Anti-Inflammatory Effects of Melatonin in Rats with Induced Type 2 Diabetes Mellitus

Introduction: Insulin resistance is associated with a pro-inflammatory state increasing the risk for complications in patients with type 2 diabetes mellitus (T2DM). In addition to its chronobi-otic effects, the pineal hormone melatonin is known to exert anti-inflammatory and antioxidant ef-fects. Melatonin was also suggested to affect insulin secretion. The aim of this study was therefore to investigate the effect of melatonin on inflammation in diabetic rats and to study the possible involvement of the melatonin receptor, MT2. Materials and Methods: Male Sprague Dawley rats were randomly divided into four experimental groups (n = 10 per group): (1) control, (2) strepto-zotocin/nicotinamide induced diabetes type 2 (T2DM), (3) T2DM treated with melatonin (500 µg/kg/day), and (4) T2DM treated with melatonin (500 µg/kg/day for 6 weeks) and the selective MT2 receptor antagonist luzindole (0.25 g/kg/day for 6 weeks). Blood samples were taken for biochemical parameters and various tissue samples (liver, adipose tissue, brain) were removed for im-munohistochemistry (IHC), Western blot (WB), and Q-PCR analyses, respectively. Results: Melato-nin significantly reduced increased blood levels of liver transaminases (AST, ALT), blood urea ni-trogen (BUN), triglyceride, very low-density lipoprotein (VLDL), and cholesterol in diabetic rats with luzindole treatment partly reversing this effect regarding the lipids. Furthermore, the liver and adipose tissues of T2DM rats treated with melatonin showed lower expression of the inflammatory markers IL-1β, IL-6, TNF-α, and NF-κB as compared to the T2DM group without melatonin. The results also showed that the MT2 receptor is at least partly involved in the protective effects of mel-atonin. Conclusions: Our results suggest that melatonin exerts relevant anti-inflammatory effects on various tissues in type 2 diabetic rats. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

A novel EGFR inhibitor, HNPMI, regulates apoptosis and oncogenesis by modulating BCL-2/BAX and p53 in colon cancer

Background and Purpose: Colorectal cancer (CRC) is the second most lethal disease, with high mortality due to its heterogeneity and chemo-resistance. Here, we have focused on the epidermal growth factor receptor (EGFR) as an effective therapeutic target in CRC and studied the effects of polyphenols known to modulate several key signalling mechanisms including EGFR signalling, associated with anti-proliferative and anti-metastatic properties. Experimental Approach: Using ligand- and structure-based cheminformatics, we developed three potent, selective alkylaminophenols, 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), 2-[(1,2,3,4-tetrahydroquinolin-1-yl)(4-methoxyphenyl)methyl]phenol (THMPP) and N-[2-hydroxy-5-nitrophenyl(4′-methylphenyl)methyl]indoline (HNPMI). These alkylaminophenols were assessed for EGFR interaction, EGFR-pathway modulation, cytotoxic and apoptosis induction, caspase activation and transcriptional and translational regulation. The lead compound HNPMI was evaluated in mice bearing xenografts of CRC cells. Key Results: Of the three alkylaminophenols tested, HNPMI exhibited the lowest IC50 in CRC cells and potential cytotoxic effects on other tumour cells. Modulation of EGFR pathway down-regulated protein levels of osteopontin, survivin and cathepsin S, leading to apoptosis. Cell cycle analysis revealed that HNPMI induced G0/G1 phase arrest in CRC cells. HNPMI altered the mRNA for and protein levels of several apoptosis-related proteins including caspase 3, BCL-2 and p53. HNPMI down-regulated the proteins crucial to oncogenesis in CRC cells. Assays in mice bearing CRC xenografts showed that HNPMI reduced the relative tumour volume. Conclusions and Implications: HNPMI is a promising EGFR inhibitor for clinical translation. HNPMI regulated apoptosis and oncogenesis by modulating BCL-2/BAX and p53 in CRC cell lines, showing potential as a therapeutic agent in the treatment of CRC.Peer reviewe

Enhancement of cadmium removal by oxygen-doped carbon nitride with molybdenum and sulphur hybridization

