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ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 (AMPK/PGC-1α/SIRT3) signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling, they were randomly divided into high, medium, and low dose Tangbikang granule groups (2.5, 1.25, 0.625 g·kg-1·d-1) and lipoic acid group (0.026 8 g·kg-1·d-1), and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4, 8, 12 weeks after intervention. At the 12th week, motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), nerve blood flow velocity, mechanical pain threshold, and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin (HE) staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in sciatic nerve were determined by enzyme-related immunosorbent assay (ELISA). The mRNA expressions of AMPKα, AMPKβ, PGC-1α, and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction (Real-time PCR). ResultCompared with the normal group, fasting blood glucose in the model group was increased at each time point (P<0.01). The mechanical pain threshold was decreased (P<0.05), and the incubation time of the hot plate was extended (P<0.01). MNCV, SNCV, and nerve blood flow velocity decreased (P<0.05). The expression level of SOD was decreased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were increased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were decreased (P<0.01). The structure of sciatic nerve fibers in the model group was loose, and the arrangement was disordered. The demyelination change was obvious. Compared with the model group, the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks (P<0.01). The mechanical pain threshold increased (P<0.05). The incubation time of the hot plate was shortened (P<0.01). MNCV, SNCV, and Flux increased (P<0.05). The expression level of SOD was increased (P<0.01). The expression levels of MDA, IL-1β, and TNF-α were decreased (P<0.01). The mRNA expression levels of AMPKα, AMPKβ, PGC-1α, and SIRT3 were increased (P<0.01). The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged, with only a few demyelinating changes. The high, medium, and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.
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ObjectiveTo observe the effects of the South African herb Hoodia gordonii (HG) on glucolipid metabolism in diabetic db/db mice and explore the possible mechanisms of HG on the liver of db/db mice based on the phosphoinositide-3 kinase (PI3K)/protein kinase B (Akt)/factor forkhead protein O1 (FoxO1) signaling pathway. MethodA total of 30 db/db mice were randomly divided into five groups according to fasting blood glucose: model group, metformin group (0.195 g·kg-1), and low dose (0.39 g·kg-1), medium dose (0.78 g·kg-1), and high dose (1.56 g·kg-1) HG groups, with six m/m mice in each group, and another six m/m mice were set as normal group. The mice in the normal and model groups were given saline of 9 mL·kg-1 by gavage. Body weight, water intake, and fasting blood glucose of the mice in each group were measured weekly. After six weeks of continuous administration, serum insulin (FINS), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine (CREA) were measured, and liver sections were embedded and stained with hematoxylin-eosin (HE), periodic acid-Schiff (PAS), and oil red O. Protein expression of PI3K p85, p-Akt, and p-FoxO1 in liver was detected by immunohistochemistry. The mRNA expression of PI3K, Akt, and FoxO1 in liver tissue was detected by real-time polymerase chain reaction (Real-time PCR). ResultAfter six weeks of administration intervention, it was found that fasting blood glucose was significantly downregulated in mice in the three HG groups (P<0.05). The level of islet resistance index was significantly reduced in both the low and medium dose HG groups (P<0.05). The expression levels of TC, TG, and LDL were reduced in all HG groups (P<0.05, P<0.01). Pathologically, HG could alleviate hepatocyte steatosis, reduce the volume and content of lipid droplets in liver, and increase the distribution of glycogen granules in liver to some extent in mice. Immunohistochemical assays revealed that PI3K p85 protein expression was significantly increased in the low, medium, and high dose HG groups compared with the model group (P<0.01). p-Akt protein expression was significantly increased in the medium and high dose HG groups (P<0.05, P<0.01). p-FoxO1 protein expression was significantly increased in the low, medium, and high dose HG groups (P<0.05, P<0.01). Compared with the model group, PI3K mRNA was increased in low dose, medium dose, and high dose HG groups (P<0.05), and Akt mRNA was increased in high dose HG group (P<0.05). FoxO1 mRNA was decreased in low dose, medium dose, and high dose HG groups (P<0.05). ConclusionHG can ameliorate the disorder of glucolipid metabolism in db/db mice, which may be related to its activation of the hepatic PI3K/Akt/FoxO1 signaling pathway.
