RESUMO
BACKGROUND: Ribosomal protein L38 (RPL38) was found upregulated in osteoarthritic peripheral blood mononuclear cells, however, its role in progression of osteoarthritis has not been characterized. METHODS: The protein levels of RPL38 and SOCS2 in cartilage tissues from OA patients and controls were detected with Western blotting. IL-1ß was used to stimulate primary chondrocytes to establish an OA cell model, and RPL38 siRNA (si-RPL38) was transfected into chondrocytes to investigate the effect of RPL38 knockdown on cell viability, apoptosis, inflammatory factor secretion and extracellular matrix degradation. Then, the mechanism that RPL38 regulate the SOCS2 expression and SOCS2-induced chondrocyte dysfunction was explored. The methyltransferase-like 3 (METTL3)-mediated m6A modification of SOCS2 mRNA was confirmed, and the interaction of RPL38 and METTL3 was verified. Moreover, the effects of SOCS2 overexpression on IL-1ß-induced chondrocyte dysfunction and SOCS2 knockdown on the restoration of chondrocyte function by siRPL38 were investigated. Finally, RPL38 was knocked down in vivo and its role in OA progression was validated. RESULTS: RPL38 was upregulated and SOCS2 was downregulated in OA cartilages. RPL38 knockdown or SOCS2 overexpression either attenuated IL-1ß-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation. RPL38 directly interacted with METTL3 and it inhibited SOCS2 expression through METTL3-mediated m6A modification. SOCS2 knockdown activated the JAK2/STAT3 proinflammatory pathway and reversed the effects of RPL38 knockdown on IL-1ß-induced chondrocyte apoptosis, inflammation and ECM degradation. RPL38 knockdown alleviated cartilage tissue damage and ECM degradation in OA mice. CONCLUSION: RPL38 knockdown inhibited osteoarthritic chondrocyte dysfunction and alleviated OA progression through promoting METTL3-m6A-mediated SOCS2 expression.
Assuntos
MicroRNAs , Osteoartrite , Proteínas Ribossômicas/metabolismo , Animais , Apoptose , Condrócitos , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/farmacologia , Leucócitos Mononucleares/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Metiltransferases/farmacologia , Camundongos , MicroRNAs/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Proteínas Supressoras da Sinalização de Citocina/farmacologiaRESUMO
Although substantial progress has been made in early detection and treatment of GC, this disease remains a major burden worldwide. CircRNAs have potential as prognostic and diagnostic biomarkers in tumorigenesis. Therefore, we aimed to clarify the role and mechanism of circACC1 in GC cell proliferation. The expression levels of circACC1, miR-29c-3p and FOXP1 were validated in GC tissue samples and adjacent tissue samples. The impact of circACC1 and miR-29c-3p on overall survival was evaluated in GC specimens. A functional study was performed on MKN-45 and BGC823 cells transfected with different vectors. Cell proliferation was assayed by CCK-8 and colony formation assays. The interactions among circACC1, miR-29c-3p and FOXP1 were tested by RNA immunoprecipitation and luciferase reporter assays. This study demonstrated that circACC1 is upregulated in GC tissues, and its upregulation predicts poorer OS in GC patients. Upregulation of circACC1 promoted GC cell proliferation, as indicated by CCK-8 and colony formation assays. A mechanistic study revealed that the pro-oncogenic effect of circACC1 was mainly caused by binding to miR-29c-3p, thus regulating expression of its downstream target FOXP1. The circACC1/miR-29c-3p/FOXP1 network plays a key role in gastric cancer by regulating cell proliferation.
