Therapeutic Potential of Traditional Oriental Medicines in Targeting Tau Pathology: Insights from Cell-free and Cell-based Screening.

BACKGROUND: Traditional Oriental Medicines (TOMs) formulated using a variety of medicinal plants have a low risk of side effects. In previous studies, five TOMs, namely Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, Palmijihwanghwan, and Jowiseungchungtang have been commonly used to treat patients with Alzheimer's disease. However, only a few studies have investigated the effects of these five TOMs on tau pathology. OBJECTIVE: This study aimed to examine the effect of five TOMs on various tau pathologies, including post-translational modifications, aggregation and deposition, tau-induced neurotoxicity, and tau-induced neuroinflammation. METHODS: Immunocytochemistry was used to investigate the hyperphosphorylation of tau induced by okadaic acid. In addition, the thioflavin T assay was used to assess the effects of the TOMs on the inhibition of tau K18 aggregation and the dissociation of tau K18 aggregates. Moreover, a water-soluble tetrazolium-1 assay and a quantitative reverse transcription polymerase chain reaction were used to evaluate the effects of the TOMs on tau-induced neurotoxicity and inflammatory cytokines in HT22 and BV2 cells, respectively. RESULTS: The five TOMs investigated in this study significantly reduced okadaic acid-induced tau hyperphosphorylation. Hwanglyeonhaedoktang inhibited the aggregation of tau and promoted the dissociation of tau aggregates. Dangguijakyaksan and Hwanglyeonhaedoktang attenuated tau-induced neurotoxicity in HT22 cells. In addition, Dangguijakyaksan, Hwanglyeonhaedoktang, Ukgansan, and Palmijihwanghwan reduced tauinduced pro-inflammatory cytokine levels in BV2 cells. CONCLUSION: Our results suggest that five TOMs are potential therapeutic candidates for tau pathology. In particular, Hwanglyeonhaedoktang showed the greatest efficacy among the five TOMs in cell-free and cell-based screening approaches. These findings suggest that Hwanglyeonhaedoktang is suitable for treating AD patients with tau pathology.

Effects of Perilla frutescens Var. Acuta in Busulfan-Induced Spermatogenesis Dysfunction Mouse Model.

PURPOSE: The leaves of Perilla frutescens var. acuta (PFA) are generally reported to have antioxidant, anti-allergic, anti-inflammatory, and antitumor effects and commonly used as a traditional medicine in East Asia. This study aimed to investigate the protective effect and antioxidant activity of PFA on busulfan-induced testicular dysfunction, histological damage, oxidative stress (OS), sperm quality, and hormone levels using a mouse model. MATERIALS AND METHODS: C57BL/6 male mice were divided into four groups: control, busulfan-only treated, and varying concentrations of PFA (100 and 200 mg/kg) with busulfan. In the busulfan group, 40 mg/kg of busulfan was intraperitoneally injected to induce azoospermia. Mice were orally administered PFA for 35 consecutive days after busulfan administration. Samples were collected and assessed for testis/body weight, testicular histopathology, sperm quality, serum hormone levels, and OS to evaluate the effects of PFA treatment on spermatogenesis dysfunction induced by busulfan. RESULTS: The busulfan-induced testicular dysfunction model showed reduced testis weight, adverse histological changes, significantly decreased sex hormones and sperm quality, and attenuated OS. These results indicate that PFA treatment significantly increased testis weight, testis/body weight, epididymal sperm count, motility, and testosterone level compared with busulfan alone. PFA treatment also attenuated the busulfan-induced histological changes. Furthermore, compared with mice treated with busulfan alone, PFA supplementation upregulated the testicular mRNA expression of the antioxidant enzymes superoxide dismutase 1 (Sod1) and glutathione peroxidase 1 (Gpx1), with a decrease in malondialdehyde (MDA) production and an increase in SOD and GPx activities. CONCLUSIONS: This study shows that PFA exerts a protective effect against testicular damage by attenuating OS induced by busulfan. Our results suggest that PFA is a potentially relevant drug used to decrease the side effects induced by busulfan on testicular function and sperm during cancer chemotherapy.