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Diabetic kidney disease (DKD), a major microvascular complication of diabetes mellitus, serves as the most common cause of end-stage renal disease worldwide. The progression of DKD is closely related to oxidative stress, inflammatory response, apoptosis, and fibrosis in renal tissues activated by high glucose. Numerous studies have shown that the transduction of the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is involved in the pathological process of DKD in renal tissues, activating various pathological mechanisms, such as oxidation, inflammation, apoptosis, and fibrosis. Therefore, blocking the transduction of the p38 MAPK signaling pathway is beneficial to alleviating DKD. At present, the main treatment principles of western medicine are glucose lowering, lipid lowering, and blood pressure lowering, as well as medications with new drugs renal sodium-glucose co-transporter 2 (SGLT2), mineralocorticoid receptor, and endothelin receptor, but the progression of DKD still cannot be stopped. The treatment of DKD by traditional Chinese medicine (TCM) has the advantages of simplicity, low cost, and convenience, and the symptoms and root causes can be both treated. In recent years, the basic research on Chinese medicine intervention in DKD has greatly advanced, and p38 MAPK is the key factor of Chinese medicine intervention in DKD. The present study searched and reviewed the literature on the Chinese medicine intervention in the p38 MAPK signaling pathway in DKD treatment in the past decade. The results showed that p38 MAPK interacted with transforming growth factor-β1 (TGF-β1), cysteinyl aspartate-specific protease-3 (Caspase-3), nuclear factor-κB (NF-κB), and other factors to activate fibrosis, inflammation, oxidative stress, and apoptosis. By acting on p38 MAPK and its upstream and downstream factors, Chinese medicine blocked the pathological processes of DKD and inhibited the pathological injury of DKD and the deterioration of renal function. This study is expected to provide new ideas and directions for the prevention and treatment of DKD with Chinese medicine.
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Diabetic nephropathy (DN), the most feared microvascular complication of diabetes and one of the most common and serious complications of diabetes, is the major cause of end-stage renal disease worldwide, leading cause of morbidity and mortality in patients with diabetes, and the main non-communicable cause of death worldwide. There are many types of saponins, which are the main bioactive components of various Chinese medicinals. They have various pharmacological activities such as lowering blood glucose and blood lipids, improving insulin resistance, anti-inflammation, anti-oxidative stress, anti-tumor, and immune modulation. In recent years, it has been frequently verified that the saponins in Chinese medicinals have definite effect in regulating DN, showing multi-target, multi-pathway, multi-system, multi-effect characteristics. Thus, they have broad prospects in the prevention and treatment of this disease. There has been an explosion of research on the treatment of DN with saponins in Chinese medicinals in vivo and in vitro, but there is a lack of systematic and comprehensive summary. Therefore, this study summed up the studies of saponins in Chinese medicinals in the intervention of DN and summarized the mechanisms such as improving glucolipid metabolism, inhibiting oxidative stress, anti-inflammation, anti-apoptosis, regulating autophagy, anti-fibrosis, and protecting podocytes, with a view to providing ideas and references for the development of drugs related to DN.
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ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules(TBK) on type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats, which were then respectively treated (ig) with low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK for 12 weeks. Fasting blood glucose (FBG) and body mass were recorded every 4 weeks during the treatment. One week before sampling, the feed intake of rats was detected, and after 12 h night fasting, oral glucose tolerance test (OGTT) was performed. The area under the curve (AUC) was used to evaluate glucose tolerance, and the homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes: Fasting serum insulin (FINS), serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and nonesterified fatty acids (NEFA). The liver was weighed to calculate the liver index, and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The protein levels of insulin receptor substrate (IRS), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group (P<0.01), and the feed intake the administration groups was lower than that in the model group (P<0.05, P<0.01). At the 8th and 12th week, the body mass in the model group was lower than that in the normal group (P<0.01). Compared with the model group, TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group (P<0.01). The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group, and AUC in the administration groups was significantly different from that in the model group (P<0.01). The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group (P<0.01), and they were lower in the TBK groups than in the model group (P<0.01). Serum levels of TG, TC, HDL-C, NEFA (P<0.05, P<0.01), and LDL-C were higher in the model group than in the normal group. Serum levels of TG, TC, LDL-C, and NEFA in the TBK groups were lower than those in the model group, and the levels of TG, LDL-C, and NEFA in TBK groups were concentration-dependent (lowest levels in high-dose TBK group). Compared with the model group, high-dose TBK significantly increased the level of HDL-C (P<0.05). Liver index of the model group was higher than that in the normal group (P<0.01). The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver, the model group had unclear structure of liver lobule, enlarged cells of different sizes, and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury, particularly the high dose. For the PAS staining, compared with the normal group, the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein, p-IRS1/IRS1, and p-Akt/Akt in the model group were lower than those in the normal group (P<0.01), and they were higher in the high-dose TBK group than in the model group (P<0.01). ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.