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Proliferação de Células/genética , Fatores de Transcrição Forkhead/metabolismo , RNA Circular/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Prognóstico , RNA Circular/genética , Proteínas Repressoras/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Regulação para CimaRESUMO
OBJECTIVES: Spinal cord injury (SCI) is an acute traumatic lesion of neurons in the spinal cord which has a high prevalence in the world, and has no effective surgical treatment. HSP70 is a molecular chaperone protein, serves a protective role in several different models of nervous system injury. The aim of the present study was to investigate the anti-inflammatory role of HSP70 in spinal cord injury and explore its mechanism. METHODS: In vivo and in vitro models were constructed to mimic SCI. The Basso Mouse Scale (BMS) was applied to assess SCI degrees of the mouse model. Immunofluorescence (IF) was used for visualizing HSP70 and Iba1 in the spinal cord. Western blot assay was employed to quantify HSP70 and p65, and ELISA was for IL-1ß and TNF-α. RESULTS: The results showed that HSP70 expression decreased after SCI. HSP70 and Iba1 showed a decrease of co-localization in SCI mice. Further studies revealed that p65 was upregulated during the process of SCI. Overexpression of HSP70 inhibited the expression of p65 both in vitro and in vivo, and promoted the recovery of SCI mice. CONCLUSIONS: HSP70 was involved in the pathological process of spinal cord injury, HSP70 alleviated the spinal cord injury via inhibiting NF-κB signaling pathway.
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Proteínas de Choque Térmico HSP70/metabolismo , NF-kappa B , Traumatismos da Medula Espinal , Animais , Inflamação , Camundongos , NF-kappa B/metabolismo , Transdução de SinaisRESUMO
OBJECTIVES: S100-ß has been identified as a sensitive biomarker in central nervous system injuries. However, the functions and mechanisms of S100-ß are unknown in spinal cord injury. METHODS: Spinal cord injury (SCI) mouse model was generated by surgical operation, microglia activation model was established by inducing BV-2 cells with LPS. The SCI model was evaluated by Basso-Beattie-Bresnahan (BBB) behavioral score, HE staining, and Nissl staining. The expression level of S100-ß was detected by qRT-PCR, western blot, and immunofluorescence. qRT-PCR and western blot were used to detect the expression of iNOS and CD16. Pro-inflammatory cytokines TNF-α and IL-1ß levels were detected by qRT-PCR and ELISA. RESULTS: The expression of IL-1ß, TNF-α, iNOS, and CD16 increased at 3rd day after SCI. In BV2 microglia, LPS treatment promoted the expression of S100-ß, IL-1ß, TNF-α, iNOS, and CD16. Knockdown of S100-ß reduced the expression of iNOS stimulated by LPS. Over-expression of S100-ß increased IL-1ß and TNF-α, and S100-ß inhibition suppressed IL-1ß and TNF-α. In SCI mice, knockdown of S100-ß attenuated the spinal cord injury and inhibited the expression of iNOS, IL-1ß, and TNF-α. CONCLUSIONS: Down-regulation of S100-ß could inhibit the pathogenesis of SCI and inhibit the activation of M1 macrophages. S100-ß may be a useful diagnostic biomarker or therapeutic target for SCI.
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Traumatismos da Medula Espinal , Animais , Macrófagos , Camundongos , Microglia , Fenótipo , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
A growing number of individuals are now exposed to neodymium (Nd) owing to its extensive applications. However, the biological effects of Nd on humans, especially on learning and memory, remain elusive. To investigate whether Nd exposure affects learning and memory, in this study female ICR mice were exposed to nano Nd2 O3 via intranasal instillation at doses of 50, 100, and 150 mg/kg body weight, daily for 45 days. According to Morris water maze data, learning and memory parameters were significantly reduced in the 150 mg/kg nano-Nd2 O3 group than the sham control. Furthermore, inductively coupled plasma-mass spectroscopy analysis revealed that Nd levels were significantly higher in the hippo campus of the 100 and 150 mg/kg exposed group than the sham control; however, no significant differences were observed in the hippocampal histopathology between these groups. Furthermore, reactive oxygen species were elevated in hippocampal tissues of experimental groups than the sham control, 447.3 in high dose group and 360.0 in control group; however, malondialdehyde levels were significantly increased and superoxide dismutase activities were decreased only in mice exposed to 100 and 150 mg/kg Nd2 O3 . High-performance liquid chromatography data demonstrated that levels of glutamic acid, glycine, and gamma-aminobutyric acid were higher in the hippocampus of mice exposed to 150 mg/kg Nd2 O3 than the sham control. Our findings indicated that the neuronal injury was induced by disruption of the oxidation-antioxidation homeostasis and altered amino acid neurotransmitter levels in the hippocampus, which could result in the poor cognitive performance demonstrated by exposed mice.