Korean red ginseng polysaccharide as a potential therapeutic agent targeting tau pathology in Alzheimer's disease.

Tau is a microtubule-associated protein that plays a critical role in the stabilization and modulation of neuronal axons. Tau pathology is stronger associated with cognitive decline in patients with Alzheimer's disease (AD) than amyloid beta (Aß) pathology. Hence, tau targeting is a promising approach for the treatment of AD. Previous studies have demonstrated that the non-saponin fraction with rich polysaccharide (NFP) from Korean red ginseng (KRG) can modulate tau aggregation and exert a therapeutic effect on AD. Therefore, we investigated the efficacy of NFP isolated from KRG on tau pathology in experimental models of AD. Our results showed that NFP from KRG ameliorated deposition and hyperphosphorylation of tau in the brain of 3xTg mice. Moreover, NFP from KRG modulated the aggregation and dissociation of tau K18 in vitro. We demonstrated the alleviatory effects of NFP from KRG on hyperphosphorylated tau and tau kinase in okadaic acid-treated HT22 cells. Furthermore, NFP from KRG mitigated Aß deposition, neurodegeneration, and neuroinflammation in 3xTg mice. We revealed the neuroprotective effects of NFP from KRG on tau-induced neuronal loss in HT22 cells. Our results indicate that NFP extracted from KRG is a novel therapeutic agent for the treatment of AD associated with tau pathology.

Evolution of the Araliaceae family involved rapid diversification of the Asian Palmate group and Hydrocotyle specific mutational pressure.

The Araliaceae contain many valuable species in medicinal and industrial aspects. We performed intensive phylogenomics using the plastid genome (plastome) and 45S nuclear ribosomal DNA sequences. A total of 66 plastome sequences were used, 13 of which were newly assembled in this study, 12 from new sequences, and one from existing data. While Araliaceae plastomes showed conserved genome structure, phylogenetic reconstructions based on four different plastome datasets revealed phylogenetic discordance within the Asian Palmate group. The divergence time estimation revealed that splits in two Araliaceae subfamilies and the clades exhibiting phylogenetic discordances in the Asian Palmate group occurred at two climatic optima, suggesting that global warming events triggered species divergence, particularly the rapid diversification of the Asian Palmate group during the Middle Miocene. Nucleotide substitution analyses indicated that the Hydrocotyloideae plastomes have undergone accelerated AT-biased mutations (C-to-T transitions) compared with the Aralioideae plastomes, and the acceleration may occur in their mitochondrial and nuclear genomes as well. This implies that members of the genus Hydrocotyle, the only aquatic plants in the Araliaceae, have experienced a distinct evolutionary history from the other species. We also discussed the intercontinental disjunction in the genus Panax and proposed a hypothesis to complement the previously proposed hypothesis. Our results provide the evolutionary trajectory of Araliaceae and advance our current understanding of the evolution of Araliaceae species.

Root Extract of Trichosanthes kirilowii Suppresses Metastatic Activity of EGFR TKI-Resistant Human Lung Cancer Cells by Inhibiting Src-Mediated EMT.

The roots of Trichosanthes kirilowii (TK) have been used in traditional oriental medicine for the treatment of respiratory diseases. In this study, we investigated whether an ethanolic root extract of TK (ETK) can regulate the metastatic potency of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant human lung cancer cells. The relative migration and invasion abilities of erlotinib-resistant PC9 (PC9/ER) and gefitinib-resistant PC9 (PC9/GR) cells were higher than those of parental PC9 cells. Mesenchymal markers were overexpressed, whereas epithelial markers were downregulated in resistant cells, suggesting that resistant cells acquired the EMT phenotype. ETK reduced migration and invasion of resistant cells. The expression levels of N-cadherin and Twist were downregulated, whereas Claudin-1 was upregulated by ETK, demonstrating that ETK suppresses EMT. As a molecular mechanism, Src was dephosphorylated by ETK. The anti-metastatic effect of ETK was reduced by transfecting PC9/ER cells with a constitutively active form of c-Src. Dasatinib downregulated N-cadherin, Twist, and vimentin, suggesting that Src regulates EMT in resistant cells. Notably, CuB played a key role in mediating the anti-metastatic activity of ETK. Collectively, our results demonstrate that ETK can attenuate the metastatic ability of EGFR-TKI-resistant lung cancer cells by inhibiting Src-mediated EMT.

