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BACKGROUND AND OBJECTIVES: To assess the vitamin D nutritional status (VDN) of pregnant women in early pregnancy and investigate the effects of periconceptional supplementation with multiple micronutrients (MMs) on this status. METHODS AND STUDY DESIGN: Data were taken from the Pregnancy Health Care System and Hospital Information System in 2018 in Beijing. Vitamin D nutritional status in early pregnancy was evaluated among 4,978 pregnant women, and 4,540 women who took folic acid only (FA) or multiple mi-cronutrients supplements (MM) during the periconceptional period, were include to estimate the associations between periconceptional supplementation with MM and prevalence of vitamin D deficiency or insufficiency with logistic regression model. RESULTS: The mean early-pregnancy vitamin D concentration was 18.6 (±7.5) ng/mL, and the rates of deficiency and insufficiency were 31.6% and 60.5%, respectively. Compared to the FA group, the adjusted odds ratio (aOR, 95%confidence interval, CI) for insufficiency or deficiency of the MM group were 0.25(0.18-0.34), and the aOR (95%CI) for deficiency of the MM group were 0.17 (0.12-0.23). Women who took MMs for a longer period of time, at higher frequencies, and with higher compliance scores had lower rates of deficiency and insufficiency. In winter, spring, and autumn, taking MMs could reduce deficiency by about 70%; in summer, there was little effect. CONCLUSIONS: Among women in Beijing, serum concentrations of vitamin D in early pregnancy are relatively low, and the rates of deficiency and insufficiency are high. Taking MMs during the periconceptional period could improve this situation.
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Estado Nutricional , Vitamina D , Embarazo , Femenino , Humanos , Vitaminas , Ácido Fólico , Suplementos DietéticosRESUMEN
Bone metastasis of cancer cells leads to severe pain by disrupting bone structure and inducing central sensitization. Neuroinflammation in the spinal cord plays a decisive role in the maintenance and development of pain. In the current study, male Sprague-Dawley (SD) rats are used to establish a cancer-induced bone pain (CIBP) model by intratibial injection of MRMT-1 rat breast carcinoma cells. Morphological and behavioral analyses verify the establishment of the CIBP model, which represents bone destruction, spontaneous pain and mechanical hyperalgesia in CIBP rats. Activation of astrocytes marked by upregulated glial fibrillary acidic protein (GFAP) and enhanced production of the proinflammatory cytokine interleukin-1ß (IL-1ß) are accompanied by increased inflammatory infiltration in the spinal cord of CIBP rats. Furthermore, activation of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is consistent with increased neuroinflammation. Adenosine monophosphate-activated protein kinase (AMPK) activation is involved in attenuating inflammatory pain and neuropathic pain. Intrathecal injection of the AMPK activator AICAR in the lumbar spinal cord reduces dynamin-related protein 1 (Drp1) GTPase activity and suppresses NLRP3 inflammasome activation. This effect consequently alleviates pain behaviors in CIBP rats. Cell research on C6 rat glioma cells indicates that AICAR treatment restores IL-1ß-induced impairment of mitochondrial membrane potential and elevation of mitochondrial reactive oxygen species (ROS). In summary, our findings indicate that AMPK activation attenuates cancer-induced bone pain by reducing mitochondrial dysfunction-mediated neuroinflammation in the spinal cord.
