ABSTRACT
BACKGROUND Pulmonary artery sling (PAS) is an anatomical vascular anomaly due to the origin of the left pulmonary artery from the right pulmonary artery, which runs posteriorly between the esophagus and trachea, resulting in compression of adjacent structures. Accurate evaluation for malformation of the pulmonary artery and severity of airway obstruction is essential to surgical strategy. This report presents the diagnosis and surgical management of pulmonary artery sling in a 12-year-old boy. CASE REPORT A 12-year-old boy had chest tightness and wheezing after exercise for 6 years. He was diagnosed with PSA based on findings from imaging tests, demonstrating the left pulmonary artery originated from the middle of the right pulmonary artery and the tracheal carina was located at the site of the T6 thoracic vertebra. The main bronchus and esophagus were compressed by the left pulmonary artery due to its ectopic origin. Then, after comprehensive preoperative assessment, the patient underwent surgical repair of PAS. CONCLUSIONS This report highlights the importance of pulmonary artery sling diagnosis, imaging, and surgical planning, and the role of a multidisciplinary team in preoperative and postoperative patient management. An individualized strategy based on the preoperative assessment, intraoperative coordination among cardiologists, surgeons, and perfusionists, and careful postoperative management are the core elements for successful PAS repair.
Subject(s)
Pulmonary Artery , Humans , Pulmonary Artery/abnormalities , Pulmonary Artery/surgery , Pulmonary Artery/diagnostic imaging , Male , Child , Vascular Malformations/surgery , Vascular Malformations/diagnosisABSTRACT
BACKGROUND: Henoch-Schonlein purpura is the most common vasculitis in childhood, usually triggered by an upper respiratory tract infection and rarely observed in infective endocarditis patients. Abiotrophia defectiva is a rare causative agent of infective endocarditis associated with pre-existing heart disease, immunocompromised and prosthetic valves. Dental procedures are also a common predisposing factor. CASE PRESENTATION: We present the first pediatric congenital heart disease case of infective endocarditis caused by Abiotrophia defectiva combined with recurrent Henoch-Schonlein purpura. A 10-year-old girl with uncorrected congenital heart defects and Henoch-Schonlein purpura developed a purple petechial rash again. Transthoracic echocardiography evaluation revealed multiple irregular vegetations on the right ventricular side of the ventricular septal defect and on the tricuspid valve leaflets. Blood cultures grew Abiotrophia defectiva. The girl received cardiac surgery for vegetation resection as well as congenital heart defect correction and tricuspid valve replacement. Five months after the surgery, the patient was in satisfactory condition without any signs of endocarditis or valve insufficiency and her purpuric rash disappeared. CONCLUSIONS: The coexistence of recurrent Henoch-Schonlein purpura and infective endocarditis is possible. Abiotrophia defectiva belongs to the streptococcus with a high virulence. In addition, cardiovascular surgery is often required for pediatric infective endocarditis associated with Abiotrophia defectiva, and bioprosthetic valve replacement is considered feasible for irreparable tricuspid valve in children.
Subject(s)
Endocarditis, Bacterial , Endocarditis , Exanthema , Gram-Positive Bacterial Infections , Heart Septal Defects, Ventricular , IgA Vasculitis , Humans , Child , Female , IgA Vasculitis/complications , Gram-Positive Bacterial Infections/complications , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/surgery , Endocarditis, Bacterial/diagnosis , Endocarditis/complications , Heart Septal Defects, Ventricular/surgery , Heart Septal Defects, Ventricular/complications , Exanthema/complicationsABSTRACT
Background: Tetramethylpyrazine (TMP), a potent anti-free radical and anti-inflammations substance, has been demonstrated to possess a direct vessel relaxation property. This study aimed to evaluate the effect of TMP treatment in pulmonary hypertension (PH) and test the hypothesis that TMP prevents or reverses the process of PH. Methods: Rats (n = 36) injected with 50 mg/kg of monocrotaline (MCT) subcutaneously 4 weeks to develop PH were then randomized to TMP (5 mg/kg per day) for another 4 weeks. Hemodynamics was evaluated via the right ventricle. Pulmonary vessels structural remodeling and inflammation were examined by histologic and transmission electron microscopy observation. The expression of inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinases 1 (PKG-1) was detected by immunohistochemical staining and Western blot. Generation of reactive oxygen species (ROS) and antioxidation species was measured by biochemical analyses. Results: MCT increased PH and right ventricle hypertrophy. TMP alleviated pulmonary arterial pressure elevation, leukocyte infiltration, and structural remodeling of pulmonary arterials induced by MCT successfully. TMP treatment significantly increased the PKG-1 expression and suppressed the iNOS expression. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT) was significantly higher than control group, while malondialdehyde (MDA) levels were lower compared with MCT group. Conclusion: TMP can suppress established MCT-induced PH through the ROS/iNOS/PKG axis. The underlying mechanisms may be associated with its anti-inflammatory, antioxidant, and antiproliferative properties in pulmonary arterial.
