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AIM: Surgery for congenital scoliosis correction in children is often associated with considerable blood loss. Decrease in regional oxygen saturation (rScO2) can reflect insufficient cerebral perfusion and predict neurological complications. This retrospective observational study explored the relationship between blood loss during this surgery and a decrease in rScO2 in children. METHODS: The following clinical data of children aged 3-14 years who underwent elective posterior scoliosis correction between March 2019 and July 2021 were collected: age, sex, height, weight, baseline rScO2, basal mean invasive arterial pressure (MAP), preoperative Cobb angle, number of surgical segments, preoperative and postoperative haemoglobin level, percentage of lowest rScO2 below the baseline value that lasted 3 min or more during the operation (decline of rScO2 from baseline, D-rScO2%), intraoperative average invasive MAP, end-tidal carbon dioxide pressure, fluid infusion rate of crystalloids and colloids, operation time, and percentage of total blood loss/patient's blood volume (TBL/PBV). RESULTS: A total of 105 children were included in the study. Massive haemorrhage (TBL/PBV ≥50%) was reported in 53.3% of patients, who had significantly higher D-rScO2 (%) (t = -5.264, P < 0.001) than those who had non-massive haemorrhage (TBL/PBV <50%). Multiple regression analysis revealed that TBL/PBV (ß = 0.04, 95% CI: 0.018-0.062, P < 0.05) was significantly associated with D-rScO2%. CONCLUSIONS: Intraoperative massive blood loss in children significantly increased D-rScO2%. Monitoring should be improved, and timely blood supplementation should be performed to ensure maintenance of the blood and oxygen supply to vital organs, improve the safety of anaesthesia, and avoid neurological complications.
Subject(s)
Blood Loss, Surgical , Scoliosis , Humans , Child , Retrospective Studies , Scoliosis/surgery , Female , Male , Adolescent , Child, Preschool , Blood Loss, Surgical/prevention & control , Oxygen Saturation , Cerebrovascular Circulation/physiologyABSTRACT
Discoidin, CUB, LCCL domain-containing 2 (DCBLD2) is a type I transmembrane protein with a similar structure to neuropilin, which acts as a co-receptor for certain receptor tyrosine kinases (RTKs). The insulin receptor is an RTK and plays a critical role in endothelial cell function and glycolysis. However, how and whether DCBLD2 regulates insulin receptor activity in endothelial cells is poorly understood. Diabetes was induced through treatment of Dcbld2 global-genome knockout mice and endothelium-specific knockout mice with streptozotocin. Vascular ultrasound, vascular tension test, and hematoxylin and eosin staining were performed to assess endothelial function and aortic remodeling. Glycolytic rate assays, real-time PCR and western blotting were used to investigate the effects of DCBLD2 on glycolytic activity and insulin receptor (InsR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in endothelial cells. Co-immunoprecipitation was used to assess the effects of DCBLD2 on insulin receptor endocytosis and recycling. Membrane and cytoplasmic proteins were isolated to determine whether DCBLD2 could affect the localization of the insulin receptor. We found that Dcbld2 deletion exacerbated endothelial dysfunction and vascular remodeling in diabetic mice. Both Dcbld2 knockdown and Dcbld2 deletion inhibited glycolysis and the InsR/PI3K/Akt signaling pathway in endothelial cells. Furthermore, Dcbld2 deletion inhibited insulin receptor recycling. Taken together, Dcbld2 deficiency exacerbated diabetic endothelial dysfunction and vascular remodeling by inhibiting the InsR/PI3K/Akt pathway in endothelial cells through the inhibition of Rab11-dependent insulin receptor recycling. Our data suggest that DCBLD2 is a potential therapeutic target for diabetes and cardiovascular diseases.
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Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.
