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Hecogenin (HCG), a steroidal sapogenin, possesses good antitumor properties. However, the application of HCG for cancer treatment has been hindered primarily by its moderate potency. In this study, we incorporated triphenylphosphonium cation (TPP+) at the C-3 and C-12 positions through different lengths of alkyl chains to target mitochondria and enhance the efficacy and selectivity of the parent compound. Cytotoxicity screening revealed that most of the target compounds exhibited potent antiproliferative activity against five human cancer cell lines (MKN45, A549, HCT-116, MCF-7, and HepG2). Structure-activity relationship studies indicated that the TPP+ group significantly enhanced the antiproliferative potency of HCG. Among these compounds, 3c demonstrated remarkable potency against MKN45 cells with an IC50 value of 0.48 µM, significantly more effective than its parent compound HCG (IC50 > 100 µM). Further investigations into the mechanism of action revealed that 3c induced apoptosis of MKN45 cells through the mitochondrial pathway. In a zebrafish xenograft model, 3c inhibited the proliferation of MKN45 cells. Overall, these results suggest that 3c, with potent antiproliferative activity, may serve as a valuable scaffold for developing new antitumor agents.
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Antineoplásicos , Compostos Organofosforados , Sapogeninas , Animais , Humanos , Estrutura Molecular , Sapogeninas/farmacologia , Peixe-Zebra , Ensaios de Seleção de Medicamentos Antitumorais , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Desenho de FármacosRESUMO
OBJECTIVE: To comparatively analyze the correlation between axial symptoms (AS) and cervical sagittal alignment parameters after anterior cervical discectomy and fusion (ACDF) and hybrid surgery (HS). METHODS: From January 2018 to June 2023, 74 patients who underwent ACDF (n = 36) or HS (n = 38) for two-level or three-level cervical spondylotic myelopathy were retrospectively analyzed. The Visual Analogue Scale (VAS), Japanese Orthopedic Association (JOA), Neck Disability Index (NDI) were recorded to assess clinical outcomes. Cervical sagittal alignment parameters (Cobb's angle C2-7, C7 slope [C7S], and C2-7 sagittal vertical axis [C2-7 SVA]) were measured preoperatively, 3 days postoperatively, and at the last follow-up. The range of motion (ROM) of C2-7 and ROM of surgical segment were measured. The occurrence of AS was observed at the last follow-up. Logistic regression was used to analyze the correlation between postoperative AS and cervical sagittal alignment parameters. RESULTS: Both in ACDF group and HS group, VAS, JOA and NDI scores showed significant improvements at 3-day postoperation and at the last follow-up (P < 0.05). However, there was no significant difference between the two groups (P > 0.05). The Cobb's angle C2-7 and C7S were significantly increased at 3 days postoperation compared with pre-operatively in both groups (P < 0.05). C2-7SVA was increased in both groups 3 days after surgery compared with pre-operatively, but there was no significant difference (P > 0.05). At the last follow-up, the ROM of C2-7 in ACDF group was significantly smaller than HS group (P < 0.05). The prevalence of postoperative AS in the ACDF group and HS group was 41.7 and 18.4%, respectively, with statistical difference between the two groups (P < 0.05). When simple Logistic regression analysis was used, the last Cobb's angle C2-7 (ß = -0.088), the last C2-7SVA (ß = 0.099) in ACDF group and the last C2-7SVA (ß = 0.222) in HS group were all correlated with the occurrence of postoperative AS. When multiple Logistic regression analysis was used, only the last C2-7SVA (ß = 0.181) in the HS group was positively correlated with the occurrence of postoperative AS. CONCLUSIONS: Both ACDF and HS can achieve satisfied clinical outcomes. ACDF and HS can improve cervical sagittal balance to a certain extent, and HS is superior to ACDF in maintaining ROM. The decrease of the last Cobb's angle C2-7 and the increase of the last C2-7SVA may be related to the occurrence of AS after ACDF. The increase of the last C2-7SVA was an independent risk factor for the occurrence of AS after HS.
