DO ORAL CARE AND REHABILITATION IMPROVE COGNITIVE FUNCTION? A SYSTEMATIC REVIEW OF CLINICAL STUDIES.

OBJECTIVES: An increasing number of studies have identified an association between oral health status and cognitive function. However, the effect of oral interventions, including oral health care, dental treatment and oral motor exercises, on cognitive function remains unclear. This systematic review examined whether oral interventions contribute to the long-term improvement of cognitive status. METHODS: Four databases were searched (MEDLINE, Web of Science, Cochrane Library, and ICHUSHI Web) to identify randomized and nonrandomized controlled trial studies and prospective cohort studies from inception until 1 September 2023, published in English or Japanese. The Cochrane risk of bias tool for randomized controlled trials and the risk of bias assessment tool for nonrandomized studies were used to assess bias risk. RESULTS: A total of 20 articles were included in the qualitative analysis; 13 articles were published in English, and 7 were published in Japanese. The implemented interventions were oral care in 8 studies, dental treatment in 8 studies, and oral motor exercise in 4 studies. One study found a significant effect on attention following oral care intervention. Some dental treatments influenced cognitive function, although a clear positive effect was not determined. In 1 study, attention and working memory improved in the chewing exercise group. CONCLUSIONS: Several studies verified the improvement effects of oral interventions, such as oral care, dental treatment, and oral motor exercise, on cognitive function or impairment. However, there was still a lack of conclusive evidence that such an intervention clearly improved cognitive function. To clarify the effects of oral interventions on cognitive function, it is necessary to examine participants, interventions, and outcome measures in detail.

An in vitro study on the selection of surfactants for removal of cream denture adhesives from dentures and their application to denture cleaners.

Purpose Denture adhesives improve the stability of incompatible dentures; however, complete removal of adhesives after use is difficult. Only a few studies have focused on the removal of denture adhesives. Hence, this study aimed to assess the efficacy of surfactants in removing cream denture adhesives from acrylic resin materials.Methods Solutions of twelve surfactants with various hydrophilic-lipophilic balance (HLB) values were prepared. Two cream denture adhesives, colored for visualization, were spread onto transparent acrylic resin plates. After immersion into surfactant solutions, the effects of the surfactants on residual adhesives were evaluated. We also investigated the effect of denture cleaners (with or without the surfactants) on the removability of adhesives and artificial oily dirt, and their effects on the surface properties of denture materials. The obtained data were analyzed using appropriate statistical methods.Results Five surfactants [BT-5, BL-4.2, BT-7, BT-9, and Triton X-100 (TX)] with HLB values in the 10.5-13.5 range effectively removed adhesives. Addition of BT-9 and TX (HLB=13.5) to denture cleaners improved the adhesives' removal. Furthermore, the addition of TX to the cleaners did not interfere with the removal of artificial oily dirt and did not damage the denture materials' surface.Conclusions Surfactants with HLB values in the 10.5-13.5 range are suitable for removal of cream denture adhesives from acrylic resin materials. In particular, TX (HLB=13.5) efficiently removes adhesives without damaging denture materials or impairing original detergency.

Effects of Denture Cleaning Regimens on the Quantity of Candida on Dentures: A Cross-Sectional Survey on Nursing Home Residents.

Oral care involving a denture cleaning regimen is important for reducing the incidence of systemic diseases. However, limited information is currently available on denture cleaning frequencies and regimens. Therefore, the present study investigated the relationship between the number of Candida spp. present on the complete dentures of nursing home residents and cleaning regimens. Residents were surveyed to assess their denture cleaning methods. Plaque was collected by applying a sterile swab to the mucosal surface of each examined complete denture worn by 77 residents, and the Candida spp. collected were cultured, identified, and quantified. The relationship between denture cleaning regimens and the quantity of Candida spp. was investigated. Correlation and multivariable analyses revealed that the strongest factor influencing the number of Candida spp. on dentures was the frequency of use of denture cleansers. The number of Candida spp. was the lowest on dentures cleaned daily with a denture cleanser. The present results demonstrated that the daily use of a denture cleanser effectively controlled the adherence of Candida spp. to dentures. Oral and other healthcare providers need to provide instructions on and assist nursing home residents with the daily care of dentures, using denture cleansers, including the environment where cleaning is performed.

Properties and characteristics of foam denture cleaners as denture adhesive removers.

The need for denture adhesives is increasing worldwide, but few denture-care products target denture adhesive users. Foam denture cleaners have been recently marketed to assist brush denture cleaning, but there is a lack of objective evaluation. In this study, we compared the detergency of denture adhesives using six commercial foam-denture cleaners. For removing the adhesives, most of the tested cleaners were effective in immersion experiments, and three cleaners were more effective in the denture cleaning experiment compared to control water. However, only one could effectively remove the slime that is derived from the adhesive and detergency of artificial dirt. The surface roughnesses of the denture base and the relining material revealed that prolonged immersion in some cleaners could be affected. The results suggest that different commercial foam denture cleaners have different detergency levels, and that some cleaners may affect the properties of denture materials upon long-term use.