Subject(s)
Hypertension, Pulmonary , Monocrotaline , Animals , Rats , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/metabolism , Monocrotaline/adverse effects , Nitric Oxide Synthase Type II/metabolism , Protein Kinases/metabolism , Pyrazines , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
To analyze the effects of sodium hyaluronate combined with recombinant human epidermal growth factor (rhEGF) eye drops in patients with dry eye. Totally 97 patients who suffered dry eye after cataract surgery in our hospital from March 2018 to June 2020 were selected and randomly assigned into control group (n=57, sodium hyaluronate eye drops) and intervention group (n=63, sodium hyaluronate combined with rhEGF eye drops). The clinical efficacy, Break Up Time (BUT), schirmer I test (SLt), fluorescent test (FL) and ocular surface disease index (OSDI), the scale of quality of life for disease with visual impairment (SQOL-DVI), interleukin-6 (IL-6), tumor necrosis factor (TNF-a) level of the two groups were compared. The intervention group yielded remarkably higher effective rate than the control group (p<0.05). Markedly higher BUT, SLt, SQOL-DVI scores and lower OSDI scores were witnessed among patients in the intervention group than the control group (p<0.05). The clinical effect of sodium hyaluronate combined with rhEGF eye drops in the treatment of dry eye is superior to sodium hyaluronate alone, in terms of enhancing the stability of tear film, accelerating corneal healing, inhibiting the level of inflammatory factors and improving patients' quality of life.
Subject(s)
Dry Eye Syndromes/drug therapy , Epidermal Growth Factor/administration & dosage , Hyaluronic Acid/administration & dosage , Administration, Ophthalmic , Adult , Aged , Cataract Extraction/adverse effects , China , Drug Combinations , Dry Eye Syndromes/diagnosis , Dry Eye Syndromes/etiology , Dry Eye Syndromes/physiopathology , Epidermal Growth Factor/adverse effects , Female , Humans , Hyaluronic Acid/adverse effects , Male , Middle Aged , Ophthalmic Solutions , Prospective Studies , Quality of Life , Recombinant Proteins/administration & dosage , Recovery of Function , Time Factors , Treatment OutcomeABSTRACT
Aquaporin 1 (AQP1) is one member of the aquaporin family, also the deeply studied one. It is widely located on the endothelial cells, but the effect of AQP1 on the peritoneal mesothelial cells (PMCs) after long-term peritoneal dialysis (PD) has not been reported before. We divided normal mice into two groups, control group and dialysis group, to confirm the fibrotic changes and expression of APQ1 on peritoneal mesothelial cells. Then we assigned normal mice and AQP1 knockout mice into four groups: Control group, normal dialysis group, AQP1 knockout control group and AQP1 knockout dialysis group. The two dialysis groups received 4.25% glucose dialysis for 28 days. We found that mice in both dialysis groups showed peritoneal fibrotic changes, which were most severe in the AQP1 knockout dialysis group; the peritoneal thickness in the AQP1 knockout dialysis group was also thicker than that in the dialysis group (P < .05). We used electron microscopy to detect ultrastructural changes and observed changes in microvilli and vacuolar degeneration in mesothelial cells from all groups except the control group. The basement membranes were damaged in the AQP1 knockout dialysis group, and peritoneal mesothelial cells were disrupted and detached in this group. Together our findings indicate that AQP1 plays an important role in maintaining the physiological functions of peritoneal mesothelial cells, and AQP1 can protect mesothelial cells during dialysis.
Subject(s)
Aquaporin 1/metabolism , Endothelial Cells/metabolism , Peritoneal Dialysis , Peritoneum/cytology , Animals , Disease Models, Animal , Endothelial Cells/ultrastructure , Mice , Mice, Knockout , Microscopy, Electron , Microscopy, FluorescenceABSTRACT
[This corrects the article DOI: 10.1155/2019/7850863.].
