Efficacy and safety of vancomycin compared with those of alternative treatments for methicillin-resistant Staphylococcus aureus infections: An umbrella review.

OBJECTIVE: To summarize the evidence on the efficacy and safety of vancomycin compared with those of alternative treatments in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: PubMed, Embase, and Web of Science were searched up to December 15, 2023, for systematic reviews and meta-analyses comparing vancomycin with alternative MRSA treatments. Primary outcomes included clinical cure and microbiological eradication rates. Organ-specific safety outcomes were assessed. Summary estimates were recalculated using a random-effects model. Evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. This study was registered in PROSPERO (CRD42022340359). RESULTS: This umbrella review included 19 studies and 71 meta-analyses (46 efficacy and 25 safety) comparing vancomycin with 10 alternative treatments across different MRSA infection types and populations. GRADE assessment showed that 29.58% of the meta-analyses were of high quality. Linezolid and daptomycin showed higher efficacy in MRSA-induced skin and soft tissue infections and pneumonia (moderate evidence quality) and bacteremia (very low evidence quality), respectively, compared with that of vancomycin. Cephalosporins had a higher risk of nausea, whereas linezolid had a higher risk of nausea, diarrhea, and thrombocytopenia than that of vancomycin. Vancomycin posed a higher risk of rash, pruritus, red man syndrome, and nephrotoxicity than that of alternatives. CONCLUSIONS: The quality of evidence supporting the higher efficacy of alternative treatment over vancomycin for MRSA infection was not high. Given varying safety profiles and advancements in therapeutic monitoring, careful consideration of patient-specific factors and pharmacokinetics is crucial when selecting treatment alternatives to vancomycin.

Modified Albumin-Bilirubin Grade After Curative Treatment: Predicting the Risk of Late Intrahepatic Recurrence of Hepatocellular Carcinoma.

BACKGROUND: We aimed to identify the prognostic factors for late intrahepatic recurrence (IHR), defined as recurrence more than two years after curative treatment of newly diagnosed hepatocellular carcinoma (HCC). METHODS: This retrospective cohort study included patients with newly diagnosed, previously untreated, very early, or early HCC treated with initial curative treatment and followed up without recurrence for more than two years, excluding early IHR defined as recurrence within two years in single center. Late IHR-free survival (IHRFS) was defined as the time interval from initial curative treatment to the first IHR or death without IHR, whichever occurred first. RESULTS: Among all the enrolled 2,304 patients, 1,427 (61.9%) underwent curative intent hepatectomy and the remaining 877 (38.1%) underwent local ablative therapy (LAT). During the follow-up after curative treatment (median, 82.6 months; range, 24.1 to 195.7), late IHR was detected in 816 (35.4%) patients. In the multivariable analysis, age, male sex, cirrhotic liver at diagnosis, type of initial treatment, and modified albumin-bilirubin (mALBI) grade were significant prognostic baseline factors. Furthermore, mALBI grade at three (2a vs. 1, P = 0.02, hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.04-1.70; 2b/3 vs. 1, P = 0.03; HR, 1.42; 95% CI, 1.03-1.94) and six months (2b/3 vs. 1; P = 0.006; HR, 1.61; 95% CI, 1.13-2.30) after initial curative treatment was also a significant prognostic factor for late IHR. CONCLUSION: After curative treatment for newly diagnosed early HCC, the mALBI grade at three and six months after initial curative treatment, as well as at baseline, was one of the most crucial prognostic factors for late IHR.

Integrative analysis of H&E and IHC identifies prognostic immune subtypes in HPV related oropharyngeal cancer.

