Safety and efficacy of East Asian herbal medicine for iron deficiency anemia in children and adolescents: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of East Asian herbal medicine (HM) for iron deficiency anemia (IDA) in children and adolescents. Methods: Twelve electronic databases were searched in 28 May 2023 for randomized controlled trials (RCTs) evaluating the efficacy of HM in children with IDA. The primary outcome measures for treatment included blood hemoglobin and serum ferritin levels, whereas the secondary outcomes included the total effective rate (TER), incidence of adverse events (AEs), average healing time, and hematologic indicators related to IDA. Meta-analysis was performed using Review Manager 5.4 and R studio 4.3 software, and subgroup analyses were performed according to the different groups (type of intervention and duration of treatment). The effect size measures used were the risk ratio, mean difference, and standardized mean difference with 95% confidence intervals. The risk of bias was assessed using a revised Cochrane risk of bias tool for randomized trials, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation tools. Results: The meta-analysis included 28 studies. Five studies compared the efficacy of HM alone with that of oral iron alone, whereas 23 compared the efficacy of a combination of HM and oral iron with that of oral iron alone. The meta-analysis revealed that the HM treatment group showed significant improvements in all outcome measures compared to those observed in the oral iron group. Moreover, HM significantly reduced the incidence of gastrointestinal AE, compared to that associated with oral iron. Among the 28 studies, the most commonly used HM prescription was Xingpi Yanger Granules, and the most commonly used botanical drug was Astragali Radix, followed by Atractylodis Rhizoma Alba and Angelicae Sinensis Radix. Conclusion: This meta-analysis identified evidence of the efficacy and safety of HM in children with IDA. Compared to conventional oral iron therapy, HM improved IDA-related blood markers and TER, with fewer AEs and shorter mean healing times. However, further well-designed, large-scale clinical trials are necessary to strengthen the evidence of the efficacy and safety of botanical drugs. Systematic Review Registration: PROSPERO 2022 CRD42022334670. (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022334670).

Research status of east Asian traditional medicine treatment for chronic cough: A scoping review.

BACKGROUND: When patients continue to experience cough despite conventional treatment, East Asian traditional medicine (EATM) including herbal medicine and/or acupuncture has been frequently used. Previous systematic reviews of EATM treatment for chronic cough have been conducted mainly on herbal medicine, targeting patients with conditions that cause cough. In clinical practice, EATM interventions are not limited to herbal medicine, and considering that chronic cough is often caused by two or more conditions or unspecific causes, a comprehensive investigation is clinically relevant. We examined the current research status of EATM for chronic cough. METHODS: Based on Arksey and O'Malley's scoping review methodological framework, a total of six English, Chinese, Korean, and Japanese electronic databases were searched on August 2022. Any clinical studies on EATM targeting chronic cough patients (regardless of their cause) were included. RESULTS: Among 474 included studies, the study designs were mainly randomized controlled trials (72.4%), and the population was evenly distributed between children and adults. The cause of cough was not reported in most studies (56.1%). The common cause of cough was upper airway cough syndrome and post-respiratory infection (9.5%, each), followed by mixed cause (7.6%), nonspecific cause (5.9%), and gastroesophageal reflux disease (4.0%). EATM was conducted for a mean of 19.1 days, and herbal medicine was the most common (80.6%). Conventional medication was frequently used as a control (81.2%). For outcomes, the total effective rate was the most frequently utilized (94.3%), followed by cough severity (53.8%). EATM treatment showed positive outcomes in most studies. CONCLUSIONS: In future EATM studies, it is necessary to either specify the cause of chronic cough or to report that the study was targeting nonspecific chronic cough. In addition, high-quality studies assessing the efficacy of EATM with placebo control treatment should be conducted, using validated evaluation tools.

Water quality seasonal variation assessment of the Gongji and Yaksa streams, Chuncheon, South Korea.

