Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease

In this editorial,we comment on Yin et al’s recently published Letter to the editor.In particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic pathology.It is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive damage.Several clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve fibrosis.Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease.In particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than monotherapy.Therefore,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy.

Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity.Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain regions.Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural morphogenesis.The glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous system.After brain insult,microglia are the first cells to respond,followed by reactive astrocytosis.These activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the insult.Furthermore,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many diseases.Several processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control mechanisms.The glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry response.This review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkinson’s disease,vascular dementia,or chronic migraine.

Glucagon-like peptide 1 receptor agonist:A potential game changer for cholangiocarcinoma

Glucagon-like peptide-1 receptor(GLP-1R)agonist,a subgroup of incretin-based anti-diabetic therapies,is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection.Contrarily,concerns have been raised about GLP-1R agonists increasing the risk of particular cancers.Recently,several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma(CCA).The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA.Later studies,however,showed a null effect of incretinbased therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist.Mechanistically,glucagon-like peptide 1 receptor is multifunctional,including promoting cell growth.High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro.Unexpectedly,the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms.Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo,leading to the inhibition of CCA tumor growth.This editorial reviews recent evidence,discusses the potential effects of GLP-1R agonists in CCA patients,and proposes underlying mechanisms that would benefit from further basic and clinical investigation.

Glucagon-like-peptide-1 receptor agonists and the management of type 2 diabetes-backwards and forwards

This editorial is stimulated by the article by Alqifari et al published in the World Journal of Diabetes(2024).Alqifari et al focus on practical advice for the clinical use of glucagon-like-peptide-1(GLP-1)receptor agonists(GLP-1RAs)in the management of type 2 diabetes and this editorial provides complementary information.We initially give a brief historical perspective of the development of GLP-1RAs stimulated by recognition of the‘incretin effect’,the substantially greater insulin increase to enteral when compared to euglycaemic intravenous glucose,and the identification of the incretin hormones,GIP and GLP-1.In addition to stimulating insulin,GLP-1 reduces postprandial glucose levels by slowing gastric emptying.GLP-1RAs were developed because native GLP-1 has a very short plasma half-life.The majority of current GLP-1RAs are administered by subcutaneous injection once a week.They are potent in glucose lowering without leading to hypoglycaemia,stimulate weight loss in obese individuals and lead to cardiovascular and renal protection.The landscape in relation to GLP-1RAs is broadening rapidly,with different formulations and their combination with other peptides to facilitate both glucose lowering and weight loss.There is a need for more information relating to the effects of GLP-1RAs to induce gastrointestinal symptoms and slow gastric emptying which is likely to allow their use to become more effective and personalised.

A Retrospective Analysis of Glucagon-Like Peptide 1 Receptor Agonists in Treating Type 2 Diabetes Mellitus Complicated by Nonalcoholic Fatty Liver Disease

Background: The objective of this study was to compare and analyze the variations in clinical indices before and after treatment of type 2 mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) that were treated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Methods: The electronic medical record system was utilized to search for a total of 16 patients with type 2 diabetes complicated by NAFLD who were hospitalized at the First Affiliated Hospital of Yangtze University from October 2022 to April 2023 and treated with GLP-1RA for the first time. The clinical indices were compared before and after 12 weeks of treatment with GLP-1RA. Results: The liver-spleen CT ratio (L/S), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in all patients treated with GLP-1RA after 12 weeks were significantly different (P 0.05). The patients were categorized into two groups based on the types of GLP-1RAs. The changes in L/S, TC, TG, and LDL-C in the long-acting group after treatment were statistically significant (P Conclusions: GLP-1RAs can improve liver function, regulate lipid metabolism, and reduce the severity of fatty liver in patients with T2DM complicated by NAFLD, which demonstrates the importance of clinical applications.