BACKGROUND: Deep learning techniques excel at identifying tumor-infiltrating lymphocytes (TILs) and immune phenotypes in hematoxylin and eosin (H&E)-stained slides. However, their ability to elucidate detailed functional characteristics of diverse cellular phenotypes within tumor immune microenvironment (TME) is limited. We aimed to enhance our understanding of cellular composition and functional characteristics across TME regions and improve patient stratification by integrating H&E with adjacent immunohistochemistry (IHC) images. METHODS: A retrospective study was conducted on patients with Human Papillomavirus-positive oropharyngeal squamous cell carcinoma (OPSCC). Using paired H&E and IHC slides for 11 proteins, a deep learning pipeline was used to quantify tumor, stroma, and TILs in the TME. Patients were classified into immune inflamed (IN), immune excluded (IE), or immune desert (ID) phenotypes. By registering the IHC and H&E slides, we integrated IHC data to capture protein expression in the corresponding tumor regions. We further stratified patients into specific immune subtypes, such as IN, with increased or reduced CD8+ cells, based on the abundance of these proteins. This characterization provided functional insight into the H&E-based subtypes. RESULTS: Analysis of 88 primary tumors and 70 involved lymph node tissue images reveals an improved prognosis in patients classified as IN in primary tumors with high CD8 and low CD163 expression (p = 0.007). Multivariate Cox regression analysis confirms a significantly better prognosis for these subtypes. CONCLUSIONS: Integrating H&E and IHC data enhances the functional characterization of immune phenotypes of the TME with biological interpretability, and improves patient stratification in HPV( + ) OPSCC.

In this study, we investigated whether differences in the immune cell population surrounding head and neck cancers impact disease progression. We used advanced computer programs to analyze tissue samples from tumors and nearby lymph nodes, a part of the immune system. These tumor and lymph node samples were stained to show the structure of the tissue and to identify the different types of immune cells present. We grouped patients into different categories based on differences in their immune cells. We found that patients with certain patterns of immune cells tended to have better outcomes. This method could help doctors predict how well patients will respond to treatments.

Diagnostic Decision Point for IgE-Mediated Wheat Allergy in Children.

The diagnostic decision point can help diagnose food allergies while reducing the need for oral food challenge (OFC) tests. We performed a multicenter survey of children aged 0-7 years from January 1, 2018 to March 31, 2022. A total of 231 children were recruited from 18 institutions. Wheat allergy (WA) or non-wheat allergy (NWA) was determined on the basis of OFC results and symptoms. There were no differences in age, sex, family history of allergy or allergic comorbidities between the WA and NWA groups. According to receiver operating characteristic analysis for wheat-specific immunoglobulin E (IgE), the optimal cutoff value, positive decision point, and negative decision point were 10.2, 33.5, and 0.41 kU/L, respectively. For the ω-5 gliadin-specific IgE, their values were 0.69, 3.88, and 0.01 kU/L, respectively. This new diagnostic decision point may be used to diagnose WA in Korean children.

Immunostimulatory Activity of a Mixture of Platycodon grandiflorum, Pyrus serotine, Chaenomeles sinensis, and Raphanus sativus in RAW264.7 Macrophages.

In this study, a mixture of Platycodon grandiflorum, Pyrus serotina, Chaenomeles sinensis, and Raphanus sativus (PPCRE) was investigated for their immuno-enhancing effects, as well as the molecular mechanism of PPCRE in RAW264.7 cells. PPCRE dramatically increased nitric oxide (NO) and prostaglandin E2 (PGE2) generation depending on the concentration while exhibiting no cytotoxicity. PPCRE markedly upregulated the mRNA and protein expression of immune-related cytotoxic factors such as cyclooxygenase (COX)-1, COX-2, and inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α), as well as the mRNA level of IL-4. PPCRE increased the mitogen-activated protein kinase (MAPK) signaling pathway by upregulating the phosphorylation of extracellular signal-regulated kinase (ERK), stress-activated protein kinase/Jun N-terminal-kinase (SAPK/JNK), and p38. Furthermore, PPCRE considerably activated the nuclear factor kappa B (NF-κB) signaling pathway by increasing phosphorylation of NF-κB-p65. PPCRE-stimulated RAW264.7 cells increased macrophage phagocytic capacity. In conclusion, our study found that PPCRE improved immune function by modulating inflammatory mediators and regulating the MAPK and NF-κB pathway of signaling in macrophages.

