Prognostic and clinicopathological significance of FOXD1 in various cancers: a meta and bioinformation analysis.

Aim: To examine both predictive and clinicopathological importance underlying FOXD1 in malignant tumors, our study adopts meta-analysis. Methods: We searched from PubMed, Embase, WOS, Wanfang and CNKI. Stata SE15.1 was used to calculate the risk ratio (HR) as well as relative risk (RR) with 95% of overall CIs to assess FOXD1 and overall survival rate (OS), disease-free survival rate as well as clinicopathological parameters. Results: 3808 individuals throughout 17 trials showed high FOXD1 expression was linked to disadvantaged OS (p < 0.001) and disease-free survival (p < 0.001) and higher TNM stage (p < 0.001). Conclusion: Elevated FOXD1 had worse predictions and clinicopathological parameters in most cancers. The GEPIA database findings also support our results.

FOXD1 is a gene linked to a variety of cancers. In our article, we analyzed the results of several clinical trials in patients with different cancers. We found that when this gene is expressed in large amounts, it is often indicative of poor survival rates. From this study we can use FOXD1 to predict the course of the disease and at the same time study its upper and lower pathways to find therapeutic drugs to treat the cancer.

USP14 increases the sensitivity of retinoblastoma to cisplatin by mediating the ferroptosis.

The aim of this study is to explore the function of USP14 on the sensitivity of retinoblastoma (RB) to cisplatin (DDP) and the underlying mechanism. USP14 was knockdown in Y79 cells by transfecting three siRNAs (si-USP14-1, si-USP14-2, and si-USP14-3), with si-USP14 NC as the negative control. si-USP14-3 was selected by results of Western blotting. The CCK-8 assay was used to detect the IC50 of Y79 cells and the growth curve. The cell cycle, cell apoptosis, and ROS level were measured by flow cytometry. The expression level of P-GP, ERCC1, survivin, GPX4, FTH1, ACSL4, NOX1, COX2, and FASN was determined by the Western blotting assay. CO-IP assay was utilized to evaluate the interaction between USP14 and FASN. The IC50 of DDP in Y79 cells and Y79/DDP cells was 7.83 µM and 24.67 µM, respectively. Compared to control and si-USP14 NC groups, increased apoptotic rate and ROS level, and arrested cell cycle in S phase were observed in USP14-knockdown Y79 cells. Compared to control and si-USP14 NC groups, increased apoptotic rate and arrested cell cycle in G0/G1 phase were observed in USP14-knockdown Y79/DDP cells. Compared to control, increased ROS level was observed in USP14-knockdown Y79/DDP cells. Compared to the si-USP14 NC groups, extremely downregulated P-GP, ERCC1, survivin, GPX4, FTH1, NOX1, COX2, and FASN were observed in USP14-knockdown Y79 cells or Y79/DDP cells, accompanied by the elevated expression of ACSL4. The interaction between USP14 and FASN was identified according to the result of CO-IP assay. By silencing USP14 in Y79 and Y79/DDP cells, levels of resistance-related proteins (P-GP, ERCC1, and survivin), ferroptosis-related proteins (FTH1 and GPX4), and lipid metabolism-related proteins (NOX1, COX2, and FASN) were dramatically reduced, accompanied by enhanced ROS level, increased apoptosis, and restrained DNA content, indicating that USP14 might suppress the DDP resistance in RB by mediating ferroptosis, which is an important target for treating RB.

Mesopic pupil indices as potential risk factors for glare disability after intraocular implantable collamer lens implantation: prospective study.