ABSTRACT
E3 ubiquitin ligase gene, WWP2, is associated with acute kidney injury (AKI). This research was conducted to explore the role of WWP2 in AKI. AKI cell model was produced in human renal proximal tubular epithelial cell line (HK-2) by ischemia-reperfusion (IR) injury. CCK8 and flow cytometry assay were performed to explore the influence of WWP2 overexpression on cell proliferation and apoptosis of IR-induced HK-2 cells. Quantitative real-time PCR and immunoblotting (IB) were performed to assess the gene and protein expression. Then, the influence of WWP2 on p53 ubiquitylation and degradation was estimated by immunoprecipitation assay. Our data indicated that WWP2 was down-regulated and p53 was up-regulated in IR-induced HK-2 cells. WWP2 overexpression promoted proliferation and inhibited apoptosis of IR-induced HK-2 cells. And WWP2 interacted with p53 and regulated p53 ubiquitylation and degradation. Furthermore, the influence of WWP2 on cell proliferation and apoptosis was rescued by MG132 (proteasome inhibitor) treatment. In conclusion, our work described for the first time the role of WWP2 in AKI, showing that WWP2 ameliorated AKI by mediating p53 ubiquitylation and degradation. Moreover, the study offers some important insights into the occurrence of AKI and WWP2 may be a novel target of AKI treatment. SIGNIFICANCE OF THE STUDY: Our data elaborates that WWP2 has protective effect against AKI by mediating p53 ubiquitylation and degradation. Thus, WWP2 might be a therapeutic target for AKI.
Subject(s)
Acute Kidney Injury/metabolism , Apoptosis , Kidney Tubules/metabolism , Tumor Suppressor Protein p53/metabolism , Ubiquitin-Protein Ligases/physiology , Ubiquitination , Cell Line , Cell Proliferation , Cell Survival , Flow Cytometry , HEK293 Cells , Humans , Leupeptins/pharmacology , Real-Time Polymerase Chain Reaction , Reperfusion InjuryABSTRACT
Cordyceps militaris may show good promise in protecting against chronic kidney disease (CKD) but the molecular mechanism remains unclear. CKD risk is associated with the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Cordycepin is the main component of Cordyceps militaris and may affect the TLR4/NF-κB pathway. Cordycepin was prepared by preparative HPLC. CKD patients were assigned into Cordyceps militaris (COG, 100 mg daily) and placebo (CG) groups. Cordycepin activity was measured using human embryo kidney cells (HEK293T). Biochemical indices, the levels of TLR4, NF-κB, cyclooxygenase-2 (COX2), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß), were measured by real-time qRT-PCR, or ELISA kits and or Western blot. After 3-month treatment, cordycepin reduced the levels of urinal protein, blood urea nitrogen (BUN), and creatinine by 36.7%±8.6%, 12.5%±3.2%, and 18.3%±6.6%, respectively (P < 0.05). Cordyceps militaris improved lipid profile and redox capacity of CKD patients by reducing the serum levels of TG, TC, and LDL-C by 12.8%±3.6%, 15.7%±4.1%, and 16.5%±4.4% and increasing the HDL-C level by 10.1%±1.4% in the COG group when compared with the CG group, respectively (P < 0.05). The serum levels of cystatin-C (Cys-C), myeloperoxidase (MPO), and malondialdehyde (MDA) were reduced by 14.0%±3.8%, 26.9%±12.3%, and 19.7%±7.9% while nitric oxide (NO) and superoxide dismutase (SOD) were increased by 12.5%±2.9% and 25.3%±13.4% in the COG group when compared with the CG group, respectively (P < 0.05). Cordycepin reduced the levels of TLR4, NF-κB, COX2, TNF-α, and IL-1ß in HEK293T cells too (P < 0.05). However, cordycepin could not affect the levels anymore if TLR4 was silenced. Cordyceps militaris protected against CKD progression by affecting the TLR4/NF-κB lipid and redox signaling pathway via cordycepin.
