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Nutrition Journal Oct 2023It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is suggested that supplementation with milk protein (MP) has the potential to ameliorate the glycemic profile; however, the exact impact and certainty of the findings have yet to be evaluated. This systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) assessed the impact of MP supplementation on the glycemic parameters in adults.
METHODS
A systematic search was carried out among online databases to determine eligible RCTs published up to November 2022. A random-effects model was performed for the meta-analysis.
RESULTS
A total of 36 RCTs with 1851 participants were included in the pooled analysis. It was displayed that supplementation with MP effectively reduced levels of fasting blood glucose (FBG) (weighted mean difference (WMD): -1.83 mg/dL, 95% CI: -3.28, -0.38; P = 0.013), fasting insulin (WMD: -1.06 uU/mL, 95% CI: -1.76, -0.36; P = 0.003), and homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: -0.27, 95% CI: -0.40, -0.14; P < 0.001) while making no remarkable changes in serum hemoglobin A1c (HbA1c) values (WMD: 0.01%, 95% CI: -0.14, 0.16; P = 0.891). However, there was a significant decline in serum levels of HbA1c among participants with normal baseline body mass index (BMI) based on sub-group analyses. In addition, HOMA-IR values were significantly lower in the MP supplement-treated group than their untreated counterparts in short- and long-term supplementation (≤ 8 and > 8 weeks) with high or moderate doses (≥ 60 or 30-60 g/d) of MP or whey protein (WP). Serum FBG levels were considerably reduced upon short-term administration of a low daily dose of WP (< 30 g). Furthermore, the levels of serum fasting insulin were remarkably decreased during long-term supplementation with high or moderate daily doses of WP.
CONCLUSION
The findings of this study suggest that supplementation with MP may improve glycemic control in adults by reducing the values of fasting insulin, FBG, and HOMA-IR. Additional trials with longer durations are required to confirm these findings.
Topics: Adult; Humans; Glycated Hemoglobin; Blood Glucose; Milk Proteins; Diabetes Mellitus, Type 2; Dietary Supplements; Insulin; Insulin Resistance; Whey Proteins
PubMed: 37798798
DOI: 10.1186/s12937-023-00878-1 -
Phytotherapy Research : PTR Nov 2023Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid... (Review)
Review
Cardiovascular diseases are currently the primary cause of mortality in the whole world. Growing evidence indicated that the disturbances in cardiac fatty acid metabolism are crucial contributors in the development of cardiovascular diseases. The abnormal cardiac fatty acid metabolism usually leads to energy deficit, oxidative stress, excessive apoptosis, and inflammation. Targeting fatty acid metabolism has been regarded as a novel approach to the treatment of cardiovascular diseases. However, there are currently no specific drugs that regulate fatty acid metabolism to treat cardiovascular diseases. Many traditional Chinese medicines have been widely used to treat cardiovascular diseases in clinics. And modern studies have shown that they exert a cardioprotective effect by regulating the expression of key proteins involved in fatty acid metabolism, such as peroxisome proliferator-activated receptor α and carnitine palmitoyl transferase 1. Hence, we systematically reviewed the relationship between fatty acid metabolism disorders and four types of cardiovascular diseases including heart failure, coronary artery disease, cardiac hypertrophy, and diabetic cardiomyopathy. In addition, 18 extracts and eight monomer components from traditional Chinese medicines showed cardioprotective effects by restoring cardiac fatty acid metabolism. This work aims to provide a reference for the finding of novel cardioprotective agents targeting fatty acid metabolism.
Topics: Humans; Cardiovascular Diseases; Heart; Medicine, Chinese Traditional; PPAR alpha; Fatty Acids; Energy Metabolism
PubMed: 37533230
DOI: 10.1002/ptr.7965 -
Expert Opinion on Investigational Drugs Jun 2008Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC). (Review)
Review
BACKGROUND
Enzastaurin is a novel antineoplastic and antiangiogenic agent that acts through inhibition of protein kinase C (PKC).
OBJECTIVE
This review summarizes the scientific rationale and current clinical evidence for the use of enzastaurin in oncology.
METHODS
We performed a systematic review of the literature using the keywords protein kinase C-beta and enzastaurin in order to characterize the therapeutic target PKC-beta. We then reviewed the in-vitro, Phase I, and Phase II data for enzastaurin with a focus on hematologic malignancies.