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Dolor en Cáncer , Neoplasias , Neuralgia , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Proteínas Quinasas Activadas por AMP/metabolismo , Enfermedades Neuroinflamatorias , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Dolor en Cáncer/tratamiento farmacológico , Dolor en Cáncer/etiología , Neuralgia/metabolismo , Mitocondrias/metabolismo , Médula Espinal/metabolismo , Neoplasias/metabolismoRESUMEN
BACKGROUND: Osteoporosis is a disease threatening the health of millions of individuals. Melatonin is found to be a potential anti-osteoporosis drug. However, whether melatonin plays a role against osteoporosis at different stages of the menopause and the underlying mechanisms are unknown. METHODS: Ovariectomy was utilized as a model of perimenopausal and postmenopausal osteoporosis. A total of 100 mg/kg melatonin, or solvent alone, was added to the drinking water of the rats over 8 weeks. Perimenopausal rats immediately received intervention following ovariectomy while postmenopausal rats received intervention 8 weeks after ovariectomy. All rats underwent overdose anesthesia following intervention after which blood samples and femurs were collected for further analysis. Rat femurs were scanned using micro-CT and examined histologically. The serum levels of melatonin and osteogenic biochemical markers were measured and the expression of osteogenesis-associated genes (Runx2, Sp7) were quantified by real-time quantitative PCR. Alkaline phosphatase (ALP) activity and the gene expression (Col1a1, Runx2, Alpl, and Bglap) were measured after bone marrow mesenchymal stem cells (BMSCs) were osteogenically induced, both with and without melatonin in vitro. ALP staining and Alizarin Red S staining were used to identify osteogenesis. RESULTS: Analysis by micro-CT and histological staining demonstrated that bone mass decreased and bone microarchitecture deteriorated over time after ovariectomy. Intervention with melatonin increased bone mass in normal, perimenopausal, and postmenopausal osteoporotic rats. Serum levels of ALP continuously increased after ovariectomy while osteocalcin levels initially rose, then decreased. Melatonin increased the serum levels of ALP and osteocalcin and mRNA expression levels of Runx2 and Sp7 in normal and postmenopausal rats, the opposite of the markers in perimenopausal rats. In vitro study demonstrated that 100 µmol/L melatonin increased the mRNA expression of Col1a1, Runx2, and Alpl three and/or seven days after intervention, and Alpl and Bglap 14 d after intervention. Melatonin increased ALP activity and the extent of ALP and matrix mineralization in the late stage of osteogenesis. CONCLUSIONS: Bone mass continuously decreased after ovariectomy, while melatonin increased bone mass and ameliorated bone metabolism in normal, perimenopausal, and postmenopausal osteoporotic rats due to the induction of osteogenic differentiation in BMSCs.
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Melatonina , Células Madre Mesenquimatosas , Animales , Femenino , Melatonina/farmacología , Osteogénesis , Perimenopausia , Posmenopausia , RatasRESUMEN
OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population. METHODS: A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed. RESULTS: The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05). CONCLUSION: The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.
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Acuaporinas , Diabetes Mellitus Tipo 2 , Acuaporinas/genética , Estudios de Casos y Controles , China , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Objective: To explore the prognostic factors of adult ventricle glioma (AVG) and to construct and evaluate a survival-related prognostic nomogram model, which could provide further reference for the clinical management of AVG patients. Methods: The patients covered in the study were selected from the Surveillance Epidemiology and End Results (SEER) database (1973-2016). They all had definite histological diagnosis of AVG. They were assigned randomly to the training cohort and the validation cohort by random number table at a 2/1 ratio. Survival analysis was performed by Kaplan-Meier analysis. Cox regression analysis was employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Then, integrating the basic characteristics of patients, the survival-related nomogram predictive model for OS and CSS in the training cohort was constructed, respectively. After that, internal cross validation and external validation of the model were carried out with the training cohort and the validation cohort in succession. The authenticity and reliability of the nomogram model were evaluated by calculating the concordance index (C-index). Calibration plots were constructed to assess the agreement between the predicted values and the observed values in the training cohort and the validation cohort. Results: A total of 369 AVG patients, including 218 males and 151 females, were included. The median age of the patients was 53. According to the WHO classification of gliomas, 66 (17.9%) patients had grade â ¡ gliomas, 73 (19.8%) had grade â ¢ gliomas, and 230 (62.3%) had grade â £ gliomas. Regarding the extent of resection (EOR), 59 (16.0%) had gross total resection (GTR) and 145 (39.3%) had subtotal resection (STR) or partial resection (PR). Of all the patients, 167 (45.3%) received postoperative radiotherapy and 143 (38.8%) received postoperative chemotherapy. Patients were randomized into the training cohort ( n=246) and the validation cohort ( n=123), and there was no significant difference ( P>0.05) in the basic clinical characteristics between the training cohort and the validation cohort. In the training cohort, Cox regression analysis revealed that the independent prognostic factors for OS and CSS included age≥65, grades â ¢ and â £ according to the WHO classification of gliomas, and not receiving radiotherapy. Furthermore, 5 variables, including age, gender, WHO grades, surgery, and radiotherapy, were used to construct the nomogram model for predicting 6-month, 1-year, and 2-year OS and CSS. The results of internal cross validation in the training cohort showed that the C-indexes of OS and CSS were 0.758 and 0.765, respectively. The external validation results of the validation cohort showed that the C-indexes of OS and CSS were 0.733 and 0.719, respectively. Calibration plots for 6-month, 1-year, and 2-year OS in the training cohort showed relatively good agreement, while in the validation cohort the agreement was relatively low. The 6-month, 1-year, and 2-year CSS calibration plots had results similar to the calibration plots of OS. Conclusion: This nomogram predictive model of OS and CSS showed moderately reliable predictive performance, providing helpful reference information for clinicians to make quick and simple assessment of the survival probability of AVG patients.