Subject(s)
Deoxyadenosines/administration & dosage , NF-kappa B/metabolism , Renal Insufficiency, Chronic/drug therapy , Signal Transduction/drug effects , Toll-Like Receptor 4/metabolism , Adult , Cordyceps , Deoxyadenosines/chemistry , Female , HEK293 Cells , Humans , Interleukin-1beta/blood , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/pathology , Tumor Necrosis Factor-alpha/bloodABSTRACT
@#Objective To investigate the association of preoperative serum uric acid (UA) levels with postoperative prolonged mechanical ventilation (PMV) in patients undergoing mechanical heart valve replacement. Methods Clinical data of 311 patients undergoing mechanical heart valve replacement in The First Affiliated Hospital of Anhui Medical University from January 2017 to December 2017 were retrospectively analyzed. There were 164 males at age of 55.6±11.4 years and 147 females at age of 54.2±9.8 years. The patients were divided into a PMV group (>48 h) and a control group according to whether the duration of PMV was longer than 48 hours. Spearman's rank correlation coefficient and logistic regression analysis were conducted to evaluate the relationship between preoperative UA and postoperative PMV. The predictive value of UA for PMV was undertaken using the receiver operating characteristic (ROC) curve.. Results Among 311 patients, 38 (12.2%) developed postoperative PMV. Preoperative serum UA level mean values were 6.11±1.94 mg/dl, while the mean UA concentration in the PMV group was significantly higher than that in the control group (7.48±2.24 mg/dl vs. 5.92±1.82 mg/dl, P<0.001). Rank correlation analysis showed that UA was positively correlated with postoperative PMV (rs=0.205, P<0.001). Multivariate logistic regression analysis demonstrated that preoperative elevated UA was associated independently with postoperative PMV with odds ratio (OR)=1.44 and confidence interval (CI) 1.15–1.81 (P=0.002). The area under the ROC curve of UA predicting PMV was 0.72, 95% CI0.635–0.806, 6.40 mg/dl was the optimal cut-off value, and the sensitivity and specificity was 76.3% and 63.0% at this time, respectively. Conclusion Preoperative elevated serum UA is an independent risk factor for postoperative PMV in patients undergoing mechanical heart valve replacement and has a good predictive value.
ABSTRACT
BACKGROUND: Development of novel therapeutic strategies that specifically target diabetic kidney disease (DKD) is urgently needed. METHODS: Male KKAy mice were divided randomly into three equal groups - KK, KI, and KF; Male C57BL/6 mice were the control group. All KKAy mice were fed a high-fat diet. From the 16th week, the KI group was given IFN-γ, and the KF group was assigned to be treated with fludarabine. C57BL/6 mice were always fed a normal mouse diet. Every 4 weeks, body weight, random blood sugar, urine albumin and urea of all mice were measured. At the 20th week, all mice were killed, renal tissue was obtained to observe the pathological manifestations and extract proteins, and transforming growth factor- beta1 (TGF-ß1), collagen IV and Janus kinase 2/signal transducers and activators of transcription 1 (JAK2/STAT1) pathway proteins were measured by western blot. RESULTS: The present study showed that all KKAy mice appeared obese and hyperglycaemic from 12 weeks old and exhibited an increased urine albumin-to-creatinine ratio (ACR) from 16 weeks old. At the 20th week, compared to the KK group, the KI group showed lower ACR, more overexpression of P-STAT1 and less expression of TGF-ß1 and collagen IV proteins in renal tissue. The KI group mice showed less accumulation of glomerular mesangial matrix than those in the KK group. CONCLUSIONS: Our results indicate that IFN-γ might activate STAT1 to suppress the overexpression of TGF-ß1 and collagen IV proteins and attenuate the excessive accumulation of mesangial matrix under DKD conditions in KKAy mice.
Subject(s)
Diabetic Nephropathies/drug therapy , Interferon-gamma/pharmacology , Kidney/drug effects , Animals , Diabetic Nephropathies/metabolism , Disease Models, Animal , Glomerular Mesangium/metabolism , Janus Kinase 2/metabolism , Kidney/metabolism , Kidney Glomerulus/drug effects , Kidney Glomerulus/metabolism , Male , Mice , Mice, Inbred C57BL , STAT1 Transcription Factor/metabolism , Signal Transduction/drug effects , Transforming Growth Factor beta1/metabolismABSTRACT
This paper deals with the problems of cancer classification and grouped gene selection. The weighted gene co-expression network on cancer microarray data is employed to identify modules corresponding to biological pathways, based on which a strategy of dividing genes into groups is presented. Using the conditional mutual information within each divided group, an integrated criterion is proposed and the data-driven weights are constructed. They are shown with the ability to evaluate both the individual gene significance and the influence to improve correlation of all the other pairwise genes in each group. Furthermore, an adaptive sparse group lasso is proposed, by which an improved blockwise descent algorithm is developed. The results on four cancer data sets demonstrate that the proposed adaptive sparse group lasso can effectively perform classification and grouped gene selection.
