Efficacy of Low-Level Laser Therapy in a Rabbit Model of Rhinosinusitis.

Little is known about alternative treatment options for rhinosinusitis (RS). We aimed to evaluate the efficacy of low-level laser therapy (LLLT) for RS in experimentally induced rabbit models of RS. A total of 18 rabbits were divided into four groups: a negative control group (n = 3), an RS group without treatment (n = 5, positive control group), an RS group with natural recovery (n = 5, natural recovery group), and an RS group with laser irradiation (n = 5, laser-treated group). Computed tomography and histopathological staining were performed for each group. mRNA and protein expression levels of local cytokines (IFN-γ, IL-17, and IL-5) were also measured. Tissue inflammation revealed a significant improvement in the laser-treated group compared with the RS and natural recovery groups (p < 0.01). In addition, sinus opacification in the CT scans and cytokine expression was reduced in the laser-treated group, though without statistical significance. LLLT could be an effective option for the management of RS concerning radiological, histological, and molecular parameters.

Characterization of Latilactobacillus curvatus MS2 isolated from Korean traditional fermented seafood and cholesterol reduction effect as synbiotics with isomalto-oligosaccharide in BALB/c mice.

This study investigated the properties of Latilactobacillus curvatus MS2 isolated from Korean traditional fermented seafood as probiotics and the effect of reducing cholesterol as a synbiotic with isomalto-oligosaccharide (IMO) in BALB/c mice. The isolated strain showed high resistance to acids and bile acids and exhibited a high DPPH scavenging capacity of 72.27 ± 0.38 %. In the intestinal adhesion test using HT-29 cells, the adhesion rate of MS2 was 17.10 ± 1.78 %, which was higher than the adhesion rate of the other investigated probiotics. MS2 showed good antimicrobial activity against food-borne pathogens, especially Staphylococcus aureus, S. epidermidis, Escherichia coli, and Vibrio vulnificus. This strain had high availability for IMO among the prebiotics of fructo-oligosaccharide, inulin and IMO. Oral administration of MS2 and IMO to BALB/c mice for 5 weeks resulted in a significant reduction in blood cholesterol levels by regulating liver lipid metabolism. These results suggest that the combination of MS2 and IMO has potential for application in functional foods.

Characterization of a Bacillus sp. KRF-7 isolated from the intestine of rockfish and effects of dietary supplementation with mannan oligosaccharide in rockfish aquaculture.

The purpose of this study was to characterize the bacteria isolated from rockfish intestines and to investigate the effects of feed supplementation in rockfish aquaculture. Bacillus sp. KRF-7 isolated from the intestine of rockfish (Sebastes schlegelii) was demonstrated to be safe based on in vitro tests confirming the absence of hemolysis, cytotoxicity, and genes with toxigenic potential. In a feeding trial, providing a supplemental diet of 1 × 108 CFU g-1Bacillus sp. KRF-7 was observed to positively alter the weight gain, specific growth rate, feed conversion ratio, and protein efficiency ratio of juvenile rockfish. KRF-7 supplementation showed positive regulation of nonspecific immune parameters, such as superoxide dismutase, lysozyme activity, and myeloperoxidase activity. This analysis also revealed a change in the composition of the intestinal microbiota at the phylum level from Proteobacteria to Firmicutes. In both the kidney and spleen, the expression levels of IL-10, NF-κB, and B cell activating factors in the KRF-7-supplemented group were significantly increased compared to those in the control group. Therefore, this study verified the safety of KRF-7 isolated from the intestine of rockfish and suggests that dietary supplementation with KRF-7 enhances the growth performance of rockfish and has beneficial effects on the regulation of the intestinal microbiota and immune response.

Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents.

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: ß-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased H2O2-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl2 in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.

Mitochondrial Transplantation as a Novel Therapeutic Strategy for Mitochondrial Diseases.

Mitochondria are the major source of intercellular bioenergy in the form of ATP. They are necessary for cell survival and play many essential roles such as maintaining calcium homeostasis, body temperature, regulation of metabolism and apoptosis. Mitochondrial dysfunction has been observed in variety of diseases such as cardiovascular disease, aging, type 2 diabetes, cancer and degenerative brain disease. In other words, the interpretation and regulation of mitochondrial signals has the potential to be applied as a treatment for various diseases caused by mitochondrial disorders. In recent years, mitochondrial transplantation has increasingly been a topic of interest as an innovative strategy for the treatment of mitochondrial diseases by augmentation and replacement of mitochondria. In this review, we focus on diseases that are associated with mitochondrial dysfunction and highlight studies related to the rescue of tissue-specific mitochondrial disorders. We firmly believe that mitochondrial transplantation is an optimistic therapeutic approach in finding a potentially valuable treatment for a variety of mitochondrial diseases.