Mechanism of annexin A1/N-formylpeptide receptor regulation of macrophage function to inhibit hepatic stellate cell activation through Wnt/β-catenin pathway

BACKGROUND Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to cirrhosis.AIM To evaluate the effect and mechanism of action annexin(Anx)A1 in liver fibrosis and how this could be targeted therapeutically.METHODS CCl4(20%)and active N-terminal peptide of AnxA1(Ac2-26)and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe(Boc2)were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice,and to detect expression of inflammatory factors,collagen deposition,and the role of the Wnt/β-catenin pathway in hepatic fibrosis.RESULTS Compared with the control group,AnxA1,transforming growth factor(TGF)-β1,interleukin(IL)-1βand IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased,which promoted collagen deposition and expression ofα-smooth muscle actin(α-SMA),collagen type I and connective tissue growth factor(CTGF),and increased progressively with time.CCl4 induced an increase in TGF-β1,IL-1βand IL-6 in liver tissue of AnxA1 knockout mice,and the degree of liver inflammation and fibrosis and expression ofα-SMA,collagen I and CTGF were significantly increased compared with in wild-type mice.After treatment with Ac2-26,expression of liver inflammatory factors,degree of collagen deposition and expression of a-SMA,collagen I and CTGF were decreased compared with before treatment.Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26.AnxA1 downregulated expression of the Wnt/β-catenin pathway in CCl4-induced hepatic fibrosis.In vitro,lipopolysaccharide(LPS)induced hepatocyte and hepatic stellate cell(HSC)expression of AnxA1.Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation,decreased expression ofα-SMA,collagen I and CTGF in HSCs,and inhibited expression of the Wnt/β-catenin pathway after HSC activation.These therapeutic effects were inhibited by Boc2.CONCLUSION AnxA1 inhibited liver fibrosis in mice,and its mechanism may be related to inhibition of HSC Wnt/β-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.

Potential therapeutic targets for nonalcoholic fatty liver disease:Glucagon-like peptide 1

Nonalcoholic fatty liver disease(NAFLD)is the most rapidly growing contributor to liver mortality and morbidity.Hepatocellular injury in nonalcoholic steatohepatitis(NASH)is caused by an increase in metabolic substrates(glucose,fructose,and fatty acids),leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury.The pathogenesis of this disease is largely associated with obesity,type 2 diabetes,and increasing age.To date,there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis.Since one of the pathogenic drivers of NASH is insulin resistance,therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH.Currently,the glucagon-like peptide-1 receptor agonist(GLP-1RA)semaglutide is a safe,well-studied therapeutic for NAFLD/NASH patients.Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis.However,improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD.Given the complex pathophysiology of NASH,combining therapies with complementary mechanisms may be beneficial.Researchers have conducted trials of semaglutide in combination with antifibrotic drugs.However,the results have not fully met expectations,and it cannot be ruled out that the reason is the short trial time.We should continue to pay increasing attention to GLP-1RAs.

Postprandial glucagon-like peptide 1 secretion is associated with urinary albumin excretion in newly diagnosed type 2 diabetes patients

BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1)and microalbuminuria in newly diagnosed T2DM patients.METHODS In total,760 patients were recruited for this cross-sectional study.The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were determined.RESULTS Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria(30 min GLP-1,16.7±13.3 pmol vs 19.9±15.6 pmol,P=0.007;120 min GLP-1,16.0±14.1 pmol vs 18.4±13.8 pmol,P=0.037).The corresponding area under the curve for active GLP-1(AUCGLP-1)was also lower in microalbuminuria patients(2257,1585 to 3506 vs 2896,1763 to 4726,pmol×min,P=0.003).Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR(r=0.159,r=0.132,r=0.206,respectively,P<0.001).The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%,which decreased with increasing quartiles of AUCGLP-1 levels(27.4%,25.3%,18.9%and 15.8%).After logistic regression analysis adjusted for sex,age,hemoglobin A1c,body mass index,systolic blood pressure,estimated glomerular filtration rate,homeostasis model assessment of insulin resistance,AUC_(glucose)and AUC_(glucagon)patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1(odds ratio=0.547,95%confidence interval:0.325-0.920,P=0.01).A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria.CONCLUSION Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.

Type-2 Diabetes Mellitus and Glucagon-Like Peptide-1 Receptor toward Predicting Possible Association

Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.