Gongji Stream flows into Lake Uiam, a potable water source for the capital region of Chuncheon, South Korea. Algal blooms often occur downstream of the Gongji stream in combination with drastic flow rate variations. Downstream water quality may also be affected by Yaksa stream. Yaksa stream joins Gongji stream before it reaches Uiam Lake, which is a drinking water source for the city. Limited data exists on the Yaksa stream water quality. Therefore, water quality parameters (pH, electrical conductivity (EC), biological oxygen demand (BOD), total nitrogen (T-N), total phosphorous (T-P), chlorophyll-a (Chl-a), total coliforms, and Escherichia coli (E. coli) concentration) were sampled from Gongji (at sites GJ1 and GJ2) and Yaksa (at sites YS1 and YS2) streams from May to September, 2022. The results revealed the overall water quality of both streams was good (BOD = 0.27-3.66 mg/L; TP = 0.003-0.074 mg/L), except on August 3. On August 3, the concentrations of BOD, TP, total coliforms, and E. coli were elevated, with the highest concentrations in samples from GJ2. The recent heavy rainfall potentially caused sewage inflows near GJ2. The correlation analysis revealed positive linear relationships in the 1-day cumulative precipitation with BOD (r = 0.503), total coliforms (r = 0.547), and TP (r = 0.814). The Yaksa stream may be an Anabaena sp. source, which contaminated samples from YS1, YS2, and GJ2, but not at GJ1 (upstream of the tributary).

Position Statement: Atypical Femoral Fracture from the Korean Society for Bone and Mineral Research in 2023.

As the aging population increases, the number of patients with osteoporosis is gradually rising. Osteoporosis is a metabolic bone disease characterized by low bone mass and the microarchitectural deterioration of bone tissue, resulting in reduced bone strength and an increased risk of low-energy or fragility fractures. Thus, the use of anti-resorptive agents, such as bisphosphonates (BPs), to prevent osteoporotic fractures is growing annually. BPs are effective in reducing hip and other fractures. However, the longer a patient takes BPs, the higher the risk of an atypical femoral fracture (AFF). The exact mechanism by which long-term BP use affects the development of AFFs has not yet been clarified. However, several theories have been suggested to explain the pathogenesis of AFFs, such as suppressed bone remodeling, impaired bone healing, altered bone quality, and femoral morphology. The management of AFFs requires both medical and surgical approaches. BPs therapy should be discontinued immediately, and calcium and vitamin D levels should be evaluated and supplemented if insufficient. Teriparatide can be used for AFFs. Intramedullary nailing is the primary treatment for complete AFFs, and prophylactic femoral nailing is recommended if signs of an impending fracture are detected.

Gleditsiae fructus regulates osteoclastogenesis by inhibiting the c­Fos/NFATc1 pathway and alleviating bone loss in an ovariectomy model.

Medical and economic developments have allowed the human lifespan to extend and, as a result, the elderly population has increased worldwide. Osteoporosis is a common geriatric disease that has no symptoms and even a small impact can cause fractures in patients, leading to a serious deterioration in the quality of life. Osteoporosis treatment typically involves bisphosphonates and selective estrogen receptor modulators. However, these treatments are known to cause severe side effects, such as mandibular osteonecrosis and breast cancer, if used for an extended period of time. Therefore, it is essential to develop therapeutic agents from natural products that have fewer side effects. Gleditsiae fructus (GF) is a dried or immature fruit of Gleditsia sinensis Lam. and is composed of various triterpenoid saponins. The anti­inflammatory effect of GF has been confirmed in various diseases, and since the anti­inflammatory effect plays a major role in inhibiting osteoclast differentiation, GF was expected to be effective in osteoclast differentiation and menopausal osteoporosis; however, to the best of our knowledge, it has not yet been studied. Therefore, the present study was designed to examine the effect of GF on osteoclastogenesis and to investigate the mechanism underlying inhibition of osteoclast differentiation. The effects of GF on osteoclastogenesis were determined in vitro by tartrate­resistant acid phosphatase (TRAP) staining, pit formation assays, filamentous actin (F­actin) ring formation assays, western blotting and reverse transcription­quantitative PCR analyses. Furthermore, the administration of GF to an animal model exhibiting menopausal osteoporosis allowed for the analysis of alterations in the bone microstructure of the femur using micro­CT. Additionally, assessments of femoral tissue and serum were conducted. The present study revealed that the administration of GF resulted in a reduction in osteoclast levels, F­actin rings, TRAP activity and pit area. Furthermore, GF showed a dose­dependent suppression of nuclear factor of activated T­cells cytoplasmic, c­Fos and other osteoclastogenesis­related markers.