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ObjectiveTo explore the mechanism of Tangbikang granules (TBK) against diabetic peripheral neuropathy (DPN) based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME, the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN, which were uploaded to Metascape for Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin (STZ, ip) were employed to induce diabetes in rats, and then the model rats were respectively treated with low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK for 12 weeks. Sensory nerve conduction velocity (SNCV) was evaluated. After hematoxylin and eosin (HE) staining, the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase (AMPK) pathway-related targets in rat sciatic nerve, and Western blot to measure the protein expression of AMPK and phosphorylated (p)-AMPK in rat sciatic nerve. ResultThe main active components of TBK, such as quercetin, kaempferol, β-sitosterol, leech pteridine A, stigmasterol, and baicalein were screened out, mainly acting on interleukin-6 (IL-6), tumor necrosis factor (TNF), protein kinase B (Akt), JUN, and HSP90AA1 and signaling pathways such as AMPK, nuclear factor-κB (NF-κB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT). Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6, TNF, JUN, and HSP90AA1. As for the animal experiment, compared with the normal group, model group had low SNCV of sciatic nerve (P<0.01), disordered and loose myelinated nerve fibers with axonotmesis and demyelinization, low mRNA expression of AMPKα, AMPKβ, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Sirtuin 3 (SirT3), mitochondrial transcription factor A (TFAM), and low p-AMPK/AMPK ratio in sciatic nerve (P<0.05, P<0.01). Compared with the model group, TBK of the three doses raised the SNCV (P<0.01), restored nerve morphology and nerve compactness, and increased the mRNA expression of AMPKα, AMPKβ, PGC-1α, SirT3, and TFAM (P<0.05, P<0.01). The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group (P<0.01), while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling, which lays a basis for further study of TBK in the treatment of DPN.
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ObjectiveTo explore the effect of Tangbikang granules (TBK) on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor (NF)-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin (STZ, ip) at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group, low-dose (0.625 g·kg-1), medium-dose (1.25 g·kg-1), and high-dose (2.5 g·kg-1) TBK groups, and lipoic acid group (0.026 8 g·kg-1) according to body weight and blood glucose level, and a normal group was designed. After modeling, administration began and lasted 12 weeks. The body mass, blood glucose level, and thermal withdrawal latency (TWL) of the rats were detected before treatment and at the 4th, 8th, and 12th week of administration. At the 12th week, the sciatic nerve was collected for hematoxylin-eosin (HE) and Luxol fast blue (LFB) staining, and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in sciatic nerve were measured by enzyme-linked immunosorbent assay (ELISA), and the levels of AMPK, phosphorylated (p)-AMPK, and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point (P<0.01). The levels of IL-1β, TNF-α, and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group (P<0.01), and the p-AMPK/AMPK ratio was smaller than that in the normal group (P<0.01). Compared with the model group, TBK of the three doses lowered the TWL (P<0.05, P<0.01) and the levels of IL-1β, TNF-α, and NF-κB protein in sciatic nerve of rats (P<0.05, P<0.01), and high-dose and medium-dose TBK raised p-AMPK/AMPK (P<0.05, P<0.01). The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB, thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.