Genome-wide association study of subfoveal choroidal thickness in a longitudinal cohort of older adults.

To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10-4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 µm (AA, 73.8%) and 31.1 µm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 µm (AA, 74.2%) and 28.2 µm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration.

Effects of Nutrient Manipulation during Peripartum and Suckling Period on Productivity of Hanwoo Cows and Offspring.

This study investigated the effects of nutrient manipulation during the peripartum and suckling periods on the productivity of Hanwoo cows and their offspring. A total of 183 pregnant cows and their 180 offspring were randomly assigned to either a control group, fed a formula feed with 13.5% crude protein (CP) and 70.5% total digestible nutrients (TDN), or a treatment group, fed nutrient-enriched formula feed with 18.0% CP and 72.5% TDN. Offspring were similarly divided and fed either 17.0% CP and 69.5% TDN (control) or 21.5% CP and 72.5% TDN (treatment). Results showed that body weight recovery was higher in the treatment group, although wither height, body length, and body condition scores were similar between groups. The treatment group exhibited increased chest girth, reduced intervals for first return to estrus, and shorter days open compared to the control group. Plasma non-esterified fatty acids, albumin, and progesterone concentrations of Hanwoo cows varied between groups at the 3 months before and after calving. Offspring in the treatment group had higher body weight and average daily gain at birth, three and six months of age, with higher dry matter intake. These findings suggest that nutrient-enriched formula feed positively influences the reproductive efficiency of Hanwoo cows and the growth performance of their offspring.

User Sentiment Analysis Based on Securities Application Elements.

Designing securities applications for mobile devices is challenging due to their inherent complexity, necessitating improvement through the analysis of online reviews. However, research applying deep learning techniques to the sentiment analysis of Korean text remains limited. This study explores the use of Aspect-Based Sentiment Analysis (ABSA) as an effective alternative to traditional user research methods for securities application design. By analyzing large volumes of text-based user review data of Korean securities applications, the study identifies critical elements like "update", "screen", "chart", "login", "access", "authentication", "account", and "transaction", revealing nuanced user sentiments through techniques such as PMI, SVD, and Word2Vec. ABSA offers deeper insights compared to overall ratings, uncovering hidden areas of dissatisfaction despite positive biases in reviews. This research demonstrates the scalability and cost-effectiveness of ABSA in mobile-application design research.

Reconstructing Failure: Assessing Surgical and Patient Reported Outcomes Following Loss of Initial Breast Reconstruction.

BACKGROUND: Breast reconstruction failure, defined as the removal of a prosthetic device or flap without immediate replacement, can be traumatic for patients. We aim to describe the progression of patients who experience tissue expander (TE), implant, or autologous breast reconstructive failure and assess the patient reported outcomes (PROs) among patients who undergo additional reconstruction. METHOD: Patients undergoing TE, implant, or autologous breast reconstruction between 2017 and 2022 were included, and patients with reconstructive failures were identified. Outcomes of interests included (1) receipt of additional reconstruction and (2) BREAST-Q scores 1-year after reconstructive failure. We also performed a propensity-matched analysis between patients who undergo secondary reconstruction and patients who had an uncomplicated reconstruction. RESULTS: 4,258 TE, 4,420 implant, and 1,545 autologous breast reconstruction patients were included. Of patients who experienced reconstructive failures, 49.5% of TE, 4.8% of implant, and 53.8% of autologous patients underwent secondary reconstruction. Age, psychiatric diagnosis, chemotherapy, radiation, and mastectomy type were associated with increased likelihood of secondary reconstruction. Between patients with and without additional reconstruction, higher Psychosocial Well-being trended towards the former cohort (61 [Interquartile Range: 56, 80] vs 50 [46, 65], p=0.085). Propensity-matched analysis demonstrated comparable PROs at 1-year after definite reconstruction. CONCLUSION: Less than half of reconstructive failure patients undergo an additional reconstruction. Patients with secondary reconstruction may have improved Psychosocial Well-being than those who do not and comparable PROs to those who had uncomplicated initial reconstruction. Surgeons should counsel patients with reconstructive failures that although traumatizing, secondary reconstruction may be beneficial.