GLP-1受体激动剂对心血管作用的研究进展

胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)由肠道内分泌细胞产生。GLP-1受体激动剂(GLP-1 receptor agonists,GLP-1RAs)促进葡萄糖相关的胰岛素分泌和抑制胰高血糖素分泌。GLP-1RAs还能抑制胃排空、食物摄入和限制体质量增加。在过去的十年中,GLP-1RAs对心血管系统影响的研究已经取得重大进展。口服小分子GLP-1RAs具有潜在优势,可以提高该类药物的应用。该文综述了GLP-1RAs在心血管疾病治疗中的多种作用,为GLP-1RAs的心血管获益提供新见解。

胰高血糖素样肽1受体激动剂治疗阿尔茨海默病的潜在靶点预测及验证

背景:阿尔茨海默病的机制探究过程中揭示了生物信息学对共同靶点筛选的重要作用,能够利用其筛选结果为基础,探究药物对该疾病的治疗效果。目的:采用生物信息学与分子生物学等方法预测胰高血糖素样肽1受体激动剂利拉鲁肽治疗阿尔茨海默病的作用靶点。方法:利用DisGeNET数据库及SEA数据库获取阿尔茨海默病和利拉鲁肽作用的共同基因;利用DAVID在线数据库对共同靶点进行GO/KEGG富集分析;使用STRING数据库构建蛋白互作网络;使用CCK-8判断利拉鲁肽的最佳使用剂量;使用免疫荧光和免疫印迹技术对关键蛋白的表达情况进行分析。采用小鼠海马神经元HT22细胞系进行体外实验,细胞被随机分为3组:HT22组、HT22+Aβ组和HT22+Aβ+Lir组。HT22组不做特殊处理,HT22+Aβ组使用Aβ1-42干预HT22细胞系24 h构建Aβ损伤细胞模型,HT22+Aβ+Lir组在HT22+Aβ组的基础上添加利拉鲁肽12 h。结果与结论:①从DisGeNET数据库筛选出阿尔茨海默病相关联的基因,共得到3333个关联基因。再从SEA数据库中,得到利拉鲁肽的潜在作用靶点147个。最后使用R包筛选出阿尔茨海默病与利拉鲁肽共同靶点64个。②用DAVID数据库进行共同靶点的GO/KEGG分析,结果提示共同靶点主要富集在:神经活性配体-受体相互作用、肾素-血管紧张素系统、膀胱癌、内肽酶活性、肽受体活性、G蛋白偶联肽受体活性和转运囊泡等生物进程。③将已经得到的64个共同靶点蛋白导入至SRTING在线数据库进行蛋白互作网络构建,得到排名前3位的基因为基质金属蛋白酶2,9和白细胞介素1β。④采用CCK-8试剂盒检测了培养细胞的活性,确定利拉鲁肽拮抗Aβ1-42的最佳浓度为100 nmol/L。⑤在免疫印迹实验与免疫荧光实验中,较HT22组相比,在HT22+Aβ组内基质金属蛋白酶2,9和白细胞介素1β表达量明显上升(P<0.05);HT22+Aβ+Lir组较HT22+Aβ组相比基质金属蛋白酶2,9和白细胞介素1β的表达量显著下降(P<0.05)。⑥结合上述生物信息学数据及在GEO数据库的差异基因二次验证结果提示,基质金属蛋白酶2,9和白细胞介素1β均可作为利拉鲁肽治疗阿尔茨海默病的潜在作用靶点。

