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Cadmium (Cd) is the main heavy metal pollutant in sediments from East China. The biochar-sediment nexus can provide carbon sequestration and pollution control. In this work, an in situ study was conducted to investigate the long-term effects and control mechanism of biochar and the effect of biochar aging on Cd stabilization in overlying water-pore water-sediment. The Cd2+ concentration in the overlying water was positively correlated with total nitrogen (0.960, P < 0.05), total organic carbon (0.983, P < 0.05), and total phosphorus (0.993, P < 0.01) in pore water. Biochar stabilized Cd2+ by increasing the pH and oxidation-reduction potential of the sediment environment and promoting the formation of Cd1.25Ca0.75(P2O7) on the biochar surface in sediment from phosphorus-rich water. These changes were closely related to the Brunauer-Emmett-Teller surface area and average pore size of the biochar. Within 60 days, the biochar in the sediment underwent aging, which was closely related to the preparation temperature of the biochar. The organic composition of biochar prepared at a low temperature (≤ 300 °C) and the surface structure of biochar prepared at a high temperature (≥ 500 °C) were altered. The biochar parameter changes were in the order of pore volume > Brunauer-Emmett-Teller surface area > pore size. Our results show that biochar modification can enhance the remediation capacity of biochar, but may be unfavorable to biochar anti-aging. This knowledge will support policymakers and researchers when exploring long-term biochar use in contamination control and strengthen future research.
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Cádmio , Poluentes Químicos da Água , Cádmio/química , Fósforo , Poluentes Químicos da Água/química , Carvão Vegetal/químicaRESUMO
Neurogenesis in the adult brain comprises the entire set of events of neuronal development. It begins with the division of precursor cells to form a mature, integrated, and functioning neuronal network. Adult neurogenesis is believed to play an important role in animals' cognitive abilities, including learning and memory. In the present study, significant neuronal differentiation-promoting activity of 80% (v/v) ethanol extract of P. cocos (EEPC) was found in Neuro-2a cells and mouse cortical neural stem/progenitor cells (NSPCs). Subsequently, a total of 97 compounds in EEPC were identified by UHPLC-Q-Exactive-MS/MS. Among them, four major compounds-Adenosine; Choline; Ethyl palmitoleate; and L-(-)-arabinitol-were further studied for their neuronal differentiation-promoting activity. Of which, choline has the most significant neuronal differentiation-promoting activity, indicating that choline, as the main bioactive compound in P. cocos, may have a positive effect on learning and memory functions. Compared with similar research literature, this is the first time that the neuronal differentiation-promoting effects of P. cocos extract have been studied.
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Produtos Biológicos , Neurônios , Wolfiporia , Animais , Camundongos , Diferenciação Celular , Colina , Etanol , Neurônios/efeitos dos fármacos , Células-Tronco , Espectrometria de Massas em Tandem , Wolfiporia/química , Produtos Biológicos/farmacologiaRESUMO
BACKGROUND: B-cell lymphoma, which originates from B cells at diverse differentiation stages, is the most common non-Hodgkin lymphoma with tremendous treatment challenges and unsatisfactory clinical outcomes. Flavokawain B (FKB), a naturally occurring chalcone extracted from kava, possesses promising anticancer properties. However, evidence on the effects of FKB on hematological malignancies, particularly lymphomas, remains scarce. PURPOSE: This study aimed to investigate the antilymphoma effect of FKB and its underlying mechanisms. STUDY DESIGN/METHODS: Proliferation assays, flow cytometry, and western blotting were employed to determine whether and how FKB affected B-cell lymphoma cell lines in vitro. Xenograft mouse models were established to evaluate the antilymphoma efficacy of FKB in vivo. RESULTS: FKB reduced the viability of a panel of B-cell lymphoma cell lines in a dose- and time-dependent manner. Mitochondrial apoptosis was markedly induced by FKB, as evidenced by an increased percentage of annexin V-positive cells, a loss of mitochondrial membrane potential, and cleavage of caspase-3 and PARP. Moreover, FKB inhibited BCL-XL expression and synergized with the BCL-2 inhibitor ABT-199. Mechanistically, FKB treatment decreased the phosphorylation of Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase-3ß (GSK3ß), and ribosomal protein S6 (RPS6). Pharmacological blockage of phosphoinositide 3-kinase (PI3K), Akt, or GSK3ß potentiated the activity of FKB, indicating the involvement of the PI3K/Akt cascade in FKB-mediated inhibitory effects. In mouse xenograft models, the intraperitoneal administration of FKB significantly decreased lymphoma growth, accompanied by diminished mitosis and Ki-67 staining of tumor tissues. CONCLUSION: Our data demonstrate the robust therapeutic potential of FKB in the treatment of B-cell lymphoma.
