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Heart failure (HF) has become a major challenge in the treatment of global cardiovascular diseases. Great progress has been made in the drug treatment of HF, however, rehospitalization rate and mortality of patients with HF are still high. Hence, there is an urgent need to explore new treatment strategy and new underlying pathogenic mechanisms. In recent years, some researchers have suggested that regulation of ketone body metabolism may become a potentially promising therapeutic approach for HF. Some studies showed that the oxidative utilization of fatty acids and glucose was decreased in the failing heart, accompanied by the increase of ketone body oxidative metabolism. The enhancement of ketone body metabolism in HF is a compensatory change during HF. The failing heart preferentially uses ketone body oxidation to provide energy, which helps to improve the body's cardiac function. This review will discuss the potential significance of ketone body metabolism in the treatment of HF from three aspects: normal myocardial ketone body metabolism, the change of ketone body metabolism in HF, the effect of ketogenic therapy on HF and its treatment.
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Humans , Heart Failure/metabolism , Myocardium/metabolism , Ketone Bodies/metabolism , Cardiovascular Diseases , Fatty Acids/metabolism , Energy MetabolismABSTRACT
As the place for gas exchange, the lungs are metabolically active, and their energy consumption are essential for regulating common cell functions and maintaining the unique function of lung tissues to synthesize pulmonary surfactants. The metabolic pathways of pulmonary cells mainly include glycolysis, pentose phosphate pathway, and tricarboxylic acid cycle. Recent studies have found that changes in pulmonary cells metabolism are closely related to a variety of lung diseases. Herein, we review the main pathways of pulmonary cells metabolism and the relationship between changes in cell metabolism and the four lung diseases of chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), and pulmonary hypertension (PH), to find new ways to treat lung diseases.
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Sepsis remains a global disease with high morbidity and mortality. The changes of immune cell metabolism are of great significance in the pathophysiology of sepsis. Hypoxia-inducible factor (HIF) is not only a major regulator of hypoxic adaptive response, but also plays an important role in metabolic pathways such as glycolysis and pentose phosphate pathway of immune cells in sepsis. Current studies have found that pattern recognition receptors, transcription factors, certain metabolic byproducts and kinases all have varying degrees of influence on HIF activity or the cell metabolism involved. This review introduces the role and regulatory mechanism of HIF pathway in the metabolic changes of sepsis immune cells, so as to develop new approaches for the diagnosis and treatment of sepsis in the future.
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Immunopathogenesis of sepsis is a very complex process involving the innate immune responses mediated by mononuclear macrophages. However, the maintenance and change of macrophage function is closely associated with their immunometabolism. Macrophages take glucose oxidative phosphorylation as the main metabolic pathway under normal physiological conditions, M1 macrophages increase glucose uptake and anaerobic glycolysis, while M2 macrophages increase fatty acid uptake and oxidative phosphorylation efficiency. Recent findings showed that hypoxia-inducible factor-1α, succinate and glutamine were involved in macrophage function and metabolism regulation. Focusing on macrophages function and their immunometabolism changes in the immunopathogenesis of sepsis will make it possible to target immunometabolism as a breakthrough in the future therapy of sepsis.
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Perioperative neurocognitive disorder (PND) is one of the most common complications after operations in elderly patients. Occurrence of PND not only affects the quality of life but also increases the burden of medical care, as well as the post-operation disability and mortality rate. Previous studies have shown that the inflammatory response in central nervous system can lead to PND, however, its pathogenesis is undetermined. In this work, the role of neuro-inflammatory response and immune cell activation in the development of PND is reviewed, and the potential treatment is introduced, in order to provide insight for future research and clinical decision.
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Perioperative neurocognitive disorder (PND) is one of the most common complications after operations in elderly patients. Occurrence of PND not only affects the quality of life but also increases the burden of medical care, as well as the post-operation disability and mortality rate. Previous studies have shown that the inflammatory response in central nervous system can lead to PND, however, its pathogenesis is undetermined. In this work, the role of neuro-inflammatory response and immune cell activation in the development of PND is reviewed, and the potential treatment is introduced, in order to provide insight for future research and clinical decision.
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Immunosuppression plays a vital role in the pathophysiological mechanism of sepsis, and it is the main cause of death in patients with sepsis during the later phase. Sepsis induced immunosuppression is gradually recognized. Its underlying mechanisms involve immune cell apoptosis, autophagy, cell metabolism reprogramming, endotoxin tolerance, central nervous system regulation, and epigenetic regulation. New approaches that target the host immune response and reconstruct the immune balance are the keys to improve the prognosis of patients with sepsis. With the help of immune status monitor, novel immunomodulatory agents, such as thymosin α1, γ- interferon (IFN-γ), interleukin-7 (IL-7), granulocyte-macrophage colony stimulating factor (GM-CSF) and anti-programmed death receptor 1 (PD-1) antibody, are expected to become a new strategy for the treatment of sepsis in future.
