Biomechanical evaluation of porous biodegradable scaffolds for revision knee arthroplasty

Tibial bone defect is a critical problem for revision knee arthroplasty. Instead of using metallic spacer or cement, biodegradable scaffolds could be an alternative solution. A numerical model of a revision knee arthroplasty was thus developed to estimate the mechanical resistance of the scaffold in this demanding situation. The tibia, scaffold, and prosthesis were represented by simplified parameterised geometries. The maximal gait cycle force was applied asymmetrically to simulate a critical loading. Several parameters were analysed: 1) inter-individual variability, 2) cortical bone stiffness, 3) cortical bone thickness, 4) prosthesis fixation quality, and 5) scaffold thickness. The calculated scaffold strain was compared to its experimental ultimate strain. Among the tested parameters, failure was only predicted with scaffold thickness below 5 mm. This study suggests that biodegradable bone scaffolds could be used to fill bone defects in revision knee arthroplasty, but scaffold size seems to be the limiting factor.     

2-Hydroxyphenacyl azoles and related azolium derivatives as antifungal agents

2-Hydroxyphenacyl azole and 2-hydroxyphenacyl azolium compounds have been described as a new class of azole antifungals. Most target compounds showed significant in vitro antifungal activities against tested fungi (Candida albicans, Saccharomyces cerevisiae, Aspergillus niger, and Microsporum gypseum) with low MICs values included in the range of 0.25-32 microg/mL comparable to reference drug fluconazole. The most active compounds were also assessed for their cytotoxicity using MTT colorimetric assay on normal mouse fibroblast (NIH/3T3) cells. The results of antifungal activity and toxicity tests indicated that these compounds display antifungal activity at non-cytotoxic concentrations.     

Oleoylethanolamide: A novel pharmaceutical agent in the management of obesity-an updated review

Obesity as a multifactorial disorder has been shown a dramatically growing trend recently. Besides genetic and environmental factors, dysregulation of the endocannabinoid system tone is involved in the pathogenesis of obesity. This study reviewed the potential efficacy of Oleoylethanolamide (OEA) as an endocannabinoid-like compound in the energy homeostasis and appetite control in people with obesity. OEA as a lipid mediator and bioactive endogenous ethanolamide fatty acid is structurally similar to the endocannabinoid system compounds; nevertheless, it is unable to induce to the cannabinoid receptors. Unlike endocannabinoids, OEA negatively acts on the food intake and suppress appetite via various mechanisms. Indeed, OEA as a ligand of PPAR-α, GPR-119, and TRPV1 receptors participates in the regulation of energy intake and energy expenditure, feeding behavior, and weight gain control. OEA delays meal initiation, reduces meal size, and increases intervals between meals. Considering side effects of some approaches used for the management of obesity such as antiobesity drugs and surgery as well as based on sufficient evidence about the protective effects of OEA in the improvement of common abnormalities in people with obese, its supplementation as a novel efficient and FDA approved pharmaceutical agent can be recommended.     

Structural stability and endonuclease activity of a PI-SceI GFP-fusion protein

Homing endonucleases are site-specific and rare cutting endonucleases often encoded by intron or intein containing genes. They lead to the rapid spread of the genetic element that hosts them by a process termed 'homing'; and ultimately the allele containing the element will be fixed in the population. PI-SceI, an endonuclease encoded as a protein insert or intein within the yeast V-ATPase catalytic subunit encoding gene (vma1), is among the best characterized homing endonucleases. The structures of the Sce VMA1 intein and of the intein bound to its target site are known. Extensive biochemical studies performed on the PI-SceI enzyme provide information useful to recognize critical amino acids involved in self-splicing and endonuclease functions of the protein. Here we describe an insertion of the Green Fluorescence Protein (GFP) into a loop which is located between the endonuclease and splicing domains of the Sce VMA1 intein. The GFP is functional and the additional GFP domain does not prevent intein excision and endonuclease activity. However, the endonuclease activity of the newly engineered protein was different from the wild-type protein in that it required the presence of Mn(2+) and not Mg(2+) metal cations for activity.     

MicroRNA in leukemia: Tumor suppressors and oncogenes with prognostic potential

Leukemia is known as a progressive malignant disease, which destroys the blood-forming organs and results in adverse effects on the proliferation and development of leukocytes and their precursors in the blood and bone marrow. There are four main classes of leukemia including acute leukemia, chronic leukemia, myelogenous leukemia, and lymphocytic leukemia. Given that a variety of internal and external factors could be associated with the initiation and progression of different types of leukemia. One of the important factors is epigenetic regulators such as microRNAs (miRNAs) and long noncoding RNAs (ncRNA). MiRNAs are short ncRNAs which act as tumor suppressor (i.e., miR-15, miR-16, let-7, and miR-127) or oncogene (i.e., miR-155, miR-17-92, miR-21, miR-125b, miR-93, miR-143-p3, miR-196b, and miR-223) in leukemia. It has been shown that deregulation of these molecules are associated with the initiation and progression of leukemia. Hence, miRNAs could be used as potential therapeutic candidates in the treatment of patients with leukemia. Moreover, increasing evidence revealed that miRNAs could be used as diagnostic and prognostic biomarkers in monitoring patients in early stages of disease or after received chemotherapy regimen. It seems that identification and development of new miRNAs could pave to the way to the development new therapeutic platforms for patients with leukemia. Here, we summarized various miRNAs as tumor suppressor and oncogene which could be introduced as therapeutic targets in treatment of leukemia.     

