Smoking induced salivary microbiome dysbiosis and is correlated with lipid biomarkers.

BACKGROUND: The oral microbiome plays an essential role in maintaining oral homeostasis and health; smoking significantly affects it, leading to microbial dysbiosis. The study aims to investigate changes in the oral microbiome composition of smokers in the Qatari population and establish a correlation with lipid biomarkers. METHODS: The oral microbiota was profiled from saliva samples of 200 smokers and 100 non-smokers in the Qatari population, and 16s rRNA V3-V4 region were sequenced using the Illumina MiSeq platform. The operational taxonomic units (OTUs) were clustered using QIIME and the statistical analysis was performed by R. RESULTS: Non-smokers exhibited a more diverse microbiome, with significant alpha and beta diversity differences between the non-smoker and smoker groups. Smokers had a higher abundance of Firmicutes, Bacteroidota, Actinobacteriota, Patescibacteria, and Proteobacteria at the phylum level and of Streptococcus, Prevotella, Veillonella, TM7x, and Porphyromonas at the genus level. In contrast, non-smokers had more Bacteroidota, Firmicutes, Proteobacteria, Fusobacteriota, and Patescibacteria at the phylum level, and Prevotella, Streptococcus, Veillonella, Porphromonas, and Neisseria at the genus level. Notably, Streptococcus was significantly positively correlated with LDL and negatively correlated with HDL. Additionally, Streptococcus salivarius, within the genus Streptococcus, was substantially more abundant in smokers. CONCLUSION: This study highlights the significant influence of smoking on the composition of the oral microbiome by enriching anaerobic microbes and depleting aerobic microbes. Moreover, the observed correlation between Streptococcus abundance and the lipid biomarkers suggests a potential link between smokers-induced salivary microbiome dysbiosis and lipid metabolism. Understanding the impact of smoking on altering the oral microbiome composition and its correlation with chemistry tests is essential for developing targeted interventions and strategies to improve oral health and reduce the risk of diseases.

Exploring the role of oral microbiome dysbiosis in cardiometabolic syndrome and smoking.

Oral microbiome research has gained significant interest in recent years due to its potential impact on overall health. Smoking has been identified as a significant modulator of the oral microbiome composition, leading to dysbiosis and possible health consequences. Research has primarily focused on the association between smoking and oral microbiome, as well as smoking's association with cardiometabolic syndrome (CMS). This narrative review presents an overview of the recent findings and current knowledge on the oral microbiome and its role in CMS, including the effects of smoking and ethnicity. We discussed the development and composition of the oral microbiome and the association of periodontitis with diabetes and cardiovascular diseases. Furthermore, we highlighted the correlations between oral microbiome and CMS factors, such as diabetes, hypertension, dyslipidemia, and obesity. There is a need for further research in this area to better understand the mechanisms underlying the impact of smoking on oral microbiome dysbiosis and the development of CMS. Interestingly, geographic location and ethnicity have been shown to impact the oral microbiome profiles across populations. This knowledge will help develop personalized disease prevention and treatment approaches considering individual differences in oral microbiome composition. Understanding the complex interplay between oral microbiome, smoking, and CMS is essential for developing effective prevention and treatment strategies for a wide range of diseases.

The Effects of Spirulina Supplementation on Cardiometabolic Risk Factors: A Narrative Review.

Spirulina (Arthrospira platensis) is a cyanobacterium associated with multiple health benefits. Cardiometabolic diseases such as cardiovascular disease, nonalcoholic fatty liver disease, and diabetes are prevalent yet usually preventable non-communicable diseases. Modifiable risk factors for cardiometabolic diseases include excessive body weight, body inflammation, atherogenic lipid profile, and imbalanced glucose metabolism. This review explores the effects of spirulina on cardiometabolic diseases risk factors. Spirulina was effective in reducing body weight, body mass index, and waist circumference, with a potential dose-dependent effect. It also decreased interleukin 6, an important biomarker of body inflammation, by inhibiting NADPH oxidase enzyme, and lowering insulin resistance. spirulina supplementation also reduced triglycerides, low-density lipoprotein cholesterol, and increased high-density lipoprotein cholesterol. Additionally, spirulina reduced fasting blood sugar and post-prandial blood sugar and increased insulin sensitivity, but no effect was observed on glycated hemoglobin A1c. The diverse nutrients, such as phycocyanin, gamma-linolenic acid, and vitamin B12, present in spirulina contribute to its cardiometabolic benefits. The doses used are heterogeneous for most studies, ranging from 1 to 8 grams daily, but most studies administered spirulina for 3 months to observe an effect. The collective evidence suggests that spirulina supplements may help improve risk factors for cardiometabolic diseases, thus, preventing its development. However, due to the heterogeneity of the results, more randomized clinical trials are needed to draw robust conclusions about spirulina's therapeutic potential in ameliorating risk factors for cardiometabolic diseases and fully elucidate the mechanisms by which it exerts its effects.