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Zoysia japonica (Zoysia japonica Steud.) is a kind of warm-season turfgrass with many excellent characteristics. However, the shorter green period and longer dormancy caused by cold stress in late autumn and winter are the most limiting factors affecting its application. A previous transcriptome analysis revealed that ethephon regulated genes in chlorophyll metabolism in Zoysia japonica under cold stress. Further experimental data are necessary to understand the effect and underlying mechanism of ethephon in regulating the cold tolerance of Zoysia japonica. The aim of this study was to evaluate the effects of ethephon by measuring the enzyme activity, intermediates content, and gene expression related to ethylene biosynthesis, signaling, and chlorophyll metabolism. In addition, the ethylene production rate, chlorophyll content, and chlorophyll a/b ratio were analyzed. The results showed that ethephon application in a proper concentration inhibited endogenous ethylene biosynthesis, but eventually promoted the ethylene production rate due to its ethylene-releasing nature. Ethephon could promote chlorophyll content and improve plant growth in Zoysia japonica under cold-stressed conditions. In conclusion, ethephon plays a positive role in releasing ethylene and maintaining the chlorophyll content in Zoysia japonica both under non-stressed and cold-stressed conditions.
Subject(s)
Ethylenes , Organophosphorus Compounds , Poaceae , Chlorophyll A/metabolism , Poaceae/genetics , Ethylenes/metabolism , Chlorophyll/metabolismABSTRACT
Despite the significant success of decarboxylative radical reactions, the catalytic systems vary considerably upon different radical acceptors, requiring renewed case-by-case reaction optimization. Herein, we developed an iron catalytic condition that enables the highly efficient decarboxylation of various carboxylic acids for a range of radical transformations. This operationally simple protocol was amenable to a wide array of radical acceptors, delivering structurally diverse oxime ethers, alkenylation, alkynylation, thiolation, and amidation products in useful to excellent yields (>40 examples, up to 95% yield).
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BACKGROUND: This meta-analysis aimed to evaluate the difference in postoperative complications as urethrocutaneous fistula or glans dehiscence, in children undergoing primary hypospadias repair with caudal block (CB) versus non-caudal block (NCB). METHODS: Data were obtained from MEDLINE, Embase, Web of Science, and the Cochrane Library. Comparative studies of CB versus NCB were identified, with reports of complications published or presented until October 2022. Subgroup analyses were performed based on study type, meatal location (distal only), type of NCB, surgeon and technique, and concentration and dose of anesthetics. RESULTS: Compared to the reference group of NCB, CB was not significantly associated with the development of complications following primary hypospadias repair (OR 1.40, 95 % CI 0.88-2.23). After adjusting for confounding factors, such as type of study(OR 1.51, 95%CI: 0.29-7.91), type of NCB[PB (OR 1.82, 95 % CI: 0.87-3.84), GA (OR 1.26, 95 % CI: 0.39-4.04)], meatal location (distal only) (OR 1.22, 95 % CI: 0.61-2.43), surgeon and technique (OR 1.37, 95 % CI: 0.59-3.14) and concentration and dose of anesthetics(OR 2.74, 95 % CI: 0.82-9.20), subgroup analyses revealed no significant association between CB and NCB (P > 0.05). DISCUSSION: Previous studies have found a correlation between CB and increased incidence of postoperative complications (urethrocutaneous fistula or glans dehiscence) of hypospadias, but different literature have suggested that surgical technique, surgical duration and the severity of hypospadias, rather than CB, are closely related to the occurrence of complications. In order to reduce confounding factors, subgroup analyses were conducted. The results showed that no correlation could be found in postoperative complications and CB. CONCLUSIONS: This meta-analysis compared the incidence of urethrocutaneous fistula or glans dehiscence in the CB and NCB groups for primary hypospadias repair in children, indicating that no clear correlation could be found in postoperative complications and CB. Subgroup analyses on study type, type of NCB, meatal location (distal only), surgeon and technique, and regional anesthetic concentration and dose supported this conclusion.
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Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multiorgan failure. Health care advances have improved outcomes in critical illness, but it still remains the leading cause of death. Septic cardiomyopathy is heart dysfunction brought on by sepsis. Septic cardiomyopathy is a common consequence of sepsis and has a mortality rate of up to 70%. There is a lack of understanding of septic cardiomyopathy pathogenesis; knowledge of its pathogenesis and the identification of potential therapeutic targets may reduce the mortality rate of patients with sepsis and lead to clinical improvements. The present review aimed to summarize advances in the pathogenesis of cardiac dysfunction in sepsis, with a focus on mitochondrial dysfunction, metabolic changes and cell death modalities and pathways. The present review summarized diagnostic criteria and outlook for sepsis treatment, with the goal of identifying appropriate treatment methods for this disease.