Impact of Surface Changes and Microbial Adhesion on Mucosal Surface Finishing of Resin Denture Bases by Shot Blast Polishing Using Viscoelastic Media.

Surface changes and microbiological effects following shot blast polishing with viscoelastic media of the mucosal surface of resin denture bases were examined. Average surface roughness (Ra) and the depth of surface removal of specimens were measured over time, and the clinical number of microbial adhesions on the mucosal surface of dentures was clinically assessed. The results obtained showed no changes in Ra after 20 s of polishing, Ra of <0.2 µm, and a depth of surface removal < 20 µm. This method of finishing did not affect the fit of the mucosal surface of the dentures. Furthermore, the adhesion of microorganisms to the mucosal surface of dentures was significantly suppressed. Shot blast polishing with viscoelastic media is useful for finishing the mucosal surface of resin denture bases.

Effects of Storage Temperature and pH on the Antifungal Effects of Commercial Oral Moisturizers against Candida Albicans and Candida Glabrata.

Background and objectives: Oral moisturizers have been used to treat dry mouth. This study aimed to investigate the effects of storage temperature and pH on the antifungal effects of oral moisturizers against Candida albicans and Candida glabrata. Materials and Methods: Thirty-one oral moisturizers and amphotericin B (AMPH-B) were stored at 25 and 37 °C for 1 week. Subsequently, they were added to cylindrical holes in 50% trypticase soy agar plates inoculated with C. albicans and C. glabrata (107 cells/ml). The antifungal effects were evaluated based on the sizes of the growth-inhibitory zones formed. Two-way analysis of variance was used to determine the effects of storage temperature and pH on the growth-inhibitory zones. Results: Significant differences in the effects of storage temperature and pH of the moisturizers were observed against C. albicans and C. glabrata. The growth-inhibitory zones of samples stored at 37 °C and with neutral pH were significantly larger than those stored at 25 °C and with acidic pH, respectively. The sizes of the zones formed by most of the oral moisturizers were larger than those formed by AMPH-B (concentration, 0.63 µg/ml). Conclusion: The antifungal effects of oral moisturizers against C. albicans and C. glabrata were affected by their storage temperature and pH.

Phospholipase C-related catalytically inactive protein: A novel signaling molecule for modulating fat metabolism and energy expenditure.

BACKGROUND: Overweight and obesity are defined as excessive or abnormal fat accumulation in adipose tissues, and increase the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, and stroke, through pathophysiological mechanisms. There is strong evidence that weight loss reduces the risk of metabolic syndrome by limiting blood pressure and improving the levels of serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. To date, several attempts have been made to develop effective anti-obesity medication or weight-loss drugs; however, satisfactory drugs for clinical use have not yet been developed. Therefore, elucidation of the molecular mechanisms driving fat metabolism (adipogenesis and lipolysis) represents the first step in developing clinically useful drugs and/or therapeutic treatments to control obesity. HIGHLIGHT: In our previous study on intracellular signaling of phospholipase C-related catalytically inactive protein (PRIP), we generated and analyzed Prip-double knockout (Prip-DKO) mice. Prip-DKO mice showed tolerance against insulin resistance and a lean phenotype with low fat mass. Here, we therefore reviewed the involvement of PRIP in fat metabolism and energy expenditure. We conclude that PRIP, a protein phosphatase-binding protein, can modulate fat metabolism via phosphoregulation of adipose lipolysis-related molecules, and regulates non-shivering heat generation in brown adipocytes. CONCLUSION: We propose PRIP as a new therapeutic target for controlling obesity or developing novel anti-obesity drugs.

Suppression of cell migration by phospholipase C-related catalytically inactive protein-dependent modulation of PI3K signalling.

The metabolic processes of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] into PI(3,4,5)P3 and the subsequent PI(3,4,5)P3 signalling are involved in cell migration. Dysfunctions in the control of this pathway can cause human cancer cell migration and metastatic growth. Here we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a PI(4,5)P2-binding protein, regulates cancer cell migration. PRIP overexpression in MCF-7 and BT-549 human breast cancer cells inhibited cell migration in vitro and metastasis development in vivo. Overexpression of the PRIP pleckstrin homology domain, a PI(4,5)P2 binding motif, in MCF-7 cells caused significant suppression of cell migration. Consistent with these results, in comparison with wild-type cells, Prip-deficient mouse embryonic fibroblasts exhibited increased cell migration, and this was significantly attenuated upon transfection with a siRNA targeting p110α, a catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI(3,4,5)P3 production was decreased in Prip-overexpressing MCF-7 and BT-549 cells. PI3K binding to PI(4,5)P2 was significantly inhibited by recombinant PRIP in vitro, and thus the activity of PI3K was downregulated. Collectively, PRIP regulates the production of PI(3,4,5)P3 from PI(4,5)P2 by PI3K, and the suppressor activity of PRIP in PI(4,5)P2 metabolism regulates the tumour migration, suggesting PRIP as a promising target for protection against metastatic progression.

