The periodontal complex consisting of alveolar bone, cementum, and periodontal ligaments (PDL) supports human teeth through the systematic orchestration of mineralized tissues and fibrous tissues. ...Importantly, cementum, the outermost mineralized layer of dental roots, plays an essential role by bridging the inner ligaments from the dental root to the alveolar bone. When the periodontal complex is damaged, the regeneration of each component of the periodontal complex is necessary; however, it is still challenging to achieve complete functional regeneration. In this study, we tried to control the regeneration of cementum and PDL by using a human PDL stem cell (hPDLSC) sheet engineering technology with the pretreatment of recombinant human BMP-2 (rhBMP-2). Isolated hPDLSCs obtained from extracted human teeth were pretreated with rhBMP-2 for in vitro osteogenic differentiation and grafted on the micro/macro-porous biphasic calcium phosphate (MBCP) blocks, which represent dental roots. The MBCPs with hPDLSC sheets were implanted in the subcutaneous layer of immune-compromised mice, and rhBMP-2 pretreated hPDLSC sheets showed higher mineralization and collagen ligament deposition than the no-pretreatment group. Therefore, the rhBMP-2-hPDLSC sheet technique could be an effective strategy for the synchronized regeneration of two different tissues: mineralized tissue and fibrous tissues in periodontal complexes.
Purpose
The Janus tyrosine kinase and signal transducers and activators of transcription (JAK/STAT) pathway is involved in vascular endothelial growth factor (VEGF) expression, but the role of this ...pathway in diabetic retinopathy (DR) remains unclear. We investigated the role of the JAK/STAT pathway on DR and VEGF expression using a streptozotocin (STZ)-induced DR mouse model.
Methods
Cultured ARPE-19 cells were exposed to high-glucose conditions and treated with JAK/STAT inhibitors (JAK inhibitor I JAKiI, tofacitinib, STAT3 inhibitor STAT3i) for 48 h. Reverse-transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to investigate p-JAK/STAT and VEGF expression. Diabetes was induced by intraperitoneal injection of STZ (50 mg/kg) in C57BL/6 mice for 5 days. DR development was evaluated every 4 weeks. JAK/STAT inhibitors were administered for 8 weeks. Immunofluorescence was used to measure the activation status of the JAK/STAT pathway and VEGF production in the retinal tissue.
Results
In ARPE-19 cells exposed to high-glucose conditions, the mRNA and secretory protein levels of VEGF, p-JAK1, p-JAK2, p-STAT3, and p-STAT5 levels were significantly increased. Treatment with JAKiI, tofacitinib, and STAT3i significantly suppressed VEGF to basal levels at both the mRNA and secretory levels in vitro. In STZ-induced mice, retinal vascular leakage, p-JAK1, p-JAK2, p-JAK3, p-STAT3, and VEGF were significantly increased after diabetes induction. Diabetes-induced retinal vascular leakage was significantly reduced by treatment with JAKiI and tofacitinib. Increased p-JAK1 and VEGF in STZ-induced mice were significantly reduced by JAKiI (
p
< 0.05,
p
< 0.001) and tofacitinib (
p
< 0.001, respectively).
Conclusion
JAK1 may be more involved in VEGF production and DR progression in mice than JAK2, JAK3, and STAT3.
As pilomatricoma is a common adnexal skin tumor often occurring in exposed areas, dermatologists focus on minimizing postsurgical scarring.
This retrospective study included patients aged < 19 years ...who underwent surgical treatment for pilomatricoma at a single university hospital from 2015 to 2021. Patient demographics, tumor characteristics, and surgical outcomes were analyzed according to the surgical methods including punch incision and elliptical excision.
Overall, 75 patients and 79 lesions were included in the study. The mean age of the patients was 8.4 years, and 48 patients (64.0%) were females. The face was the most common site of pilomatricoma (51.9%), and within the face, the cheeks were the most common sites. No recurrence was observed in the elliptical excision group, while one case of recurrence (4.5%) was observed in the punch incision group. The mean length of the wound was 2.00 cm in the elliptical excision group, which was longer than that in the punch incision group (0.49 cm;
< .001).