Subject(s)
Cardiomyopathies , Heart Diseases , Sepsis , Humans , Sepsis/metabolism , Cardiomyopathies/metabolism , Multiple Organ Failure/complicationsABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and its incidence continues to increase each year. Yet, there is still no definitive drug that can stop its development. This review focuses mainly on lipotoxicity, oxidative stress, inflammation, and intestinal flora dysbiosis to understand NAFLD's pathogenesis. In this review, we used NCBI's PubMed database for retrieval, integrating in vivo and in vitro experiments to reveal the therapeutic effects of natural compounds on NAFLD. We also reviewed the mechanisms by which the results of these experiments suggest that these compounds can protect the liver from damage by modulating inflammation, reducing oxidative stress, decreasing insulin resistance and lipid accumulation in the liver, and interacting with the intestinal microflora. The natural compounds discussed in these papers target a variety of pathways, such as the AMPK pathway and the TGF-ß pathway, and have significant therapeutic effects. This review aims to provide new possible therapeutic lead compounds and references for the development of novel medications and the clinical treatment of NAFLD. It offers fresh perspectives on the development of natural compounds in preventing and treating NAFLD.
Subject(s)
Insulin Resistance , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/metabolism , Liver , Inflammation/metabolism , Oxidative StressABSTRACT
BACKGROUND: It is believed that negative postoperative behavioral changes (NPOBC) is associated with negative perioperative outcomes in children. The importance of development of a predictive model of NPOBC was noted. This study aims to identify potential risk factors develop a nomogram to predict NPOBC on postoperative day 3 based on a prospective cohort. METHODS: A prospective observational study was conducted on children(American Society of Anesthesiologists I ~ III) aged 2 ~ 12 years who underwent selective surgery under general anesthesia between September 2022 and February 2023. The patient's clinical data were analyzed. The method of measuring NPOBC is with the The Posthospital Behaviour Questionnaire (PHBQ), and all of children remained hospitalized at the time of assessment. The enrolled patients were categorized into the NPOBC group and the non-NPOBC group according to if children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop the nomogram to predict NPOBC. Internal validation was performed using the parametric bootstrapping method. RESULTS: One hundred ninety-two patients were enrolled in the study, 44.8% (86/192 patients) of children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analysis demonstrated that the Pediatric Anesthesia Behavior (PAB) score (OR: 1.23, 95%CI: 1.14-1.33), cerebral desaturation (OR: 1.16, 95%CI: 1.02-1.32), and postoperative pain score (OR: 1.07, 95%CI: 1.02-1.13) were independent predictors for NPOBC on postoperative day 3 (P < 0.05). They were used to develop the prediction model. The calibration curve demonstrated satisfied discrimination and calibration of the prediction model. The model presented with good discriminative ability (area under the receiver operating characteristic curve: 0.762 [95%CI: 0.691-0.833]). The decision curve analysis also revealed the great clinical utility of the nomogram. CONCLUSION: Based on our prospective observational study, pre-anesthesia patients with higher PAB scores, presence of cerebral desaturation, and higher postoperative pain score were more likely to develop NPOBC on postoperative day 3. We established and validated a nomogram for predicting NPOBC, which could help assess patients individually, identify high-risk groups of NPOBC and improve patient prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-2,200,059,776. Registered 11 May 2022.
Subject(s)
Anesthesia, General , Nomograms , Child , Humans , Anesthesia, General/adverse effects , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Prognosis , Prospective Studies , Retrospective StudiesABSTRACT
Objectives: To assess whether decreased regional cerebral oxygen saturation (rScO2) is associated with the emergence delirium (ED) following general anesthesia in the pediatric population. Methods: A retrospective observational cohort study was conducted on 113 children (ASA I-III) aged 2-14 years who underwent selective surgery under general anesthesia between 2022-01 and 2022-04. Intraoperatively, the rScO2 was monitored using a cerebral oximeter. The Pediatric Anesthesia Emergence Delirium (PAED) score was used to evaluate the patients for ED. Results: The incidence of ED was 31%. Low rScO2 was reported in 41.6% of patients, who had a higher incidence of ED (P < 0.001) than those who did not experience desaturation. Logistic regression analysis revealed that decreased rScO2 was significantly associated with incident ED events [odds ratio (OR), 10.77; 95% confidence interval, 3.31-35.05]. Children under 3 years of age had a higher incidence of ED after rScO2 desaturation during anesthesia compared to older children (OR, 14.17 vs. 4.64). Conclusion: Intraoperative rScO2 desaturation significantly increased the incidence of ED following general anesthesia. Monitoring should be enhanced to improve the oxygen balance in vital organs to improve the quality and safety of anesthesia.