Therapeutic Effects of High-Intensity Interval Training Exercise Alone and Its Combination with Ecdysterone Against Amyloid Beta-Induced Rat Model of Alzheimer’s Disease: A Behavioral,Biochemical, and Histological Study

Neurochemical Research - Hippocampal oxidative stress has a vital role in the pathophysiology of Alzheimer’s disease (AD)-associated behavioral deficits. Ecdysterone (Ecdy), a natural product...     

Tropisetron restores normal expression of BAD,SIRT1, SIRT3, and SIRT7 in the rat pressure overload-induced cardiac hypertrophy model

Tropisetron exerts a protective effect against cardiac complications, particularly cardiac hypertrophy. Oxidative stress and apoptosis are the main contributors to the pathogenesis of cardiac hypertrophy. Sirtuins, a family of histone deacetylases, are connected to cellular oxidative stress signaling and antioxidant defense. Sirtuins are also linked to apoptosis which is an important mechanism in the progression of cardiac hypertrophy to heart failure. Literature also suggests that tropisetron impedes apoptosis, partly mediated through an antioxidant mechanism. Therefore, we examined if tropisetron fights cardiac hypertrophy by adjusting sirtuin family proteins (Sirts) and components of mitochondrial death pathway, Bcl-associated X (BAX), Bcl-2-associated death promoter (BAD). Male Sprague–Dawley rats got divided into four groups, including control (Ctl), tropisetron (Trop), cardiac hypertrophy (Hyp), and hypertrophic rats under tropisetron treatment (Hyp + Trop). Pathological cardiac hypertrophy was induced by surgical abdominal aortic constriction (AAC). The increased expression of brain natriuretic peptide (BNP) in the Hyp group confirms the cardiac hypertrophy establishment. The mRNA levels of SIRT1, SIRT3, SIRT7, and BAD also upregulated in the hypertrophic group (p < 0.001). Postoperational administration of tropisetron for 3 weeks lowered the increased expression of BNP (p < 0.05) and BAD (p < 0.001), though the reduction of BAX expression was statistically insignificant (p > 0.05). Tropisetron treatment also restored the normal level of SIRT1/3/7 genes expression in the Hyp + Trop group (p < 0.05). Present findings suggest that tropisetron can suppress cardiomyocyte hypertrophy progression to heart failure by counteracting BNP, SIRT1, SIRT3, Sirt7, and BAD overexpression-mediated apoptosis in a rat model of cardiac hypertrophy.     

The lost correlation between heat shock protein 70 (HSPA1A) and plasminogen activator inhibitor-1 in patients with type 2 diabetes and albuminuria

We aimed to study the relation between plasma levels of stress-induced heat shock protein 70 (HSPA1A) with plasminogen activator inhibitor-1 (PAI-1) and high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and HDL-C/Apo-A1 ratio. In a matched case-control study on patients with diabetes (40 patients with albuminuria and 40 without albuminuria matched for age, sex, and body mass index), we observed that plasma levels of HSPA1A and PAI-1 are increased in patients with albuminuria (0.55 ± 0.02 vs. 0.77 ± 0.04 ng/ml, p value <0.001 for HSPA1A; 25.9 ± 2 vs. 31.8 ± 2.4 ng/ml, p value <0.05 for PAI-1). There was a significant correlation between HSPA1A and PAI-1 in diabetic patients without albuminuria (r = 0.28; p value = 0.04), but not in those with albuminuria (r = 0.07; p value = 0.63). No association was found between HSPA1A and HDL-C, between HSPA1A and Apo-A1, or between HSPA1A and HDL-C/Apo-A1 ratio. We concluded that there is a direct correlation between plasma HSPA1A and PAI-1 levels in patients with diabetes, which is lost when they develop albuminuria.     

Highly Efficient Solar‐Driven Carbon Dioxide Reduction on Molybdenum Disulfide Catalyst Using Choline Chloride‐Based Electrolyte

Conversion of CO₂ to energy‐rich chemicals using renewable energy is of much interest to close the anthropogenic carbon cycle. However, the current photoelectrochemical systems are still far from being practically feasible. Here the successful demonstration of a continuous, energy efficient, and scalable solar‐driven CO₂ reduction process based on earth‐abundant molybdenum disulfide (MoS₂) catalyst, which works in synergy with an inexpensive hybrid electrolyte of choline chloride (a common food additive for livestock) and potassium hydroxide (KOH) is reported. The CO₂ saturated hybrid electrolyte utilized in this study also acts as a buffer solution (pH ≈ 7.6) to adjust pH during the reactions. This study reveals that this system can efficiently convert CO₂ to CO with solar‐to‐fuel and catalytic conversion efficiencies of 23% and 83%, respectively. Using density functional theory calculations, a new reaction mechanism in which the water molecules near the MoS₂ cathode act as proton donors to facilitate the CO₂ reduction process by MoS₂ catalyst is proposed. This demonstration of a continuous, cost‐effective, and energy efficient solar driven CO₂ conversion process is a key step toward the industrialization of this technology.