Selection of Catechin Biosynthesis-Related Genes and Functional Analysis from Chromosome-Level Genome Assembly in C. sinensis L. Variety 'Sangmok'.

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.

Effect of Abiotic Signals on the Accumulation of Saponarin in Barley Leaves in Hydroponics Under Artificial Lights.

Functional flavonoid production is a new agenda in the agricultural industry, and young barley leaves (YBL) are one of the highlighted crops due to their health-beneficial flavonoid, saponarin. For the year-round cultivation of a high saponarin content of YBL, abiotic signal effects on the biosynthesis and metabolism in YBL need to be understood clearly. In this research, the effects of reactive oxygen species (ROS)-related abiotic signals, such as light, potassium, and sodium, were investigated on the biosynthetic metabolism in YBL cultivation under artificial lights. A higher quantity of blue-rich white light (6500 K of light temperature) irradiation enhanced ROS levels and the related enzyme activities (APX and CAT), as well as photosynthesis and saponarin amount, while red-rich white light (3000 K of light temperature) increased the photosynthesis only. In addition, 1.0 g L-1 K+ treatment in water slightly reduced ROS levels and increased saponarin accumulation in YBL. These blue-rich light and K+ supplemental conditions relatively increased OGT expression and reduced 4-coumaric acid and isovitexin as saponarin precursors. Furthermore, the relative ratio of lutonarin as an oxidized product of saponarin increased in increments of light quantity. Finally, the abiotic conditions for saponarin production were optimized with the mixture solution treatment of 1.0 g L-1 Na+ and 1.0 g L-1 K+ under 500 PPFD of 6500 K light, and the saponarin amount per leaf was 219.5 µg plant-1; it was comparable amount with that under sunlight condition.

Flavor characteristics of garlic fish cakes using electronic nose and tongue analyses.

This study investigated the utility of garlic powder as a functional ingredient. The aim was to develop fish cakes with improved functionality and sensory preference based on the antioxidant activity and quality characteristics. Increasing amounts of garlic powder in the prepared fish cakes were associated with increasing total polyphenol and flavonoid contents, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS+) radical scavenging activity, and reducing power. Furthermore, electronic tongue and electronic nose analyses showed an increased the intensity of umami and sourness and increased the levels of volatile compounds. The lowest trimethylamine peak corresponded to the highest amount of garlic powder. Sensory evaluation indicated that 3% garlic powder had the highest score for all criteria. Fishy odor decreased as the proportion of garlic powder increased. These findings suggest that the addition of 3% garlic powder improves quality characteristics, sensory preference, and antioxidant activity of fish cakes.

Cell-type specific circadian transcription factor BMAL1 roles in excitotoxic hippocampal lesions to enhance neurogenesis.

Circadian clocks, generating daily rhythms in biological processes, maintain homeostasis in physiology, so clock alterations are considered detrimental. Studies in brain pathology support this by reporting abnormal circadian phenotypes in patients, but restoring the abnormalities by light therapy shows no dramatic effects. Recent studies on glial clocks report the complex effects of altered clocks by showing their beneficial effects on brain repairs. However, how neuronal clocks respond to brain pathology is elusive. This study shows that neuronal BMAL1, a core of circadian clocks, reduces its expression levels in neurodegenerative excitotoxicity. In the dentate gyrus of excitotoxic hippocampal lesions, reduced BMAL1 in granule cells precedes apoptosis. This subsequently reduces BMAL1 levels in neighbor neural stem cells and progenitors in the subgranular zone, enhancing proliferation. This shows the various BMAL1 roles depending on cell types, and its alterations can benefit brain repair. Thus, cell-type-specific BMAL1 targeting is necessary to treat brain pathology.

Importance of dietary supplementation of soluble and insoluble fibers to sows subjected to high ambient temperatures during late gestation and effects on lactation performance.

