Antiaging activity of low molecular weight peptide from Paphia undulate

Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats was investigated. P. undulate flesh was homogenized and digested using papain under optimal conditions, then subjected to Sephadex G-25 chromatography to isolate the LMWP. Administration of LMWP significantly reversed D-galactose-induced oxidative stress by increasing the activities of glutathione peroxidase (GPx) and catalase (CAT), and by decreasing the level of malondialdehyde (MDA). This process was accompanied by increased collagen synthesis. The LMWP prevented photoaging and promoted dermis recovery and remission of elastic fiber hyperplasia. Furthermore, treatment with the LMWP helped to regenerate elastic fibers and the collagen network, increased superoxide dismutase (SOD) in the serum and significantly decreased MDA. Thermal scald-induced inflammation and edema were also relieved by the LWMP, while wound healing in skin was promoted. These results suggest that the LMWP from P. undulate could serve as a new antiaging substance in cosmetics.

Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy

AIM:To investigate the relationship between the function of vagus nerve and peptide YY 3-36 and ghrelin levels after subtotal gastrectomy.METHODS:We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer.All surgeries were performed by a single skilled surgeon.We measured peptide YY 3-36,ghrelin,leptin,insulin,growth hormone levels,and body weight immediately before and one month after surgery.RESULTS:Vagus nerve preservation group showed less body weight loss and less increase of peptide YY 3-36 compared with vagotomy group(-5.56 ± 2.24 kg vs-7.85 ± 1.57 kg,P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL,P = 0.021,respectively).Moreover,patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY 3-36 level,typically less than 20% [6(66.7%) vs 0(0.0%),P = 0.011,odd ratio = 3.333,95% confidence interval(1.293,8.591)].CONCLUSION:Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy,and this phenomenon may be related to the suppressed activity of peptide YY 3-36.

Glucagon-like peptide-1 receptor agonists favorably address all components of metabolic syndrome

Cardiovascular death is the leading cause of mortality for patients with type 2 diabetes mellitus. The etiologyof cardiovascular disease in diabetes may be divided into hyperglycemia per se and factors operating through components of metabolic syndrome(Met S). Hyperglycemia causes direct injury to vascular endothelium and possibly on cardiac myocytes. Met S is a cluster of risk factors like obesity, hyperglycemia, hypertension and dyslipidemia. The incidence of this syndrome is rising globally. Glucagon-like peptide-1 receptor agonists(GLP-1RA) are a group of drugs, which address all components of this syndrome favorably. Experimental evidence suggests that they have favorable actions on myocardium as well. Several compounds belonging to GLP-1RA class are in market now and a large number awaiting their entry. Although, originally this class of drugs emerged as a treatment for type 2 diabetes mellitus, more recent data generated revealed beneficial effects on multiple metabolic parameters. We have studied literature published between 2000 and 2016 to look into effects of GLP-1RA on components of Met S. Results from recently concluded clinical trials suggest that some of the molecules in this class may have favorable effects on cardiovascular outcome.

Liver decompensation after rapid weight loss from semaglutide in a patient with non-alcoholic steatohepatitis -associated cirrhosis

There is rapidly increasing uptake of GLP-1 (glucagon-like peptide-1) agonistssuch as semaglutide worldwide for weight loss and management of non-alcoholicsteatohepatitis (NASH). remains a paucity of safety data in the vulnerable NASHcirrhotic population. We report herein the first documented case of liver decompensationand need for liver transplant waitlisting in a patient with NASHcirrhosistreated with semaglutide. Rapid weight loss led to the development ofascites and hepatic encephalopathy and an increase in the patients Model forEndstage Liver Disease-Na (MELD-Na) score from 11 to 22. Aggressive nutritionalsupplementation was commenced and the semaglutide was stopped. Overthe following months she regained her weight and her liver recompensated andher MELD-Na decreased to 13, allowing her to be delisted from the transplantwaitlist. This case serves as a cautionary tale to clinicians using semaglutide in thecirrhotic population and highlights the need for more safety data in this patientgroup.

