Improvement effect of gemigliptin on salivary gland dysfunction in exogenous methylglyoxal-injected rats.

The symptom of hyposalivation associated with hypofunction of the salivary glands is a common feature of diabetes. Inadequate saliva production can cause tissue damage in the mouth, making it susceptible to infections and leading to oral health diseases. Previous studies have highlighted the harmful effects of methylglyoxal (MGO) and MGO-derived advanced glycation end products (AGEs) in diabetes. In this study, we investigated the protective effects of gemigliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, against MGO-induced salivary gland dysfunction. MGO treatment of immortalized human salivary gland acinar cells induced apoptosis via reactive oxygen species (ROS)-mediated pathways, but this effect was mitigated by gemigliptin. In vivo experiments involved the simultaneous administration of MGO (17.25 mg/kg) with aminoguanidine (100 mg/kg) and gemigliptin (10 and 100 mg/kg) daily to rats for two weeks. Gemigliptin increased the saliva volume and amylase levels in MGO-injected rats. Gemigliptin reduced the DPP-4 activity in both the salivary glands and serum of MGO-injected rats. Furthermore, gemigliptin exerted anti-glycation effects by reducing the accumulation of AGEs in the saliva, salivary glands, and serum and suppressing the expression of the receptor for AGEs. These actions protected the salivary gland cells from ROS-mediated apoptosis. Overall, gemigliptin protected the salivary gland cells from ROS-mediated cell death, reduced the accumulation of amylase and mucins in the salivary glands, and enhanced the salivary function by upregulating aquaporin 5 expression, and it exerted protective effects against MGO-induced salivary gland dysfunction by enhancing the anti-glycation, antioxidant, and salivary secretion activities. Our findings suggest gemigliptin as a potential therapeutic for patients with salivary gland dysfunction caused by the complications of diabetes.

Maternal nanoplastic ingestion induces an increase in offspring body weight through altered lipid species and microbiota.

The rapidly increasing prevalence of obesity and overweight, especially in children and adolescents, has become a serious societal issue. Although various genetic and environmental risk factors for pediatric obesity and overweight have been identified, the problem has not been solved. In this study, we examined whether environmental nanoplastic (NP) pollutants can act as environmental obesogens using mouse models exposed to NPs derived from polystyrene and polypropylene, which are abundant in the environment. We found abnormal weight gain in the progeny until 6 weeks of age following the oral administration of NPs to the mother during gestation and lactation. Through a series of experiments involving multi-omic analyses, we have demonstrated that NP-induced weight gain is caused by alterations in the lipid composition (lysophosphatidylcholine/phosphatidylcholine ratio) of maternal breast milk and he gut microbiota distribution of the progeny. These data indicate that environmental NPs can act as obesogens in childhood.

Fc-fused IL-7 provides broad antiviral effects against respiratory virus infections through IL-17A-producing pulmonary innate-like T cells.

Repeated pandemics caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have resulted in serious problems in global public health, emphasizing the need for broad-spectrum antiviral therapeutics against respiratory virus infections. Here, we show the protective effects of long-acting recombinant human interleukin-7 fused with hybrid Fc (rhIL-7-hyFc) against major respiratory viruses, including influenza virus, SARS-CoV-2, and respiratory syncytial virus. Administration of rhIL-7-hyFc in a therapeutic or prophylactic regimen induces substantial antiviral effects. During an influenza A virus (IAV) infection, rhIL-7-hyFc treatment increases pulmonary T cells composed of blood-derived interferon γ (IFNγ)+ conventional T cells and locally expanded IL-17A+ innate-like T cells. Single-cell RNA transcriptomics reveals that rhIL-7-hyFc upregulates antiviral genes in pulmonary T cells and induces clonal expansion of type 17 innate-like T cells. rhIL-7-hyFc-mediated disease prevention is dependent on IL-17A in both IAV- and SARS-CoV-2-infected mice. Collectively, we suggest that rhIL-7-hyFc can be used as a broadly active therapeutic for future respiratory virus pandemic.

