Biomedical Research and Therapy

Pathophysiology of diabetes mellitus complications: Metabolic events and control

2021-04-16T15:06:57+00:00

Background: Diabetes mellitus (DM) is a metabolic disorder that is characterized by hyperglycemia and glucose intolerance, which is associated with impaired insulin secretion and peripheral sensitivity and eventual b-cell dysfunction. This review summarized the major metabolic pathways leading to both microvascular and macrovascular complications in DM, with a view of highlighting the enzymes involved and the possible inhibition of the enzymes facilitating these processes as a measure of diabetic control.

Methods: Data used in writing this review were sourced online from scientific search engines such as Google Scholar, Scopus, EMBASE, PubMed, ResearchGate, Mendeley, Medline, and SpringerLink, using keywords such as 'diabetic complications', 'hyperglycemia-induced diabetic mechanisms', 'diabetic enzymes' and 'diabetic enzyme inhibitors'. A total number of 109 references published online between 1990 and 2020 were generated and cited in this review.

Results: The most scourging and dilapidating effects of DM as well as associated vascular complications are classified into four categories viz.: nephropathy, retinopathy, neuropathy and cardiovascular disease. Hyperglycemia, which is associated with uncontrolled DM, elicits abnormal metabolism such that the enzymes involved in metabolic events leading to diabetic complications are expressed and amplified. The disorders associated with DM are linked to various metabolic pathways facilitated by enzyme activities of the polyol pathway, hexosamine biosynthetic pathway, glucose autoxidation as well as increased synthesis of advanced glycation end-products (AGEs), hexokinase-2 driven glycolytic overload, increased activities of the cyclooxygenase (COX), lipoxygenase (LOX) and pyruvate kinase (PKC) enzymes. The inhibition of the enzymes involved in these pathways could serve to mitigate and arrest diabetic complications.

Conclusion: Thus, suitable inhibitors for enzymes involved in DM metabolic events could serve as panaceas against DM complications, which will add to the growing list of new and more efficacious antidiabetic drugs.

Antigen-presenting cell-derived extracellular vesicles in accelerating atherosclerosis

2021-04-16T15:07:02+00:00

Extracellular vesicles (EVs) are a population of heterogeneous particles that originate from the endosomal system or plasma membrane. Antigen-presenting cells (APCs) produce and release a broad spectrum of EVs involved in the pathogenesis of atherosclerosis. APC-derived EVs contain several bioactive molecules, such as non-coding RNAs, cytokines, chemokines, active proteins, immunomodulatory factors, and growth factors. The review focuses on the role of APC-derived EVs in regulating the transformation of macrophage phenotype, shaping foam cells, driving autophagy and/or inhibiting apoptosis of Th4⁺ cells, T regulatory cells, endothelial and smooth muscle cells (SMCs), as well as in facilitating oxidative stress in vasculature. APC-derived EVs act as triggers of angiogenesis, neovascularization and inflammation through their participation in microvascular inflammation, angiogenesis, development of atherosclerotic plaques, and modulation of their instability.

Antioxidant and anti-Helicobacter pylori activities of Hericium erinaceus mycelium and culture filtrate

2021-04-16T15:07:01+00:00

Introduction: Hericium erinaceus is known as a medicinal edible mushroom owing to its antimicrobial, antioxidant, anti-tumor and immunomodulatory effects. Helicobacter pylori infection is one of the major health concerns worldwide due to its high rate in global populations, frequent recurrence, and rapid emergence of drug-resistant strains. The present study aims to investigate antioxidant anti-H. pylori and urease inhibitory activities of solvent fractions from H. erinaceus mycelium and culture filtrate.

Methods: H. erinaceus mycelium was purely cultured in a liquid medium. A polysaccharide fraction was obtained from the culture filtrate by precipitation with ethanol. The mycelium and culture filtrate were extracted by liquid extraction to obtain solvent-soluble fractions. The antibacterial effects of these fractions were determined using paper disc diffusion and broth microdilution assays. Urease inhibition was determined using the salicylate-hypochlorite method. The antioxidant activity of H. erinaceus was evaluated via 2,2,1-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity.