Considering that surgery is the gold standard treatment for pilomatricoma, punch incision may be useful as an alternative surgical option for pilomatricoma in children.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Dear Editor, Pyoderma gangrenosum(PG) is a rare neutrophilic dermatosis that causes the development of painful ulcers on the skin, initially starting with nodules or abscesses, and quickly ...progressing at the peripheral regions into ulcers.1 The exact cause is not yet known, and 20-30% of patients are said to experience a pathergy phenomenon in which lesions occur in the sites of previous trauma.2 In addition, pyoderma gangrenosum is accompanied by systemic diseases, such as Crohn's disease or inflammatory colitis, rheumatoid arthritis, and hyperthyroidism.3 Although numerous reports indicate that pyoderma gangrenosum is associated with systemic diseases,4 case reports on the association of pyoderma gangrenosum with skin diseases, especially blistering disorders, are very rare. ...
Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease that is characterized by complex immune dysregulation and skin barrier dysfunction with a wide variety of clinical phenotypes. ...Until recently, conventional therapeutic modalities for AD remained rather non-specific despite AD's complex etiology. Failing to take into account the underlying inflammatory pathways led to treatments with inadequate efficacy or unacceptable long-term toxicities. We are currently in the midst of a therapeutic renaissance in AD. Recent progress in molecular medicine provides us a better understanding of the AD pathogenesis, suggesting a dominant helper T cell (Th) 2/Th22 response with a varying degree of Th1/Th17 overexpression. Targeted therapeutic agents including biologics and small molecule inhibitors in development hold promises for more effective and safer therapeutic approaches for AD. A better understanding of individual differences amongst AD patients will allow for a more tailored approach in the future. This review aims to cover the most promising emerging therapies in the field of atopic dermatitis utilizing recently published manuscripts and up-to-date conference abstracts and presentations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prurigo pigmentosa is a rare inflammatory skin disease characterized by an unexpected onset of diffuse erythematous papules and macules usually on the chest, neck, and back. These generally resolve, ...leaving reticular hyperpigmentation. Rarely, vesicular or bullous forms have been reported. We present a case of exfoliative vesiculobullous prurigo pigmentosa in a 13-year-old boy. He presented with symmetrical eruption of papules and vesicles on his back, neck, and chest in the last 10 days, causing pruritis and prickling sensation. Within a few days, the bullous lesions and all affected areas of the skin showed exfoliation. Histological study and clinical findings indicated the condition to be vesiculobullous prurigo pigmentosa with exfoliation. Treatment with doxycycline 200 mg/day and topical tacrolimus ointment showed a good response. The lesions resolved, leaving a light-brown reticulated hyperpigmentation. In conclusion, this was a case of exfoliative vesiculobullous prurigo pigmentosa in an adolescent man successfully treated with doxycycline and topical tacrolimus as an effective and safe treatment option.
Prolonged hyperglycemia results in pancreatic β‐cell dysfunction and apoptosis, referred to as glucotoxicity. Although both oxidative and endoplasmic reticulum (ER) stresses have been implicated as ...major causative mechanisms of β‐cell glucotoxicity, the reciprocal importance between the two remains to be elucidated. The aim of this study was to evaluate the differential effect of oxidative stress and ER stress on β‐cell glucotoxicity, by employing melatonin which has free radical‐scavenging and antioxidant properties. As expected, in β‐cells exposed to prolonged high glucose levels, cell viability and glucose‐stimulated insulin secretion (GSIS) were significantly impaired. Melatonin treatment markedly attenuated cellular apoptosis by scavenging reactive oxygen species via its plasmalemmal receptor‐independent increase in antioxidant enzyme activity. However, treatments with antioxidants alone were insufficient to recover the impaired GSIS. Interestingly, 4‐phenylbutyric acid (4‐PBA), a chemical chaperone that attenuate ER stress by stabilizing protein structure, alleviated the impaired GSIS, but not apoptosis, suggesting that glucotoxicity induces oxidative and ER stress independently. We found that cotreatment of glucotoxic β‐cells with melatonin and 4‐PBA dramatically improved both their survival and insulin secretion. Taken together, these results suggest that ER stress may be the more critical mechanism for prolonged high‐glucose‐induced GSIS impairment, whereas oxidative stress appears to be more critical for the impaired β‐cell viability. Therefore, combinatorial therapy of melatonin with an ER stress modifier may help recover pancreatic β‐cells under glucotoxic conditions in type 2 diabetes.
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