Arabidopsis cryptochromes interact with SOG1 to promote the repair of DNA double-strand breaks.

Cryptochromes (CRYs) are blue light (BL) photoreceptors to regulate a variety of physiological processes including DNA double-strand break (DSB) repair. SUPPRESSOR OF GAMMA RADIATION 1 (SOG1) acts as the central transcription factor of DNA damage response (DDR) to induce the transcription of downstream genes, including DSB repair-related genes BRCA1 and RAD51. Whether CRYs regulate DSB repair by directly modulating SOG1 is unknown. Here, we demonstrate that CRYs physically interact with SOG1. Disruption of CRYs and SOG1 leads to increased sensitivity to DSBs and reduced DSB repair-related genes' expression under BL. Moreover, we found that CRY1 enhances SOG1's transcription activation of DSB repair-related gene BRCA1. These results suggest that the mechanism by which CRYs promote DSB repair involves positive regulation of SOG1's transcription of its target genes, which is likely mediated by CRYs-SOG1 interaction.

Amputation Triggered by Gefitinib: An Unusual Clinical Presentation.

Gefitinib is an epidermal growth factor tyrosine kinase inhibitor used as a targeted chemotherapeutic agent in the treatment of lung cancer and other solid malignancies. The most common adverse effects of gefitinib include dermatological side effects and gastrointestinal symptoms, with rare reports of vascular side effects such as myocardial infarction and stroke. We recently reported a case of a patient with diabetes and multiple comorbidities who developed a serious lower limb vascular adverse event after gefitinib treatment, ultimately leading to amputation surgery. This is the first reported case of lower extremity amputation following gefitinib therapy in a patient with type 2 diabetes mellitus and lung adenocarcinoma. This case highlights the potential risk of amputation in diabetic patients receiving targeted therapies like gefitinib, especially in those with vascular complications. It emphasizes the importance of exercising extra caution when dealing with these patients.

Effects of synovial macrophages in osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease in mammals. However, its pathogenesis remains unclear. Studies indicate that OA is not only an aging process that but also an inflammation-related disease. Synovitis is closely related to the progression of OA, and synovial macrophages are crucial participants in synovitis. Instead of being a homogeneous population, macrophages are polarized into M1 or M2 subtypes in OA synovial tissues. Polarization is highly associated with OA severity. However, the M1/M2 ratio cannot be the only factor in OA prognosis because intermediate stages of macrophages also exist. To better understand the mechanism of this heterogeneous disease, OA subtypes of synovial macrophages classified by gene expression were examined. Synovial macrophages do not act alone; they interact with surrounding cells such as synovial fibroblasts, osteoclasts, chondrocytes, lymphocytes and even adipose cells through a paracrine approach to exacerbate OA. Treatments targeting synovial macrophages and their polarization are effective in relieving pain and protecting cartilage during OA development. In this review, we describe how synovial macrophages and their different polarization states influence the progression of OA. We summarize the current knowledge of the interactions between macrophages and other joint cells and examine the current research on new medications targeting synovial macrophages.

Efficacy of Photodynamic Therapy for the Treatment of Bowen's Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Photodynamic therapy is an established treatment option for Bowen's disease. Our meta-analysis was aimed at evaluating the efficacy and recurrence of photodynamic therapy or other topical treatments (5-fluorouracil, cryotherapy) and of photodynamic therapy alone or in combination with other therapies (ablative fractional CO2 laser or plum-blossom needle) for the treatment of Bowen's disease. METHODS: Trials that met our inclusion criteria were identified from PubMed, EMBASE, Web of Science, and Cochrane Library databases, and meta-analyses were conducted with RevMan V.5.4. The risk of bias was estimated with the Cochrane Collaboration's risk of bias tools. Complete response rate, recurrence, pain/visual analogue scale score, cosmetic outcome, and adverse events were considered as outcomes. RESULTS: Of the 2,439 records initially retrieved, 8 randomized controlled trials were included in this meta-analysis. According to our analyses, photodynamic therapy exhibited a significantly higher complete response rate (RR = 1.36, 95% CI [1.01, 1.84], I2 = 86%, p = 0.04), less recurrence (RR = 0.53, 95% CI [0.30, 0.95], I2 = 0%, p = 0.03), and better cosmetic outcome (RR = 1.34, 95% CI [1.15, 1.56], I2 = 0%, p = 0.0002) compared with other treatments. Moreover, there was a significant difference between the complete response rate of photodynamic therapy combined with ablative fractional CO2 laser and that of photodynamic therapy (RR = 1.85, 95% CI [1.38, 2.49], I2 = 0%, p < 0.0001). Photodynamic therapy combined with ablative fractional CO2 laser or plum-blossom needle also showed significantly less recurrence (RR = 0.21, 95% CI [0.09, 0.51], I2 = 0%, p = 0.0005) and a lower visual analogue scale score (RR = 0.51, 95% CI [0.06, 0.96], I2 = 0%, p = 0.03) than photodynamic therapy alone. However, there was no significant difference in the complete response rate between photodynamic therapy combined with ablative continuous CO2 laser and photodynamic therapy combined with ablative fractional CO2 laser (RR = 1.00, 95% CI [0.54, 1.86], I2 not applicable, p = 1.00). CONCLUSIONS: This meta-analysis shows that photodynamic therapy can be used in the treatment of Bowen's disease with better efficacy, less recurrence, and better cosmetic outcomes than cryotherapy and 5-FU. Some methods, including ablative fractional CO2 laser, can be applied in combination with photodynamic therapy to improve efficacy. However, which laser-assisted photodynamic therapy scheme has the most advantages in the treatment of Bowen's disease warrants further exploration.

Efficacy and Safety of Polyphenols for Osteoarthritis Treatment: A Meta-Analysis.

PURPOSE: Osteoarthritis (OA) is a chronic and degenerative disorder associated with joint pain and loss of joint function. It is reported that polyphenols could yield articular benefits in patients with OA through the inhabitation of key inflammatory pathways. This meta-analysis was conducted to assess the efficacy and safety of polyphenol products for OA treatment. METHODS: This study included searches of PubMed, EMBASE, and the Cochrane Library databases from inception to November 6, 2019. Randomized controlled trials (RCTs) comparing polyphenols versus NSAIDs or placebo for human OA were included. Standardized mean differences (SMD) or risk ratios (RRs) were calculated for all relevant outcomes. Meta-analyses were conducted by using random effect models, and heterogeneity was assessed by using the I2 statistic. FINDINGS: A total of 18 RCTs (N = 1724) were eligible for analysis. Polyphenol products showed a significant advantage over placebo on pain relief (SMD, -1.11; 95% CI, -1.35 to -0.87) and functional improvement (SMD, -1.14; 95% CI, -1.38 to -0.90). No differences in safety outcomes were detected between polyphenols and placebo. There were no differences in efficacy outcomes between polyphenols and NSAIDs, although patients receiving polyphenols had a lower but nonsignificant risk of experiencing gastrointestinal dysfunction compared with those treated with NSAIDs. Polyphenols and NSAIDs in combination yielded more significant benefits in efficacy than NSAIDs alone. IMPLICATIONS: The results of our study suggest that polyphenols may be a promising alternative for OA by relieving symptoms while reducing safety risks. However, the generalizability of our results may be limited by the quality and sample size of the available research, as well as the heterogeneity between RCTs. High-quality clinical trials are needed to make meaningful clinical practice recommendations.