1.The mechanisms of type 2 diabetic skeletal muscle atrophy and the effects of commonly used hypoglycemic drugs: a review
Mei-dai LIANG ; Xiu-ying YANG ; Guan-hua DU
Acta Pharmaceutica Sinica 2022;57(3):568-575
Type 2 diabetes is a hypermetabolic disease characterized with disorders of glucose/lipid metabolism, absolute or relative lack of insulin, and can induce skeletal muscle atrophy. Hyperglycemia, hyperlipidemia, insulin resistance, and abnormal release of inflammatory factors can lead to abnormal signal transduction in skeletal muscle, thus make protein synthesis and degradation imbalance and eventually causing muscle atrophy. Under normal conditions, insulin-like growth factor 1 (IGF-1)/insulin can activate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT). AKT not only increases protein synthesis through mammalian target protein of rapamycin (mTOR), but also phosphorylates forkhead box O (FoxO) transcription factor and then inhibits the transcription of several ubiquitin ligases (such as MAFbx/atrogin-1 and MuRF1), or autophagy related genes. The weakened IGF-1/PI3K/AKT pathway in type 2 diabetes is an important factor leading to skeletal muscle atrophy. Studies have shown that the commonly used anti-type 2 diabetic drugs have different effects in regulating the synthesis and degradation of skeletal muscle protein. Studies reported that drugs with effect of anti-diabetic muscle atrophy include thiazolidinediones, glucagon-like peptide analogs, glucose-sodium cotransporter 2 inhibitors, etc.; drugs that are still in controversial or even promote skeletal muscle atrophy include metformin, and some sulfonylurea or non-sulfonylurea insulin secretagogues. This article overviewed and analyzed the currently commonly used drugs for type 2 diabetes and summarized the related mechanisms, with the aim to provide references for the rational applications of drugs for type 2 diabetes.
2.Advances in research on mechanisms of diabetic wound healing
Nuo-qi WANG ; Xiu-ying YANG ; Guan-hua DU
Acta Pharmaceutica Sinica 2020;55(12):2811-2817
Wound healing is a complex and highly regulated process to maintaining the skin barrier function. Wounds of diabetic patients are hard or even not healing. Non-healing diabetic foot ulcers can lead to lower-extremity amputations. Diabetic wound healing problem is the main complication that leads to high disability rate of diabetes and can threaten the lives in severe cases. The healing of skin wounds requires the synergy of multiple factors to restore the injured skin to its barrier function. The mechanisms that cause it difficult to heal diabetic wounds are complex, including oxidative stress, chronic inflammation, decreased neovascularization, peripheral neuropathy, and imbalance of extracellular matrix accumulation and remodeling. This review classifies mechanisms of diabetic wound healing and provides a reference for its further research.
3.Lectin-like oxidized low-density lipoprotein receptor-1: protein, ligands, expression and pathophysiological significance.
Chinese Medical Journal 2007;120(5):421-426
OBJECTIVETo review the recent research progress in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) including its protein, ligands, expression and pathophysiological significance. Data sources Information included in this article was identified by searching of PUBMED (1997 - 2006) online resources using the key term LOX-1.
STUDY SELECTIONMainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected.
RESULTSThe key issues related to the LOX-1 protein as well as ligands for LOX-1. Factors regulating the expression of LOX-1 were summarized. The pathophysiological functions of LOX-1 in several diseases were discussed.
CONCLUSIONSIdentification of LOX-1 and a definition of its biological role in pathophysiologic states provide deeper insight into the pathogenesis of some cardiovascular diseases especially in atherosclerosis and provide a potential selective therapeutic approach. LOX-1 is unlocking and drugs targeting LOX-1 might be a promising direction to explore.
Animals ; Arthritis, Rheumatoid ; etiology ; Atherosclerosis ; etiology ; Humans ; Ligands ; Myocardial Infarction ; etiology ; Osteoarthritis ; etiology ; Scavenger Receptors, Class E ; chemistry ; genetics ; physiology
4.Effect of dexamethasone on nitric oxide synthase and Caspase-3 gene expressions in endotoxemia in neonate rat brain.
Hua WANG ; Yu-Bin WU ; Xiu-Hua DU
Biomedical and Environmental Sciences 2005;18(3):181-186
OBJECTIVETo investigate the gene and protein expressions of three isoforms of nitric oxide synthase (NOS) and gene expression of Caspase-3, and effect of dexamethasone on them in neonatal rats with lipopolysaccharide (LPS)-induced endotoxemic brain damage.
