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1.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1011465

RESUMO

Insulin resistance (IR) is an important pathological and physiological mechanism of type 2 diabetes (T2DM), and the treatment of IR has become the key to the prevention and treatment of T2DM. IR is a state of insensitivity or reduced sensitivity of insulin-stimulated tissue cells to glucose, resulting in cells that are unable to efficiently take up glucose in the bloodstream and thus causing hyperglycemia. Adenosine monophosphate-activated protein kinase (AMPK) is an energy-sensing enzyme that can regulate multiple metabolic pathways and maintain the stability of adenosine triphosphate (ATP) in the cell. In recent years, traditional Chinese medicine (TCM) has played an increasingly important role in the prevention and treatment of T2DM. The research on exploring the AMPK signaling pathway of TCM intervention in the progress of T2DM has gradually increased. Many pharmacological studies have shown that TCM has advantages such as safety and high efficiency in the prevention and treatment of T2DM. AMPK signaling pathway is one of the key pathways for the active ingredients of TCM and TCM extracts to improve IR. Active ingredients such as phenols, flavonoids, polysaccharides, alkaloids, and saponins, as well as other herbal extracts can improve IR by activating the AMPK signaling pathway cascade response, thereby improving IR by regulating glucolipid metabolism, inhibiting inflammatory response, anti-oxidative stress and maintaining mitochondrial homeostasis. Based on this, this paper reviews the pharmacological and experimental research results of TCM intervening the AMPK signaling pathway to improve IR in recent years, expecting to provide reference for further research, development and application of TCM in intervening IR and treating T2DM.

2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1006268

RESUMO

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.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-953948

RESUMO

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.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1014601

RESUMO

AIM: To study the effects of augmented renal clearance (ARC) on vancomycin pharmacokinetics, efficacy, and safety in patients with infective endocarditis, so as to provide better guidance for vancomycin medication. METHODS: The retrospective analysis was conducted. Patients data from the hospital medical record system from April 2020 to April 2023 during the cardiovascular surgery with use of vancomycin were collected. The subjects were divided into normal group and ARC group according to glomerular filtration rate (eGFR). According to the population pharmacokinetic model, the measured trough concentration was used for a Bayesian approach to estimate individual pharmacokinetic parameters and analyze influence of ARC on vancomycin pharmacokinetics. RESULTS: A total of 163 patients were included in this study. The incidence of ARC was 23.31%. The age of patients in ARC group was significantly lower than that in normal group (P<0.05). Moreover, the steady-state trough concentration (Cmin), trough concentration compliance rate, area under the curve (AUC), and elimination half life (t1/2) were significantly lower in ARC group than that in normal group (P<0.05). In addition, ARC group had significantly higher clearance (CL) and elimination rate than normal group (P<0.05). Correlation analysis showed that Cmin was positively correlated with AUC (r

5.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-965653

RESUMO

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.

6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973770

RESUMO

Diabetic nephropathy (DN) is a serious complication of diabetes, a major risk factor for chronic renal failure and end-stage renal disease, a major cause of deaths of diabetic patients, and a major cause of noncommunicable disease-associated deaths in the world. Pyroptosis and inflammasome activation are closely associated with the occurrence and development of DN. They can mediate a variety of pathological changes such as the loss and fusion of podocytes, up-regulated expression of inflammatory cytokines, macrophage infiltration, glomerular mesangial matrix expansion, and increased urinary albumin-to-creatinine ratio, eventually leading to nephron loss and kidney injury. The available studies have reported that the active ingredients in Chinese medicinal herbs or classical prescriptions play a role in the treatment of DN by lowering blood glucose and lipid levels, mitigating insulin resistance, reducing inflammation, alleviating oxidative stress, and regulating immunity. Moreover, the active ingredients can inhibit the activation of inflammasomes and the pyroptosis of renal cells, repair the inflammation-induced damage, improve renal function, and slow the progression of DN, demonstrating definite therapeutic effect. Chinese medicines can treat DN in a multi-target, multi-pathway, and multi-system manner, possessing broad prospects in the prevention and treatment of DN. Despite the extensive studies about the traditional Chinese medicine (TCM) intervention of DN in vivo and in vitro, a comprehensive summary of experimental studies on the TCM intervention of DN model remains to be carried out. This paper reviews the research progress in pyroptosis, inflammasomes, roles of pyroptosis and inflammasomes in DN, and TCM intervention of DN, aiming to provide ideas and reference for the research and development of drugs for this disease.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-973133