APP-C31: An Intracellular Promoter of Both Metal-Free and Metal-Bound Amyloid-ß40 Aggregation and Toxicity in Alzheimer's Disease.

Intracellular C-terminal cleavage of the amyloid precursor protein (APP) is elevated in the brains of Alzheimer's disease (AD) patients and produces a peptide labeled APP-C31 that is suspected to be involved in the pathology of AD. But details about the role of APP-C31 in the development of the disease are not known. Here, this work reports that APP-C31 directly interacts with the N-terminal and self-recognition regions of amyloid-ß40 (Aß40 ) to form transient adducts, which facilitates the aggregation of both metal-free and metal-bound Aß40 peptides and aggravates their toxicity. Specifically, APP-C31 increases the perinuclear and intranuclear generation of large Aß40 deposits and, consequently, damages the nucleus leading to apoptosis. The Aß40 -induced degeneration of neurites and inflammation are also intensified by APP-C31 in human neurons and murine brains. This study demonstrates a new function of APP-C31 as an intracellular promoter of Aß40 amyloidogenesis in both metal-free and metal-present environments, and may offer an interesting alternative target for developing treatments for AD that have not been considered thus far.

Automated precision localization of peripherally inserted central catheter tip through model-agnostic multi-stage networks.

BACKGROUND: Peripherally inserted central catheters (PICCs) have been widely used as one of the representative central venous lines (CVCs) due to their long-term intravascular access with low infectivity. However, PICCs have a fatal drawback of a high frequency of tip mispositions, increasing the risk of puncture, embolism, and complications such as cardiac arrhythmias. To automatically and precisely detect it, various attempts have been made by using the latest deep learning (DL) technologies. However, even with these approaches, it is still practically difficult to determine the tip location because the multiple fragments phenomenon (MFP) occurs in the process of predicting and extracting the PICC line required before predicting the tip. OBJECTIVE: This study aimed to develop a system generally applied to existing models and to restore the PICC line more exactly by removing the MFs of the model output, thereby precisely localizing the actual tip position for detecting its misposition. METHODS: To achieve this, we proposed a multi-stage DL-based framework post-processing the PICC line extraction result of the existing technology. Our method consists of the following three stages: 1. Existing PICC line segmentation network for a baseline, 2. Patch-based PICC line refinement network, 3. PICC line reconnection network. The proposed second and third-stage models address MFs caused by the sparseness of the PICC line and the line disconnection due to confusion with anatomical structures respectively, thereby enhancing tip detection. RESULTS: To verify the objective performance of the proposed MFCN, internal validation and external validation were conducted. For internal validation, learning (130 samples) and verification (150 samples) were performed with 280 data, including PICC among Chest X-ray (CXR) images taken at our institution. External validation was conducted using a public dataset called the Royal Australian and New Zealand College of Radiologists (RANZCR), and training (130 samples) and validation (150 samples) were performed with 280 data of CXR images, including PICC, which has the same number as that for internal validation. The performance was compared by root mean squared error (RMSE) and the ratio of single fragment images (RatioSFI) (i.e., the rate at which model predicts PICC as multiple sub-lines) according to whether or not MFCN is applied to seven conventional models (i.e., FCDN, UNET, AUNET, TUNET, FCDN-HT, UNET-ELL, and UNET-RPN). In internal validation, when MFCN was applied to the existing single model, MFP was improved by an average of 45 %. The RMSE improved over 63% from an average of 27.54 mm (17.16 to 35.80 mm) to 9.77 mm (9.11 to 10.98 mm). In external validation, when MFCN was applied, the MFP incidence rate decreased by an average of 32% and the RMSE decreased by an average of 65%. Therefore, by applying the proposed MFCN, we observed the consistent detection performance improvement of PICC tip location compared to the existing model. CONCLUSION: In this study, we applied the proposed technique to the existing technique and demonstrated that it provides high tip detection performance, proving its high versatility and superiority. Therefore, we believe, in countries and regions where radiologists are scarce, that the proposed DL approach will be able to effectively detect PICC misposition on behalf of radiologists.