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Immunotherapy of PD-L1/PD-1 blockage elicited impressive clinical benefits for cancer treatment. However, the relative low response and therapy resistance highlight the need to better understand the molecular regulation of PD-L1 in tumors. Here, we report that PD-L1 is a target of UFMylation. UFMylation of PD-L1 destabilizes PD-L1 by synergizing its ubiquitination. Inhibition of PD-L1 UFMylation via silencing of UFL1 or Ubiquitin-fold modifier 1 (UFM1), or the defective UFMylation of PD-L1, stabilizes the PD-L1 in multiple human and murine cancer cells, and undermines antitumor immunity in vitro and mice, respectively. Clinically, UFL1 expression was decreased in multiple cancers and lower expression of UFL1 negatively correlated with the response of anti-PD1 therapy in melanoma patients. Moreover, we identified a covalent inhibitor of UFSP2 that promoted the UFMylation activity and contributed to the combination therapy with PD-1 blockade. Our findings identified a previously unrecognized regulator of PD-L1 and highlighted UFMylation as a potential therapeutic target.
Subject(s)
B7-H1 Antigen , Melanoma , Humans , Animals , Mice , Tumor Escape , Programmed Cell Death 1 Receptor/genetics , Ubiquitination , Cysteine EndopeptidasesABSTRACT
Objective: To explore the effective response strategies for infections in infants with short bowel syndrome and solid abdominal tumours, treated with totally implantable venous access ports (TIVAPs). Methods: A total of 210 children who were treated with a TIVAP in our department from 2020 to 2021 were selected for this retrospective study. Eight of these children diagnosed with a catheter-related bloodstream infection were studied in this study; antibiotic lock therapy (ALT) and cluster nursing management were used for treatment, and their effects on the infection outcome were observed. Results: Among the eight children, seven access ports were successfully protected, and one catheter was removed from the right chest wall port due to repeated infection. In this one child, the left side was re-implanted. Conclusion: The use of the ALT combined with cluster-based nursing can better treat infections of TIVAPs, improve the children's healing time, and has important clinical significance in the prevention of complications from the infection and improving the treatment and nursing of the patients diagnosed with these infections.
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An unprecedented DMAP-catalysed amidation of aryl and alkyl carboxylic acids with organo-cyanamides has been developed. Unlike the use of N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as an electrophilic cyanating reagent, an unusual desulfonylation/decyanation reaction model has been disclosed for the first time. Remarkable features of this reaction include readily available substrates, simple operation and broad scope, enabling the efficient synthesis of structurally diverse amides. The synthetic utility of this protocol was demonstrated by the late-stage amidation of bioactive carboxylic acids and a scale-up reaction.
Subject(s)
Carboxylic Acids , Cyanamide , Indicators and Reagents , Molecular Structure , AmidesABSTRACT
Two new prenylated flavonoid glycosides (1-2), together with five known compounds (3-7) were isolated from the EtOAc-soluble extract of the stems of Celastrus orbiculatus. The structures of new compounds were elucidated with spectroscopic and physico-chemical analyses. All isolates were evaluated for in vitro cytotoxic activities against HepG2, MCF-7, A549, and A2780 cancer cells. Among them, compound 1 showed potential antiproliferative activity on A2780 cells with IC50 value of 10.76 µM. In addition, compound 2 exhibited selective cytotoxic activity on A2780 cells with IC50 value of 26.30 µM.