Enhancing viability and angiogenic efficacy of mesenchymal stem cells via HSP90α and HSP27 regulation based on ROS stimulation for wound healing.

Light-based therapy has been reported as a potential preconditioning strategy to induce intracellular reactive oxygen species (ROS) signaling and improve the angiogenic properties of various types of cells. However, bio-stimulation mechanisms of light therapy in terms of ROS-heat shock proteins (HSPs) mediated anti-apoptotic and angiogenic pathways in human adult stem cells have not been fully delineated yet. Commonly used light sources such as light-emitting diode (LED) and laser are accompanied by drawbacks, such as phototoxicity, thermal damage, and excessive ROS induction, so the role and clinical implications of light-induced HSPs need to be investigated using a heat-independent light source. Here, we introduced organic LED (OLED) at 610 nm wavelength as a new light source to prevent thermal effects from interfering with the expression of HSPs. Our results showed that light therapy using OLED significantly upregulated anti-apoptotic and angiogenic factors in human bone marrow mesenchymal stem cells (hMSCs) at both gene and protein levels via the activation of HSP90α and HSP27, which were stimulated by ROS. In a mouse wound-closing model, rapid recovery and improved re-epithelization were observed in the light-treated hMSCs transplant group. This study demonstrates that the upregulation of Akt (protein kinase B)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, caused by HSP90α and HSP27 expression, is the mechanism behind the anti-apoptotic and angiogenic effects of OLED treatment on stem cells.

How Service Employees' Mindfulness Links to Task Performance through Psychological Resilience, Deep Acting, and Customer-Oriented Behavior.

This study investigates the specific pathways through which mindfulness influences task performance, focusing on the sequential mediating roles of psychological resilience, customer-oriented behavior, and deep acting. Structural equation modeling is used to analyze data collected from 359 employees in the service industry in Korea. The results confirm that mindfulness has a significant direct and indirect relationship with task performance. Improved resilience through mindfulness can be the basis for fostering customer-oriented behavior and deep acting, which sequentially enhance task performance. This study provides a comprehensive understanding of how mindfulness leads to improvements in task performance and highlights the significance of mindfulness for both customers and service employees. It also expands the existing knowledge of mindfulness by empirically integrating resilience, customer-oriented behavior, and deep acting, which have not been extensively studied in mindfulness research. The findings have practical implications from a managerial perspective, emphasizing the importance of mindfulness resources in the workplace.

DESIGNER fraction concept unmasks minor bioactive constituents in red clover (Trifolium pratense L.).

In botanical extracts, highly abundant constituents can mask or dilute the effects of other, and often, more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredients to Generate Normalized Extract Resources. The present study applied this concept to clinical Red Clover Extract (RCE) and combined phytochemical and biological methodology to help rationalize the utility of RCE supplements for symptom management in postmenopausal women. Previous work has demonstrated that RCE reduces estrogen detoxification pathways in breast cancer cells (MCF-7) and, thus, may serve to negatively affect estrogen metabolism-induced chemical carcinogenesis. Clinical RCE contains ca. 30% of biochanin A and formononetin, which potentially mask activities of less abundant compounds. These two isoflavonoids are aryl hydrocarbon receptor (AhR) agonists that activate P450 1A1, responsible for estrogen detoxification, and P450 1B1, producing genotoxic estrogen metabolites in female breast cells. Clinical RCE also contains the potent phytoestrogen, genistein, that downregulates P450 1A1, thereby reducing estrogen detoxification. To identify less abundant bioactive constituents, countercurrent separation (CCS) of a clinical RCE yielded selective lipophilic to hydrophilic metabolites in six enriched DESIGNER fractions (DFs 01-06). Unlike solid-phase chromatography, CCS prevented any potential loss of minor constituents or residual complexity (RC) and enabled the polarity-based enrichment of certain constituents. Systematic analysis of estrogen detoxification pathways (ERα-degradation, AhR activation, CYP1A1/CYP1B1 induction and activity) of the DFs uncovered masked bioactivity of minor/less abundant constituents including irilone. These data will allow the optimization of RCE with respect to estrogen detoxification properties. The DFs revealed distinct biological activities between less abundant bioactives. The present results can inspire future carefully designed extracts with phytochemical profiles that are optimized to increase in estrogen detoxification pathways and, thereby, promote resilience in women with high-risk for breast cancer. The DESIGNER approach helps to establish links between complex chemical makeup, botanical safety and possible efficacy parameters, yields candidate DFs for (pre)clinical studies, and reveals the contribution of minor phytoconstituents to the overall safety and bioactivity of botanicals, such as resilience promoting activities relevant to women's health.