RESUMO

ObjectiveTo investigate the effect of Loulianwan on the gut microbiota of db/db mice with type 2 diabetes mellitus (T2DM). MethodMale db/m+ mice aged 4-5 weeks were assigned to the normal group, and male db/db model mice of the same age were randomly divided into model group, metformin group (0.25 g·kg-1·d-1), and Loulianwan group (13 g·kg-1·d-1), with six mice in each group. Drug intervention lasted five weeks. The body weight, water intake, and fasting blood glucose (FBG) of the mice were recorded every week. After five weeks, the FBG, liver triglyceride (TG), liver total cholesterol (TC), glycated serum protein (GSP), and fasting serum insulin (FINS) were detected, and the insulin resistance index (HOMA-IR) was calculated. The feces in the mouse intestines were collected, and the 16S rRNA sequencing technology was used to detect the structural changes in the fecal gut microbiota of mice in each group. ResultCompared with the normal group, the model group showed increased body weight, water intake, FBG, liver TG, liver TC, GSP, FINS, and HOMA-IR (P<0.01). Compared with the model group, the Loulianwan group showed reduced water intake, FBG, liver TG, liver TC, GSP, FINS, and HOMA-IR (P<0.01). The gut microbiota in the Loulian Lills group changed from phylum to genus level. The relative abundance of beneficial bacteria increased and the relative abundance of harmful bacteria decreased. Among them, the abundance of Akkermansia muciniphila, Blautia, Ruminococcus, and Parabacteroides increased (P<0.01). ConclusionLoulianwan can significantly improve glucose and lipid metabolism in db/db mice with T2DM, and its mechanism may be related to the increase in the abundance of Akkermansia muciniphila, Blautia, Ruminococcus, and Parabacteroides in the intestine.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-972309

RESUMO

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance, hyperinsulinemia, and disturbance of glucose and lipid metabolism, with elevated blood glucose as the main clinical manifestation. Due to its complex etiology and pathogenesis, there is no effective treatment, which critically threatens human health and places a heavy burden on society and families. Saponins are a class of glycosides with complex structures that have the advantage of a wide range of sources, elevated safety, and low adverse effects. As an essential active ingredient in Chinese medicine, Chinese medicine saponins have a variety of biological activities such as hypoglycemia, hypoglycaemia, anti-inflammation, antioxidation, anti-tumor, and immune modulation. In recent years, numerous studies have shown that Chinese medicine saponins are effective in preventing and treating T2DM. Although there have been numerous studies on the hypoglycemic effects and mechanisms of Chinese medicine saponins, there has been no systematic review of the mechanisms of Chinese medicine saponins in the treatment of T2DM. Therefore, to provide a theoretical basis for an in-depth study of the hypoglycemic effects of Chinese medicine saponins and a scientific basis for the development and clinical application of drugs, this paper systematically summarized the hypoglycemic mechanisms of Chinese medicine saponins, such as improving islet β-cell function, improving insulin resistance, inhibiting glycosidase activity, reducing the inflammatory response, anti-oxidative stress, and regulating intestinal flora, and analyzed the current research problems and development trends.

