Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.

Objective: This study aimed to illustrate the techniques of unilateral biportal endoscopic transforaminal lumbar interbody fusion (UBE-TLIF) using double cages and compare surgical outcomes with those using a single cage. Methods: We retrospectively analyzed 62 patients who underwent single-level UBE-TLIF using 3-dimensional (3D)-printed titanium cages (29 with a single cage and 33 with double cages). Radiological parameters, including Bridwell fusion and subsidence grading, were assessed via x-ray and computed tomography at 6 months and 1 year. Clinical outcomes were measured using the visual analogue scale (VAS) for lower back and leg pain, as well as the Oswestry Disability Index (ODI). Results: At the 6-month follow-up, the overall fusion rate (grades I + II) was significantly higher in the double-cage group (86.2% vs. 100%, p=0.04); however, no significant difference was noted at the 1-year follow-up (89.6% vs. 100%). The double-cage group showed lower cage subsidence rates at both follow-ups (3% vs. 31%, p=0.01; 12.1% vs. 38%, p=0.03). The double-cage group exhibited significantly greater improvements in leg pain (VAS: 7.6 to 1.7 vs. 7.2 to 1.4, p=0.03) and ODI (28.6 to 10.8 vs. 28.3 to 9.4, p=0.01) at 1 year. Conclusion UBE-TLIF with 3D-printed titanium cages achieved a favorable fusion rate at the 1-year follow-up, regardless of whether single or double cages were used. However, double cages accelerated fusion at the 6-month follow-up and significantly reduced cage subsidence at both the 6-month and 1-year follow-ups. These benefits contributed to improved VAS scores for leg pain and ODI at the final follow-up.

Objective: This study compared the clinical and radiological outcomes of uniportal endoscopic and biportal endoscopic transforaminal lumbar interbody fusion (TLIF) for lumbar degenerative disease during the early learning stage of the technique. Methods: We retrospectively analyzed patients who underwent uniportal endoscopic TLIF (n=15) and biportal endoscopic TLIF (n=19) between January and October 2021 during the first year of adoption of these techniques. Radiological parameters, including Bridewell fusion and subsidence grading, were evaluated by x-ray and computed tomography (CT) at 3-month, 6-month, and 1-year follow-up visits. Clinical outcomes were evaluated using the visual analogue scale (VAS) and the Oswestry Disability Index (ODI). Results: Uniportal endoscopic TLIF showed significantly higher frequencies of intraoperative endplate injuries (uniportal [20%] vs. biportal [0%], p=0.01) and 1-year cage subsidence (uniportal [60%] vs. biportal [26.3%], p=0.04) than biportal endoscopic TLIF. The 1-year fusion rates did not differ significantly between the 2 surgical groups (uniportal [93.3%] vs. biportal [89.5%], p=0.37). Neural complications such as postoperative dysesthesia and dural tears occurred in uniportal endoscopic TLIF. There were no significant differences in the VAS for back and leg pain or ODI. Conclusion Complete endplate preparation under endoscopic guidance improved interbody fusion, and this procedure may be feasible in the early learning stage, regardless of the type of endoscope. Both endoscopic TLIF techniques achieved good clinical outcomes and fusion rates. However, unskilled use of the cage guide device caused endplate breakage and neural injury during uniportal endoscopic cage insertion. Uniportal endoscopic TLIF may require more experience for appropriate cage insertion.