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Memória , Neodímio , Animais , Feminino , Hipocampo/metabolismo , Aprendizagem , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos ICR , Óxidos , Superóxido Dismutase/metabolismoRESUMO
Basic medical laboratory courses (BMLCs) play an important role in medical educational courses helping the student acquire three important skills of surgical operating, collaborative learning, and problem solving. The outcome-based student assessment (OBSA) is a learning evaluation method that establishes specific evaluation points based on performance of students in three aspects: surgical operating, collaborative learning, and problem solving in the BMLC curriculum practices. The purpose of the present randomized controlled trial study is to explore the efficiency of OBSA program in BMLCs. The 233 students attending BMLCs were randomly divided into 2 groups, 118 in the OBSA group and 115 in the control group. We conducted multiple-choice examination questions (MCQs) test and two questionnaires with the method of two-sample t test for statistics. The results of MCQs in total eight BMLC blocks showed that the academic performance of the OBSA group was significantly better than that of the control group (P < 0.05). In addition, the average scores of direct observation of procedural skills (DOPS) and mini-experimental evaluation exercise in OBSA group were significantly higher than those in control group (P < 0.05). The majority of the medical students preferred the OBSA and considered OBSA could effectively improve their surgical operating skills (83.9%), collaborative learning skills (92.1%), and problem-solving skills (91.1%). From the above, OBSA is an effective evaluation method for the implementation of the BMLC curriculum.
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Desempenho Acadêmico , Educação de Graduação em Medicina , Estudantes de Medicina , Competência Clínica , Currículo , Avaliação Educacional , Humanos , Laboratórios , Aprendizagem Baseada em ProblemasRESUMO
Traumatic nerve injuries have become a common clinical problem, and axon regeneration is a critical process in the successful functional recovery of the injured nervous system. In this study, we found that peripheral axotomy reduces PTEN expression in adult sensory neurons; however, it did not alter the expression level of PTEN in IB4-positive sensory neurons. Additionally, our results indicate that the artificial inhibition of PTEN markedly promotes adult sensory axon regeneration, including IB4-positive neuronal axon growth. Thus, our results provide strong evidence that PTEN is a prominent repressor of adult sensory axon regeneration, especially in IB4-positive neurons.
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Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/antagonistas & inibidores , Crescimento Neuronal/fisiologia , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Fenantrenos/farmacologia , Lectinas de Plantas/análise , Neuropatia Ciática/fisiopatologia , Células Receptoras Sensoriais/metabolismo , Animais , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Gânglios Espinais/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Camundongos Knockout , Regeneração Nervosa/efeitos dos fármacos , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Crescimento Neuronal/efeitos dos fármacos , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Células Receptoras Sensoriais/química , Células Receptoras Sensoriais/classificação , Células Receptoras Sensoriais/efeitos dos fármacosRESUMO
A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.
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COVID-19/epidemiologia , Fezes/virologia , SARS-CoV-2/fisiologia , Eliminação de Partículas Virais , Adolescente , Antivirais/uso terapêutico , COVID-19/transmissão , Portador Sadio/epidemiologia , Portador Sadio/virologia , Criança , Pré-Escolar , China/epidemiologia , Família , Feminino , Hospitalização , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/patogenicidadeRESUMO
PURPOSE: To determine the safe range of shortening the spinal column at middle thoracic spine and to observe the changes in blood-spinal cord barrier (BSCB), microglia/macrophage activation and inducible nitric oxide synthase (iNOS) activity after shortening-induced spinal cord injury. METHODS: Dogs were allocated to four groups. Group A (control) underwent laminectomy of T7 without shortening the spinal column. Groups B, C and D had 1/3, 1/2, and 2/3 of T7 resected, respectively, followed by spinal shortening. Somatosensory evoked potential (SSEP) and hind-limb function were recorded periodically for 14 days after operation. Spinal cord blood flow (SCBF) and BSCB were detected at the acute phase of shortening. Microglia/macrophage reactions and iNOS activity were observed by immunohistochemistry. RESULTS: Shortening of 1/3 of a vertebral height caused no significant changes in SSEP and hind-limb function after operation, whereas shortening of 1/2 of the height caused SSEP abnormality and paraparesis, and severe neurologic deficit of hind-limb was observed when the shortening reached 2/3 of the height. SCBF increased temporarily and showed a trend of recovery when the shortening was within 1/2 of a vertebral segment height. When it reached 1/2 or 2/3 of the height, SCBF at 6 h post-operation was 86.33% or 74.95% of the baseline, and an increasing BSCB permeability was observed. In the subsequent 7 days, obvious activation of macrophage and increased number of iNOS-positive cells were observed. CONCLUSION: It is safe to shorten the spinal cord within 1/3 of a vertebral height in middle thoracic spine under two-segment laminectomy in canine. The BSCB disruption, macrophage activation, and increased iNOS activity were observed in the acute phase of the injury. These slides can be retrieved under Electronic Supplementary Material.
