L-Arginine Enhances Oral Keratinocyte Proliferation under High-Glucose Conditions via Upregulation of CYP1A1, SKP2, and SRSF5.

High glucose inhibits oral keratinocyte proliferation. Diabetes can lead to delayed oral wound healing and periodontal disease. L-Arginine, one of the most versatile amino acids, plays an important role in wound healing, organ maturation, and development. In this study, L-Arginine was found to enhance oral keratinocyte proliferation under high-glucose conditions. RNA sequencing analysis discovered a significant number of genes differentially upregulated following L-Arginine treatment under high-glucose conditions. Cytochrome P450 family 1 subfamily A member 1 (CYP1A1) was the most significantly upregulated gene at 24 and 48 h after L-Arginine treatment. Gene Ontology enrichment analysis found that cell proliferation- and mitosis-related biological processes, such as mitotic nuclear division, mRNA processing, and positive regulation of cell cycle processes, were significantly upregulated. Pathway enrichment analysis found that S-phase kinase-associated protein 2 (SKP2) and serine- and arginine-rich splicing factor 5 (SRSF5) were the top upregulated genes in cell cycle and spliceosome pathways, respectively. Indirect immunofluorescent cytochemistry confirmed increased protein levels of CYP1A1, SKP2, and SRSF5 after L-Arginine treatment. Knockdown of CYP1A1, SKP2, and SRSF5 abolished the enhanced proliferative effect of L-Arginine on oral keratinocytes under high-glucose conditions. In conclusion, L-Arginine enhances oral keratinocyte proliferation under high-glucose conditions via upregulation of CYP1A1, SKP2, and SRSF5, suggesting that supplemental L-Arginine in oral care products may be beneficial for oral tissue repair and regeneration.

Dietary Saturated, Monounsaturated, or Polyunsaturated Fatty Acids and Estimated 10-Year Risk of a First Hard Cardiovascular Event.

BACKGROUND: The effects of dietary saturated, monounsaturated, or polyunsaturated fatty acids on the risk of cardiovascular events remain controversial. METHODS: This cross-sectional study was performed in 4211 patients, aged 40 to 79 years, from the National Health and Nutrition Examination Survey between 1999 and 2018. The independent variables were saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. The dependent variable was the 10-year risk of a first hard atherosclerotic cardiovascular event. The other variables were considered as the potential confounding factors. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between saturated fatty acids, polyunsaturated fatty acids, or monounsaturated fatty acids and the 10-year risk. RESULTS: There was no association between dietary saturated fatty acids and 10-year risk after adjusting for all the potential confounding factors; 10-year risk decreased by 0.022% each 1-g increase in monounsaturated fatty acids intake from 0 to 153.772 g, and 0.025% each 1-g increase in polyunsaturated fatty acids intake from 0 to 98.323 g, respectively. Moreover, subgroup analysis showed that monounsaturated fatty acids and polyunsaturated fatty acids were both negatively correlated to 10-year risk in nondiabetes and non-high-low-density lipoprotein patients; monounsaturated fatty acids were also negatively associated with 10-year risk in hypertensive patients. CONCLUSIONS: There was no association between dietary saturated fatty acids and 10-year risk. Increased dietary intake of monounsaturated fatty acids or polyunsaturated fatty acids decreased 10-year risk, particularly in nondiabetes, non-high-low density lipoprotein patients.

Effects of Microbiota-Driven Therapy on Circulating Indoxyl Sulfate and P-Cresyl Sulfate in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, exacerbate the deterioration of renal function and increase the risk of cardiovascular events in chronic kidney disease (CKD) patients. The effects of microbiota-driven therapy (probiotics, prebiotics, or synbiotics) on decreasing circulating IS and PCS concentrations are controversial; thus, we performed the present systematic review and meta-analysis to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients. PubMed, EMBASE, and Cochrane Library databases were systematically searched from inception to 22 July, 2021, and randomized controlled trials (RCTs) investigating the effects of microbiota-driven therapy on circulating IS and PCS concentrations in CKD patients were included. In all, 14 RCTs with 513 participants were eligible for the meta-analysis. The effects of microbiota-driven therapy on the circulating IS and PCS concentrations were evaluated with weighted mean differences (WMDs) measured by a fixed-effects model or a random-effects model. Compared with placebo, microbiota-driven therapy had no statistically significant effect on the circulating IS concentration (WMD: -1.64 mg/L; 95% CI: -3.46, 0.18 mg/L; P = 0.077) but it decreased the circulating PCS concentration (WMD: -2.42 mg/L; 95% CI: -3.81, -1.04 mg/L; P = 0.001). In the subgroup analyses, prebiotic (n = 6) and synbiotic (n = 3) supplementation significantly decreased the circulating PCS concentration, whereas probiotic (n = 3) supplementation did not. Meta-regression showed that the effects of microbiota-driven therapy were not associated with the supplementation time or the year of publication. Moreover, there was no significant evidence of publication bias. This review found that microbiota-driven therapy decreased the circulating PCS concentration in CKD patients. Additional large, well-designed RCTs with improved methodology and reporting are necessary to assess the effects of microbiota-driven therapy on circulating IS and PCS concentrations in the long term. This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42021269146.