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Chalconas , Kava , Linfoma de Células B , Humanos , Animais , Camundongos , Chalconas/farmacologia , Glicogênio Sintase Quinase 3 beta , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Linfoma de Células B/tratamento farmacológico , MamíferosRESUMO
Eutrophication has spread from shallow lakes in temperature zones to lakes in cold regions as a result of a continuous warm climate and human activities. Little proof for the importance of dissolved organic phosphorus (DOP) in contributing to phosphorus cycling and algae growth has been generated for aquatic ecosystems, particularly in cold eutrophic lakes. In this study, a comprehensive in situ study was conducted in overlying water, suspended particulate matter, and sediment during and after algal bloom (in July and September, respectively) in Lake Hulun. Multiple methods of 31P NMR, enzymatic hydrolysis, and UV-visible technologies were combined to detect phosphorus occurrence, bioavailability, and molecular structure from a novel angle. The 31P NMR analysis results showed that DNA-P is mainly stored in the dissolved phase and has not been detected in suspended particulate matter or sediment. Enzymatic hydrolysis was used to determine the bioavailability of DOP, which revealed that in July and September, respectively, 85% and 79% of DOP were hydrolyzable. UV-visible analysis represented that the degree of humification and molecular weight of DOP were high during the algal bloom, but these values considerably dropped following the algal bloom. The large amount of DNA-P present in the overlying water is the main reason for the high degree of humification and high molecular weight of the water body. Besides, Lake Hulun's DNA-P remains highly bioavailable during algal blooms, despite its high degree of humification and molecular weight. These findings can serve as a theoretical basis for understanding the migration and transformation of DOP, as well as the persistence of algal blooms in eutrophic lakes located in cold regions.
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Lagos , Poluentes Químicos da Água , Humanos , Lagos/química , Monitoramento Ambiental/métodos , Ecossistema , Poluentes Químicos da Água/análise , Eutrofização , Fósforo/química , Matéria Orgânica Dissolvida , Água/análise , Material Particulado/análise , China , Sedimentos Geológicos/químicaRESUMO
Acute myeloid leukemia (AML) is a highly heterogeneous and rapidly progressive hematopoietic neoplasm characterized by frequent relapses and variable prognoses. The development of new treatment options, therefore, is of crucial importance. Platycodin D (PD) is a triterpenoid saponin, extracted from the roots of the traditional Chinese herbal medicine Platycodon grandiflorum (Jacq.) A. DC., which has been reported to exhibit therapeutic potential against a broad range of cancers. Although the effects of PD on AML remain unclear, in the present study, we observed a concentration-dependent reduction in the viability of multiple human AML cell lines in response to treatment with PD. In addition to triggering mitochondria-dependent apoptosis via the upregulation of BAK and BIM, treatment with PD also induced cell cycle arrest at the G0/G1 phase. Western blot analyses revealed marked suppression of the phosphorylation of protein kinase B (AKT), glycogen synthase kinase-3ß, ribosomal protein S6, and extracellular signal-regulated kinase (ERK) by PD, in turn implying the participation of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK pathways. Pre-incubation with LY294002, MK2206, AR-A014418, or U0126 was consistently found to significantly aggravate PD-induced inhibition of viability. Additionally, PD combined with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax elicited synergistically enhanced cytotoxic effects. The anti-leukemic activity of PD was further validated using primary samples from de novo AML patients. Given the results of the present study, PD may be a potent therapeutic candidate for the treatment of AML.
