ABSTRACT
BACKGROUND: There is no available viable treatment for Sepsis-Induced Cardiomyopathy (SIC), a common sepsis complication with a higher fatality risk. The septic patients showed an abnormal activation of the renin angiotensin (Ang) aldosterone system (RAAS). However, it is not known how the Ang II and Ang-(1-7) affect SIC. METHODS: Peripheral plasma was collected from the Healthy Control (HC) and septic patients and Ang II and Ang-(1-7) protein concentrations were measured. The in vitro and in vivo models of SIC were developed using Lipopolysaccharide (LPS) to preliminarily explore the relationship between the SIC state, Ang II, and Ang-(1-7) levels, along with the protective function of exogenous Ang-(1-7) on SIC. RESULTS: Peripheral plasma Ang II and the Ang II/Ang-(1-7) levels in SIC-affected patients were elevated compared to the levels in HC and non-SIC patients, however, the HC showed higher Ang-(1-7) levels. Furthermore, peripheral plasma Ang II, Ang II/Ang-(1-7), and Ang-(1-7) levels in SIC patients were significantly correlated with the degree of myocardial injury. Additionally, exogenous Ang-(1-7) can attenuate inflammatory response, reduce oxidative stress, maintain mitochondrial dynamics homeostasis, and alleviate mitochondrial structural and functional damage by inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thus alleviating SIC. CONCLUSIONS: Plasma Ang-(1-7), Ang II, and Ang II/Ang-(1-7) levels were regarded as significant SIC biomarkers. In SIC, therapeutic targeting of RAAS, for example with Ang-(1-7), may exert protective roles against myocardial damage.
Subject(s)
Cardiomyopathies , Sepsis , Humans , NF-kappa B/metabolism , Mitogen-Activated Protein Kinases , Cells, Cultured , Angiotensin II/metabolism , Cardiomyopathies/drug therapy , Cardiomyopathies/etiology , Sepsis/complications , Sepsis/drug therapyABSTRACT
To compare the pancreatic proteomics and autophagy between Rehmanniae Radix-and Rehmanniae Radix Praeparata-treated mice with type 2 diabetes mellitus(T2DM). The T2DM mouse model was established by high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days). The mice were then randomly assigned into a control group, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) catalpol groups, low-(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, low-(150 mg·kg~(-1)) and high-dose(300 mg·kg~(-1)) 5-hydroxymethyl furfuraldehyde(5-HMF) groups, and a metformin(250 mg·kg~(-1)) group. In addition, a normal group was also set and each group included 8 mice. The pancreas was collected after four weeks of administration and proteomics tools were employed to study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on protein expression in the pancreas of T2DM mice. The expression levels of proteins involved in autophagy, inflammation, and oxidative stress response in the pancreatic tissues of T2DM mice were determined by western blotting, immunohistochemical assay, and transmission electron microscopy. The results showed that the differential proteins between the model group and Rehmanniae Radix/Rehmanniae Radix Prae-parata group were enriched in 7 KEGG pathways, such as autophagy-animal, which indicated that the 7 pathways may be associated with T2DM. Compared with the control group, drug administration significantly up-regulated the expression levels of beclin1 and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR and down-regulated those of the inflammation indicators, Toll-like receptor-4(TLR4) and Nod-like receptor protein 3(NLRP3), in the pancreas of T2DM mice, and Rehmanniae Radix showed better performance. In addition, the expression levels of inducible nitric oxide synthase(iNOS), nuclear factor erythroid 2-related factor 2(Nrf2), and heine oxygenase-1(HO-1) in the pancreas of T2DM mice were down-regulated after drug administration, and Rehmanniae Radix Praeparata demonstrated better performance. The results indicate that both Rehmanniae Radix and Rehmanniae Radix Praeparata can alleviate the inflammatory symptoms, reduce oxidative stress response, and increase the autophagy level in the pancreas of T2DM mice, while they exert the effect on different autophagy pathways.
Subject(s)
Diabetes Mellitus, Type 2 , Mice , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/genetics , Streptozocin/pharmacology , Diet, High-Fat/adverse effects , Proteomics , Inflammation , TOR Serine-Threonine Kinases , Autophagy , MammalsABSTRACT
Sepsis-induced cardiomyopathy (SIC) is a serious complication of sepsis with high mortality but no effective treatment. The renin angiotensin (Ang) aldosterone system (RAAS) is activated in patients with sepsis but it is unclear how the Ang II/Ang II type 1 receptor (AT1R) axis contributes to SIC. This study examined the link between the Ang II/AT1R axis and SIC as well as the protective effect of AT1R blockers (ARBs). The Ang II level in peripheral plasma and AT1R expression on monocytes were significantly higher in patients with SIC compared with those in non-SIC patients and healthy controls and were correlated with the degree of myocardial injury. The ARB losartan reduced the infiltration of neutrophils, monocytes, and macrophages into the heart and spleen of SIC mice. Additionally, losartan regulated macrophage polarization from the M1 to the M2 subtype via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby maintaining the mitochondrial dynamics balance in cardiomyocytes and reducing oxidative stress and cardiomyocyte apoptosis. In conclusion, the plasma Ang II level and AT1R expression on plasma monocytes are an important biomarker in SIC. Therapeutic targeting of AT1R, for example with losartan, can potentially protect against myocardial injury in SIC.
