Objective
Cuproptosis, a nascent and unique pattern of cell death, is poised to spark a new rush of biological research. Yet, the subsumed mechanism of cuproptosis in carcinoma is not wholly ...clarified. The exclusive aim of this work is to define a novel classification algorithm and risk-prognosis scoring framework based on the expression modalities of cuproptosis genes to monitor clear cell renal cell carcinoma (ccRCC) patients’ prognosis and immunotherapeutic response.
Methods
We pooled ccRCC data from three large-scale databases as the training subset and gathered a panel of clinical queues, termed the Taizhou cohort, which served as the validation setup. Wilcox test was conducted for comparison of expression variation, while the cox analysis and KM curves were utilized to visualize prognosis. Unsupervised clustering analysis was used to identify cuproptosis phenotypes in ccRCC. Concurrently, LASSO regression-based computational scoring model. A step further, gene set enrichment analysis (GSEA) was performed to check potential biological processes and the “CIBERSORT” R package was used to estimate the proportion of immune cells. To last, immunohistochemistry and qRT-PCR were carried out for the assay of critical genes for cuproptosis.
Results
Here, we glimpse the prognostic power of cuproptosis genes in pan-cancer by investigating 33 cancers with multi-omics data to map their genetic heterogeneity landscape. In parallel, we devoted extra attention to their strategic potential role in ccRCC, identifying two phenotypes of cuproptosis with different immune microenvironmental characteristics by pooling ccRCC data from three large-scale databases. Additionally, we compiled a cuproptosis scoring system for clinicians to determine the prognosis, immunotherapy response, and chemosensitivity of ccRCC patients. Notably, we assembled a clinical cohort sample to validate the pivotal gene for cuproptosis, FDX1, to supply more clues to translate the biological significance of cuproptosis in ccRCC.
Conclusion
In all, our investigations highlight that cuproptosis is involved in various components of ccRCC and assists in the formation of the tumor immune microenvironment. These results provide partial insights to further comprehend the molecular mechanisms of cuproptosis in ccRCC and could be helpful for the development of personalized therapeutic strategies targeting copper or cuproptosis.
Objective Ankylosing spondylitis (AS), an autoimmune disease, often leads to lower cervical spine fractures, with the potential for severe spinal nerve damage even from low-energy injuries. The ...optimal treatment approach remains debated. Methods A retrospective study involved 17 AS patients with lower cervical spine fractures who received anterior cervical fixation. Most presented cervicothoracic or thoracolumbar kyphosis, with 11 exhibiting neurological deficits. Patient characteristics, clinical data, visual analog scale (VAS), complications, and nerve recovery were analyzed. Results No postoperative neurological deterioration occurred. All cases experienced complete fusion of fractures during the follow-up period. Preoperative VAS significantly decreased at 3 days and 3 months post-surgery. Of the 11 patients with preoperative neurological deficits, approximately 54.5% showed improvement post-surgery. No complications were reported, such as esophageal fistula, wound infection, or fixation failure. Conclusion Anterior internal fixation is a possible treatment for AS-related lower cervical fractures. This approach ensures satisfactory spinal stability and neurological recovery with proper cranial traction and external fixation post-surgery. Our findings demonstrate that this surgical method is safe and effective.
This study aimed to develop a self-made C-arm camera shooting locator and verify its accuracy and advantages. A total of 60 physicians and nurses from the Surgical System of Sanmen People's Hospital, ...Zhejiang Province, China, were randomly selected as filming operators. The C-arm machine with a self-made locator and a C-arm machine without a locator were used to measure the center of the circular plate. The iron nails were used to shoot. The distance between the iron nail and the center point of the circular display area on display was defined as the shooting deviation. When it was less than 3 cm, the shooting was stopped. The number of shots, total shooting time, and first-shot deviation in the C-arm camera shooting groups with and without the locator were statistically analyzed, and the advantages and disadvantages of the two were compared. The average number of shots, average total shooting time, and average first-shot deviation of the C-arm camera using the locator were significantly better than those in the group without the locator, and the differences were statistically significant. When the shooting distance (X) was equal to 30 cm and the shooting angle (Y) was equal to 0°, the average number of shots, average total shooting time, and average first-shot deviation were optimal. The C-arm camera shooting locator can improve the shooting accuracy of the C-arm camera and effectively reduce the number of shots and total shooting time. Hence, it can be applied in clinical and surgical practice.
To investigate the effectiveness and feasibility of a novel vertebral osteotomy technique, transpedicular opening-wedge osteotomy (TOWO) was used to correct rigid thoracolumbar kyphotic deformities ...in patients with ankylosing spondylitis (AS).
Eighteen AS patients underwent TOWO to correct rigid thoracolumbar kyphosis. Radiographic parameters were compared before surgery, 1 week after surgery and at the last follow-up. The SRS-22 questionnaire was given before surgery and at the last follow-up to evaluate clinical improvement. The operating time, estimated blood loss and complications were analyzed.