Assuntos
Traumatismos da Medula Espinal , Coluna Vertebral , Animais , Cães , Potenciais Somatossensoriais Evocados , Laminectomia , Medula Espinal/cirurgia , Traumatismos da Medula Espinal/cirurgia , Coluna Vertebral/cirurgiaRESUMO
To optimize the ethanol extraction technology parameters of Fengyin Decoction by orthogonal experiment combined with beetle antennae search(BAS)-genetic algorithm(GA)-back propagation neural network(BPNN). Based on single factor investigation, the extraction temperature, ethanol volume, extraction time, and ethanol concentration were used as orthogonal experiment factors, and entropy weight method was used to calculate the comprehensive scores of aloe-emodin, glycyrrhizic acid ammonium salt, rhein, emodin, chrysophanol, physcion, cinnamaldehyde, 6-gingerol, extraction ratio and fingerprint similarity. BAS-BPNN model was established, and then, GA was used to predict the optimal extraction process. The results showed that BAS-BPNN was optimized to obtain the optimal ethanol extraction process of Fengyin Decoction as follows: extraction temperature of 87 â, adding 9 times of 75 % ethanol, and extracting for 47 minutes, with a comprehensive score of 1.052 9. Meanwhile, the optimal process parameters obtained by orthogonal design were as follows: the extraction temperature of 80 â, adding 10 times of 75% ethanol, extracting for 30 minutes, with a comprehensive score of 1.003 7. The comprehensive score of the process obtained from the BAS-BPNN model was slightly better than that from the orthogonal test, indicating that the optimized process from BAS-BPNN model was more ideal, so it was finally determined as the best extraction process for Fengyin Decoction. The process of Fengyin Decoction obtained from BAS-GA-BPNN has high extraction efficiency and good stability, which provides reference for the subsequent development and quality control.
Assuntos
Medicamentos de Ervas Chinesas , Redes Neurais de Computação , Entropia , Etanol , Controle de QualidadeRESUMO
Cerium oxide (CeO2), one of many engineered nanomaterials (ENMs), is composed primarily of metal oxides, such as cerium oxide (CeO2). CeO2-containing materials are widely used as a polishing agent for glass mirrors, plate glass, television tubes, ophthalmic lenses, and precision optics. The widespread use of this nanomaterial (NM) resulted in increased environmental contamination levels and consequent human exposure. However, the influence of Ce on humans remains to be determined. The aim of this study was to expose female ICR mice to varying nanoparticle sizes of 35 nm, 300 nm as well as a mixture of 1-5 µM CeO2 particles through intranasal (i.n.) instillation at 40 mg/kg dose on day 1, 3 and 5, and the experiment terminated on day 7. Histopathology findings demonstrated that hydropic degeneration was prominently associated with hemorrhage in renal cortex and medulla in all CeO2-administered groups. In liver of CeO2-exposed mice, hydropic degeneration was also prominent. Serum chemistries also indicated signs of renal and hepatic lesion as evidenced by significantly decreased serum levels of total bilirubin (TBIL) and total phosphate (TP) and activity of alkaline phosphatase (ALP). ICP-MS analysis group demonstrated that Ce levels were not significantly higher in liver and kidneys of mice exposed to 35 nm CeO2. An increase in Ce content was observed in hepatic and renal tissues of mice exposed to 300 nm or 1-5 µM CeO2. The levels of Ce were similar in these two groups suggesting a threshold level of Ce was attained regardless of NP size. Data thus demonstrated that i.n. instillation of different-sized CeO2 particles translocated to liver and kidney and that size difference of CeO2 particles did not exert significant in the observed histopathology responses.