9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-972303

RESUMO

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.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-979467

RESUMO

Zishenwan, also known as Tongguanwan, is composed of three herbs:Anemarrhenae Rhizoma, Phellodendri Chinensis Cortex, and Cinnamomi Cortex, which thus is thought to be the representative formula to clear heat, purge fire, nourish Yin, and tonify Qi, and it is often used for treating anuresis and renal arthralgia. In recent years, this formula has become a commonly used combination of herbs and is used to treat diabetes (consumptive thirst disease) diagnosed with "lower consumption" syndrome. This article systematically reviewed the development of traditional Chinese medicine (TCM) theory for Zishenwan. Moreover, based on modern pharmacological research, the previous studies on the components of Zishenwan, the improvement of diabetes-related diseases by Zishenwan, and the relationship between the single herd of Zishenwan and the treatment of diabetes were summarized, and the chemical components and the mechanisms for treating diabetes by the three herbs were discussed. It is found that Zishenwan can alleviate diabetes and diabetic nephropathy by performing anti-inflammation, enhancing insulin sensitivity, and inhibiting pyroptosis of renal tubular epithelial cells. Three herbs in Zishenwan and several components of them, including mangiferin, timosaponins, berberine, jatrorrhizine, cinnamaldehyde, and cinnamic acid can ameliorate diabetes and maintain stable glycometabolism by a variety of mechanisms such as improving insulin resistance in insulin target tissues, suppressing inflammation, anti-oxidation, regulating lipid metabolism, enhancing insulin secretion, and regulating gut microbiota. This review provides a theoretical foundation and reference for subsequent studies on the mechanisms of the anti-diabetic effect of Zishenwan.

11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978451

RESUMO

ObjectiveTo investigate the effect of modified Huangqi Guizhi Wuwutang (MHGW) on the protein and mRNA expression of B-cell lymphoma-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase-12 (Caspase-12) related to the apoptosis of sciatic nerve cells in diabetes rats to explore the mechanism of MHGW in the treatment of peripheral neuropathy in diabetes. MethodAnimal experiments were conducted. A diabetes model was induced in sixty male sprague-dawley (SD) rats by feeding on a high-sugar and high-fat diet combined with streptozotocin (STZ) intraperitoneal injection. Rats with random blood glucose levels ≥ 16.7 mmol·L-1 for three consecutive days were considered to have successfully developed diabetes. Forty-eight rats that successfully developed diabetes were randomly divided into a model group, an α-lipoic acid group (0.026 8 g·kg-1·d-1), a high-dose MHGW group (2.5 g·kg-1·d-1), and a low-dose MHGW group (1.25 g·kg-1·d-1), with 12 rats in each group. Another 10 rats were assigned to the normal group. Body weight and random blood glucose levels of the rats were monitored. At the end of a 16-week intervention period, the sciatic nerve conduction velocity of the rats was measured using the Key point electromyography collection system. The protein and mRNA expression of Bax and Caspase-12 in the sciatic nerve cells was detected by Western blot analysis and real-time quantitative polymerase chain reaction (Real-time PCR), respectively. ResultCompared with the normal group, the model group showed a significant decrease in body weight (P<0.01) and a significant increase in random blood glucose levels (P<0.01). After a 16-week intervention, compared with the model group, the high-dose MHGW group exhibited a significant increase in body weight (P<0.05), while there were no statistically significant differences in body weight changes among the other treatment groups. Random blood glucose levels significantly decreased in all treatment groups (P<0.01). After 16 weeks of intervention, compared with the normal group, the model group had significantly reduced motor and sensory nerve conduction velocities (P<0.01). Compared with the model group, all treatment groups showed significant increases in motor and sensory nerve conduction velocities (P<0.05, P<0.01). The expression of Bax and Caspase-12 proteins in the sciatic nerve cells was significantly elevated in the model group compared with that in the normal group (P<0.01). In contrast, all treatment groups showed significant reductions in the expression of Bax and Caspase-12 proteins in the sciatic nerve cells as compared with that in the model group (P<0.01). The expression of Bax and Caspase-12 mRNA in the sciatic nerve cells significantly increased in the model group compared with that in the normal group (P<0.01). Compared with the model group, the α-lipoic acid group and the high-dose MHGW group showed significant reductions in the expression of Bax mRNA in the sciatic nerve cells (P<0.05, P<0.01), while the low-dose MHGW group showed a decreasing trend in the expression of Bax mRNA. The expression of Caspase-12 mRNA in the sciatic nerve cells significantly decreased in all treatment groups (P<0.01). ConclusionMHGW may improve and repair sciatic nerve damage in diabetes rats by inhibiting sciatic nerve cell apoptosis.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978449