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Objective:To prepare mesalazineβ-cyclodextrin inclusion compound and observe its properties. Methods:The struc-ture was characterized by UV, IR and DSC. The inclusion process of mesalazine andβ-cyclodextrin was simulated using molecular doc-king technique. The solubility and dissolution of inclusion compound were determined. Results:UV, IR and DSC were used to deter-mine the formation of inclusion complex. The inclusion ratio was 1: 1 and the phase solubility diagram was AL type. The solubility of inclusion compound in deionized water (25 ℃, pH 7. 0) was 7. 8 mg·ml-1 . The preparation of mesalazine β-cyclodextrin inclusion compound could significantly increase the dissolution rate and solubility of mesalazine. Conclusion:The prepared mesalazineβ-cyclo-dextrin inclusion compound can obviously improve the poor water solubility and dissolution of mesalazine.
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Intestinal disorders often co-occur with inflammation and dysmotility. However, drugs which simultaneously improve intestinal inflammation and co-occurring dysmotility are rarely reported. Atractylodin, a widely used herbal medicine, is used to treat digestive disorders. The present study was designed to characterize the effects of atractylodin on amelioration of both jejunal inflammation and the co-occurring dysmotility in both constipation-prominent (CP) and diarrhea-prominent (DP) rats. The results indicated that atractylodin reduced proinflammatory cytokines TNF-α, IL-1β, and IL-6 in the plasma and inhibited the expression of inflammatory mediators iNOS and NF-kappa B in jejunal segments in both CP and DP rats. The results indicated that atractylodin exerted stimulatory effects and inhibitory effects on the contractility of jejunal segments isolated from CP and DP rats respectively, showing a contractile-state-dependent regulation. Atractylodin-induced contractile-state-dependent regulation was also observed by using rat jejunal segments in low and high contractile states respectively (5 pairs of low/high contractile states). Atractylodin up-regulated the decreased phosphorylation of 20 kDa myosin light chain, protein contents of myosin light chain kinase (MLCK), and MLCK mRNA expression in jejunal segments of CP rats and down-regulated those increased parameters in DP rats. Taken together, atractylodin alleviated rat jejunal inflammation and exerted contractile-state-dependent regulation on the contractility of jejunal segments isolated from CP and DP rats respectively, suggesting the potential clinical implication for ameliorating intestinal inflammation and co-occurring dysmotility.
Subject(s)
Animals , Rats , Constipation , Cytokines , Diarrhea , Herbal Medicine , Inflammation , Interleukin-6 , Myosin Light Chains , Myosin-Light-Chain Kinase , NF-kappa B , Phosphorylation , Plasma , RNA, MessengerABSTRACT
Objective To establish a statistical model that can quantitatively analyze the dosimetric sparing of the bladder based on individual patient’ s anatomy in the static intensity-modulated radiotherapy (IMRT) plans for rectal cancer.Methods Static IMRT plans (7 AP fields) for 100 rectal cancer patients were used to train the model from 2012 to 2013.The anatomical features were quantitatively analyzed by the sizes of overlap regions of bladder-planning target volume (PTV) and bladder-PTV+0.5(0.5 cm margin around the PTV) .The mathematic relationship between anatomical features and dosimetric sparing of the bladder was evaluated after the bladder sparing dose was analyzed using dose-volume histogram.The established model was verified in the IMRT plans for additional 20 rectal cancer patients.Results Bladder V50 was linearly correlated with the ratio of bladder-PTV overlap size to bladder volume ( denoted as x%) , with an equation of V50=0.89x-0.99.Bladder V40 showed an approximately linear correlation with the ratio of bladder-PTV+0.5 overlap size to bladder volume (denoted as y%).The mean dose depended on both x%and y%.For the additional 20 plans, the absolute deviation between predicted and actual values for V50 and V40 were (-3.13%-3.78%) and (-5.30%-5.66%) , respectively, and the relative deviation for the mean dose was (-3.94%-3.76%) .Conclusions The model obtained in this work provides an effective method for quantitatively estimating the bladder sparing dose in IMRT plans for rectal cancer.
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Through the system of medicine centralized bidding and purchasing, it intends to solve the problems of high medicine price and drug rebate; however, it failed which was against the willing. It requires exploding regardless hospital regulation system and the current drug production and circulation system to finally stop the high medicine price and drug debate.
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Background and purpose: Recent literature has high lighted an important role of inflammation in promoting cancer. CRP (C reactive protein) is a way of building the bridge between inflammation and cancer. We aimed to explore correlations between CRP levels and clinical stages of nasopharyngeal carcinoma(NPC). Methods: We analyzed 108 cases, among which 68 cases were NPC, 20 cases were benign inflammatory diseases of nasopharynx, and another 20 were healthy volunteers as control. We detected the level of CRP using immunoturbidimetry (ITM), q test was calculated by SPSS. Results: The mean concentrations of CRP in NPC[(19.8±4.7) mg/L] were significantly increased compared to those in the control group[(6.2±1.8) mg/L], while they were significantly lower than those in benign inflammatory group[(45.6±7.9) mg/L]. In NPC, The mean concentrations of CRP in T4[(25.6±3.9) mg/L] were higher than those in T1[(17.4±5.8) mg/L], T2[(18.6±8.5) mg/L] and T3[(15.6±1.8) mg/L] respectively. The mean concentrations of CRP in N3[(28.0±7.1) mg/L] were higher than those in N0[(17.6±6.8) mg/L], N1[(21.3±5.1) mg/L] and N2[(18.6±5.6) mg/L] respectively. The mean concentrations of CRP in 1V[(25.7±5.5) mg/L] were higher than those in Ⅰ[(14.2±1.9) mg/L], Ⅱ[(16.1±3.9) mg/L] and Ⅲ[(23.0±7.7) mg/L] respectively (P<0.05). There were no statistic differences between the other groups. Conclusion: The serum CRP level is associated with the occurrence of NPC and benign inflammatory disease of nasopharynx. In NPC, the higher the CRP level is, the more advanced the TNM stage will be.