Application of Machine Learning Algorithm in Predicting Axillary Lymph Node Metastasis from Breast Cancer on Preoperative Chest CT.

Axillary lymph node (ALN) status is one of the most critical prognostic factors in patients with breast cancer. However, ALN evaluation with contrast-enhanced CT (CECT) has been challenging. Machine learning (ML) is known to show excellent performance in image recognition tasks. The purpose of our study was to evaluate the performance of the ML algorithm for predicting ALN metastasis by combining preoperative CECT features of both ALN and primary tumor. This was a retrospective single-institutional study of a total of 266 patients with breast cancer who underwent preoperative chest CECT. Random forest (RF), extreme gradient boosting (XGBoost), and neural network (NN) algorithms were used. Statistical analysis and recursive feature elimination (RFE) were adopted as feature selection for ML. The best ML-based ALN prediction model for breast cancer was NN with RFE, which achieved an AUROC of 0.76 ± 0.11 and an accuracy of 0.74 ± 0.12. By comparing NN with RFE model performance with and without ALN features from CECT, NN with RFE model with ALN features showed better performance at all performance evaluations, which indicated the effect of ALN features. Through our study, we were able to demonstrate that the ML algorithm could effectively predict the final diagnosis of ALN metastases from CECT images of the primary tumor and ALN. This suggests that ML has the potential to differentiate between benign and malignant ALNs.

Double Emulsion-Mediated Delivery of Polyphenol Mixture Alleviates Atopic Dermatitis.

Although the polyphenols have been studied to alleviate inflammation, there are still challenges to delivering the polyphenols with stabilized formulation due to their low water solubility and susceptibility to oxidation. Herein, the transdermal delivery system of polyphenol mixture (PM), including quercetin (Q), phloretin (P), and ellagic acid (E), is developed using double emulsion for applying to atopic dermatitis (AD). Through the in vitro anti-degranulation assay, the optimal molar ratio of each polyphenol (Q:P:E = 5:1:1) is obtained, and the PM shows at most a 43.6% reduction of degranulation of immune cells, which is the primary factor of AD. Moreover, the water-in-oil-in-water double emulsion (W/O/W) enhances the PM's stability and has a higher anti-degranulation effect than the oil-in-water emulsion (O/W). In the in vivo 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice AD model, PM reduces more AD symptoms than every single polyphenol. The PM-encapsulated W/O/W (PM_W/O/W) shows the most effectiveness in AD by decreasing dermatitis score, i.e., skin/ear thickness, mast cells, and serum IgE level. Finally, this suggests that the findings on the optimal ratio of PM and double emulsion-based delivery would be beneficial in treating AD and can be applied to other allergic diseases.

Projection mapping system for laser speckle contrast image: feasibility study for clinical application.

Significance: Laser speckle contrast images (LSCIs) have been utilized to monitor blood flow perfusion. However, they have conventionally been observed on monitor screens, resulting in potential spatial mismatching between the imaging region of interest (IROI) and monitor screen. Aim: This study proposes a projection mapping (PM) system for LSCIs (PMS_LSCI) that projects LSCIs to directly observe the blood flow perfusion in the IROI. Approach: The PMS_LSCI consists of a camera, imaging optics, a laser projector, and graphic user interface software. The spatial matching in the regions of interest was performed by adjusting the software screen of the LSCI in the IROI and evaluated by conducting in-vitro and in-vivo studies. An additional in-vivo study was performed to investigate the feasibility of real-time PM of the LSCI. Results: The spatial mismatching in the regions of interest was ranged from 2.74% to 6.47% depending on the surface curvature. The PMS_LSCI could enable real-time PM of LSCI at four different blood flow states depending on blood pressure. Conclusions: The PMS_LSCI projects the LSCI in the IROI by interacting with a projector instead of the monitor screen. The PMS_LSCI presented clinical feasibility in the in-vitro and in-vivo studies.

