Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia.

Ginseng is a traditional herbal medicine used for prevention and treatment of various diseases as a tonic. Recent scientific cohort studies on life prolongation with ginseng consumption support this record, as those who consumed ginseng for more than 5 years had reduced mortality and cognitive decline compared to those who did not. Clinical studies have also shown that acute or long-term intake of ginseng total extract improves acute working memory performance or cognitive function in healthy individuals and those with subjective memory impairment (SMI), mild cognitive impairment (MCI), or early Alzheimer's disease (AD) dementia who are taking AD medication(s). Ginseng contains various components ranging from classical ginsenosides and polysaccharides to more recently described gintonin. However, it is unclear which ginseng component(s) might be the main candidate that contribute to memory or cognitive improvements or prevent cognitive decline in older individuals. This review describes recent clinical contributors to ginseng components in clinical tests and introduces emerging evidence that ginseng components could be novel candidates for cognitive improvement in older individuals, as ginseng components improve SMI cognition and exhibits add-on effects when co-administered with early AD dementia drugs. The mechanism behind the beneficial effects of ginseng components and how it improves cognition are presented. Additionally, this review shows how ginseng components can contribute to SMI, MCI, or early AD dementia when used as a supplementary food and/or medicine, and proposes a novel combination therapy of current AD medicines with ginseng component(s).

miRNA profiling of B16F10 melanoma cell exosomes reveals melanin synthesis-related genes.

This study investigates the communication between skin cells, specifically melanocytes, keratinocytes, and fibroblasts, which is crucial for the process of melanin production known as melanogenesis. We aimed to understand the role of melanocyte exosomes in regulating melanogenesis and to uncover the microRNAs influencing this process. We isolated exosomes and characterized them using advanced microscopy and protein analysis to achieve this. We conducted experiments on melanoma cells to study melanin production regulation and examined how exosomes influenced gene expression related to melanogenesis. The results revealed that melanocyte exosomes increased certain types of tyrosinases, thereby enhancing melanin production. Furthermore, we acquired the miRNA profile of exosomes and hypothesized that specific siRNAs, such as miR-21a-5p, could potentially facilitate melanin synthesis. Our findings shed light on the importance of exosomes in skin health and provide valuable insights into intercellular communication mechanisms. Understanding these processes can pave the way for innovative therapies to treat melanin-related disorders and maintain healthy skin.

Evaluating Free Thermal Expansion and Glass Transition of Ultrathin Polymer Films on Heated Liquid.

Thermomechanical properties of ultrathin films are crucial for fabrication and use of reliable thin electronic devices. Due to the lack of precise measurement techniques, the thermal deformation behavior of ultrathin films has not yet been clarified. Here, we propose a film on heated liquid (FOHL) method to simultaneously measure the coefficient of thermal expansion (CTE) and glass transition temperature (Tg) of multiple ultrathin polymer films. Free thermal expansion of thin films without substrate interaction can be guaranteed when the thin films are afloat on a liquid surface. To investigate the thermal behavior in a wide temperature range, glycerol is adopted as a thermally stable heating platform owing to its high boiling point of 290 °C. The thin films are transferred onto the glycerol surface from the water surface using the hygroscopic properties of glycerol. Highly accurate and high-throughput thermal strain measurement is achieved using three-dimensional digital image correlation (3D-DIC). The thermomechanical properties of ultrathin polystyrene thin films of various thicknesses (25-400 nm) are precisely characterized utilizing the FOHL and 3D-DIC method.

Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

3D epigenomics and 3D epigenopathies.

Mammalian genomes are intricately compacted to form sophisticated 3-dimensional structures within the tiny nucleus, so called 3D genome folding. Despite their shapes reminiscent of an entangled yarn, the rapid development of molecular and next-generation sequencing technologies (NGS) has revealed that mammalian genomes are highly organized in a hierarchical order that delicately affects transcription activities. An increasing amount of evidence suggests that 3D genome folding is implicated in diseases, giving us a clue on how to identify novel therapeutic approaches. In this review, we will study what 3D genome folding means in epigenetics, what types of 3D genome structures there are, how they are formed, and how the technologies have developed to explore them. We will also discuss the pathological implications of 3D genome folding. Finally, we will discuss how to leverage 3D genome folding and engineering for future studies. [BMB Reports 2024; 57(5): 216-231].

Heat-Killed Lactilactobacillus sakei WB2305 and Lactiplantibacillus plantarum WB2324 Inhibited LPS-Induced Inflammation in Human Airway Epithelial Cells.