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Cério/administração & dosagem , Rim/metabolismo , Fígado/metabolismo , Nanopartículas Metálicas/administração & dosagem , Administração Intranasal , Animais , Feminino , Camundongos , Camundongos Endogâmicos ICR , Tamanho da PartículaRESUMO
In this study, we investigated the expression, correlation to clinical outcomes and biological functions of microRNA-15a-3p (miR-15a-3p) in human osteosarcoma. MiR-15a-3p expressions in osteosarcoma cell lines and clinical tissues of osteosarcoma patients were measured by qPCR. Relevance of endogenous miR-15a-3p to osteosarcoma patients' clinicopathological factors or overall survival was statistically analyzed. In addition, the independence of miR-15a-3p predicting cancer patients' overall survival was analyzed by Cox regression method. Furthermore, in osteosarcoma cell lines, Saos-2 and HOS cells, miR-15a-3p was overexpressed through stable lentiviral transduction. The functional regulations of miR-15a-3p overexpression on cancer ell proliferation and migration were then analyzed. MiR-15a-3p was significantly downregulated in osteosarcoma cell lines and human osteosarcoma tumors. Downregulation of endogenous miR-15a-3p in osteosarcoma tumors was significantly associated with cancer patient's poor clinical outcomes and low survival rate. Also, endogenous miR-15a-3p was confirmed to be an independent biomarker for predicating cancer patients' survival. In Saos-2 and HOS cells, lentivirus-induced miR-15a-3p overexpression had significantly tumor suppressing functions, by inhibiting both proliferation and migration. Significant downregulation of miR-15a-3p in osteosarcoma may be an independent biomarker to predicting cancer patients' poor prognosis. Overexpression miR-15a-3p may be an efficient functional meaning to suppress osteosarcoma development.
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Neoplasias Ósseas/patologia , Regulação para Baixo , MicroRNAs/genética , Osteossarcoma/patologia , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Estadiamento de Neoplasias , Osteossarcoma/genética , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: The accuracy of total calcium and its corrected value for predicting critically high and critically low ionized calcium in critical illness is controversial. The aim of this study was to investigate whether the concentration of total serum calcium, either corrected for albumin or not, could predict critically high or low values in critical illness. METHODS: This report describes a retrospective study using the Medical Information Mart for Intensive Care (MIMIC) III database. Test panels that contained serum albumin, total calcium, and ionized calcium (named ATI panels) with order time intervals of less than one hour were extracted. The predictive accuracy of total calcium, either corrected for albumin or not, was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 12 118 ATIs with 103 critically low and 92 critically high ionized calcium results were extracted. The areas under ROC curves (AUCs) of corrected and uncorrected total calcium for predicting critically low ionized calcium were 0.69 (95% CI: 0.61-0.76) and 0.70 (95% CI: 0.63-0.78), respectively. For predicting critically high ionized calcium, the AUCs were 0.98 (95% CI: 0.97-1.00) and 0.97 (95% CI: 0.95-1.00), respectively. With positive predictive values (PPVs) of 0.05 and 0.10, the sensitivities (both corrected and uncorrected) were approximately 0.50 for predicting critically low ionized calcium and 0.95 for predicting critically high ionized calcium. CONCLUSIONS: Total calcium, either corrected for albumin or not, is not a reliable test to predict critically low ionized calcium in critical illness. Total calcium's predictive accuracy for critically high ionized calcium is high.