Subject(s)
Cardiomyopathies , Sepsis , Mice , Animals , Losartan/pharmacology , Losartan/therapeutic use , NF-kappa B/metabolism , Angiotensin Receptor Antagonists , Toll-Like Receptor 4 , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Mitogen-Activated Protein Kinases , Angiotensin-Converting Enzyme Inhibitors , Receptor, Angiotensin, Type 1/metabolism , Angiotensin II/pharmacology , Sepsis/complications , Sepsis/drug therapy , Cardiomyopathies/drug therapy , Cardiomyopathies/etiology , Macrophages/metabolismABSTRACT
BACKGROUND: The evidence about the effect of essential trace element (ETE) mixture on cognitive function amongst older adults is limited. This study aims to evaluate the associations of single ETEs and ETE mixture with cognitive function using a representative sample of community-dwelling older adults in China. METHODS: A total of 3814 older adults were included in the study. Urinary concentrations of selenium (Se), vanadium (V), cobalt (Co), strontium (Sr), and molybdenum (Mo) were detected by inductively coupled plasma mass spectrometry. Cognitive function in older adults was assessed using the Chinese version of the Mini-Mental State Examination (MMSE). Linear regression and Bayesian kernel machine regression (BKMR) were performed to explore the associations of single ETEs and ETE mixture with cognitive function, respectively. RESULTS: Linear regression showed that urinary levels of Se and V were positively associated with MMSE scores in the adjusted single-element models. BKMR also showed marginally positive associations of Se and V with MMSE scores. Moreover, higher urinary levels of ETE mixture were significantly associated with increased MMSE scores in a dose-response pattern, and Se was the most important contributor within the mixture. Both Se and V demonstrated positive additive effects on the associations of other ETEs with MMSE scores, whereas Co had a negative additive effect. CONCLUSIONS: V and Se are positively associated with cognitive function, individually and as a mixture. ETE mixture exhibits a linear dose-response association with improved cognitive function, with Se being the most important component within the mixture. Mixture analyses rather than single ETE analyses may provide a real-world perspective on the relationship between ETE mixture and cognitive function. Further cohort studies are needed to clarify the association of multiple ETEs with cognitive function.
Subject(s)
Selenium , Trace Elements , Aged , Bayes Theorem , Cognition , Humans , Independent LivingABSTRACT
BACKGROUND: Previous studies have found associations between single toxic metals, such as arsenic and cadmium, and kidney function in adults with diabetes. However, studies with regards to other metals and metal mixtures are still limited. OBJECTIVE: Our study aimed to investigate the associations between urinary concentrations of 5 selected metals and metal mixtures and kidney function using a sample of older adults with diabetes mellitus in Chinese communities. METHODS: In a sample of older adults (n = 5186), 592 eligible subjects were included in this study. Urinary concentrations of 5 metals, i.e., arsenic (As), cadmium (Cd), vanadium (V), cobalt (Co), and thallium (Tl), were measured by inductively coupled plasma mass spectrometer (ICP-MS). Estimated glomerular filtration rate (eGFR) was calculated and dichotomized into indicator of chronic kidney disease (CKD). Logistic analysis and Bayesian kernel machine regression (BKMR) were used to explore the associations between single metals and metal mixtures and CKD, respectively. RESULTS: Urinary levels of As and V were positively correlated with CKD (OR=2.37, 95% CI: 1.31-4.30 for As; OR=2.24, 95% CI: 1.25-4.03 for V), when compared the 4th quartile with the 1st quartile. After adjustment for potential confounders, the significant association between As and CKD still existed (OR=2.73, 95% CI: 1.23-6.07). BKMR analyses showed strong linear positive associations between As and V and CKD. Higher urinary levels of the mixture were significantly associated with higher odds of CKD in a dose-response pattern. As and V showed the highest posterior inclusion probabilities. CONCLUSION: Urine As and V were positively associated with CKD in older adults with diabetes mellitus, separately and in a mixture. The metals mixture showed a linear dose-response association with the odds of CKD. The analyses of mixtures, rather than of single metals, may provide a real-world perspective on the relationship between metals and kidney function.