Effects of Incretin-based Therapies on Weight-related Indicators among Patients with Type 2 Diabetes: A Network Meta-analysis

Objective To evaluate the effects of incretin-based therapies on body weight as the primary outcome,as well as on body mass index(BMI)and waist circumference(WC)as secondary outcomes.Methods Databases including Medline,Embase,the Cochrane Library,and clinicaltrials.gov(www.clinicaltrials.gov)were searched for randomized controlled trials(RCTs).Standard pairwise meta-analysis and network meta-analysis(NMA)were both carried out.The risk of bias(ROB)tool recommended by the Cochrane handbook was used to assess the quality of studies.Subgroup analysis,sensitivity analysis,meta-regression,and quality evaluation based on the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)were also performed.Results A total of 292 trials were included in this study.Compared with placebo,dipeptidyl-peptidase IV inhibitors(DPP-4 Is)increased weight slightly by 0.31 kg[95%confidence interval(CI):0.05,0.58]and had negligible effects on BMI and WC.Compared with placebo,glucagon-like peptide-1 receptor agonists(GLP-1 RAs)lowered weight,BMI,and WC by-1.34 kg(95%CI:-1.60,-1.09),-1.10 kg/m2(95%CI:-1.42,-0.78),and-1.28 cm(95%CI:-1.69,-0.86),respectively.Conclusion GLP-1 RAs were more effective than DPP-4 Is in lowering the three indicators.Overall,the effects of GLP-1 RAs on weight,BMI,and WC were favorable.

Effects of Sleeve Gastrectomy Surgery with Modified Jejunoileal Bypass on Body Weight, Food Intake and Metabolic Hormone Levels of Rats

This study examined the effects of a combined surgery of sleeve gastrectomy （SG） and modified jejunoileal bypass （JIB） on the body weight, food intake, and the plasma levels of active glucagon-like peptide-1 （GLP-1） and total ghrelin of rats. Rats were divided into 3 groups in terms of different surgical protocol： SG-JIB （n=12）, SG （n=12）, JIB （n=12） and sham surgery groups （n-10）. In SG-JIB group, rats was subjected to sleeve gastrectomy and end to side anastomosis of part of the jejunum （25 cm from the ligament of Treitz） to the ileum 25 cm proximal to the cecum. The body weight and food intake were evaluated during 10 consecutive weeks postoperatively. The levels of active GLP-1 and total ghrelin in the plasma of the rats were measured by ELISA assay. The results showed that the SG-JIB treated rats relative to SG- or JIB-treated ones produced a sustained reduction in food intake and weight gain. The level of active GLP-1 was elevated and total ghrelin level decreased in SG-JIB-treated rats as compared with SG- or JIB-treated ones. It was concluded that SG-JIB could efficiently reduce the body weight and food intake, alter obesity-related hormone levels of the rats, indicating that SG-JIB may be potentially used for the treatment of obesity.

In vivo biodistribution of topical low molecular weight heparin-taurocholate in a neovascularized mouse cornea

AIM： To investigate the ocular biodistribution and clearance of topically administered 7-taurocholic acid conjugated low-molecular weight heparin（LHT7） in a neovascularized mouse cornea using an in vivo optical imaging system. METHODS： A total of 10 eyes of 6 to 8-week-old BALB/c mice were analyzed. Corneal neovascularization（CoNV） was induced in the inferior cornea（IC） of each animal by penetrating the stroma with two interrupted sutures. The development of CoNV was verified after one week and the area of each neovascularized region was measured. A near-infrared fluorescent probe of 20 μmol/L Cy5.5 labeled LHT7（LHT7-Cy5.5） in 0.02 mL solution was topically instilled onto the cornea in the experimental group（n=5）. Free-Cy5.5 of 20 μmol/L in 0.02 mL was instilled in the control group（n=5）. In vivo optical images were obtained before instillation and 5 min, 2, 4, and 6 h after instillation. The intensities were separately measured at the superior cornea（SC） and the IC. RESULTS： The mean CoNV areas were 1.97±0.17 mm^2 and 1.92±0.96 mm^2 in the experimental and control groups, respectively（P=0.832）. The SC remained normal in all 10 subject animals. The IC intensity of the LHT7-Cy5.5 was greater than the SC intensity at 5 min（P=0.038）, 2 h（P=0.041）, and 4 h（P=0.041） after application. The IC intensity fell to less than half of its initial value（42.9%±8.6%） at 6 h in the experimental group. In the control mice, here were no significant differences in the free-Cy5.5 intensity between the IC and SC. CONCLUSION： Topically administered LHT7 shows a high biodistribution in CoNV areas for 4 h and should be reapplied accordingly to maintain its effects. In vivo optical imaging can be a useful tool for evaluating the ocular biodistribution of a drug in an animal model.