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Leucemia Mieloide Aguda , Saponinas , Triterpenos , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Sistema de Sinalização das MAP Quinases , Linhagem Celular Tumoral , Leucemia Mieloide Aguda/patologia , Saponinas/farmacologia , Saponinas/uso terapêutico , Triterpenos/farmacologia , ApoptoseRESUMO
BACKGROUND: Traditional Chinese medicine (TCM) indicates that Alzheimer's disease (AD) is considered the consequence produced by Kidney Yang Deficiency Syndrome (KDS-Yang), which has similar clinical characteristics to glucocorticoid withdrawal syndrome. Ginsenoside Re (G-Re) has been found to ameliorate the symptoms and pathological impairments of AD. However, it's not clear whether G-Re could protect memory and synapse lesions against kidney deficiency dementia. METHODS: Subcutaneous injection of hydrocortisone for 14 days was used to produce KDS-Yang. On the 15th day, Aß25-35 peptide was injected into the intracerebroventricular (icv) of KDS-Yang rats. Spine density was analyzed by Golgi staining and the ultrastructural morphology of the synapse was detected using Transmission Electron Microscopy (TEM). Western blot was used to examine the expression of pS396, pS404, Tau-5, tGSK-3ß, pS9GSK-3ß, Syt, Syn I, GluA1, GluN2B, PSD93, PSD95, ß2-AR and pS346-b2-AR. RESULTS: Hyperphosphorylation of tau in Aß25-35-injected rats with KDS-Yang was stronger than in Aß25-35-injected rats at the sites of Ser396 and Ser404. G-Re improved spatial memory damage detected by Morris water-maze (MWM), enhanced spines density, the thickness of postsynaptic density (PSD) and increased the expression of Syt, Syn I, GluA1, GluN2B, PSD93 and PSD95. Moreover, GRe decreased the hyperphosphorylation of ß2-AR at serine 346 in Aß25-35-injected rats with KDS-Yang. CONCLUSION: KDS-Yang might exacerbate AD pathological lesions. Importantly, G-Re is a potential ingredient for protecting against memory and synapse deficits in kidney deficiency dementia.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Ratos , Animais , Peptídeos beta-Amiloides/toxicidade , Deficiência da Energia Yang , Doença de Alzheimer/metabolismo , Proteína 4 Homóloga a Disks-Large , Rim/metabolismo , Rim/patologia , Sinapses/metabolismo , Modelos Animais de Doenças , Fragmentos de Peptídeos/toxicidadeRESUMO
Nitrogen (N) in sediments was a key element of lake eutrophication. The spatial distribution characteristics of four parts N in surface sediments were investigated by sequential extraction method, including free nitrogen (FN), exchangeable nitrogen (EN), hydrolyzable nitrogen (HN), and residual nitrogen (RN). Modified models were utilized to describe the adsorption isotherms of ammonia nitrogen (NH4+-N) in sediments and thus predict the risk of N release. The correlation between environmental factors and N concentration was discussed, as well as the migration or transformation and release risk of N between different mediums. The results showed that spatial variations characteristics of N fractions were influenced by the lake topography and surrounding human activities. The content of total nitrogen (TN) in the sediments was 933.4 ~ 3006.8 mg/kg, with an average of 1835 mg/kg. The HN, RN, FN, and EN in sediments accounted for 66.85%, 21.35%, 6.82%, and 4.92% of TN, respectively. There was a significant correlation between each fraction of N and TN and also between different fractions of N (p < 0.01). Fitting by modified Langmuir model indicated that the adsorbed amounts of N in the sediments at maximum (Qmax) was, from greatest to least, southeast lake (2905.3 mg/kg) > southwest lake (1415.4 mg/kg) ≈ north lake (1424.6 mg/kg). Environmental parameters (pH, DO, C/N, etc.) affected the occurrence fraction of nitrogen, which could cause the persistent and increased risk of sustained release of high concentrations of endogenous N. N pollution in sediment and interstitial water is severe, and the risk of endogenous N release will gradually increase in the future.