Objective: Biportal endoscopic surgery was developed to treat degenerative pathologies that cause myelopathy. Thoracic disc herniation accelerates myelopathy at the level of thoracic stenosis caused by ossification of the ligamentum flavum (OLF). This study describes a feasible surgical technique for the biportal endoscopic posterior approach for removing the thoracic OLF and herniated disc that cause thoracic myelopathy. Methods: Bilateral laminar thinning was performed while preserving the midline and contralateral bony structures. The thoracic OLF was thinned and cut at the bony drilled edge using a diamond drill. The OLF was elevated and removed using an en bloc technique after epidural dissection. The herniated disc was removed through the space created after medial facetectomy. All the procedures were performed without neural injury. Results: Postoperatively, the neurological symptoms of thoracic myelopathy improved, as did the upper back and chest wall pain. Conclusion We successfully treated double-crushing lesions of the thoracic herniated disc and OLF using biportal endoscopy. In biportal endoscopic surgery, drills and instruments can be smoothly used in the narrow spinal canal of the upper thoracic vertebrae. The biportal endoscopic posterior thoracic approach may be an attractive surgical option for treating thoracic myelopathy caused by combined degenerative pathologies.

Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.
Animals ; Antibodies, Monoclonal, Humanized/administration & dosage/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Mice ; Mice, Inbred BALB C ; Neovascularization, Pathologic/drug therapy ; Receptor, erbB-2/*antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/administration & dosage/*therapeutic use ; Recombinant Fusion Proteins/administration & dosage/*therapeutic use ; Stomach Neoplasms/*drug therapy/pathology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Xenograft Model Antitumor Assays

Here, we show that radicicol, a fungal antibiotic, resulted in marked inhibition of inducible nitric oxide synthase (iNOS) transcription by the pancreatic beta cell line MIN6N8a in response to cytokine mixture (CM: TNF-alpha, IFN-gamma, and IL-1beta). Treatment of MIN6N8a cells with radicicol inhibited CM-stimulated activation of NF-kappaB/Rel, which plays a critical role in iNOS transcription, in a dose-related manner. Nitrite production in the presence of PD98059, a specific inhibitor of the extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) pathway, was dramatically diminished, suggesting that the ERK1/2 pathway is involved in CM-induced iNOS expression. In contrast, SB203580, a specific inhibitor of p38, had no effect on nitrite generation. Collectively, this series of experiments indicates that radicicol inhibits iNOS gene expression by blocking ERK1/2 signaling. Due to the critical role that NO release plays in mediating destruction of pancreatic beta cells, the inhibitory effects of radicicol on iNOS expression suggest that radicicol may represent a useful anti-diabetic activity.
Flavonoids ; Gene Expression ; Imidazoles ; Insulin-Secreting Cells ; Macrolides ; Negotiating ; Nitric Oxide Synthase Type II ; Pyridines ; Tumor Necrosis Factor-alpha

The familial environment may also play an important role in the epidemiology of HCV infection through vertical and horizontal transmission by infected household members. However, it is still controversial whether familial clustering of HCV occurs. We experienced a case of familial clustering of hepatitis C virus. A 10-year old girl presented with nausea, vomiting and anorexia for a month was diagnosed as hepatitis C. Her mother, grandmother, a maternal aunt and her daughter had contracted with HCV. Her laboratory findings showed AST/ALT 63/122 IU/L, positive anti-HCV Ab and HCV RNA (3.54 x 10(5) copies/mL). Pathologic findings of the liver biopsy revealed chronic hepatitis with minimal lobular activity, mild porto-periportal activity and mild portal fibrosis. After treatment with interferon-alpha 2b for 6 months, the clinical symptoms and laboratory findings were normalized.
Anorexia ; Biopsy ; Child ; Cluster Analysis* ; Epidemiology ; Family Characteristics ; Female ; Fibrosis ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Hepatitis, Chronic ; Humans ; Interferon-alpha ; Liver ; Mothers ; Nausea ; Nuclear Family ; RNA ; Vomiting