Assuntos
Vértebras Cervicais , Discotomia , Doenças da Medula Espinal , Fusão Vertebral , Espondilose , Humanos , Fusão Vertebral/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Discotomia/métodos , Espondilose/cirurgia , Espondilose/diagnóstico por imagem , Idoso , Estudos Retrospectivos , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico por imagem , Amplitude de Movimento Articular/fisiologia , Adulto , Resultado do TratamentoRESUMO
PURPOSE: This study compared the recovery of motor function and the safety of early and delayed surgical intervention in patients with central cord syndrome (CCS). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were employed to retrieve the targeted studies published from inception to February 19, 2023. Comparative studies of early versus delayed surgical decompression in CCS based on American Spinal Injury Association motor score (AMS) recovery, complication rates, and mortality were selected. The statistical analyses were performed using STATA 16.0 and RevMan 5.4. RESULTS: Our meta-analysis included 13 studies comprising 8424 patients. Results revealed that early surgery improved AMS scores significantly compared with delayed surgery, with an increase in MDs by 7.22 points (95% CI 1.98-12.45; P = 0.007). Additionally, early surgery reduced the complication rates than delayed surgery (OR 0.53, 95% CI 0.42-0.67, P < 0.00001). However, no significant difference was observed in mortality between the two groups (OR 0.97; 95% CI 0.75-1.26; P = 0.84). CONCLUSIONS: Early surgical decompression for CCS can improve motor function and reduce the incidence of complications without affecting the mortality rate in patients. Future research should focus on investigating and analyzing the optimal window period for early CCS surgery. Additionally, the timing of surgery should be determined based on the patient's condition and available medical resources.
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OBJECTIVE: To examine the short-term efficacy and imaging results of using the Mobi-C in cervical hybrid surgery on 2-level cervical spondylolisthesis. To observe post-operative changes in the flexion-extension centre of rotation (FE-COR) and anterior bone loss (ABL) of the anterior cervical disc replacement (ACDR) segment. METHODS: Forty-two patients (20 males and 22 females, aged 42â67 years) who underwent cervical hybrid surgery were retrospectively analysed. Their ACDR segment used Mobi-C, and the fusion segment used ROI-C, with a follow-up of 25â42 months (31.1 ± 4.8 months). The modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and visual analogue scale (VAS) were used to assess clinical outcomes. Pre-operative, 6-month post-operative, and final follow-up radiographs were collected to compare total cervical spine curvature (C2-C7), curvature of the operated segments, range of motion (ROM) in the total cervical spine, operated segmental ROM, ACDR segmental ROM, and operated adjacent segmental ROM. The height of the superior articular process (HSAP), the orientation of zygapophyseal joint spaces (OZJS), and the length of the superior articular surface (LSAS) were measured. The FE-COR of the ACDR segment was measured using the mid-plumb line method. The translation distance of the Mobi-C was measured. The degree of disc degeneration in the adjacent segment, bony fusion of the ACDF segment, and ABL of the upper and lower vertebra of the ACDR segment were observed. RESULTS: In our group, all patients have shown improvements in their postoperative mJOA, NDI, and VAS scores. Overall cervical ROM and surgical segmental ROM decreased (P < 0.05). However, there was no significant decrease in ACDR segmental ROM and upper or lower adjacent segmental ROM compared with pre-operatively (P > 0.05). For FE-COR-X, only the last follow-up compared with pre-surgery showed statistical significance (46.74 ± 7.71% vs. 50.74 ± 6.92%, P < 0.05). For FE-COR-Y, the change was statistically significant at both 6 months post-operation and the final follow-up compared to pre-operation (45.37% ± 21.11% vs. 33.82% ± 10.87%, 45. 37% ± 21.11% vs. 27.48% ± 13.58%, P < 0.05). No significant difference in the Mobi-C translation distance was observed (P > 0.05). Moreover, the difference in HSAP was not statistically significant at each node (P > 0.05). The OZJS and LSAS were significantly different at the final follow-up compared to the pre-operative period (P < 0.05). All the ACDF segments were observed in a stable condition at the final follow-up. Furthermore, 9 of the adjacent segments showed imaging ASD (9/82, 10.98%), and all were present at the last follow-up, of which 6 were mild, and 3 were moderate. Twenty of the 42 Mobi-C segments had no significant ABL (grade 0) 6 months post-operatively (47.62%). Sixteen cases (38.10%) showed mild ABL (grade 1), and 6 cases (14.28%) showed moderate ABL (grade 2). No severe ABL occurred. CONCLUSION: The cervical hybrid surgery using Mobi-C artificial cervical discs can achieve satisfactory results. The Mobi-C segmental FE-COR-X shows a slow forward shift trend, and FE-COR-Y drops noticeably within 6 months post-surgery before stabilizing. It's common to see mild to moderate ABL after cervical hybrid surgery using Mobi-C, and significant progression is unlikely in the short term. Furthermore, changes in the FE-COR after hybrid surgery in the Mobi-C segment might not affect clinical outcomes.
Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Substituição Total de Disco , Feminino , Humanos , Masculino , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Seguimentos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Rotação , Fusão Vertebral/métodos , Resultado do Tratamento , Corpo Vertebral/cirurgia , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: Sacral screw loosening is a typical complication after internal fixation surgery through the vertebral arch system. Bicortical fixation can successfully prevent screw loosening, and how improving the rate of bicortical fixation is a challenging clinical investigation. OBJECTIVE: To investigate the feasibility of improving the double corticality of sacral screws and the optimal fixation depth to achieve double cortical fixation by combining the torque measurement method with bare hands. METHODS: Ninety-seven cases of posterior lumbar internal fixation with pedicle root system were included in this study. Based on the tactile feedback of the surgeon indicating the expected penetration of the screw into the contralateral cortex of the sacrum, the screws were further rotated by 180°, 360°, or 720°, categorized into the bicortical 180° group, bicortical 360° group, and bicortical 720° group, respectively. Intraoperatively, the torque during screw insertion was recorded. Postoperatively, the rate of double-cortex engagement was evaluated at 7 days, and screw loosening was assessed at 1 year follow-up. RESULTS: The bicortical rates of the 180° group, 360° group, and 720° group were 66.13%, 91.18% and 93.75%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05).The rates of loosening of sacral screws in the 180° group, 360° group, and 720° group were 20.97%, 7.35% and 7.81%, respectively. There were statistically significant differences between the 180° group and both the 360° and 720° groups (P < 0.05). However, there was no statistically significant difference between the 360° group and the 720° group (P > 0.05). The bicortical 360° group achieved a relatively satisfactory rate of dual cortical purchase while maintaining a lower rate of screw loosening. CONCLUSION: Manual insertion of sacral screws with the assistance of a torque measurement device can achieve a relatively satisfactory dual cortical purchase rate while reducing patient hospitalization costs.
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Parafusos Ósseos , Vértebras Lombares , Sacro , Fusão Vertebral , Torque , Humanos , Masculino , Feminino , Sacro/cirurgia , Sacro/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Fusão Vertebral/efeitos adversos , Vértebras Lombares/cirurgia , Adulto , Estudos de Viabilidade , Resultado do Tratamento , SeguimentosRESUMO
Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.
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Extratos Vegetais , Zea mays , Pressão Sanguínea , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologiaRESUMO
Isoniazid (INH) and pyrazinamide (PZA) are both the first-line anti-tuberculosis drugs in clinical treatment. It is notable that there are serious side effects of the drugs along with upregulation of reactive nitrogen species, mainly including peripheral neuritis, gastrointestinal reactions, and acute drug-induced liver injury (DILI). Among them, DILI is the most common clinical symptom as well as the basic reason of treatment interruption, protocol change, and drug resistance. As vital reactive nitrogen species (RNS), peroxynitrite (ONOO-) has been demonstrated as a biomarker for evaluation and pre-diagnosis of drug-induced liver injury (DILI). In this work, we developed a red-emitting D-π-A type fluorescence probe DIC-NP which was based on 4'-hydroxy-4-biphenylcarbonitrile modified with dicyanoisophorone as a fluorescent reporter and diphenyl phosphinic chloride group as the reaction site for highly selective and sensitive sensing ONOO-. Probe DIC-NP displayed a low detection limit (14.9 nM) and 60-fold fluorescent enhancement at 669 nm in the sensing of ONOO-. Probe DIC-NP was successfully applied to monitor exogenous and endogenous ONOO- in living HeLa cells and zebrafish. Furthermore, we verified the toxicity of isoniazid (INH) and pyrazinamide (PZA) by taking the oxidative stress induced by APAP as a reference, and successfully imaged anti-tuberculosis drug-induced endogenous ONOO- in HepG2 cells. More importantly, we developed a series of mice models of liver injury and investigated the hepatotoxicity caused by the treatment of anti-tuberculosis drugs. At the same time, H&E of mice organs (heart, liver, spleen, lung, kidney) further confirmed the competence of probe DIC-NP for estimating the degree of drug-induced liver injury, which laid a solid foundation for medical research.