Inner retinal layer thickness alterations in adult and pediatric patients with neurofibromatosis 1.

This study compared the thickness of each intraretinal layer in patients with neurofibromatosis 1 (NF1) and controls to analyze the association between intraretinal layer thickness and visual function. The macular spectral-domain optical coherence tomography volumetric dataset obtained from 68 eyes (25 adult eyes, 43 pediatric eyes) with NF1 without optic glioma and 143 control eyes (100 adult eyes, 43 pediatric eyes) was used for image auto-segmentation. The intraretinal layers segmented from the volumetric data included the macular retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer. Cases and controls were compared after adjusting for age, sex, refractive error, and binocular use. The association between retinal layer thickness and visual acuity was also analyzed. The GCIPL was significantly thinner in both adult and pediatric patients with NF1 compared with healthy controls. Average RNFL and GCIPL thicknesses were associated with visual acuity in adult patients with NF1. In pediatric patients, average GCIPL thickness was associated with visual acuity. These results suggest that changes in the inner retinal layer could be a biomarker of the structural and functional status of patients with NF1.

[Factors Influencing Oncofertility in Gynecological Cancer Patients: Application of Mixed Methods Study].

PURPOSE: This study aimed to identify factors influencing oncofertility and to explore the oncofertility experiences of patients with gynecological cancer using quantitative and qualitative methods, respectively. METHODS: An explanatory sequential mixed-methods study was conducted. The quantitative study involved 222 patients with gynecological cancer recruited from online cafes and hospitals. Data were analyzed using IBM SPSS Statistics 28. For qualitative research, eight patients with gynecological cancer were interviewed. Data were analyzed using theme analysis method. RESULTS: Oncofertility performance was quantitatively assessed in 40 patients (18.0%). Factors that significantly affected oncofertility were fertility preservation awareness (odds ratio [OR] = 14.97, 95% confidence interval [CI]: 4.22~53.08), number of children planned before cancer diagnosis (OR = 6.08, 95% CI: 1.89~19.62; OR = 5.04, 95% CI: 1.56~16.29), monthly income (OR= 3.29, 95% CI: 1.23~8.86), social support (OR = 1.08, 95% CI: 1.01~1.17), and anxiety (OR = 0.79, 95% CI: 0.66~0.95). Qualitative results showed three theme clusters and eight themes: (1) themes for determinant factors affecting oncofertility selection: 'desire to have children' and 'special meaning of the uterus and ovaries;' (2) themes for obstructive factors affecting oncofertility selection: 'fertility preservation fall behind priorities,' 'confusion caused by inaccurate information,' and 'my choice was not supported;' (3) themes for support factors affecting oncofertility selection: 'provide accurate and reasonable information about oncofertility,' 'addressing the healthcare gap,' and 'need financial support for oncofertility.' CONCLUSION: Financial support, sufficient information, social support, and anxiety-relief interventions are required for oncofertility in patients with gynecological cancer.

Sensitive Electrochemical and Thermal Detection of Human Noroviruses Using Molecularly Imprinted Polymer Nanoparticles Generated against a Viral Target.