METHODSExpressions of the three isoforms of NOS and caspase-3 mRNA in the brain were investigated by RT-PCR in postnatal 7-day Wistar rats with acute endotoxemia by intraperitoneal administration of LPS. Regional distributions of NOSs were examined by immunohistochemical technique.
RESULTSnNOS and Caspase-3 mRNA were obviously detected. eNOS mRNA was faintly expressed, but iNOS mRNA was undetectable in the control rat brain. The expressions of NOS mRNA of three isoforms were weak 2 h after LPS (5 mg/mg) delivery, peaked at 6 h, and thereafter, reduced gradually up to 24 h. The expression intensity was in the order of nNOS> iNOS> eNOS. Widespread nNOS, scattered eNOS distribution and negative iNOS were identified in the control rat brain and all isoforms of NOS could be induced by LPS which reached the apex at 24 h in the order of nNOS> iNOS> eNOS as detected by immunostaining. Although Caspase-3 mRNA could be found in all groups, DNA fragmentation was only seen at 6 h and 24 h. The expressions of NOS and Caspase-3 mRNA were inhibited in the rat brain when dexamethasone was administrated.
CONCLUSIONLPS-induced NO production induces apoptosis of neurons through mechanism involving the Caspase-3 activation, which may play an important role in the pathogenesis of brain damage during endotoxemia, and neuro-protective effects of dexamethasone may be partially realized by inhibiting the expression of NOS mRNA.
Animals ; Animals, Newborn ; Apoptosis ; Brain ; drug effects ; enzymology ; Caspase 3 ; Caspases ; genetics ; metabolism ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Endotoxemia ; chemically induced ; enzymology ; Female ; Lipopolysaccharides ; Male ; Nerve Tissue Proteins ; genetics ; metabolism ; Nitric Oxide Synthase ; genetics ; metabolism ; Nitric Oxide Synthase Type I ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction
5.Effect of evidence-based nursing in preoperative interview for abdominal surgery patients' recovery after general anesthesia
Xiu-Hua DU ; Feng-Ling ZHAO ; Ru-Juan ZHUANG ; De-Hua LIAN ; Yan-Qiu FENG
Chinese Journal of Modern Nursing 2011;17(13):1508-1511
Objective To explore the effect of evidence-based nursing during preoperative interview for abdominal surgery patients' recovery after general anesthesia. Methods 124 patients who accepted selective operation on abdominal region were randomly divided into evidence-based group and control group, 62 cases ineach group. On the base of routine method in the preoperative interview, the evidence-based group established evidence-based information supporting system, which aimed to dredge the psychological stress of the patients'response to surgery individually and intervene by demonstrating simulation of operation process. According to the traditional way, control group accepted routine preoperative interview. To compare patients' indexes of two groups before and after anesthesia. Results Patients' heart rate and the mean arterial pressure lower than control group before anesthesia in evidence-based group. The dosage of midazolam in evidence-based group was less than the control group (t =6. 73,7. 24,8. 17;P <0. 05). The difference of pre-anesthesia anxiety scores was statistically significant between evidence-based group and control group (t =7. 68 ,P <0. 01 ). But the difference of the anxiety scores after operation wasn' t statistically significant between two groups ( t = 0. 62, P > 0. 05 ). Patients in evidence-based group took shorter revival time than control group ( t = 9. 71,10. 45,11.32 ; P < 0. 01 ). Compared the different period pain score of two groups, patients of evidence-based group were lower than those of the control group, and the patients' satisfaction scores also were higher than those of control group, the differences were statistically significant (t =2. 38,5. 22,2. 63,7. 62;P <0. 05). Conclusions Application evidence-based nursing information support in preoperative interview effectively relieves the preoperative anxiety, can reduce the dosage of narcotic and sedative drugs, shorten the revival time, improve patient' s satisfaction and have reached the antieipant effects.
6.Changes of the elastic fibers and collagen fibers during the development and progression of experimentally induced tongue carcinoma in hamsters.
Peng ZHANG ; Yu-bin DU ; Miao YU ; Xiang YIN ; Yan-hong LV ; Zhong-xiu-zi GAO ; Jin-hua ZHENG
Journal of Southern Medical University 2010;30(12):2696-2698
OBJECTIVETo investigate the relationship between the extracellular matrix (ECM) and neoplastic progression in hamster with tongue cancer.