Heat stress adversely affects sows' performance, which can be improved by applying proper nutritional strategies. This study was conducted to investigate the interactive effects of dietary fiber levels and sources on sows' reproductive performance, metabolic response during gestation, and the carry-over influence on litter performance in the lactation period during heat stress (average room temperature of 27.1 °C). Fifty-four multiparous sows (Landrace × Yorkshire; initial body weight of 236.3 ± 16 kg; 2, 3 and 4 parities) at d 90 of gestation were assigned to a 2 × 3 factorial arrangement (9 sows/treatment), involving 2 dietary fiber levels (4.5% and 6% crude fiber) and 3 dietary fiber sources (wheat bran [WB], palm kernel meal [PK], and beet pulp [BP]). Sows fed the BP diet had highest (P < 0.01) feed intake and constipation index and lowest (P < 0.01) farrowing duration. Piglet weight (P = 0.041) and litter weight (P < 0.01) at weaning were higher in sows in the BP treatment compared to PK treatment. Sows in the BP treatment showed the greatest (P < 0.01) digestibility of crude protein and neutral detergent fiber. The fecal concentration of acetate was the lowest (P < 0.01) in the PK treatment. Total short-chain fatty acid production was increased in the WB and BP treatments compared with the PK. Sows in the BP treatment showed the lowest (P = 0.036) hair cortisol. The blood insulin concentration of sows was higher (P = 0.026) in the high fiber (6%) treatment compared with the low fiber (4.5%) treatment at 90 min and 120 min after the meal. The concentration of phthalic acid, succinic acid, phenylethylamine, hydrocinnamic acid, iron, linoleic acid, glycerol, ketone, and formamide were increased (P < 0.05) in the BP treatment compared with the WB. The BP treatment with high soluble fiber content improved the constipation index, farrowing duration, and litter performance, while high insoluble fibers increased sows comfort and reduced stress factors including respiratory rate and rectal temperature. Therefore, both soluble and insoluble sources of fiber are necessary to be added to the diet of gestating sows.

Artificial Octopus-Limb-Like Adhesive Patches for Cupping-Driven Transdermal Delivery with Nanoscale Control of Stratum Corneum.

Drug delivery through complex skin is currently being studied using various innovative structural and material strategies due to the low delivery efficiency of the multilayered stratum corneum as a barrier function. Existing microneedle-based or electrical stimulation methods have made considerable advances, but they still have technical limitations to reduce skin discomfort and increase user convenience. This work introduces the design, operation mechanism, and performance of noninvasive transdermal patch with dual-layered suction chamber cluster (d-SCC) mimicking octopus-limb capable of wet adhesion with enhanced adhesion hysteresis and physical stimulation. The d-SCC facilitates cupping-driven drug delivery through the skin with only finger pressure. Our device enables nanoscale deformation control of stratum corneum of the engaged skin, allowing for efficient transport of diverse drugs through the stratum corneum without causing skin discomfort. Compared without the cupping effect of d-SCC, applying negative pressure to the porcine, human cadaver, and artificial skin for 30 min significantly improved the penetration depth of liquid-formulated subnanoscale medicines up to 44, 56, and 139%. After removing the cups, an additional acceleration in delivery to the skin was observed. The feasibility of d-SCC was demonstrated in an atopic dermatitis-induced model with thickened stratum corneum, contributing to the normalization of immune response.

Vitamin D supplementation can enhance therapeutic effects of excimer laser in patients with vitiligo.

PURPOSE: Vitiligo is a disease of acquired depigmentation characterized by the destruction of melanocytes. A theoretical association between low level of 25-hydroxyvitamin D [25(OH)D] and vitiligo has been previously suggested. The objective of this study was to determine the efficacy of intramuscular injection of cholecalciferol with excimer laser compared with the excimer laser alone for vitiligo treatment. METHODS: This study included 26 patients diagnosed with non-segmental vitiligo and low serum 25(OH)D levels (<20 ng/mL). The participants were randomly divided into two groups through randomization. The treatment using a 308-nm excimer laser was administered to both groups, and the study group additionally received cholecalciferol injection. RESULTS: The Vitiligo Area Scoring Index (VASI) scores showed an 83.6% improvement over the initial score in the study group, whereas the control group showed a 54.7% improvement after 6 months of treatment. After 6 months of treatment, the study group showed a significantly higher proportion of patients who achieved VASI50 and VASI75 compared with the control group. CONCLUSION: Intramuscular injection of cholecalciferol can be a supplemental option for the treatment of vitiligo patients with vitamin D deficiency with excimer laser therapy.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

BACKGROUND/AIMS: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. METHODS: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. RESULTS: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. CONCLUSION: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Antarctic Krill Oil from Euphausia superba Ameliorates Carrageenan-Induced Thrombosis in a Mouse Model.

