BACKGROUND/OBJECTIVES: Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.MATERIALS/METHODS: Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations. RESULTS: AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect. CONCLUSION These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Mesenchymal stem cells in the dental tissue indicate a disposition for differentiation into diverse dental lineages and contain enormous potential as the important means for regenerative medicine in dentistry. Among various dental tissues, the dental pulp contains stem cells, progenitor cells and odontoblasts for maintaining dentin homeostasis. The conventional culture of stem cells holds a limit as the living tissue constitutes the three-dimensional (3D) structure. Recent development in the organoid cultures have successfully recapitulated 3D structure and advanced to the assembling of different types. In the current study, the protocol for 3D explant culture of the human dental pulp tissue has been established by adopting the organoid culture. After isolating dental pulp from human tooth, the intact tissue was placed between two layers for Matrigel with addition of the culture medium. The reticular outgrowth of pre-odontoblast layer continued for a month and the random accumulation of dentin was observed near the end. Electron microscopy showed the cellular organization and in situ development of dentin, and immunohistochemistry exhibited the expression of odontoblast and stem cell markers in the outgrowth area. Three-dimensional explant culture of human dental pulp will provide a novel platform for understanding stem cell biology inside the tooth and developing the regenerative medicine.

Purpose: There is a lack of a report about the trajectories of allergen sensitization, although it is important to understand the change of allergen sensitization to manage allergic disease. This study aimed to analyze the change and trajectories of allergen sensitization in children with respiratory and allergic diseases. Methods: From 2006 to 2020, children with respiratory and allergic diseases or screened for allergic sensitization were evaluated. We visualized the alterations and the trajectories of allergen sensitization using stacked area graphs, box plots, and Sankey diagrams. Results: A total of 2,804 subjects were included, and allergic rhino-conjunctivitis was diagnosed in 1,931 children (68.9%). The mean age for the first test was 4.1 years, and that for the second test was 6.5 years. Children sensitized to class 1 food allergen before age 5 showed sensitizations more for other allergens and at a younger age after age 5 than children who were not. The atopic tendency continued once it had been obtained before the early school age in the persistence or the new development of sensitization. Conclusion Allergen sensitization has changed over time and has shown different patterns according to age. Its trajectory has taken a wide variety of courses in children with respiratory and allergic diseases until the early school age. These changes reflect the allergic diseases and socio-environmental characteristics of children and adolescents.

Purpose: Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. Materials and Methods: A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. Results: A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. Conclusion A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.

The prevalence of small bowel cancer is relatively low. The abdominal pain that patients with small bowel cancer present as a symptom is non-specific and often interpreted as a normal finding on radiographic studies. To prevent delayed diagnosis of small bowel cancer, practitioners must maintain a certain level of suspicion. We report a case of delayed diagnosis of jejunal cancer as it was misdiagnosed as gastroparesis. A 69-year-old woman complained of recurrent nausea and vomiting. At the beginning of her hospitalization, we could not diagnose mechanical obstruction through esophagogastroduodenoscopy and abdominal computed tomography. A gastric emptying study revealed delayed gastric emptying. Although the patients received treatments, including administration of prokinetics and botulinum toxin injection, for gastroparesis, her symptoms aggravated. Subsequently, plain radiography of the abdomen revealed a double-bubble sign. Abdominal computed tomography was performed under the suspicion of small bowel obstruction; however, the diagnosis was not clear. Consequently, exploratory laparoscopy was performed. She underwent surgical management, including small bowel segmental resection and duodenojejunostomy, due to the jejunal mass with involvement of the stomach, pancreatic head, and mesentery of the transverse colon. The postoperative pathological results revealed a moderately differentiated adenocarcinoma of the jejunum.
Abdomen ; Abdominal Pain ; Adenocarcinoma ; Aged ; Botulinum Toxins ; Colon, Transverse ; Delayed Diagnosis ; Diagnosis ; Endoscopy, Digestive System ; Female ; Gastric Emptying ; Gastroparesis ; Head ; Hospitalization ; Humans ; Jejunal Neoplasms ; Jejunum ; Laparoscopy ; Mesentery ; Nausea ; Prevalence ; Radiography ; Stomach ; Vomiting