Subject(s)
Diabetes Mellitus , Kidney , Metals/urine , Aged , Bayes Theorem , China , Diabetes Mellitus/chemically induced , HumansABSTRACT
Apple valsa canker (AVC), caused by Valsa mali, is one of the most important diseases of apple trees in China. AVC occurred severely along with cold winter or cold spring. However, the effect of lower temperature on V. mali is poorly understood. This study evaluated the influence of lower temperature pretreatment of V. mali on the infection of apple twigs and leaves. The results showed that exposing V. mali to lower temperatures (between -10°C and 10°C) for more than 18 h significantly increased the disease severity of apple leaves and twigs, with a higher lesion area ratio (LAR), lesion length, and disease incidence (DI) than that at 25°C. In addition, cold treatment ranging from -5°C to 10°C promoted colony growth. Meanwhile, the relative expression of four cell wall degrading enzyme (CWDE)-related genes pretreated at -5°C and 5°C were significantly higher than that at 25°C. The results indicated that the virulence of V. mali mycelium is sensitive to lower temperatures. After sensing lower temperature changes, V. mali can adjust its infection of apple trees by regulating the expression of pathogenicity gene and growth rate. Spring has very frequent temperature changes, and V. mali is highly invasive in this season. Therefore, more attention should be paid in spring to protecting apple trees from infection of V. mali, by reducing pruning wound formation in spring and applying protective agents to pruning wounds in time.
Subject(s)
Ascomycota , Malus , Ascomycota/genetics , Plant Diseases , TemperatureABSTRACT
This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1ß(IL-1ß), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.
Subject(s)
Diabetes Mellitus, Experimental , NF-kappa B , AMP-Activated Protein Kinases/genetics , Animals , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , StreptozocinABSTRACT
To compare the blood-cooling and hemostasis effects of Rehmanniae Radix before and after carbonizing on rats with blood heat and hemorrhage syndrome. The blood heat and hemorrhage syndrome rat model was established. Indexes including rectal temperature,whole blood viscosity,plasma viscosity,thrombin time(TT),activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen content(FIB),red blood cell(RBC),hemoglobin(Hb),hematocrit(HCT),blood platelet count(PLT),mean platelet volume(MPV),serum IL-1,serum IL-6 and lung histopathology were detected to investigate the blood-cooling and hemostasis effects of Rehmanniae Radix and its carbonized products. Compared with the blank control group,the rectal temperature was significantly increased with rise of the high,middle and low whole blood viscosities and plasma viscosity(P<0.05); both the high and low whole blood restore viscosity and the high and low whole blood relative viscosity were increased significantly(P< 0.05); TT,APTT and PT were notably prolonged with the increase in FIB content(P<0.05); RBC,Hb and HCT increased significantly(P< 0.05); concentrations of serum IL-1 and IL-6 were also increased(P< 0.05) in model group. Additionally,obvious hemorrhages in lung and stomach were observed in rats of the model group. Rehmanniae Radix and its carbonized products can significantly reduce rectal temperature,high middle and low whole blood viscosities and plasma viscosity(P<0.05). TT and APTT were shortened,with lower expression of FIB in group of Rehmannia Radix and its carbonized products. Hemorrhages of lung and stomach were improved by Rehmannia Radix and its carbonized products. The results indicated that Rehmannia Radix before and after carbonizing had the hemostasis and blood-cooling effects by promoting coagulation,improving blood rheology and inhibiting expressions of IL-1 and IL-6.
Subject(s)
Blood Coagulation , Drugs, Chinese Herbal/pharmacology , Hemorrhage/drug therapy , Hemostasis , Rehmannia/chemistry , Animals , Blood Viscosity , Body Temperature , Interleukin-1/metabolism , Interleukin-6/metabolism , Partial Thromboplastin Time , Plant Roots , Rats , Thrombin TimeABSTRACT
PURPOSE: This study evaluates baseline patient characteristics and surgical parameters for risk factors of medical complications in ASD patients received posterior long level internal fixation. METHODS: Analysis of consecutive patients who underwent posterior long-level instruction fixation for adult degenerative scoliosis (ADS) with a minimum of two year follow-up was performed. Pre-operative risk factors, intraoperative variables, peri-operative radiographic parameters, and surgical-related risk factors were collected to analyze the effect of risk factors on medical complications. Patients were separated into groups with and without medical complication. Then, complication group was further classified as major or minor medical complications. Potential risk factors were identified by univariate testing. Multivariate logistic regression was used to evaluate independent predictors of medical complications. RESULTS: One hundred and thirty-one ADS patients who underwent posterior long segment pedicle screws fixation were included. Total medical complication incidence was 25.2%, which included infection (12.2%), neurological (11.5%), cardiopulmonary (7.6%), gastrointestinal (6.1%), and renal (1.5%) complications. Overall, 7.6% of patients developed major medical complications, and 17.6% of patients developed minor medical complications. The radiographic parameters of pre-operative and last follow-up had no significant difference between the groups of medical complications and the major or minor medical complications subgroups. However, the incidence of cerebrospinal fluid leak (CFL) in patients who without medical complications was much lower than that with medical complications (18.4 vs. 42.4%, P = 0.005). Independent risk factors for development of medical complications included smoking (OR = 6.45, P = 0.012), heart disease (OR = 10.07, P = 0.012), fusion level (OR = 2.12, P = 0.001), and length of hospital stay (LOS) (OR = 2.11, P = 0.000). Independent risk factors for development of major medical complications were diabetes (OR 6.81, P = 0.047) and heart disease (OR = 5.99, P = 0.049). Except for the last follow-up, Oswestry Disability Index and visual analog scale of the patient experienced medical complications trend higher score; the clinical outcomes have no significant difference between the medical and major complications groups. CONCLUSION: Heart disease comorbidity is an independent risk factor for both medical and major medical complications. Smoking, fusion level, and LOS are independent risk factors for medical complication. Diabetes is the independent risk factors for major medical complications.