Nutrition Therapy for Patients With Traumatic Brain Injury: A Narrative Review.

Traumatic brain injury (TBI) is a global health and socio-economic problem, resulting in significant disability and mortality. Malnutrition is common in TBI patients and is associated with increased vulnerability to infection, higher morbidity and mortality rates, as well as longer stays in the intensive care unit and hospital. Following TBI, various pathophysiological mechanisms, such as hypermetabolism and hypercatabolism, affect patient outcomes. It is crucial to provide adequate nutrition therapy to prevent secondary brain damage and promote optimal recovery. This review includes a literature review and discusses the challenges encountered in clinical practice regarding nutrition in TBI patients. The focus is on determining energy requirements, timing and methods of nutrition delivery, promoting enteral tolerance, providing enteral nutrition to patients receiving vasopressors, and implementing trophic enteral nutrition. Enhancing our understanding of the current evidence regarding appropriate nutrition practices will contribute to improving overall outcomes for TBI patients.

Survey of Clinical Practice Patterns of Korean Medicine Doctors for Anorexia in Children: A Preliminary Study for Clinical Practice Guidelines.

Parents often have concerns regarding anorexia in their children and visiting medical institutions for the intervention of it. This study aimed to investigate the clinical practice patterns of Korean medicine doctors (KMDs) for anorexia in children using a web-based survey. A link to the questionnaire was sent via email to all KMDs that were affiliated with the Association of Korean Medicine. The questionnaire covered items on the sociodemographic characteristics and clinical characteristics related to Korean medicine (KM), such as diagnosis, treatment, awareness, safety, and effectiveness. Of 23,910 KMDs, 384 agreed to participate and complete the questionnaire. Anorexia in children was diagnosed mainly by clinical features (36.4%) and the pattern identification (PI) theory of 'Qi, Blood, Fluid, Humor, and Organ system diagnoses' (32.8%). The most frequently used PIs was 'spleen-stomach qi deficiency' (38.6%), which was followed by 'spleen failure in transportation' (23.3%), 'stomach yin deficiency' (15.5%), and 'liver depression' (14.2%). Herbal medicine (38.1%) was the primary KM treatment for anorexia, and the names of the most frequently prescribed herbal decoctions were Sogunjung-tang (16.5%), Hyangsayukgunja-tang (15.9%), and Bojungikgi-tang (13.9%). This study provides information on the existing clinical practice patterns of KMDs for anorexia in children. Based on this survey, the clinical practice guidelines will be developed.

Changes in cesarean section rate before and after the end of the Korean Value Incentive Program.

BACKGROUND: The Korean government implemented a value incentive program providing incentives to providers based on C-section rates, with the rates being publicized. The program ended in 2014 after the administration decided that the effects of the incentive program were limited. In this report, we analyzed changes in C-section rates with the value incentive program. METHODS: The analysis used claim data from Korea's National Health Insurance. The study period (2011-2016) was divided into two phases: before and after the program. This study included 95 providers that were tertiary or general hospitals having more than 200 deliveries per year during the study period. The dependent variable was the risk-adjusted C-section rate. Independent variables included time and hospital characteristics such as hospital type, district, and ownership. Interrupted time series analysis was performed to analyze the data. RESULTS: Our results showed that risk-adjusted C-section rates increased immediately after the end of the incentive program for C-sections. The immediate effect of intervention, a change of 1.73% (P < .05), was statistically significant, as was the trend after intervention, at 0.21% (P < .0001). The slope showed an increase after the intervention to 0.25% per medical institution, which was contrary to the trend of the preintervention decline (negative slope). CONCLUSION: Risk-adjusted C-section rates increased immediately after the discontinuation of a value incentive program. Tertiary hospitals showed greater increases in C-section rates than general hospitals after the intervention.

Fine-Tuning BERT Models to Classify Misinformation on Garlic and COVID-19 on Twitter.