The Effects of Sargassum horneri Extract and Fucoidan on Tear Hyposecretion and Ocular Surface Injury in Rats with Dry Eye Diseases.

Hyperosmotic stress caused by tear hyposection is a leading cause of dry eye disease. We investigated the prevention of dry eye disease in corneal epithelial cells and in rats that were induced to develop dry eye disease via unilateral excision of their exorbital lacrimal gland using Sargassum horneri extract (AB_SH) and its bioactive component fucoidan. Oral administration of AB_SH (250 mg/kg and 500 mg/kg) and fucoidan (100 mg/kg) was conducted for 7 days. In order to measure tear secretion, phenol red thread tear tests were performed along with corneal irregularity measurements. The apoptotic injury in the cornea and the lacrimal gland was evaluated using TUNEL staining. AB_SH and fucoidan were shown to suppress apoptosis and the expression of apoptosis-related proteins in human corneal epithelial cells under hyperosmotic conditions. Oral administration of AB_SH and fucoidan attenuated tear hyposecretion and corneal irregularity in the lacrimal gland-excised rats. In addition, AB_SH and fucoidan also reduced apoptosis in the cornea and lacrimal gland. This study suggests that S. horneri extract and fucoidan can effectively ameliorate dry eye disease by suppressing the apoptosis of ocular tissues.

Ishige okamurae Celluclast extract ameliorates non-alcoholic fatty liver in high-fructose diet-fed mice by modulation of lipid metabolism and gut microbiota composition.

Recently, a new mechanism has revealed that gut microbiota plays a pivotal role in metabolizing fructose to acetate that facilitates hepatic lipogenesis. Therefore, our study investigated the role of microbiome on abnormal lipid synthesis in the presence of fructose and identified attenuating effects of Ishige okamurae Celluclast extract (IOCE) against fructose-induced fatty liver. The results indicated that oral administration of IOCE (150 and 300 mg/kg/day for 12 weeks) significantly reduced both gut microbiota-mediated and -non-mediated hepatic lipogenesis simultaneously triggered by fructose metabolism. IOCE reduced hepatic triglyceride accumulation and expression levels of key enzymes for glucolipid metabolism. In addition, IOCE regulated fatty acid synthesis, ß-oxidation, and improved hepatic inflammation. Furthermore, IOCE inhibited direct fructose-to-acetate conversion and altered the compositions of gut microbiota. These findings suggest that IOCE might serve as a potential prebiotic dietary supplement by ameliorating fatty liver through dual regulation of classical lipogenic pathway and gut microbiota.

Estimating the Volume of Nodules and Masses on Serial Chest Radiography Using a Deep-Learning-Based Automatic Detection Algorithm: A Preliminary Study.

BACKGROUND: The purpose of this study was to assess the volume of the pulmonary nodules and masses on serial chest X-rays (CXRs) from deep-learning-based automatic detection algorithm (DLAD)-based parameters. METHODS: In a retrospective single-institutional study, 72 patients, who obtained serial CXRs (n = 147) for pulmonary nodules or masses with corresponding chest CT images as the reference standards, were included. A pre-trained DLAD based on a convolutional neural network was developed to detect and localize nodules using 13,710 radiographs and to calculate a localization map and the derived parameters (e.g., the area and mean probability value of pulmonary nodules) for each CXR, including serial follow-ups. For validation, reference 3D CT volumes were measured semi-automatically. Volume prediction models for pulmonary nodules were established through univariable or multivariable, and linear or non-linear regression analyses with the parameters. A polynomial regression analysis was performed as a method of a non-linear regression model. RESULTS: Of the 147 CXRs and 208 nodules of 72 patients, the mean volume of nodules or masses was measured as 9.37 ± 11.69 cm3 (mean ± standard deviation). The area and CT volume demonstrated a linear correlation of moderate strength (i.e., R = 0.58, RMSE: 9449.9 mm3 m3 in a linear regression analysis). The area and mean probability values exhibited a strong linear correlation (R = 0.73). The volume prediction performance based on a multivariable regression model was best with a mean probability and unit-adjusted area (i.e. , RMSE: 7975.6 mm3, the smallest among the other variable parameters). CONCLUSIONS: The prediction model with the area and the mean probability based on the DLAD showed a rather accurate quantitative estimation of pulmonary nodule or mass volume and the change in serial CXRs.