RESULTS/CONCLUSIONS
After preliminary Phase I trials established a favorable toxicity profile, enzastaurin has been studied in completed and ongoing Phase II and III studies in solid and hematologic malignancies, including B-cell lymphomas where the rationale for its use is most promising.
Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Clinical Trials as Topic; Enzyme Activation; Humans; Indoles; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasms; Neovascularization, Pathologic; Phosphoinositide-3 Kinase Inhibitors; Phosphorylation; Protein Kinase C; Protein Kinase C beta; Protein Kinase Inhibitors; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt; Salvage Therapy; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 18491994
DOI: 10.1517/13543784.17.6.939 -
Journal of Genetics and Genomics = Yi... Mar 2024Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating...
Protein post-translational modifications (PTMs), such as ubiquitination, phosphorylation, and small ubiquitin-like modifier (SUMO)ylation, are crucial for regulating protein stability, activity, subcellular localization, and binding with cofactors. Such modifications remarkably increase the variety and complexity of proteomes, which are essential for regulating numerous cellular and physiological processes. The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development. Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations. Thus, a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes. This review discusses the progress of protein ubiquitination, phosphorylation, histone acetylation and methylation, SUMOylation, and S-nitrosylation in the regulation of auxin signaling.
Topics: Indoleacetic Acids; Protein Processing, Post-Translational; Signal Transduction; Sumoylation; Ubiquitination
PubMed: 37451336
DOI: 10.1016/j.jgg.2023.07.002 -
Cardiovascular Research Mar 2024The function of perilipin 1 in human metabolism was recently highlighted by the description of PLIN1 variants associated with various pathologies. These include severe...
The function of perilipin 1 in human metabolism was recently highlighted by the description of PLIN1 variants associated with various pathologies. These include severe familial partial lipodystrophy and early onset acute coronary syndrome. Additionally, certain variants have been reported to have a protective effect on cardiovascular diseases. The role of this protein remains controversial in mice and variant interpretation in humans is still conflicting. This literature review has two primary objectives (i) to clarify the function of the PLIN1 gene in lipid metabolism and atherosclerosis by examining functional studies performed in cells (adipocytes) and mice and (ii) to understand the impact of PLIN1 variants identified in humans based on the variant's location within the protein and the type of variant (missense or frameshift). To achieve these objectives, we conducted an extensive analysis of the relevant literature on perilipin 1, its function in cellular models and mice, and the consequences of its mutations in humans. We also utilized bioinformatics tools and consulted the Human Genetics Cardiovascular Disease Knowledge Portal to enhance the pathogenicity assessment of PLIN1 missense variants.
Topics: Animals; Humans; Mice; Atherosclerosis; Lipid Metabolism; Lipodystrophy, Familial Partial; Mutation; Perilipin-1; Perilipin-2; Phosphoproteins
PubMed: 38214891
DOI: 10.1093/cvr/cvae005 -
The Aging Male : the Official Journal... Dec 2023This study aimed to determine whether the C-reactive protein-to-albumin ratio (CAR) can serve as a prognostic marker in patients with sepsis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine whether the C-reactive protein-to-albumin ratio (CAR) can serve as a prognostic marker in patients with sepsis.
METHODS
Chinese and English databases were searched to retrieve the included literature. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) with their 95% confidence interval (CI) were calculated using the bivariate model. Moreover, the hazard ratio (HR) and 95% CI were calculated using the random effect model.
RESULTS
Nine articles comprising 3224 patients with sepsis were included in the meta-analysis. The pooled SEN was 0.73 (95% CI 0.65-0.80), the pooled SPE was 0.78 (95% CI 0.69-0.84), the pooled PLR was 3.29 (95% CI 2.15-5.03), the pooled NLR was 0.35 (95% CI 0.24-0.49), and the pooled DOR was 9.50 (95% CI 4.38-20.59). The AUC under the SROC was 0.82 (95% CI 0.78-0.85) for the prognostic meta-analysis. The pooled HR was 1.10 (95% CI 1.02-1.18).
CONCLUSIONS
This meta-analysis suggests that a high CAR level is associated with increased mortality and a poor prognosis.
Topics: Humans; C-Reactive Protein; Prognosis; Albumins; Sepsis; Area Under Curve
PubMed: 37752726
DOI: 10.1080/13685538.2023.2261540 -
International Journal of Molecular... Jun 2023Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII...