OBJECTIVES: Kikuchi-Fujimoto disease (KFD) is characterized by lymphadenopathy and fever, and is usually self-limited. This study analyzed the clinical characteristics of pediatric patients with KFD. METHODS: This retrospective, observational, single-center study was conducted in South Korea from March 2008 to October 2015. KFD was diagnosed based on clinical, radiological or histological findings and excluded when there were any other causes of lymphadenopathy. Medical records were reviewed for clinical and laboratory manifestations. RESULTS: A total of 35 cases were included. The mean patient age was 12.1±2.9 years (range, 5 to 17 years); the male-to-female ratio was 1:0.8. The main clinical manifestations were cervical lymphadenopathy and fever in 34 cases (97%). The mean duration of fever was 12.2±8.3 days (range, 2 to 37 days). We noted enlargement of lymph nodes in the cervical, mesenteric (n=5, 14%), axillary (n=2, 6%), and inguinal (n=1, 3%) regions. Hepatosplenomegaly, loss of appetite, and rash were observed. On laboratory examinations, elevation of ferritin, leukopenia, and positivity for anti-nuclear antibodies were frequently observed. Twelve patients underwent biopsy and 23 cases were diagnosed by radiological findings. The mean duration of hospitalization for all cases was 7.9±2.9 days (range, 3 to 13 days) and steroids were administered in 10 cases. KFD recurrence was observed in 2 cases (5.7%) with the time to relapse of 7 months and 4 years. There were no cases with systemic lupus erythematous or other autoimmune disease. CONCLUSION: KFD should be considered in pediatric patients with lymphadenopathy and prolonged fever. Patients with KFD should be monitored for recurrence and the development of autoimmune disease.
Adolescent* ; Antibodies ; Appetite ; Autoimmune Diseases ; Biopsy ; Child* ; Exanthema ; Ferritins ; Fever ; Histiocytic Necrotizing Lymphadenitis* ; Hospitalization ; Humans ; Korea ; Leukopenia ; Lymph Nodes ; Lymphatic Diseases ; Medical Records ; Pediatrics ; Recurrence ; Retrospective Studies ; Steroids

HACEK is a rare cause of prosthetic valve endocarditis (PVE). We describe 42-year-old male patient who presented with Aggregatibacter aphrophilus PVE and cerebral infarct. A. aphrophilus was isolated from his blood cultures as the sole pathogen, which was confirmed by subsequent 16S rRNA sequencing. He was treated with valve replacement surgery and an 8 week course of pathogen-directed antibiotic therapy and followed for 20 months without recurrence.
Adult ; Aggregatibacter aphrophilus ; Endocarditis* ; Heart Valve Prosthesis ; Humans ; Male ; Recurrence

Attention-deficit hyperactivity disorder (ADHD) occurs with a high prevalence of comorbid disorders, and these comorbid disorders can affect assessment, clinical symptoms, prognosis, and treatment strategies for children with ADHD. The goal of this study was to develop a clinical practice guideline for ADHD and its specific comorbid disorders. Due to limited numbers of previous clinical studies, current recommendations are based on literature review and expert consensus among Korean child and adolescent psychiatrists. We suggest the use of multidisciplinary evaluations, interview techniques, and assessment tools in order to differentiate major comorbid disorders from ADHD. Specific ADHD comorbid disorders (e.g., medical comorbidity, oppositional defiant disorder, conduct disorder, bipolar disorder, major depressive disorder, anxiety disorder, specific learning disorder, tic disorder, and substance use disorder) have suggested treatment protocols that include pharmacological and behavioral treatments. Children and adolescents with ADHD may have comorbid disorders. The use of current clinical practice guidelines will be helpful when treating ADHD children with comorbid disorders.
Adolescent ; Anxiety Disorders ; Attention Deficit and Disruptive Behavior Disorders ; Bipolar Disorder ; Child ; Clinical Protocols ; Comorbidity ; Conduct Disorder ; Consensus ; Depressive Disorder, Major ; Humans ; Prevalence ; Prognosis ; Psychiatry ; Specific Learning Disorder ; Tic Disorders

Primary small cell carcinoma of the paranasal sinuses is extremely rare. It is aggressively locally invasive, with high recurrence and metastatic rates. A combination of systemic chemotherapy and locoregional treatment, such as radiotherapy, is currently recommended based on the treatment of small cell carcinoma of lung. We report a case of small cell carcinoma originating from the maxillary sinus with distant metastasis at the time of diagnosis. The patient had a good initial therapeutic response to etoposide-cisplatin chemotherapy, but the cancer progressed after the sixth cycle of chemotherapy and the prognosis was poor.
Carcinoma, Small Cell* ; Diagnosis ; Drug Therapy ; Humans ; Lung ; Maxillary Sinus* ; Neoplasm Metastasis* ; Paranasal Sinuses ; Prognosis ; Radiotherapy ; Recurrence