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.

Enzyme-derived deer velvet extract activate the immune response in cyclophosphamide-induced immunosuppressive mice.

Deer velvet (DV) is an oriental traditional medicine used to treat various diseases. The present study examined the effect of flavourzyme-derived DV extract (YC-1101) on macrophages and an immunosuppressed mouse model. YC-1101 induced activation of macrophages as measured by nitric oxide production, cell proliferation, and cytokine release via concentration-dependent phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and AKT, and nuclear translocation of p65 in macrophages. In addition, oral YC-1101 administration significantly increased splenocyte proliferation and natural killer cell activity in the immunosuppressed mouse model. Moreover, the levels of immune-related cytokines such as tumor necrotic factor-α, interferon-γ, and interleukin-2 were significantly increased by YC-1101 treatment comparable to the control group. Thus, these results suggest that YC-1101 is an efficient natural ingredient that has an immune-enhancing effect, and it might be a potential functional food for improving immunity.

Effects of acupuncture on earthquake survivors with major psychiatric disorders and related symptoms: A scoping review of clinical studies.

BACKGROUND: This scoping review aimed to determine the current research status of acupuncture for major psychiatric disorder (MPD) in earthquake survivors. METHOD: We followed the scoping review process described previously. A literature search on 14 electronic databases was conducted from inception to November 29, 2022. Data from the included studies were collected and descriptively analyzed to address our research question. Extracted data were collated, synthesized, and summarized the according to the analytical framework of a scoping review. RESULT: This scoping review included nine clinical studies: four randomized controlled trials (RCTs) and five before-after studies. The most frequent MPD type among the included acupuncture studies was posttraumatic stress disorder (PTSD; 6/9, 66.67%). The most frequent acupuncture type was scalp electro-acupuncture (4/9, 44.44%), followed by manual acupuncture and ear acupressure/ear acupuncture (3/9, 33.33%). Studies using scalp electro-acupuncture all used common acupoints, including GB20, GV20, GV24, and EX-HN1. In general, the treatment period lasted between 4 and 12 weeks. Validated assessment tools for PTSD severity and accompanying symptoms were used for patients with PTSD, while the corresponding evaluation tools were used for patients with other diagnoses or clinical symptoms. Acupuncture-related adverse events were generally mild and temporary, such as mild bleeding and hematoma, and syncope was a rare but potentially serious adverse event (1/48 patients and 1/864 sessions over a treatment period of 4 weeks). CONCLUSION: Acupuncture studies for MPD after an earthquake mainly focused on PTSD. RCTs accounted for around half of the included studies. Scalp electro-acupuncture was the most common acupuncture type, and EX-HN1 and GV24 were the most important acupoints in the acupuncture procedures for MPD. The included studies mostly used validated symptom assessment tools, though some did not. Clinical studies in this field need to be further expanded regardless of the study type. PROTOCOL REGISTRATION: https://osf.io/wfru7/.

Assessment of the Antioxidant and Anti-inflammatory Properties of Aqueous Extract of Rosa sempervirens Leaves.