Graphitic carbon nitride, as a popular material in the field of environmental remediation, still suffers from unsatisfactory performance for heavy metals adsorption owing to lack of specific adsorption sites. In this study, molybdenum (Mo) and sulphur (S) were simultaneously introduced onto the surface of oxygen-doped graphitic carbon nitride (OCN) for the enhancement of Cd2+ adsorption. The synthesized MOS/OCN-1 exhibited substantially increased maximum adsorption capacity of 293.8 mg/g, calculated from Sips isotherm model, which was 8.7 times higher than that for pristine OCN (33.9 mg/g). The adsorption efficiency of MOS/OCN-1 was >94% even under high concentration of coexisting ions (ie. Ca2+, Mg2+ and Zn2+). MoO3 and MoS2 on the surface of OCN were proven to interact with Cd2+ by forming CdMoO4 and CdS species. OCN provided a stable matrix with a large surface area making more active sites exposed, which greatly facilitated Mo(IV) oxidation and Cd2+ precipitation. Our findings revealed that as well as the well-known Cd-S interaction, Mo atoms in the hybrid composites also played an important role in Cd2+ removal, which opened up the application possibility of OCN with Mo and S hybridization for in-situ Cd2+ remediation

Atomic spectrometry update: Review of advances in the analysis of metals, chemicals and materials

There has been a large increase in the number of papers published that are relevant to this review over this review period. The growth in popularity of LIBS is rapid, with applications being published for most sample types. This is undoubtedly because of its capability to analyse in situ on a production line (hence saving time and money) and its minimally destructive nature meaning that both forensic and cultural heritage samples may be analysed. It also has a standoff analysis capability meaning that hazardous materials, e.g. explosives or nuclear materials, may be analysed from a safe distance. The use of mathematical algorithms in conjunction with LIBS to enable improved accuracy has proved a popular area of research. This is especially true for ferrous and non-ferrous samples. Similarly, chemometric techniques have been used with LIBS to aid in the sorting of polymers and other materials. An increase in the number of papers in the subject area of alternative fuels was noted. This was at the expense of papers describing methods for the analysis of crude oils. For nanomaterials, previous years have seen a huge number of single particle and field flow fractionation characterisations. Although several such papers are still being published, the focus seems to be switching to applications of the nanoparticles and the mechanistic aspects of how they retain or bind with other analytes. This is the latest review covering the topic of advances in the analysis of metals, chemicals and materials. It follows on from last year's review1-6 and is part of the Atomic Spectrometry Updates series

Effect of different zinc contents on the structural, mechanical and tribological properties of EN AC-48100 (Al-17Si-4Cu-Mg) Alloy

WOS: 000552077900008In this study, Al-17Si-4Cu-0.6Mg-0.2Ti which is based of the EN AC-48100 alloy, Al-17Si-4Cu-0.6Mg0.2Ti-1Zn, Al-17Si-4Cu-0.6Mg-0.2Ti-2Zn, Al- 17Si-4Cu-0.6Mg-0.2Ti-3Zn, Al-17Si-4Cu-0.6Mg-0.2Ti-4Zn and Al-17Si-4Cu-0.6Mg-0.2Ti-5Zn alloys were produced by permanent mold casting method. Chemical composition of the produced alloys was determined by the spark optical emission spectrometer method. the microstructures of the alloys were examined by optical and scanning electron microscopy. the hardness and microhardness of the alloys were determined by Brinell and Vickers measurement methods, respectively, and their mechanical properties were determined by tensile tests performed by a universal test machine. It was observed that the microstructure of the Al-17Si-4Cu-0.6Mg-0.2Ti-(0-5) Zn alloys consisted of aluminum-rich alpha, eutectic Al-Si, primary silicon, copper-rich theta (CuAl2), Mg2Si and pi phases. It was also observed that zinc additions did not lead to a new phase formation in the Al-17Si-4Cu-0.6Mg-0.2Ti alloy. the hardness of the produced alloys increased with increasing zinc content, but yield and tensile strength and wear resistance increased up to 3% zinc content and decreased after this ratio. Smearing layers, fine scratches and peeling occurred are seen on the surfaces of the wear samples. the morphology of the wear particles collected after wear tests did not show significant change with the zinc content. the results obtained from the mechanical and tribological tests of the produced alloys were discussed in terms of the microstructural features of the alloys

Interleukin-1 beta effect on the endogenous ADP-ribosylation and phosphorylation of eukaryotic elongation factor 2