Subject(s)
Postoperative Complications/etiology , Scoliosis/surgery , Spinal Fusion/adverse effects , Adult , Aged , Female , Humans , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors , Treatment Outcome , Young AdultABSTRACT
In the thermal analysis, the pyrolysis characteristics of crude Kansui Radix, alcohol extract of Kansui Radix, petroleum ether extract, chloroform extract, ethyl acetate extract, n-butanol extract, and licorice vinegar were analyzed with simulated air (N2-O2 4:1) as the carrier gas, at a temperature increase rate of 10 °C·min⻹ and a volume flow rate of 60 mL·min⻹, respectively. The results showed that due to the different polarity of the extraction solvent, the type and quantity of the chemical components contained in each polar part were different, and with the increase in the amount of solid powder of licorice, the peak of the maximum heat loss rate occurred in advance. For petroleum ether, chloroform, and ethyl acetate fractions, (157.40±1.06), 3.50, (25.83±1.66) °C in advance respectively, but the weight loss rate of the chloroform fraction was increased by (2.62±5.19) °C, while decreased by (33.90±1.72), (19.28±1.11) °C for the petroleum ether and ethyl acetate fractions. So we can conclude that with the addition of licorice, the pyrolysis rate of the petroleum ether and chloroform fractions in the toxic part of Kansui Radix was increased; the temperature point at the peak of the maximum weight loss rate was decreased, and the ethyl acetate fraction (effective part) showed a decrease in temperature rising process, but its overall ratio of weight loss and weight loss rate were relatively small, retaining the effect of medicinal ingredients. This proved the mechanism of licorice system Kansui Radix on attenuating toxicity after processing and the scientificity and rationality of licorice system Kansui Radix. At the same time, as the proportion of glycyrrhizin was increased, the peak of the maximum heat loss rate of petroleum ether, chloroform and ethyl acetate fractions occurred in advance; the peak temperature was decreased, with easy pyrolysis. Among them, the thermogravimetric rate of the mixture of petroleum ether and chloroform fractions (10:1) was relatively large, with a low peak temperature, while ethyl acetate fraction showed opposite results. This conclusion has certain guiding significance for the ratio of gansui to licorice.
Subject(s)
Drugs, Chinese Herbal/chemistry , Euphorbia/chemistry , Glycyrrhiza/chemistry , Plant Extracts/chemistry , Technology, Pharmaceutical , Plant Roots/chemistry , TemperatureABSTRACT
PURPOSE: To report our 11-year minimum clinical and radiological outcomes, as well as complications of the Charite III total disc replacement (TDR). METHODS: A total of 35 patients indicated for total disc replacement were implanted with the Charite III prosthesis. Clinical evaluation included visual analog scale (VAS) for back pain and the Oswestry disability index (ODI). Radiological parameters of intervertebral disc height (IDH), range of motion (ROM), lumbar lordosis, lumbar scoliosis and prosthesis position were evaluated. Complications and reoperation rates were also assessed. RESULTS: Thirty-two patients had a minimum 11-year follow-up, and 33 prostheses were implanted. The mean follow-up time was 11.8 years, ranging from 11.3 to 13.8 years. Twenty-eight patients (87.5 %) had a successful outcome, as defined by the FDA. Reoperation was performed in 2 patients for adjacent segment degeneration and pedicle fracture (1 case each). Both VAS and ODI scores showed significant improvement compared to baseline. At the final follow-up, the ROM of both the index- and adjacent-level showed an obvious decrease. The IDH of the index level showed a tendency to decrease, but the difference was not significant. The IDH of adjacent levels were not significantly affected by the surgery. Mean lumbar lordosis was increased at the final follow-up, and lumbar scoliosis over 3° was observed in 12 patients (37.5%), with a mean angle of 5.6° (range 3°-12°). Of all 35 prostheses, 15 were left-shifted, 3 were right-shifted and 14 were just in the middle. In the coronal plane, 25 were rated as ideally placed, 5 were discretely shifted, 4 were slightly shifted and 1 was markedly shifted. In the sagittal plane, only 12 prostheses were rated as ideally placed, 14 were discretely shifted and 9 were suboptimally placed. Prosthesis subsidence was noted in 3 (9.4%) patients (the subsidence distances were 3.1, 4.2 and 2.8 mm, respectively). Heterotopic ossification was detected in 25 segments (71.4%), consisting of Class-I heterotopic ossification in 7 segments (20.0%), Class-II in 9 segments (25.7%), and Class-III in 9 segments (25.7%). Class-IV heterotopic ossification was not observed. CONCLUSION: The cumulative survival was 100% at a mean follow-up of 11.8 years. Clinical and radiological results were satisfactory and long-term clinical results were maintained for a mean follow-up of 11.8 years. Reoperation and complication rates are acceptable, and our study does not substantiate the fear of reoperation or late complications. The results of our long-term follow-up indicate that, with strict indication, TDR is a safe and effective procedure as an alternative to lumbar fusion.