General anesthetic actions on GABAA receptors in vivo are reduced in phospholipase C-related catalytically inactive protein knockout mice.

PURPOSE: The aim of this study was to investigate the action of general anesthetics in phospholipase C-related catalytically inactive protein (PRIP)-knockout (KO) mice that alter GABAA receptor signaling. METHODS: PRIP regulates the intracellular trafficking of ß subunit-containing GABAA receptors in vitro. In this study, we examined the effects of intravenous anesthetics, propofol and etomidate that act via ß subunit-containing GABAA receptors, in wild-type and Prip-KO mice. Mice were intraperitoneally injected with a drug, and a loss of righting reflex (LORR) assay and an electroencephalogram analysis were performed. RESULTS: The cell surface expression of GABAA receptor ß3 subunit detected by immunoblotting was decreased in Prip-knockout brain compared with that in wild-type brain without changing the expression of other GABAA receptor subunits. Propofol-treated Prip-KO mice exhibited significantly shorter duration of LORR and had lower total anesthetic score than wild-type mice in the LORR assay. The average duration of sleep time in an electroencephalogram analysis was shorter in propofol-treated Prip-KO mice than in wild-type mice. The hypnotic action of etomidate was also reduced in Prip-KO mice. However, ketamine, an NMDA receptor antagonist, had similar effects in the two genotypes. CONCLUSION: PRIP regulates the cell surface expression of the GABAA receptor ß3 subunit and modulates general anesthetic action in vivo. Elucidation of the involved regulatory mechanisms of GABAA receptor-dependent signaling would inform the development of safer anesthetic therapies for clinical applications.

Phospholipase C-related catalytically inactive protein can regulate obesity, a state of peripheral inflammation.

Obesity is defined as abnormal or excessive fat accumulation. Chronic inflammation in fat influences the development of obesity-related diseases. Many reports state that obesity increases the risk of morbidity in many diseases, including hypertension, dyslipidemia, type 2 diabetes, coronary heart disease, stroke, sleep apnea, and breast, prostate and colon cancers, leading to increased mortality. Obesity is also associated with chronic neuropathologic conditions such as depression and Alzheimer's disease. However, there is strong evidence that weight loss reduces these risks, by limiting blood pressure and improving levels of serum triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol. Prevention and control of obesity is complex, and requires a multifaceted approach. The elucidation of molecular mechanisms driving fat metabolism (adipogenesis and lipolysis) aims at developing clinical treatments to control obesity. We recently reported a new regulatory mechanism in fat metabolism: a protein phosphatase binding protein, phospholipase C-related catalytically inactive protein (PRIP), regulates lipolysis in white adipocytes and heat production in brown adipocytes via phosphoregulation. Deficiency of PRIP in mice led to reduced fat accumulation and increased energy expenditure, resulting in a lean phenotype. Here, we evaluate PRIP as a new therapeutic target for the control of obesity.

Phospholipase C-related catalytically inactive protein (PRIP) regulates lipolysis in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase.

Phosphorylation of hormone-sensitive lipase (HSL) and perilipin by protein kinase A (PKA) promotes the hydrolysis of lipids in adipocytes. Although activation of lipolysis by PKA has been well studied, inactivation via protein phosphatases is poorly understood. Here, we investigated whether phospholipase C-related catalytically inactive protein (PRIP), a binding partner for protein phosphatase 1 and protein phosphatase 2A (PP2A), is involved in lipolysis by regulating phosphatase activity. PRIP knockout (PRIP-KO) mice displayed reduced body-fat mass as compared with wild-type mice fed with standard chow ad libitum. Most other organs appeared normal, suggesting that mutant mice had aberrant fat metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated compared to that in wild-type mice. Starvation of wild-type mice or stimulation of adipose tissue explants with the catabolic hormone, adrenaline, translocated both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes was significantly reduced and was independent of adrenaline stimulation. Lipolysis activity, as assessed by measurement of non-esterified fatty acids and glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were treated with a phosphatase inhibitor, they showed a high lipolysis activity at the similar level to PRIP-KO adipocytes. Collectively, these results suggest that PRIP promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis.

