NF-kB affects migration of vascular smooth muscle cells after treatment with heparin and ibrutinib

The migration of vascular smooth muscle cells (VSMCs) is one of the most important events in the remodeling of atherosclerosis plaque. The aim of study was to investigate the role of Heparin in the VSMC migration and its association with the NF-kB, collagen 1 and collagen 3 expression levels. Moreover, the incorporation of Heparin was studied in the VSMC cultures including Betulinic acid and Ibrutinib. Twelve cell groups were cultured and treated with the Heparin, Betulinic acid and Ibrutinib based on the viability and toxicity in 24-h and 48-h periods. The gene and protein expression levels were measured by RT-qPCR and western blotting techniques. The VSMC migration was determined by scratch test. In contrast with Ibrutinib (2 μM), Heparin (30 IU) increased significantly (P < 0.05) the NF-kB gene and protein expression levels and the VSMC migration during the exposure periods. Heparin (15 IU and 30 IU) also increased the collagen 1 gene expression level in the 48-h period while Heparin (5 IU and 15 IU) increased the collagen 3 gene expression levels in both periods. Incorporating Heparin into the cultures including Betulinic acid and Ibrutinib affected the collagen 1 and collagen 3 expression levels. The data suggested that the cell migration relates to NF-kB in the VSMCs treated with Heparin and Ibrutinib. Furthermore, the Heparin doses (5 IU and 15 IU) were safe for VSMCs based on the NF-kB, and collagen 3 expression levels

Anti Streptococcus mutans non fluoride and fluoride containing sealants after adding nano-silver particles

Background and Aims: Since recurrent caries are one of the major causes of failure in resin restorations, the production of antibacterial resin composites was always under investigation. The aim of this study was to evaluate the efficacy of fissure sealants containing nanosilver particles against the Streptococcus mutans.   Materials and Methods: In this experimental study, the antibacterial properties of two sealants (with fluoride (Clinpro 3M) and without fluoride (Concise 3M) was investigated with 0, 0.01, 0.02, 0.03, 0.04, 0.05% w/w after adding nano-silver using direct contact test. Sealants formed on the walls of 500ml micro tube and after curing, they left in contact with bacterial suspension. In periods of 3, 24, 48h, a 10 µl volume of liquid medium was placed in blood agar culture and after 24 h incubation at 37ºC, the number of S.mutans colony was counted by colony counter. Data were analyzed using ANOVA andT-test.   Results: Results reported sealants with fluoride comparing to non fluoride ones had significant effect on inhibition of S.mutans growth (P<0.001). The direct contact test demonstrated that by increasing the amount of nano particles, the bacterial growth was significantly diminished (P<0.001).   Conclusion: While sealants with fluoride demonstrated antibacterial effect, sealants with incorporation of higher weight percentage of nanosilver particles, had stronger and more significant antibacterial effect in direct contact test

Differential Effects of Resveratrol on the Expression of Brain-Derived Neurotrophic Factor Transcripts and Protein in the Hippocampus of Rat Brain

Background: The induction of brain-derived neurotrophic factor (BDNF) expression in the hippocampus has shown to play a role in the beneficial effects of resveratrol (RSV) on the learning and memory. The BDNF gene has a complicated structure with eight 5’ noncoding exons (I-IXa), each of which can splice to a common coding exon (IX) to form a functional transcript. Estrogens increase levels of BDNF transcripts in the hippocampus of rats. The aim of this study was to evaluate the effects of the phytoestrogen, RSV, on the splicing pattern of BDNF transcripts and on the pro-BDNF protein in the hippocampi of mother rats and their embryos. Methods: RSV (60 or 120 mg/kg BW/day) was administered orally to pregnant rats from days 1 to 20 of gestation. Hippocampi of adults and embryos were dissected 24 h after the last administration of RSV. Extracts from hippocampi were subject to quantitative (q) RT-PCR and Western blotting to assess splicing pattern of the BDNF transcripts and levels of pro-BDNF protein, respectively. Results: RSV (120 mg/kg BW/day) caused a statistically significant increase in the expression levels of BDNF exons III, IV and IX, but not the exon I in the hippocampi of adult rats (P≤0.05). Levels of pro-BDNF protein remained unchanged in the hippocampal tissues from both adult and embryonic rats treated by RSV (60 or 120 mg/kg BW/day). Conclusion: Our results showed that RSV differentially activates promoters of the BDNF gene in the hippocampus of pregnant rats, but fails to affect the pro-BDNF level neither in adult nor in the embryonic hippocampal tissues

Efficacy and Safety of Alirocumab and Evolocumab as Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors in Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis.

BACKGROUND Familial hypercholesterolemia (FH) is a prevalent and potentially fatal illness that causes a substantial elevation in low-density lipoprotein cholesterol (LDL-C). OBJECTIVE The aim of this study was to investigate the effects of monoclonal antibodies alirocumab and evolocumab on LDL-C and other lipid parameters, as well as their safety in familial hypercholesterolemia patients. METHODS A comprehensive search was done on PubMed/MEDLINE, EMBASE, Web of Science (WOS/ ISI), Scopus, ClinicalTrials (www. CLINICALTRIALS gov), and conferences/ congress research papers. Random effect models were used to calculate mean differences (%) and risk ratios (RRs), and confidence intervals (95%). RESULTS Ten studies (n=1489 patients) were included in this study. PCSK9 inhibitors decreased the levels of LDL-C by -49.59% (95%CI -55.5%, -43.67%) as compared to placebo. They also didn't alter the Treatment-Emergent Adverse Event (TEAE) and neuronal events by RR 0.92 (0.75, 1.13) and 1.31 (0.66, 2.59), respectively. PCSK9 inhibitors were effective and safe in treating patients with FH. CONCLUSION There was high-quality evidence showing that monoclonal antibodies (alirocumab & evolocumab) lower LDL-C (GRADE: high), lipoprotein (a) (GRADE: High), triglycerides (TG) (GRADE: High), total cholesterol (GRADE: High), non-high-density lipoprotein cholesterol (nonHDL-C) (GRADE: Moderate), and apolipoprotein B (GRADE: High), and increase the HDL-C (GRADE: High) as well as apolipoprotein A1 (GRADE: High). Comparing PCSK9 inhibitors against placebo, neither TEAE (GRADE: high) nor neuronal events (GRADE: moderate) were changed. Registration number PROSPERO-CRD42022334035