Exploring genetic signatures of obesity: hub genes and miRNAs unveiled through comprehensive bioinformatic analysis.

Objectives: Adipogenesis, the process of fat accumulation in adipose tissue, is closely linked to obesity, a condition characterized by excessive fat storage. Genetic factors significantly contribute to an individual's susceptibility to adipogenesis and the development of obesity.

Methods: In this study, we conducted a comprehensive bioinformatic analysis, including Weighted Gene Co-expression Analysis, differentially expressed gene analysis, and protein-protein interaction analysis, to identify hub genes and miRNAs associated with obesity.

The role of Sirtuin 1 in regulation of fibrotic genes expression in pre-adipocytes.

Purpose: Considering inhibition of pre-adipocyte cells differentiation in adipose tissue fibrosis, we aimed to explore whether Sirt1 and Hif-1α in pre-adipocytes have a significant effect on fibrotic gene expression.

Methods: 3T3-L1 pre-adipocytes were transfected with SIRT1-specific siRNA, confirmed by real-time polymerase chain reaction (RT-PCR) and western blotting. Additionally, cells were treated with varying concentrations of resveratrol and sirtinol as the activator and inhibitor of Sirt1, respectively.

Exploring the impact of naltrexone on the THBS1/eNOS/NO pathway in osteoporotic bile duct-ligated rats.

Hepatic osteodystrophy, a prevalent manifestation of metabolic bone disease, can arise in the context of chronic liver disease. The THBS1-eNOS-NO signaling pathway plays a pivotal role in the maturation of osteoclast precursors. This study aimed to investigate the impact of Naltrexone (NTX) on bone loss by examining the THBS1-eNOS-NO signaling pathways in bile duct ligated (BDL) rats.

Chondroitinase as a therapeutic enzyme: Prospects and challenges.

The chondroitinases (Chase) are bacterial lyases that specifically digest chondroitin sulfate and/or dermatan sulfate glycosaminoglycans via a β-elimination reaction and generate unsaturated disaccharides. In recent decades, these enzymes have attracted the attention of many researchers due to their potential applications in various aspects of medicine from the treatment of spinal cord injury to use as an analytical tool. In spite of this diverse spectrum, the application of Chase is faced with several limitations and challenges such as thermal instability and lack of a suitable delivery system.

A novel approach to type 3 diabetes mechanism: The interplay between noncoding RNAs and insulin signaling pathway in Alzheimer's disease.

Today, growing evidence indicates that patients with type 2 diabetes (T2D) are at a higher risk of developing Alzheimer's disease (AD). Indeed, AD as one of the main causes of dementia in people aged more than 65 years can be aggravated by insulin resistance (IR) and other metabolic risk factors related to T2D which are also linked to the function of the brain. Remarkably, a new term called "type 3 diabetes" has been suggested for those people who are diagnosed with AD while also showing the symptoms of IR and T2D.

Naltrexone protects against BDL-induced cirrhosis in Wistar rats by attenuating thrombospondin-1 and enhancing antioxidant defense system via Nrf-2.

Aims: It is well-established that thrombospondin-1 (THBS-1), vascular endothelial growth factor-A (VEGF-A), nuclear factor-erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and transforming growth factor-beta 1 (TGF-β1) are the pivotal players of liver fibrosis. Recent studies have shown that endogenous opioid levels increase during liver cirrhosis. Therefore, the present study aimed to clarify the effect of naltrexone (NTX), an opioid antagonist, on the alteration of these factors following bile duct ligation (BDL)-induced liver cirrhosis.

Improvement of thermostability of cholesterol oxidase from streptomyces Sp. SA-COO by random mutagenesis.

To enhance the thermal stability of Streptomyces Sp. SA-COO cholesterol oxidase, random mutagenesis was used. A random mutant library was generated using two types of error-prone PCR (single step and serial dilution) and two mutants (ChOA-M1 and ChOA-M2) with improved thermostability were obtained.

The emerging role of noncoding RNAs in neuroinflammation: Implications in pathogenesis and therapeutic approaches.