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Glioma , Nomogramas , Adulto , Anciano , Femenino , Humanos , Masculino , Pronóstico , Reproducibilidad de los Resultados , Programa de VERFRESUMEN
BACKGROUND: Osteoarthritis (OA) is a disease of the entire joint involving synovial fibrosis and inflammation. Pathological changes to the synovium can accelerate the progression of OA. Pirfenidone (PFD) is a potent anti-fibrotic drug with additional anti-inflammatory properties. However, the influence of PFD on OA is unknown. METHODS: Proliferation of human fibroblast-like synoviocytes (FLSs) after treatment with TGF-ß1 or PFD was evaluated using a Cell Counting Kit-8 assay and their migration using a Transwell assay. The expression of fibrosis-related genes (COL1A1, TIMP-1, and ACTA-2) and those related to inflammation (IL-6 and TNF-α) was quantified by real-time quantitative PCR. The protein expression levels of COL1A1, α-SMA (coded by ACTA-2), IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay. A rabbit model of OA was established and then PFD was administered by gavage. The expression of genes related to fibrosis (COL1A1, TIMP-1, and ADAM-12) and inflammation (IL-6 and TNF-α) was measured using RNA extracted from the synovium. Synovial tissue was examined histologically after staining with H&E, Masson's trichrome, and immunofluorescence. Synovitis scores, the volume fraction of collagen, and mean fluorescence intensity were calculated. Degeneration of articular cartilage was analyzed using a Safranin O-fast green stain and OARSI grading. RESULTS: The proliferation of FLSs was greatest when induced with 2.5 ng/ml TGF-ß1 although it did not promote their migration. Therefore, 2.5 ng/ml TGF-ß1 was used to stimulate the FLSs and evaluate the effects of PFD, which inhibited the migration of FLSs at concentrations as low as 1.0 mg/ml. PFD decreased the expression of COL1A1 while TGF-ß1 increased both mRNA and protein expression levels of IL-6 but had no effect on α-SMA or TNF-α expression. PFD decreased mRNA expression levels of COL1A1, IL-6, and TNF-α in vivo. H&E staining and synovitis scores indicated that PFD reduced synovial inflammation, while Masson's trichrome and immunofluorescence staining suggested that PFD decreased synovial fibrosis. Safranin O-Fast Green staining and the OARSI scores demonstrated that PFD delayed the progression of OA. CONCLUSIONS: PFD attenuated synovial fibrosis and inflammation, and postponed the progression of osteoarthritis in a modified Hulth model of OA in rabbits, which was related to its anti-fibrotic and anti-inflammatory properties.