Skeletogenesis occurs through either intramembranous or endochondral ossification. In addition, some parts of the skeletal components maintain their cartilaginous characteristics throughout life without mineralization. Runx2 is known to be a pivotal transcription factor for all skeletogenic processes. In this study, we examined the expression patterns of two major isoforms of Runx2 in early skeletogenesis. During intramembranous bone formation, Runx2-type I (Runx2-I) was widely expressed in osteoprogenitor cells and active osteoblasts, while Runx2-type II (Runx2-II) expression was stringently restricted to cells lining mineralized bones. Cells in permanent cartilage expressed collagen type II (Col-II) but never expressed Runx2 or Col-X. These permanent cartilages were well circumscribed by Runx2-I positive cells, in which Runx2-II was negative. In endochondral bone formation, Runx2 expression temporarily disappeared in Col-II-positive proliferating chondrocytes, but a secondary surge of Runx2-I expression occurred in the prehypertrophic zone before the mineralization of cartilage. Collectively, both Runx2 isoforms showed very similar expression patterns in active bone forming areas; however, Runx2-I has an exclusive role in the early commitment stage of intramembranous or endochondral bone forming processes or in cells surrounding permanent cartilage.
Animals ; *Bone Development ; Cartilage/cytology/growth & development/metabolism ; Embryo and Fetal Development/genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; In Situ Hybridization ; Mice ; Mice, Inbred ICR ; Protein Isoforms/genetics/metabolism ; Time Factors ; Transcription Factors/*genetics/metabolism

PURPOSE:Rapidly progressive glomerulonephritis (RPGN) is characterized by the rapid increase in serum creatitnin and crescents formation involving more than 50% of glomeruli. 10 patients who had been treated for RPGN were studied retrospectively for thier underlying diseases and clinical features. METHOD: Cilinical review was performed on 10 children who were diagnosed with RPGN by clinical features and renal biopsy and followed up at department of pediatrics during the last 10 years, from May 1990 to May 2000. RESULT: There were 6 males and 4 females between the ages of 2.1 and 14.3 years (mean 10.9+/-.8). 3 had Henoch-Sch nlein purpura nephritis; 2, idiopathic rapidly progressive glomerulonephritis; 2, lupus nephritis; 1, hemolytic uremic syndrome; 1, membranous glomerulonephritis and 1, microscopic polyangiitis. The most common chief complaints were gross hematuria and oliguria. Initial clinical features included proteinuria, edema, hypertension, nausea and arthralgia. Mean serum BUN was 74.2+/-39.1 mg/dL; mean serum creatinin, 3.2+/-1.8 mg/dL and mean creatinin clearance, 26.5+/-13.2 mL/min/1.73m2. Antineutrophil cytoplasmic antibody was positive only in microscopic polyangiitis. ANA and Anti-DNA antibody were positive in two lupus nephritis patients. Serum complements were decreased in 4 patients. All patients except Hemolytic uremic syndrome received steroid pulse therapy and immunosupressive agents. 3 patients were performed acute peritoneal dialysis and 2 patients were given plasmapheresis. At the last follow up, 1 patient was dead, 4 patients had elevated serum creatinin, 2 of these 4 patients were on chronic ambulatory peritoneal dialysis and 6 patients had normal renal function. CONCLUSION: Rapidly progressive glomerulonephritis is a medical emergency that requires very rapid diagnosis, classification, and therapy. Appropriate therapy selected on the basis of underlying disease mechanism can substantially improve renal survival.
Antibodies, Antineutrophil Cytoplasmic ; Arthralgia ; Biopsy ; Child ; Classification ; Complement System Proteins ; Creatinine ; Diagnosis ; Edema ; Emergencies ; Female ; Follow-Up Studies ; Glomerulonephritis* ; Glomerulonephritis, Membranous ; Hematuria ; Hemolytic-Uremic Syndrome ; Humans ; Hypertension ; Lupus Nephritis ; Male ; Microscopic Polyangiitis ; Nausea ; Nephritis ; Oliguria ; Pediatrics ; Peritoneal Dialysis ; Plasmapheresis ; Proteinuria ; Purpura ; Renal Insufficiency ; Retrospective Studies

No Abstract Available.
Animals ; Base Sequence* ; Cattle* ; Serotyping*