Assuntos
Cálcio/sangue , Estado Terminal , Adolescente , Adulto , Idoso , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Albumina Sérica/metabolismo , Adulto JovemRESUMO
Taspoglutide has elicited a long-lasting glycemic control effect with favorable body weight loss. The objective of this study was to develop a quantitative model to delineate the net efficacy of taspoglutide on body weight (WT) loss from the response of placebo in type 2 diabetes patients, and further find pharmacodynamic potency of taspoglutide for half of maximum reduction response of WT. Several PD data about taspoglutide treatments for type 2 diabetes patients were digitalized from the published papers. The model based metaanalysis (MBMA) study for WT loss was performed with Monolix 4.3 software. The MBMA successfully described the effects of placebo and taspoglutide on the pharmacological index of WT loss in clinical trials. The pharmacodynamic potency (41.7 pmol/l) produced 50% of maximum response of WT (-1.85 kg) from the responses of placebo (-1.33 kg). The longitudinal MBMA could be utilized to quantitatively describe the efficacy of taspoglutide on body weight loss and may lead to a clinical guideline for treatment of type 2 diabetes patients in the future.
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Peptídeos/farmacologia , Redução de Peso/efeitos dos fármacos , Algoritmos , Diabetes Mellitus Tipo 2/complicações , Humanos , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos RetrospectivosRESUMO
The objective of this study was to develop quantitative models to delineate the net efficacy of taspoglutide on fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) from the response of placebo in type 2 diabetes patients, and further find pharmacodynamic potency of taspoglutide and FPG for half of maximum reduction responses of FPG and HbA1c, respectively. Several PD data about taspoglutide treatments for type 2 diabetes patients were digitalized from the published papers related with the clinical development of taspoglutide. The model based meta-analysis (MBMA) studies for FPG and HbA1c were performed with Monolix 4.2 software. The MBMA successfully described the effects of placebo and taspoglutide on pharmacological indexes of FPG and HbA1c through mono and multiple combination therapies in clinical trials. The pharmacodynamic potency (25.3 pmol/l) produced 50% of maximum responses of FPG (-2.39 mmol/l) from the responses of placebo for FPG (-0.371 mmol/l); the response change of FPG (-1.81 mmol/l) affected 50% of maximum response change (-1.74%) for HbA1c from the response of placebo (-0.253%). The leveraging prior knowledge from the longitudinal MBMA will be utilized to guide clinical development of taspoglutide and further support study designs including optimization of dose and duration of therapy.
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OBJECTIVE: To investigate the regulation of Cha Gan Beng Ga on the activity of biomarker PGC-1α in vivo and in vitro, and lay the foundation for studying the efficacy result of Cha Gan Beng Ga on xenograft tumor model and extracting active constituents. METHOD: (1) The coarse powder of Cha Gan Beng Ga was extracted with 70% ethanol solution through heating and refluxing, and finally was used to freeze dry powder. (2) 50 mg x kg(-1) of freeze-dried power was orally administrated to KM and C57BL/6J mice once daily, lasting for 5 consecutive days; different concentrations of extracted materials was given to non-small cell lung cells A549. (3) The expression level of PGC-1α mRNA was quantitatively determined in lung tissue of mice and non-small cell lung cells A549. RESULT: The expression levels of PGC-1α in lung tissue of different mice strains had an increasing tendency. Furthermore, the expression levels of PGC-1α in non-small cell lung cells A549 also had an increasing tendency, showing dose and time-dependent relationships. CONCLUSION: Mongolian Medicine Cha Gan Beng Ga could induce the over-expression of PGC-1α mRNA in lung tissue of mice and in non-small cell lung cells A549. The present results will lay foundation for studying the efficacy result of antitumor and active constitutes in future.
Assuntos
Aconitum/química , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Medicina Tradicional da Mongólia , Extratos Vegetais/farmacologia , Fatores de Transcrição/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos C57BL , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which manifests as joint destruction and bone erosion, could be caused by both genetic and environmental factors. Currently, the causes of RA are unknown, and targeted therapies are often associated with side effects and contraindications. The detection rate of RA in women is higher than men (3:1), however, there is still a lack of comprehensive understanding of the relationship between sex and RA. We hypothesized gender differences in RA prevalence and their associated mechanisms by performing genome-wide transcriptome analysis of synovial biopsy samples. The results indicated that myoglobin (MB) was differentially expressed between males and females, with higher expression in males than females in healthy populations, while the opposite was observed in RA patients. MB interacted with HLA class II histocompatibility antigen, DM beta (HLA-DMB) and the inflammatory factor interleukin 6 (IL-6) in the human synovial cell line MH7A.