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Objective To study the diagnostic and prognostic value of procalcitonin (PCT)in patients with sepsis in early stage. Methods In the perspective study, 168 patients enrolled were classified into three groups,ncluding 31 cases in control group,37 cases in SIRS group and 100 cases in general sepsis group. The latter were com-posed of moderate sepsis sub-group with 36 cases, severe sepsis sub-group with 40 cases and septic shock sub-group with 24 cases. Indexes of inflammation, SOFA and concentration of PCT in all patients were determined and their cor-relation with sepsis prognosis was analyzed. Results The level of PCT and CRP is 3.1 ± 2.3 μg/L and 34.7 ± 28.0 mg/L in SIRS group,is 10.8 ± 8.1 μg/L and 106.8 ± 69.3 mg/L in general sepsis group respectively. Which are higher than the level of PCT (0.3 ± 0.2 μg/L )and CRP (4.1 ± 2.9 mg/L)in control group (P < 0.01 ). Higher con-centration of PCT and CRP were found in general sepsis groups than these in SIRS group. The difference is prominem.Moreover,an increasing trend of PCT with the more serious of illness was found in subgroup analysis ,but not in CRP.According to the receiver operating characteristic curves( ROC curves) ,The best cutoff values in the diagnosis of sep-sis were >4.395 μg/L for PCT,>51.8 mg/L for CRP and >4.0 for SOFA score. Condusion PCT and CRP are useful diagnostic parameters with high specificity in early sepsis. PCT combining with SOFA score can be used as ide-al quantitative index to estimate the severity of sepsis and prognosis in patients with sepsis.
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Objective To explore the role of PI3K/AKT signaling pathway in total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats.Methods This study was divided into 2 sub-projects.(1)36 rats were killed respectively at preischemia and after reperfusion,the lung tissue was then sampled.(2)12 rats were randomly divided into Wortmannin group and model control group. AKT,p-AKT protein expression,apoptotic cells and PCNA protein expression were tested respectively by Western blot,TUNEL and immunohistochemistry analysis.Results(1)Compared with that in preiscemia group,after I/R the apoptotic index (AI)was increased,the p-AKT/AKT ratio and PCNA-positive index showed bidirectional changes,and the histological changes were well identified.(2)p-AKT/AKT ratio showed a positive correlation with PCNA-positive index and a negative correlation with AI.(3)Compared with control group,the p-AKT/AKT ratio and PCNA-positive index were lower,histological changes was more significant and AI was higher in Wortmannin group. Conclusion PI3K/AKT signaling pathway had protective effect on lung injury induced by hepatic I/R,which was potentially mediated by anti-apoptosis and promoting proliferation.
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Objective:To explore total hepatic ischemia-reperfusion(I/R)-induced lung injury in rats,its related mechanism and the protective effects of melatonin on lungs.Methods: This study was divided into 2 parts.In the first part,72 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: I/R group(ischemia-reperfusion,n=36) and sham-operation group(n=36).Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes,and the occlusion was then released for reperfusion.The animals were killed at 5 minutes prior to ischemia and 0 h,0.5 h,1 h,3 h and 6 h after reperfusion in sham-operation group and I/R group(n=6 at each time point),and the lung tissue was taken.Through comparisons of these two groups,we observed the dynamic changes of lung tissue after total hepatic I/R.In the second part,12 healthy male SD rats weighing 250-300 g were randomly divided into 2 groups: melatonin group(n=6) and vehicle group(n=6).Melatonin(0.5%,10 mg/kg)or vehicle of the same volume was injected via femoral vein 15 min before ischemia and 10 min before reperfusion,the animals were killed at 1 h after reperfusion,and the lung tissue was taken.Through comparisons of these two groups,we observed the effects of melatonin.Results:(1)Total hepatic I/R led to severe histological injury in lungs.Compared with those in sham-operation group,the MDA content and apoptotic index were increased,the SOD activity was decreased,the p-ERK/ERK ratio and PCNA-positive index were decreased respectively 0 h and 0.5 h after reperfusion,and then were increased gra-dually.Histological examination revealed that the alveolar architecture was destroyed with interstitial thickening and neutrophil infiltration in I/R group.Correlate analysis revealed that p-ERK/ERK ratio showed a positive correlation with PCNA-positive index(r=0.56,P