Noncoding RNAs (ncRNAs) are important regulators of gene expression in different cell processes. Due to their ability in monitoring neural development genes, these transcripts confer neurons with the potential to exert broad control over the expression of genes for performing neurobiological functions. Although the change of ncRNA expression in different neurodegenerative diseases has been reviewed elsewhere, only recent evidence drove our attention to unravel the involvement of these molecules in neuroinflammation within these devastating disorders.

Tumor-derived urinary exosomal long non-coding RNAs as diagnostic biomarkers for bladder cancer.

Bladder cancer (BC) is the sixth most common malignancy in men and 17th in women. Exosomal long non-coding RNAs (lncRNAs) have been defined as a novel biomarker for BC. The aim of this study is to evaluate the clinical significance of urine exosomal PVT-1, ANRIL and PCAT-1 as a biomarker in BC patients with tumors classified as T1 or T2.

Enhancing myelin repair in experimental model of multiple sclerosis using immobilized chondroitinase ABC I on porous silicon nanoparticles.

Removal of chondroitin sulfate proteoglycans (CSPGs) with chondroitinase ABC I (ChABC) facilitates axonal plasticity, axonal regeneration and remyelination, following injury to the central nervous system (CNS). However, the ChABC rapidly undergoes thermal inactivity and needs to be injected repeatedly. Here this limitation was overcame by immobilizing the ChABC on porous silicon (PSi) nanoparticles (ChABC@PSi).

Protein Detection of Excretory-Secretory Products and Somatic Extracts from and Using Two-Dimensional Electrophoresis.

Background: The aim of this research was to compare excretory-secretory and somatic extract materials of and to detect protein maps of two species.

Methods: Twenty infected livers were collected from sheep in industrial slaughterhouse in Tehran, 2017-2019. Worms were detached from bile ducts, then recognized according to morphologic and morphometric criteria.

The influence of TRAIL, adiponectin and sclerostin alterations on bone loss in BDL-induced cirrhotic rats and the effect of opioid system blockade.

Aims: Osteoporosis is a common extra-hepatic complication in patients with chronic liver disease. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL), sex hormones, adiponectin, and sclerostin are involved in the regulation of bone turnover but little is known about their role in the promotion of hepatic osteodystrophy. Endogenous opioids are reported to increase during cholestasis and may influence bone resorption.

N∆89 and C∆274 Truncated Enzymes of Chondroitinase ABC I Regain More Imperturbable Microenvironments Around Structural Components in Comparison to their Wild Type.

Immune response stimulation and inactivation of chondroitinase ABC I in physiological condition have been limited its use in various clinical conditions as a bacterial enzyme drug. In the present study, we have investigated some structural and functional features of N∆89, C∆274 and N∆89C∆274; three designed truncated cABC I, in order to clarify the unclear role of two terminal parts of cABC I i.e.

Expression optimization, purification, and functional characterization of cholesterol oxidase from Chromobacterium sp. DS1.

Cholesterol oxidase is a bifunctional bacterial flavoenzyme which catalyzes oxidation and isomerization of cholesterol. This valuable enzyme has attracted a great deal of attention because of its wide application in the clinical laboratory, synthesis of steroid derived drugs, food industries, and its potentially insecticidal activity. Therefore, development of an efficient protocol for overproduction of cholesterol oxidase could be valuable and beneficial in this regard.

lncRNA involvement in hepatocellular carcinoma metastasis and prognosis.

Eukaryotic lncRNAs are RNA molecules defined to be greater than 200 bp in length that are not translated to a protein and operate through several mechanisms, including participating in chromatin remodeling and methylation, influencing the integrity and stability of proteins and complexes, or acting as a sponge for miRNA inhibition. A number of recent studies have concentrated on the relationship between long non-coding RNAs (lncRNAs) and cancer. Hepatocellular carcinoma (HCC) is the most prevalent histological type of liver tumors, accounting for about 80 % of the cases worldwide.

Expression optimization of recombinant cholesterol oxidase in Escherichia coli and its purification and characterization.

