Search

Osteoclasts (OCs) and regulatory CD4+ T cells (CD4+Tregs) are important components in the tumor microenvironment (TME) of osteosarcoma. In this study, we collected six osteosarcoma samples from our previous study (GSE162454). We also integrated a public database (GSE152048), which included single cell sequencing data of 11 osteosarcoma patients. We obtained 138,192 cells and then successfully identified OCs and CD4+Tregs. Based on the interaction gene set between OCs and CD4+Tregs, patients from GSE21257 were distinguished into two clusters by consensus clustering analysis. Both the tumor immune microenvironment and survival prognosis between the two clusters were significantly different. Subsequently, five model genes were identified by protein–protein interaction network based on differentially upregulated genes of cluster 2. Quantitative RT‐PCR was used to detect their expression in human osteoblast and osteosarcoma cells. A prognostic model was successfully established using these five genes. Kaplan–Meier survival analysis found that patients in the high‐risk group had worse survival (p = 0.029). Therefore, our study first found that cell–cell communication between OCs and CD4+Tregs significantly alters TME and is connected to poor prognosis of OS. The model we constructed can accurately predict prognosis for osteosarcoma patients. [ABSTRACT FROM AUTHOR]

Hypertrophic scars (HSs) form due to unchecked proliferation of fibrous tissue after an injury to the skin. Recently, lncRNA MIR503HG was shown to be involved in HS. However, the mechanism by which MIR503HG affects the formation and progression of HS still needs further study. qRT‐PCR was applied to examine the levels of MIR503HG and miR‐143‐3p in HS tissues and human hypertrophic scar fibroblasts (hHSFs). The relationships of MIR503HG, miR‐143‐3p and Smad3 were explored with a dual‐luciferase reporter assay. Cell proliferation, apoptosis, and invasion were measured by CCK‐8 assay, flow cytometry and transwell assay, respectively. The protein level of Smad3 was tested via Western blotting. MIR503HG was upregulated and miR‐143‐3p was downregulated in HS versus normal skin tissues. The knockdown of MIR503HG and the overexpression of miR‐143‐3p suppressed the proliferation and invasion of hHSF, and promoted cell apoptosis. MIR503HG bound to miR‐143‐3p while miR‐143‐3p directly targeted Smad3 to inhibit its expression. Suppression of miR‐143‐3p and overexpression of Smad3, respectively, reversed these effects of knockdown of MIR503HG and overexpression of miR‐143‐3p on hHSFs. Our research supports a model in which the MIR503HG/miR‐143‐3p/Smad3 axis serves as a critical regulator of HS, highlighting a promising therapeutic option for HS. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HS) is a pathological scar that often occurs in burn patients. Its histology is characterized by the excessive proliferation of fibroblasts (FB) and excessive accumulation of extracellular matrix (ECM). Inhibition of proliferation and activation of FB is essential for the treatment of HS. The crude extracts of traditional Chinese medicines have beneficial therapeutic effects on HS besides possessing fewer side effects and being easily available. Polyphyllin VII (PP7) is an isoprene saponin isolated from Rhizoma paridis. It has a pro-apoptotic effect on cancer cells. In the present study, we demonstrate that PP7 exerts a significant inhibitory effect on hypertrophic scar fibroblasts (HSFs) in vitro. We also demonstrate that PP7 considerably induces the apoptosis of HSFs and inhibits their activity. Our data show that the PP7-induced HSFs cell apoptosis was mainly due to the enhanced expression of apoptotic genes (Bax, Caspase-3, Caspase-9) and decreased expression of Bcl-2. Moreover, PP7 treatment also enhances the expression of JNK, but that of extracellular protein kinases (ERK) was reduced, and induces apoptosis through ERK/JNK pathways. Thus, PP7 can be used as a drug to prevent the formation of HS. [ABSTRACT FROM AUTHOR]