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Antituberculosos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Camundongos , Animais , Antituberculosos/toxicidade , Isoniazida/toxicidade , Pirazinamida/toxicidade , Células HeLa , Peixe-Zebra , Corantes Fluorescentes/farmacologia , Ácido PeroxinitrosoRESUMO
AIM: To investigate the regulatory role of miR-155 and Kinesin Superfamily Proteins-5C (KIF-5C) in the progression of pulpitis based on bioinformatic analysis. METHODOLOGY: Normal pulp tissues and pulpitis pulp tissues were collected and subjected to high-throughput sequencing and the differentially expressed miRNAs were determined. An in vitro and in vivo pulpitis model was established. HE, IHC staining and histological evaluation were used to verify the inflammatory state of human and mouse pulp tissues. The mRNA expression of IL-1ß and TGF-ß1 were determined by RT-qPCR and protein expression of IL-1α, IL-4, IL-8, IL-13, IFN-γ, IL-6, IL-10 and MCP-1 were determined by protein chip. The target genes of miR-155 were predicted by miRanda database and verified by Dual-luciferase reporter assay, RT-qPCR and western blotting. MiR-155 lentivirus were used to upregulate or downregulate miR-155 and the siRNA of KIF-5C was used to downregulate KIF-5C. The expression of miR-155 or KIF-5C was determined by RT-qPCR. All statistics were analysed using GraphPad prism 8.2. RESULTS: The high-throughput sequencing results showed that 6 miRNAs (miR-155, miR-21, miR-142, miR-223, miR-486, miR-675) were significantly upregulated in diseased human pulp tissues, and miR-155 was significantly elevated among the six miRNAs. RT-qPCR results demonstrated that miR-155 expression was upregulated in human pulpitic tissue, mice pulpitic tissue and LPS-HDPCs. IL-1ß was increased while TGF-ß1 was decreased in lenti-miR-155 transfected LPS-HDPCs. Analysis of protein chip results indicated that lenti-miR-155 transfected LPS-HDPCs produced higher levels of IL-8, IL-6, MCP-1. The opposite results were obtained when miR-155 was inhibited. Through miRanda database screen and Dual-luciferase reporter assay, the target gene (KIF-5C) of miR-155 was identified. In lenti-miR-155 transfected LPS-HDPCs, the expression of KIF-5C was downregulated. However, when shRNA-miR-155 was transfected to LPS-HDPCs, the opposite result was obtained. Silent RNA was used to knock down KIF-5C, the results showed that when both KIF-5C and miR-155 were knocked down simultaneously, the downregulated expression of inflammatory factors observed in LPS-HDPCs following miR-155 knockdown was rescued. CONCLUSION: MiR-155 plays an important role in promoting pulpitis through targeting KIF-5C and may serve as a potential therapeutic target.
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MicroRNAs , Pulpite , Humanos , Camundongos , Animais , Pulpite/genética , Pulpite/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Cinesinas/genética , Cinesinas/metabolismo , Lipopolissacarídeos/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Polpa Dentária/metabolismo , Luciferases/metabolismoRESUMO
BACKGROUND: As we all know, the numbers of aesthetic surgery are increasing around the world. After the surgery, the scar would be a problematic issue for both the surgeons and the patients. Silicone has proven to be effective for keloids, hypertrophic scars, and prevention of scar formation in many literatures for a long time. In terms of scar prevention, silicone has been used in the form of silicone sheets in early times, which is later improved to be the form of silicone gel with the advantage of easier usage. Although silicone gel has improved greatly in the aspect of appearance and convenience of the silicone sheets, there are still some disadvantages of the gel form. Therefore, the LeniScar silicone stick (AnsCare) is invented. OBJECTIVE: This article aimed to compare the results of scar treatment and prevention of the AnsCare LeniScar Silicone Stick versus the traditional silicone gel (Dermatix Ultra). METHODS: This study was a prospective, nonblinded, randomized clinical study. There were a total of 68 patients from September 2018 to January 2020. Patients were divided into 2 groups with AnsCare (n = 43) and Dermatix (n = 25), who both were required to schedule regular outpatient clinic follow-up, and photographs were taken before use, 1, 2, and 3 months later after the usage for the record. The physician assessed the scar condition by the Vancouver Scar Scale (VSS). The scores of the VSS were further analyzed and compared. RESULTS: The overall P value of total score of VSS was 0.635, which indicates that there is no significant difference in using AnsCare LeniScar Silicone Stick versus Dermatix Ultra silicone gel in terms of scar prevention and treatment. Individual items of VSS such as pliability, height, vascularity, and pigmentation all show no significant statistical difference in the 2 treatment products, with P = 0.980, 0.778, 0.528, and 0.366, respectively. CONCLUSION: Traditional Dermatix Ultra silicone gel has been effective in the treatment of scar formation. AnsCare LeniScar Silicone Stick is statistically not different from the Dermatix Ultra silicone gel when comparing the treatment results of scar prevention. Furthermore, the AnsCare LeniScar Silicone Stick has the advantages of being time-saving with no need to wait for it to dry and application of precise amount to precise location, preventing waste or overuse.