Subject(s)
Computational Biology/methods , Gene Expression Profiling/methods , Gene Regulatory Networks/genetics , Neoplasms/genetics , Algorithms , Humans , Neoplasms/metabolismABSTRACT
Oxidative stress contributes to the pathogenesis of diabetic nephropathy (DN). Nuclear factor erythroid 2-related factor 2 (NRF2) plays a key role in cellular defense against oxidative stress. NRF2 activators have shown promising preventive effects on DN. Sodium butyrate (NaB) is a known activator of NRF2. However, it is unknown whether NRF2 is required for NaB protection against DN. Therefore, streptozotocin-induced diabetic C57BL/6 Nrf2 knockout and their wild-type mice were treated in the presence or absence of NaB for 20 weeks. Diabetic mice, but not NaB-treated diabetic mice, developed significant renal oxidative damage, inflammation, apoptosis, fibrosis, pathological changes and albuminuria. NaB inhibited histone deacetylase (HDAC) activity and elevated the expression of Nrf2 and its downstream targets heme oxygenase 1 and NAD(P)H dehydrogenase quinone 1. Notably, deletion of the Nrf2 gene completely abolished NaB activation of NRF2 signaling and protection against diabetes-induced renal injury. Interestingly, the expression of Kelch-like ECH-associated protein 1, the negative regulator of NRF2, was not altered by NaB under both diabetic and non-diabetic conditions. Moreover, NRF2 nuclear translocation was not promoted by NaB. Therefore, the present study indicates, for the first time, that NRF2 plays a key role in NaB protection against DN. Other findings suggest that NaB may activate Nrf2 at the transcriptional level, possibly by the inhibition of HDAC activity.
Subject(s)
Butyric Acid/therapeutic use , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/drug therapy , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases/metabolism , NF-E2-Related Factor 2/metabolism , Animals , Apoptosis/drug effects , Butyric Acid/pharmacology , Diabetic Nephropathies/metabolism , Histone Deacetylase Inhibitors/pharmacology , Kidney/drug effects , Mice , Oxidative Stress/drug effects , Signal Transduction/drug effectsABSTRACT
OBJECTIVE: To validate a visual ability instrument for school-aged children with visual impairment in China by translating, culturally adopting and Rasch scaling the Cardiff Visual Ability Questionnaire for Children (CVAQC). METHODS: The 25-item CVAQC was translated into Mandarin using a standard protocol. The translated version (CVAQC-CN) was subjected to cognitive testing to ensure a proper cultural adaptation of its content. Then, the CVAQC-CN was interviewer-administered to 114 school-aged children and young people with visual impairment. Rasch analysis was carried out to assess its psychometric properties. The correlation between the CVAQC-CN visual ability scores and clinical measure of vision (visual acuity; VA and contrast sensitivity, CS) were assessed using Spearman's r. RESULTS: Based on cultural adaptation exercise, cognitive testing, missing data and Rasch metrics-based iterative item removal, three items were removed from the original 25. The 22-item CVAQC-CN demonstrated excellent measurement precision (person separation index, 3.08), content validity (item separation, 10.09) and item reliability (0.99). Moreover, the CVAQC-CN was unidimensional and had no item bias. The person-item map indicated good targeting of item difficulty to person ability. The CVAQC-CN had moderate correlations between CS (-0.53, p<0.00001) and VA (0.726, p<0.00001), respectively, indicating its validity. CONCLUSIONS: The 22-item CVAQC-CN is a psychometrically robust and valid instrument to measure visual ability in children with visual impairment in China. The instrument can be used as a clinical and research outcome measure to assess the change in visual ability after low vision rehabilitation intervention.
Subject(s)
Vision, Low/diagnosis , Adolescent , Child , China , Disability Evaluation , Humans , Prevalence , Reproducibility of Results , Sickness Impact Profile , Visual Acuity , Visually Impaired PersonsABSTRACT
OBJECTIVE: To investigate the protective effects of high-dose ulinastatin on the vital organs in patients undergoing total arch replacement for type A aortic dissection. METHODS: Between September 2014 and March 2016, 66 patients with type A aortic dissection underwent total arch replacement at our center. Thirty-six of the patients received ulinastatin treatment at 300 000 U/8 h from admission to 3 days postoperatively and at 300 000 U/2 h during cardiopulmonary bypass surgery (UTI group), and the other 30 patients did not receive perioperative ulinastatin treatment (control group). The surgical data and blood biochemistry profiles on days 1, 3, and 5 postoperatively were compared between the two groups, and the postoperative ICU stay, re-operation for bleeding, ventilation for over 7 days, ultrafiltration for postoperative renal failure, tracheotomy, incidences of pulmonary and neurological complications and hospital death were also compared. RESULTS: s The operating time, cardiopulmonary bypass time, ACP time, cardiac arrest time, the lowest rectal temperature and frequency of bilateral and unilateral antegrade selective cerebral perfusion were similar between the two groups (P>0.05). Compared with those in the control group, patients in UTI group had lower lactate, S-100 and neuron specific enolase levels on the first postoperative day and higher OI on the 1st, 3rd, and 5th postoperative days (P<0.05), but serum creatinine, blood urea nitrogen, total bilirubin, and alanine aminotransferase levels were comparable between the two groups (P>0.05). No significant differences were found in the frequency of re-operation for bleeding, ultrafiltration for renal failure, tracheotomy, neurological complications or hospital death after the operation between the two groups, but the patients in UTI group had a shorter ICU time, a less frequent long-term ventilation and a lower incidence of pulmonary infection (P<0.05). CONCLUSION: High-dose ulinastatin offers protection on pulmonary function and lowers the specific brain injury markers in patients with type A aortic dissection after total arch replacement, but its protective effects on brain is uncertain.