Garlic-related misinformation is prevalent whenever a virus outbreak occurs. With the outbreak of COVID-19, garlic-related misinformation is spreading through social media, including Twitter. Bidirectional Encoder Representations from Transformers (BERT) can be used to classify misinformation from a vast number of tweets. This study aimed to apply the BERT model for classifying misinformation on garlic and COVID-19 on Twitter, using 5929 original tweets mentioning garlic and COVID-19 (4151 for fine-tuning, 1778 for test). Tweets were manually labeled as 'misinformation' and 'other.' We fine-tuned five BERT models (BERTBASE, BERTLARGE, BERTweet-base, BERTweet-COVID-19, and BERTweet-large) using a general COVID-19 rumor dataset or a garlic-specific dataset. Accuracy and F1 score were calculated to evaluate the performance of the models. The BERT models fine-tuned with the COVID-19 rumor dataset showed poor performance, with maximum accuracy of 0.647. BERT models fine-tuned with the garlic-specific dataset showed better performance. BERTweet models achieved accuracy of 0.897-0.911, while BERTBASE and BERTLARGE achieved accuracy of 0.887-0.897. BERTweet-large showed the best performance with maximum accuracy of 0.911 and an F1 score of 0.894. Thus, BERT models showed good performance in classifying misinformation. The results of our study will help detect misinformation related to garlic and COVID-19 on Twitter.

Dendrobium nobile Lindley Administration Attenuates Atopic Dermatitis-like Lesions by Modulating Immune Cells.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly affect daily life by causing sleep disturbance due to extreme itching. In addition, if the symptoms of AD are severe, it can cause mental disorders such as ADHD and suicidal ideation. Corticosteroid preparations used for general treatment have good effects, but their use is limited due to side effects. Therefore, it is essential to minimize the side effects and study effective treatment methods. Dendrobium nobile Lindley (DNL) has been widely used for various diseases, but to the best of our knowledge, its effect on AD has not yet been proven. In this study, the inhibitory effect of DNL on AD was confirmed in a DNCB-induced Balb/c mouse. In addition, the inhibitory efficacy of inflammatory cytokines in TNF-α/IFN-γ-induced HaCaT cells and PMACI-induced HMC-1 cells was confirmed. The results demonstrated that DNL decreased IgE, IL-6, IL-4, scratching behavior, SCORAD index, infiltration of mast cells and eosinophils and decreased the thickness of the skin. Additionally, DNL inhibited the expression of cytokines and inhibited the MAPK and NF-κB signaling pathways. This suggests that DNL inhibits cytokine expression, protein signaling pathway, and immune cells, thereby improving AD symptoms in mice.

Triangulation supports agricultural spread of the Transeurasian languages.

The origin and early dispersal of speakers of Transeurasian languages-that is, Japanese, Korean, Tungusic, Mongolic and Turkic-is among the most disputed issues of Eurasian population history1-3. A key problem is the relationship between linguistic dispersals, agricultural expansions and population movements4,5. Here we address this question by 'triangulating' genetics, archaeology and linguistics in a unified perspective. We report wide-ranging datasets from these disciplines, including a comprehensive Transeurasian agropastoral and basic vocabulary; an archaeological database of 255 Neolithic-Bronze Age sites from Northeast Asia; and a collection of ancient genomes from Korea, the Ryukyu islands and early cereal farmers in Japan, complementing previously published genomes from East Asia. Challenging the traditional 'pastoralist hypothesis'6-8, we show that the common ancestry and primary dispersals of Transeurasian languages can be traced back to the first farmers moving across Northeast Asia from the Early Neolithic onwards, but that this shared heritage has been masked by extensive cultural interaction since the Bronze Age. As well as marking considerable progress in the three individual disciplines, by combining their converging evidence we show that the early spread of Transeurasian speakers was driven by agriculture.

Lycopus lucidus Turcz ameliorates DNCB­induced atopic dermatitis in BALB/c mice.

