Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

To address the limitations of animal testing, scientific research is increasingly focused on developing alternative testing methods. These alternative tests utilize cells or tissues derived from animals or humans for in vitro testing, as well as artificial tissues and organoids. In western countries, animal testing for cosmetics has been banned, leading to the adoption of artificial skin for toxicity evaluation, such as skin corrosion and irritation assessments. Standard guidelines for skin organoid technology becomes necessary to ensure consistent data and evaluation in replacing animal testing with in vitro methods. These guidelines encompass aspects such as cell sourcing, culture techniques, quality requirements and assessment, storage and preservation, and organoid-based assays.

Objectives: Korea and Japan have managed the spread of coronavirus disease 2019 (COVID-19) using markedly different policies, referred to as the “3T” and “3C” strategies, respectively. This study examined these differences to assess the roles of active testing and contact tracing as non-pharmaceutical interventions (NPIs). We compared the proportion of unlinked cases (UCs) and test positivity rate (TPR) as indicators of tracing and testing capacities. Methods: We outlined the evolution of NPI policies and investigated temporal trends in their correlations with UCs, confirmed cases, and TPR prior to the Omicron peak. Spearman correlation coefficients were reported between the proportion of UCs, confirmed cases, and TPR. The Fisher r-to-z transformation was employed to examine the significance of differences between correlation coefficients. Results: The proportion of UCs was significantly correlated with confirmed cases (r=0.995, p<0.001) and TPR (r=0.659, p<0.001) in Korea and with confirmed cases (r=0.437, p<0.001) and TPR (r=0.429, p<0.001) in Japan. The Fisher r-to-z test revealed significant differences in correlation coefficients between the proportion of UCs and confirmed cases (z=16.07, p<0.001) and between the proportion of UCs and TPR (z=2.12, p=0.034) in Korea and Japan. Conclusions Higher UCs were associated with increases in confirmed cases and TPR, indicating the importance of combining testing and contact tracing in controlling COVID-19. The implementation of stricter policies led to stronger correlations between these indicators. The proportion of UCs and TPR effectively indicated the effectiveness of NPIs. If the proportion of UCs shows an upward trend, more testing and contact tracing may be required.

BACKGROUND/OBJECTIVES: This study aimed to identify preschool children’s eating behaviors associated with early childhood obesity and its multi-level, socio-ecological determinants. SUBJECTS/METHODS: In a cross-sectional study of 364 mothers of preschool children aged 3–5 years, these children’s healthy eating behaviors were assessed using a validated preschool nutrition quotient (NQ-P) questionnaire. The children’s overweight or obesity statuses were determined based on body mass index percentiles from the 2017 Korean National Growth Chart. The associations between the NQ-P score and risk of overweight or obesity were examined using multivariable logistic regression. The associations of individual, maternal, physical, and media environmental factors with the NQ-P score were also examined using multivariable linear regression. RESULTS: Preschool children with greater NQ-P scores were at a significantly lower risk of overweight or obesity (P < 0.01). The NQ-P score had a significantly positive association with maternal body mass index and an inverse association with household income (all P < 0.05). Maternal parenting and feeding practices exhibited associations with the NQ-P score.Positive associations were observed with “warm,” “structured,” and “autonomy-supportive” parenting as well as monitoring feeding practices (all P < 0.05). In addition, the NQ-P score had a significantly positive association with the childcare center’s anti-obesogenic environment, such as the provision of nutritional and physical-activity support and vicinity of the built food environment to the home, including access to good-quality food, fruits and vegetables, and low-fat foods (all P < 0.05). Regarding media environments, the NQ-P score demonstrated more significant associations with viewing and eating and/or cooking content displayed on online video platforms (all P < 0.05) than with that on television. CONCLUSIONS Our findings confirm the significance of healthy eating behaviors in earlychildhood-obesity prevention and underscore the importance of multilevel maternal, physical, and media environmental interventions that effectively guide eating behaviors in preschool children.