Subject(s)
Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Glycoproteins/therapeutic use , Protective Agents/therapeutic use , Aorta, Thoracic/surgery , Body Temperature , Brain/drug effects , Cardiopulmonary Bypass , Cerebrovascular Circulation , Humans , Incidence , Lactic Acid/blood , Lung/drug effects , Perfusion , Phosphopyruvate Hydratase/blood , Postoperative Period , S100 Proteins/blood , Time FactorsABSTRACT
Heat stress (HS) is commonly used to refer to the heat load that an individual is subjected to due to either metabolic heat, or environmental factors, including high temperatures and high humidity levels. HS has been reported to affect and even damage the functioning of various organs; overexposure to high temperatures and high humidity may lead to accidental deaths. It has been suggested that the cardiovascular system is primarily targeted by exposure to HS conditions; the HS-induced dysfunction of cardiomyocytes, which is characterized by mitochondrial dysfunction, may result in the development of cardiovascular diseases. The excessive production of reactive oxygen species (ROS) also participates in mitochondrial dysfunction. However, effective methods for the prevention and treatment of mitochondrial and cardiovascular dysfunction induced by exposure to HS are lacking. In the present study, we hypothesized that vitamin E (VE), an antioxidant, is capable of preventing oxidative stress and mitochondrial injury in cardiomyocytes induced by exposure to HS. The results revealed that pretreatment with VE increased the expression of metallothionein (MT), which has previously been reported to confer cytoprotective effects, particularly on the cardiovascular system. Pre-treatment with VE restored mitochondrial function in cardiomyocytes under conditions of HS by increasing the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), and by increasing adenosine triphosphate (ATP) levels. Furthermore, pre-treatment with VE decreased the production of ROS, which was induced by exposure to HS and thus exerted antioxidant effects. In addition, pre-treatment with VE attenuated oxidative stress induced by exposure to HS, as demonstrated by the increased levels of antioxidant enzymes [superoxide dismutase (SOD) and glutathione (GSH)], and by the decreased levels of markers of oxidative injury [malondialdehyde (MDA) and lactate dehydrogenase (LDH)]. Taken together, these findings suggest that pre-treatment with VE can prevent mitochondrial dysfunction and oxidative stress in cardiomyocytes induced by exposure to HS, by increasing the expression of MT.
Subject(s)
Gene Expression Regulation/drug effects , Heat-Shock Response/genetics , Metallothionein/genetics , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Protective Agents/pharmacology , Vitamin E/pharmacology , Adenosine Triphosphate/metabolism , Animals , Antioxidants/metabolism , Disease Models, Animal , Heat Stress Disorders/genetics , Heat Stress Disorders/metabolism , Metallothionein/metabolism , Mice , Mitochondria, Heart/drug effects , Mitochondria, Heart/metabolism , Oxidative Stress , Reactive Oxygen SpeciesABSTRACT
Diabetic nephropathy (DN) is the most serious chronic complications of diabetes; 20-40% of diabetic patients develop into end stage renal disease (ESRD). However, exact pathogenesis of DN is not fully clear and we have great difficulties in curing DN; poor treatment of DN led to high chances of mortality worldwide. A lot of western medicines such as ACEI and ARB have been demonstrated to protect renal function of DN but are not enough to delay or retard the progression of DN; therefore, exploring exact and feasible drug is current research hotspot in medicine. Traditional Chinese medicine (TCM) has been widely used to treat and control diabetes and its complications such as DN in a lot of scientific researches, which will give insights into the mechanism of DN, but they are not enough to reveal all the details. In this paper, we summarize the applications of herbal TCM preparations, single herbal TCM, and/or monomers from herbal TCM in the treatment of DN in the recent 10 years, depicting the renal protective effects and the corresponding mechanism, through which we shed light on the renal protective roles of TCM in DN with a particular focus on the molecular basis of the effect and provide a beneficial supplement to the drug therapy for DN.
