The effects of oral trehalose on glycaemia, inflammation, and quality of life in patients with type 2 diabetes: a pilot randomized controlled trial.

Introduction: Trehalose is a naturally occurring disaccharide of 2 glucose molecules, which has been suggested as a potential therapeutic agent to reduce blood glucose and ameliorate diabetes-related complications in type 2 diabetes (T2D). This study aimed to determine the efficacy of medium-term trehalose treatment in patients with T2D. Material and methods: A double-blind, randomized, placebo-controlled trial in 40 patients with T2D was undertaken; 20 ingested trehalose 3.3 g/day and 20 placebo (sucrose), for 3 months. Parameters of glycaemic indices, high-sensitivity C-reactive protein (CRP), mood status, and quality of life were measured. Results: CRP was significantly lower with trehalose treatment (-0.62 ±0.3 mg/l, p = 0.02); however, no differences in glycaemic indices of fasting blood glucose (FBG) (-7.1 ±10.7 mg/dl, p = 0.15), glycated hemoglobin (HbA1c) (-0.1 ±0.4%, p = 0.73), insulin (0.73 ±0.8 µU/ml, p = 0.39), or insulin resistance (HOMA-IR) (0.19 ±0.33, p = 0.56) were seen between groups after 12 weeks. Depression and stress scores were lower with trehalose compared to the placebo group (p = 0.02 and p = 0.05, respectively), whilst the quality-of-life score was higher with trehalose compared to placebo (p = 0.03) at the end of study. Between-group differences in these indices did not reach statistical significance (-2.36 ±1.20, -2.21 ±1.39 and 3.00 ±1.76 for depression, stress, and quality-of-life score, respectively) (p > 0.05). The pro-oxidant antioxidant balance (PAB) did not differ between groups (-4.6 ±12.8, p = 0.72). Conclusions: 12 weeks of treatment with 3.3 g/day of oral trehalose significantly improves CRP as a marker of inflammation, with potential favourable effects on quality of life, depression, and stress levels, but overall glycaemic control and pro-oxidant-antioxidant balance were unaltered during this time frame.

An in vitro investigation of the effects of urolithins A and B on low-density lipoprotein uptake and its regulatory genes.

Introduction: This study aimed to evaluate the possible role of urolithin A (UA) and urolithin B (UB) on the mRNA expression levels of LDL receptor (LDLR) and PSCK9 genes, and also of the uptake of LDL particles in HepG2 cells. Material and methods: The potential role of UA and UB on the induction of LDL uptake and the expression of its regulatory genes was explored using HepG2 cells and curcumin (20 µM), berberine (50 µM), UA (80 µM), and UB (80 µM) as the treatments in the experimental tests. Results: The LDL uptake and cell-surface LDLR were higher in cells treated with UA in comparison with cells treated with UB, and even in relation to the cells treated with curcumin and berberine as positive controls. In addition, cells treated with UB showed approximately 2 times greater LDLR expression levels compared with curcumin (FC = 2.144, p = 0.013) and berberine (FC = 2.761, p = 0.006). However, UA treatment resulted in significantly lower expression levels of LDLR compared with curcumin (FC = 0.274, p < 0.001) and berberine (FC = 0.352, p = 0.009). UB demonstrated approximately 8 times higher LDLR expression levels when compared with UA (FC = 7.835, p = 0.001). Compared with UB, as well as curcumin and berberine as positive controls, UA was more efficient in reducing PCSK9 expression levels. Although UB did not show any significant differences compared with curcumin and berberine, it showed higher levels of PCSK9 expression when compared with the UA group (FC = 3.694, p < 0.001). Conclusions: The present results suggest that UA was more effective than UB in promoting LDL uptake as well as cell surface LDLR in HepG2 cells. This effect seems to be mostly mediated through the suppression of PCSK9 expression but not the induction of LDLR expression.