Atopic dermatitis (AD) is a chronic inflammatory allergic skin disease, characterized by pruritic and eczematous skin lesions. Lycopus lucidus Turcz (LLT) is a perennial herb that has been reported to have various biological properties, including effects on blood circulation, as well as anti­inflammatory, antioxidant, anti­vascular inflammation and wound­healing effects. However, whether LLT improves dermatitis and the underlying mechanisms has yet to be determined. The aim of the present study was to determine whether LLT can improve 2,4­dinitrochlorobenzene (DNCB)­induced dermatitis and to verify the inhibitory effect of LLT on the expression of chemokines and pro­inflammatory cytokines in the HaCaT immortalized keratinocyte cell line. In addition, the anti­inflammatory function of LLT in RAW264.7 mouse macrophages was investigated. In the DNCB­induced AD mouse model, LLT inhibited infiltration by mast cells, eosinophils and CD8+ cells in the dorsal skin tissue of AD mice, and suppressed the expression of IgE and IL­6 in serum. In addition, LLT inhibited the phosphorylation of ERK and JNK, as well as NF­κB in skin tissue. In the HaCaT cell model induced by TNF­α/IFN­Î³, LLT inhibited the expression of thymus and activation­regulated chemokine, granulocyte­macrophage colony­stimulating factor, monocyte chemoattractant protein­1, TNF­α and IL­1ß, whilst inhibiting the phosphorylation of NF­κB. In addition, in the lipopolysaccharide­induced RAW 264.7 cell inflammation model, LLT inhibited the expression of TNF­α and IFN­Î³, the nuclear translocation of NF­κB and the phosphorylation of ERK and JNK. These results suggested that LLT may be a promising candidate for the treatment of inflammatory dermatitis.

Effects of chloroform fraction of Fritillariae Thunbergii Bulbus on atopic symptoms in a DNCB-induced atopic dermatitis-like skin lesion model and in vitro models.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae thunbergii Bulbus (FT), knowns as "Jeolpaemo ()" in Korean traditional medicine, is a perennial plant belonging to the Liliaceae family and has been used to treat symptoms such as cough, sputum formation, and purulent pneumonia. Owing to its effects of lowering heat, removing sputum, and reducing swelling, the plant has also been used as an external prescription medicine to treat inflammation. AIM OF THE STUDY: To analyze the anti-inflammatory effects of FT-ethanol extract (FT-Et) and FT-chloroform fraction extract (FT-Cl) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in vivo and in vitro. MATERIALS AND METHODS: The effect of FT-Et and FT-Cl on AD was observed using an AD-like skin lesion model induced by DNCB in vivo. HaCaT and RBL2H3 cells were used to determine the effects of FT-Et and FT-Cl in vitro. After inducing AD-like skin lesions in vivo, FT was topically applied to the skin lesion for 35 days. Epidermal thickness, dermal thickness, scratching behavior, infiltration of inflammatory cells, and expression of skin barrier proteins were measured. TARC, MDC, and IL-4 levels were analyzed using ELISA in HaCaT cells. Beta-hexosaminidase and IL-4 levels were measured in RBL2H3 cells. The expression of filaggrin (FLG), loricrin (LOR), involucrin (INV), and aquaporin-3(AQP-3) was measured by PCR. Phosphorylation of MAPKs was analyzed using Western blot technique. RESULTS: FT-Cl significantly reduced ear swelling, scratching behavior, SCORAD index, epidermal thickness, infiltration of inflammatory cells, and loss of skin barrier proteins. FT-Et inhibited the infiltration of mast cells and CD8+ cells and decreased the loss of skin barrier proteins. In TNF-α/IFN-γ-stimulated HaCaT cells, FT-Cl inhibited TRAC, MDC, and IL-4 expression and upregulated the expression of FLG, INV, and AQP-3, whereas FT-Et inhibited the expression of TRAC and MDC and increased the expression of FLG, INV, and AQP-3 at high concentrations. In RBL2H3, FT-Cl downregulated ß-hexosaminidase and IL-4 expression. In addition, FT-Cl inhibited the phosphorylation of ERK and p-38 in HaCaT and RBL2H3 cells. CONCLUSIONS: Collectively, FT-Cl showed better effect than FT-Et in vivo and in vitro. These results suggest that a specific component present in FT-Cl acted against AD. Future research should focus on the analysis of components contained in FT-Cl and the anti-inflammatory effects of the active ingredient.

