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Transcription-coupled nucleotide excision repair is coordinated by ubiquitin and SUMO in response to ultraviolet irradiation
摘要: Cockayne Syndrome (CS) is a severe neurodegenerative and premature aging autosomal-recessive disease, caused by inherited defects in the CSA and CSB genes, leading to defects in transcription-coupled nucleotide excision repair (TC-NER) and consequently hypersensitivity to ultraviolet (UV) irradiation. TC-NER is initiated by lesion-stalled RNA polymerase II, which stabilizes the interaction with the SNF2/SWI2 ATPase CSB to facilitate recruitment of the CSA E3 Cullin ubiquitin ligase complex. However, the precise biochemical connections between CSA and CSB are unknown. The small ubiquitin-like modifier SUMO is important in the DNA damage response. We found that CSB, among an extensive set of other target proteins, is the most dynamically SUMOylated substrate in response to UV irradiation. Inhibiting SUMOylation reduced the accumulation of CSB at local sites of UV irradiation and reduced recovery of RNA synthesis. Interestingly, CSA is required for the efficient clearance of SUMOylated CSB. However, subsequent proteomic analysis of CSA-dependent ubiquitinated substrates revealed that CSA does not ubiquitinate CSB in a UV-dependent manner. Surprisingly, we found that CSA is required for the ubiquitination of the largest subunit of RNA polymerase II, RPB1. Combined, our results indicate that the CSA, CSB, RNA polymerase II triad is coordinated by ubiquitin and SUMO in response to UV irradiation. Furthermore, our work provides a resource of SUMO targets regulated in response to UV or ionizing radiation.
关键词: SUMOylation,DNA damage response,transcription-coupled nucleotide excision repair,Cockayne Syndrome,UV irradiation,ubiquitination
更新于2025-09-12 10:27:22
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Near‐infrared imaging and optical coherence tomography for intraoperative visualization of tumors
摘要: Surgical excision is the foundation of treatment for early-stage solid tumors in man and companion animals. Complete excision with appropriate margins of surrounding tumor-free tissue is crucial to survival. Intraoperative imaging allows real-time visualization of tumors, assessment of surgical margins, and, potentially, lymph nodes and satellite metastatic lesions, allowing surgeons to perform complete tumor resections while sparing surrounding vital anatomic structures. This Review will focus on the use of near-infrared imaging and optical coherence tomography for intraoperative tumor visualization.
关键词: optical coherence tomography,tumors,intraoperative visualization,surgical excision,near-infrared imaging
更新于2025-09-11 14:15:04
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Long-term outcomes of laser treatment for congenital melanocytic nevi
摘要: Background: Although various laser treatments have been tried for congenital melanocytic nevi (CMNs), only small retrospective studies with short-term follow-up had been done to assess outcomes. Objective: We analyzed the long-term outcomes of laser treatment for CMN and compared these outcomes with those of a combination treatment including partial excision and lasers. Methods: Patients with CMN treated with lasers were retrospectively reviewed, and patients with [3 years of follow-up were grouped as the long-term follow-up group. Results: A total of 67 cases of CMN were reviewed. Among 20 patients (20/52, 38.5%) with near total clearance during laser-only treatment, 11 patients were in the long-term follow-up group, and 5 of 11 showed repigmentation. In total, 15 patients showed repigmentation regardless of clearance, and the mean period until repigmentation was 3.93 years from the initial treatment. Patients with partial excision and laser combination treatment showed higher Investigator’s Global Assessment scores, fewer laser treatments, and shorter treatment periods compared with patients with laser-only treatment. Limitations: This is a retrospective study, and various laser devices were used. Conclusion: More than 4 years of follow-up is required to evaluate the efficacy of lasers in CMN, and partial excision and laser combination treatment might be an effective treatment option.
关键词: repigmentation,partial excision,laser treatment,congenital melanocytic nevi
更新于2025-09-11 14:15:04
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Removal of an Extra-large Irritation Fibroma With a Combination of Diode Laser and Scalpel
摘要: Introduction: Irritation fibroma is the most common tumor like and sub mucosal reactive lesion in the oral cavity. Usually it is measured less than 1.5 cm in diameter; however in rare case it has more than 3 cm in diameter. Different kind of treatment for soft tissue lesions include scalpel excision, electrical surgery, and laser surgery. The diode laser can be more effective than conventional surgery, electrosurgery and cryosurgery in reduction of bleeding and pain. Case Report: We reported a very large irritation fibroma in right lingual side of retromolar pad which was less prone to be traumatized under local irritation, in a woman wearing maxillary complete denture and use of both diode laser and scalpel for its excision.
关键词: Diode laser,Fibroma,Excision
更新于2025-09-11 14:15:04
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Transanal total mesorectal excision for rectal cancer with indocyanine green fluorescence angiography
摘要: Background The aim of this study was to evaluate the impact of fluorescence angiography (FA) on any change in proximal resection margin and/or anastomotic leak (AL) following transanal total mesorectal excision (TaTME) for rectal cancer (RC). Methods This retrospective cohort study was conducted at two centers by three senior surgeons. Both institutions’ prospectively maintained Institutional Review Board-approved databases were retrospectively queried for all consecutive patients between July 2015 and May 2017 who had laparoscopic hybrid trans-abdominal total mesorectal excision (TME) and TaTME for RC with colorectal or coloanal anastomosis < 10?cm from the anal verge. All patients had intraoperative FA to assess colonic perfusion of the planned proximal resection margin before bowel transection and after construction of the anastomosis. Primary outcomes measured any changes in proximal resection margins and AL rates. Results Fifty-four patients (31 males; mean age 63 ± 12?years) were included; 30 (55%) of whom received neoadjuvant chemoradiation. The average anastomotic height was 3.6?cm from the anal verge and 8 (14.5%) patients required intersphincteric dissection. Forty-six patients (85%) had loop ileostomy. FA led to a change in the proximal resection margin in 10 patients (18.5%), one of whom had AL on postoperative day 3 requiring diagnostic laparoscopy and loop ileostomy. A second patient, without a change in the proximal resection margin, also had an AL. The overall AL rate was 3.7%. Conclusions FA changed the planned proximal resection margin in 18.5% of patients, possibly accounting for the relatively low AL rate. FA is imperfect, and subjective but does have the potential to improve outcomes.
关键词: Transanal total mesorectal excision,Fluorescence angiography,Indocyanine green,Anastomotic leak,Rectal cancer,Resection margin
更新于2025-09-10 09:29:36