How Three Self-Secreted Biofilm Exopolysaccharides of Pseudomonas aeruginosa, Psl, Pel, and Alginate, Can Each Be Exploited for Antibiotic Adjuvant Effects in Cystic Fibrosis Lung Infection.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to their failure to eradicate infection but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. The three biofilm-associated EPSs secreted by P. aeruginosa (alginate, Psl, and Pel) are each under investigation and are being exploited in ways that potentiate antibiotics. In this review, we describe the development and structure of P. aeruginosa biofilms before examining each EPS as a potential therapeutic target for combating pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

Fabrication of Assembled FeS2 Nanosheet and Application for High-Performance Supercapacitor Electrodes.

To overcome the low-energy-density limitation of supercapacitors, we aimed to achieve a material with a high specific capacitance by manipulating the nanostructure of FeS2, which comprises the most abundant and affordable elements. In this study, nanosheet-assembled FeS2 (NSA-FeS2) was fabricated using a novel method. Sub-micron droplets of sulfur particles stabilized with polyvinylpyrrolidone were formed in silicone oil medium, and Fe(CO)5 was absorbed and reacted on the surface to form core-shell particles, ES/[Fe], with a sulfur core and an iron-containing outer shell. The high temperature treatment of ES/[Fe] produced NSA-FeS2, in which pyrite FeS2 nanosheets grew and were partially interconnected. In a three-electrode system, the as-prepared NSA-FeS2 and NSA-FeS2/polyaniline (PANI) composites exhibited specific capacitances of 763 and 976 Fg-1, respectively, at a current density of 0.5 Ag-1, with corresponding capacitance retentions of 93 and 96% after 3000 charge-discharge cycles. The capacitance retention of the NSA-FeS2/PANI composites was 49% when the current density was increased from 0.5 to 5 Ag-1. Notably, the obtained specific capacitances exhibited the highest values in pure FeS2 and FeS2-based composites, indicating the significant potential for the utilization of iron sulfide in pseudocapacitive electrode materials.

Prevalence of Mental Disorders and Associated Factors in Korean Adults: National Mental Health Survey of Korea 2021.

OBJECTIVE: Mental health is a global concern and needs to be studied more closely. We aimed to estimate the prevalence of mental disorders and their associated factors among the general population in Korea. METHODS: The National Mental Health Survey of Korea 2021 was conducted between June 19 and August 31, 2021 and included 13,530 households; 5,511 participants completed the interview (response rate: 40.7%). The lifetime and 12-month diagnosis rates of mental disorders were made using the Korean version of the Composite International Diagnostic Interview 2.1. Factors associated with alcohol use disorder (AUD), nicotine use disorder, depressive disorder, and anxiety disorder were analyzed, and mental health service utilization rates were estimated. RESULTS: The lifetime prevalence of mental disorders was 27.8%. The 12-month prevalence rates of alcohol use, nicotine use, depressive, and anxiety disorders were 2.6%, 2.7%, 1.7%, and 3.1%, respectively. The risk factors associated with 12-month diagnosis rates were as follows: AUD: sex and age; nicotine use disorder: sex; depressive disorder: marital status and job status; anxiety disorder: sex, marital status, and job status. The 12-month treatment and service utilization rates for 12-month AUD, nicotine use disorder, depressive disorder, and anxiety disorder were 2.6%, 1.1%, 28.2%, and 9.1%, respectively. CONCLUSION: Approximately 25% of adults in the general population were diagnosed with mental disorders during their lifetime. The treatment rates were substantially low. Future studies on this topic and efforts to increase the mental health treatment rate at a national level are needed.