Through a process termed , platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from , , and that diminish clot retraction and have numerous other health benefits. Caffeic acid and diindolylmethane, both common in plants and vegetables, likewise reduce clot retraction, as do all-trans retinoic acid (a vitamin A derivative), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib. Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) both enhance clot retraction. Most studies aiming to identify mechanisms of clot retraction modulators have focused on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I and the decreased phosphorylation of various phospholipases (e.g., phospholipase A2 (PLA) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ), c-Jun N-terminal kinase, and (PI3Ks). One study focused on the decreased phosphorylation of Sarcoma Family Kinases (SFK), and others have focused on increased cAMP levels and the downregulation of inflammatory markers such as thromboxanes, including thromboxane A2 (TXA) and thromboxane B2 (TXB); prostaglandin A2 (PGE2); reactive oxygen species (ROS); and cyclooxygenase (COX) enzyme activity. Additionally, pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus all seem to affect, or at least have some relation with, clot retraction. All the clot retraction modulators need in-depth study to explain these effects.
Topics: Blood Platelets; Clot Retraction; Phosphorylation; Platelet Aggregation; Signal Transduction
PubMed: 37445780
DOI: 10.3390/ijms241310602 -
International Journal of Molecular... Nov 2022Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth... (Review)
Review
Fibroblast growth factor 21 is a pleiotropic hormone secreted mainly by the liver in response to metabolic and nutritional challenges. Physiologically, fibroblast growth factor 21 plays a key role in mediating the metabolic responses to fasting or starvation and acts as an important regulator of energy homeostasis, glucose and lipid metabolism, and insulin sensitivity, in part by its direct action on the central nervous system. Accordingly, pharmacological recombinant fibroblast growth factor 21 therapies have been shown to counteract obesity and its related metabolic disorders in both rodents and nonhuman primates. In this systematic review, we discuss how fibroblast growth factor 21 regulates metabolism and its interactions with the central nervous system. In addition, we also state our vision for possible therapeutic uses of this hepatic-brain axis.
Topics: Animals; Fibroblast Growth Factors; Liver; Insulin Resistance; Brain; Energy Metabolism
PubMed: 36362103
DOI: 10.3390/ijms232113318 -
European Journal of Clinical Nutrition Jul 2012Numerous randomised controlled trials (RCTs) published in first tier medical journals have evaluated the health effects of diets high in protein. We conducted a rigorous... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND/OBJECTIVES
Numerous randomised controlled trials (RCTs) published in first tier medical journals have evaluated the health effects of diets high in protein. We conducted a rigorous systematic review of RCTs comparing higher- and lower-protein diets.
METHODS
We searched several electronic databases up to July 2011 for studies focusing on patient-important outcomes (for example, cardiovascular disease) and secondary outcomes such as risk factors for chronic disease (for example, adiposity).
RESULTS
We identified 111 articles reporting on 74 trials. Pooled effect sizes using standardised mean differences (SMDs) were small to moderate and favoured higher-protein diets for weight loss (SMD -0.36, 95% confidence interval (CI) -0.56 to -0.17), body mass index (-0.37, CI -0.56 to 0.19), waist circumference (-0.43, CI -0.69 to -0.16), blood pressure (systolic: -0.21, CI -0.32 to -0.09 and diastolic: -0.18, CI -0.29 to -0.06), high-density lipoproteins (HDL 0.25, CI 0.07 to 0.44), fasting insulin (-0.20, CI -0.39 to -0.01) and triglycerides (-0.51, CI -0.78 to -0.24). Sensitivity analysis of studies with lower risk of bias abolished the effect on HDL and fasting insulin, and reduced the effect on triglycerides. We observed nonsignificant effects on total cholesterol, low-density lipoproteins, C-reactive protein, HbA1c, fasting blood glucose, and surrogates for bone and kidney health. Adverse gastrointestinal events were more common with high-protein diets. Multivariable meta-regression analysis showed no significant dose response with higher protein intake.
CONCLUSIONS
Higher-protein diets probably improve adiposity, blood pressure and triglyceride levels, but these effects are small and need to be weighed against the potential for harms.
Topics: Adiposity; Blood Pressure; Body Constitution; Body Mass Index; Diet; Diet, Protein-Restricted; Dietary Proteins; Health; Humans; Insulin; Triglycerides; Waist Circumference; Weight Loss
PubMed: 22510792
DOI: 10.1038/ejcn.2012.37 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2