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Lagos , Poluentes Químicos da Água , Humanos , Lagos/química , Nitrogênio/análise , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , China , Eutrofização , Fósforo/análise , Monitoramento AmbientalRESUMO
31P Nuclear Magnetic Resonance (31P NMR) is an important analytical tool for identifying and quantifying phosphorus-based compounds in aquatic environments. However, the precipitation method typically used for analyzing phosphorus species via 31P NMR has limited application. To expand the scope of the method and apply it to highly mineralized rivers and lakes worldwide, we present an optimization technique that employs H resin to assist phosphorus (P) enrichment in highly mineralized lake water. To explore how to reduce analysis interference from salt in highly mineralized water and improve the accuracy of P analysis using 31P NMR, we conducted case studies on Lake Hulun and Qing River. This study aimed to increase the efficiency of phosphorus extraction in highly mineralized water samples by using H resin and optimizing key parameters. The optimization procedure included determining the enriched water volume, H resin treatment time, AlCl3 addition amount, and precipitation time. The final recommended optimization enrichment procedure involves treating 10 L of filtered water sample with 150 g of Milli-Q water-washed H resin for 30 s, adjusting the pH of the treated sample to 6-7, adding 1.6 g of AlCl3, stirring the mixture, and allowing the solution to settle for 9 h to collect the flocculated precipitate. The precipitate was then extracted with 30 mL of 1 M NaOH +0.05 M DETA extraction solution at 25 °C for 16 h, and the supernatant was separated and lyophilized. The lyophilized sample was redissolved in 1 mL of 1 M NaOH +0.05 M EDTA. This optimized analytical method using 31P NMR effectively identified phosphorus species in highly mineralized natural waters and can be applied to other highly mineralized lake waters globally.
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Fósforo , Poluentes Químicos da Água , Fósforo/química , Lagos/química , Hidróxido de Sódio , Sedimentos Geológicos/química , Espectroscopia de Ressonância Magnética/métodos , Poluentes Químicos da Água/análise , Água/análise , China , Monitoramento Ambiental/métodosRESUMO
A comprehensive understanding of the mobility of both nitrogen (N) and phosphorus (P) and the inter-relationships between P, N, and iron (Fe) in sediments is important for controlling the "internal loadings" of nutrients in lakes. In this research, diffusive gradients in thin film (DGT) assemblies with binding layers (ZrO-AT, chelex, and ZrO) were designed for PO4-P, Fe, ammonium (NH4-N), and nitrate (NO3-N) at sediment/water interface (SWI) in Western Lake Taihu (China). The biogeochemical processes of N and P related to the physicochemical properties, the dynamic P transfer, the distribution characteristics of P microniches, and the estimation of the release risks in sediments in Western Lake Taihu were simultaneously revealed by the passive sampling technique-DGT with the high spatial resolutions (millimeter and sub-millimeter). Based on DGT concentration (CDGT) related to physicochemical properties in sediments, (1) P biogeochemical reactions included P release from Fe-bound P during Fe reduction, algae biomass decomposition, and phosphatase enzyme activity increased by NH4-N; (2) denitrification and dissimilatory nitrate reduction to ammonium (DNRA) led to exchangeable ammonium (NH4ex) enrichment and NH4-N release; anammox depleted NH4-N transfer; organic matter (OM) mineralization favored NH4-N release; and (3) aerobic nitrification led to NO3-N remobilization; denitrification and DNRA reduced NO3-N release. Redox status, OM, Fe, aluminum, or calcium influenced mobilization of nutrients. The numerical model of DGT-induced fluxes in sediments was used for dynamic P transfers with resupply types ("slow" ~ "fast") controlled by labile P pool, resupply constant, response time, and Dspt rate. The formation of P microniches in two dimensions was revealed. Sediment P release risk index (0.49 ~ 36.85 [lg (nmol cm-3 d-1)]) with "light" ~ "high" risks and diffusive fluxes across SWI (µg m-2 d-1) of 15.0 ~ 639 (PO4-P), - 1403 ~ 5010 (NH4-N), and - 1395 ~ 149 (NO3-N) were derived and lake management strategies were provided. The DGT technique provides the characterization of the mobilization of nutrients and evidence for biogeochemical processes at the fine spatial scales for control of internal loadings in sediments.