Protective Effect of Ciclopirox against Ovariectomy-Induced Bone Loss in Mice by Suppressing Osteoclast Formation and Function.

Postmenopausal osteoporosis is closely associated with excessive osteoclast formation and function, resulting in the loss of bone mass. Osteoclast-targeting agents have been developed to manage this disease. We examined the effects of ciclopirox on osteoclast differentiation and bone resorption in vitro and in vivo. Ciclopirox significantly inhibited osteoclast formation from primary murine bone marrow macrophages (BMMs) in response to receptor activator of nuclear factor kappa B ligand (RANKL), and the expression of genes associated with osteoclastogenesis and function was decreased. The formation of actin rings and resorption pits was suppressed by ciclopirox. Analysis of RANKL-mediated early signaling events in BMMs revealed that ciclopirox attenuates IκBα phosphorylation without affecting mitogen-activated protein kinase activation. Furthermore, the administration of ciclopirox suppressed osteoclast formation and bone loss in ovariectomy-induced osteoporosis in mice and reduced serum levels of osteocalcin and C-terminal telopeptide fragment of type I collagen C-terminus. These results indicate that ciclopirox exhibits antiosteoclastogenic activity both in vitro and in vivo and represents a new candidate compound for protection against osteoporosis and other osteoclast-related bone diseases.

Gamma Aminobutyric Acid-Enriched Fermented Oyster (Crassostrea gigas) Increases the Length of the Growth Plate on the Proximal Tibia Bone in Sprague-Dawley Rats.

Bone growth during childhood and puberty determines an adult's final stature. Although several prior studies have reported that fermented oyster (FO) consisting of a high amount of gamma aminobutyric acid can be attributed to bone health, there is no research on the efficacy of FO on growth regulation and the proximal tibial growth plate. Therefore, in this study, we investigated the effect of FO oral administration on hepatic and serum growth regulator levels and the development of the proximal tibial growth plate in young Sprague-Dawley rats. Both oral administration of FO (FO 100, 100 mg/kg FO and FO 200, 200 mg/kg FO) and subcutaneous injection of recombinant human growth hormone (rhGH, 200 µg/kg of rhGH) for two weeks showed no toxicity. Circulating levels of growth hormone (GH) significantly increased in the FO 200 group. The expression and secretion of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were enhanced by FO administration. FO administration promoted the expression of bone morphogenic proteins IGF-1 and IGFBP-3 in the proximal tibial growth plate. This positive effect of FO resulted in incremental growth of the entire plate length by expanding the proliferating and hypertrophic zones in the proximal tibial growth plate. Collectively, our results suggested that oral administration of FO is beneficial for bone health, which may ultimately result in increased height.

Establishing a nurse-managed health center for the urban poor in Dhaka, Bangladesh.

OBJECTIVES: Despite the rise in community health problems in populations living in urban slums, activities of community health nurses are limited in Bangladesh. This study aimed to describe how a nurse-managed health center (NMHC) was developed in Dhaka, Bangladesh. DESIGN: An exploratory-descriptive research design was used. SAMPLE AND MEASUREMENTS: The commitment phase was conducted to establish partnerships in the community. Involvement of community leaders and members and partnerships with various organizations were established successfully in the commitment phase. The assessment phase was completed by implementing personal interviews, community site visits, and household surveys of 172 households in the community. Action plans were developed and strategies were followed to change the community during the planning phase. RESULTS: Household survey results showed that community people suffered from non-communicable diseases, risk behaviors, and inadequate housing conditions. The high-priority community needs included nutrition and chronic management services, behavior change programs, and a clean environment. Action plans for health programs based on community needs and strategies such as securing manpower and equipment were developed. CONCLUSIONS: The systematic process of creating a NMHC, and the necessity of the community health nurse's role in responding to health needs of the urban poor in Dhaka, Bangladesh was confirmed.

A de novo KMT2D mutation in a girl with Kabuki syndrome associated with endocrine symptoms: a case report.

BACKGROUND: Kabuki syndrome is characterized by distinctive facial features and varying degrees of growth retardation. It leads to malformations in skeletal, urogenital and cardiac structures; moreover, endocrine conditions such as premature thelarche, precocious puberty, growth hormone deficiency, diabetes insipidus, thyroid dysfunction and obesity have been reported. Kabuki syndrome is caused by a heterozygous mutation in the KMT2D or KDM6A genes. CASE PRESENTATION: An 11-year-old girl with the typical facial features of Kabuki syndrome visited our hospital due to her short stature. She was found to have the de novo heterozygous mutation of c.8200C > T, p(Arg2734*) in exon 32 of the KMT2D gene and was diagnosed with Kabuki syndrome. The patient also exhibited endocrine abnormalities such as a constitutional delay of puberty, transiently congenial hypothyroidism, obesity and growth hormone deficiency. CONCLUSIONS: This is a case of a mutation in the KMT2D gene in a girl with Kabuki syndrome who presented with endocrine symptoms (constitutional delay of puberty, hypothyroidism, obesity and growth hormone deficiency).