Subject(s)
Intervertebral Disc Degeneration/surgery , Intervertebral Disc/surgery , Joint Prosthesis , Lumbar Vertebrae/surgery , Total Disc Replacement/methods , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Range of Motion, Articular , Reoperation , Treatment OutcomeABSTRACT
OBJECTIVE: To observe the regulatory effect of Esculentoside A (EsA) on urination and the expression of AQP2 and AQP4 protein of kidney in water-loaded rats, and to discuss its mechanism of diuresis. METHODS: 50 male SD rats were randomly divided into five groups, including blank control group, hydrochlorothiazide group (0.4 mg/kg) and EsA high, middle and low dose groups (5.2, 2.6 and 1.3 mg/kg, respectively). After intraperitoneally injecting of different concentrations of EsA, urinary amount of model rats in continuous six hours was measured. Then the expression of AQP2 and AQP4 protein and mRNA of kidney were detected by immunohistochemistry method and Real-Time quantitative PCR. RESULTS: Compared with blank control group, the expression of AQP2 and AQP4 protein and mRNA of kidney were significantly reduced as well as the urinary amount was significantly increased in EsA high dose group (P < 0.05), while the expression of AQP2, AQP4 protein and mRNA of kidney as well as urinary amount had no obvious difference in EsA middle and low dose groups. CONCLUSION: 5.2 mg/kg of EsA can reduce the expression of AQP2 and AQP4 protein and mRNA of kidney and the reabsorption of water, which results in diuresis.
Subject(s)
Aquaporin 2/metabolism , Aquaporin 4/metabolism , Diuresis/drug effects , Kidney/drug effects , Oleanolic Acid/analogs & derivatives , Saponins/pharmacology , Animals , Male , Oleanolic Acid/pharmacology , RNA, Messenger/metabolism , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine (PPA) have various biological activities, but their properties after oral administration are not clear. In this study, the absorption, digestion and fermentation properties of PPA were studied using in vivo fluorescence tracking, in vitro simulated digestion and fecal fermentation experiments. The absorption experiment showed that fluorescence was only observed in the gastrointestinal system, indicating that PPA could not be absorbed. Simulated digestion results showed that there were no significant changes in the molecular weight, Fourier transform infrared spectroscopy (FT-IR) spectrum, monosaccharides and reducing sugar of PPA during the digestion process, showing that the overall structure of PPA was not damaged. However, the carbohydrate gel electrophoresis bands of PPA enzymatic hydrolysates after simulated digestion were significantly changed, indicating that simulated digestion might impact the configuration of PPA. In vitro fermentation showed that PPA could be degraded by microorganisms to produce short chain fatty acids, leading to a decrease in pH value. PPA can promote the proliferation of Bacteroideaceae, Megasphaera, Bacteroideaceae, and Bifidobacteriaceae, and inhibit the growth of Desulfobacteriota and Enterobacteriaceae. The results indicated that PPA could treat diseases by regulating gut microbiota, providing a scientific basis for the application and development of PPA.
Subject(s)
Digestion , Feces , Fermentation , Gastrointestinal Microbiome , Polysaccharides , Gastrointestinal Microbiome/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , Humans , Feces/microbiology , Feces/chemistry , Digestion/drug effects , Pinellia/chemistry , AnimalsABSTRACT
Thermogravimetry (TG), TG-MS, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM)-energy dispersive spectrometer(EDS) were adopted to investigate the pyrolysis characteristics of calamina. According to the findings of the qualitative and quantitative studies on the changes in the content of relevant elements, the whole shape, the functional groups, and the volatile components of calamina before and after being pyrolyzed, the 200-360, 580-750 degrees C were two sensitive temperature ranges related to the changes in effective component during calamina processing. Thermal weight loss was observed for ZnCO3, Zn(OH)2 and ZnCO3-2Zn(OH)2-H2O under 200-360 degrees C and for CaCO3 under 580-750 degrees C. The results of studies on chemical reaction kinetics showed good linear relations. This experiment integrated relevant methods and theories of physical chemistry and science of traditional Chinese medicine processing, and interpretes calamina processing techniques and mechanism, in order to provide a good example for modem studies on other traditional Chinese medicine processing.