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Cicatriz Hipertrófica , Queloide , Humanos , Géis de Silicone/uso terapêutico , Estudos Prospectivos , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/prevenção & controle , Queloide/etiologia , Queloide/prevenção & controle , Resultado do TratamentoRESUMO
This study investigated the effect of the landscape pattern of permeable/impermeable patches on NO3--N and particulate organic nitrogen (PON) concentrations during stormwater runoff transport and their source contributions. Six landscape pattern indices, namely, mean proximity index (MPI), largest patch index (LPI), mean shape index (MSI), landscape shape index (LSI), connect index (CONNECT), and splitting index (SPLIT), were selected to reflect the fragmentation, complexity, and connectivity of permeable patches in urban catchments. The results show that lower fragmentation, higher complexity, and greater connectivity can reduce NO3--N concentrations in road runoff and drainage flow (i.e., the flow in the stormwater drainage network), as well as PON concentrations in road runoff. Further, the above landscape pattern is effective for mitigating the contributions of NO3--N and PON from road runoff. Low impact development (LID) can be incorporated with the landscape pattern of permeable/impermeable patches to mitigate nitrogen pollution in urban stormwater at the catchment scale by optimizing the spatial arrangement.
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Nitratos , Poluentes Químicos da Água , Nitratos/análise , Nitrogênio/análise , Monitoramento Ambiental/métodos , Movimentos da Água , Poluentes Químicos da Água/análise , Chuva , Compostos Orgânicos/análise , PoeiraRESUMO
Chemoselective terpolymerization can produce polymer materials with diverse compositions and sequential structures, and thus have attracted considerable attention in the field of polymer synthesis. However, the intrinsic complexity of three-component system also brings great chanllenge, in regard to the reactivity and selectivity of different monomers. Herein, we report the terpolymerization of CO2 /epoxide/anhydride by a binary organocatalytic C3 N3 -Py-P3 /TEB (triethylborane) system. Both the activity and chemoselectivity were highly dependent upon the molar ratio of C3 N3 -Py-P3 to TEB, and sequence-controlled poly(ester-carbonate) copolymers were readily synthesized through one-pot/one-step methodology by tuning the stoichiometric ratio of phosphazene/TEB. In particular, C3 N3 -Py-P3 /TEB with a molar ratio of 1/0.5 exhibited an unprecedentedly high chemoselectivity for ring-opening alternating copolymerization (ROAC) of cyclohexene oxide (CHO) and phthalic anhydride (PA) first and then ROAC of CO2 /CHO. Thus, well-defined triblock polycarbonate-b-polyester-b-polycarbonate copolymers can be produced from the mixture of CO2 , CHO and PA using a bifunctional initiator. With C3 N3 -Py-P3 /TEB=1/1, tapered copolymers were obtained, while random copolymers with high content of polycarbonate (PC) were synthesized with further increasing the amount of TEB. The mechanism of the unexpected chemoselectivity was further investigated by DFT calculations.