碱性蛋白酶酶解蛋白制备活性肽的质控研究

以胶原蛋白和大豆分离蛋白为主要研究对象,应用体积排阻色谱(SEC)结合多角度激光光散射(MALLS)及示差折光(RI)联用技术对碱性蛋白酶酶解蛋白制备肽段的过程进行了详细分析。在酶解过程中,不同来源的胶原蛋白(牛、鸡)和大豆分离蛋白在分子量分布、体系的分散度及粒径变化规律上表现出了典型的差异。结果表明,牛胶原蛋白在酶解开始时就迅速被降解产生了大量小分子肽段,鸡胶原蛋白相对于牛胶原蛋白在相同的酶解条件下更难产生小分子肽段,大豆分离蛋白随着酶的加入则是表现出了先聚集再降解的特性。SEC-MALLS技术可以有效把控蛋白酶解的过程以及体系中肽段分子量分布,该技术可以为活性肽产品的开发及品质检测提供依据。

海鲜菇美拉德肽的制备及其风味特性研究

以海鲜菇(Hypsizygus marmoreus)蛋白肽为原料,采用响应面法分析优化海鲜菇美拉德肽制备工艺,并通过褐变程度、产物分子量分布、感官评价、电子舌及超滤等特征性指标和评价手段,明确美拉德反应对海鲜菇蛋白肽风味特性的影响。结果表明,海鲜菇美拉德肽的最佳制备条件为葡萄糖与D-木糖质量比4∶1、反应温度110℃和反应时间56 min。与海鲜菇蛋白肽相比,制备的海鲜菇美拉德肽咸味强烈,并伴有鲜味产生,整体接受度好,在294 nm和420 nm下吸光值显著增加,并推测分子量大于180~500 Da的组分可能为美拉德反应的主要活性肽段。超滤结果表示,海鲜菇美拉德肽呈咸鲜味的肽分子量主要集中在500 Da以下。该研究结果证明美拉德反应可有效提升海鲜菇蛋白肽的咸鲜味,使其风味层次更加丰富,可为扩展可替代钠盐的新型食用菌调味领域的研究和应用提供理论基础。

响应面法优化金鲳鱼皮抗氧化肽制备工艺及其组成分析

为促进金鲳鱼皮资源的综合利用,本研究以金鲳鱼皮为原料,探究其抗氧化肽的最佳制备工艺。以水解度和DPPH自由基清除率为考察指标,在单因素实验的基础上,结合响应面试验对金鲳鱼皮的酶解条件包括蛋白酶种类、酶解时间、加酶量、酶解温度以及酶解pH进行优化,得到金鲳鱼皮抗氧化肽的最佳酶解条件,并测定最佳条件下得到的酶解产物的分子量分布及氨基酸组成。结果表明,制备金鲳鱼皮抗氧化肽酶解效果最优的酶为碱性蛋白酶,其最佳酶解工艺为:酶解温度52.3℃、酶解pH10.0、酶解时间8.4 h、加酶量15409 U/g。通过最佳酶解条件制备得到的酶解产物的DPPH自由基清除率为81.59%±2.96%,其分子量主要分布在3000 Da以下,占比高达79.20%,其含有17种氨基酸,甘氨酸为主要氨基酸,疏水性氨基酸占比35.28%。本研究结果为金鲳鱼皮的高值化利用与抗氧化肽的筛选提供了一定的理论依据。