Norovirus (NoV) is the predominant cause of foodborne illness globally; current detection methods are typically expensive, have inadequate sensitivities, and utilize biological receptors with poor stability. Therefore, accurate, cost-effective, and highly stable detection methods are needed to screen for NoV in foods. We developed molecularly imprinted polymer nanoparticles (nanoMIPs) to detect NoV using a small target epitope (12 amino acids) with a solid-phase synthesis approach. The performance of three batches of nanoMIPs with varying monomer compositions (nanoMIP-1, -2, and -3) were compared both experimentally and computationally. Surface plasmon resonance examined nanoMIP binding affinity to norovirus virus-like particles (NoV-LPs), whereby nanoMIP-1 had the lowest KD value of 0.512 µM. This is significant, as traditional targets for generation of norovirus ligands previously reported were generated against drastically larger norovirus capsid segments that have limitations in ease of production. Further, an electrochemical sensor was developed by covalently attaching the nanoMIPs to glassy carbon electrodes. In agreement with our predictions from density functional theory simulations, electrochemical impedance spectroscopy showed a sensitive response toward NoV-LPs for nanoMIP batches tested; however, nanoMIP-1 was optimal, with an excellent detection limit of 3.4 pg/mL (1.9 × 105 particles/mL). Due to its exceptional performance, nanoMIP-1 was immobilized to screen-printed electrodes and utilized within a thermal sensor, where it exhibited a low detection limit of 6.5 pg/mL (3.7 × 105 particles/mL). Crucially, we demonstrated that nanoMIP-1 could detect NoV in real food samples (romaine lettuce) by using electrochemical and thermal sensors. Consequently, the study highlights the exceptional potential of nanoMIPs to replace traditional biological materials (e.g., antibodies) as sensitive, versatile, and highly stable receptors within NoV sensors.

Mie Magnetic Structural Colors from Short Chains of TiO2 Nanospheres.

We demonstrate distinctive structural colors within a small footprint by using a short chain of nanospheres. Rather than using high-index materials like Si (n ∼ 4), which ensure strong modal confinement, TiO2 is employed. TiO2 has an intermediate index (n ∼ 2), promoting stronger modal coupling between the magnetic dipoles of each particle. This approach enables selective engineering of the magnetic response and yields larger spectral changes compared to that of Si. Despite the lower refractive index, the absence of absorption in TiO2 also produces higher scattering intensities than Si. We develop a quasistatic analytical model that describes the dipolar modal coupling in a trimer and use it to reveal distinct magnetic field strengths in the outer or central particle depending on the polarization of incident light. These results suggest pathways to manipulate the magnetic field in chains of particles and create vibrant structural colors with simple configurations.

National Trends in the Prevalence of Unmet Health Care and Dental Care Needs During the COVID-19 Pandemic: Longitudinal Study in South Korea, 2009-2022.

BACKGROUND: Although previous studies have investigated trends in unmet health care and dental care needs, most have focused on specific groups, such as patients with chronic conditions and older adults, and have been limited by smaller data sets. OBJECTIVE: This study aims to investigate the trends and relative risk factors for unmet health care and dental care needs, as well as the impact of the COVID-19 pandemic on these needs. METHODS: We assessed unmet health care and dental care needs from 2009 to 2022 using data from the Korea Community Health Survey (KCHS). Our analysis included responses from 2,750,212 individuals. Unmet health care or dental care needs were defined as instances of not receiving medical or dental services deemed necessary by experts or desired by patients. RESULTS: From 2009 to 2022, the study included 2,700,705 individuals (1,229,671 men, 45.53%; 673,780, 24.95%, aged 19-39 years). Unmet health care needs decreased before the COVID-19 pandemic; however, during the pandemic, there was a noticeable increase (ßdiff 0.10, 95% CI 0.09-0.11). Unmet dental care needs declined before the pandemic and continued to decrease during the pandemic (ßdiff 0.23, 95% CI 0.22-0.24). Overall, the prevalence of unmet dental care needs was significantly higher than that for unmet health care needs. While the prevalence of unmet health care needs generally decreased over time, the ß difference during the pandemic increased compared with prepandemic values. CONCLUSIONS: Our study is the first to analyze national unmet health care and dental care needs in South Korea using nationally representative, long-term, and large-scale data from the KCHS. We found that while unmet health care needs decreased during COVID-19, the decline was slower compared with previous periods. This suggests a need for more targeted interventions to prevent unmet health care and dental care needs.