Subject(s)
Antineoplastic Agents , Celastrus , Ovarian Neoplasms , Female , Humans , Celastrus/chemistry , Cell Line, Tumor , Glycosides/pharmacology , Flavonoids/pharmacology , Molecular StructureABSTRACT
Sepsis is a serious complication of infection, and its further development may lead to multi-organ dysfunction syndrome. Sepsis cardiomyopathy is a common complication of sepsis and has been directly linked to high mortality. Although the pathogenesis of septic cardiomyopathy is not fully understood, in-depth study of the pathogenesis of septic cardiomyopathy and the identification of its potential therapeutic targets may reduce mortality in patients with sepsis. Ferroptosis is an iron-dependent mode of cell death that has been shown to be involved in the pathophysiological mechanisms of many diseases. Some related studies have reported that ferroptosis may be a potential mechanism of septic cardiomyopathy. This review provides new insights into the mechanisms of mitochondrial dysfunction, lipid peroxidation, xc-system, glutathione peroxidase 4 (GPX4), iron metabolism and the role of ferroptosiswith septic cardiomyopathy for further research and treatment of septic cardiomyopathy.
Subject(s)
Cardiomyopathies , HumansABSTRACT
Background: Previous studies of the relationship of regional cerebral oxygen saturation (rScO2) and postoperative pulmonary complications (PPCs) in pediatric patients are not well established, and further investigation is warranted. The aim of this prospective study was to determine whether a decrease in intraoperative rScO2 is associated with PPCs in children undergoing thoracoscopic surgery requiring one-lung ventilation (OLV). Methods: One hundred and six children of ages 3 months to 8 years who received one-lung ventilation were enrolled in the study. Upon entering the operating room, regional cerebral oxygen saturation was continuously monitored bilaterally by near-infrared spectroscopy. Patients were divided into low rScO2 (L-rScO2) or high rScO2 (H- rScO2) groups according to whether the lowest intraoperative rScO2 value was 15% lower than the baseline value. Outcome is defined as PPCs occurring within 7 days after surgery. Results: After propensity score matching, 23 pediatric patients with decreased rScO2 and 46 pediatric patients without a decrease in rScO2 were included in this study. According to logistic regression analysis, patients in the H- rScO2 group were less likely to have PPCs than those in the L-rScO2 group (OR = 3.16; 95% CI = 1.05-9.5; P = 0.04). Moreover, intraoperative rScO2 reduction was associated with an increase in the severity of PPCs (OR = 3.90; 95% CI = 1.19-12.80; P = 0.025). Conclusions: The decrease in regional cerebral oxygen saturation during surgery increases the likelihood of postoperative pulmonary complications.
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Background: BIS-guided total intravenous anesthesia (TIVA) is widely used in children, but few studies have attempted to evaluation of the effect of BIS-guided TIVA in younger children. This study aimed to evaluate the effect of bispectral index (BIS) guidance during TIVA in younger children during anesthesia. Methods: This study is a prospective, randomized, single-blind and controlled clinical trial. This study enrolled pediatric patients (aged 1-3 years) who were scheduled for surgery under TIVA with propofol and remifentanil. The children were randomly assigned to the BIS group (group B) and standard clinical practice group (group S). The BIS values in group B were maintained at 45-60. The anesthesiologist controlled the depth of anesthesia in group S according to the variation in the clinical signs of the children. The time of extubation, duration of stay in post-anesthesia care unit (PACU), as well as BIS values, heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation at eight time points 1 min before induction (T1), 1 min after induction (1 min after the induction drugs were administrated) (T2), immediately after intubation (T3), immediately after skin incision (T4), 30 min after the start of the operation (T5), 60 min after the start of operation (T6), immediately after drug withdrawal (T7), and immediately after extubation (T8), propofol consumption, and postoperative adverse reactions were recorded. Results: There was no significant difference in time to extubation 15(10,21) vs 14 (11,20) and duration of stay in PACU 27 (20,37) vs. 29 (22,39) between the group B and group S. At the time points 30 min after the start of the operation, 60 min after the start of operation and immediately after drug withdrawal, the BIS values in group S were significantly higher than those in group B (57 ± 9, 57 ± 9, 60 ± 8 vs 52 ± 7, 54 ± 7, 57 ± 6). Conclusions: The use of BIS-guided total intravenous anesthesia in younger children does not shorten the time of extubation and the duration of stay in the PACU. Trial registration: Chictr.org.cn identifier: 24/11/2017, ChiCTR-IOR-17013530.