Subject(s)
Drug Compounding/methods , Ferric Compounds/chemistry , Temperature , Zinc Oxide/chemistry , Drug Combinations , KineticsABSTRACT
OBJECTIVES: Sepsis can cause myocardial injury, which is one of the leading causes of death in critically ill patients. Fish oil rich in omega-3 polyunsaturated fatty acids (PUFAs) in ultralong chains has immunomodulatory effects and can inhibit the production of various critically ill proinflammatory cytokines. Therefore, this study focused on whether ω-3 PUFAs have a protective effect on sepsis-induced cardiomyopathy (SIC). METHODS: Male 6-8 weeks old C57BL/6 mice were pretreated with 3% special fish oil supplement rat food for seven consecutive days prior to surgery. Cecal ligation and puncture (CLP) was perfromed to induce polymicrobial sepsis.The cardiac function was assessed by echocardiography, apoptosis of cardiomyocyte were detected by TUNEL assay and Western blotting, and the level of TNF-α, IL-6, and IL-1ß in plasma was determined 24h after CLP. RESULTS: Pretreatment with omega-3 PUFAs attenuated cardiomyocyte apoptosis, decreased the production of proinflammatory cytokines, attenuated the SIC, and improved the survival rate of septic mice induced by CLP. CONCLUSIONS: ω-3 PUFAs alleviate SIC through attenuating cardiomyocyte apoptosis, which provides a new direction for the prevention and treatment of SIC.
Subject(s)
Apoptosis , Cardiomyopathies , Fatty Acids, Omega-3 , Myocytes, Cardiac , Animals , Male , Mice , Apoptosis/drug effects , Cardiomyopathies/drug therapy , Critical Illness , Cytokines , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/therapeutic use , Fish Oils/pharmacology , Fish Oils/therapeutic use , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Sepsis/complicationsABSTRACT
Most of studies relating ambient nitrogen dioxide (NO2) exposure to hospital admissions for cardiovascular diseases (CVDs) were conducted among urban population. Whether and to what extent these results could be generalizable to rural population remains unknown. We addressed this question using data from the New Rural Cooperative Medical Scheme (NRCMS) in Fuyang, Anhui, China. Daily hospital admissions for total CVDs, ischaemic heart disease, heart failure, heart rhythm disturbances, ischaemic stroke, and haemorrhagic stroke in rural regions of Fuyang, China, were extracted from NRCMS between January 2015 and June 2017. A two-stage time-series analysis method was used to assess the associations between NO2 and CVD hospital admissions and the disease burden fractions attributable to NO2. In our study period, the average number (standard deviation) of hospital admissions per day were 488.2 (117.1) for total CVDs, 179.8 (45.6) for ischaemic heart disease, 7.0 (3.3) for heart rhythm disturbances, 13.2 (7.2) for heart failure, 267.9 (67.7) for ischaemic stroke, and 20.2 (6.4) for haemorrhagic stroke. The 10-µg/m3 increase of NO2 was related to an elevated risk of 1.9% (RR: 1.019, 95% CI: 1.005 to 1.032) for hospital admissions of total CVDs at lag0-2 days, 2.1% (1.021, 1.006 to 1.036) for ischaemic heart disease, and 2.1% (1.021, 1.006 to 1.035) for ischaemic stroke, respectively, while no significant association was observed between NO2 and hospital admissions for heart rhythm disturbances, heart failure, and haemorrhagic stroke. The attributable fractions of total CVDs, ischaemic heart disease, and ischaemic stroke to NO2 were 6.52% (1.87 to 10.94%), 7.31% (2.19 to 12.17%), and 7.12% (2.14 to 11.85%), respectively. Our findings suggest that CVD burdens in rural population are also partly attributed to short-term exposure to NO2. More studies across rural regions are required to replicate our findings.