Suspected paroxysmal dyskinesia in four small-breed dogs: Clinical presentation, diagnosis, management and prognosis.

This case report details the clinical presentation, diagnosis, management and prognosis of paroxysmal dyskinesia (PD) in four small-breed dogs, each weighing under 6 kg: A 7-year-old spayed female Pomeranian, an 8-year-old female mixed breed, a 1-year-old female Pomeranian and a 9-year-old castrated male Poodle. These dogs were referred to our hospital due to movement disorders. Diagnosis was facilitated by video recordings of the episodes, assessing motor activity, consciousness, episode duration, any pre- or post-episodic behaviour as well as the presence of autonomic signs. Magnetic resonance imaging conducted on two of the dogs returned unremarkable results. Treatment trials included a gluten-free diet for all four dogs, with two also receiving acetazolamide. This intervention led to a decrease in the frequency of abnormal movement in all patients. Our findings suggest that PD in dogs can be effectively diagnosed through detailed symptom description using videos and questionnaires. Furthermore, once diagnosed, a combination of nutritional and medical management can be beneficial.

Titania-Cored Janus Multipods as UV-Protective Pickering Emulsifiers for Sunscreens.

Pickering emulsifiers have gained significant interest as alternatives for conventional surfactants in various applications that includes pharmaceutics, food, homecare products, and cosmetics. However, their function is primarily focused on enhancing emulsion stability of which still remains to be resolved. Herein, Janus multipods are presented that simultaneously shield UV while offering high emulsion stability. These particles are prepared by growing multiple silicon dioxide (SiO2) nanopods using sol-gel method on a spherical titanium dioxide (TiO2) core with a thin SiO2 shell. The incorporation of high refractive index TiO2 in the core is shown to effectively shield UV while the SiO2 shell suppresses the photocatalytic activity. Moreover, by utilizing wax colloidosomes as templates, these multipod nanoparticles are further modified to exhibit Janus characteristics. This leads to strong adsorption of the Janus multipods at the oil/water emulsion interface where the multipod feature additionally reinforces the interfacial stabilization by interdigitation and interlocking of the Janus multipods to suppress detachment of the highly dense particles from the interface. As these Janus multipods offer effective UV protection as well as excellent emulsion stability, it is envisioned that they have great potential in advanced cosmetic formulations which require both enhanced sunscreen performance and better feeling in skincare products.

Triplet Energy Transfer (EnT)-Promoted 1,3-Dipolar Cycloaddition Reactions of N-(Trimethylsilyl)methylphthalimide with Electron-Deficient Alkynes and Alkenes.

Triplet energy transfer (EnT)-promoted photochemical pathways, arisen by visible light and its photosensitizers, have gained significant attention as a complementary strategy for initiating organic transformations in photochemical reactions that are unlikely to occur through a single electron transfer (SET) process. In the present study, we investigated the triplet EnT-promoted 1,3-dipolar cycloaddition reactions of N-(trimethylsilyl)methylphthalimide with electron-deficient alkynyl and alkenyl dipolarophiles. The triplet excited state of N-(trimethylsilyl)methylphthalimide, promoted by the triplet EnT from thioxanthone (TXA) photosensitizer, underwent sequential intramolecular SET and carbon-to-oxygen migration of the silyl group to form azomethine ylide. This generated ylide cycloadded to alkynes or alkenes to regioselectively and stereospecifically produce a nitrogen-containing benzopyrrolizidine scaffold with multiple stereogenic centers. Crucially, the stereoselectivity of these cycloaddition reactions (i.e., endo versus exo addition) was influenced by the nature of the dipolarophiles.

Phlorotannin Supplement Improves Scopolamine-Induced Memory Dysfunction by Rescuing Synaptic Damage in Mice.