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Osteoartritis , Animales , Antiinflamatorios/uso terapéutico , Fibrosis , Osteoartritis/tratamiento farmacológico , Piridonas , Conejos , Membrana SinovialRESUMEN
Inflammatory pain activates astrocytes and increases inflammatory cytokine release in the spinal cord. Mitochondrial fusion and fission rely on the functions of dynamin-related protein 1 (Drp1) and optic atrophy 1 (OPA1), which are essential for the synaptic transmission and plasticity. In the present study, we aimed to explore the effects of 2-bromopalmitate (2-BP), an inhibitor of protein palmitoylation, on the modulation of pain behavior. Rats were intraplantar injected with complete Freund's adjuvant (CFA) to establish an inflammatory pain model. In the spinal cord of rats with CFA-induced inflammatory pain, the expression of astrocyte-specific glial fibrillary acidic protein (GFAP) and contents of proinflammatory cytokines IL-1ß and TNF-α were increased. Mitochondrial Drp1 was increased, while OPA1 was decreased. Consequently, CFA induced reactive oxygen species (ROS) production and Bcl-2-associated X protein (BAX) expression. The intrathecal administration of 2-BP significantly reversed the pain behaviors of the inflammatory pain in rats. Moreover, 2-BP also reduced the Drp1 expression, elevated the OPA1 expression, and further reduced the GFAP, IL-1ß, and TNF-α expression and ROS production. Furthermore, in vitro study proved a similar effect of 2-BP on the regulation of Drp1 and OPA1 expression. 2-BP also increased the mitochondrial membrane potential and decreased the levels of BAX, ROS, and proinflammatory cytokines. These results indicate that 2-BP may attenuate the inflammatory pain of CFA-treated rats via regulating mitochondrial fission/fusion balance and function.
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Antiinflamatorios/farmacología , Dinámicas Mitocondriales/efectos de los fármacos , Dolor/tratamiento farmacológico , Palmitatos/farmacología , Animales , Antiinflamatorios/uso terapéutico , Astrocitos/metabolismo , Conducta Animal/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Dinaminas/metabolismo , Adyuvante de Freund/toxicidad , GTP Fosfohidrolasas/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Dolor/inducido químicamente , Dolor/metabolismo , Palmitatos/uso terapéutico , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Paeonol has been proved to have potential anti-inflammatory activity, but its clinical application is not extensive due to the poor anti-inflammatory activity (14.74% inhibitory activity at 20 µM). In order to discover novel lead compound with high anti-inflammatory activity, series of paeonol derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. Structure-activity relationships (SARs) have been fully concluded, and finally (E)-N-(4-(2-acetyl-5-methoxyphenoxy)phenyl)-3-(3,4,5-trimet-hoxyphenyl)acrylamide (compound 11a) was found to be the best active compound with low toxicity, which showed 96.32% inhibitory activity at 20 µM and IC50 value of 6.96 µM against LPS-induced over expression of nitric oxide (NO) in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4, resulting in inhibiting of NF-κB and MAPK pathways. Further studies have shown that compound 11a has obvious therapeutic effect against the adjuvant-induced rat arthritis model.
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Acetofenonas/farmacología , Antiinflamatorios no Esteroideos/farmacología , Artritis Experimental/tratamiento farmacológico , Diseño de Fármacos , FN-kappa B/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Acetofenonas/síntesis química , Acetofenonas/química , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Artritis Experimental/inducido químicamente , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Adyuvante de Freund/administración & dosificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Estructura Molecular , FN-kappa B/metabolismo , Óxido Nítrico/análisis , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Relación Estructura-ActividadRESUMEN
Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.
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Benzofuranos/farmacología , Depresión/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Estrés Psicológico/complicaciones , Acetiltransferasas/metabolismo , Animales , Técnicas de Observación Conductual , Conducta Animal/efectos de los fármacos , Benzofuranos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/diagnóstico , Depresión/patología , Depresión/psicología , Modelos Animales de Enfermedad , Dopamina , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Masculino , Ratones , Neurotransmisores/metabolismo , Norepinefrina/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Serotonina/metabolismo , Organismos Libres de Patógenos Específicos , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception. METHODS: Electrophysiological experiments were performed on both rat DRG neurons and Chinese hamster ovary (CHO) cells expressing ASIC3 and PAR2. Nociceptive behavior was induced by acetic acid in rats. RESULTS: PAR2-AP, PAR2-activating peptide, concentration-dependently increased the ASIC3 currents in CHO cells transfected with ASIC3 and PAR2. The proton concentration-response relationship was not changed, but that the maximal response increased 58.7 ± 3.8% after pretreatment of PAR2-AP. PAR2 mediated the potentiation of ASIC3 currents via an intracellular cascade. PAR2-AP potentiation of ASIC3 currents disappeared after inhibition of intracellular G protein, PLC, PKC, or PKA signaling. Moreover, PAR2 activation increased proton-evoked currents and spikes mediated by ASIC3 in rat dorsal root ganglion neurons. Finally, peripheral administration of PAR2-AP dose-dependently exacerbated acidosis-induced nocifensive behaviors in rats. CONCLUSIONS: These results indicated that PAR2 signaling sensitized ASIC3, which may contribute to acidosis-induced nociception. These represent a novel peripheral mechanism underlying PAR2 involvement in hyperalgesia by sensitizing ASIC3 in primary sensory neurons.