Subject(s)
Air Pollutants , Air Pollution , Brain Ischemia , Cardiovascular Diseases , Heart Failure , Hemorrhagic Stroke , Ischemic Stroke , Myocardial Ischemia , Stroke , Humans , Cardiovascular Diseases/epidemiology , Nitrogen Dioxide/analysis , Air Pollution/analysis , Brain Ischemia/epidemiology , Rural Population , Stroke/epidemiology , China/epidemiology , Myocardial Ischemia/epidemiology , Air Pollutants/analysis , Particulate Matter/analysis , Environmental Exposure/analysisABSTRACT
The effects of interactions between the toxic and essential metal mixtures on cognitive function are poorly understood. This study aims to identify the joint association of arsenic (As), cadmium (Cd), and lead (Pb) with cognitive function in older adults and the moderating role of selenium (Se), zinc (Zn), and copper (Cu) in this association. This study included 1000 community-dwelling older adults. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). Blood concentrations of As, Cd, Pb, Se, Zn, and Cu were measured using inductively coupled plasma mass spectrometry. Linear regression and Bayesian kernel machine regression (BKMR) models were applied to assess the individual and joint associations of As, Cd, and Pb with cognitive function and to examine whether Se, Zn, and Cu (individually and as a mixture) modified these associations. In the adjusted single-metal models, both Cd (ß = - 0.37, 95% CI: - 0.73 to - 0.01) and Pb (ß = - 0.44, 95% CI: - 0.86 to - 0.02) were associated with MMSE scores, while Se (ß = 0.71, 95% CI: 0.30 to 1.13) exhibited a positive relationship with MMSE scores. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the toxic metal mixture (As, Cd, and Pb) exhibited a significant negative association with MMSE scores in a dose-response pattern, with Pb being the greatest contributor within the mixture. The negative association of Pb alone or the toxic metal mixture with MMSE scores became weaker at higher concentrations of Se within its normal range, especially when Se levels were greater than the median (89.18 µg/L). Our findings support that Se can attenuate the negative associations of exposure to single Pb or the As, Cd, and Pb mixtures with cognitive function. Future prospective studies are needed to replicate our findings.
Subject(s)
Metals, Heavy , Selenium , Aged , Humans , Arsenic/toxicity , Bayes Theorem , Cadmium/toxicity , Cognition , East Asian People , Heavy Metal Poisoning , Lead/toxicity , Metals, Heavy/toxicity , Selenium/pharmacologyABSTRACT
BACKGROUND: It is known that excess reducing equivalents in the form of NADPH in chloroplasts can be transported via shuttle machineries, such as the malate-oxaloacetate (OAA) shuttle, into the mitochondria, where they are efficiently oxidised by the mitochondrial alternative oxidase (AOX) respiratory pathway. Therefore, it has been speculated that the AOX pathway may protect plants from photoinhibition, but the mechanism by which this protection occurs remains to be elucidated. RESULTS: The observation that the malate-OAA shuttle activity and the AOX pathway capacity increased markedly after intense light treatment in Rumex K-1 leaves indicates that excess NADPH was transported from the chloroplasts and oxidised by the AOX pathway. The inhibition of the AOX pathway by salicylhydroxamic acid (SHAM) caused the over-reduction of the photosystem I (PSI) acceptor side, as indicated by the increases in the extent of reduction of P700+. Furthermore, the photosynthetic linear electron flow was restricted, which was indicated by the decreases in the PSII electron transport rate (ETR) and the photosynthetic O2 evolution rate. The restriction of the photosynthetic linear electron flow, which generates the thylakoid ΔpH, inevitably decreased the de-epoxidation of the xanthophyll cycle (ΔPRI). Therefore, the induction of non-photochemical quenching (NPQ) was suppressed when the AOX pathway was inhibited. The effect of the inhibition of the AOX pathway on NPQ induction was less at 20 mM NaHCO3 than at 1 mM NaHCO3. The suppression of NPQ induction by the inhibition of the AOX pathway was also observed during the induction phase of photosynthesis. In addition, the inhibition of the AOX pathway increased the accumulation of hydrogen peroxide (H2O2), suggesting that the AOX pathway functions as an antioxidant mechanism. CONCLUSIONS: The inhibition of the AOX pathway resulted in the rapid accumulation of NADPH in the chloroplasts, which caused the over-reduction of the PSI acceptor side. Furthermore, the restriction of the photosynthetic linear electron flow due to the inhibition of the AOX pathway limited the generation of the thylakoid ΔpH and suppressed the induction of NPQ. Therefore, the mitochondrial AOX pathway protected the photosynthetic apparatus against photodamage by alleviating the over-reduction of the PSI acceptor side and accelerating the induction of NPQ in Rumex K-1 leaves.