达格列净联合胰高血糖素样肽-1受体激动剂对2型糖尿病的疗效研究

目的探讨达格列净联合胰高血糖素样肽-1受体激动剂(GLP-1 RAs)对2型糖尿病患者血液流变学及胰岛素抵抗的影响。方法将2020年11月—2022年10月泉州市中医院收治的102例2型糖尿病患者随机分为2组,每组51例。对照组给予达格列净治疗,研究组采用达格列净联合GLP-1 RAs(利拉鲁肽)的治疗方案。比较2组临床疗效、血糖指标[空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(HbA1c)]、空腹胰岛素(FINS)及胰岛素抵抗[胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)]、血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、血液流变学指标[红细胞聚集指数(EAI)、红细胞压积(HCT)、红细胞变形指数(EDI)、血浆黏度(PV)]和不良反应。结果研究组总有效率为94.12%,高于对照组的80.39%,差异有统计学意义(P<0.05)。研究组和对照组治疗后FBG、2 hPG、HbAlc、BMI均低于治疗前,且研究组治疗后FBG、2 hPG、HbAlc水平低于对照组,差异有统计学意义(P<0.05)。治疗后,研究组FINS、HOMA-β水平高于对照组,HOMA-IR水平低于对照组,差异有统计学意义(P<0.05)。研究组和对照组治疗后HDL-C均高于治疗前,TC、TG、LDL-C水平均低于治疗前;研究组治疗后HDL-C水平高于对照组,TC、TG、LDL-C水平低于对照组,差异均有统计学意义(P<0.05)。治疗后,研究组和对照组EAI、HCT、EDI、PV水平均低于治疗前,且研究组EAI、HCT、EDI、PV水平低于对照组,差异均有统计学意义(P<0.05)。研究组不良反应总发生率为11.76%,与对照组的9.80%比较,差异无统计学意义(P>0.05)。结论达格列净联合GLP-1 RAs(利拉鲁肽)治疗2型糖尿病的疗效确切,可有效调节患者血糖及血脂水平,缓解胰岛素抵抗,改善血液流变学指标。

胰高血糖素样肽-1受体激动剂治疗儿童及青少年肥胖的疗效与安全性的系统评价

目的:系统评价胰高血糖素样肽-1(GLP-1)受体激动剂治疗儿童及青少年肥胖的疗效与安全性。方法:计算机检索PubMed、Embase、Web of Science、the Cochrane Library、中国知网、万方数据库、维普数据库中关于GLP-1受体激动剂对比安慰剂治疗儿童及青少年肥胖的随机对照试验(RCT)文献(数据库建库至2023年12月31日),根据纳入与排除标准进行文献筛选和数据提取后,运用RevMan 5.3软件进行Meta分析。结果:共纳入11篇RCT文献,涉及981例儿童及青少年肥胖患者,其中研究组542例(利拉鲁肽227例,艾塞那肽78例,司美格鲁肽134例,度拉糖肽103例),对照组439例。文献偏倚风险中等。Meta分析结果显示,与安慰剂相比,GLP-1受体激动剂可降低儿童及青少年肥胖患者的体重(MD=-3.83,95%CI=-5.94~-1.71,P=0.000 4)、体重指数(BMI)(MD=-1.94,95%CI=-3.17~-0.70,P=0.002)、BMI-Z评分(MD=-0.18,95%CI=-0.33~-0.03,P=0.02)、糖化血红蛋白水平(MD=-0.22,95%CI=-0.38~-0.07,P=0.005)、空腹血糖水平(MD=-4.43,95%CI=-8.18~-0.68,P=0.02),差异均有统计学意义。亚组分析结果显示,周制剂在降低患者体重方面可能不具有优势,但周制剂相比于日制剂能更好地降低患者的BMI、BMI-Z评分;同时,相比于不伴有2型糖尿病的儿童及青少年肥胖患者,GLP-1受体激动剂可以更好地降低伴有2型糖尿病的儿童及青少年肥胖患者的空腹血糖和糖化血红蛋白水平。相对于安慰剂,使用GLP-1受体激动剂的儿童及青少年肥胖患者的恶心(OR=3.13,95%CI=2.23~4.39,P<0.000 01)、呕吐(OR=5.97,95%CI=3.79~9.41,P<0.000 01)、腹泻(OR=1.45,95%CI=1.02~2.06,P=0.04)、头晕(OR=2.68,95%CI=1.36~5.26,P=0.004)等不良反应发生率升高,差异均有统计学意义。结论:GLP-1受体激动剂可降低儿童及青少年肥胖患者的体重、BMI、糖化血红蛋白、空腹血糖水平,但胃肠道不良反应发生率较高,使用时应注意。