Asthma is characterized by inflammation of the airways, including the inflammatory and airway structural cells. Probiotics, which have diverse effects, even within the same species, are being studied to prevent and mitigate the severity of asthma. Lactilactobacillus sakei WB2305 and Lactiplantibacillus plantarum WB2324 were isolated from kimchi. These strains have acceptable probiotic properties and are safe. In addition, the anti-inflammatory potential of the heat-killed isolates against lipopolysaccharide (LPS)-induced inflammation in the human pulmonary epithelial cell line (A549) was investigated. The heat-killed Lact. sakei WB2305 and Lact. plantarum WB2324 reduced the chemokine and cytokines mRNA expression levels, as shown by the results of using real-time polymerase chain reaction. Western blotting results showed that the nuclear factor-kappa B (NF-κB) activation and mitogen-activated protein kinases (MAPK) signaling pathways were suppressed by treatment with the heat-killed strains. The production amounts of eotaxin, tumor necrosis factor-ɑ (TNF-α), and interleukin-6 (IL-6) were lower than those in LPS-only treated cells. Additionally, 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining confirmed decreased reactive oxygen species (ROS) production in A549 cells. Therefore, the results of present study demonstrate the anti-inflammatory and anti-asthmatic activities of heat-killed Lact. sakei WB2305 and Lact. plantarum WB2324 in human airway epithelial cells.

CRISPR-aided genome engineering for secondary metabolite biosynthesis in Streptomyces.

The demand for discovering novel microbial secondary metabolites is growing to address the limitations in bioactivities such as antibacterial, antifungal, anticancer, anthelmintic, and immunosuppressive functions. Among microbes, the genus Streptomyces holds particular significance for secondary metabolite discovery. Each Streptomyces species typically encodes approximately 30 secondary metabolite biosynthetic gene clusters (smBGCs) within its genome, which are mostly uncharacterized in terms of their products and bioactivities. The development of next-generation sequencing has enabled the identification of a large number of potent smBGCs for novel secondary metabolites that are imbalanced in number compared with discovered secondary metabolites. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system has revolutionized the translation of enormous genomic potential into the discovery of secondary metabolites as the most efficient genetic engineering tool for Streptomyces. In this review, the current status of CRISPR/Cas applications in Streptomyces is summarized, with particular focus on the identification of secondary metabolite biosynthesis gene clusters and their potential applications.This review summarizes the broad range of CRISPR/Cas applications in Streptomyces for natural product discovery and production. ONE-SENTENCE SUMMARY: This review summarizes the broad range of CRISPR/Cas applications in Streptomyces for natural product discovery and production.

Unraveling diffusion behavior in Cu-to-Cu direct bonding with metal passivation layers.

Cu/SiO2 hybrid bonding presents a promising avenue for achieving high-density interconnects by obviating the need for microbumps and underfills. Traditional copper bonding methods often demand temperatures exceeding 400 °C, prompting recent endeavors to mitigate bonding temperatures through investigations into metal passivation bonding. In this study, we scrutinized the diffusion behavior associated with various metal passivation layers (Platinum, Titanium, Tantalum, and Chromium) in the context of low-temperature direct copper bonding and delved into the essential bonding mechanisms. We observed a deviation from conventional metal-metal bonding factors, such as surface roughness and grain size, in the diffusion behavior. Remarkably, our analysis revealed a pronounced correlation between the crystallinity of the metal passivation layers and diffusion behavior, surpassing the influence of other experimental factors. Subsequent post-bonding examinations corroborated consistent diffusion behavior in Pt and Cr passivation samples with disparate crystallinities, reinforcing the significance of crystallinity in the bonding process. Our findings underscore crystallinity as a pivotal factor governing diffusion behavior, even under varied bonding conditions. These insights are instrumental in achieving exceptional bonding characteristics at lower temperatures in Cu/SiO2 hybrid bonding. Implications of this study extend to the prospect of advancing highly integrated systems through die-to-wafer bonding, marking a substantial stride toward future applications.

Atypical formations of gintonin lysophosphatidic acids as new materials and their beneficial effects on degenerative diseases.