Association between dental amalgam restoration and urine mercury concentrations among young women: a cross-sectional study.

BACKGROUND: The association between dental amalgam fillings and urine mercury concentrations was investigated in this study to assess the health risks associated with dental amalgams. METHODS: This cross-sectional study included 99 women in their 20s who visited the dental clinic in Daegu, Korea. The 99 participants were composed of 68 subjects who had dental amalgam fillings (exposure group) and 31 subjects who did not have dental amalgam fillings (nonexposure group). Oral examinations were conducted by a single dental hygienist, sociodemographic features were investigated as confounding variables, and urine mercury concentrations were measured using an automatic mercury analyzer. RESULTS: The mean±standard deviation of the urine mercury concentrations of the exposure and nonexposure groups were 1.50±1.78 µg/g creatinine and 0.53±0.63 µg/g creatinine, respectively. The exposure group showed significantly higher levels than the nonexposure group (p<0.01). The urine mercury concentration significantly increased with an increase in the number of teeth filled with amalgam, cavity surfaces involved, and number of defective amalgam fillings, and according to the latest exposure time (p<0.001). In the multiple regression analysis of amalgam-related factors and urine mercury concentrations after correction for confounding factors, the urine mercury concentration in the group with six or more amalgam-filled teeth, 11 or more cavity surfaces, and two or more defective amalgams was significantly higher than that in the nonexposure group (p<0.001). CONCLUSION: According to this study, exposure to dental amalgams was confirmed to significantly affect urine mercury concentrations.

Associations between chronic conditions and death in hospital among adults (aged 20+ years) during first acute care hospitalizations with a confirmed or suspected COVID-19 diagnosis in Canada.

PURPOSE: We aimed to quantify life course-specific associations between death in hospital and 30 chronic conditions, and comorbidity among them, in adults (aged 20+ years) during their first acute care hospitalization with a confirmed or suspected COVID-19 diagnosis in Canada. METHODS: We identified 35,519 first acute care hospitalizations with a confirmed or suspected COVID-19 diagnosis in the Discharge Abstract Database as of March 31, 2021. For each of five life-course age groups (20-34, 35-49, 50-64, 65-79, and 80+ years), we used multivariable logistic regression to examine associations between death in hospital and 30 chronic conditions, comorbidity, period of admission, and pregnant status, after adjusting for sex and age. RESULTS: About 20.9% of hospitalized patients with COVID-19 died in hospital. Conditions most strongly associated with in-hospital death varied across the life course. Chronic liver disease, other nervous system disorders, and obesity were statistically significantly associated (α = 0.05) with in-hospital death in the 20-34 to 65-79 year age groups, but the magnitude of the associations decreased as age increased. Stroke (aOR = 5.24, 95% CI: 2.63, 9.83) and other inflammatory rheumatic diseases (aOR = 4.37, 95% CI: 1.64, 10.26) were significantly associated with in-hospital death among 35 to 49 year olds only. Among 50+ year olds, more chronic conditions were significantly associated with in-hospital death, but the magnitude of the associations were generally weaker except for Down syndrome in the 50 to 64 (aOR = 8.49, 95% CI: 4.28, 16.28) and 65 to 79 year age groups (aOR = 5.19, 95% CI: 1.44, 20.91). Associations between comorbidity and death also attenuated with age. Among 20 to 34 year olds, the likelihood of death was 19 times greater (aOR = 18.69, 95% CI: 7.69, 48.24) in patients with three or more conditions compared to patients with none of the conditions, while for 80+ year olds the likelihood of death was two times greater (aOR = 2.04, 95% CI: 1.70, 2.45) for patients with six or more conditions compared to patients with none of the conditions. CONCLUSION: Conditions most strongly associated with in-hospital death among hospitalized adults with COVID-19 vary across the life course, and the impact of chronic conditions and comorbidity attenuate with age.

Multiscale Architectured Membranes, Electrodes, and Transport Layers for Next-Generation Polymer Electrolyte Membrane Fuel Cells.