RESUMO

ObjectiveTo investigate the protective effect of modified Huangqi Guizhi Wuwutang (MHGW) on endoplasmic reticulum stress in the sciatic nerve of diabetes rats based on the pathways of inositol-requiring enzyme 1α (IRE1α) and CCAAT/enhancer-binding protein homologous protein (CHOP). MethodSixty rats were fed on a high-sugar and high-fat diet for six weeks, followed by intraperitoneal injection of streptozotocin at a dose of 35 mg·kg-1. Random blood glucose levels were measured three days later and rats with a sustained blood glucose level ≥ 16.7 mmol·L-1 were included in study (n=48). The rats were randomly divided into a model group, an α-lipoic acid group (0.026 8 g·kg-1·d-1), a high-dose MHGW group (2.5 g·kg-1·d-1), and a low-dose MHGW group (1.25 g·kg-1·d-1). Another 10 rats were assigned to the normal group. The intervention lasted for 16 weeks. After 16 weeks, the sciatic nerve structure of the rats in each group was observed under light microscopy using Luxol fast blue (LFB) staining. Transmission electron microscopy was used to observe the ultrastructure of the sciatic nerve. Chemiluminescence method was employed to measure the serum reactive oxygen species (ROS) levels. Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to evaluate the expression of p-IRE1α protein, IRE1α mRNA, CHOP protein, and CHOP mRNA in the sciatic nerve of the rats. ResultCompared with the normal group, the model group showed elevated serum ROS levels (P<0.01). In contrast, the serum ROS levels were significantly reduced in the treatment groups compared with those in the model group (P<0.01). The sciatic nerve of the model group showed pathological changes compared with that in the normal group, while the treatment groups exhibited improvement in sciatic nerve pathology compared with the model group. The protein expression of p-IRE1α and CHOP in the sciatic nerve significantly increased in the model group as compared with that in the normal group (P<0.01). However, the treatment groups showed a significant decrease in the protein expression of p-IRE1α and CHOP in the sciatic nerve compared with the model group (P<0.05, P<0.01). Furthermore, compared with the normal group, the model group showed upregulated mRNA expression of IRE1α and CHOP in the sciatic nerve (P<0.01), while the treatment groups exhibited a significant decrease in the mRNA expression of IRE1α and CHOP compared with the model group (P<0.01). ConclusionMHGW can alleviate endoplasmic reticulum stress-induced cell apoptosis and improve the structure and function of the sciatic nerve in diabetes rats by inhibiting the expression of IRE1α/CHOP pathway-related proteins and mRNA, thereby preventing and treating peripheral neuropathy in diabetes.