The antioxidant and anti-inflammatory properties of an aqueous natural extract obtained from Rosa sempervirens leaves were assessed. The ability of the extract to scavenge DPPH, •OH, and H2O2 radicals, chelate ferrous ions, reduce ferric ions, and protect ß-carotene-linoleic acid in emulsion from peroxidation was investigated in vitro. Furthermore, the anti-inflammatory activity of the extract was evaluated by measuring the stability of the membrane of human red blood cells against different hypotonic concentrations of NaCl and heat, as well as by inhibiting the denaturation of albumin. A high total phenolic content (278.38± 11.07 mg GAE/g) and flavonoid content (34.22± 0.12 mg QE /g) were found in the extract. The extract exhibited significant scavenging activity of DPPH (IC50 6.201 ± 0.126 µg/ ml), •OH (IC50 = 894.57 ± 21.18 µg/ml), and H2O2 (IC50= 107±09.58 µg/ml) radicals, and good antioxidant activity by chelating ferrous ions (IC50 = 2499.086 ± 28.267µg/ml), reducing ferric ions (IC50=141.33±2.34 µg/ml), exhibiting total antioxidant capacity (IC50 465.65 ± 9.71 µg/ml), and protecting ß-carotene-linoleic acid against peroxidation (I% = 90.05 ± 1.65% at 1000µg/ml). R. sempervirens displayed anti-inflammatory activity in aqueous extract by inhibiting heat-induced albumin denaturation and stabilizing the membrane of human red blood cells. It was suggested from the results that R. sempervirens aqueous extract could help prevent oxidative and inflammatory processes due to its good antioxidant and anti-inflammatory properties.

Acupuncture Treatment for Hip Pain: A Systematic Review and Meta-Analysis.

Acupuncture treatment (AT) is an effective treatment for pain relief; however, there are few systematic reviews that have reported on the effectiveness of AT for hip pain. This systematic review aimed to evaluate the efficacy and safety of AT of hip pain. We searched eight databases for randomised controlled trials (RCTs) evaluating the effect of AT on hip pain until August 2022. Twelve RCTs (806 patients) were included: two reported a significant effect of AT compared with that of conventional medicine (CM) alone for hip pain; two reported significant effects of AT + CM compared with that of CM alone in terms of Visual Analogue Scale (VAS); two reported a significant effect of AT + CM compared with that of Sham AT + CM in terms of anaesthetic dosage; two reported a significant effect of AT + CM compared with that of Sham AT + CM in terms of the side effects associated with analgesic use; one study reported a significant effect of AT compared to that of no-treatment. No serious adverse events were reported. Our findings demonstrate the potential of AT in managing hip pain. Given the low quality and small sample sizes of the studies, the evidence supporting AT for hip pain management was weak. Further clinical trials and systematic reviews are required. The protocol of the current study was registered in the PROSPERO International prospective register of systematic reviews (CRD42017079586).

Botulinum neurotoxin injection in the deltoid muscle: application to cosmetic shoulder contouring.

BACKGROUND AND OBJECTIVES: This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. METHODS: The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. RESULTS: The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. CONCLUSION: We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results.

Weight Changes and Unhealthy Weight Control Behaviors Are Associated With Dysmenorrhea in Young Women.