Retrospective study of the efficacy of vascularized tissue transfer for treating antibiotic-resistant bacteria-infected wound: Comparison with clean and antibiotic-sensitive bacteria-infected wound.

ABSTRACT: If wounds are infected with bacteria resistant to an empirical antibiotic regimen, effective wound treatment will be delayed. This can delay wound healing and lengthen hospital stays, increasing the costs to patients. Long-term antibiotic use can also result in minor and major complications, such as diarrhea, antibiotic resistance, or life-threatening leukopenia. Multidrug-resistant (MDR) bacteria make wound treatment even more difficult. Traditionally, surgeons thought that adequate infection control should be established before soft tissue coverage. However, wounds infected by MDR do not heal well with this traditional method and there are no optimal treatment guidelines for MDR bacteria-contaminated wounds.We reviewed 203 patients who underwent vascularized flap surgery from 2012 to 2019 to cover wounds. Class IV and I wounds were compared according to the Centers for Disease Control and Prevention classification. Class IV was further classified as antibiotic-resistant (ARB) and antibiotic-sensitive (ASB) bacteria. Wound size, mode, location, pathogens, healing time, and basic demographics were evaluated. Data were compared using Cramer's V and one-way ANOVA or independent t tests.The average healing time was longer in the ARB (19.7 [range 7-44] days) and ASB (17.9 [range 2-36] days) groups than in the Clean group (16.5 [range 7-28] days). Healing time differed in the 3 groups (P = .036). It was longer in the class IV group than in the class I group (P = .01). However, it was not statistically different between the ARB and ASB groups (P = .164).In our study the difference in healing time was small when vascularized tissue transfer was done in ARB-infected wound compared with ASB-infected and clean wound. It is necessary to perform surgery using vascularized tissue for the infected wound of antibiotic-resistant bacteria.

Solanum nigrum Line inhibits osteoclast differentiation and suppresses bone mineral density reduction in the ovariectomy­induced osteoporosis model.

Bone homeostasis is maintained by osteoclasts that absorb bone and osteoblasts that form bone tissue. Menopausal osteoporosis is a disease associated with aging and hormonal changes due to menopause causing abnormal activation of osteoclasts, resulting in a decrease in bone density. Existing treatments for osteoporosis have been reported to have serious side effects, such as jawbone necrosis and breast and uterine cancer; therefore, their use by patients is decreasing, whilst studies focusing on alternative treatments are increasingly popular. Solanum nigrum Line (SL) has been used as a medicinal plant that possesses several pharmacological effects, such as anti­inflammatory and hepatotoxic protective effects. To the best of our knowledge, however, its effects on osteoporosis and osteoclasts have not been demonstrated previously. In the present study, the anti­osteoporotic effect of SL was investigated using a postmenopausal model of osteoporosis in which Sprague­Dawley rat ovaries were extracted. In addition, the inhibitory effects on osteoclast differentiation and function of SL was confirmed using an osteoclast model treated with receptor activator of NF­κB ligand (RANKL) on murine RAW 264.7 macrophages. In vivo experiments showed that SL reduced the decrease in bone mineral density and improved changes in the morphological index of bone microstructure, such as trabecular number and separation. In addition, the number of tartrate resistant acid phosphatase­positive cells in the femur and the expression levels of nuclear factor of activated T­cells cytoplasmic 1 (NFATc1) and cathepsin K protein were inhibited. In vitro, SL suppressed RANKL­induced osteoclast differentiation and bone resorption ability; this was mediated by NFATc1/c­Fos, a key transcription factor involved in osteoclast differentiation, ultimately inhibiting expression of various osteoclast­associated genes. These experimental results show that SL may be an alternative treatment for osteoporosis caused by abnormal activation of osteoclasts in the future.

Effects of Melandrium firmum Rohrbach on RANKL­induced osteoclast differentiation and OVX rats.

Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density (BMD), which results in an increased risk of fracture. Melandrium firmum (Siebold & Zucc.) Rohrbach (MFR), 'Wangbulryuhaeng' in Korean, is the dried aerial portion of Melandrii Herba Rohrbach, which is a member of the Caryophyllaceae family and has been used to treat several gynecological conditions as a traditional medicine. However, to the best of our knowledge, the effect of MFR on osteoclast differentiation and osteoporosis has not been assessed. To evaluate the effects of MFR on osteoclast differentiation, tartrate­resistant acid phosphatase staining, actin ring formation and bone resorption assays were used. Additionally, receptor activator of nuclear factor­κB ligand­induced expression of nuclear factor of activated T cell, cytoplasmic 1 (NFATc1) and c­Fos were measured using western blotting and reverse transcription­PCR. The expression levels of osteoclast­related genes were also examined. To further investigate the anti­osteoporotic effects of MFR in vivo, an ovariectomized (OVX) rat model of menopausal osteoporosis was established. Subsequently, the femoral head was scanned using micro­computed tomography. The results revealed that MFR suppressed osteoclast differentiation, formation and function. Specifically, MFR reduced the expression levels of osteoclast­related genes by downregulating transcription factors, such as NFATc1 and c­Fos. Consistent with the in vitro results, administration of MFR water extract to OVX rats reduced BMD loss, and reduced the expression levels of NFATc1 and cathepsin K in the femoral head. In conclusion, MFR may contribute to alleviate osteoporosis­like symptoms. These results suggested that MFR may exhibit potential for the prevention and treatment of postmenopausal osteoporosis.

Lycii radicis cortex inhibits glucocorticoid­induced bone loss by downregulating Runx2 and BMP­2 expression.

Lycii radicis cortex (LRC) has been used to regulate high blood pressure, body temperature, pain and bone disorders in East Asia. Glucocorticoids (GCs), also known as steroids, are potent immunity regulators widely used in the treatment of inflammatory diseases. However, despite their effectiveness, GC usage is strictly controlled due to severe side­effects, such as osteoporosis. However, further research is required as to date, at least to the best of our knowledge, there is no appropriate model to overcome secondary osteoporosis as a side­effect of GC use. Thus, the aim of the present study was to establish an experimental model of osteoporosis induced by GC. Furthermore, the present study aimed to establish the research methodology for medical evaluations of the effectiveness and side­effects of GCs. A secondary osteoporosis animal model was established, and the animals were divided into two groups as follows: The allergic contact dermatitis (ACD)­induced group and the non­ACD­induced group. In the ACD­induced group, a GC topical application group was compared with a GC subcutaneous injection group. The results revealed that the presence of ACD affected the induction of GC­mediated osteoporosis. Therefore, the group exhibiting induced ACD that was treated with a topical application of GC was selected for examining the side­effects of GCs. The effects of LRC on secondary osteoporosis were confirmed in vivo and in vitro. The results indicated that LRC regulated dexamethasone­induced osteoblast apoptotic markers, including caspase­6, caspase­9, X­linked inhibitor of apoptosis, apoptosis inhibitor 1 and apoptosis inhibitor 2, and increased the expression of osteoblast differentiation­related genes, such as Runt­related transcription factor 2 and bone morphogenetic protein 2 in the MC3T3E­1 cell line. LRC also significantly reduced GC­induced osteoporosis and exerted anti­inflammatory effects in vivo. In addition, LRC inhibited the reduction of calbindin­D28k in the kidney. Overall, the results of the present study suggest that the use of LRC alleviates GC­induced secondary osteoporosis.

Crataegus pinnatifida Bunge Inhibits RANKL-Induced Osteoclast Differentiation in RAW 264.7 Cells and Prevents Bone Loss in an Ovariectomized Rat Model.