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The early stages of osteoarthritis (OA) in the joints are typically characterized by two key factors: the dysfunction of articular cartilage lubrication and inflammation resulting from the excessive production of reactive oxygen species (ROS). Synthetic injectable macromolecular materials present great potential for preventing the progression of early OA. In this study, to mimic the excellent lubricity of brush-like aggregates found in natural synovial fluid, we develop a novel macromolecular biolubricant (CS-PS-DA) by integrating adhesion and hydration groups onto backbone of natural biomacromolecules. CS-PS-DA exhibits a strong affinity for cartilage surfaces, enabling the formation of a stable lubrication layer at the sliding interface of degraded cartilages to restore joint lubrication performance. In vitro results from ROS scavenging and anti-inflammatory experiments indicate the great advantage of CS-PS-DA to decrease the levels of proinflammatory cytokines by inhibiting ROS overproduction. Finally, in vivo rats OA model demonstrates that intra-cavitary injection of CS-PS-DA could effectively resist cartilage wear and mitigated inflammation in the joints. This novel biolubricant provides a new and timely strategy for the treatment of OA.
Assuntos
Osteoartrite , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Lubrificação , Masculino , Cartilagem Articular/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Propriedades de Superfície , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
For hazardous gas monitoring and non-invasive diagnosis of diabetes using breath analysis, porous foams assembled by Co3O4 nanoparticles were designed as sensing electrode materials to fabricate efficient yttria-stabilized zirconia (YSZ)-based acetone sensors. The sensitivity of the sensors was improved by varying the sintering temperature to regulate the morphology. Compared to other materials sintered at different temperatures, the porous Co3O4 nanofoams sintered at 800 °C exhibited the highest electrochemical catalytic activity during the electrochemical test. The response of the corresponding Co3O4-based sensor to 10 ppm acetone was -77.2 mV and it exhibited fast response and recovery times. Moreover, the fabricated sensor achieved a low detection limit of 0.05 ppm and a high sensitivity of -56 mV/decade in the acetone concentration range of 1-20 ppm. The sensor also exhibited excellent repeatability, acceptable selectivity, good O2/humidity resistance, and long-term stability during continuous measurements for over 30 days. Moreover, the fabricated sensor was used to determine the acetone concentration in the exhaled breaths of patients with diabetic ketosis. The results indicated that it could distinguish between healthy individuals and patients with diabetic ketosis, thereby proving its abilities to diagnose and monitor diabetic ketosis. Based on its excellent sensitivity and exhaled breath measurement results, the developed sensor has broad application prospects.
Assuntos
Acetona , Testes Respiratórios , Cobalto , Eletrodos , Óxidos , Ítrio , Zircônio , Acetona/análise , Zircônio/química , Testes Respiratórios/instrumentação , Testes Respiratórios/métodos , Ítrio/química , Humanos , Porosidade , Cobalto/química , Cobalto/análise , Óxidos/química , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Limite de DetecçãoRESUMO
BACKGROUND: Due to mechanical imbalance in the spine, elderly scoliosis patients tend to develop vertebral fracture nonunion, i.e., Kümmell disease, when osteoporotic vertebral compression fractures occur. However, accompanying vertebral rotational deformities make surgical procedures challenging risky. Such patients are usually compelled to undergo conservative treatment and there are very few reports on minimally invasive surgeries for them. We first-time report a patient with Kümmell disease and lumbar scoliosis treated with percutaneous kyphoplasty (PKP) under O-arm guidance. CASE SUMMARY: An 89-year-old female was admitted to the hospital due to delayed low back pain after a fall. She was diagnosed with Kümmell disease based on physical and radiologic examinations. The patient experienced severe scoliosis and subsequently underwent O-arm-guided kyphoplasty, resulting in a significant alleviation of low back pain. CONCLUSION: PKP has good efficacy in treating Kümmell disease. However, surgical risks are elevated in scoliosis patients with Kümmell disease due to the abnormal anatomical structure of the spine. O-arm assisted operations play a crucial role in decreasing surgical risks.