超声辅助酶法制备富锌低分子牡蛎肽的工艺研究

以香港牡蛎为原料,通过酶解法制备富锌牡蛎酶解产物并对其相对分子量图谱和氨基酸组成进行分析。经过蛋白酶筛选、超声预处理后应用单因素试验、正交试验以及时间曲线优化酶解工艺,提高酶解产物的水解度和生物锌释放量。采用超声功率500 W、超声时间10 min进行预处理,选择动物蛋白酶进行酶解。最佳酶解工艺为加酶量1.6%、酶解时间4 h、酶解温度50℃、料液比1∶4、pH 6.5,得到牡蛎酶解产物水解度为49.581%。酶解产物的锌含量(以干基计)为680.831 mg/kg。牡蛎肽相对分子量小于1000 Da的组分达到81.87%,富含酸性氨基酸谷氨酸和天冬氨酸。香港牡蛎酶解产物中含有丰富的小分子肽,氨基酸组成较完善,锌含量较高,可为后续富锌产品的开发奠定基础。

九香虫的营养评价及酶解多肽制备工艺优化

目的:探究九香虫营养成分组成与九香虫多肽的最佳酶解工艺条件。方法:按照国标法测定脂肪、蛋白质、总糖含量和脂肪酸组成,采用标准曲线法测定总黄酮和多酚含量;以九香虫多肽得率为指标,采用响应面法优化九香虫的酶解工艺条件;采用氨基酸分析仪、高效凝胶渗透色谱法测定九香虫酶解物的氨基酸组成和相对分子质量分布;考察九香虫酶解物对DPPH自由基和ABTS+自由基的清除能力及总还原能力。结果:九香虫粗脂肪含量为43.40%,蛋白质含量为37.08%,总糖含量为7.64%,总黄酮含量为1.67%,总酚含量为1.90%;九香虫最佳酶解工艺为蒸煮时间5 h,酶解pH 10,酶解时间6 h,酶解温度55℃,该条件下多肽得率为35.74%;九香虫酶解物必需氨基酸和非必需氨基酸的比值为70.46%,九香虫酶解物相对分子质量<1000所占比例为88.1%;九香虫酶解物质量浓度为1.0 mg/mL时ABTS+自由基清除率达到88.44%。结论:在最佳酶解工艺下,九香虫多肽得率为35.74%,具有较高的营养价值和较好的抗氧化活性。

血浆N末端B型钠尿肽前体对中重度支气管肺发育不良的预测价值

目的探讨血浆N末端B型钠尿肽前体(N-terminal pro-B-type natriuretic peptide,NTproBNP)在预测中重度支气管肺发育不良(bronchopulmonary dysplasia,BPD)风险中的临床价值。方法采用前瞻观察性研究方法,选择2021年6月—2022年12月福建省妇幼保健院新生儿科收治的胎龄<30周极/超早产儿95例。分别于出生后第1、7、14、21天检测NTproBNP水平并收集住院期间基本资料,根据美国国家儿童健康与人类发展研究所(National Institute of Child Health and Human Development,NICHD)诊断标准,分为无-轻度BPD组(n=74)和中-重度BPD组(n=21)。比较2组不同时间点NTproBNP水平。结果中-重度BPD组胎龄、出生体质量均低于无-轻度BPD组(P<0.05);中-重度BPD组胎膜早破>18 h、≥3级新生儿呼吸窘迫综合征(respiratory distress syndrome,RDS)、有创机械通气时间>7 d、症状性动脉导管未闭(symptomatic patent ductus arteriosus,sPDA)、晚发型败血症、早产儿视网膜病(retinopathy of prematurity,ROP)的发生率均高于无-轻度BPD组,差异有统计学意义(P<0.05)。无-轻度BPD组NTproBNP水平在出生后第1天最高,中-重度BPD组NTproBNP水平在出生后第7天最高,随后逐渐降低。中-重度BPD组各时间点NTproBNP水平均高于无-轻度BPD组,差异有统计学意义(P<0.05)。出生后第1天NTproBNP水平为5631.52 pg/mL,是中重度BPD最佳预测参考值,受试者工作特征(receiver operating characteristic,ROC)曲线下面积为0.89(95%CI0.83~0.95),诊断准确性为85.71%。结论出生后第1天NTproBNP水平有助于早期预测中重度BPD发病风险,动态监测NTproBNP趋势可能对疾病防治提供一定参考价值。