Developmental Toxicity of Surface-Modified Gold Nanorods in the Zebrafish Model.

BACKGROUND: nanotechnology is one of the fastest-growing areas, and it is expected to have a substantial economic and social impact in the upcoming years. Gold particles (AuNPs) offer an opportunity for wide-ranging applications in diverse fields such as biomedicine, catalysis, and electronics, making them the focus of great attention and in parallel necessitating a thorough evaluation of their risk for humans and ecosystems. Accordingly, this study aims to evaluate the acute and developmental toxicity of surface-modified gold nanorods (AuNRs), on zebrafish (Danio rerio) early life stages. METHODS: in this study, zebrafish embryos were exposed to surface-modified AuNRs at concentrations ranging from 1 to 20 µg/mL. Lethality and developmental endpoints such as hatching, tail flicking, and developmental delays were assessed until 96 h post-fertilization (hpf). RESULTS: we found that AuNR treatment decreases the survival rate in embryos in a dose-dependent manner. Our data showed that AuNRs caused mortality with a calculated LC50 of EC50,24hpf of AuNRs being 9.1 µg/mL, while a higher concentration of AuNRs was revealed to elicit developmental abnormalities. Moreover, exposure to high concentrations of the nanorods significantly decreased locomotion compared to untreated embryos and caused a decrease in all tested parameters for cardiac output and blood flow analyses, leading to significantly elevated expression levels of cardiac failure markers ANP/NPPA and BNP/NPPB. CONCLUSIONS: our results revealed that AuNR treatment at the EC50 induces apoptosis significantly through the P53, BAX/BCL-2, and CASPASE pathways as a suggested mechanism of action and toxicity modality.

Design and Microinjection of Morpholino Antisense Oligonucleotides and mRNA into Zebrafish Embryos to Elucidate Specific Gene Function in Heart Development.

The morpholino oligomer-based knockdown system has been used to identify the function of various gene products through loss or reduced expression. Morpholinos (MOs) have the advantage in biological stability over DNA oligos because they are not susceptible to enzymatic degradation. For optimal effectiveness, MOs are injected into 1-4 cell stage embryos. The temporal efficacy of knockdown is variable, but MOs are believed to lose their effects due to dilution eventually. Morpholino dilution and injection amount should be closely controlled to minimize the occurrence of off-target effects while maintaining on-target efficacy. Additional complementary tools, such as CRISPR/Cas9 should be performed against the target gene of interest to generate mutant lines and to confirm the morphant phenotype with these lines. This article will demonstrate how to design, prepare, and microinject a translation-blocking morpholino against hand2 into the yolk of 1-4 cell stage zebrafish embryos to knockdown hand2 function and rescue these "morphants" by co-injection of mRNA encoding the corresponding cDNA. Subsequently, the efficacy of the morpholino microinjections is assessed by first verifying the presence of morpholino in the yolk (co-injected with phenol red) and then by phenotypic analysis. Moreover, cardiac functional analysis to test for knockdown efficacy will be discussed. Finally, assessing the effect of morpholino-induced blockage of gene translation via western blotting will be explained.

Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model.

Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells' proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles (NPs) as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, with the aim to reduce Ponatinib cardiotoxicity, Poly(D,L-lactide-co-glycolide)-b-poly(ethyleneoxide)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was used to synthesize Ponatinib in loaded PLGA-PEG-PLGA NPs for chronic myeloid leukemia (CML) treatment. In addition to physicochemical NPs characterization (NPs shape, size, size distribution, surface charge, dissolution rate, drug content, and efficacy of encapsulation) the efficacy and safety of these drug-delivery systems were assessed in vivo using zebrafish. Zebrafish are a powerful animal model for investigating the cardiotoxicity associated with anti-cancer drugs such as TKIs, to determine the optimum concentration of smart NPs with the least side effects, and to generate a xenograft model of several cancer types. Therefore, the cardiotoxicity of unloaded and drug-loaded PLGA-PEG-PLGA NPs was studied using the zebrafish model by measuring the survival rate and cardiac function parameters, and therapeutic concentration for in vivo efficacy studies was optimized in an in vivo setting. Further, the efficacy of drug-loaded PLGA-PEG-PLGA NPs was tested on the zebrafish cancer xenograft model, in which human myelogenous leukemia cell line K562 was transplanted into zebrafish embryos. Our results demonstrated that the Ponatinib-loaded PLGA-PEG-PLGA NPs at a concentration of 0.001 mg/mL are non-toxic/non-cardio-toxic in the studied zebrafish xenograft model.

Physiological Changes and Interactions Between Microbiome and the Host During Pregnancy.

In recent years, it has become clear that microbiome play a variety of essential roles in human metabolism, immunity, and overall health and that the composition of these microbiome is influenced by our environment, diet, weight, hormones, and other factors. Indeed, numerous physiological and pathological conditions, including obesity and metabolic syndrome, are associated with changes in our microbiome, referred to as dysbiosis. As a result, it is not surprising that such changes occur during pregnancy, which includes substantial weight gain and significant changes in metabolism and immune defenses. The present review relates physiological changes during pregnancy to alterations in the microbial composition at various sites, including the gut, oral cavity, and vagina. Pregnancy has been linked to such microbial changes, and we believe that, in contrast to certain disease states, these microbial changes are vital for a healthy pregnancy, probably through their influence on the mother's immunological, endocrinological, and metabolic status.

Effect of Water-Pipe Smoking on the Normal Development of Zebrafish.

BACKGROUND: Among all types of tobacco consumption, Water-Pipe Smoking (WPS) is the most widely used in the Middle East and second-most in several other countries. The effect of WPS on normal development is not yet fully understood, thus the aim of this study is to explore the acute toxicity effects of WPS extract on zebrafish larvae. METHODS: In this study, we compared the effects of WPS smoke condensates at concentrations varying from 50 to 200 µg/mL on developmental, cardiac, and behavioural (neurotoxicity) functions. Gene expression patterns of cardiac biomarkers were also evaluated by RT-qPCR. RESULTS: Exposing zebrafish embryos to 50, 100, 150 and 200 µg/mL WPS for three days did not affect the normal morphology of Zebrafish embryos, as the tail flicking, behavioural and locomotion assays did not show any change. However, WPS deregulated cardiac markers including atrial natriuretic peptide (ANP/NPPA) and brain natriuretic peptide (BNP/NPPB). Furthermore, it induced apoptosis in a dose-dependent manner. CONCLUSION: Our data demonstrate that WPS can significantly affect specific cardiac parameters during the normal development of zebrafish. Further investigations are necessary to elucidate the pathogenic outcome of WPS on different aspects of human life, including pregnancy.

The Effect of Surface-Modified Gold Nanorods on the Early Stage of Embryonic Development and Angiogenesis: Insight into the Molecular Pathways.

Gold nanorods have been implicated in several biomedical applications. Herein, the effect of two surface-modified gold nanorods on the early stages of embryogenesis and angiogenesis was investigated using avian embryos at three days and their chorioallantoic membrane (CAM) at five days of incubation. We found that gold nanorods (GNR) modified with PEGylated phospholipid moiety show a high mortality rate in embryos after four days of exposure compared to GNR modified with PEGylated cholesterol moiety. Meanwhile, our data revealed that surface modified-GNR significantly inhibit the formation of new blood vessels in the treated CAM model after 48 h of exposure. Moreover, we report that surface-modified GNR significantly deregulate the expression of several genes implicated in cell proliferation, invasion, apoptosis, cellular energy metabolism, and angiogenesis. On the other hand, our data point out that GNR treatments can modulate the expression patterns of JNK1/2/3, NF-KB/p38, and MAPK, which could be the main molecular pathways of the nanorods in our experimental models.