FJH-KO obtained from Antarctic krill, especially Euphausia superba, has been reported to contain high amounts of omega-3 polyunsaturated fatty acids (n-3 PUFA) and to exhibit anticancer and anti-inflammatory properties. However, its antithrombotic effects have not yet been reported. This study aimed to investigate the antithrombotic effects of FJH-KO in carrageenan-induced thrombosis mouse models and human endothelial cells. Thrombosis was induced by carrageenan injection, whereas the mice received FJH-KO pretreatment. FJH-KO attenuated carrageenan-induced thrombus formation in mouse tissue vessels and prolonged tail bleeding. The inhibitory effect of FJH-KO was associated with decreased plasma levels of thromboxane B2, P-selectin, endothelin-1, ß-thromboglobulin, platelet factor 4, serotonin, TNF-α, IL-1ß, and IL-6. Meanwhile, FJH-KO induced plasma levels of prostacyclin I2 and plasminogen. In vitro, FJH-KO decreased the adhesion of THP-1 monocytes to human endothelial cells stimulated by TNF-α via eNOS activation and NO production. Furthermore, FJH-KO inhibited the expression of TNF-α-induced adhesion molecules such as ICAM-1 and VCAM-1 by suppressing the NF-κB signaling pathway. Taken together, our study demonstrates that FJH-KO protects against carrageenan-induced thrombosis by regulating endothelial cell activation and has potential as an antithrombotic agent.

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Approaching Theoretical Limits in the Performance of Printed P-Type CuI Transistors via Room Temperature Vacancy Engineering.

Development of a novel high performing inorganic p-type thin film transistor could pave the way for new transparent electronic devices. This complements the widely commercialized n-type counterparts, indium-gallium-zinc-oxide (IGZO). Of the few potential candidates, copper monoiodide (CuI) stands out. It boasts visible light transparency and high intrinsic hole mobility (>40 cm2 V-1 s-1 ), and is suitable for various low-temperature processes. However, the performance of reported CuI transistors is still below expected mobility, mainly due to the uncontrolled excess charge- and defect-scattering from thermodynamically favored formation of copper and iodine vacancies. Here, a solution-processed CuI transistor with a significantly improved mobility is reported. This enhancement is achieved through a room-temperature vacancy-engineering processing strategy on high-k dielectrics, sodium-embedded alumina. A thorough set of chemical, structural, optical, and electrical analyses elucidates the processing-dependent vacancy-modulation and its corresponding transport mechanism in CuI. This encompasses defect- and phonon-scattering, as well as the delocalization of charges in crystalline domains. As a result, the optimized CuI thin film transistors exhibit exceptionally high hole mobility of 21.6 ± 4.5 cm2 V-1 s-1 . Further, the successful operation of IGZO-CuI complementary logic gates confirms the applicability of the device.

Phytochemical Investigation of Equisetum arvense and Evaluation of Their Anti-Inflammatory Potential in TNFα/INFγ-Stimulated Keratinocytes.

Equisetum arvense L. (Equisetaceae), widely known as 'horsetail', is a perennial plant found extensively across Asia. Extracts of E. arvense have been used in traditional medicine, particularly for the treatment of inflammatory disorders. This study aimed to determine the phytochemical compounds in E. arvense ethanolic extract and their anti-inflammatory properties. Subsequently, we isolated and identified nine secondary metabolites, including kaempferol 3,7-di-O-ß-D-glucopyranoside (1), icariside B2 (2), (Z)-3-hexenyl ß-D-glucopyranoside (3), luteolin 5-O-ß-D-glucopyranoside (4), 4-O-ß-D-glucopyranosyl caffeic acid (5), clemastanin B (6), 4-O-caffeoylshikimic acid (7), (7S,8S)-threo-7,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-4-O-ß-D-glucopyranoside (8), and 3-O-caffeoylshikimic acid (9). The chemical structures of the isolated compounds (1-9) were elucidated using HR-ESI-MS data, NMR spectra, and ECD data. Next, the anti-inflammatory effects of the isolates were evaluated in tumor necrosis factor (TNF)α/interferon (IFN)γ-induced HaCaT, a human keratinocyte cell line. Among the isolates, compound 3 showed the highest inhibitory effect on the expression of pro-inflammatory chemokines, followed by compounds 6 and 8. Correspondingly, the preceding isolates inhibited TNFα/IFNγ-induced activation of pro-inflammatory transcription factors, signal transducer and activator of transcription 1, and nuclear factor-κB. Collectively, E. arvense could be employed for the development of prophylactic or therapeutic agents for improving dermatitis.