胰高血糖素样肽-1减肥应用的伦理探讨

针对胰高血糖素样肽-1受体激动剂类药物在治疗肥胖方面的医学价值和潜在滥用的现实情况,深入探讨了该类药物在非糖尿病肥胖治疗中的超适应证应用及其伦理问题,包括医疗资源的合理分配、患者知情同意的重要性以及社会审美标准对医疗决策的影响。并针对上述伦理问题,提出了包括加强药物处方规范、提高公众药物知识、确保患者知情同意等建议。旨在促进胰高血糖素样肽-1受体激动剂类药物在肥胖治疗中的合理及伦理使用,保障医疗伦理和患者安全。

仿刺参不同部位ACE抑制活性分析及活性肽制备工艺优化

本文对仿刺参具有高降血压活性部位进行筛选并优化其活性肽制备工艺。采用酶解法对仿刺参不同部位(体壁、肠、卵)进行水解,以血管紧张素转换酶(Angiotensin converting enzyme,ACE)抑制率为指标筛选最适蛋白酶,通过对各酶解物ACE抑制率的半数抑制浓度(IC_(50))测定比较筛选出最优抑制活性部位。经单因素实验与响应面试验优化确定活性肽最佳酶解制备条件,对蛋白酶解物进行分子量测定确定其分布范围,经超滤膜分离后对不同组分的ACE抑制活性分析。结果显示,选用碱性蛋白酶为最适水解酶,体壁、肠、卵各蛋白酶解物的ACE抑制率的IC50分别为1.11、4.02、0.65 mg/mL,仿刺参卵具有更好的ACE抑制效果,为最优抑制活性部位。其最佳的酶解制备工艺参数为:酶解时间5 h,加酶量3.5 U/mg,酶解温度65.26℃,底物浓度3.51%,酶解pH9.02,在该条件下仿刺参卵酶解产物的ACE抑制率为80.65%±0.52%,与预测值接近。蛋白酶解产物的分子量集中分布在3000 Da以下,占总含量的98.37%,其中1000~3000 Da占比9.50%,小于1000 Da占比88.87%。超滤膜分离所得低聚肽组分ACE抑制活性(IC_(50)=0.30 mg/mL)显著(P<0.05)强于经工艺优化后酶解物及截留液组分。本研究结果为仿刺参副产物高值化利用提供理论依据,可作为分离纯化制备降血压肽的优质资源。

胰高糖素样肽-1受体激动剂临床应用合理性和安全性分析

目的调查住院患者接受胰高糖素样肽-1受体激动剂(GLP-1RA)治疗的情况,了解该类药物的应用现状和不良反应并分析其危险因素,为规范其临床合理应用提供依据。方法汇总国内外GLP-1RA权威指南、临床研究和专家共识,结合说明书形成GLP-1RA临床应用合理性评价标准。回顾性收集2021年1月至2023年4月广州医科大学附属第二医院使用GLP-1RA的住院患者的病历资料,按照已制订的评价标准进行合理性和安全性分析,并提出合理用药建议。结果共有261例患者应用GLP-1RA,其中有效病例258例,不合理使用病例共160例,不合理使用率达62.02%,以超适应证用药不合理和用法用量不适宜为主要原因;发生不良反应共3例,发生率为1.16%,主要是低血糖和转氨酶升高;临床使用期间应多关注患者血糖和肝肾功能指标,关注GLP-1RA的适应证、用法用量、禁忌证和联合用药等方面。结论GLP-1RA降糖、减重及保护心血管的作用备受关注,本研究针对医生使用GLP-1RA临床实践存在的问题和不良反应,提供具体可行的指导建议,以促进GLP-1RA的合理使用。