METHODSForty-eight specimens of hamster tongue cancer were divided into control group (n=6) and experimental group (n=42). The pathological grade of the specimens was assessed (including 3 stages, namely atypical hyperplasia, carcinoma in situ and early invasive carcinoma). The sections of the tongue were stained with Masson and aldehyde-fuchsin (AF) staining for microscopic observation of the elastic fiber and collagen fiber changes.
RESULTSWithin the connective tissue cores (CTC) of the papillae in the control group was a framework of numerous and fine Gomrori's aldehyde fuchsin-positive elastic fibers. But in the stages of dysplasia and carcinoma in situ, these elastic fibers decreased and further diminished in the CTC in early invasive carcinoma. In dysplasia and carcinoma in situ stages, most of the elastic fibers collapsed with scattered elastic fibers, and the elastic fibers decreased significantly in early invasive carcinoma. The control group showed a significantly greater number of elastic fibers in the experimental group. The collagen fiber was obviously increased and irregularly arranged in dysplasia and carcinoma in situ stage; in early invasive carcinoma, the collagen fibers became thicker with deposition in the lamina propria.
CONCLUSIONAn excessive deposition of collagen fiber and reduction of the elastic fibers is an important factor contributing to the development of tongue carcinoma in hamsters.
Animals ; Carcinoma ; pathology ; Collagen ; metabolism ; Connective Tissue ; pathology ; Cricetinae ; Elastic Tissue ; pathology ; Extracellular Matrix ; pathology ; Neoplasms, Experimental ; pathology ; Tongue Neoplasms ; pathology
7.In vitro expansion of cord blood mononuclear cells supported by fetal bone marrow stromal cells and cytokines.
Ping MAO ; Cai-Xia WANG ; Xiu-Mei LIN ; Qing-Hua DU
Journal of Experimental Hematology 2005;13(3):422-428
This study was aimed to explore the role of human fetal bone marrow stromal cells (FBMSC) in combination with exogenous cytokines in supporting the in vitro expansion of cord blood mononuclear cells and the expression of CXCR4(+) and CD49d(+) in CD34(+) cells. Mononuclear cells (MNC) separated from cord blood (CB) were cultured in a serum-free support culture system with FBMSC or exogenous cytokines or both of them. On day 0, 6, 10 and 14, total cells were counted, CD34(+), CD34(+)CXCR4(+) and CD34(+)CD49d(+) cells were quantitated by FACS, and hematopoietic progenitor cells were assessed by semisolid culture assay. The results showed that after culturing for 14 days, CD34(+) cells, CD34(+)CXCR4(+) cells, CD34(+) CD49d(+) cells and colony forming unit (CFU) were significantly increased (P < 0.05). Compared with other groups, expansion multiple of CD34(+), CD34(+)CXCR4(+), CD34(+)CD49d(+) cells and CFU were higher than that in FBMSC and cytokine group (P < 0.05). It is concluded that the culture system used in this study can not only support the expansion of CB MNCs but also increase the number of hematopoietic stem and progenitor cells which has chemokine and adhesion capacity. This culture system may be a feasible way for in vitro culture of cord blood cells.
Antigens, CD34
;
blood
;
Bone Marrow Cells
;
cytology
;
immunology
;
Cell Proliferation
;
drug effects
;
Cells, Cultured
;
Coculture Techniques
;
Cytokines
;
pharmacology
;
Fetal Blood
;
cytology
;
Fetus
;
Flow Cytometry
;
Granulocyte-Macrophage Colony-Stimulating Factor
;
pharmacology
;
Humans
;
Integrin alpha4
;
blood
;
Interleukin-3
;
pharmacology
;
Leukocytes, Mononuclear
;
cytology
;
immunology
;
Receptors, CXCR4
;
blood
;
Stromal Cells
;
cytology
;
immunology
;
Time Factors
8.Salvianolic acid A ameliorates AGEs-induced glomerular endothelial dysfunction and protects against diabetic nephropathy
HOU BI-YU ; ZHAO YUE-RONG ; QIANG GUI-FEN ; CHEN XI ; YANG XIU-YING ; ZHANG LI ; DU GUAN-HUA
Chinese Journal of Pharmacology and Toxicology 2017;31(10):1011-1012
OBJECTIVE Diabetic nephropathy (DN) has been one of the most common complications of diabetes and the leading cause of end-stage renal disease. Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities. Salvi?anolic acid A (SalA) has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy. The present study was designed to investigate the effects of SalAon glomerular endothelial dysfunctionand diabetic nephropathy. METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products (AGEs). AGEs-induced changes of RhoA/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunoflu?orescence. The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin (35 mg·kg- 1, ip). Renal function and architectonic changes were evaluated by biochemical assay and PAS staining. RESULTS SalA 3μMameliorated AGEs- induced glomerular endothelial permeability (P<0.05) and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-RhoA/ROCK pathway. SalA 1 mg · kg- 1 markedly reduced endothelium loss (P<0.01) and glomerular hyperfiltration (P<0.05) in diabetic kidney. Subsequently,SalA 1 mg·kg-1 suppressed glomerular hypertrophy and mesangial matrix expansion, eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen (BUN), serum creatinine (Scr) and serum n-acetyl-β-d-glucosaminidase (NAG). AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg-1. CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability, and effec?tively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway. Thus, SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.