Assessment of Effects of Low-Level Light Therapy on Scalp Condition and Hair Growth.

Background: The appearance of the scalp and hair is very important aesthetically regardless of age or sex. Although there are many drugs and treatment methods for scalp problems and hair loss, the treatment response is still insufficient. Aims and Objectives: To evaluate the efficacy of low-level light therapy in a helmet-like device. Materials and Methods: This study was designed as a 24-week trial with 50 participants. All participants used a helmet-shaped device emitting 630-690, 820-880, and 910-970 nm light wavelengths, for 20 minutes, daily for 24 weeks. A phototrichogram for hair density and thickness, Global Aesthetic Improvement Scale score, erythema index, and sebum secretions of the scalp were evaluated at baseline and at 12 and 24 weeks. Results: After 24 weeks of treatment, hair density and hair thickness were found to have significantly increased (P <.01 and P =0.013, respectively) and sebum secretion of vertex area had decreased significantly (P <.01). Of 49 participants, 73.47% of the participants showed improvement in the overall appearance of the scalp (n = 36). Conclusion: A helmet-like low-level light therapy device can improve the appearance of the hair, with thickening and increase in the density of the hair, and can improve scalp condition by decreasing sebum secretion.

Protopanaxadiol-Enriched Rice Exerted Antiadipogenic Activity during 3T3-L1 Differentiation and Anti-Inflammatory Activity in 3T3-L1 Adipocytes.

Ginseng is a traditional medicine with health benefits for humans. Protopanaxadiol (PPD) is an important bioactive compound found in ginseng. Transgenic rice containing PPD has been generated previously. In the present study, extracts of this transgenic rice were evaluated to assess their antiadipogenic and anti-inflammatory activities. During adipogenesis, cells were treated with transgenic rice seed extracts. The results revealed that the concentrations of the rice seed extracts tested in this study did not affect cell viability at 3 days post-treatment. However, the rice seed extracts significantly reduced the accumulation of lipids in cells and suppressed the activation of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which in turn inhibited the expression of adipogenesis-related mRNAs, such as adiponectin, PPARγ, C/EBPα, sterol regulatory element-binding protein 1, glucose transport member 4, and fatty acid synthase. In adipocytes, the extracts significantly reduced the mRNA expression of inflammation-related factors following LPS treatment. The activation of NF-κB p65 and ERK 1/2 was inhibited in extract-treated adipocytes. Moreover, treatment with extract #8 markedly reduced the cell population of the G2/M phase. Collectively, these results indicate that transgenic rice containing PPD may act as an obesity-reducing and/or -preventing agent.

Anatomical proposal of local anesthesia injection for median nerve block in treating hyperhidrosis with botulinum neurotoxin.

INTRODUCTION: Hyperhidrosis, causing excessive sweat, can be treated with Botulinum neurotoxin injection. Botulinum toxin, an effective and safe treatment for hyperhidrosis, unfortunately involves significant pain due to multiple injections. This study aims to propose a more efficient and less painful approach to nerve blocks for relief, by identifying optimal injection points to block the median nerve, thereby enhancing palmar hyperhidrosis treatment. METHODS: This study, involving 52 Korean cadaver arms (mean age 73.5 years), measured the location of the median nerve relative to the transverse line at the pisiform level to establish better nerve block injection sites. RESULTS: In between the extensor carpi radialis and palmaris longus, the median nerve was located at an average distance of 47.39 ± 6.43 mm and 29.39 ± 6.43 mm from the transverse line at the pisiform level. DISCUSSION: To minimize discomfort preceding the botulinum neurotoxin injection, we recommend the optimal injection site for local anesthesia to be located 4 cm distal to the transverse line of the pisiform, within the tendons of the palmaris longus and flexor carpi radialis muscles.

Inhibitory Effects of Polyphenol- and Flavonoid-Enriched Rice Seed Extract on Melanogenesis in Melan-a Cells via MAPK Signaling-Mediated MITF Downregulation.