Fresh ginseng is prone to spoilage due to its high moisture content. For long-term storage, most fresh ginsengs are dried to white ginseng (WG) or steamed for hours at high temperature/pressure and dried to form Korean Red ginseng (KRG). They are further processed for ginseng products when subjected to hot water extraction/concentration under pressure. These WG or KRG preparation processes affect ginsenoside compositions and also other ginseng components, probably during treatments like steaming and drying, to form diverse bioactive phospholipids. It is known that ginseng contains high amounts of gintonin lysophosphatidic acids (LPAs). LPAs are simple lipid-derived growth factors in animals and humans and act as exogenous ligands of six GTP-binding-protein coupled LPA receptor subtypes. LPAs play diverse roles ranging from brain development to hair growth in animals and humans. LPA-mediated signaling pathways involve various GTP-binding proteins to regulate downstream pathways like [Ca2+]i transient induction. Recent studies have shown that gintonin exhibits anti-Alzheimer's disease and anti-arthritis effects in vitro and in vivo mediated by gintonin LPAs, the active ingredients of gintonin, a ginseng-derived neurotrophin. However, little is known about how gintonin LPAs are formed in high amounts in ginseng compared to other herbs. This review introduces atypical or non-enzymatic pathways under the conversion of ginseng phospholipids into gintonin LPAs during steaming and extraction/concentration processes, which exert beneficial effects against degenerative diseases, including Alzheimer's disease and arthritis in animals and humans via LPA receptors.

A retrospective comparative study of maxillofacial injury patterns caused by electric scooters and bicycles.

BACKGROUND/AIM: The emergence of shared stand-up electric scooters has led to an increase in their usage and, subsequently, an increase in the incidence of maxillofacial trauma. This study aimed to investigate the trauma pattern associated with the use of stand-up electric scooters compared with that related to the use of bicycles, which was a popular mode of personal mobility before the emergence of stand-up electric scooters. MATERIALS AND METHODS: This study investigated the medical records of patients who visited Wonju Christian Hospital for maxillofacial trauma due to the use of stand-up electric scooter and bicycles between November 1, 2017 and October 31, 2022. Maxillofacial trauma was analyzed based on medical records, including those in the evaluation results of teeth, maxillofacial bones, and soft tissues. RESULTS: Crown fractures and tooth avulsions were observed more frequently with the use of stand-up electric scooters than with the use of bicycles. In contrast, crown-root fractures, tooth subluxation, and extrusive luxation were more commonly observed in bicycle riders. Additionally, the proportion of root fractures was similar between the two groups. However, no vertical root fractures were observed in patients who rode bicycles. The maxillofacial bone fracture rates between the two groups were similar, although the fracture patterns were different. CONCLUSION: The number of patients using stand-up electric scooters is increasing, and they are likely to have a worse prognosis compared with those using existing personal mobility devices.

Gintonin Alleviates HCl/Ethanol- and Indomethacin-Induced Gastric Ulcers in Mice.

Gintonin, newly extracted from ginseng, is a glycoprotein that acts as an exogenous lysophosphatidic acid (LPA) receptor ligand. This study aimed to demonstrate the in vivo preventive effects of gintonin on gastric damage. ICR mice were randomly assigned to five groups: a normal group (received saline, 0.1 mL/10 g, p.o.); a control group (administered 0.3 M HCl/ethanol, 0.1 mL/10 g, p.o.) or indomethacin (30 mg/kg, p.o.); gintonin at two different doses (50 mg/kg or 100 mg/kg, p.o.) with either 0.3 M HCl/ethanol or indomethacin; and a positive control (Ranitidine, 40 mg/kg, p.o.). After gastric ulcer induction, the gastric tissue was examined to calculate the ulcer index. The expression of gastric damage markers, such as tumor necrosis factor (TNF)-α, cyclooxygenase 2 (COX-2), and LPA2 and LPA5 receptors, were measured by Western blotting. Interleukin-6 (IL-6) and prostaglandin E2 (PGE2) levels were measured by enzyme-linked immunosorbent assay. The platelet endothelial cell adhesion molecule (PECAM-1), Evans blue, and occludin levels in gastric tissues were measured using immunofluorescence analysis. Both HCl/ethanol- and indomethacin-induced gastric ulcers showed increased TNF-α, IL-6, Evans blue permeation, and PECAM-1, and decreased COX-2, PGE2, occludin, and LPA5 receptor expression levels. However, oral administration of gintonin alleviated the gastric ulcer index induced by HCl/ethanol and indomethacin in a dose-dependent manner. Gintonin suppressed TNF-α and IL-6 expression, but increased COX-2 expression and PGE2 levels in mouse gastric tissues. Gintonin intake also increased LPA5 receptor expression in mouse gastric tissues. These results indicate that gintonin can play a role in gastric protection against gastric damage induced by HCl/ethanol or indomethacin.

Spatially coordinated heterochromatinization of long synaptic genes in fragile X syndrome.