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Boranos , Dióxido de Carbono , Dióxido de Carbono/química , Polímeros/química , CarbonatosRESUMO
To discover new lead compounds with anti-tumour activities, in the present study, natural diosgenin was hybridised with the reported benzoic acid mustard pharmacophore. The in vitro cytotoxicity of the resulting newly synthesised hybrids (8-10, 14a-14f, and 15a-15f) was then evaluated in three tumour cells (HepG2, MCF-7, and HeLa) as well as normal GES-1 cells. Among them, 14f possessed the most potential anti-proliferative activity against HepG2 cells, with an IC50 value of 2.26 µM, which was 14.4-fold higher than that of diosgenin (IC50 = 32.63 µM). Furthermore, it showed weak cytotoxicity against GES-1 cells (IC50 > 100 µM), thus exhibiting good antiproliferative selectivity between normal and tumour cells. Moreover, 14f could induce G0/G1 arrest and apoptosis of HepG2 cells. From a mechanistic perspective, 14f regulated cell cycle-related proteins (CDK2, CDK4, CDK6, cyclin D1 and cyclin E1) as well mitochondrial apoptosis pathway-related proteins (Bax, Bcl-2, caspase 9, and caspase 3). These findings suggested that hybrid 14f serves as a promising anti-hepatoma lead compound that deserves further research.
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Carcinoma Hepatocelular , Diosgenina , Neoplasias Hepáticas , Ácido Benzoico , Carcinoma Hepatocelular/patologia , Proliferação de Células , Diosgenina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , MostardeiraRESUMO
Ent-abietane diterpenoids are the main active constituents of Euphorbia fischeriana. In the continuing search for new anti-breast cancer drugs, 11 ent-abietane diterpenoids (1-11) were isolated from E. fischeriana. The structures of these compounds were clearly elucidated on the basis of 1D and 2D NMR spectra as well as HRESIMS data. Among them, compound 1 was a novel compound, compound 10 was isolated from Euphorbia genus for the first time, compound 11 was firstly discovered from E. fischeriana. These compounds exhibited varying degrees of growth inhibition against the MCF-10A, MCF-7, ZR-75-1 and MDA-MB-231 cell lines in vitro. The experimental data obtained permit us to identify the roles of the epoxy group, hydroxyl group and acetoxyl group on their cytotoxic activities. Extraction is an important means for the isolation, identification, and application of valuable compounds from natural plants. To maximize yields of ent-abietane diterpenoids of E. fischeriana, 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A were selected as quality controls to optimize the salting-out-assisted liquid-liquid extraction (SALLE) by response surface methodology (RSM). The optimized conditions for SALLE were 0.47 g sodium dihydrogen phosphate, 5.5 mL acetonitrile and 4.5 mL water at pH 7.5. The experimental values of 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A (2.134, 0.529, 0.396, and 0.148 mg/g, respectively) were in agreement with the predicted values, thus demonstrating the appropriateness of the model.
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Antineoplásicos Fitogênicos , Diterpenos , Euphorbia , Neoplasias , Abietanos/análise , Abietanos/farmacologia , Antineoplásicos Fitogênicos/química , Diterpenos/química , Euphorbia/química , Estrutura Molecular , Neoplasias/tratamento farmacológico , Raízes de Plantas/químicaRESUMO
BACKGROUND: GenoLab M is a recently established next-generation sequencing platform from GeneMind Biosciences. Presently, Illumina sequencers are the globally leading sequencing platform in the next-generation sequencing market. Here, we present the first report to compare the transcriptome and LncRNA sequencing data of the GenoLab M sequencer to NovaSeq 6000 platform in various types of analysis. RESULTS: We tested 16 libraries in three species using various library kits from different companies. We compared the data quality, genes expression, alternatively spliced (AS) events, single nucleotide polymorphism (SNP), and insertions-deletions (InDel) between two sequencing platforms. The data suggested that platforms have comparable sensitivity and accuracy in terms of quantification of gene expression levels with technical compatibility. CONCLUSIONS: Genolab M is a promising next-generation sequencing platform for transcriptomics and LncRNA studies with high performance at low costs.