Semaglutide for the management of diabesity:The real-world experience

BACKGROUND Diabesity(diabetes as a consequence of obesity)has emerged as a huge healthcare challenge across the globe due to the obesity pandemic.Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials.However,more real-world data is needed to further improve the clinical practice.AIM To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity.METHODS We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States.Several parameters were analyzed including demographic information,the data on improvement of glycated hemoglobin(HbA1c),body weight reduction and insulin dose adjustments at 6 and 12 months,as well as at the latest follow up period.The data was obtained from the electronic patient records between January 2019 to May 2023.RESULTS 106 patients(56 males)with type 2 diabetes mellitus(T2DM),mean age 60.8±11.2 years,mean durations of T2DM 12.4±7.2 years and mean semaglutide treatment for 2.6±1.1 years were included.Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4±24.6 kg to 99.9±24.9 kg at 12 months and 96.8±22.9 kg at latest follow up and HbA1c improvement from baseline of 82±21 mmol/mol to 67±20 at 12 months and 71±23 mmol/mol at the latest follow up.An insulin dose reduction from mean baseline of 95±74 units to 76.5±56.2 units was also observed at the latest follow up.Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide.CONCLUSION Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight,HbA1c and insulin doses without major adverse effects.Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of patients with diabesity.

不同分子量核桃肽在小鼠体内分布的初步探究

目的制备相对分子质量(M_(r))不同的核桃肽,并初步探究核桃肽经Cy7标记后在小鼠体内分布情况。方法利用不同酶降解核桃粕制备核桃肽,GPC色谱法测定核桃肽M_(r),利用Cy7标记的核桃肽进行小鼠活体成像,观察其在小鼠体内的分布情况。结果不同酶酶解得到的样品M_(r)占比不同,样品Ⅰ小分子量成分占比高,收率高,通过Cy7标记不同样品在小鼠体内呈现不同的荧光强度,Cy7-样品Ⅰ在脑部显现荧光信号,Cy7-样品Ⅱ和Cy7-样品Ⅲ仅在接受注射的尾部显现强荧光信号。结论不同酶制备的核桃肽在小鼠体内呈现不同的分布,样品Ⅰ中可能含有增强脑部荧光的肽段。

口服生物活性胶原蛋白肽的筛选与体外功效评价

本文研究9个胶原蛋白肽的溶解度、羟脯氨酸含量、肽相对分子量和促进人真皮成纤维细胞生长功效四个方面的特性,为开发人真皮成纤维细胞生长的生物活性胶原蛋白肽功能性饮品提供参考。

牡蛎肽对酒精性肝损伤与体力疲劳的影响

研究牡蛎肽对酒精性肝损伤和体力疲劳的影响。采用液相色谱测定牡蛎肽的分子质量和氨基酸含量,并通过动物实验研究牡蛎肽缓解小鼠酒精性肝损伤和体力疲劳的作用。设置低(0.25 g/kg bw)、中(0.5 g/kg bw)、高(1.0 g/kg bw)3个剂量组,以及模型对照组。研究结果显示:牡蛎肽的分子质量<1500 u的占比85%;氨基酸总量为58.44 g/100g;体内实验结果显示,缓解酒精性肝损伤实验中,3个剂量组小鼠肝脏的丙二醛(MDA)、甘油三酯(TG)含量显著低于对照组,谷胱甘肽(GSH)含量显著高于对照组。肝脏组织病理切片结果显示,高剂量组小鼠肝脏组织病理损伤有不同程度的改善;缓解体力疲劳动物实验中,中、高剂量组的小鼠游泳时间显著提升,3个剂量组小鼠血乳酸、血清尿素含量与对照组相比显著性下降。结论:牡蛎肽的分子质量较小,氨基酸含量较高,具有缓解酒精性肝损伤和体力疲劳的作用。