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Cartilage is frequently used as a scaffolds for repairing and reconstructing body surface organs. However, after successful plastic surgery, transplanted cartilage scaffolds often exhibit deformation and absorption over time. To enhance the shaping stability of cartilage scaffolds and improve patients' satisfaction after reconstructions, we employed the ear folding models in New Zealand rabbits to confirm whether the 1064nm neodymium‐doped yttrium aluminum garnet (Nd:YAG) laser could promote cartilage reshaping. There was an increase in collagen and aromatase (Cyp19) expression within the ear cartilage after laser treatment. Moreover, we have found that the Cyp19 inhibitor can inhibit the laser's effect on cartilage shaping and reduce collagen and Cyp19 expression. The overall findings suggest that treatment with 1064nm Nd:YAG laser irradiation can enhance estrogen levels in local cartilage tissues by upregulating Cyp19 expression in chondrocytes through photobiomodulation, thereby promoting the proliferation and collagen secretion of chondrocytes to improve cartilage reshaping and stability. [ABSTRACT FROM AUTHOR]

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome‐dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin‐3 and K63‐linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy‐dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 suppresses tumor growth and lung metastasis, and enhances the effect of BRAFV600E inhibition. Thus, we demonstrate critical roles of CCDC50‐mediated clearance of damaged lysosomes in supporting tumor growth, hereby identifying a potential therapeutic target of melanoma. Synopsis: CCDC50 acts as a lypophagy receptor, monitors lysosomal damage induced by metabolic stresses, and clears damaged organelles, which reduces ROS accumulation and supports tumor growth. CCDC50 recognizes and delivers damaged lysosomes to autophagosomes for degradation.The timely clearance of damaged lysosomes by CCDC50‐mediated lysophagy contributes to tumor maintenance and progression.A combination of CCDC50 interference and BRAF inhibitor treatment shows an additive effect on the regression of xenografted tumors. [ABSTRACT FROM AUTHOR]

Malignant gliomas are one of the most common and lethal brain tumors with poor prognosis. Most patients with glioblastoma (GBM) die within 2 years of diagnosis, even after receiving standard treatments including surgery combined with concomitant radiotherapy and chemotherapy. Temozolomide (TMZ) is the first-line chemotherapeutic agent for gliomas, but the frequent acquisition of chemoresistance generally leads to its treatment failure. Thus, it's urgent to investigate the strategies for overcoming glioma chemoresistance. Currently, many studies have elucidated that cancer chemoresistance is not only associated with the high expression of drug-resistance genes in glioma cells but also can be induced by the alterations of the tumor microenvironment (TME). Numerous studies have explored the use of antifibrosis drugs to sensitize chemotherapy in solid tumors, and surprisingly, these preclinical and clinical attempts have exhibited promising efficacy in treating certain types of cancer. However, it remains unclear how tumor-associated fibrotic alterations in the glioma microenvironment (GME) mediate chemoresistance. Furthermore, the possible mechanisms behind this phenomenon are yet to be determined. In this review, we have summarized the molecular mechanisms by which tumor-associated fibrotic reactions drive glioma transformation from a chemosensitive to a chemoresistant state. Additionally, we have outlined antitumor drugs with antifibrosis functions, suggesting that antifibrosis strategies may be effective in overcoming glioma chemoresistance through TME normalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhang, Chen and Ni.)

Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how PTEN deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that PTEN deficiency induces a symbiotic glioma-M2 macrophage interaction to support glioma progression. Mechanistically, PTEN -deficient GBM cells secrete high levels of galectin-9 (Gal-9) via the AKT-GSK3β-IRF1 pathway. The secreted Gal-9 drives macrophage M2 polarization by activating its receptor Tim-3 and downstream pathways in macrophages. These macrophages, in turn, secrete VEGFA to stimulate angiogenesis and support glioma growth. Furthermore, enhanced Gal-9/Tim-3 expression predicts poor outcome in glioma patients. In GBM models, blockade of Gal-9/Tim-3 signaling inhibits macrophage M2 polarization and suppresses tumor growth. Moreover, α-lactose attenuates glioma angiogenesis by down-regulating macrophage-derived VEGFA, providing a novel antivascularization strategy. Therefore, our study suggests that blockade of Gal-9/Tim-3 signaling is effective to impair glioma progression by inhibiting macrophage M2 polarization, specifically for PTEN -null GBM.