BACKGROUND: This study aimed to evaluate the prevalence of dysmenorrhea and to investigate the effect of weight changes or unhealthy weight control behaviors on dysmenorrhea in young Korean women. METHODS: We used large-scale data of women, aged 14 to 44 years, who participated in the Korean Study of Women's Health-Related Issues. Dysmenorrhea was measured using a visual analog scale and was categorized as none, mild, moderate, and severe according to the severity. Weight changes and unhealthy weight control behaviors (any of the behaviors, fasting/meal skipping, drugs, the use of unapproved dietary supplements, and one-food diets) over the past year were self-reported. We used multinomial logistic regression to investigate the association between weight changes or unhealthy weight control behaviors and dysmenorrhea. RESULTS: Of the 5,829 young women participating in the study, 5,245 (90.0%) participants experienced dysmenorrhea [2,184 (37.5%) had moderate and 1,358 (23.3%) had severe]. After adjusting for confounders, the odds ratios for moderate and severe dysmenorrhea in participants with weight changes ≥ 3 kg (vs. < 3 kg) were 1.19 (95% confidence interval: 1.05-1.35) and 1.25 (95% confidence interval: 1.08-1.45), respectively. The odds ratios in participants with any unhealthy weight control behaviors were 1.22 (95% confidence interval: 1.04-1.42) and 1.41 (95% confidence interval: 1.19-1.67) for those with moderate and severe dysmenorrhea, respectively. CONCLUSION: Weight changes (≥ 3 kg) or unhealthy weight control behaviors are common among young women, which may adversely affect dysmenorrhea. Therefore, attention needs to be paid to excessive weight changes and unhealthy weight control behaviors to improve dysmenorrhea in young women.

Novel Herbal Therapeutic YH23537 Improves Clinical Parameters in Ligature-Induced Periodontal Disease Model in Beagle Dogs.

Currently, available medicine does not satisfy the clinical unmet needs of periodontal disease. Therefore, novel drugs with improved efficacy profiles are needed. We previously demonstrated that YH14642, water extracts of Notoginseng Radix and Rehmanniae Radix Preparata, improved probing depths in double-blind phase II clinical trial. However, it still has hurdles for commercialization due to the low efficiency of active compound extraction. To resolve this issue, we developed YH23537 through process optimization to extract active compounds efficiently while still achieving the chemical profile of YH14642. In this study, we investigated the therapeutic effects of YH23537 compared with YH14642 using a canine model of ligature-induced periodontitis. Human gingival fibroblast (hGF) cells were treated with various concentrations of YH23537 or YH14642 with lipopolysaccharide (LPS) for 24 hr. IL-6 and IL-8 levels in the conditioned media were determined using Luminex. Sixteen 3-year-old male beagle dogs had their teeth scaled and polished using a piezo-type ultrasonic scaler under general anesthesia and brushed once daily for the following 2 weeks. Two weeks after the scaling procedure, the left upper second premolar (PM2), third premolar (PM3), and fourth premolar (PM4) as well as the left lower PM3, PM4, and first molar (M1) were ligated with silk-wire twisted ligatures. The dogs were fed with soft moistened food to induce periodontitis for 8 weeks, and the ligatures were then removed. YH23537 and YH14642 were administered for 4 weeks, and clinical periodontal parameters such as plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BoP) were determined before and 1, 2, 3, and 4 weeks after treatment. YH23537 inhibited IL-6 and IL-8 secretion in a dose-dependent manner in hGF cells stimulated with LPS. The IC50 values for YH23537 were 43 and 54 µg/ml for IL-6 and IL-8, respectively, while the values for YH14642 were 104 and 117 µg/ml, respectively. In the animal study, clinical parameters including GI, PD, CAL, and BoP were significantly increased after 8 weeks of ligature-induced periodontitis. The YH23537 300 and YH23537 900 mg groups had significant improvements in CAL from 1 to 4 weeks after treatment in comparison to the placebo group. GR values in the YH23537 900 mg group were decreased throughout the treatment period. GI values were also reduced significantly after 4-week treatment with 300 and 900 mg of YH23537. YH23537 at 300 mg doses showed comparable efficacy for CAL and GR with 1,000 mg of YH14642. YH23537 showed therapeutic efficacy against periodontitis in dogs, mediated by anti-inflammatory effects. These findings indicate that YH23537 has the potential for further development as a new drug for patients suffering from periodontal disease.

Evaluation of the efficacy and safety of conventional and interlaminar full-endoscopic decompressive laminectomy to treat lumbar spinal stenosis (ENDO-F trial): Protocol for a prospective, randomized, multicenter trial.