9.Experimental Study of Rehabilitation of Rats with Anal Edema with Traditional Chinese Medicine
Xiu-Jun GUO ; Juan QIN ; Xiao-Yin ZHAO ; Yu-Hua BIAN ; Yuan DU ; Xiang JIN
Chinese Journal of Modern Nursing 2009;15(36):3860-3864
Objective To investigate the effects of different time duration hip bathing with traditional Chinese medicine for rehabilitation of rats with anal edema, which can provide evidence for a best effective hip bathing method in the clinical application. Methods The rat model of anal edema was induced with carrageenan injection. Ninty six SD rats were divided into early intervene and latter intervene batches, every batches were randomly divided into six groups; normal control group 1, normal control group2, model matched groupl, model matched group2, hip bathing with TCM groupl, hip bathing with TCM group2. Hip bathing time duration were lOminutes and 20minutes. The rehabilitation of rats anal edema were observed. Results The comparison has been made among edema area, the ratio of dry/wet weight, microcirculation change, skin temperature, the difference is statistically significant in TCM early intervene hip bathing groups (P < 0. 05). There was a significant difference of edema proportion with 20 minutes duration between TCM hip bathing groups and model control groups (P < 0. 01 ). The comparison has been made among the ratio of dry/wet weight, microcirculation change, the difference is statistically significant in TCM latter intervene hip bathing groups(P< 0. 05). Histopathological examination showed local tissue inflammatory cell infiltration, the loosen degree of tissue space and capillary congestion of modle group were improved. Conclusions Hip bathing with traditional Chinese medicine in early intervene have obvious effect on rehabilitation of rats with anal edema, which can dispell anal edema, improving microcirculation could descend the temperature and promote the rehabilitation of anal edema, relieve inflammation and hyperemia. In the respect of edema proportion relieving, hip bathing with 20 minutes duration showed better effect than 10 minutes.
10.The effect of improved inhalation therapy as adjuvant treatment for infants with severe pneumonia
Xiu-Ping ZHANG ; Yi-Xia DU ; De-Hua LIAN
Chinese Journal of Modern Nursing 2010;16(8):879-882
Objective To investigate the effect of improved therapy-trace intermittent inhalation therapy as the adjuvant treatment for infants and children with severe pneumonia. Methods A total of 148 cases of infants and children with severe pneumonia were randomly divided into test group and control group, each group contained 74 patients. We used trace-intermittent inhalation therapy for the test group and selected the appropriate inhalation time and intermittent time according to children' s age and the degree of choke gasp. In the control group, we used the traditional continuous inhalation method. Breathing, heart rate, oxygen saturation, indicators of blood gas analysis and the extent of choke before and after inhalation were compared. Results The two group showed no differences in breathing, heart rate, oxygen saturation, indicators of blood gas analysis and the degree of choke before inhalation (P > 0. 05) , while significant difference were showed after inhalation (P < 0. 01), and the difference of the choke degree was statistically significant (P < 0. 05). This study showed that the trace-intermittent inhalation treatment was significantly superior to the traditional continuous inhalation treatment (P <0. 01). Conclusions Trace intermittent inhalation therapy can promote the effective oxygen supply of the organization, improve ventilation and oxygenation function and blood gas results in children, relieve the different degrees of choke gasp, shorten the course of disease and improve the therapeutic effect significantly.