PURPOSE: Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining. We also analyzed the effect of NaCl on Th17 differentiation from peripheral blood monocytes of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and evaluated the contents of sodium and IL-17 in the synovial fluid of RA and OA patients. RESULTS: NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na+ and IL-17 were more abundant in RA synovial fluid. CONCLUSION: This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.
Animals ; Arthritis* ; Arthritis, Experimental ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Diet ; Flow Cytometry ; Humans ; Interleukin-17 ; Intestines ; Joints ; Mice ; Monocytes ; Osteoarthritis ; Sodium Chloride* ; Sodium* ; Spleen ; Synovial Fluid ; T-Lymphocytes, Helper-Inducer ; Th17 Cells

Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically results in strong inflammation and bone destruction in the joints. It is generally known that the pathogenesis of RA is linked to cardiovascular and periodontal diseases. Though rheumatoid arthritis and periodontitis share many pathologic features such as a perpetual inflammation and bone destruction, the precise mechanism underlying a link between these two diseases has not been fully elucidated. Collagen-induced arthritis (CIA) mice were orally infected with Porphyromonas gingivalis (Pg) or Pg preincubated with an anti-FimA antibody (FimA Ab) specific for fimbriae that are flexible appendages on the cell surface. Pg-infected CIA mice showed oral microbiota disruption and increased alveolar bone loss and had synovitis and joint bone destruction. However, preincubation with FimA Ab led to a significant reduction in the severity of both oral disease and arthritis. Moreover, FimA Ab attenuated bacterial attachment and aggregation on human gingival and rheumatoid arthritis synovial fibroblasts. In addition, we discovered bacteria may utilize dendritic cells, macrophages and neutrophils to migrate into the joints of CIA mice. These results suggest that disrupting Pg fimbriae function by FimA Ab ameliorates RA.

BACKGROUND AND OBJECTIVE: Whabyung is a Korean cultural disorder characterized by a combination of emotional stress and physical symptoms. Acupuncture, herbal medicines and other complementary medicinal treatments are used to treat the symptoms of whabyung. The purpose of this study is to investigate the effects of acupuncture treatment and herbal medicine treatments on anger, anxiety and depression of whabyung. METHODS: Using PubMed, CENTRAL, AMED, MEDLINE, EMBASE, MEDLINE, CINAHL, Cnii, CNKI, J-SATGE, PsycArticles, KISS, KoreaMed, kmbase, NDSL, RISS, OASIS and Korean Traditional Knowledge Portal, articles published by March 2017 for whabyung or whabyung-related syndrome were searched. The quality of selected articles was evaluated using RoB and RoBANS. The effects of acupuncture and herbal medicines on anger, anxiety, and depression levels of whabyung patients were considered for meta-analyses. RESULTS: Of the total 2408 articles retrieved from the database, 11 were finally selected and 4 articles were used for meta-analyses. Acupuncture reduced whabyung patients' anger and anxiety. Especially, the state anxiety was significantly reduced (effect size= −0.676, p= .026). Herbal medicine had effects on reducing anxiety and state anger while trait anger was increased without statistical significance. CONCLUSION: The present study showed the effectiveness of acupuncture and herbal medicines for whabyung patients in general. However, considering the limited availability of articles and the heterogeneity between them included for the meta-analysis, the results should be generalized with caution. In the future, more studies within the structure of evidence-based medicine need to be conducted to generate objective and valid evidences of korean medicine.

Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-alpha and then treated with eupatilin, and the levels of IL-6 and IL-1beta mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-alpha treatment of synoviocytes increased the expression of IL-6 and IL-1beta mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.
Animals ; Anti-Inflammatory Agents/pharmacology/*therapeutic use ; Arthritis, Experimental/chemically induced/*drug therapy ; Arthritis, Rheumatoid/drug therapy/pathology ; Cell Differentiation/*drug effects ; Cells, Cultured ; Collagen Type II ; Cytokines/biosynthesis ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use ; Female ; Flavonoids/pharmacology/*therapeutic use ; Humans ; Inflammation/drug therapy/immunology ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Lymph Nodes/cytology ; Mice ; Mice, Inbred DBA ; Monocytes/cytology ; Osteoclasts/*cytology ; Plant Extracts/pharmacology ; RNA, Messenger/biosynthesis ; Synovial Membrane/cytology ; T-Lymphocytes, Regulatory/cytology/immunology ; Tumor Necrosis Factor-alpha/pharmacology