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Lagos , Poluentes Químicos da Água , Lagos/química , Nitratos , Ferro/química , Fósforo/análise , China , Nutrientes , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodosRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION: Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
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Paroxetina , Baço , Humanos , Paroxetina/efeitos adversos , Ansiedade , Síndrome , Medicina Tradicional Chinesa , Resultado do Tratamento , Método Duplo-CegoRESUMO
OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Assuntos
Humanos , Paroxetina/efeitos adversos , Baço , Ansiedade , Síndrome , Medicina Tradicional Chinesa , Resultado do Tratamento , Método Duplo-CegoRESUMO
Introduction: Vitamin K deficiency may elevate the incidence of musculoskeletal disorders (MSD), whereas it lacks validation for pediatric populations and has uncertain dose recommendations. In this context, we hypothesized that serum vitamin K levels are associated with MSD in preschool children, and the widely used vitamin A and vitamin D supplements may mediate these associations based on potential mechanisms, which expects to provide guidance for future practice. Methods: A cross-sectional study was conducted in Sichuan province in southwestern China, from January 2021 to May 2022. Serum levels of vitamin K1/K2 and 25(OH)D were determined using the high-performance liquid chromatography method, and the diagnosis of MSD was executed by clinicians. Overall and stratified logistic regression analysis based on categorized 25(OH)D levels were conducted to assess association between serum vitamin K levels and MSD prevalence after adjusting for confounders. Mediation analysis was further performed and vitamin A and D supplementation was regressed as the mediator. Results: A total of 6,368 children aged 0-6 years old were enrolled. MSD was identified in 1179 (18.51%) of the children, while 5,189 (81.49%) of them did not present such disorder. After adjusting confounders, a significant difference was found in serum vitamin K1 level between children in MSD and Non-MSD group (OR = 0.802, 95%CI 0.745-0.864). No significant difference was found in serum vitamin K2 level between the two groups (OR = 0.975, 95%CI 0.753-1.261). The association between vitamin K1 level and MSD prevalence was partly (36.8%) mediated by vitamin A and D supplementation. Conclusions: A low serum vitamin K1 level is connected with an increased risk of MSD among children, highlighting that vitamin A and D supplementation is a helpful intervention to prevent MSD in children with vitamin K deficiency.