Subject(s)
Mitochondria/enzymology , Mitochondrial Proteins/metabolism , Oxidoreductases/metabolism , Photosynthesis , Plant Leaves/radiation effects , Plant Proteins/metabolism , Rumex/enzymology , Chlorophyll/metabolism , Chloroplasts/drug effects , Chloroplasts/metabolism , Electron Transport , Enzyme Activation , Hydrogen Peroxide/metabolism , Hydrogen-Ion Concentration , Light , Malate Dehydrogenase (NADP+)/metabolism , Mitochondrial Proteins/antagonists & inhibitors , NADP/metabolism , Oxidation-Reduction , Oxidoreductases/antagonists & inhibitors , Oxygen/metabolism , Photosystem I Protein Complex/metabolism , Photosystem II Protein Complex/metabolism , Plant Leaves/drug effects , Plant Leaves/enzymology , Plant Proteins/antagonists & inhibitors , Rumex/drug effects , Rumex/radiation effects , Salicylamides/pharmacology , Sodium Bicarbonate/pharmacologyABSTRACT
OBJECTIVE: To investigate device implanted complications and corresponding therapeutic strategies of Coflex interspinous dynamic stabilization system for lumbar spine intraoperatively and postoperatively. METHODS: From September 2008 to August 2010, 133 cases of degenerative disease of lumbar spine including 62 males and 71 females, ranging from 35 to 81 years of age (mean 60.8 years), underwent or planed to be underwent decompression with Coflex interspinous dynamic stabilization system were reviewed retrospectively, and 13 cases including 6 males and 7 females, ranging from 41 to 71 years of age (mean 58.6 years), occurred device implanted complications. The Coflex implanted complications were analyzed, and therapeutic strategies according to different character were carried out, scores of visual analogue scale (VAS), Oswestry disability index(ODI) and effect-related data preoperatively, postoperatively, after conservative treatment and in final follow-up were evaluated with paired-samples t test. RESULTS: Thirteen cases of Coflex implanted complications and treatment applied included: 3 cases occurred fracture of spinous processes intraoperatively were treated by pedicle screws instead; 2 cases occurred fracture of spinous processes postoperatively or during follow-up, including 1 case underwent revision with pedicle screws, another 1 case treated with conservative treatment; 4 cases with degenerative coronal spondylolysis in surgical segments, 1 case with sagittal instability preoperatively, and 1 case with device dislodgment in follow-up all suffered aggravated pain and received conservative treatment; 1 case suffered implanted malposition intraoperatively was underwent internal fixation with pedicle screws instead; at length, 1 case with aggravated pain postoperatively and without definite reason received revision with internal fixation of pedicle screws demolishing the Coflex. The follow-up time of 13 cases ranged from 20 to 38 months (mean 27.6 months); and 7 cases implanted Coflex with aggravated pain of lumbar and lower limb, but the position of device can still maintained, were received conservative treatment, and whose score of VAS and ODI in the final follow-up were 1.9 ± 0.7 and 23.2 ± 3.4, and comparing to 6.1 ± 1.1 and 58.1 ± 3.0 preoperatively, evident improvement was got finally (t = 8.2 and 18.2, P < 0.01). Scores of VAS and ODI of 2 cases with Coflex implanted complications underwent revision with pedicle screws were also improved correspondingly. CONCLUSIONS: Coflex interspinous dynamic stabilization system implanted should be avoided to cases who suffered with osteoporosis, too narrow interspinous space and intervertebral coronal spondylolysis or sagittal instability; and choice of device, depth of implantation and intensity of clumping should be appropriate. For patients with symptom but device still in right position, conservative treatment can be carried out; but for patients subjected to malposition of device, failure of implantation intraoperatively or intolerance to device, revisions and salvages should be underwent with internal fixation of pedicle screws.
Subject(s)
Internal Fixators/adverse effects , Lumbar Vertebrae/surgery , Postoperative Complications , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Intervertebral Disc Degeneration/surgery , Male , Middle Aged , Retrospective Studies , Spinal Fusion/adverse effects , Spinal Fusion/instrumentation , Spinal Fusion/methods , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the processing mechanism of Zushima which was stir-fried with licorice. METHOD: Study of pyrolysis characteristics for extraction of Zushima effective part, petroleum ether, chloroform, ethyl acetate, n-butanol parts and the mixture of Zushima effective parts and licorice solid powder according to the proportion of 10: 1, 10: 2, 10: 3 was carried out in the thermogravimetric analyzer, the simulation of air (N2-O2 4:1) was chosen as carrier gas and heating rate was 5 degrees C x min(-1). RESULT: Compared with TG-DTG curve of Zushima effective parts, the major weightloss temperature range of petroleum ether extraction which has strong stimulation was 320-390 degrees C, 0.69% x min(-1) weightlessness rate peak gradually moved forward with the addition of licorice powder, finally it was merged with the peak around 265 degrees C. In addition, effective department of Zushima at 291, 516 degrees C for 2.38% x min(-1) and 2.42% x min(-1) thermal weightlessness rate peak shift to lower temperature, the moving range were about 20-26, 19-50 degrees C, the former was significantly reduced, the latter was significantly increased. CONCLUSION: In the course of programmed temperature heating, petroleum ether department was easy to lose with the addition oflicorice solid powder. At the same time, the main efficacy components of Zushima had a slow loss rate, which supported the processing mechanisms of TG-DTG method to research traditional Chinese medicine, and verified irritating characteristics that stimulus reduced after stir-fried with licorice.