PURPOSE: To explore the influence of preoperative factors, including varying pupil sizes and refractive attributes, on postoperative glare disability in patients undergoing implantable collamer lens (ICL) implantation. SETTING: Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China. DESIGN: Prospective observational study. METHODS: The preoperative ocular characteristics and 6-month postoperative glare status in eligible patients who underwent EVO-Visian ICL V4c (VICMO) implantation were analyzed. The glare disability criteria encompassed a glare symptom score >6 and glare sensitivity exceeding 1:2.7. Logistic regression analysis was used to explore the relationship between the preoperative ocular parameters and post-ICL glare. RESULTS: The study included 95 patients (mean age, 26.04 ± 6.29 years), comprising 30 men (58 eyes) and 65 women (129 eyes). Multivariate analysis revealed a significant correlation between postoperative glare disability and increased spherical power in preoperative mesopic pupils (ß = -0.124, P = .039), as well as elevated cylinder power in preoperative mesopic (ß = -0.412, P = .009) and photopic pupils (ß = -0.430, P = .007). Moreover, a larger preoperative mesopic pupil diameter (ß = 0.561, P = .005) demonstrated a significant correlation with glare disability. CONCLUSIONS: Preoperative mesopic pupil dimensions and associated refractive parameters, such as sphere and cylinder, were correlated with glare disability, including the cylinder aspect in photopic pupils, which can assist clinicians in optimizing preoperative selection for ICL implantation, aiding in the anticipation of potential glare disability risks.

Deubiquitinase USP33 promotes the glycolysis and growth of osteosarcoma by modifying PFKFB3 ubiquitination and degradation.

Osteosarcoma (OS) is the most common malignant tumor of the bone tissue with the lowest survival rate among all pediatric cancers. OS cells grow vigorously under malnutrition; however, the mechanism by which they adapt to metabolic stress via metabolic reprogramming remains undefined. Here, we demonstrated that USP33, a member of the DUBs family, was significantly upregulated in the tissues of patients with OS compared to normal tissues. Moreover, high USP33 expression was significantly associated with poor survival. Functional assays suggested that USP33 promoted OS cell growth through the induction of aerobic glycolysis. Additionally, we confirmed that 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) was critical for USP33-induced proliferation and aerobic glycolysis in OS cells, and the protein expression levels of PFKFB3 and USP33 were positively correlated in the OS tissues. Mechanistically, USP33 stabilized the expression of PFKFB3 by suppressing the ubiquitin mediated PFKFB3 degradation. Collectively, these findings reveal a mechanism by which OS cells survive in a dystrophic tumor microenvironment, with the USP33-PFKFB3 axis as a critical driver of aerobic glycolysis and OS proliferation. Furthermore, these findings reveal novel insights into the adaptation of cancer cells to metabolic stress in OS.

The Application of Platelet-Rich Plasma for Patients Following Total Joint Replacement: A Meta-Analysis of Randomized Controlled Trials and Systematic Review.

Background: The clinical efficacy of platelet-rich plasma (PRP) in the treatment of total joint replacement (TJR) remains inconclusive. In this paper, systematic review and meta-analysis was adopted to assess the efficacy of using PRP for the treatment of TJR. Methods: A comprehensive search of Medline, Embase, and Cochrane library databases for randomized controlled trial (RCT) articles recording data of PRP for TJR was conducted from inception to February 2022. Outcomes concerned were pain, range of motion (ROM), WOMAC score, length of hospital stay (LOS), hemoglobin (Hb) drop, total blood loss, wound healing rate, and wound infection. The methodological quality of the included RCTs was evaluated by using the Cochrane Risk of Bias Tool 2.0 (RoB 2.0). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was utilized to assess the level of evidence for the outcomes. Subgroup analysis was conducted according to the type of TJR. Results: Ten RCTs were included in the meta-analysis. In the TKA subgroup, the available data demonstrated that there were significant differences in the outcomes of pain and Hb drop, while it was the opposite of ROM, WOMAC score, LOS, total blood loss, wound healing rate, and wound infection. In the THA subgroup, no significant differences could be seen between two groups in the outcomes of LOS and wound infection. However, the PRP group gained a higher wound healing rate in the THA subgroup. Conclusion: The application of PRP did not reduce blood loss but improved the wound healing rate. However, more prospective and multicenter studies are warranted to confirm these results.

Long noncoding RNA UCA1 promotes carboplatin resistance in retinoblastoma cells by acting as a ceRNA of miR-206.