Over the past few decades, considerable advances have been achieved in polymer electrolyte membrane fuel cells (PEMFCs) based on the development of material technology. Recently, an emerging multiscale architecturing technology covering nanometer, micrometer, and millimeter scales has been regarded as an alternative strategy to overcome the hindrance to achieving high-performance and reliable PEMFCs. This review summarizes the recent progress in the key components of PEMFCs based on a novel architecture strategy. In the first section, diverse architectural methods for patterning the membrane surface with random, single-scale, and multiscale structures as well as their efficacy for improving catalyst utilization, charge transport, and water management are discussed. In the subsequent section, the electrode structures designed with 1D and 3D multiscale structures to enable low Pt usage, improve oxygen transport, and achieve high electrode durability are elucidated. Finally, recent advances in the architectured transport layer for improving mass transportation including pore gradient, perforation, and patterned wettability for gas diffusion layer and 3D structured/engineered flow fields are described.

Gemigliptin Improves Salivary Gland Dysfunction in D-Galactose-Injected Aging Rats.

Oral dryness is among the most common conditions experienced by the elderly. As saliva plays a crucial role in maintaining oral health and overall quality of life, the condition is increasingly taking its toll on a rapidly growing aging population. D-galactose (D-gal) stimulates their formation, which in turn cause oxidative stress and accelerate age-related decline in physical function. In this study, we observed a reduction in salivary secretion and amylase levels in aged rats injected with D-gal, confirming salivary gland dysfunction. Treatment with gemigliptin increased DPP-4 inhibition and GLP-1 levels in the salivary glands of aging rats and reduced the expression of AGEs and receptors for advanced glycation end products (RAGE). This effect was caused by the presence of additional reactive oxygen species (ROS) in the salivary glands of the examined rats. Gemigliptin's cytoprotective effect reduced amylase and mucin accumulation and increased AQP5 expression, which are important indicators of salivary gland function. In sum, gemigliptin was shown to improve D-gal-induced decline in the salivary gland function of aged rats through its anti-glycation and antioxidant activities. Gemigliptin shows promise as a treatment strategy for patients experiencing decreased salivary function associated with their advancing age.

Kaempferol Interferes with Varicella-Zoster Virus Replication in Human Foreskin Fibroblasts.

Kaempferol, a natural flavonoid abundantly found in plants, is known to have pharmacological properties, such as anti-inflammatory and anti-cancer effects. In this study, we investigated the antiviral effects of kaempferol against a varicella-zoster virus (VZV) clinical isolate in vitro. We found that kaempferol significantly inhibited VZV replication without exhibiting cytotoxicity. Kaempferol exerted its antiviral effect at a similar stage of the VZV life cycle as acyclovir, which inhibits VZV DNA replication. Taken together, our results suggest that kaempferol inhibits VZV infection by blocking the DNA replication stage in the viral life cycle.

Antioxidant Efficacy of Esculetin against Tert-Butyl Hydroperoxide-Induced Oxidative Stress in HEK293 Cells.

Esculetin is an antioxidant and anti-inflammatory compound derived from coumarin. Oxidative stress can cause overproduction of reactive oxygen species (ROS), which can lead to the development of chronic kidney failure. In this study, human embryonic kidney 293 (HEK293) cells were treated with tert-butyl hydroperoxide (t-BHP) to determine the antioxidant effects of esculetin. HEK293 cells were treated with t-BHP to validate changes in cell viability, ROS production, and apoptosis, and then treated with esculetin to evaluate the changes. Changes in mRNA and protein levels were analyzed using a proteome kit, PCR, and Western blotting. Esculetin improved HEK293 cell viability and reduced apoptosis caused by t-BHP-induced oxidative stress. At the mRNA and protein levels, esculetin decreased pro-apoptotic factor expression as well as increased anti-apoptotic factor expression. The antioxidant efficacy of esculetin was validated when it inhibited the apoptosis caused by t-BHP-induced oxidative stress in HEK293 cells.