Short tandem repeat (STR) instability causes transcriptional silencing in several repeat expansion disorders. In fragile X syndrome (FXS), mutation-length expansion of a CGG STR represses FMR1 via local DNA methylation. Here, we find megabase-scale H3K9me3 domains on autosomes and encompassing FMR1 on the X chromosome in FXS patient-derived iPSCs, iPSC-derived neural progenitors, EBV-transformed lymphoblasts, and brain tissue with mutation-length CGG expansion. H3K9me3 domains connect via inter-chromosomal interactions and demarcate severe misfolding of TADs and loops. They harbor long synaptic genes replicating at the end of S phase, replication-stress-induced double-strand breaks, and STRs prone to stepwise somatic instability. CRISPR engineering of the mutation-length CGG to premutation length reverses H3K9me3 on the X chromosome and multiple autosomes, refolds TADs, and restores gene expression. H3K9me3 domains can also arise in normal-length iPSCs created with perturbations linked to genome instability, suggesting their relevance beyond FXS. Our results reveal Mb-scale heterochromatinization and trans interactions among loci susceptible to instability.

Reassembled Vacuoles for Drug Delivery Carriers Using Yeast Vacuoles for Enhanced Antibacterial Activity.

In this study, we aimed to develop an efficient drug delivery system by reassembling vacuoles isolated from Saccharomyces cerevisiae. Initially, we assessed the impact of vacuolar enzymes on the efficacy of the loaded antibiotic polymyxin B (PMB), by conducting antibacterial activity tests using Shigella flexneri and Salmonella enteritidis. The results showed that vacuolar enzymes inhibited the effectiveness of PMB, highlighting the limitations of using natural vacuoles as drug carriers. To overcome this, we proposed a new drug delivery system called reassembled vacuoles (ReV). ReV particles were created by removing vacuolar enzymes and reassembling the vacuolar membrane through extrusion. ReV demonstrated improved structural stability, a more uniform size, and enhanced PMB release compared to natural vacuoles. Encapsulation efficiency tests revealed high loading efficiency for both normal vacuoles (NorV) and ReV, with over 80% efficiency at concentrations up to 600 µg/mL. The antibacterial activity of PMB-loaded ReV showed comparable results to PMB alone, indicating the potential of ReV as a drug delivery system. In conclusion, reassembled vacuoles offer a promising approach for drug delivery, addressing the limitations of natural vacuoles and providing opportunities for targeted and efficient drug release.

Increase CO2 recycling of Escherichia coli containing CBB genes by enhancing solubility of multiple expressed proteins from an operon through temperature reduction.

IMPORTANCE: In a previous study, we successfully engineered Escherichia coli capable of endogenous CO2 recycling through the heterologous expression of the Calvin-Benson Bassham genes. Establishing an efficient gene expression environment for recombinant strains is crucial, on par with the importance of metabolic engineering design. Therefore, the primary objective of this study was to further mitigate greenhouse gas emissions by investigating the effects of culture temperature on the formation of inclusion bodies (IB) and CO2 fixation activity in the engineered bacterial strain. The findings demonstrate that lowering the culture temperature effectively suppresses IB formation, enhances CO2 recycling, and concurrently increases the accumulation of organic acids. This temperature control approach, without adding or modifying compounds, is both convenient and efficient for enhancing CO2 recycling. As such, additional optimization of various environmental parameters holds promise for further enhancing the performance of recombinant strains efficiently.

Gintonin-Induced Wound-Healing-Related Responses Involve Epidermal-Growth-Factor-like Effects in Keratinocytes.

Epidermal growth factor (EGF) receptor activation and related downstream signaling pathways are known to be one of the major mechanisms of the proliferation and migration of keratinocytes. The heparin-binding EGF-like growth factor (HB-EGF) binds to EGF receptors and stimulates keratinocyte proliferation and migration. Gintonin, a novel ginseng compound, is a lysophosphatidic acid (LPA) receptor ligand. Gintonin has skin-wound-healing effects. However, the underlying mechanisms for these gintonin actions remain unclear. In this study, we aimed to elucidate the involvement of EGFRs in gintonin-induced wound repair in HaCaT keratinocytes. In this study, a water-soluble tetrazolium salt-based assay, a modified Boyden chamber migration assay, and immunoblotting were performed. Gintonin increased EGF receptor activation in HaCaT cells. However, the gintonin-induced phosphorylation of the EGF receptor was markedly reduced via treatment with the LPA inhibitor Ki16425 or the EGF receptor inhibitor erlotinib. Gintonin-enhanced proliferation and migration were blocked by the EGF receptor inhibitors (erlotinib and AG1478). Additionally, gintonin stimulated the expression and release of HB-EGF in HaCaT cells. EGF receptor inhibitors blocked gintonin-enhanced HB-EGF expression. These results indicate that the wound-healing effects of gintonin are closely related to the collaboration between EGF receptor activation and HB-EGF release-mediated downstream signaling pathways.