Organocatalytic enantioselective synthesis of acyclic pyrimidine nucleosides by aza-Michael reaction.

An efficient diarylprolinol triphenylsilyl ether-catalyzed enantioselective aza-Michael reaction of pyrimidines as N-centered nucleophiles to α,ß-unsaturated aldehydes, followed by reduction, provided chiral acyclic pyrimidine nucleosides in good yields (51-78% yields for two steps) and excellent enantioselectivities (91-98% ee). In addition, the chiral acyclic pyrimidine nucleoside having the tert-butyldiphenylsilyl-protected hydroxyl substituent was successfully applied to the synthesis of the corresponding chiral cyclic pyrimidine nucleoside analogue bearing the tetrahydrofuranyl ring.

Idh2 deficiency accelerates renal dysfunction in aged mice.

The free radical or oxidative stress theory of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species (ROS) that are produced as by-products of normal metabolic processes in mitochondria. The oxidative stress may arise as a result of either increased ROS production or decreased ability to detoxify ROS. The availability of the mitochondrial NADPH pool is critical for the maintenance of the mitochondrial antioxidant system. The major enzyme responsible for generating mitochondrial NADPH is mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2). Depletion of IDH2 in mice (idh2-/-) shortens life span and accelerates the degeneration of multiple age-sensitive traits, such as hair grayness, skin pathology, and eye pathology. Among the various internal organs tested in this study, IDH2 depletion-induced acceleration of senescence was uniquely observed in the kidney. Renal function and structure were greatly deteriorated in 24-month-old idh2-/- mice compared with wild-type. In addition, disruption of redox status, which promotes oxidative damage and apoptosis, was more pronounced in idh2-/- mice. These data support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice, and thus support the oxidative stress theory of aging.

Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists.

A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome proliferator-activated receptor (PPAR) agonists. Structure-activity relationship study indicated that PPARα/γ/δ activities were dependent on the nature of the hydrophobic group, the attachment position of the alkoxy linker to the indole ring, and N-alkylation of indole nitrogen. Some compounds presented significant PPARγ/δ activity and molecular modeling suggested their putative binding modes in the ligand binding domain of PPARγ. Of these, compound 51 was selected for in vivo study via an evaluation of microsomal stability in mouse and human liver. Compound 51 lowered the levels of fasting blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When compound 51 was treated, hepatic triglycerides level and the size of adipocytes in white adipose tissue of db/db mice were also reduced as opposed to treatment with rosiglitazone. Taken together, compound 51 shows high potential warranting further studies in models for diabetes and related metabolic disorders and may be in use as a chemical tool for the understanding of PPAR biology.

Protective Effects of the Postbiotic Levilactobacillus brevis BK3 against H2O2-Induced Oxidative Damage in Skin Cells.

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and anti-obesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H2O2 and reduces intracellular reactive oxygen species (ROS) production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.

Effects of alternative sweeteners with or without xanthan gum on the physicochemical properties of scone products.

The physicochemical properties of scones made with alternative sweeteners (stevia, sucralose, and allulose) at different ratios (30, 70, and 100%) with or without xanthan gum were investigated. Nineteen samples were evaluated for crust color, moisture content, specific volume, and texture properties. Scones with allulose had lower L values but higher a and b values due to the Maillard and caramelization reactions. The moisture content increased with xanthan gum addition, thereby decreasing the specific volume. The sample with 30% of stevia (ST30), 30% of sucralose (SC30), and 30% of allulose and xanthan gum (AL30G) had similar characteristics to the sample with sucrose (CON). In the consumer acceptance test, CON was the most preferred, but ST30 showed no significant difference. AL30G was less preferred because of its lack of sweetness. Overall, the physicochemical properties and consumer acceptance of ST30 were closest to those of CON, suggesting its potential use in scone products. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01416-9.

Curcumin Mitigates the High-Fat High-Sugar Diet-Induced Impairment of Spatial Memory, Hepatic Metabolism, and the Alteration of the Gut Microbiome in Alzheimer's Disease-Induced (3xTg-AD) Mice.