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Canales Iónicos Sensibles al Ácido/metabolismo , Acidosis/complicaciones , Nocicepción/fisiología , Dolor/inducido químicamente , Receptor PAR-2/metabolismo , Transducción de Señal/fisiología , Canales Iónicos Sensibles al Ácido/genética , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Animales , Células CHO , Células Cultivadas , Cricetulus , Modelos Animales de Enfermedad , Ganglios Espinales/citología , Concentración de Iones de Hidrógeno , Masculino , Neuronas/efectos de los fármacos , Nocicepción/efectos de los fármacos , Oligopéptidos/farmacología , Técnicas de Placa-Clamp , Ratas , Receptor PAR-2/genética , Transducción de Señal/efectos de los fármacosRESUMEN
Live poultry markets (LPM) are one of the most important sources of human infection with avian influenza virus (AIV). During our routine surveillance of AIV, we identified an H9N6 virus (JX-H9N6) in a LPM in Nanchang city, Jiangxi Province, China. Using Bayesian coalescent analysis, it was predicted that JX-H9N6 had originated from a reassortment event between H9N2 and H6N6 AIVs in early 2014, instead of being derived from an H9N6 virus reported previously. Mutations in HA, PB1, PA, M, and NS protein, which could increase mammalian transmission and virulence, were also detected. Currently, both H9N2 and H6N6 AIVs are widely distributed in poultry and contribute to the generation of novel reassortant viruses causing human infection. Our findings highlight the importance of enhanced surveillance in birds for early prediction of human infections.
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Virus de la Influenza A/clasificación , Virus de la Influenza A/aislamiento & purificación , Aves de Corral/virología , Virus Reordenados/clasificación , Virus Reordenados/aislamiento & purificación , Animales , China , Evolución Molecular , Virus de la Influenza A/genética , Mutación , Virus Reordenados/genética , Proteínas Virales/genéticaRESUMEN
Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states.
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Canales Iónicos Sensibles al Ácido/análisis , Autofagia/efectos de los fármacos , Neoplasias Óseas/fisiopatología , Dolor en Cáncer/tratamiento farmacológico , Estilbenos/farmacología , Proteínas Quinasas Activadas por AMP/fisiología , Canales Iónicos Sensibles al Ácido/fisiología , Animales , Línea Celular Tumoral , Femenino , Ratas , Ratas Sprague-Dawley , Resveratrol , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To investigatethe clinical significance of hip rotation center location after reconstruction with modular hemipelvic prostheses for periacetabula tumors. METHODS: Forty-two patients who received periacetabular tumor resection and reconstruction with modular hemipelvic prosthesis between January 2004 and January 2014 in our institute were included. Postoperative complications, function (measured by MSTS score), survival rate and recurrence rate were analyzed. The position of prosthetic hip rotation center was measured. By its deviation angle from the ideal rotation center, the patients were divided into inward group, normal group and outward group in the horizontal level, and upward group, normal group and downward group in the vertical direction. And the relationship between positional difference of prosthetic hip rotation center and function at 1 month, 3 months, 6 months and 12 months after surgery was analyzed. RESULTS: Of forty-two cases in total, 25 patients were male and 17 patients were female. The age of the patients ranged from 12 and 69 years (median, 38 years). The minimal followup period was 12 months (mean,36 months; range,12-86 months). The complication rate was 31.0% and hip dislocation rate was 7.1%. The overall survival rate was 69.4% at 3 years and 43.7% at 5 years. After 1 month, 3 months, 6 months, the function of the reconstructed hip gradually improved, with MSTS score showing an increasing trend. The MSTS scores at these three time points were compared, the difference was statistically significant (P < 0.05). The improvement of function after 6 months and 12 months was not obvious, with the difference not being statistically significant (P > 0.05). The deviation of hip rotation center in the longitudinal direction and the horizontal direction did not affect the function of the hip (P > 0.05). CONCLUSION: It is safe and effective for patients with pelvic tumor to receive modular hemipelvic prosthesis reconstruction once the prosthesis is fixed in the most firmly position, where soft tissue fully covered, the muscles could be rebuilt more easily and where the eccentricity of the femoral got a certain degree of recovery. The relationship between the deviation of hip rotation center and postoperative function needs to be confirmed.