Phospholipase C-related catalytically inactive protein (PRIP) controls KIF5B-mediated insulin secretion.

We previously reported that phospholipase C-related catalytically inactive protein (PRIP)-knockout mice exhibited hyperinsulinemia. Here, we investigated the role of PRIP in insulin granule exocytosis using Prip-knockdown mouse insulinoma (MIN6) cells. Insulin release from Prip-knockdown MIN6 cells was higher than that from control cells, and Prip knockdown facilitated movement of GFP-phogrin-labeled insulin secretory vesicles. Double-immunofluorescent staining and density step-gradient analyses showed that the KIF5B motor protein co-localized with insulin vesicles in Prip-knockdown MIN6 cells. Knockdown of GABAA-receptor-associated protein (GABARAP), a microtubule-associated PRIP-binding partner, by Gabarap silencing in MIN6 cells reduced the co-localization of insulin vesicles with KIF5B and the movement of vesicles, resulting in decreased insulin secretion. However, the co-localization of KIF5B with microtubules was not altered in Prip- and Gabarap-knockdown cells. The presence of unbound GABARAP, freed either by an interference peptide or by Prip silencing, in MIN6 cells enhanced the co-localization of insulin vesicles with microtubules and promoted vesicle mobility. Taken together, these data demonstrate that PRIP and GABARAP function in a complex to regulate KIF5B-mediated insulin secretion, providing new insights into insulin exocytic mechanisms.

Phospholipase C-related catalytically inactive protein, a novel microtubule-associated protein 1 light chain 3-binding protein, negatively regulates autophagosome formation.

Upon starvation, cells undergo autophagy, an intracellular bulk-degradation process, to provide the required nutrients. Here, we observed that phospholipase C-related catalytically inactive protein (PRIP) binds to microtubule-associated protein 1 light chain 3 (LC3), a mammalian autophagy-related initiator that regulates the autophagy pathway. Then, we examined the involvement of PRIP in the nutrient depletion-induced autophagy pathway. Enhanced colocalization of PRIP with LC3 was clearly seen in nutrient-starved mouse embryonic fibroblasts under a fluorescent microscope, and interaction of the proteins was revealed by immunoprecipitation experiments with an anti-LC3 antibody. Under starvation conditions, there were more green fluorescent protein fused-LC3 dots in mouse embryonic fibroblasts from PRIP-deficient mice than in fibroblasts from wild type cells. The formation of new dots in a single cell increased, as assessed by time-lapse microscopy. Furthermore, the increase in autophagosome formation in PRIP-deficient cells was notably inhibited by exogenously overexpressed PRIP. Taken together, PRIP is a novel LC3-binding protein that acts as a negative modulator of autophagosome formation.

Role of PRIP-1, a novel Ins(1,4,5)P3 binding protein, in Ins(1,4,5)P3-mediated Ca2+ signaling.

PRIP-1 was isolated as a novel inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] binding protein with a domain organization similar to phospholipase C-delta1 (PLC-delta1) but lacking the enzymatic activity. Further studies revealed that the pleckstrin homology (PH) domain of PRIP-1 is the region responsible for binding Ins(1,4,5)P3. In this study we aimed to clarify the role of PRIP-1 at the physiological concentration in Ins(1,4,5)P3-mediated Ca2+ signaling, as we had previously used COS-1 cells overexpressing PRIP-1 (Takeuchi et al., 2000, Biochem J 349:357-368). For this purpose we employed PRIP-1 knock out (PRIP-1-/-) mice generated previously (Kanematsu et al., 2002, EMBO J 21:1004-1011). The increase in free Ca2+ concentration in response to purinergic receptor stimulation was lower in primary cultured cortical neurons prepared from PRIP-1-/- mice than in those from wild type mice. The relative amounts of [3H]Ins(1,4,5)P3 measured in neurons labeled with [3H]inositol was also lower in cells from PRIP-1-/- mice. In contrast, PLC activities in brain cortex samples from PRIP-1-/- mice were not different from those in the wild type mice, indicating that the hydrolysis of Ins(1,4,5)P3 is enhanced in cells from PRIP-1-/- mice. In vitro analyses revealed that type1 inositol polyphosphate 5-phosphatase physically interacted with a PH domain of PRIP-1 (PRIP-1PH) and its enzyme activity was inhibited by PRIP-1PH. However, physical interaction with these two proteins did not appear to be the reason for the inhibition of enzyme activity, indicating that binding of Ins(1,4,5)P3 to the PH domain prevented its hydrolyzation. Together, these results indicate that PRIP-1 plays an important role in regulating the Ins(1,4,5)P3-mediated Ca2+ signaling by modulating type1 inositol polyphosphate 5-phosphatase activity through binding to Ins(1,4,5)P3.