The escalating prevalence of metabolic diseases and an aging demographic has been correlated with a concerning rise in Alzheimer's disease (AD) incidence. This study aimed to access the protective effects of curcumin, a bioactive flavonoid from turmeric, on spatial memory, metabolic functions, and the regulation of the gut microbiome in AD-induced (3xTg-AD) mice fed with either a normal chow diet (NCD) or a high-fat high-sugar diet (HFHSD). Our findings revealed an augmented susceptibility of the HFHSD-fed 3xTg-AD mice for weight gain and memory impairment, while curcumin supplementation demonstrated a protective effect against these changes. This was evidenced by significantly reduced body weight gain and improved behavioral and cognitive function in the curcumin-treated group. These improvements were substantiated by diminished fatty acid synthesis, altered cholesterol metabolism, and suppressed adipogenesis-related pathways in the liver, along with modified synaptic plasticity-related pathways in the brain. Moreover, curcumin enriched beneficial gut microbiota, including Oscillospiraceae and Rikenellaceae at the family level, and Oscillibacter, Alistipes, Pseudoflavonifractor, Duncaniella, and Flintibacter at the genus level. The observed alteration in these gut microbiota profiles suggests a potential crosswalk in the liver and brain for regulating metabolic and cognitive functions, particularly in the context of obesity-associated cognitive disfunction, notably AD.

Antibiotic Resistance in Acetic Acid Bacteria Originating from Vinegar.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use as a starter. In this research, we investigated the antibiotic resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against 10 different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

Fabrication of atelocollagen-coated bioabsorbable suture and the evaluation of its regenerative efficacy in Achilles tendon healing using a rat experimental model.

Recently, the incidence of Achilles tendon ruptures (ATRs) has become more common, and repair surgery using a bioabsorbable suture is generally preferred, particularly in the case of healthy patients. Sutures composed of poly(lactic-co-glycolic acid) (PLGA) are commonly used in ATR surgeries. Nevertheless, owing to the inherent limitations of PLGA, novel bioabsorbable sutures that can accelerate Achilles tendon healing are sought. Recently, several studies have demonstrated the beneficial effects of atelocollagen on tendon healing. In this study, poly(3,4-dihydroxy-L-phenylalanine) (pDOPA), a hydrophilic biomimetic material, was used to modify the hydrophobic surface of a PLGA suture (Vicryl, VC) for the stable coating of atelocollagen on its surface. The main objective was to fabricate an atelocollagen-coated VC suture and evaluate its performance in the healing of Achilles tendon using a rat model of open repair for ATR. Structural analyses of the surface-modified suture indicated that the collagen was successfully coated on the VC/pDOPA suture. Postoperative in vivo biomechanical analysis, histological evaluation, ultrastructural/morphological analyses, and western blotting confirmed that the tendons in the VC/pDOPA/Col group exhibit superior healing than those in the VC and VC/pDOPA groups after 1 and 6 weeks following the surgery. The this study suggests that atelocollagen-coated PLGA/pDOPA sutures are preferable for future medical applications, especially in the repair of ATR.

Glycinamide Facilitates Nanocomplex Formation and Functions Synergistically with Bone Morphogenetic Protein 2 to Promote Osteoblast Differentiation In Vitro and Bone Regeneration in a Mouse Calvarial Defect Model.

BACKGROUND: This study aimed to identify glycine analogs conducive to the formation of cell-absorbable nanocomplexes, enhancing collagen synthesis and subsequent osteogenesis in combination with BMP2 for improved bone regeneration. METHODS: Glycine and its derivatives were assessed for their effects on osteogenic differentiation in MC3T3-E1 cells and human bone marrow mesenchymal stem cells (BMSCs) under osteogenic conditions or with BMP2. Osteogenic differentiation was assessed through alkaline phosphatase staining and real-time quantitative polymerase chain reaction (RT-qPCR). Nanocomplex formation was examined via scanning electron microscopy, circular dichroism, and ultraviolet-visible spectroscopy. In vivo osteogenic effects were validated using a mouse calvarial defect model, and bone regeneration was evaluated through micro-computed tomography and histomorphometric analysis. RESULTS: Glycine, glycine methyl ester, and glycinamide significantly enhanced collagen synthesis and ALP activity in conjunction with an osteogenic medium (OSM). GA emerged as the most effective inducer of osteoblast differentiation marker genes. Combining GA with BMP2 synergistically stimulated ALP activity and the expression of osteoblast markers in both cell lines. GA readily formed nanocomplexes, facilitating cellular uptake through strong electrostatic interactions. In an in vivo calvarial defect mouse model, the GA and BMP2 combination demonstrated enhanced bone volume, bone volume/tissue volume ratio, trabecular numbers, and mature bone formation compared to other combinations. CONCLUSION: GA and BMP2 synergistically promoted in vitro osteoblast differentiation and in vivo bone regeneration through nanocomplex formation. This combination holds therapeutic promise for individuals with bone defects, showcasing its potential for clinical intervention.

Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD).

Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as arachidonate 5-lipoxygenase (ALOX5) and ALOX5 activating protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6 days training, they exhibit enhanced TNF-α and IL-6 production to lipopolysaccharide (LPS). Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.