13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-978447

RESUMO

ObjectiveTo explore the effect of Zishenwan on glucose and lipid metabolism in spontaneous type 2 diabetes (db/db) mice and investigate the underlying mechanism for improving diabetes based on intestinal barrier function and skeletal muscle transcriptome sequencing results. MethodLiquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the components of Zishenwan. Sixteen 6-week-old db/db mice were divided into a model group and a Zishenwan group, while eight wild-type mice were assigned to the normal group. The Zishenwan group received oral administration of drugs for six weeks, during which fasting blood glucose, body weight, and food intake were measured. Serum total cholesterol (TC) and triglyceride (TG) levels were determined, and fasting insulin levels were measured to calculate the homeostatic model assessment of insulin resistance (HOMA-IR). After the treatment, skeletal muscle and ileum tissues were collected, followed by hematoxylin-eosin (HE) staining. Immunohistochemistry was used to detect the expression of tight junction proteins occludin and zonula occludens-1 (ZO-1) in the ileum. Transcriptome sequencing was performed to detect the skeletal muscle transcriptome, and enrichment analysis was conducted for differentially expressed genes. ResultMultiple active components were identified in Zishenwan. Compared with the normal group, the model group showed increased fasting blood glucose, body weight, TC, TG, and HOMA-IR (P<0.01). Compared with the model group, Zishenwan significantly reduced fasting blood glucose, body weight, TC, TG, and HOMA-IR in db/db mice (P<0.01), while there was no statistically significant difference in food intake. Compared with the normal group, the model group exhibited lipid deposition in skeletal muscle, as well as structural changes in the ileum, with significant decreases in the protein expression levels of intestinal occludin and ZO-1 (P<0.01). Compared with the model group, Zishenwan improved the pathological changes in skeletal muscle and ileum, and increased the protein expression of occludin and ZO-1 in the ileum (P<0.01). Transcriptome analysis suggested that Zishenwan might improve skeletal muscle metabolism and increase insulin sensitivity in mice. ConclusionZishenwan can improve glucose and lipid metabolism in db/db mice, and this effect may be related to its protection of intestinal barrier function and transcriptional regulation of skeletal muscle metabolism-related genes.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-994270

RESUMO

Objective:To evaluate the role of small ubiquitin-associated modifier (SUMO) E3 ligase (PIAS)-regulated SUMOylation of peroxisome proliferator-activated receptor γ (PPARγ) in the endogenous protective mechanism against endotoxin-induced acute lung injury (ALI) in mice.Methods:Experiment Ⅰ Twenty-four clean-grade wild type male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), ALI group, ALI+ PPARγ inducer TZD group (ALI+ T group) and ALI+ TZD+ SUMOylation inhibitor anacardic acid group (ALI+ T+ A group). Lipopolysaccharide (LPS) 15 mg/kg was injected into the tail vein to develop the ALI model. In ALI+ T+ A group, anacardic acid 5 mg/kg was intraperitoneally injected at 1 h before LPS administration. In ALI+ T group and ALI+ T+ A group, TZD 50 mg/kg was intraperitoneally injected at 30 min before LPS administration. The mice were sacrificed at 12 h after LPS administration, and the lung tissues were obtained to examine the pathological changes which were scored and to determine the wet/dry (W/D) weight ratio, and expression of PIAS1, PIAS2, PIAS3 and PIASy protein and mRNA (by Western blot or polymerase chain reaction). Experiment Ⅱ Mouse alveolar macrophages (MH-S cells) were cultured in vitro and divided into 4 groups ( n=5 each) using a random number table method: control group (C group), LPS group, LPS+ PIAS2 siRNA group (L+ P group) and LPS+ Con siRNA group (L+ C group). Cells were routinely cultured in group C. Cells were stimulated with 10 μg/ml LPS to develop the model of endotoxin challenge. PIAS2 siRNA 50 nmol/L and Con siRNA 50 nmol/L were transfected at 48 h before LPS was added in L+ P group and L+ C group, respectively. The cells were collected at 24 h of incubation with LPS to determine the cell viability, levels of M1 and M2 alveolar macrophages (by flow cytometry), expression of PIAS2 and PPARγ (by Western blot), co-expression of PPARγ-SUMO1 (by immunoprecipitation) and expression of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) mRNA (by polymerase chain reaction). The ratio of M1/M2 was calculated. Results:Experiment Ⅰ Compared with C group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was up-regulated in the other three groups ( P<0.05). Compared with ALI group, the lung injury scores and W/D ratio were significantly decreased, and the expression of PIAS2 protein and mRNA was up-regulated in ALI+ T group and ALI+ T+ A group ( P<0.05). Compared with ALI+ T group, the lung injury scores and W/D ratio were significantly increased, and the expression of PIAS2 protein and mRNA was down-regulated in ALI+ T+ A group ( P<0.05). There was no significant difference in the expression of PIAS1, PIAS3 and PIASy protein and mRNA in lung tissues among the four groups ( P>0.05). Experiment Ⅱ Compared with C group, the cell viability was significantly decreased, the expression of PPARγ and co-expression of PPARγ-SUMO1 was up-regulated, the levels of M1 and M2 macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was up-regulated, and the expression of IL-10 mRNA was down-regulated in the other three groups, and PIAS2 expression was significantly up-regulated in L group and L+ C group ( P<0.05). Compared with L group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and PPARγ-SUMO1 co-expression were down-regulated, the M1 macrophage level and M1/M2 ratio were increased, TNF-α mRNA expression was up-regulated, and the expression of IL-10 mRNA was down-regulated in L+ P group ( P<0.05), and no significant change was found in the parameters mentioned above in L+ C group ( P>0.05). Compared with L+ C group, the cell viability was significantly decreased, the expression of PIAS2 and PPARγ and co-expression of PPARγ-SUMO1 were down-regulated, the level of M1 alveolar macrophages and M1/M2 ratio were increased, the expression of TNF-α mRNA was down-regulated, and the expression of IL-10 mRNA was up-regulated in L+ P group ( P<0.05). Conclusions:PIAS2-regulated SUMOylation of PPARγ is the endogenous protective mechanism against endotoxin-induced ALI in mice, which may be related to inhibition of macrophage polarization into M1 type and alleviation of inflammatory responses.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-989647