Cholesterol oxidase is a bacterial flavoenzyme which catalyzes oxidation and isomerization of cholesterol. This enzyme has a great commercial value because of its wide applications in cholesterol analysis of clinical samples, synthesis of steroid-derived drugs, food industries, and potentially insecticidal activity. Accordingly, development of an efficient protocol for overexpression of cholesterol oxidase can be very valuable and beneficial.

A study on OPG/RANK/RANKL axis in osteoporotic bile duct-ligated rats and the involvement of nitrergic and opioidergic systems.

Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown.

Investigating the role of loop 131-140 in activity and thermal stability of chondroitinase ABC I.

Previously, we attempted to improve the thermostability of chondroitinase ABC I by substituting proline in flexible sites and successfully obtained a mutant; E138P, with increased thermostability (Kheirollahi et al., 2017). In this study, we focused on the role of Glu138 in activity and stability of the enzyme using its further mutation to Ala, Lys, and Asp.

Evidence for the link between defective autophagy and inflammation in peripheral blood mononuclear cells of type 2 diabetic patients.

Autophagy was shown to modulate inflammation in immune cells. This study was designed to evaluate the association between autophagy and inflammation in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and non-diabetic (ND) subjects. The autophagy markers were measured by real-time PCR and western blot.

Establishment of Aromatic Pairs at the Surface of Chondroitinase ABC I: the Effect on Activity and Stability.

Removal of chondroitin sulfate glycosaminoglycan (GAG) chains with chondroitinase ABC I (chABC I) in CNS injury models promotes both saxon regeneration and plasticity. It has been suggested that direct interaction between an aromatic pair appears to contribute about - 1.3 kcal/mol to the stability of a folded protein, so introducing an aromatic pair by point mutation might increase the enzyme activity and thermal stability as in the case of mesophilic xylanase, although using this approach destabilized T4 lysozyme.

Reduced gene expression of sirtuins and active AMPK levels in children and adolescents with obesity and insulin resistance.

Background: Sirtuins, including SIRT1 and SIRT2, are longevity-associated deacetylase enzymes that modulate metabolic homeostasis in response to the cellular energy state. Adenosine monophosphate activated protein kinase (AMPK) and SIRT1 are interrelated and share several common target pathways. This study aimed to evaluate the SIRT1 and SIRT2 gene expression in peripheral blood mononuclear cells (PBMCs) as well as plasma levels of AMPK, in obese children and adolescents.

Role of His-His interaction in Ser-His-Tyr sequence of chondroitinase ABC I in the enzyme activity and stability.

Despite clinical importance of chondroitinase ABC I, its application has been limited due to thermal instability as reported in the literature. There are various approaches to improve thermal stability of enzymes, among them, His-His interactions are believed generally as an effective means. In the present study and for preparing a His-His interaction, various mutations in the sequence of Ser-His-Tyr at catalytic domain of the enzyme were performed using site directed mutagenesis method.

Extracellular NAMPT/visfatin causes p53 deacetylation via NAD production and SIRT1 activation in breast cancer cells.

Visfatin, which is secreted as an adipokine and cytokine, has been implicated in cancer development and progression. In this study, we investigated the NAD-producing ability of visfatin and its relationship with SIRT1 (silent information regulator 2) and p53 to clarify the role of visfatin in breast cancer. MCF-7 breast cancer cells were cultured and treated with visfatin.

Improvement of activity and stability of Chondroitinase ABC I by introducing an aromatic cluster at the surface of protein.

Chondroitinase ABC I (ChABC I) has been shown to depolymerize a variety of glycosaminoglycan substrates and promote regeneration of damaged spinal cord. However, to date, intrathecal delivery methods have been suboptimal largely due to enzyme instability which necessitates repeated administration to the injured loci. Among the aromatic amino acids, tyrosine has been shown to be more effective in creation of stable clusters and further stabilize of the proteins.

Calcium and TNFα additively affect the chondroitinase ABC I activity.

Experimental models have repeatedly shown the therapeutic potential of cABC I in spinal cord injury (SCI) by degrading chondroitin sulfate proteoglycans that hinder neurite outgrowth. Following SCI, some molecules are released from injured cells. This study is designed to determine the effects of some of these molecules at the SCI loci on activity, stability and structure of wild type and Q140A variant of cABC I.