The effect of vitamin K4 supplementation on insulin resistance in individuals with type 2 diabetes: a double-blind randomised placebo-controlled clinical trial.

Article

作者: Ali, Amani M ; Abbassi, Maggie M ; Sabry, Nirmeen A ; Fawzi, May ; Mousa, Shrook

PURPOSEThe purpose of this study was to assess the possible clinical effects of vitamin K4 supplementation in individuals with type 2 diabetes namely insulin resistance, glycaemic control, and lipid profile.METHODSThis was a prospective randomised double-blind placebo-controlled clinical trial. A total of 106 patients were randomised to receive either 1 mg of vitamin K4 (menadiol diacetate) or placebo for 24 weeks.RESULTSNinety patients (n = 45 in each study group) were included in the final analysis. After 24 weeks, homeostatic model assessment of insulin resistance (HOMA-IR) (16.54 ± 7.81 vs. 29.09 ± 36.56, P = 0.027) and fasting serum insulin (FSI) (6.86 ± 3.45 vs. 11.13 ± 12.66 µU/ml, P = 0.032) were significantly lower in the vitamin K group compared to placebo. Additionally, triglycerides (TG) (144.94 ± 50.7 vs. 172.8 ± 101.5 mg/dl, P = 0.031) and very low-density lipoproteins (VLDL) levels (28.9 ± 9.88 vs. 34.6 ± 20.30 mg/dl, P = 0.027) decreased significantly in the vitamin K group after 24 weeks compared to baseline. Moreover, more patients in the vitamin K group (35.6%) had their antidiabetic medication doses reduced after 24 weeks compared to placebo (13.3%, P = 0.029).CONCLUSIONVitamin K4 supplementation for 24 weeks is capable of improving insulin resistance and TG levels in individuals with type 2 diabetes. In addition, the improvement in insulin resistance was reflected in the decrease in antidiabetic medication doses. However, it did not affect fasting plasma glucose (FPG) or glycated haemoglobin (HbA₁c).TRIAL REGISTRATIONThe study was registered on clinicaltrials.gov with ID: NCT04285450.

2023-12-01·Journal of Taibah University Medical Sciences

Protective effect of moringa seed extract on kidney damage in rats fed a high-fat and high-fructose diet

Article

作者: Siwi, Gita N ; Budiani, Dyah R ; Rezkita, Bastomy E ; Putri, Indah S

ObjectiveMoringa is a common plant that contains high levels of antioxidants. In this study, we aimed to analyze the protective effect of moringa seed extract on the kidneys of a rat model maintained on a high-fat and high-fructose (HFHF) diet.MethodsAn experiment with a pretest-posttest control group design was used to measure metabolic parameters and determine kidney function, while a posttest-only method was used for the control group to determine glomerular volume and superoxide dismutase (SOD) expression. Purposive sampling was used on 28 rats divided into four groups: a control (K1) group, and three groups fed a HFHF diet for 53 days (K2, K3, and K4). Subsequently, K3 and K4 were given 150 and 200 mg/kg BW per day moringa seed extract for 28 days. Data were analyzed using IBM® SPSS® Statistics version 22 software.ResultsAnalysis showed that the diet increased the risk of metabolic syndrome, as evidenced by weight gain, glucose, and triglycerides. The optimal dose of moringa seed extract significantly improved glomerular volume (p = 0.001). The expression of SOD in kidney tubules and glomeruli was significantly different with each group (p = 0.002 and p = 0.001) respectively.ConclusionThe administration of moringa seed extract provided a protective effect on the kidney by reducing serum creatinine levels, improving overall structure, and increasing the expression of SOD, a key antioxidant.

2023-09-01·Small (Weinheim an der Bergstrasse, Germany)

Enhanced Liposomal Drug Delivery Via Membrane Fusion Triggered by Dimeric Coiled-Coil Peptides.

Article

作者: Shen, Mengjie ; Boyle, Aimee L ; Singhal, Ankush ; Crone, Niek ; Kros, Alexander ; Sevink, Geert Jan Agur ; Zeng, Ye

An ideal nanomedicine system improves the therapeutic efficacy of drugs. However, most nanomedicines enter cells via endosomal/lysosomal pathways and only a small fraction of the cargo enters the cytosol inducing therapeutic effects. To circumvent this inefficiency, alternative approaches are desired. Inspired by fusion machinery found in nature, synthetic lipidated peptide pair E4/K4 is used to induce membrane fusion previously. Peptide K4 interacts specifically with E4, and it has a lipid membrane affinity and resulting in membrane remodeling. To design efficient fusogens with multiple interactions, dimeric K4 variants are synthesized to improve fusion with E4-modified liposomes and cells. The secondary structure and self-assembly of dimers are studied; the parallel PK4 dimer forms temperature-dependent higher-order assemblies, while linear K4 dimers form tetramer-like homodimers. The structures and membrane interactions of PK4 are supported by molecular dynamics simulations. Upon addition of E4, PK4 induced the strongest coiled-coil interaction resulting in a higher liposomal delivery compared to linear dimers and monomer. Using a wide spectrum of endocytosis inhibitors, membrane fusion is found to be the main cellular uptake pathway. Doxorubicin delivery results in efficient cellular uptake and concomitant antitumor efficacy. These findings aid the development of efficient delivery systems of drugs into cells using liposome-cell fusion strategies.

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