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RNA Longo não Codificante , Transcriptoma , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Mutação INDEL , RNA Longo não Codificante/genéticaRESUMO
OBJECTIVE: Ultrasound has an excellent diagnostic accuracy for fractures that is reportedly comparable to plain radiographs. We aim to summarize the diagnostic accuracy of ultrasound for upper extremity fractures in children. METHODS: Databases were searched from inception through November 2019 using pre-defined index terms, including "ultrasound," "fractures of upper extremities" and "children". The study is reported using Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA). Meta-analysis of the diagnostic accuracy of ultrasound for fractures was conducted using the random-effects bivariate model. Subgroup analysis of fracture site (elbow vs non-elbow fractures) was also performed. Meta-regression was performed to determine if the site of fracture affected the diagnostic accuracy. RESULTS: Thirty-two studies were identified in the meta-analysis. Ultrasound for fractures of the upper extremities has a sensitivity: 0.95 (95% CI: 0.93-0.97), specificity: 0.95 (95% CI: 0.91-0.98), positive likelihood ratio: 21.1 (95% CI: 10.8-41.5) and negative likelihood ratio: 0.05 (95% CI: 0.03-0.07), with an area under ROC (AUROC) curve of 0.98 (95% CI: 0.97-0.99). Subgroup analysis for elbow fracture showed ultrasound has a sensitivity: 0.95 (95% CI: 0.86-0.98), specificity: 0.87 (95% CI: 0.76-0.94), positive likelihood ratio: 7.3 (95% CI: 3.7-14.4) and negative likelihood ratio: 0.06 (95% CI: 0.02-0.16), with an AUROC of 0.96 (95% CI: 0.94-0.97). Meta-regression suggested the fracture sites would affect diagnostic accuracy of ultrasound (elbow vs non-elbow, pâ¯<â¯0.01). CONCLUSIONS: Current evidence suggests ultrasound has excellent diagnostic accuracy for non-elbow upper extremity fractures in children, serving as an alternative diagnostic modality to plain radiographs.
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Fraturas Ósseas/diagnóstico por imagem , Ultrassonografia , Extremidade Superior/diagnóstico por imagem , Extremidade Superior/lesões , Criança , Serviço Hospitalar de Emergência , Humanos , Testes ImediatosRESUMO
OBJECTIVE: To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer (SC) and its subclasses (basal cell carcinoma BCC; squamous cell carcinoma SCC; melanoma; nonmelanoma skin cancer NMSC) in general, American and European populations. METHODS: PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure and ClinicalTrials.gov were searched up to 24 February 2019. Pooled effect sizes and 95% confidence intervals were used to estimate associations. RESULTS: Results based on 26 original studies including 223,619 cases and 1,398,507 controls showed both NSAIDs and nonselective Cyclooxygenase (COX) inhibitors to be statistically significantly associated with a reduced risk of SC, BCC, SCC and NMSC but not with melanoma. Conversely, no association was observed between selective Cyclooxygenase 2 (COX-2) inhibitors and SC or its subclasses. Further subgroup analysis showed that the results analyzed for American populations were almost the same as those for the general population. For European populations, neither NSAIDs nor its subtypes correlated significantly with susceptibility to SC or its subclasses. CONCLUSIONS: The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias Cutâneas/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Stratification analyses have been widely utilized in molecular association meta-analyses to estimate the interaction between genetic and environmental factors or to control for the confounding variables linked to a disease. Two calculation methods utilized in practical research, which are known as the variants of factorial stratification analysis and confounder-controlling stratification analysis in our nomenclature, have been applied in previous studies, but none of which have presented a methodology and application for these analyses. METHODS: In this paper, these two approaches are integrated and further developed into a standard procedure for stratification analysis. We first propose the advanced statistical methodology and theoretical algorithm of these three types of stratification analysis and then provide two example applications in meta-analyses of molecular association to illustrate the computing processes and interpretation of the results. RESULTS: The standard stratification analysis synthesizes the advantages of the first two practical methods, including identifying and controlling confounding moderators or revealing and calculating gene-environment interactions, to efficiently classify the real influence of various investigated factors on a disease in the general population. Additional challenges concerning this method and their potential solutions are also discussed, such as the approach to utilizing only the partially stratified data available in meta-research practice. CONCLUSIONS: The standard stratification method will be extensively applicable to rapidly expanding future research on the complex relationships among genetics, environment, disease, and other variables.