RESUMO

Objective:To explore the effectiveness and safety of comprehensive treatment of type 2 diabetes mellitus (T2DM) based on syndrome differentiation and diet.Methods:Prospective clinical study. A total of 147 patients with T2DM from September 2021 to August 2022 who met the inclusion criteria were included in the self-controlled trial. On the basis of diet and exercise intervention, the subjects were treated and observed with comprehensive treatment based on syndrome differentiation for 120 days. The main outcome indicators including TCM symptom score, fasting blood glucose (FPG), 2 hPG, HbA1c , Fasting insulin (FINS), C-peptide(C-PR), and the secondary outcome indicators including blood lipid (TC, TG, HDL-C, LDL-C), blood pressure, and safety indicators were performed before and after treatment.Results:After treatment, the FPG of subjects decreased from (8.75±2.26) mmol/L to (7.05±1.23) mmol/L, 2 hPG decreased from (10.75±3.01) mmol/L to (7.07±0.78) mmol/L, HbA1c decreased from (6.82±1.47)% to (5.49±0.63)%, and FINS decreased from (15.4±9.33) μIU/ml to (8.82±7.28) μIU/ml, C-PR decreases from (1.95±0.91) nmol/L to (1.72±1.53) nmol/L, SBP decreased from (137.51±17.94) mmHg to (125.79±7.57) mmHg, DBP decreased from (82.85±9.65) mmHg to (77.54±6.21) mmHg,TG decreased from (1.57±1.04) mmol/L to (1.25±1.24) mmol/L, HDL-C increased from (1.48±0.41) mmol/L to (1.66±0.46)mmol/L. The above differences were statistically significant ( P<0.05). Conclusion:The comprehensive treatment of T2DM based on syndrome differentiation and diet can significantly reduce the blood glucose indicators including FPG, 2 hPG, HbA1c, FINS and C-PR, and benefit blood pressure and blood lipids with no adverse reactions.