Melanin production is an important process that prevents the host skin from harmful ultraviolet radiation; however, an overproduction of melanin results in skin diseases. In the present study, we determined the antioxidative and anti-melanogenic activities of polyphenol- and flavonoid-enriched rice seed extracts in melan-a cells. The polyphenol and flavonoid content of Hopum (HP) and Sebok (SB) rice seed extracts was measured. The antioxidant capacity was determined using the ABTS radical scavenging method. SB contained high amounts of polyphenols and flavonoids, which significantly increased antioxidative activity compared with HP. Various concentrations of these extracts were evaluated in a cytotoxicity using melan-a cells. At 100 µg/mL, there was no significant difference for all treatments compared with untreated cells. Therefore, 100 µg/mL was selected as a concentration for the further experiments. SB significantly suppressed the phosphorylation/activation of p-38 MAPK, increased the expression of phosphorylated ERK 1/2 and Akt, and downregulated the microphthalmia-associated transcription factor (MITF). This resulted in decreased levels of tyrosinase and tyrosinase-related protein-1 and -2. These results indicate the potential of polyphenol- and flavonoid-enriched rice seed as a treatment for hyperpigmentation.

The effects of music therapy on labor pain, childbirth experience, and self-esteem during epidural labor analgesia in primiparas: a non-randomized experimental study.

PURPOSE: This non-randomized study was performed to evaluate the effects of music therapy on labor pain, the childbirth experience, and self-esteem in women during vaginal delivery. METHODS: In total, 136 primiparous women over 37 weeks of gestation receiving epidural analgesia during vaginal delivery were recruited via convenience sampling. To minimize diffusion effects, data from the control group (n=71) were collected first (April 2020 to March 2021), followed by data from the music group (n=65; April 2021 to May 2022). Participants in the music group listened to classical music during labor, while the control group was offered usual care (no music). Labor pain was measured using a numeric rating scale (NRS), and self-esteem and childbirth experience were collected using self-report questionnaires. Data were analyzed using the independent t-test, chi-square test and Cronbach's α coefficients. RESULTS: The overall pain level (NRS) at baseline was 0 in both groups. Mothers in the music therapy group had lower levels of latent pain (t=1.95, p=.005), active pain (t=3.69, p<.001) and transition-phase pain (t=7.07, p<.001) than the control group. A significant difference was observed between the two groups, and the music therapy group expressed more positive perceptions of the childbirth experience (t=-1.36, p=.018). For self-esteem, the experimental group's score was slightly higher, but without a statistically significant difference from the control group. CONCLUSION: Using music therapy during labor decreased labor pain and improved the childbirth experience. Music therapy can be clinically recommended as a non-pharmacological, safe, and easy method for nursing care in labor. Clinical trail number: KCT008561.

Antidepressant effects of p-coumaric acid isolated from Vaccinium bracteatum leaves extract on chronic restraint stress mouse model and antagonism of serotonin 6 receptor in vitro.

BACKGROUND: Vaccinium bracteatum Thunb. leaves (VBL) are used in traditional herbal medicines to treat various biological diseases. p-coumaric acid (CA), the main active component of VBL, has neuroprotective effects against corticosterone-induced damage in vitro. However, the effects of CA on immobility induced by chronic restraint stress (CRS) in a mouse model and 5-HT receptor activity have not been investigated. HYPOTHESIS/PURPOSE: We investigated the antagonistic effects of VBL, NET-D1602, and the three components of Gαs protein-coupled 5-HT receptors. Additionally, we identified the effects and mechanism of action of CA, the active component of NET-D1602, in the CRS-exposed model. METHODS: For in vitro analyses, we used 1321N1 cells stably expressing human 5-HT6 receptors and CHO-K1 expressing human 5-HT4 or 5-HT7 receptors cell lines to study the mechanism of action. For in vivo analyses, CRS-exposed mice were orally administered CA (10, 50, or 100 mg/kg) daily for 21 consecutive days. The effects of CA were analyzed by assessing behavioral changes using a forced swim test (FST), measuring levels of hypothalamic-pituitary-adrenal (HPA) axis-related hormones in ntial therapeutic effects as 5-HT6 receptor antagonists for neurodegenerative diseases and depressioserum, and acetylcholinesterase (AChE), monoamines, including 5-HT, dopamine, and norepinephrine, using enzyme-linked immunosorbent assay kits. The underlying molecular mechanisms of the serotonin transporter (SERT), monoamine oxidase A (MAO-A), and extracellular signal-regulated kinase (ERK)/protein kinase B (Akt)/mTORC1 signaling were detected using western blotting. RESULTS: CA was confirmed to be an active component in the antagonistic effects of NET-D1602 on 5-HT6 receptor activity through decreases in cAMP and ERK1/2 phosphorylation. Moreover, CRS-exposed mice treated with CA showed a significantly reduced immobility time in the FST. CA also significantly decreased corticosterone, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) levels. CA enhanced 5-HT, dopamine, and norepinephrine levels in the hippocampus (HC) and prefrontal cortex (PFC) but decreased MAO-A and SERT protein levels. Similarly, CA significantly upregulated the ERK, Ca2+/calmodulin-dependent protein kinase II (CaMKII), Akt/mTOR/p70S6K/S6 signaling pathways in both HC and the PFC. CONCLUSION: CA contained in NET-D1602 may play the antidepressant effects against CRS-induced depression-like mechanism and the selective antagonist effect of 5-HT6 receptor.