Osteoclast activation by wear particles has caused major difficulties for surgeons. Wear particles are the main causes of aseptic prosthetic loosening. Gö6983, a protein kinase C inhibitor, inhibits five subtypes of protein kinase C family members. Here, we found that Gö6983 had an obviously inhibitory effect on wear-particles-induced osteolysis in vivo . In vitro , Gö6983 inhibited RANKL-stimulated osteoclast formation and function by inhibiting the RANKL-stimulated nuclear factor-κB/JNK/p38 signaling pathway. We also observed that Go6983 had no effect on the differentiation of osteoblasts and osteoblast-associated genes expression. According to our data, Gö6983 has potential therapeutic effects for aseptic prosthetic loosening caused by osteoclast activation. [ABSTRACT FROM AUTHOR]

Introduction: The Meek micrografting technique used in STSG expansion is effective in achieving wide and rapid coverage of burn wounds. Certain growth factors have also been shown to modulate or mediate wound healing., Objective: In this study, a combined treatment approach for severe burns involving the Meek micrografting technique, systemic application of rhGH, and topical application of rhEGF was evaluated., Materials and Methods: A retrospective study was conducted of 7 extensively burned patients who were treated with the Meek technique, systemic application of rhGH, and topical application of rhEGF between January 2017 and December 2019., Results: The mean percent TBSA burned was 89%. An average of 9.5 surgical procedures were performed to obtain skin cover, with an average of 5.8 Meek micrograft procedures performed in the 6 surviving patients. Complete wound healing was achieved at an average of 120 days in the 6 surviving patients. The mean graft take rate was 81%. Infection was the main reason for graft failure. Donor sites were used for up to 5 re-harvestings without additional morbidity., Conclusions: A multipronged treatment approach that combines the Meek micrografting technique, systemic application of rhGH, and topical application of rhEGF is a promising tool for the management of severe and extensive burns.

Osteoclasts (OCs) and regulatory CD4 + T cells (CD4 + Tregs) are important components in the tumor microenvironment (TME) of osteosarcoma. In this study, we collected six osteosarcoma samples from our previous study (GSE162454). We also integrated a public database (GSE152048), which included single cell sequencing data of 11 osteosarcoma patients. We obtained 138,192 cells and then successfully identified OCs and CD4 + Tregs. Based on the interaction gene set between OCs and CD4 + Tregs, patients from GSE21257 were distinguished into two clusters by consensus clustering analysis. Both the tumor immune microenvironment and survival prognosis between the two clusters were significantly different. Subsequently, five model genes were identified by protein-protein interaction network based on differentially upregulated genes of cluster 2. Quantitative RT-PCR was used to detect their expression in human osteoblast and osteosarcoma cells. A prognostic model was successfully established using these five genes. Kaplan-Meier survival analysis found that patients in the high-risk group had worse survival (p = 0.029). Therefore, our study first found that cell-cell communication between OCs and CD4 + Tregs significantly alters TME and is connected to poor prognosis of OS. The model we constructed can accurately predict prognosis for osteosarcoma patients., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Ferula lehmannii Boiss (FLB) is a perennial plant that belongs to the family Apiaceae, which is a traditional remedy used to treat gastric ulcers in Xinjiang. The main purpose of the research is to investigate the possible antiulcer effect of three different extracts, water decoction (WD), fresh liquid (FL), and chloroform extract (CE), using a model of acetic acid-induced gastric ulcer. 56 rats were divided into seven groups (n=8) and treated ranitidine and extracts of FLB. After 12 days of treatment, the ulcer index and biochemical parameters were evaluated. In all tested groups, the results indicated that the chloroform extract and water decoction highly significantly decreased the mucosal damage index as compared to the model group, restoration of glutathione per oxidase (GSH-PX) levels and super oxide dismutase (SOD) activity, and reduction of malondialdehyde (MDA) levels. The ulcer inhibition rate of water decoction group, fresh liquid and chloroform extract group reached 25.30%, 4.96% and 30.87%, respectively. The macroscopic observations were supported by histological findings. 44, 31, 32 compounds were identified through GC-MS analysis of different extracts. In conclusion, FLB exhibits potential anti-ulcer activity attributed to its high content terpenoid, phytosterin and fatty acid, the underlying antiulcer mechanism might be relevant to the reduction in inflammation and oxidative stress.