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Diabetic peripheral neuropathy (DPN) is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN, one of the most common complications of diabetes mellitus, can lead to disability, foot ulcers, and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage, oxidative stress, mitochondrial disorders, and apoptosis in neural tissues. The p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is a key mechanism mediating the expression of inflammatory factors, oxidative factors, and apoptotic factors of neural tissues in DPN. The inflammatory response, oxidative stress damage, and apoptosis, induced by the activation of p38 MAPK phosphorylation by factors such as high glucose, can cause cell lipid peroxidation, protein modification, and nucleic acid damage, which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years, the research on traditional Chinese medicine (TCM) in the prevention and treatment of DPN has gradually increased, and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN, such as inflammation regulation, oxidative stress, polyol pathway regulation, and Schwann cell apoptosis in the past 10 years. In addition, the literature on Chinese medicine monomers, Chinese patent medicines, and Chinese medicine compounds in inhibiting inflammatory reactions, oxidative injury, and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway, resisting axonal degeneration and demyelination changes, improving sensory and motor abnormalities, relieving peripheral pain sensitization, and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.
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ObjectiveTo investigate the effect of Chuanshanlong granule on Toll-like receptor 4 (TLR4)/myeloid differentiation protein 88 (MyD88)/nuclear transcription factor -κB (NF-κB) signaling pathway, and to explore the mechanism of its treatment of autoimmune thyroiditis (AIT) in rats. MethodForty AIT models were established following excess iodine and injection of porcine thyroglobulin and Freund's adjuvant into Lewis rats for six weeks. Then the rats were randomly divided into the model group, Chuanshanlong granule low-, medium- and high-dose group (0.52, 1.03, 2.06 g·kg-1·d-1), with ten in each group. Rats in the Chuanshanlong granule low-, medium- and high-dose groups were separately given 0.01 mL·g-1·d-1 Chuanshanlong granule, and those in the normal group and the model group were given the same volume of deionized water for eight weeks. Serum of rats was taken to measure thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) by enzyme-linked immunosorbent assay (ELISA), and the concentrations of free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) were detected. The rat thyroid lobes were stained with hematoxylin and eosin (HE), and the pathological changes were observed under light microscope. In addition, the relative expression of TLR4, MyD88, NF-κB protein and mRNA was determined by immunohistochemistry and real-time polymerase chain reaction (Real-time PCR). ResultCompared with the conditions in the normal group, the serum concentrations of TPOAb and TgAb (P<0.01) and FT3 and FT4 (P<0.01) increased and TSH decreased (P<0.01) in the model group. Compared with the conditions in the model group, the concentrations of TPOAb and TgAb in the Chuanshanlong granule treatment groups reduced (P<0.01), and the concentrations of FT3 and FT4 were lowered (P<0.01) while TSH increased (P<0.01) in the Chuanshanlong granule high-dose group. HE staining showed that there was lymphocyte infiltration in the thyroid follicular space, a large number of destroyed or diminished follicular cavities, decreased colloid content, and thinned or destroyed follicular wall in the model group, while the thyroid lymphocyte infiltration in the Chuanshanlong granule treatment groups was significantly less and the structure of thyroid follicles was more complete than those in the model group. Compared with the normal group, the model group had up-regulated relative expression of TLR4, MyD88 and NF-κB protein (P<0.01) and mRNA (P<0.01). Compared with the model group, the Chuanshanlong granule high-dose group had down-regulated relative expression of TLR4 protein and mRNA (P<0.05), MyD88 protein (P<0.01) and mRNA (P<0.05), and NF-κB protein and mRNA (P<0.01). ConclusionChuanshanlong granule may play a therapeutic role in AIT by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway.