Results: The ethyl-acetate (EtOAc) fractions derived from H. erinaceus culture filtrate (fEtOAc Fr.) and mycelium (mEtOAc Fr.) showed the strongest anti-H. pylori activity with MIC (MBC) of 1.25 – 1.5 (5.0 – 7.5) mg/mL and potential urease inhibitory activity with IC₅₀ of 0.34 – 0.35 mg/mL. In addition, fEtOAc Fr. exhibited the greatest antioxidant activity (IC₅₀, 11.83 mg/mL), which was slightly stronger than that of mEtOAc Fr. (IC₅₀, 14.75 mg/mL). Moreover, our study also found that the water fractions from the culture filtrate (fWater Fr.) and the mycelium (mWater Fr.) displayed considerable inhibitory activities against bacterial urease (IC₅₀, 1.26 – 1.40 mg/mL), although they had low or no anti-H. pylori activities and low antioxidant properties.

Conclusion: The present study revealed that the EtOAC fractions derived from the H. erinaceus mycelium and culture filtrate potentially have anti-H. pylori, anti-urease and antioxidant activities. These results suggest that H. erinaceus mycelium and culture filtrate could be utilized to develop functional foods and nutraceuticals to prevent H. pylori infection. More research is needed to prove the safety of the H. erinaceus mycelium and culture filtrate fractions and their in vivo efficacy in the treatment of H. pylori infection.

Advantages of functional analysis in comparison of different chemometric techniques for selecting obesity-related genes of adipose tissue from high-fat diet-fed mice

2021-04-16T15:07:00+00:00

Introduction: Obesity is a lifestyle disease that is becoming prevalent nowadays and is associated with a surplus in energy balance related to lipid metabolism, inflammation and hypoxic condition, resulting in maladaptive adipose tissue expansion. This study used the publicly available gene dataset to identify a small subset of important genes for diagnostics or as potential targets for therapeutics.

Methods: Chemometric analyses by principal component analysis (PCA), random forest (RF), and genetic algorithm (GA) were used to identify 50 genes that differentiate adipose samples from high-fat diet- and normal diet-fed mice. The first 30 important genes were studied for classifying the samples using six different classification techniques. Gene ontology (GO), pathway analysis, and protein-protein interaction studies on the 50 selected genes were subsequently done to identify important functional genes. Finally, gene regulatory effects by microRNA were assessed to confirm the genes’ potential as targets for new therapeutic drugs.

Results: The genes identified by RF are best for differentiating the samples, followed by PCA, with the least predictability shown by genes chosen by GA. However, PCA identified more genes with functional importance, such as the hub genes ATP5a1 and Apoa1. ATP5a1 is the main hub gene, whereas Apoa1 is involved in cholesterol metabolism. Vapa and Npc2 are crosstalk genes that link both of these main genes and could be targeted for therapeutic drug design.

Conclusion: The combination of different chemometric techniques and functional analysis of genes could be used to select for a small number of genes which could serve as more suitable diagnostic or therapeutic targets.

Oxidative stress in osteomyelitis and burns: Specific features of its role in development of pathology

2021-04-16T15:06:58+00:00

Introduction: The purpose of this study was to evaluate and compare the features of the initiation and development of oxidative stress in patients with osteomyelitis and burns.

Methods: We studied the oxidative metabolism of blood of 20 healthy subjects (controls), 15 patients with burns, and 18 patients with chronic osteomyelitis. All patients included in the second group had thermal burns of the I-II-III degree in trunk and limbs on an area of 31 - 80% of the body surface without thermal inhalation trauma. After standard sample preparation, a wide range of parameters of oxidative metabolism was determined in the blood. The intensity of free radical processes in blood plasma and red blood cells, and the total antioxidant activity was evaluated by Fe-induced biochemiluminescence. The concentration of malonic dialdehyde in blood plasma and red blood cells was determined. The level of diene and triene conjugates and Schiff bases was determined spectrophotometrically using reagent kits. The catalase and superoxide dismutase activities in the red blood cells of patients from each of the groups was also determined.

Results: We showed that in osteomyelitis, which is a long-lasting process, changes in the balance of free radical generation and activity of the antioxidant system were compensatory and mostly related to changes in blood plasma. On the contrary, in burn victims, oxidative stress signs had a maladaptive character. They were seen in blood plasma and red blood cells, and accompanied by a pronounced depletion of enzyme antioxidant system reserves.

Conclusion: Our study demonstrate the role of oxidative stress in patients with burns and chronic osteomyelitis, and demonstrate some specific features leading to formation of disease pathology. Such features of oxidative stress may be useful in future design of new approaches to correct the pathology of diseases.