WOS: 000387773800039PubMed ID: 27510652Eukaryotic elongation factor 2 (eEF2) plays an important role in eukaryotic polypeptide chain elongation. Adenosine diphosphate (ADP)-ribosylation is a post-translational modification reaction that catalyzes the transfer of ADP-ribose group to eEF2 and this causes the inhibition of protein synthesis. Indeed, in the absence of diptheria toxin, endogenous ADP-ribosylation can occur. eEF2 is phosphorylated by eEF2 kinase which prevents binding to ribosomes thus inhibiting its activity. Increase in endogenous ADP-ribosylation level approximately 70-75 % was observed in IL-1 beta treated HUVECs. Moreover, a 70 % rise of phosphorylation of eEF2 was measured. Alteration of endogenous ADP-ribosylation of eEF2 activity was related with cellular mono-ADP-ribosyltransferases (ADPrT). Increment of endogenous ADP-ribosylation on eEF2 did not seem to occur as a direct effect of IL-1 beta; it arises from the activation of ADPrT. This 2.5 fold increase was abolished by ADPrT inhibitors. Due to these post-translational modifications, global protein synthesis is inhibited. After dephosphorylation of phospho-eEF2, around 20 % increase in protein synthesis was observed. In conclusion, systemic IL-1 beta has an important role in the regulation of global protein synthesis.Istanbul University [31384]This work was supported by the Research Fund of the Istanbul University (Grant 31384)

Knowledge and behavior of dentists in a dental school regarding toothbrush disinfection.

The aim of this study was to evaluate the knowledge and behavior of dentists regarding toothbrush disinfection. This study included 147 dentists (88 women and 59 men) who were actively employed at a dental school in Ankara, Turkey. Participants were asked to fill out a standard questionnaire, which contained questions regarding their demographics, brushing habits, toothbrush storage and disinfection habits, toothpaste use, knowledge about toothbrush disinfection, and whether they advised their patients about toothbrush storage. Descriptive statistics were calculated, and statistical analyses were performed with t-tests, chi-squared tests, and Fisher exact tests, where appropriate. Among the 147 surveyed dentists, 62.6% and 85.7% reported that they did not have any knowledge about toothbrush disinfection and did not disinfect their toothbrushes, respectively. However, approximately two thirds of surveyed dentists thought that toothbrush disinfection should be performed by everyone, including healthy individuals. Significant associations were found between knowledge about toothbrush disinfection and the professional title of dentists, how they stored their toothbrushes, and whether their toothbrushes were in contact with each other during storage (p < 0.05). A minority of dentists reported that they disinfected their toothbrushes

A novel wound healing agent with anti-microbial properties: BSA-inorganic hybrid nanoflowers

Bovine serum albumin (BSA), which has been used for a long time in medias for mammalian cell cultures, stimulates DNA syn- thesis and has a growth-stimulating effect. It leads to a consider- ation of the extracellular and intracellular actions of the molecule, and importantly the role of its interactions with numer- ous ligands or bioactive factors that influence the growth of cells in culture: these include hormones, growth factors, lipids, amino acids, metal ions, reactive oxygen and nitrogen species. However, free proteins have some disadvantages, such as short lifetime in solution, inconvenient recovery and reusability, which strictly hinder their aforementioned applications. The study has been focused on the synthesis and characterization of BSA-inorganic hybrid nanoflowers (BSA-Nfs), then evaluating wound healing with anti-microbial properties. CCD-1072Sk fibroblast cell line was studied to observe effect of BSA-Nfs on wound healing. Firstly, cell proliferation was tested with 3-(4,5-Dimethylthiazol- 2-yl)-2,5-Diphenyltetrazolium to determine the best concentration of BSA-Nfs. Then, the spreading and migration capabilities of CCD-1072Sk fibroblasts were assessed using a scratch wound assay which measures the expansion of a cell population on sur- faces. Fibroblasts were treated with BSA free (2 ng/ml), BSA-Nfs (100 ng/ml), CuSO4(100 ng/ml) and Cu-Nfs(100 ng/ml). There was a non-significant, but marked increase in the number of cells present at 24 h in BSA-Nfs versus control and BSA free. Besides, the in vitro antimicrobial activities of the BSA nfs against Gram- positive and Gram-negative bacteria and C. albicans were deter- mined by the microbroth dilutions technique using the Clinical Laboratory Standards Institute recommendations. BSA Nfs showed antimicrobial activity against S. epidermidis, E. faecalis, E. coli and K. pneumoniae with the MIC = 1250 lg/ml. How- ever, BSA-Nfs did not exhibit any activity on the yeast C. albi- cans in the study