Subject(s)
Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal/therapeutic use , Medicine, Chinese Traditional , Phytotherapy , Humans , Treatment OutcomeABSTRACT
OBJECTIVE: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a persistent elevation of pulmonary artery pressure and ventricular hypertrophy. Tetrandrine is a bisbenzylisoquinoline alkaloid that can decrease blood pressure, inhibit the proliferation of vascular smooth muscle cells, and block cardiac hypertrophy, but whether it has a therapeutic effect on PAH remains poorly defined. This study was undertaken to investigate the efficacy of tetrandrine on PAH. METHODS: Forty-eight male Sprague-Dawley rats were randomly and equally divided into four groups. The control group was injected with normal saline; the others were injected with monocrotaline (MCT) to induce PAH, then treated with saline, tetrandrine, and vardenafil, respectively, from day 21 to day 42. On day 43, we measured the mean pulmonary artery pressure under general anesthesia, dissected the rat, and calculated the right ventricular hypertrophy index [right ventricle/(left ventricle plus septum)]. Later we observed the changes in the pulmonary vascular wall; measured the expression of cyclic guanosine monophosphate-dependent protein kinase type 1 and inducible nitric oxide synthase; measured the levels of superoxide dismutase, glutathione, malondialdehyde, and catalase; and then compared the results among groups. RESULTS: Compared with the MCT group, rats treated with tetrandrine had attenuated mean pulmonary artery pressure (20.48 ± 1.49 vs 30.07 ± 1.51; P < .01) and right ventricular hypertrophy index (49.19 ± 2.45 vs 68.50 ± 1.95; P < .01), inhibited proliferation of pulmonary artery smooth muscle cells, and improved endothelial function. Tetrandrine also upregulated the expression of protein kinase type 1 (90.86 ± 1.95 vs 67.34 ± 1.50; P < .01); downregulated the expression of inducible nitric oxide synthase (74.76 ± 1.48 vs 80.19 ± 0.28; P < .01); increased levels of superoxide dismutase (245.54 ± 12.98 vs 166.16 ± 21.42; P < .01), glutathione (0.699 ± 0.032 vs 0.514 ± 0.056; P < .01), and catalase (32.13 ± 2.33 vs 27.19 ± 2.72; P < .01); and decreased malondialdehyde (1.027 ± 0.039 vs 1.462 ± 0.055; P < .01). CONCLUSIONS: Tetrandrine alleviated MCT-induced PAH through regulation of nitric oxide signaling pathway and antioxidant and antiproliferation effects.
Subject(s)
Antihypertensive Agents/pharmacology , Arterial Pressure/drug effects , Benzylisoquinolines/pharmacology , Cyclic GMP-Dependent Protein Kinase Type I/metabolism , Hypertension, Pulmonary/prevention & control , Monocrotaline , Nitric Oxide Synthase Type II/metabolism , Pulmonary Artery/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Catalase/metabolism , Cell Proliferation/drug effects , Disease Models, Animal , Glutathione/metabolism , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/enzymology , Hypertension, Pulmonary/physiopathology , Hypertrophy, Right Ventricular/chemically induced , Hypertrophy, Right Ventricular/enzymology , Hypertrophy, Right Ventricular/physiopathology , Hypertrophy, Right Ventricular/prevention & control , Male , Malondialdehyde/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/enzymology , Muscle, Smooth, Vascular/physiopathology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/enzymology , Oxidative Stress/drug effects , Pulmonary Artery/enzymology , Pulmonary Artery/physiopathology , Rats, Sprague-Dawley , Signal Transduction/drug effects , Superoxide Dismutase/metabolism , Time Factors , Vascular Remodeling/drug effects , Ventricular Remodeling/drug effectsABSTRACT
Exposure to humid heat stress leads to the initiation of serious physiological dysfunction that may result in heat-related diseases, including heat stroke, heat cramp, heat exhaustion, and even death. Increasing evidences have shown that the humid heat stress-induced dysfunction of the cardiovascular system was accompanied with severe cardiomyocyte injury; however, the precise mechanism of heat stress-induced injury of cardiomyocyte remains unknown. In the present study, we hypothesized that humid heat stress promoted oxidative stress through the activation of angiotensin II (Ang II) in cardiomyocytes. To test our hypothesis, we established mouse models of humid heat stress. Using the animal models, we found that Ang II levels in serum were significantly up-regulated and that the Ang II receptor AT1 was increased in cardiomyocytes. The antioxidant ability in plasma and heart tissues which was detected by the ferric reducing/antioxidant power assay was also decreased with the increased ROS production under humid heat stress, as was the expression of antioxidant genes (SOD2, HO-1, GPx). Furthermore, we demonstrated that the Ang II receptor antagonist, valsartan, effectively relieved oxidative stress, blocked Ang II signaling pathway and suppressed cardiomyocyte apoptosis induced by humid heat stress. In addition, overexpression of antioxidant genes reversed cardiomyocyte apoptosis induced by Ang II. Overall, these results implied that humid heat stress increased oxidative stress and caused apoptosis of cardiomyocytes through the Ang II signaling pathway. Thus, targeting the Ang II signaling pathway may provide a promising approach for the prevention and treatment of cardiovascular diseases caused by humid heat stress.