骨形成肽1和聚多巴胺复合涂层修饰提高聚醚醚酮表面活性

背景:聚醚醚酮具有与人体皮质骨相近的弹性模量及良好的射线透射性、化学稳定性和生物相容性等优点,有望应用于口腔种植领域,然而其具有生物惰性,难以与周围组织形成骨结合,因此如何提高聚醚醚酮的表面活性是目前的主要问题。目的:分析聚醚醚酮表面骨形成肽1和聚多巴胺复合涂层的促成骨和成血管作用。方法:将聚醚醚酮片浸泡于多巴胺溶液中24 h,制备聚醚醚酮-聚多巴胺材料;将聚醚醚酮-聚多巴胺材料浸泡于骨形成肽1溶液中24 h,制备聚醚醚酮-聚多巴胺-骨形成肽1材料,表征材料的微观形貌、亲水性与元素组成。将骨髓间充质干细胞分别接种于聚醚醚酮、聚醚醚酮-聚多巴胺、聚醚醚酮-聚多巴胺-骨形成肽1材料表面,通过活死细胞染色和细胞骨架染色评估细胞活性与黏附状态,茜素红和骨钙素免疫荧光染色检测细胞成骨分化能力。将人脐静脉内皮细胞分别接种于3组材料表面,通过活死细胞染色和细胞骨架/血管内皮生长因子免疫荧光染色评估细胞活性及成血管水平。结果与结论:①扫描电镜下可见聚醚醚酮材料表面光滑,聚醚醚酮-聚多巴胺材料表面出现凹凸不平的沉积物,聚醚醚酮-聚多巴胺-骨形成肽1材料表面有小颗粒突起;接触角测试结果显示,聚醚醚酮-聚多巴胺-骨形成肽1材料的亲水性优于其他两种材料;X射线光电子能谱测试结果显示,骨形成肽1成功修饰于聚醚醚酮材料表面;②活死细胞染色和细胞骨架染色显示,相较于其他两种材料,聚醚醚酮-聚多巴胺-骨形成肽1材料可提高骨髓间充质干细胞的活性与黏附;茜素红和骨钙素免疫荧光染色显示,相较于其他两种材料,聚醚醚酮-聚多巴胺-骨形成肽1材料可促进骨髓间充质干细胞的成骨分化;③活死细胞染色和免疫荧光染色显示,相较于其他两种材料,聚醚醚酮-聚多巴胺-骨形成肽1材料可提高人脐静脉内皮细胞的活性与黏附及血管内皮生长因子蛋白的表达;④结果表明,骨形成肽1和聚多巴胺复合涂层可提高聚醚醚酮表面的促成骨和成血管活性。

温胆汤加减治疗气虚血瘀痰阻型缺血性脑卒中急性期的疗效及对NT-proBNP、ICAM-1和MCP-1的影响研究

目的:探讨温胆汤加减治疗气虚血瘀痰阻型缺血性脑卒中急性期患者的疗效,以及对N末端脑钠肽前体(NT-proBNP)、细胞间黏附分子-1(ICAM-1)和单核细胞趋化蛋白-1(MCP-1)水平的影响。方法:以2021年5月至2022年5月该院收治的气虚血瘀痰阻型缺血性脑卒中急性期患者100例为研究对象,根据随机数字表法分为对照组和观察组,每组50例。对照组患者给予常规治疗,观察组患者在对照组的基础上给予温胆汤加减治疗。比较两组患者的临床疗效,NT-proBNP、ICAM-1和MCP-1水平,美国国立卫生院卒中神经功能缺损评分量表(NIHSS)评分、改良Rankin量表(mRS)评分及中医证候积分。结果:治疗1个月后,观察组患者的总有效率为94.00%(47/50),显著高于对照组的80.00%(40/50),差异有统计学意义(P<0.05)。治疗1个月后,观察组患者NT-proBNP、ICAM-1和MCP-1水平显著低于对照组,血液流变学各指标(血浆黏度、血低切黏度、血高切黏度、纤维蛋白原和红细胞压积)水平显著低于对照组,差异均有统计学意义(P<0.05)。治疗7 d、1个月后,观察组患者的NIHSS评分低于对照组;治疗1个月后,观察组患者的mRS评分、中医证候积分低于对照组,差异均有统计学意义(P<0.05)。结论:温胆汤加减治疗气虚血瘀痰阻型缺血性脑卒中急性期患者的效果较好,可显著降低NT-proBNP、ICAM-1和MCP-1水平,促进血液流通和疾病的恢复,提高患者的生活质量。

Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer's disease?

Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiologic hallmarks, such as amyloid β （Aβ）, phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD.

穴位埋线结合降糖药对糖尿病患者胰高血糖素样肽-1水平的影响

目的:探讨穴位埋线结合降糖药对糖尿病患者胰高血糖素样肽-1(GLP-1)水平的影响。方法:将74例糖尿病病患者随机分为降糖药加穴位埋线组、穴位埋线组和降糖药组3组,观察患者的胰高血糖素样肽-1(GLP-1)水平变化。结果:降糖药加穴位埋线组患者的胰高血糖素样肽-1(GLP-1)水平治疗前后对比有统计学意义(P<0.05),且治疗后降糖药加穴位埋线组与穴位埋线组、降糖药组比较差异均有统计学意义(P<0.05)。通过观察对比三组糖尿病患者治疗前后GLP-1水平,评判治疗效果,降糖药加穴位埋线组有效率92.00%,穴位埋线组有效率66.67%,降糖药组有效率80.00%。降糖药加穴位埋线组有效率高于穴位埋线组、降糖药组,且有统计学意义(P<0.05)。结论:穴位埋线结合降糖药对糖尿病具有显著临床疗效。这可能是通过调节患者胰高血糖素样肽-1(GLP-1)的水平来实现的。

GLP-1RAs在治疗非典型抗精神病药相关代谢紊乱中的研究进展

接受非典型抗精神病药物(Atypical antipsychotics, AAPs)治疗的精神障碍患者发生代谢紊乱的风险明显升高。然而,针对AAPs相关代谢紊乱的干预措施有限。近年来,胰高血糖素样肽-1受体激动剂(GLP-1RAs)的减重作用已在非糖尿病患者中得到认可,且此类药物用于治疗AAPs导致的代谢紊乱的研究也愈加广泛,这可能具有显著临床意义。本文主要对GLP-1RAs治疗AAPs相关代谢紊乱的研究进展进行综述。

血清SCUBE1、Lp-PLA2水平与急性STEMI患者冠状动脉高血栓负荷的关系

目的探讨血清可溶性信号肽-CUB-表皮生长因子样结构域蛋白1(SCUBE1)、脂蛋白磷脂酶A2(Lp-PLA2)与急性ST段抬高型心肌梗死(STEMI)患者冠状动脉高血栓负荷(HTB)的关系。方法选取126例急性STEMI患者(急性STEMI组),根据血栓分级分为HTB患者57例和非HTB患者69例;另选取87名健康体检者为对照组。用酶联免疫吸附法检测血清SCUBE1、Lp-PLA2;用多因素Logistic回归分析急性STEMI患者冠状动脉HTB的影响因素;用受试者工作特征(ROC)曲线评估血清SCUBE1、Lp-PLA2水平对急性STEMI患者冠状动脉HTB的预测价值。结果急性STEMI组血清SCUBE1、Lp-PLA2水平高于对照组(P均<0.05)。HTB患者年龄、吸烟比例、低密度脂蛋白胆固醇、白细胞计数、SCUBE1、Lp-PLA2水平高于非HTB患者(P均<0.05),两者性别、基础疾病、罪犯血管、Gensini评分、左室射血分数比较差异无统计学意义(P均>0.05)。多因素Logistic回归分析显示,年龄增加、吸烟和血清SCUBE1、Lp-PLA2水平升高为急性STEMI患者冠状动脉HTB的独立危险因素(P均<0.05)。ROC曲线分析显示,血清SCUBE1、Lp-PLA2水平联合预测急性STEMI患者冠状动脉HTB的曲线下面积为0.874,大于二者单独预测的0.794、0.791(P均<0.05)。结论急性STEMI患者血清SCUBE1、Lp-PLA2水平升高与冠状动脉HTB密切相关,二者联合检测对急性STEMI患者冠状动脉HTB的预测价值较高。