Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition of Metastatic Phenotype.

Understanding the role of biased taste T1R2/T1R3 G protein-coupled receptors (GPCR) agonists on glycosylated receptor signaling may provide insights into the opposing effects mediated by artificial and natural sweeteners, particularly in cancer and metastasis. Sweetener-taste GPCRs can be activated by several active states involving either biased agonism, functional selectivity, or ligand-directed signaling. However, there are increasing arrays of sweetener ligands with different degrees of allosteric biased modulation that can vary dramatically in binding- and signaling-specific manners. Here, emerging evidence proposes the involvement of taste GPCRs in a biased GPCR signaling crosstalk involving matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu-1) activating glycosylated receptors by modifying sialic acids. The findings revealed that most natural and artificial sweeteners significantly activate Neu-1 sialidase in a dose-dependent fashion in RAW-Blue and PANC-1 cells. To confirm this biased GPCR signaling crosstalk, BIM-23127 (neuromedin B receptor inhibitor, MMP-9i (specific MMP-9 inhibitor), and oseltamivir phosphate (specific Neu-1 inhibitor) significantly block sweetener agonist-induced Neu-1 sialidase activity. To assess the effect of artificial and natural sweeteners on the key survival pathways critical for pancreatic cancer progression, we analyzed the expression of epithelial-mesenchymal markers, CD24, ADLH-1, E-cadherin, and N-cadherin in PANC-1 cells, and assess the cellular migration invasiveness in a scratch wound closure assay, and the tunneling nanotubes (TNTs) in staging the migratory intercellular communication. The artificial and natural sweeteners induced metastatic phenotype of PANC-1 pancreatic cancer cells to promote migratory intercellular communication and invasion. The sweeteners also induced the downstream NFκB activation using the secretory alkaline phosphatase (SEAP) assay. These findings elucidate a novel taste T1R2/T1R3 GPCR functional selectivity of a signaling platform in which sweeteners activate downstream signaling, contributing to tumorigenesis and metastasis via a proposed NFκB-induced epigenetic reprogramming modeling.

Biopolymer collagen-chitosan scaffold containing Aloe vera for chondrogenic efficacy on cartilage tissue engineering.

The chondrogenic efficacy of aloe vera blended collagen-chitosan (COL-CS-AV) porous scaffold was investigated using articular chondrocytes in a standard condition. Cytocompatibility was analyzed using fluorescent dyes (calcein AM/ethidium bromide) and the viable cells were quantified by MTT assay. Glycosaminoglycan (GAG) content of ECM was estimated by using 1, 9-Dimethyl methylene Blue (DMMB). The total RNA content was quantified and the cartilage specific genes (col2a1, Acan) were amplified by reverse transcription-PCR from the cell lysate of the scaffolds. Histological examination was made using Haematoxylin and Eosin (H&E), safranin-O, masson's trichrome, alcian blue, and alizarin red to stain the specific component of ECM secreted on the construct. The cartilage specific collagen type II was estimated by immunohistochemistry using monoclonal type II collagen antibody. The results of these studies proved that COL-CS-AV scaffold has more chondrogenic efficacy than COL-CS, thus the aloe vera blend COL-CS-AV scaffold might be used as suitable candidate for cartilage tissue engineering.

Impact of timing and severity of COVID-19 infection in pregnancy on intrauterine fetal growth- a registry-based study from Qatar.

BACKGROUND: The novel coronavirus disease (COVID-19) pandemic has impacted pregnant women, increasing maternal and neonatal morbidity. The placenta is a potential target for the pathophysiological processes due to the increased thrombotic inflammatory activation and inadequate uteroplacental perfusion and oxygenation, potentially causing intrauterine growth restriction. This study investigates the impact of gestational age at diagnosis of COVID-19 and the presence of symptoms on intrauterine fetal growth in pregnant women. METHODS: A retrospective review of COVID-19 positive pregnant women in Qatar from March 2020 to March 2021 was conducted. They were divided based on trimester of pregnancy in which they were infected. The outcomes included birthweight, customised fetal birthweight centiles, small for gestational age (SGA) baby and daily growth increments, compared between the trimesters and between symptomatic and asymptomatic women. RESULTS: In our cohort, 218 women (20.5%) were infected in the first trimester, 399 (37.5%) in the second and 446 (42%) in the third. Women in the second trimester were significantly younger and symptomatic. Women infected in the first trimester were least likely to have diabetes. The mean birthweight, risk of SGA (11.5% vs 10% vs 14.6%, p = 0.302), and median customized growth centiles (47.6% vs 45.9% vs 46.1%)were similar between the groups. Symptomatic women had significantly lower mean birthweight (3147 gms vs 3222 gms) and median birthweight centiles (43.9% vs 54.0%)compared to the asymptomatic (p<0.05 for both). In women infected within 20 weeks of gestation, a delay in daily fetal growth increments was noted with symptomatic disease, although not statistically significant. CONCLUSION: This study shows that women with symptomatic disease had lower birth centiles and birth weights. This was regardless of the gestational age at which they were infected. Early symptomatic disease seems to have an impact on fetal growth velocity; however, larger studies are needed to corroborate these findings.