Assuntos
Algoritmos , Projetos de Pesquisa , Fatores de Confusão Epidemiológicos , HumanosRESUMO
A novel and simple method was established for the extraction and determination of seven compounds in Anemarrhena asphodeloides Bge. using silica gel-based vortex-homogenized matrix solid-phase dispersion and ultra-high performance liquid chromatography quadrupole-time of-flight mass spectrometer. The conditions for the extraction were optimized. Silica gel was used as the dispersant, 50% methanol-water was selected as an elution solvent and the grinding time was 3 min. Compared with the traditional ultrasonic-assisted extraction, the developed method was rapid and efficient. In order to screen potential antioxidants, extract dealing with the optimized method was applied to a polyamide chromatography column and a D-101 macroporous resin column. Fr.2.2 showed the highest antioxidant activities with the most content of flavonoid. A total of 25 peaks were identified from the active fraction. A 2,2'-diphenyl-1-picrylhydrazyl ultra-high performance liquid chromatography coupled with mass spectrometry approach was adopted for the rapid and exact screening and identification of antioxidant compounds. It indicated that flavonoids exhibited potential antioxidant activities. The antioxidant activities of nine monomeric compounds in vivo were tested. Structure-activity relationships were discussed. Five flavonoids with the concentration of 500 µg/mL would reduce the oxidative stress of PC12 cells that were induced with 2,2'-azobis[2-methylpropionamidine] dihydrochloride.
Assuntos
Anemarrhena/química , Antioxidantes/análise , Flavonoides/análise , Extratos Vegetais/isolamento & purificação , Extração em Fase Sólida , Amidinas/antagonistas & inibidores , Amidinas/farmacologia , Animais , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Sílica Gel/químicaRESUMO
OBJECTIVE: It is unclear whether point-of-care ultrasound (POCUS) by emergency medicine physicians is as accurate as radiology-performed ultrasound (RADUS). We aim to summarize the diagnostic accuracy of ultrasonography for intussusception and to compare the performance between POCUS and RADUS. METHODS: Databases were searched from inception through February 2018 using pre-defined index terms. Peer-reviewed primary studies that investigated the diagnostic accuracy of ultrasound for intussusception in children were included. The study is reported using Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA). Meta-analysis of the diagnostic accuracy of ultrasound for intussusception was conducted using the random-effects bivariate model. Subgroup analysis (POCUS vs RADUS) was also performed. Meta-regression was utilized to determine if the diagnostic accuracy between POCUS and RADUS was significantly different. RESULTS: Thirty studies (nâ¯=â¯5249) were included in the meta-analysis. Ultrasonography for intussusception has a sensitivity: 0.98 (95% CI: 0.96-0.98), specificity: 0.98 (95% CI: 0.95-0.99), positive likelihood ratio: 43.8 (95% CI: 18.0-106.7) and negative likelihood ratio: 0.03 (95% CI: 0.02-0.04), with an area under ROC (AUROC) curve of 0.99 (95% CI: 0.98-1.00). Meta-regression suggested no significant difference in the diagnostic accuracy for intussusception between POCUS and RADUS (AUROC: 0.95 vs 1.00, pâ¯=â¯0.128). CONCLUSIONS: Current evidence suggested POCUS has a high diagnostic accuracy for intussusception not significantly different from that of RADUS.
Assuntos
Intussuscepção/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito/normas , Ultrassonografia/normas , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/normas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Stainless steel wire mesh supported molecularly imprinted composite membranes for selective separation of Ebracteolata Compound B (ECB) were prepared based on surface polymerization using ECB separated from Euphorbia fischeriana as a template, acrylamide as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, azodiisobutyronitrile as an initiator, and stainless steel wire mesh as support. Structure and purity of ECB were characterized by nuclear magenetic resonance (¹H-NMR, 13C-NMR) and ultra high performance liquid chromatography (UHPLC). The molecularly imprinted composite membranes were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The membrane adsorbed on the ECB reached equilibrium about 30 min later, with a maximum adsorption amount of 3.39 µmol/cm². Adsorption behavior between ECB and the molecularly imprinted composite membranes followed pseudo-second-order kinetics equation and Freundlich isotherm model. The molecularly imprinted composite membranes that could selectively identify and transport ECB in similar structures have a permeation rate of 38.71% to ECB. The ECB content in the permeation solution derived from the extract of Euphorbia fischeriana through the imprinted membrane was 87%. Overall, the obtained results demonstrated that an efficient approach with the molecularly imprinted composite membranes for selective separation of ECB from Euphorbia fischeriana.