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Objective:To investigate the 12-lead electrocardiogram findings and their clinical significance in children with orthostatic hypertension (OHT), providing evidence for clinical diagnosis and treatment of OTH.Methods:Thirty-four children with OHT who received diagnosis and treatment in the Zhuji Second People's Hospital from January 2017 to December 2019 were included in the OHT group. An additional 34 healthy children who concurrently received routine physical examination were included in the control group. Both groups of children underwent a 12-lead electrocardiogram in lying and standing positions. The changes in ST-segment and T-wave amplitudes in the lying position relative to the standing position were compared between the two groups.Results:The changes in T-wave amplitude of leads II, V 5, and V 6 in the OHT group were (0.07 ± 0.11) mV, (0.13 ± 0.12) mV, and (0.14 ± 0.11) mV, respectively, which were significantly higher than those in the control group [(0.02 ± 0.07) mV, (0.05 ± 0.06) mV, (0.03 ± 0.04) mV, t = 2.24, 3.48, 5.48, P = 0.029, 0.001, < 0.001). There were no significant differences in the changes in T-wave amplitude of other leads between the two groups (all P > 0.05). There was no significant difference in change in ST-segment amplitude on 12-lead electrocardiogram images between the two groups (all P > 0.05). The area under the curve of the changes in T-wave amplitude of leads II and V 5 in predicting OHT in children was 0.596 and 0.672 respectively, the sensitivity was 64.71% and 55.88%, respectively, and the specificity was 70.59% and 61.76%, respectively. The changes in T-wave amplitude of leads II and V 5 had low efficacy in predicting OHT in children. The area under the curve of the change in T-wave amplitude of lead V 6 in predicting OHT in children was 0.738, and the sensitivity and specificity were 76.47% and 67.65%, respectively. The change in T-wave amplitude of lead V 6 had moderate efficacy for predicting OHT in children. Conclusion:The changes in T-wave amplitude of lead V 6 on the electrocardiogram image taken in the lying position relative to the standing position are of certain value in predicting OHT in children. The 12-lead electrocardiogram can provide important evidence for clinical prediction and diagnosis of OHT in children.
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DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires(DNA-NWs)as a polymer of DNA-triangles.Circularizing a scaffold strand(84-NT)was the critical step followed by annealing with various staple strands to make stiff DNA-triangles.Atomic force microcopy(AFM),native polyacrylamide gel electrophoresis(PAGE),UV-analysis,MTT-assay,flow cytometry,and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin(CPT)loading.The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs,with lengths ranging from 2 to 4 μm and diameters ranging from 150 to 300 nm.One sharp band at the top of the lane(500 bp level)with the loss of electrophoretic mobility during the PAGE(native)gel analysis revealed the successful fabrication of DNA-NWs.The loading efficiency of CPT ranged from 66.85%to 97.35%.MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95%concentration compared with the CPT-loaded DNA-NWs.The CPT-loaded DNA-NWs exhibited enhanced apoptosis(22%)compared to the apoptosis(7%)induced by the blank DNA-NWs.The release of CPT from the DNA-NWs was sustained at<75%for 6 h in the presence of serum,demonstrating suitability for systemic applications.The IC50 of CPT@DNA-NWs was reduced to 12.8 nM CPT,as compared with the free CPT solution exhibiting an IC50 of 51.2 nM.Confocal imaging revealed the targetability,surface binding,and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line(HepG2)compared with the control cell line.
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This study was aimed to explore the mechanism of Jia-Yan-Kang-Tai (JYKT) on Th1/Th2 immune cell imbalance in rats with autoimmune thyroiditis (AIT).A total of 40 Lewis rats were made into AIT rat model.Six week later,AIT rats were randomly divided into the model group,low-dose,middle-dose and high-dose JYKT group,with 10 rats in each group.Intragastric administration of deionized water,0.708 g· kg-1,1.417 g· kg-1 and 2.834 g· kg-1 JYKT was given to rats in each group,respectively for 8 consecutive weeks.Serum TgAb and TPOAb were detected.The ratio of Th1 cell,Th2 cell and Th1/Th2 was measured.Contents of IL-4,IL-5,IFN-γ,TNF-α and IL-1oα in plasma were detected.The pathology of thyroid tissues was observed by HE dyeing.The protein expressions of IFN-γ and IL-4 in thyroid tissues were observed under immunohistochemical staining.The results showed that high-dose JYKT group can reduce the level of TPOAb and TGAb,the incidence of thyroiditis,the ratio of Th1 cell,Th2 cell and Th1/Th2;decrease contents of IFN-γ,TNF-α,IL-1α,IL-4 and IL-5 in plasma;reduce the protein expression of IFN-γ and IL-4 in thyroid tissues.It was concluded that JYKT was able to suppress thyroid autoantibodies of AIT rats,which may be related to the regulation of cytokine level and Th 1/Th2 immune cell imbalance.