Comparison of clinical outcomes between intense pulsed light therapy using two different filters in meibomian gland dysfunction: prospective randomized study.

Our study compared treatment efficacy between cut-off and notch filters in intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD) through a prospective, randomized paired-eye trial. Additionally, the efficacy of IPL treatment alone was investigated by restricting other conventional treatments. One eye was randomly selected for an acne filter and the other for a 590-nm filter. Identical four regimens of IPL treatments were administered. The tear break-up time (TBUT), Oxford scale, Sjögren's International Clinical Collaborative Alliance (SICCA) staining score, tear matrix metalloproteinase-9 (MMP-9) expression, tear osmolarity, and Ocular Surface Disease Index (OSDI) questionnaires were evaluated before and after IPL. Meibomian gland (MG) parameters were measured. When combining the results from both filters, the TBUT, SICCA staining score, OSDI score, and upper and lower lid meibum expressibility were improved after IPL. No significant differences were found between the two filters in the TBUT, Oxford scale, SICCA staining score, MMP-9 expression, tear osmolarity, and MG parameters. Although not significant, the acne filter showed better treatment efficacy than that in the 590-nm filter. IPL alone is efficacious in terms of ocular surface parameters, MG function, and subjective symptoms. Regarding filter selection, both acne and 590-nm filters are promising options for MGD treatment.

Comparison of full-endoscopic and tubular-based microscopic decompression in patients with lumbar spinal stenosis: a randomized controlled trial.

PURPOSE: We aimed to demonstrate non-inferiority in terms of functional outcomes in patients with lumbar spinal stenosis who underwent full-endoscopic decompression compared with tubular-based microscopic decompression. METHODS: This prospective, randomized controlled, non-inferiority trial included 60 patients with single-level lumbar spinal stenosis who required decompression surgery. The patients were randomly assigned in a 1:1 ratio to the full-endoscopic group (FE group) or the tubular-based microscopic group (TM group). Based on intention-to-treat analysis, the primary outcome was the Oswestry Disability Index score at 24 months postoperative. The secondary outcomes included the visual analog scale (VAS) score for back and leg pain, European Quality of Life-5 Dimensions (EQ-5D) score, walking time, and patient satisfaction rate according to the modified MacNab criteria. Surgery-related outcomes were also analyzed. RESULTS: Of the total patients, 92% (n = 55) completed a 24-month follow-up. The primary outcomes were comparable between the two groups (p = 0.748). However, the FE group showed a statistically significant improvement in the mean VAS score for back pain at day 1 and at 6, 12, and 24 months after surgery (p < 0.05). No significant difference was observed in the VAS score for leg pain, EQ-5D score, or walking time (p > 0.05). Regarding the modified MacNab criteria, 86.7% of patients in the FE group and 83.3% in the TM group had excellent or good results at 24 months after surgery (p = 0.261). Despite the similar results in surgery-related outcomes, including operative time, radiation exposure, revision rate, and complication rate, between the two groups (p > 0.05), less blood loss and shorter length of hospital stay were observed in the FE group (p ≤ 0.001 and 0.011, respectively). CONCLUSION: This study suggests that full-endoscopic decompression is an alternative treatment for patients with lumbar spinal stenosis because it provides non-inferior clinical efficacy and safety compared with tubular-based microscopic surgery. In addition, it offers advantages in terms of less invasive surgery. Trial registration number (TRN): TCTR20191217001.