Restoring Epigenetic Reprogramming with Diet and Exercise to Improve Health-Related Metabolic Diseases.

Epigenetic reprogramming predicts the long-term functional health effects of health-related metabolic disease. This epigenetic reprogramming is activated by exogenous or endogenous insults, leading to altered healthy and different disease states. The epigenetic and environmental changes involve a roadmap of epigenetic networking, such as dietary components and exercise on epigenetic imprinting and restoring epigenome patterns laid down during embryonic development, which are paramount to establishing youthful cell type and health. Nutrition and exercise are among the most well-known environmental epigenetic factors influencing the proper developmental and functional lifestyle, with potential beneficial or detrimental effects on health status. The diet and exercise strategies applied from conception could represent an innovative epigenetic target for preventing and treating human diseases. Here, we describe the potential role of diet and exercise as therapeutic epigenetic strategies for health and diseases, highlighting putative future perspectives in this field.

Maternal risk factors of COVID-19-affected pregnancies: A comparative analysis of symptomatic and asymptomatic COVID-19 from the Q-PRECIOUS registry.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic has had consequences on the pregnant population, as disease severity is associated with the quality of maternal health and pregnancy complications, increasing maternal and neonatal morbidity. Worldwide descriptive data help describe risk factors that could predict symptomatic and severe COVID-19 in pregnancy. OBJECTIVES: To describe demographic features and risk factors of pregnant women with COVID-19 in Qatar and compare symptomatic versus asymptomatic disease. STUDY DESIGN AND METHODOLOGY: Clinical characteristics and risk factors of pregnant women with COVID-19 in Qatar from March 2020 to March 2021 was retrospectively reviewed, comparing the cohort with the general pregnant population. Crude and adjusted odds ratios (aORs) were computed, comparing symptomatic versus asymptomatic infection. RESULTS: Of the 500 women, 347 reported at least one symptom at diagnosis (347/500; 69.4%). The majority fell in the 30-39 years age group (241/500; 48%), with more than half in the obese body mass index (BMI) category. The cohort was 66% (332/500) Qatari women, compared with the 26% expected in the population (26.4% vs 66.4% p < 0.001). Compared with the 2019 national statistics, the number of women was higher in the >40 years age group (5% vs 7.6%, p = 0.027) and grand multiparous group (5.4% vs 13.6%, p < 0.001). The symptom most commonly reported by the symptomatic group was cough (276/500; 55%), followed by fever, fatigue, and myalgia. In the adjusted analysis, the symptomatic group had 2.7 times higher odds of being asthmatic (OR = 2.67, 95% CI 1.1-6.7, p = 0.037). Women aged >40 years had 6.6 times higher odds of symptomatic disease (aOR = 6.6, 95% CI 1.08-39.73, p = 0.041). A history of contact with a patient with symptomatic COVID and earlier gestational age at diagnosis increased the odds (aOR = 2.06, 95% CI 1.2-3.54, p = 0.009; aOR = 0.73 95% CI 0.57-0.96; p = 0.017). CONCLUSIONS: This study cohort included significantly more Qatari women, older women, grand multiparous women, a higher proportion with pre-existing and gestational diabetes, and higher BMI than national data. In addition, contact to a patient with symptomatic disease, history of asthma, older age, and earlier gestational age at diagnosis were significantly associated with symptomatic disease.

Preparation and characterization of aloe vera blended collagen-chitosan composite scaffold for tissue engineering applications.

Collagen-Chitosan (COL-CS) scaffolds supplemented with different concentrations (0.1-0.5%) of aloe vera (AV) were prepared and tested in vitro for their possible application in tissue engineering. After studying the microstructure and mechanical properties of all the composite preparations, a 0.2% AV blended COL-CS scaffold was chosen for further studies. Scaffolds were examined by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and thermogravimetry analysis (TGA) to understand the intermolecular interactions and their influence on the thermal property of the complex composite. Swelling property in phosphate buffered saline (pH 7.4) and in vitro biodegradability by collagenase digestion method were monitored to assess the stability of the scaffold in a physiological medium in a hydrated condition, and to assay its resistance against enzymatic forces. The scanning electron microscope (SEM) image of the scaffold samples showed porous architecture with gradual change in their morphology and reduced tensile properties with increasing aloe vera concentration. The FTIR spectrum revealed the overlap of the AV absorption peak with the absorption peak of COL-CS. The inclusion of AV to COL-CS increased the thermal stability as well as hydrophilicity of the scaffolds. Cell culture studies on the scaffold showed enhanced growth and proliferation of fibroblasts (3T3L1) without exhibiting any toxicity. Also, normal cell morphology and proliferation were observed by fluorescence microscopy and SEM. The rate of cell growth in the presence/absence of aloe vera in the scaffolds was in the order: COL-CS-AV > COL-CS > TCP (tissue culture polystyrene plate). These results suggested that the aloe vera gel-blended COL-CS scaffolds could be a promising candidate for tissue engineering applications.