Lumbar spinal stenosis is a common spinal degenerative condition. Minimally invasive interlaminar full-endoscopic decompressive laminectomy provides greater patient satisfaction and faster recovery than open decompressive laminectomy. The aim of our randomized controlled trial will be to compare the safety and efficacy of interlaminar full-endoscopic laminectomy and open decompressive laminectomy. Our trial will include 120 participants (60 per group) who will undergo surgical treatment for lumbar spinal stenosis. The primary outcome will be the Oswestry Disability Index measured at 12 months postoperatively. Secondary patient-reported outcomes will include back and radicular leg pain measured via a visual analog scale; the Oswestry Disability Index; the Euro-QOL-5 Dimensions score measured at 2 weeks and at 3, 6, and 12 months postoperatively; and patient satisfaction. The functional measures will include time to return to daily activities postoperatively and walking distance/time. The surgical outcomes will include postoperative drainage, operation time, duration of hospital stay, postoperative creatine kinase (an indicator of muscle injury) level, and postoperative surgical scarring. Magnetic resonance and computed tomography images and simple radiographs will be obtained for all patients. The safety outcomes will include surgery-related complications and adverse effects. All evaluations will be performed by a single assessor at each participating hospital who will be blinded to group allocation. The evaluations will be conducted preoperatively and at 2 weeks and 3, 6, and 12 months postoperatively. The randomized, multicenter design of the trial, blinding, and justification of the sample size will reduce the risk of bias in our trial. The results of the trial will provide data regarding the use of interlaminar full-endoscopic laminectomy as an alternative to open decompressive laminectomy that results in similar surgical findings with less invasiveness. Trial registration: This trial is registered at cris.nih.go.kr. (KCT0006198; protocol version 1; 27 May 2021).

The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age.

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host-microbiome crosstalk in IDA.

Comparative transcriptome and metabolome analyses of four Panax species explore the dynamics of metabolite biosynthesis.

Background: The genus Panax in the Araliaceae family has been used as traditional medicinal plants worldwide and is known to biosynthesize ginsenosides and phytosterols. However, genetic variation between Panax species has influenced their biosynthetic pathways is not fully understood. Methods: Simultaneous analysis of transcriptomes and metabolomes obtained from adventitious roots of two tetraploid species (Panax ginseng and P. quinquefolius) and two diploid species (P. notoginseng and P. vietnamensis) revealed the diversity of their metabolites and related gene expression profiles. Results: The transcriptome analysis showed that 2,3-OXIDOSQUALENE CYCLASEs (OSCs) involved in phytosterol biosynthesis are upregulated in the diploid species, while the expression of OSCs contributing to ginsenoside biosynthesis is higher in the tetraploid species. In agreement with these results, the contents of dammarenediol-type ginsenosides were higher in the tetraploid species relative to the diploid species. Conclusion: These results suggest that a whole-genome duplication event has influenced the triterpene biosynthesis pathway in tetraploid Panax species during their evolution or ecological adaptation. This study provides a basis for further efforts to explore the genetic variation of the Panax genus.

Efficacy and Safety of Maca (Lepidium meyenii) in Patients with Symptoms of Late-Onset Hypogonadism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PURPOSE: To evaluated the efficacy and safety of gelatinized Maca (Lepidium meyenii) for eugonadal patients with late onset hypogonadism symptoms (LOH). MATERIALS AND METHODS: Participants were instructed to receive 1,000 mg of Maca or placebo, two pills at a time, three times per day for 12 weeks before food intake. To evaluate the efficacy of the drug, Aging Males' Symptoms scale (AMS), Androgen Deficiency in the Aging Males (ADAM), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) questionnaires, serologic tests (total testosterone and free testosterone, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride), body weight, and waist circumference were assessed at 4 and 12 weeks after treatment. RESULTS: A total of 80 participants were enrolled and randomly assigned to Maca treated group (n=41) or the placebo group (n=39). AMS, IIEF, and IPSS were significantly (p<0.05) improved in Maca treated group than in the placebo group. ADAM positive rate was also significantly (p<0.0001) decreased in Maca treated group. CONCLUSIONS: Maca may be considered an effective and safe treatment for eugonadal patients with late onset hypogonadism symptoms.