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Neuropathic pain remains a chronic and intractable pain. Recent studies have shown a close relationship between gamma-aminobutyric acid A (GABAA) receptor and neuropathic pain. Spinal cord GABAA receptors are key modulators of pain processing. Electroacupuncture (EA) is currently used worldwide to relieve pain. The immunomodulatory effect of EA in animals has been proposed in previous studies. However, it remains unclear how EA contributes to alleviating neuropathic pain. In this study, the chronic constriction injury (CCI) rat model was used to explore the relationship between GABAA receptor and neuropathic pain. We also investigated whether EA treatment could ameliorate pain hypersensitivity by modulating the GABAA receptor. To determine the function of EA in neurological diseases, in this study, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were assessed to determine the threshold of pain. In addition, we used Western blot, immunofluorescence, and real-time quantitative PCR to confirm whether EA treatment relieves pain hypersensitivity by regulating GABAA receptors. The morphology of synapse was examined using an electron microscope. In the present study, EA relieved mechanical allodynia and thermal hyperalgesia. EA also inhibited microglial activation in the spinal cord, accompanied by increased levels of GABAARα2, GABAARα3, and GABAARγ2 subunits. However, the analgesic effect of EA was attenuated by treatment with the GABAA receptor antagonist bicuculine. Overall, the present results indicate that microglia and GABAA receptor might participate in EA analgesia. These results contribute to our understanding of the impact of EA on rats after sciatic nerve compression, providing a theoretical basis for the clinical application of EA analgesia.
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Prunus mume has been cultivated for more than three millennia with important edible, ornamental, and medicinal value. Due to its sour taste, the Prunus mume fruit (called Meizi in Chinese and Ume in Japanese) is not very popular compared to other fruits. It is, however, a very favorite food for the Bai people living in Eryuan County, Dali of Yunnan, China. The local people are masters of making various local products with plum in different ways. In this research, we conducted field investigations in Eryuan County using ethnobotanical methods from August 2019 to July 2021, focusing on the Prunus mume (for its edible fruits). A total of 76 key informants participated in our semi-structured interviews. The survey recorded 37 species (and varieties) belonging to 11 families related to the Bai people's Meizi-consuming culture. Among them, there are 14 taxa of plum resources, including one original species and 13 varieties. These 37 species are either used as substitutes for plum due to their similar taste or as seasonings to improve the sour taste of plum. The higher Cultural Food Significance Index value implies that Prunus mume, Chaenomeles speciosa, Phyllanthus emblica, Prunus salicina, and Chaenomeles cathayensis have high acceptance and use value in the Bai communities. Among the various local products traditionally made by the Bai people, carved plums, preserved plums, perilla-wrapped plums, and stewed plums are the most famous and popular categories in the traditional markets. Currently, the plum business based on the traditional Meizi-consuming culture of the Bai people is already one of Eryuan's economic pillars. This study showed that plums play an important role in expressing the local cultural diversity, and they also help the local people by improving their livelihood through their edible value. In turn, for the sustainable use of plum resources, the Bai people positively manage local forests through a series of measures to protect the diversity of plum resources and related plant communities.
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Icariin (ICA), extracted from Epimedium, is a flavonoid used in traditional Chinese medicine. Di(2-ethylhexyl) phthalate (DEHP) is a phthalate used in commercial products as a plasticizer that can influence the human endocrine and reproduction system. We previously found that ICA reversed DEHP-induced damage through the prevention of reactive oxygen species accumulation and promotion of testosterone secretion. Here we investigated the mechanisms of ICA in promoting testosterone secretion from murine Leydig cells. We used ICA, DEHP, the Akt agonist SC-79, the Akt inhibitor MK2206, and the Creb inhibitor KG501 to determine the effect of these treatments on the expression levels of the steroidogenic enzymes, Cyp11a1 and Hsd3b, which play critical roles in androgen production, in Leydig cells. Bioinformatic analysis was used to search for ICA-targeted proteins and their associated pathways. We found that icariin interacted with estrogen receptor on the cell membrane, leading to increased phosphorylation levels of Akt and Creb proteins and enhanced transcription of genes encoding steroidogenic enzymes and testosterone synthesis. We further investigated ICA activity in vivo using male mice pretreated with 100 mg/kg ICA and then treated with 750 mg/kg DEHP. ICA pretreatment reversed the reduced protein expression levels of Cyp11a1 and Hsd3b induced by DEHP in Leydig cells in vivo. Furthermore, while the phosphorylation levels of Akt and Creb were decreased in testes of mice exposed to DEHP alone, these effects were reversed by ICA pretreatment. These findings indicate that ICA promotes testosterone synthesis via the Esr1/Src/Akt/Creb/Sf-1 signaling pathway.
