in the treatment group was lower than the control group with significant difference (P<0.05).②Comparison on D-dimer changes:D-dimer at the 1st and 14th day were (0.782 ± 0.472) mg/1 and (0.320 ± 0.102) mg/1 in the treatment group and (0.720±0.421)mg/1 and (0.417 ± 0.217) mg/l in the control group.Comparing with the same group before treatment [the treatment group was(0.548±0.245)mg/1; the control group was (0.560±0.195) mg/l],D-dimer was increased at the 1 st day with obvious difference (P< 0.05),but reduced at the 14th day,without statistical difference (P>0.05).Conclusion Buyang-huanwu decoction did not show good effects as low molecular heparin at the beginning of the treatment,but the its whole therapeutic effects and safety was better in treating lower limb deep vein thrombosis after major orthopedic surgery.
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The solvent extraction of rare earths with mixtures of di-( 2-ethylhexyl) phosphoric acid (D2EHPA,H2A2) and sec-nonylphenoxy acetic acid (CA100,H_2B_2) has been carried out. The separation abilities among rare earths were determined and compared with those with D_2EHPA alone. The mechanism of synergistic extraction of lanthanum was discussed. The methods of slope analysis and constant mole were used to examine the extraction stoichiometry. Effects of acidities,concentrations of extractants,and temperature on the extractabilities have been investigated. The results showed that the synergistic effects decrease with increasing atomic numbers of rare earths. At proper ratios of the extractants,the separation abilities of some rare earths with D2EHPA +CA100 were higher than those with D2EHPA alone,which may be applied to the separation of these rare earths. The extracted complex of lanthanum with D2EHPA + CA100 was determined as LaH5A6B2. The synergistic extraction is endothermically driven.