Effects of bioactive glass with high phosphorus content on mineralization of type I collagen fibrils.

PURPOSE: To study effects of bioactive glass with high phosphorus content (10.8% P2O5, 54.2% SiO2, 35% CaO, mol%, named PSC) on mineralization of type I collagen fibrils. METHODS: (1) PSC, and PSC combining 0.1 mg/mL, 0.5 mg/mL, or 1.0 mg/mL polyacrylic acid (PAA), were used to induce the mineralization of self-assembled type I collagen fibrils. After 3 and 7 days of mineralization, collagen fibrils were observed by transmission electron microscopy (TEM) and selected area electron diffraction (SAED). (2) PSC suspension was dialyzed in simulated body fluid (SBF), or in SBF containing 0.1 mg/mL, 0.5 mg/mL, or 1.0 mg/mL PAA, to form amorphous calcium phosphate (ACP), then observed by TEM. RESULTS: (1) PSC and PSC combining 0.1 mg/mL or 0.5 mg/mL PAA induced mainly extrafibrillar mineralization. PSC combining 1.0 mg/mL PAA induced both extrafibrillar and intrafibrillar mineralization. (2) The ACP induced by PSC or PSC combining 0.1 mg/mL PAA partly formed lattice structure after 24 h. The particle size of the ACP induced by PSC combining 0.5 mg/mL PAA was 100-150 nm, and that induced by PSC combining 1.0 mg/mL PAA was 30-50 nm. CONCLUSION: PSC induced mainly extrafibrillar mineralization, and PSC combining an appropriate concentration (1.0 mg/mL) of PAA induced both extrafibrillar and intrafibrillar mineralization.

Panax Quinquefolium Saponins Attenuate Myocardial Dysfunction Induced by Chronic Ischemia.

BACKGROUND/AIMS: Previous studies in rat models of myocardial ischemia showed that Panax quinquefolium saponins (PQS) could attenuate ischemic/reperfusion injury, increase vessel density and improve cardiac function. In the current study, we examined whether PQS could attenuate myocardial dysfunction in a swine model of chronic myocardial ischemia (CMI). METHODS: CMI was established in Bama mini-pigs by placing amroid constrictor on the left anterior descending artery (LAD). Starting from 2 months after the surgery, pigs randomly received PQS (30 mg/kg/day), atorvastatin (1.5 mg/kg/day), or no drug for one month (n=6). A group of pigs receiving sham surgery was included as an additional control. Glucose utilization was assessed with positron emission tomography-computer tomography (PET-CT). Cardiac function was assessed with echocardiography. Myocyte size, nuclear density, and arteriolar density were examined in tissue section obtained from the ischemia area. Potential molecular targets of PQS were identified using proteomic analysis with isobaric tags for relative and absolute quantitation (iTARQ) and network pharmacology. RESULTS: In comparison to the sham controls, pigs implanted with ameroid constrictor had decreased ventricular wall motion, left ventricular ejection fraction (LVEF), and glucose utilization. PQS significantly increased cardiac function and glucose utilization. Arteriole density and myocyte nuclear density were increased. Myocyte diameter was decreased. PQS also attenuated the CMI-induced change of protein expression profile. The effects of atorvastatin were generally similar to that of PQS. However, PQS attenuated the reduction of left ventricular systolic WT induced by CMI more robustly than atorvastatin. CONCLUSION: The results from the current study supports the use of PQS in patients with coronary artery disease.