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Non-alcoholic fatty liver disease (NAFLD) is one of the most serious global public health concerns. However, there are currently no effective drugs for treatment of this disease. Icariin (ICA), a small-molecule natural product extracted from Epimedium brevicornu Maxim, offers various pharmacological activities. In the present work, we wondered whether ICA can attenuate NAFLD in db/db mice treated with ICA for 8 weeks and how ICA exerts an influence on NAFLD. In db/db mice, ICA treatment had a robust effect on inhibition of lipogenesis associated with NAFLD amelioration by decreasing liver lipid deposition, together with ameliorating insulin sensitivity, glucose tolerance, and fasting serum glucose. Of note, ICA-treated rats showed a much higher concentration of icaritin (ICT) in plasma, a major metabolite of ICA, about 2000 times higher than that of ICA by liquid chromatography mass spectrometry (LC-MS). Interestingly, ICT, rather than ICA, can dramatically decrease hepatic lipogenesis-related markers in oleate acid/palmitate acid (OA/PA)-induced steatosis in primary hepatocytes (PH) and HepG2 cells, and hepatic lipid accumulation in db/db mice, demonstrating the inhibitory effect of ICT on lipogenesis. Mechanistically, we found that anti-lipogenic activities of ICT were related to reducing endoplasmic reticulum (ER) stress as evidenced by Western blot, qPCR, and other assays in thapsigargin (THP) induced-ER stress models. To our knowledge, this is the first report showing the unexpected and key role for ICT on the prevention of NAFLD in db/db mice through an ER stress mechanism.
Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Rats , Animals , Humans , Non-alcoholic Fatty Liver Disease/metabolism , Lipogenesis , Lipid Metabolism , Hep G2 Cells , Glucose/adverse effects , LipidsABSTRACT
Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and its prevalence is still growing rapidly. However, the efficient therapies for this kidney disease are still limited. The pathogenesis of DKD involves glucotoxicity, lipotoxicity, inflammation, oxidative stress, and renal fibrosis. Glucotoxicity and lipotoxicity can cause oxidative stress, which can lead to inflammation and aggravate renal fibrosis. In this review, we have focused on in vitro and in vivo experiments to investigate the mechanistic pathways by which natural compounds exert their effects against the progression of DKD. The accumulated and collected data revealed that some natural compounds could regulate inflammation, oxidative stress, renal fibrosis, and activate autophagy, thereby protecting the kidney. The main pathways targeted by these reviewed compounds include the Nrf2 signaling pathway, NF-κB signaling pathway, TGF-ß signaling pathway, NLRP3 inflammasome, autophagy, glycolipid metabolism and ER stress. This review presented an updated overview of the potential benefits of these natural compounds for the prevention and treatment of DKD progression, aimed to provide new potential therapeutic lead compounds and references for the innovative drug development and clinical treatment of DKD.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Diabetes Mellitus/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/prevention & control , Fibrosis , Glycolipids/pharmacology , Humans , Inflammasomes/metabolism , Inflammation/metabolism , Kidney , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Transforming Growth Factor beta/metabolismABSTRACT
Buyang Huanwu Decoction (BHD) has lipid-lowering and antioxidant effects. In this study, HPLC was used to establish the fingerprint of extracts from different polar parts of BHD. Through the L02 cell lipid deposition model induced by oleic acid, extracts from different polar parts of BHD were administered for treatment. Oil red O staining, TG detection, and MDA detection were used to determine lipid deposition and antioxidant activity. The component-effect relationship is established by using grey relational analysis and PLSR analysis. The results showed that the extracts from different polar parts of BHD could reduce the levels of TG and MDA. The grey relational analysis showed that the peaks that contributed greatly to the reduction of TG and MDA were peaks 3, 16, 14, 10, 1, 15, 2, and 11, respectively. Peaks 1, 4, 9, 10, 14, 16, and 17 could reduce TG and MDA through PLSR analysis. According to the results of grey relational analysis and PLSR analysis, peaks 1, 10, 14, and 16 may have good lipid-lowering and antioxidant effects. This study provides a certain preliminary basis for follow-up research on lipid-lowering drugs.