16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-989338

RESUMO

Objective:To explore the molecular mechanism of the effect of the histone methylase zeste gene enhancer homolog 2 (EZH2) on the proliferation and apoptosis of human hypertrophic cardiomyocytes AC16.Methods:The AC16 hypertrophic cardiomyocyte model was constructed by adding angiotensin Ⅱ to the AC16 cell culture medium. The cells were divided into four groups, including the blank control group, the angiotensin Ⅱ group, the empty vector + angiotensin Ⅱ group, and the EZH2 overexpression + angiotensin Ⅱ group. The expression levels of EZH2 and brain natriuretic peptide ( BNP) genes were measured using fluorescent quantitative PCR. The EZH2, trimethylation of lysine at position 27 of histone H3 (H3K27me3), and BNP proteins expression were detected by Western Blot. The MTS method was used to detect the proliferation of AC16 cell. The Annexin V-FITC/PI double staining method was used to detect the apoptosis of AC16 cell. Results:Compared with the blank control group, the expression levels of EZH2 and H3K27me3 in the angiotensin Ⅱ group were decreased, the expression level of BNP was increased, cell proliferation was decreased, and apoptosis was increased (all P < 0.001). Compared with the empty vector + angiotensin Ⅱ group, the expression levels of EZH2 and H3K27me3 in the EZH2 overexpression + angiotensin Ⅱ group were increased, the expression level of BNP was decreased, the cell proliferation level was increased, and the apoptosis level was decreased (all P < 0.001). There was no significant difference between the angiotensin Ⅱ group and the empty vector + angiotensin Ⅱ group (all P > 0.05). Conclusions:Histone methylase EZH2 has an effect on the proliferation and apoptosis of AC16 cell, providing a reference for the treatment of myocardial hypertrophy and revealing the exact pathogenesis of myocardial hypertrophy.

17.
China Pharmacy ; (12): 2250-2255, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-988786

RESUMO

OBJECTIVE To establish a physiologically-based pharmacokinetic (PBPK) model of amikacin in elderly patients with renal insufficiency. METHODS PK-SIM® software was adopted for model building, optimization and simulation. The physical and chemical properties and pharmacokinetic parameters related to amikacin were collected by literature review. The PBPK model on adults was established and extrapolated to the elderly population based on the built-in human model. Data from clinical PK studies were used to optimize and validate the model. The goodness of fit, relative residual, and mean folding error (MFE) were used to evaluate the performance of forecasting. The final model was employed to simulate the exposure of amikacin in the elderly population with renal insufficiency, and the efficacy and safety of commonly used clinical dosing regimens were evaluated, and the recommended regimens were proposed. RESULTS The established PBPK model of amikacin had good prediction performance in both adult and elderly populations, with the absolute mean of relative residual value of 25%; the MFE of peak concentration (cmax) and area under the plasma concentration curve (AUC0-∞) in all simulation occasions ranged >0.5-<2. The simulation results showed that, compared with healthy adults, no significant clinical difference in cmax was observed in the elderly with renal insufficiency at the same dosing regimen, but the trough concentration increased significantly due to accumulation. Prolonging the administration interval of amikacin rather than reducing the dosage was more helpful to ensure the efficacy and to reduce the occurrence of nephrotoxicity. CONCLUSIONS The PBPK model for amikacin is successfully established in the elderly patient with renal insufficiency, and shows good predictive performance.

18.
BMC Gastroenterol ; 22(1): 502, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474169

RESUMO

BACKGROUND: Previous studies have shown that the Kyoto classification of gastritis can accurately predict H. pylori infection status on conventional gastroscopy. The aim of this study was to test whether the Kyoto classification of gastritis applies well to magnetic controlled capsule endoscopy (MCCE). METHODS: We consecutively recruited 227 participants who underwent both MCCE and urea breath tests (UBTs). Two physicians who were blinded to the UBT results independently made the diagnosis of H. pylori infection status according to 10 findings listed in the Kyoto classification of gastritis after reviewing MCCE images. We also developed 2 predictive models to assess H. pylori infection status by combining these 10 findings. RESULTS: The MCCE's overall diagnostic accuracy for H. pylori infection status was 80.2%. The sensitivity, specificity and diagnostic odds ratio (DOR) for current infection were 89.4%, 90.1% and 77.1, respectively. Major specific findings were mucosal swelling and spotty redness for current infection, regular arrangement of collecting venules (RAC), streak redness, fundic gland polyp (FGP) for noninfection, and map-like redness for past-infection. In the two prediction models, the area under the curve (AUC) values for predicting noninfection and current infection were 84.7 and 84.9, respectively. CONCLUSIONS: The Kyoto classification of gastritis applied well to MCCE. H. pylori infection status could be accurately assessed on MCCE according to the Kyoto classification of gastritis.