Inhibition of tau phosphorylation and Aß accumulation by S. cerevisiae-derived vacuoles in LPS-induced SH-SY5Y cells.

Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by the accumulation of intracellular tau and amyloid beta (Aß) proteins, which lead to neuroinflammation and neuronal apoptosis. In this study, we investigated the potential of a bioengineered vacuoles derived from Saccharomyces cerevisiae-derived vacuoles to treat neuroinflammation and protein accumulation in AD. The yeast-derived vacuole is a small organelle that achieves efficient degradation by utilizing a diverse array of hydrolytic enzymes. These hydrolytic enzymes break down and process proteins into smaller fragments. We found that vacuoles treatment significantly reduced LPS-primed cell apoptosis and diminished Aß42 secretion in vitro, potentially through the inhibition of the NF-kB p65 signaling pathway. Additionally, vacuole pre-treatment down-regulated NF-κB translocation and reduced phosphorylated tau levels in LPS-induced SH-SY5Y cells. Our results suggest that the vacuoles have potential as a therapeutic agent for neurodegenerative diseases. The vacuole's small size and diverse hydrolytic enzymes make it a promising drug delivery system for targeting intracellular proteins. Future studies may explore the use of vacuoles in animal models of AD to determine their therapeutic potential.

Yeast vacuolar enzymes as novel hatching inhibitors for aquatic organisms, Daphnia magna and Danio rerio eggs.

Concerns over the spread of non-native species in aquatic environments have led to the need for effective methods to prevent and control their spread while protecting native species. This study investigated the potential of yeast vacuolar enzymes as a natural hatching inhibitor for controlling aquatic organisms. Hatching experiments with Daphnia magna eggs demonstrated that exposure to yeast vacuole enzymes inhibited hatching in a concentration-dependent manner, suggesting their potential as an effective inhibitor of egg hatching in aquatic organisms. Interestingly, the protease used for comparative purposes did not inhibit hatching, but instead increased the mortality of hatched D. magna. Additionally, chorionic changes were observed in non-hatched D. magna eggs and zebrafish eggs exposed to yeast vacuole enzymes, suggesting that the enzyme can alter the chorion and interfere with hatching. These findings suggest that yeast vacuolar enzymes may be a promising and natural management tool for controlling the spread of harmful aquatic organisms, and further research is warranted to explore their potential for species-specific control.

The cover of an ear thermometer probe as a split-thickness skin graft mold in external auditory canal reconstruction.

Maintaining the patency of the external auditory canal (EAC) during reconstruction is important because of its physiological role in hearing and immunological protective functions. The curved shape of the EAC presents a challenge when performing a skin graft. One of the key points for a successful skin graft is to ensure compression on the wound bed, and many novel methods, including prefabricated ear molds, have been reported for this purpose. In this study, we present a case of a skin graft performed to reconstruct a skin defect following excision of actinic keratosis in the EAC, using the cover of an ear thermometer probe as a mold for the graft to match the curvature of the EAC. This is an economical and practical method for secure compression dressing of a skin graft in the EAC.

Volunteer Plants' Occurrence and the Environmental Adaptability of Genetically Modified Fodder Corn upon Unintentional Release into the Environment.

The number of corn cultivars that have been improved using genetically modified technology continues to increase. However, concerns about the unintentional release of living-modified organisms (LMOs) into the environment still exist. Specifically, there are cases where LMO crops grown as fodder are released into the environment and form a volunteer plant community, which raises concerns about their safety. In this study, we analyzed the possibility of weediness and volunteer plants' occurrence when GMO fodder corn grains distributed in Korea are unintentionally released into the environment. Volunteer plants' occurrence was investigated by directly sowing grains in an untreated field. The results showed that the germination rate was extremely low, and even if a corn seed germinated, it could not grow into an adult plant and would die due to weed competition. In addition, the germination rate of edible and fodder grains was affected by temperature (it was high at 20 °C and 30 °C but low at 40 °C and extremely low at 10 °C), and it was higher in the former than in the latter. And the germination rate was higher in Daehakchal (edible corn grains) than in Gwangpyeongok (fodder corn grains). The environmental risk assessment data obtained in this study can be used for future evaluations of the weediness potential of crops and the development of volunteer plant suppression technology in response to unintentional GMO release.