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Neoplasias Óseas/cirugía , Procedimientos de Cirugía Plástica , Prótesis e Implantes , Implantación de Prótesis , Rotación , Adolescente , Adulto , Anciano , Niño , Femenino , Fémur , Luxación de la Cadera , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Complicaciones Posoperatorias , Tasa de Supervivencia , Adulto JovenRESUMEN
Bartonella species can infect a variety of mammalian hosts and cause a broad spectrum of diseases in humans, but there have been no reports of Bartonella infection in Ochotonidae. This is the first study to detect Bartonella in plateau pikas in the Qinghai plateau, providing baseline data for the risk assessment of human Bartonella infection in this area. We obtained 15 Bartonella strains from 79 pikas in Binggou and Maixiu areas of Qinghai with a positive rate of 18.99%. Based on the phylogenetic analysis of the Bartonella citrate synthase (gltA) gene sequences, most strains were closely related to B. taylorii (3/15) and B. grahamii (12/15). The latter is a pathogenic strain in humans. Our results suggest that a corresponding prevention and control strategy should be taken into consideration in the Qinghai province.
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Infecciones por Bartonella/veterinaria , Bartonella/aislamiento & purificación , Lagomorpha , Animales , Bartonella/clasificación , Bartonella/genética , Infecciones por Bartonella/epidemiología , Infecciones por Bartonella/microbiología , Infecciones por Bartonella/transmisión , China/epidemiología , Femenino , Genotipo , Humanos , Masculino , FilogeniaRESUMEN
Determination of chloride salt solution by near infrared spectrum plays a very important role in Biomedicine. The near infrared spectrum analysis of Sodium chloride, potassium chloride, calcium chloride aqueous solution shows that the concentration change of chloride salt can affect hydrogen bond, resulting in the variation of near infrared spectrum of water. The temperature influence on NIR spectrum has been decreased by choosing reasonable wavelength range and the wavelength where the temperature effects are zero (isosbestic point). Chlorine salt prediction model was established based on partial least squares method and used for predicting the concentration of the chlorine ion. The impact on near infrared spectrum of the cation ionic radius, the number of ionic charge, the complex effect of ionic in water has also discussed in this article and the reason of every factor are analysed. Experimental results show that the temperature and concentration will affect the near-infrared spectrum of the solution, It is found that the effect of temperature plays the dominant role at low concentrations of chlorine salt; rather, the ionic dominates at high concentration. Chloride complexes are formed in aqueous solution, It has an effect on hydrogen bond of water combining with the cations in chlorine salt solution, Comparing different chloride solutions at the same concentration, the destruction effects of chloride complexes and catnions on the hydrogen bond of water increases in the sequences: CaCl2 >NaCl>KC. The modeling result shows that the determination coefficients (R2) = 99.97%, the root mean square error of cross validation (RM- SECV) = 4.51, and the residual prediction deviation (RPD) = 62.7, it meets the daily requirements of biochemical detection accuracy.