The Effects of Statin Therapy on Circulating Levels of Trimethylamine N-oxide: A Systematic Review and Meta-analysis.

BACKGROUND: Gut microbiota is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) through the metabolites, which can induce atherogenesis. One of these metabolites is trimethylamine N-oxide (TMAO). Some studies indicate that statins do not only decrease LDL-cholesterol and thus ASCVD risk, but they also affect gut microbiota. There are only a few studies on humans suggesting that statins might also decrease TMAO, but their results are not unanimous. This meta-analysis aimed to provide an answer as to whether statins do affect decreasing the plasma levels of atherogenic TMAO. METHODS: A systematic literature search in PubMed, Scopus, Embase, and Web of Science was performed from inception to January 1st, 2023. To assess the quality of each study included in the meta-analysis, the Cochrane Quality Assessment tool 1 (ROB 1) was used. Comprehensive Meta-Analysis V3 software was used to perform the meta-analysis. The weighted mean difference was also used. A random effects meta-analysis was used to calculate the overall estimate of effect size. In the leave-one-out approach, one study was excluded from each analysis to evaluate the effect of each study on the overall effect size. RESULTS: Random-effects meta-analysis of 3 studies including 244 patients demonstrated a significant decrease in plasma TMAO levels after statin treatment (WMD: -1.839, 95% CI: -2.391, -1.287, p<0.001; I2 :0). The reduction in TMAO was robust in the leaveone-out sensitivity analysis. CONCLUSION: Statins might reduce TMAO levels, but there is a need for further evidence from long-term studies taking into account different types and doses of statins.

Statins: Beneficial Effects in Treatment of COVID-19.

The recent viral disease COVID-19 has attracted much attention. The disease is caused by SARS-CoV-19 virus which has different variants and mutations. The mortality rate of SARS-CoV-19 is high and efforts to establish proper therapeutic solutions are still ongoing. Inflammation plays a substantial part in the pathogenesis of this disease causing mainly lung tissue destruction and eventually death. Therefore, anti-inflammatory drugs or treatments that can inhibit inflammation are important options. Various inflammatory pathways such as nuclear factor Kappa B (NF-κB), signal transducer of activators of transcription (STAT), nod-like receptor family protein 3 (NLRP), toll-like receptors (TLRs), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) pathways and mediators, such as interleukin (IL)-6, IL-1ß, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ), cause cell apoptosis, reduce respiratory capacity and oxygen supply, eventually inducing respiratory system failure and death. Statins are well known for controlling hypercholesterolemia and may serve to treat COVID-19 due to their pleiotropic effects among which are anti-inflammatory in nature. In this chapter, the anti-inflammatory effects of statins and their possible beneficial effects in COVID-19 treatment are discussed. Data were collected from experimental and clinical studies in English (1998-October 2022) from Google Scholar, PubMed, Scopus, and the Cochrane Library.

Liposomal CpG-ODN: An in vitro and in vivo study on macrophage subtypes responses, biodistribution and subsequent therapeutic efficacy in mice models of cancers.

CpG oligodeoxynucleotides (CpG-ODN), a common immune stimulator and vaccine adjuvant, was reported to switch Tumor Associated Macrophages (TAMs) from M2 to M1 phenotype inducing anti-tumor responses. Liposomes are of the successfully applied carriers for CpG-ODN. The aim of present study was design and preparation of a liposomal formulation containing phosphodiester CpG-ODN, evaluation of its effect on macrophages responses, and subsequent antitumor responses in mice. Liposomal formulations containing phosphodiester CpG-ODN or non-CpG-ODN were prepared and characterized. MTT reduction assay in four different cell lines, uptake, arginase and iNOS activity evaluation in macrophage cell lines, biodistribution study and therapeutic anti-tumor effects of formulations in mice bearing C26 colon carcinoma or B16F0 melanoma were carried out. The size of liposomes containing CpG-ODN was ~200 nm with the encapsulation efficiency of 33%. The iNOS activity assay showed high nitric oxide (NO) level in M2 phenotype of macrophage cell lines treated by liposomes containing CpG-ODN. In mice which received liposomes containing CpG-ODN as a monotherapy, maximum tumor growth delay with remarkable survival improvement was observed compared to control groups. Biodistribution study showed the accumulation of liposomal formulation in tumor micro-environment. In conclusion, considerable anti-tumor responses observed by liposomes containing CpG-ODN was due to enhanced delivery of CpG-ODN to immune cells and subsequent initiation of anti-tumoral immune responses.