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Diabetes is the general chronic metabolic disease,with chronic hyperglycemia as the main clinical characteristic.Proteomics discusses and explores the pathogenesis of diabetes more deeply from the overall level of proteins,which has been frequently applied in Chinese medicine research.This paper summarized proteomics application in the study of Chinese medicine intervening diabetes mellitus,including screening and verification of proteomics in Chinese medicine syndromes of diabetes and its complications,as well as proteomics analysis of pharmacological mechanism of related Chinese medicine.This paper also prospected its outlook,in hope toprovide new clues and basis for the pathogenesis theory of diabetes in traditional Chinese medicine (TCM) and functioning targets,and to deepen research on Chinese medicine intervening diabetes.
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This study aimed to investigate the effects of kaempferol on the skeletal muscle of KKAy mice via PI3K-AKT-GLUT4 signaling.Spontaneous type 2 diabetic KKAy mice were made up for the model group.After 6-week treatment of kaempferol by intragastric administration,key targets of PI3K-AKT-GLUT4 signaling were detected using biochemical and immunohistochemical technique,and western blot.It was found that the body weight,fast blood glucose and random blood glucose were decreased after kaempferol administration.ITT results show that blood glucose at 30 min after injecting insulin and the area under the curve drop were reduced in the kaempferol group,and so was the insulin resistance index in the kaempferol group.In addition,the mRNA expressions of PI3K,AKT and GLUT4 in the kaempferol group increased significantly,while the protein levels of AKT and GLUT4 were up-regulated by kaempferol administration.It was concluded that kaempferol can significantly regulate the blood glucose,body weight and insulin resistance in mice through activating the PI3K-AKT-GLUT4 signaling.
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This study aimed to elucidate the mechanism behind the effects of oleuropein (OL) on improving insulin resistance in obese db/db mice.Twelve 6-to 8-week-old male db/db mice were randomly divided into the model group and the OL group with 6 in each group according to their levels of blood glucose and body weight,while six C57BL/6J mice with the same age were made up for the normal group.Mice of the OL group was intragastrically administered with (50 mg·kg-1) once a day.The mice of the other groups were treated with the saline solution with the same dosage.After treatment for four weeks,OGTT test was carried out,while fast blood glucose and serum insulin were tested.RT-PCT and western blot were used to quantify the mRNA and protein expressions of certain targets in the liver.As a result,it was found that the body weight,fast blood glucose,serum insulin level and insulin resistance index were significantly decreased in the mice of the OL group when compared with model group after the treatment for 4 weeks (P<0.05 or P<0.01).Plasma glucose levels at each time point of OGTT tests were lower in the mice of the OL group than those of the model group (P<0.01).The mRNA and protein expressions of InsR,IRS-1 and GLUT-2 in the mice of the OL group increased significantly (P<0.01).In conclusion,it was demonstrated that oleuropein may reduce the blood glucose and improve the insulin resistance in db/db mice through up-regulating the mRNA and protein expressions of InsR,IRS-1 and GLUT-2 in the liver.