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Soluciones Farmacéuticas/química , Cloruro de Sodio/análisis , Enlace de Hidrógeno , Iones , Análisis de los Mínimos Cuadrados , Modelos Químicos , Soluciones , Espectroscopía Infrarroja Corta , Temperatura , AguaRESUMEN
Stroke brings the pathological changes of brain tissues such as hematoma formation or ischemia and hypoxia, which leads to neuronal death and axon degeneration. Axon regeneration after its injury is mainly dependent on the surrounding microenvironment and the related proteins, including glial scar, myelin associated inhibitory factors, axon guidance molecules, and neurotrophic factors. All of them affect axon growth by regulating the morphology and orientation of growth cones, the synaptic stability, and the proliferation and differentiation of neural stem cells. This article summarizes the mechanism of acupuncture in regulating axon regeneration after stroke. Acupuncture inhibits glial scar formation, alleviates the inhibitory effects of its physical and chemical barriers on axon growth, reverses the inhibitory effects of myelin-related inhibitory factors on axon growth, and adjusts the level of axon guidance molecules to promote the proliferation and differentiation of neural stem cells and the regeneration of injured axons, and up-regulates neurotrophic factors. Eventually, post-stroke nerve injury can be ameliorated.
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Terapia por Acupuntura , Axones , Regeneración Nerviosa , Accidente Cerebrovascular , Humanos , Animales , Axones/metabolismo , Axones/fisiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/fisiopatología , Células-Madre Neurales/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Osteosarcoma (OS) is characterized by rapid growth and frequent pulmonary metastasis. Eurycoma longifolia Jack, a flowering plant primarily found in Southeast Asian countries, is commonly used in traditional herbal medicine. Its root extract is mainly used for against cancer, malaria, parasites and other conditions. The active compound in its root extract, eurycomanone (EUR), has been proven to inhibit lung and liver cancer proliferation. AIM OF THE STUDY: Our research aimed to investigate the inhibitory effect and underlying molecular mechanism of EUR on OS growth and metastasis. MATERIALS AND METHODS: In vitro experiments: western blotting (WB) screened 41 compounds that inhibited GRP78 expression and evaluated the protein levels of GRP78, PARP, cleaved-PARP, MMP2, and MMP9. Cell proliferation was evaluated using CCK-8, EdU, colony formation assay, and cell apoptosis was assessed by flow cytometry. Transwell, wound healing, and tube formation assays were performed to determine the effect of EUR on tumor invasion, migration, and angiogenesis, respectively. Quantitative real-time polymerase chain (qRT-PCR) and dual-luciferase activity assays detected GRP78 mRNA stability and transcription levels post-EUR and thapsigargin treatment. RNA-Seq identified signaling pathways inhibited by EUR. In vivo experiments: effects of EUR in mice were evaluated by H&E staining to detect lung metastasis and potential toxic effects in tissues. Immunohistochemical (IHC) staining detected the expression of Ki-67, CD31, and cleaved caspase-3 in tumors. RESULTS: GRP78 is highly expressed in OS and correlated with poor prognosis. In vitro, eurycomanone (EUR) significantly downregulated GRP78 expression, inhibited cell proliferation, migration, invasion, tube formation, and induced apoptosis. Moreover, it enhanced trichostatin A (TSA) sensitivity and exhibited inhibitory effects on other cancer types. Mechanistically, EUR decreased GRP78 mRNA stability and transcription. In vivo, EUR inhibited proliferation and invasion in tibial and PDX models. CONCLUSIONS: Our study demonstrated that EUR inhibits the growth and metastasis of OS by reducing GRP78 mRNA stability and inhibiting its transcription, which offers a novel approach for clinical treatment of OS.