This study investigated the efficacy of a phlorotannin supplement (PS) in ameliorating scopolamine (SCO)-induced memory deficits in mice, focusing on synaptic function and the underlying molecular mechanisms. Male C57BL/6N mice were divided into six groups and treated with vehicle, donepezil (5 mg/kg body weight (BW)), or PS (100, 250, or 500 mg/kg BW) for 6 weeks. Behavioral tests were conducted , followed by Golgi staining , immunofluorescence , and immunoblotting to assess synaptic protein expression and signaling pathways . Behavioral tests showed that PS administration significantly improved SCO-induced memory impairment and restored synaptic protein expression (synaptophysin , synapsin 1, and postsynaptic density protein 95) in the hippocampus . Additionally , PS enhanced brain-derived neurotrophic factor (BDNF ) signaling and activated the extracellular signal-regulated kinase/CAMP response element binding protein ( ERK-CREB) pathway, essential for synaptic plasticity. Our findings demonstrate that PS mitigates SCO-induced memory dysfunction by protecting synaptic integrity and activating the BDNF-ERKCREB signaling pathway , indicating the potential of PS as a natural intervention for treating memory deficits.

Rice bran supplement ameliorates chronic restraint stress-induced depression-like behaviors in mice.

Depression is emerging as a social and health-related issue worldwide. Rice bran possesses a variety of biological properties; however, its potential efficacy and molecular mechanisms in depression remain unclear. This study investigated the antidepressant effects of rice bran supplement (RBS) in a mouse model of chronic restraint stress (CRS)-induced depression. RBS was administered to mice subjected to CRS for 5 weeks. RBS improved depressive symptoms in CRS-exposed mice, as evidenced by increased sucrose preference and reduced immobility time. It reduced hypothalamic-pituitary-adrenal (HPA) axis-related hormones. Additionally, RBS downregulated the glucocorticoid receptor (GR) pathway and upregulated the ERK-CREB-BDNF pathway in the prefrontal cortex and hippocampus. Furthermore, RBS increased neurotransmitter levels and decreased monoamine oxidase levels in the brain. Molecular docking analysis indicated that γ-oryzanol (ORY) interacts with GR. Moreover, ORY inhibited GR activity in GR-transfected HEK293T cells. The effects of ORY were not significantly altered by treatment with GR antagonist mifepristone or GR siRNA, suggesting ORY functions as a GR antagonist. Additionally, ORY administration improved depressive behaviors in CRS-exposed mice and modulated the imbalance of HPA axis-related hormones in mice. Mechanisms of action in the RBS were partially attributed by ORY, a key component of RBS, suggesting that ORY contributes synergistically to the effect of RBS. Thus, RBS administration could be a promising therapeutic approach to treating CRS-induced depression.

ECM stiffness regulates calcium influx into mitochondria via tubulin and VDAC1 activity.

Calcium ions (Ca2+) play pivotal roles in regulating numerous cellular functions, including metabolism and growth, in normal and cancerous cells. Consequently, Ca2+ signaling is a vital determinant of cell fate and influences both cell survival and death. These intracellular signals are susceptible to modulation by various factors, including changes in the extracellular environment, which leads to mechanical alterations. However, the effect of extracellular matrix (ECM) stiffness variations on intracellular Ca2+ signaling remains underexplored. In this study, we aimed to elucidate the mechanisms of Ca2+ regulation through the mitochondria, which are crucial to Ca2+ homeostasis. We investigated how Ca2+ regulatory mechanisms adapt to different levels of ECM stiffness by simultaneously imaging the mitochondria and endoplasmic reticulum (ER) in live cells using genetically encoded biosensors. Our findings revealed that the uptake of mitochondrial Ca2+ through Voltage-Dependent Anion Channel 1 (VDAC1), facilitated by intracellular tubulin, is influenced by ECM stiffness. Unraveling these Ca2+ regulatory mechanisms under various conditions offers a novel perspective for advancing biomedical studies involving Ca2+ signaling.