Subject(s)
Angiotensin II/metabolism , Apoptosis , Heat Stress Disorders/metabolism , Hot Temperature , Humidity , Myocytes, Cardiac/metabolism , Oxidative Stress , Signal Transduction , Angiotensin II/blood , Angiotensin II Type 1 Receptor Blockers/pharmacology , Animals , Antioxidants/metabolism , Antioxidants/pharmacology , Apoptosis/drug effects , Disease Models, Animal , Female , HEK293 Cells , Heat Stress Disorders/drug therapy , Heat Stress Disorders/etiology , Heat Stress Disorders/pathology , Humans , Male , Mice, Inbred C57BL , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Receptor, Angiotensin, Type 1/metabolism , Signal Transduction/drug effects , Time Factors , Valsartan/pharmacologyABSTRACT
In our previous study, we demonstrated that Xuebijing (XBJ), a traditional Chinese medicine, attenuates hypotension in rats suffering from heatstroke (HS). However, the underlying mechanisms have not yet been fully elucidated. Thus, the current study was carried out to investigate the mechanisms underlying the effects of XBJ on hypotension n rats suffering from HS. For this purpose, 72 anesthetized rats were randomized into 3 groups and intravenously injected twice daily for 3 days with XBJ (4 ml/kg body weight, XBJ group) or phosphatebuffered saline (PBS) (HS and sham-operated groups). Models of HS were established in the HS and XBJ groups by placing the rats in a simulated climate chamber with a temperature of 40ËC and a humidity of 60%. Rectal temperature, arterial pressure and heart rate were monitored and recorded. Angiotensin â ¡ (Ang â ¡) levels were increased during HS (shown by ELISA), and XBJ had no apparent effect on Ang â ¡ levels. The levels of Ang â ¡ type 1 (AT1) receptor surface expression and AT1 receptor-associated protein 1 (Arap1) were decreased during HS; however, these effects were attenuated by pre-treatment with XBJ (shown by RT-qPCR and western blot analysis). For in vitro experiments, rat macrophages pre-treated with XBJ were stimulated with lipopolysaccharide (LPS). Pre-treatment with XBJ induced a marked inhibitory effect on the release of pro-inflammatory cytokines in the LPS-stimulated macrophages. Furthermore, XBJ inhibited the activation of nuclear factor κB (NF-κB) induced by LPS in the macrophages. Taken together, our data demonstrate that XBJ promotes Arap1 expression by inhibiting the activation of the NF-κB signaling pathway and the release of pro-inflammatory cytokines, which may be the molecular mechanisms through which XBJ alleviates blood pressure reduction in rats suffering from HS.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Drugs, Chinese Herbal/pharmacology , Heat Stroke/prevention & control , Hypotension/prevention & control , Up-Regulation/drug effects , Adaptor Proteins, Signal Transducing/genetics , Angiopoietin-Like Protein 2 , Angiopoietin-like Proteins , Angiotensin II/blood , Angiotensin II/metabolism , Animals , Blotting, Western , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Cytokines/metabolism , Gene Expression/drug effects , Heat Stroke/genetics , Heat Stroke/metabolism , Hypotension/genetics , Hypotension/metabolism , Inflammation Mediators/metabolism , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Male , NF-kappa B/metabolism , Phytotherapy , Rats, Wistar , Receptor, Angiotensin, Type 1/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effectsABSTRACT
High glucose (HG) has been reported to be associated with renal dysfunction. And one potential mechanism underlining the dysfunction is the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Present study showed that EMT was induced in the HG-treated renal tubular epithelial cells by promoting the expression of mesenchymal phenotype molecules, such as α-SMA and collagen I, and down-regulating the expression of epithelial phenotype molecule E-cadherin. Moreover, we have identified the down-regulation of miR-15a which was accompanied with the HG-induced EMT. And the miR-15a overexpression inhibited the α-SMA, collagen I expression, and the promotion of E-cadherin expression by targeting and down-regulating AP4 which was also significantly promoted by the HG in the renal tubular epithelial cells. Thus, this study revealed that the weakening regulation on the AP4 expression by miR-15a might contribute to the HG-induced EMT in the renal tubular epithelial cells.