Osteoporosis is characterized by a decrease in bone microarchitecture with an increased risk of fracture. Long-term use of primary treatments, such as bisphosphonates and selective estrogen receptor modulators, results in various side effects. Therefore, it is necessary to develop alternative therapeutics derived from natural products. Crataegus pinnatifida Bunge (CPB) is a dried fruit used to treat diet-induced indigestion, loss of appetite, and diarrhea. However, research into the effects of CPB on osteoclast differentiation and osteoporosis is still limited. In vitro experiments were conducted to examine the effects of CPB on RANKL-induced osteoclast differentiation in RAW 264.7 cells. Moreover, we investigated the effects of CPB on bone loss in the femoral head in an ovariectomized rat model using microcomputed tomography. In vitro, tartrate-resistant acid phosphatase (TRAP) staining results showed the number of TRAP-positive cells, and TRAP activity significantly decreased following CPB treatment. CPB also significantly decreased pit formation. Furthermore, CPB inhibited osteoclast differentiation by suppressing NFATc1, and c-Fos expression. Moreover, CPB treatment inhibited osteoclast-related genes, such as Nfatc1, Ca2, Acp5, mmp9, CtsK, Oscar, and Atp6v0d2. In vivo, bone mineral density and structure model index were improved by administration of CPB. In conclusion, CPB prevented osteoclast differentiation in vitro and prevented bone loss in vivo. Therefore, CPB could be a potential alternative medicine for bone diseases, such as osteoporosis.

Effect of Cone of Pinus densiflora on DNCB-Induced Allergic Contact Dermatitis-Like Skin Lesion in Balb/c Mice.

Cone of Pinus densiflora (CP), or Korean red pinecone, is a cluster of Pinus densiflora fruit. CP has also been verified in several studies to have anti-oxidation, anti-fungal, anti-bacterial, and anti-melanogenic effects. However, anti-inflammatory effects have not yet been confirmed in the inflammatory responses of pinecones to allergic contact dermatitis. The purpose of this study is to prove the anti-inflammatory effect of CP on allergic contact dermatitis (ACD) in vitro and in vivo. CP inhibited the expression of TSLP, TARC, MCP-1, TNF-α, and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells and MCP-1, GM-CSF, TNF-α, IL-6, and IL-8 in PMACI (phorbol-12-myristate-13-acetate plus A23187)-stimulated HMC-1 cells. CP inhibited the phosphorylation of mitogen-activated protein kinase (MAPKs), as well as the translocation of NF-κB on TNF-α/IFN-γ stimulated in HaCaT cells. In vivo, CP decreased major symptoms of ACD, levels of IL-6 in skin lesion, thickening of the epidermis and dermis, infiltration of eosinophils and mast cells, and the infiltration of CD4+ T cells and CD8+ T cells. This result suggests that CP represents a potential alternative medicine to ACD for diseases such as chronic skin inflammation.

Effects of Sparganii Rhizoma on Osteoclast Formation and Osteoblast Differentiation and on an OVX-Induced Bone Loss Model.

Postmenopausal osteoporosis is caused by an imbalance between osteoclasts and osteoblasts and causes severe bone loss. Osteoporotic medicines are classified into bone resorption inhibitors and bone formation promoters according to the mechanism of action. Long-term use of bisphosphonate and selective estrogen receptor modulators (SERMs) can cause severe side effects in postmenopausal osteoporosis patients. Therefore, it is important to find alternative natural products that reduce osteoclast activity and increase osteoblast formation. Sparganii Rhizoma (SR) is the dried tuberous rhizome of Sparganium stoloniferum Buchanan-Hamilton and is called "samreung" in Korea. However, to date, the effect of SR on osteoclast differentiation and the ovariectomized (OVX)-induced bone loss model has not been reported. In vitro, tartrate-resistant acid phosphatase (TRAP) staining, western blots, RT-PCR and other methods were used to examine the effect of SR on osteoclast differentiation and osteoblasts. In vivo, we confirmed the effect of SR in a model of OVX-induced postmenopausal osteoporosis. SR inhibited osteoclast differentiation and decreased the expression of TNF receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells 1 (NFATc1) and c-Fos pathway. In addition, SR stimulates osteoblast differentiation and increased protein expression of the bone morphogenetic protein 2 (BMP-2)/SMAD signaling pathway. Moreover, SR protected against bone loss in OVX-induced rats. Our results appear to advance our knowledge of SR and successfully demonstrate its potential role as a osteoclastogenesis-inhibiting and osteogenesis-promoting herbal medicine for the treatment of postmenopausal osteoporosis.