Chemoresistance has become a major obstacle to effective retinoblastoma treatment. The urothelial cancer-associated gene 1 (UCA1) is commonly considered an oncogene in certain types of cancer and is related to drug resistance. Nonetheless, the molecular mechanism and effect of UCA1 in carboplatin resistance in retinoblastoma are unclear. In this study, UCA1 expression was determined by sequential screening and lncRNA profile analysis, which is highly abundant in carboplatin-resistant retinoblastoma cells. Functional analyses revealed that UCA1 promoted carboplatin resistance by promoting c-Met and AXL expression. Mechanistic studies revealed that UCA1 facilitated c-Met and AXL expression as a ceRNA of miR-206. Importantly, retinoblastoma nude mouse model experiments revealed that targeting UCA1 or c-Met and AXL can restore drug sensitivity in carboplatin-resistant retinoblastoma. Collectively, we found that UCA1 is a mediator of carboplatin resistance in retinoblastoma cells. It competes with others as the endogenous RNA of miR-206, thus upregulating its targets, c-MET and AXL expression.

Possible role of miR-204 in optic nerve injury through the regulation of GAP-43.

Optic nerve injury is a common disease. The present study aimed to examine the possible role of microRNA­204 (miR­204) in optic nerve injury through the regulation of growth­associated protein-43 (GAP­43). Initially, optic nerve injury models were established in Sprague­Dawley (SD) rats, and the function of miR­204 was either enhanced or inhibited through injection of miR­204 mimic and inhibitor, respectively. Subsequently, the mRNA and protein levels of miR­204, GAP­43, toll­like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor­κB (NF­κB) were examined in retinal tissues using reverse transcription­quantitative polymerase chain reaction and western blot analyses. The apoptosis of retinal tissue cells was also detected using a terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay. There was a significant increase in the level of miR­204 in retinal blood vessels of the model SD rats, compared with that in the normal SD rats (P<0.05), and the expression of GAP­43 was significantly decreased (P<0.05). The results confirmed that the expression of GAP­43 was significantly reduced, compared with that in the normal control group when the rats were treated with miR­204 mimic (P<0.05), which was similar to the result in the model group. By contrast, its expression of GAP­43 was significantly increased when treated with the miR­204 inhibitor (P<0.05). Compared with the normal control group, the expression levels of TLR4, MyD88 and NF­κB were significantly increased in the miR­204 mimic group and model group (P<0.05), whereas the same three factors in the miR­204 inhibitor group were effectively inhibited, compared with those in the model group, and showed similar results to the normal control group. The apoptotic rates of retinal cells in the miR­204 mimic group and model group were significantly increased, compared with that in the normal control group (P<0.05), whereas miR­204 inhibitor effectively reversed the effects on apoptotic rate observed in the model group, showing similar results to those in the normal control group. Taken together, miR­204 promoted the apoptosis of retinal cells through inhibiting GAP­43, providing theoretical guidance for the function of GAP­43 in retinal injury.

Study on the genetic mutations of 17 alpha-hydroxylase/17,20-lyase deficiency in Chinese patients.

OBJECTIVE: To investigate the CYP17A1 gene mutations in Chinese patients with 17 alpha-hydroxylase/17, 20-lyase deficiency. METHODS: Clinical data were retrospectively analyzed. The CYP17A1 gene mutations were detected in 5 cases with 17 alpha-hydroxylase/17, 20-lyase deficiency and their relatives. The genomic DNA of the patients was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then sequenced. Sequencing results were compared to the established human CYP17A1 sequence. RESULTS: Briefly, we found 2 kinds of compound mutations, of which were: (1) 6436-6438(TAC-->AA), causing amino acid Y329K, 418X; (2) 6531-6532(GC-->A), causing amino acid L361F, 418X. Among the five cases, four were homozygous for 6436-6438(TAC-->AA), whereas one was compound heterozygous for 6436-6438(TAC-->AA)/6531-6532(GC-->A). The clinical characteristics of 5 cases were all completely combined defects of 17 alpha-hydroxylase/17, 20-lyase, and they all carried two alleles of CYP17A1 gene mutations that all shifted the reading frame and resulted in truncated protein which lack of the activity center site of P450C17, of which corresponding with their clinical feature. CONCLUSION: Nine alleles have the mutation of 6436-6438(TAC-->AA), accounting for 90% of total alleles (9/10). That suggests this kind of mutation may have racial specificity. More study should be done to have better understanding of the function of the truncated P450C17 enzymes.