Assuntos
Dietilexilftalato , Células Intersticiais do Testículo , Animais , Enzima de Clivagem da Cadeia Lateral do Colesterol , Dietilexilftalato/farmacologia , Flavonoides , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Testículo , Testosterona/metabolismoRESUMO
Primary aldosteronism (PA) is a well-documented cause of secondary hypertension, often accompanied by hypokalemia. However, PA with normal blood pressure and hypokalemic rhabdomyolysis (RM) is rare. We report a case of hypokalemia-induced RM as the first symptom of PA. A 65-year-old woman was admitted due to intermittent limb weakness and myalgia. She denied a history of hypertension. Laboratory findings showed profound hypokalemia (1.8 mmol/L) and extreme elevation of creatinine kinase (CK) levels (18,370 U/L), suggestive of hypokalemia-induced RM. She was administered intravenous fluids as well as active oral and intravenous potassium supplements. CK and myoglobin levels gradually decreased, but the serum potassium recovery was poor. Further evaluations strongly suggested PA by an aldosterone-producing adenoma, which was surgically removed. After surgery, the patient recovered well. The systolic blood pressure decreased by approximately 10-20 mmHg and the diastolic blood pressure decreased by approximately 5-10 mmHg. After discontinuation of spironolactone and oral potassium supplementation, the patient had normal serum potassium levels. This case indicates that PA is a cause of hypokalemic RM, even in patients with normal blood pressure. In addition, attention should be paid to changes in serum aminotransferase levels associated with RM. If the patient had no liver disease, it might be a marker for skeletal muscle injury instead of hepatocyte damage.
Assuntos
Hiperaldosteronismo , Hipertensão , Hipopotassemia , Rabdomiólise , Idoso , Feminino , Humanos , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipopotassemia/complicações , Hipopotassemia/diagnóstico , Potássio , Rabdomiólise/complicações , Rabdomiólise/diagnósticoRESUMO
OBJECTIVE: To observe the effect of Fu's subcutaneous needling therapy on pain degree, quality of life, serum 5-hydroxytryptamine (5-HT) and neuropeptide Y (NPY) in patients with intercostal pain after surgery for osteoporotic thoracic vertebral compression fracture (OVCF) and explore the application value of Fu's subcutaneous needling in treatment of post-operative intercostal pain. METHODS: A total of 60 patients with intercostal pain after OVCF surgery were divided into a medication group and a Fu's subcutaneous needling therapy group, with 30 cases in each group. In the medication group, zoledronic acid injection, salmon calcitonin injection, calcitonin D tablets and mecobalamin tablets were prescribed. The duration of treatment was 8 weeks. In the Fu's subcutaneous needling therapy group, on the base of treatment as the medicine group, Fu's subcutaneous needling therapy was provided for 2 weeksï¼once every other day. The needle is inserted 6 cm away from the most painful point. Separately, in 2, 4 and 8 weeks of treatment, as well as in 16 weeks after treatment, the visual analogue scale (VAS) and the generic quality of life inventory-74 (GQOLI-74) were adopted to evaluate intercostal pain and quality of life in the patients of both groups and analyze the incidence of adverse reaction. Radioimmunoassay was used to measure the levels of serum 5-HT and NPY. RESULTS: Compared with the results before treatment, in 2, 4 and 8 weeks of treatment as well as in 16 weeks after treatment, VAS scores of both groups were all reduced (P<0.05), GQOLI-74 scores increased obviously (P<0.05) and the levels of serum 5-HT and NPY increased obviously (P<0.05) in the two groups. In 2, 4 and 8 weeks of treatment as well as in 16 weeks after treatment, VAS score in the Fu's subcutaneous needling therapy group was lower than that in the medication group (P<0.05), GQOLI-74 score and the levels of serum 5-HT and NPY were higher than those in the medication group (P<0.05). During the treatment and in 16 weeks after treatment, the difference was not significant in the incidence of adverse reaction between the two groups (P>0.05). CONCLUSION: Fu's subcutaneous needling therapy can relieve intercostal pain and improves the quality of life in the patients after surgery for OVCF.