Gankyrin: a novel promising therapeutic target for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is known as fifth common malignancies and third common cause of cancer-related death worldwide. The identification of various mechanisms which are involved in hepatocarcinogenesis contributes in finding a variety of cellular and molecular targets for HCC diagnosis, prevention and therapy. Among various identified targets in HCC pathogenesis, Gankyrin is a crucial oncoprotein that is up-regulated in HCC and plays a pivotal role in the initiation and progression of the HCC. Oncogenic role of Gankyrin has been found to stem from inhibition of two ubiquitous tumour suppressor proteins, retinoblastoma protein (pRb) and P53, and also modulation of several vital cellular signalling pathways including Wnt/ß-Catenin, NF-κB, STAT3/Akt, IL-1ß/IRAK-1 and RhoA/ROCK. As a result, Gankyrin can be considered as a potential candidate for diagnosis and treatment of HCC. In this review, we summarized the physiological function and the significant role of Gankyrin as an important therapeutic target in HCC.

Acute toxicity of functionalized single wall carbon nanotubes: A biochemical, histopathologic and proteomics approach.

Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150µg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice). One or 7 days after intravenous injection, the mice were killed and serum and livers were collected. The oxidative stress markers, biochemical and histopathological changes were studied. Subsequently, proteomics approach was used to investigate the alterations of protein expression profiles in the liver. Results showed that there were not any significant differences in malondealdehyde (MDA), glutathione (GSH) levels and biochemical enzymes (ALT and AST) between groups, while the histopathological observations of livers showed some injuries. The results of proteomics analysis revealed indolethylamine N-Methyltransferase (INMT), glycine N-Methyltransferase (GNMT), selenium binding protein (Selenbp), thioredoxin peroxidase (TPx), TNF receptor associated protein 1(Trap1), peroxiredoxin-6 (Prdx6), electron transport flavoprotein (Etf-α), regucalcin (Rgn) and ATP5b proteins were differentially expressed in functionalized SWCNTs groups. Western blot analyses confirmed that the changes in Prdx6 were consistent with 2-DE gel analysis. In summary, acute toxicological study on two functionalized SWCNTs did not show any significant toxicity at selected doses. Proteomics analysis also showed that following exposure to functionalized SWCNTs, the expression of some proteins with antioxidant activity and detoxifying properties were increased in liver tissue.

Protective effects of glucosamine hydrochloride against free radical-induced erythrocytes damage.

Glucosamine (GlcN) is an important precursor in the biochemical synthesis of glycosylated proteins and lipids in human body. It gains importance because of its contribution to human health and its multiple biological and therapeutic effects. In this study, the in vitro oxidative hemolysis of rat erythrocyte was used as a model to study the potential protective effect of glucosamine hydrochloride against free radical-induced damage of biological membranes. Glucosamine hydrochloride exhibited dose-dependent DPPH antioxidant activity. Oxidative hemolysis and lipid/protein peroxidation of erythrocytes induced by a water-soluble free radical initiator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) were significantly suppressed by GlcN in a time and dose dependent manner. GlcN also prevented the depletion of cytosolic antioxidant glutathione (GSH) in erythrocytes. These results indicated that glucosamine hydrochloride efficiently protected erythrocytes against free radicals and it could be recommended as a pharmaceutical supplement to alleviate oxidative stress.