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<p><b>BACKGROUND</b>Apical abscess is an inflammatory process in the peri-radicular tissues caused by biofilms in the necrotic root canal systems. Therefore, a comprehensive analysis of the bacterial colonization is required for a better understanding of the pathogenesis. This study aimed to investigate the patterns of bacterial infection of root canals of teeth with apical abscesses and to determine whether histological and microbiological findings correlated with clinical conditions.</p><p><b>METHODS</b>Eighteen samples from 18 teeth with apical pathological lesions were analyzed. Nine patients with acute apical abscesses experienced severe pain, and nine patients were asymptomatic with a sinus tract. After extraction, each affected root was divided into two halves. One half was processed for histobacteriologic analysis and examined using light microscopy, and the other half was analyzed using scanning electron microscopy (SEM) to determine the patterns of microbial colonization of the root canals.</p><p><b>RESULTS</b>The appearance of each sample subjected to SEM was consistent with the histobacteriologic findings despite the presence or absence of clinical symptoms. Intraradicular biofilms comprising cocci, rods, and/or filaments of amorphous materials were observed in the apical third of the main root canals in all samples. The bacterial biofilms covering the main root canal walls also penetrated the dentinal tubules to varying depths. The morphologies of biofilms varied, and a unique pattern of intraradicular infection was not identified.</p><p><b>CONCLUSION</b>Intraradicular infections formed complex and variable multispecies biofilms and their presence did not correlate with clinical symptoms.</p>
Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Abscesso , Microbiologia , Infecções Bacterianas , Microbiologia , Biofilmes , Cavidade Pulpar , Microbiologia , Microscopia Eletrônica de VarreduraRESUMO
<p><b>OBJECTIVE</b>To investigate the efficiency of different angle projection radiograph in diagnosing multiple canals of mandibular first premolars.</p><p><b>METHODS</b>Eighty-eight mandibular first premolars that needed endodontic treatment in vivo were selected. The radiograph was taken at a horizontal angles of 0, 20-30 degrees from mesial or distal direction of the tooth preoperative. According to the different angle projection radiographic evaluation, radiographic diagnosis of multiple canals were suspected. After the root canal orifice were detected and located with K files, the root canals were prepared using crown-down technique and obturated using cold lateral condensation technique. The configurations and numbers of root canals were identified and recorded. The postoperative radiograph was taken. According to configurations and postoperative radiograph, the root canal configuration was classified into type I -V.</p><p><b>RESULTS</b>In eighty-eight mandibular first premolars, 31 multiple canals teeth were suspected in preoperative radiographic diagnosis, 30 multiple canal teeth were detected under clinical evaluation. In case of 31 multiple canal teeth suspected by preoperative radiographic diagnosis, 3 teeth were not found multiple canals under clinical evaluation. While in case of 2 teeth of one canal suspected by preoperative radiographic diagnosis, multiple canal was detected under clinical evaluation. In 31 multiple canal teeth suspected by preoperative radiographic diagnosis, 13 teeth were detected at a horizontal angles of 0 degree and 25 teeth were detected at a horizontal angles of 20-30 degree, 7 teeth were suspected at different angle projection. Clinical detected rate of multiple canal in mandibular first premolar were 34.09% (30/88), 70.00% of which were type IV and V.</p><p><b>CONCLUSION</b>Different angulation radiograph of preoperative will assist to increase clinical detection rate of multiple canals in mandibular first premolar.</p>
Assuntos
Humanos , Dente Pré-Molar , Cavidade Pulpar , Incisivo , Mandíbula , Maxila , Dente Molar , Período Pós-Operatório , Tratamento do Canal RadicularRESUMO
Objective:To evaluate the results of repairing furcation and root perforation using Mineral Trioxide Aggregate(MTA).Methods:Cases with furcation perforations were divided into two groups randomly,MTA and IRM(control group)methods were adopted in present study.Cases that had root perforations were treated with MTA.Pretreatment,immediate posttreatment,and 1year follow-up radiographs were evaluated in a double-blind manner to determine the presence or absence of any pathologic changes adjacent to the perforation site.Results:21 cases were involved.The healing rate of furcation perforation in MTA group was higher(80%)when compared with that in IRM group(75%).However,statistical analysis showed no significant difference in success rates between both groups(P=0.722).The healing rate of root perforation using MTA was 100%.Conclusion:MTA provides an effective seal of furcation /root perforations,and promises in improving the prognosis of perforated teeth.
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Objective:To evaluate the effect of retrograde preparation by using slow-speed handpiece or by ultrasonic tips.Methods:Forty-eight extracted premolars were inspected with Scanning Electron Microscope for the minimum dentine thickness recorded after preparation of root-end cavities by low-speed handpiece and ultrasonic instrument respectively.Results:By using slow-speed handpiece,the minimum dentine thickness recorded after the preparation of root-end cavities was 0.15 mm;whereas that was 0.82 mm and 0.76 mm by ultrasonic instrument with S12 9D and S12 9 respectively(handpiece vs ultrosonic instrument,P