Assuntos
Helicobacter pylori , Humanos , Cápsulas Endoscópicas , Fenômenos Magnéticos
19.
Front Public Health ; 10: 1025271, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36419999

RESUMO

Background: The purpose of this study is to develop an artificial intelligence (AI)-based automated diabetic retinopathy (DR) grading and training system from a real-world diabetic dataset of China, and in particular, to investigate its effectiveness as a learning tool of DR manual grading for medical students. Methods: We developed an automated DR grading and training system equipped with an AI-driven diagnosis algorithm to highlight highly prognostic related regions in the input image. Less experienced prospective physicians received pre- and post-training tests by the AI diagnosis platform. Then, changes in the diagnostic accuracy of the participants were evaluated. Results: We randomly selected 8,063 cases diagnosed with DR and 7,925 with non-DR fundus images from type 2 diabetes patients. The automated DR grading system we developed achieved accuracy, sensitivity/specificity, and AUC values of 0.965, 0.965/0.966, and 0.980 for moderate or worse DR (95 percent CI: 0.976-0.984). When the graders received assistance from the output of the AI system, the metrics were enhanced in varying degrees. The automated DR grading system helped to improve the accuracy of human graders, i.e., junior residents and medical students, from 0.947 and 0.915 to 0.978 and 0.954, respectively. Conclusion: The AI-based systemdemonstrated high diagnostic accuracy for the detection of DR on fundus images from real-world diabetics, and could be utilized as a training aid system for trainees lacking formal instruction on DR management.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Inteligência Artificial , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Prospectivos , Sensibilidade e Especificidade
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-956945

RESUMO

Objective:To retrospectively analyze the relationship between patterns of local recurrence and radiotherapy target dose after adjuvant radiotherapy for the pancreatic ductal adenocarcinoma(PDAC), aiming to provide reference for exploring reasonable target and dosage.Methods:Clinical data of 138 patients with T 1-4N 0-2M 0 PDAC who underwent adjuvant radiotherapy after radical resection from April 2012 to December 2020 were analyzed retrospectively. The influencing factors of local recurrence and the correlation between local recurrence site and radiotherapy target dose were analyzed. Results:The median follow-up time was 37.2 months. The median overall survival (mOS) was 29.9 months. The 5-year OS rate was 27.4%. And the median progression-free survival (mPFS) was 13.9 months. There were 24 cases of local recurrence (17.4%), and 10 cases of local recurrence complicated with distant metastasis (7.2%). The correlation between local recurrence site and radiotherapy target dose could be evaluated in 19 patients with complete clinical data. The first local recurrence occurred near the para-aortic (Ao), the celiac axis (CA) and the superior mesenteric artery (SMA) were 8, 5 and 4 cases, respectively. The radiotherapy doses of 8 patients with local recurrence only in the PTV field were above 45 Gy. There were 8 cases of local recurrence both in and out of the PTV field, including 3 cases with dose line between 40 and 52 Gy, 2 cases with dose line between 20 and 47.5 Gy, and 3 cases with dose line between 0.5 and 52.5 Gy. There were 3 cases of local recurrence out of the PTV field, and the dose line ranged from 0 to 20 Gy.Conclusions:The local recurrence rate of PDAC after radical surgery combined with postoperative radiotherapy is low, but a small number of patients have recurrence in the high-dose range of radiation field and regional recurrence out of the field. For these patients, it may be necessary to explore a more appropriate target dose and range for adjuvant radiotherapy.

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