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Antineoplásicos Fitogénicos , Neoplasias Óseas , Proliferación Celular , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico , Osteosarcoma , Animales , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Humanos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/aislamiento & purificación , Ratones , Ratones Desnudos , Ratones Endogámicos BALB C , Apoptosis/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Movimiento Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , FemeninoRESUMEN
BACKGROUND: Neovascular glaucoma (NVG) is likely to occur after pars plana vitrectomy (PPV) for diabetic retinopathy (DR) in some patients, thus reducing the expected benefit. Understanding the risk factors for NVG occurrence and building effective risk prediction models are currently required for clinical research. AIM: To develop a visual risk profile model to explore factors influencing DR after surgery. METHODS: We retrospectively selected 151 patients with DR undergoing PPV. The patients were divided into the NVG (NVG occurrence) and No-NVG (No NVG occurrence) groups according to the occurrence of NVG within 6 months after surgery. Independent risk factors for postoperative NVG were screened by logistic regression. A nomogram prediction model was established using R software, and the model's prediction accuracy was verified internally and externally, involving the receiver operator characteristic curve and correction curve. RESULTS: After importing the data into a logistic regression model, we concluded that a posterior capsular defect, preoperative vascular endothelial growth factor ≥ 302.90 pg/mL, glycosylated hemoglobin ≥ 9.05%, aqueous fluid interleukin 6 (IL-6) ≥ 53.27 pg/mL, and aqueous fluid IL-10 ≥ 9.11 pg/mL were independent risk factors for postoperative NVG in patients with DR (P < 0.05). A nomogram model was established based on the aforementioned independent risk factors, and a computer simulation repeated sampling method was used to internally and externally verify the nomogram model. The area under the curve (AUC), sensitivity, and specificity of the model were 0.962 [95% confidence interval (95%CI): 0.932-0.991], 91.5%, and 82.3%, respectively. The AUC, sensitivity, and specificity of the external validation were 0.878 (95%CI: 0.746-0.982), 66.7%, and 95.7%, respectively. CONCLUSION: A nomogram constructed based on the risk factors for postoperative NVG in patients with DR has a high prediction accuracy. This study can help formulate relevant preventive and treatment measures.
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Accurate classification and identification of chicken parts are critical to improve the productivity and processing speed in poultry processing plants. However, the overlapping of chicken parts has an impact on the effectiveness of the identification process. To solve this issue, this study proposed a real-time classification and detection method for chicken parts, utilizing YOLOV4 deep learning. The method can identify segmented chicken parts on the assembly line in real time and accurately, thus improving the efficiency of poultry processing. First, 600 images containing multiple chicken part samples were collected to build a chicken part dataset after using the image broadening technique, and then the dataset was divided according to the 6:2:2 division principle, with 1200 images as the training set, 400 images as the test set, and 400 images as the validation set. Second, we utilized the single-stage target detector YOLO to predict and calculate the chicken part images, obtaining the categories and positions of the chicken leg, chicken wing, and chicken breast in the image. This allowed us to achieve real-time classification and detection of chicken parts. This approach enabled real-time and efficient classification and detection of chicken parts. Finally, the mean average precision (mAP) and the processing time per image were utilized as key metrics to evaluate the effectiveness of the model. In addition, four other target detection algorithms were introduced for comparison with YOLOV4-CSPDarknet53 in this study, which include YOLOV3-Darknet53, YOLOV3-MobileNetv3, SSD-MobileNetv3, and SSD-VGG16. A comprehensive comparison test was conducted to assess the classification and detection performance of these models for chicken parts. Finally, for the chicken part dataset, the mAP of the YOLOV4-CSPDarknet53 model was 98.86% on a single image with an inference speed of 22.2 ms, which was higher than the other four models of YOLOV3-Darknet53, YOLOV3-MobileNetv3, SSD-MobileNetv3, and SSD-VGG16 mAP by 3.27%, 3.78%, 6.91%, and 6.13%, respectively. The average detection time was reduced by 13, 1.9, 6.2, and 20.3 ms, respectively. In summary, the chicken part classification and detection method proposed in this study offers numerous benefits, including the ability to detect multiple chicken parts simultaneously, as well as delivering high levels of accuracy and speed. Furthermore, this approach effectively addresses the issue of accurately identifying individual chicken parts in the presence of occlusion, thereby reducing waste on the assembly line. PRACTICAL APPLICATION: The aim of this study is to offer visual technical assistance in minimizing wastage and resource depletion during the sorting and cutting of chicken parts in poultry production and processing facilities. Furthermore, considering the diverse demands and preferences regarding chicken parts, this research can facilitate product processing that caters specifically to consumer preferences.