Assuntos
Fraturas por Compressão , Fraturas da Coluna Vertebral , Fraturas por Compressão/cirurgia , Humanos , Agulhas , Dor , Qualidade de Vida , Resultado do TratamentoRESUMO
Electroacupuncture (EA) has been used to treat neuropathic pain induced by peripheral nerve injury (PNI) by applying an electrical current to acupoints with acupuncture needles. However, the mechanisms by which EA treats pain remain indistinct. High P2X4 receptor (P2X4R) expression levels demonstrate a notable increase in hyperactive microglia in the ipsilateral spinal dorsal horn following PNI. In order to demonstrate the possibility that EA analgesia is mediated in part by P2X4R in hyperactive microglia, the present study performed mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) tests in male SpragueDawley rats that had undergone spinal nerve ligation (SNL). The expression levels of spinal P2X4R were determined using reverse transcriptionquantitative PCR, western blotting analysis and immunoï¬uorescence staining. Furthermore, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded using wholecell patch clamp to demonstrate the effect of EA on synaptic transmission in rat spinal substantia gelatinosa (SG) neurons. The results of the present study demonstrated that EA increased the MWT and TWL and decreased overexpression of P2X4R in hyperactive microglia in SNL rats. Moreover, EA attenuated the frequency of sEPSCs in SG neurons in SNL rats. The results of the present study indicate that EA may mediate P2X4R in hyperactive spinal microglia to inhibit nociceptive transmission of SG neurons, thus relieving pain in SNL rats.
Assuntos
Eletroacupuntura , Microglia/metabolismo , Neurônios/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Nervos Espinhais/metabolismo , Substância Gelatinosa/metabolismo , Animais , Ligadura , Masculino , Microglia/patologia , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/patologia , Substância Gelatinosa/patologiaRESUMO
Vitamin D has been associated with a variety of human complex traits and diseases in observational studies, but a causal relationship remains unclear. To examine a putative causal effect of vitamin D across phenotypic domains and disease categories, we conducted Mendelian randomization (MR) analyses using genetic instruments associated with circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We leveraged genome-wide significant 25(OH)D-associated SNPs (N = 138) from a meta-analysis combining a vitamin D GWAS conducted in 401,460 white British UK Biobank (UKBB) participants and an independent vitamin D GWAS including 42,274 samples of European ancestry, and examined 190 large-scale health-related GWAS spanning a broad spectrum of complex traits, diseases and biomarkers. We applied multiple MR methods to estimate the causal effect of vitamin D while testing and controlling for potential biases from horizontal pleiotropy. Consistent with previous findings, genetically predicted increased 25(OH)D levels significantly decreased the risk of multiple sclerosis (OR = 0.824; 95% CI 0.689-0.986). The protective effect estimate was consistent across different MR methods and four different multiple sclerosis GWAS with varying sample sizes and genotyping platforms. On the contrary, we found limited evidence in support of a causal effect of 25(OH)D on anthropometric traits, obesity, cognitive function, sleep behavior, breast and prostate cancer, and autoimmune, cardiovascular, metabolic, neurological and psychiatric traits and diseases, and blood biomarkers. Our results may inform ongoing and future randomized clinical trials of vitamin D supplementation.
Assuntos
Doença/genética , Análise da Randomização Mendeliana , Vitamina D/análogos & derivados , Adulto , Biomarcadores/sangue , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Vitamina D/sangueRESUMO
Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC50 = 3.52 µM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.