The mean operating time and estimated blood loss were 236 min and 595 ml, respectively. The mean preoperative sagittal vertical axis (SVA), thoracic kyphosis (TK), pelvic tilt (PT) and thoracolumbar kyphosis (TLK) were 158.97 mm, 51.24 mm, 43.63 mm and 41.74 mm, respectively, and decreased to 66.72 mm, 35.96 mm, 27.21 mm and 8.67 mm at the last follow-up. The mean preoperative lumbar lordosis (LL) and sacral slope (SS) were 8.30 ± 24.43 mm and 19.67 ± 9.40 mm, respectively, which increased to 38.23 mm and 28.13 mm at the last follow-up. The mean height of the anterior column of osteotomized vertebrae increased significantly from 25.17 mm preoperatively to 37.59 mm at the last follow, but the height of the middle column did not change significantly. SRS-22 scores were improved significantly at the last follow-up compared with preoperatively. Solid bone union was achieved in all patients after 12 months of follow-up, and no screw loosening, screw removal or rod breakage was noticed at the last follow-up.
TOWO could achieve satisfactory kyphosis correction by opening the anterior column instead of vertebral body decancellation and posterior column closing, thus simplifying the osteotomy procedure and improving surgical efficacy.
Platelet-derived growth factor-BB (PDGF-BB) is a cytokine involved in tissue repair and tumor progression. It has been found to have expression differences between normal and degenerative ...intervertebral discs. However, it is not clear whether PDGF-BB has a protective effect on intervertebral disc degeneration (IDD). In this experiment, we treated nucleus pulposus cells (NPCs) with IL-1β to simulate an inflammatory environment and found that the extracellular matrix (ECM) anabolic function of NPCs in an inflammatory state was inhibited. Moreover, the induction of IL-1β also enhanced the expression of NLRP3 and the cleavage of caspase-1 and IL-1β, which activated the pyroptosis of NPCs. In this study, we studied the effect of PDGF-BB on IL-1β-treated NPCs and found that PDGF-BB not only significantly promotes the ECM anabolism of NPCs, but also inhibits the occurrence of pyroptosis and the production of pyroptosis products of NPCs. Consistent with this, when we used imatinib to block the PDGF-BB receptor, the above-mentioned protective effect disappeared. In addition, we found that PDGF-BB can also promote the ECM anabolism of NPCs by regulating the ERK, JNK, PI3K/AKT signaling pathways, but not the P38 signaling pathway.
studies, mice that blocked PDGF-BB receptors showed more severe histological manifestations of intervertebral disc degeneration. In summary, our results indicate that PDGF-BB participates in inhibiting the occurrence and development of IDD by inhibiting pyroptosis and regulating the MAPK signaling pathway.
Objectives:
Osteoarthritis (OA) is a common disease that mainly manifests as inflammation and destruction of cartilage and subchondral bone. Recently, necroptosis has been reported to play an ...important role in the development of OA. Selumetinib displays a contrasting expression pattern to necroptosis-related proteins. The present study aimed to investigate the potential therapeutic effects of selumetinib in OA process.
Methods:
In vitro
experiments, interleukin-1β (IL-1β) was used to induce necroptosis of chondrocytes. We used high-density cell culture, Western Blot and PT-PCR to observe the effect of different concentrations of selumetinib on the extracellular matrix of cartilage. Afterwards, we visualized the effect of selumetinib on osteoclast formation by TRAP staining and F-actin rings.
In vivo
experiment, we induced experimental osteoarthritis in mice by surgically destabilizing the medial meniscus (DMM) while administering different concentrations of selumetinib intraperitoneally.
Results:
Selumetinib promoted cartilage matrix synthesis and inhibited matrix decomposition. We found that selumetinib exerted a protective function by inhibiting the activation of RIP1/RIP3/MLKL signaling pathways in chondrocytes. Selumetinib also inhibited the activation of RANKL-induced NF-κB and MAPK signaling pathways in BMMs, thereby interfering with the expression of osteoclast marker genes. In the DMM-induced OA model, a postsurgical injection of selumetinib inhibited cartilage destruction and lessened the formation of TRAP-positive osteoclasts in subchondral bone.
Conclusion:
Selumetinib can protect chondrocytes by regulating necroptosis to prevent the progression of OA and reduce osteoclast formation. In summary, our findings suggest that selumetinib has potential as a therapeutic agent for OA.
Acylglycerol kinase (AGK) is a recently discovered mitochondrial lipid kinase, and mutation of its gene is the fundamental cause of Sengers syndrome. AGK is not only involved in the stability of ...lipid metabolism but also closely related to mitochondrial protein transport, glycolysis, and thrombocytopoiesis. Evidence indicates that AGK is an important factor in the occurrence and development of tumors. Specifically, AGK has been identified as an oncogene that partakes in the regulation of tumor cell growth, invasion, metastasis, and drug resistance. The versatility of AGK and its unique role in different types of cancerous and normal cells greatly piqued our interest. We believe that AGK is a promising target for cancer therapy. Therefore, this review summarizes the main research advances concerning AGK, including the discovery of its physiological/pathogenic mechanisms, and provides a reference for the feasible evaluation of AGK as a therapeutic target for human diseases, particularly tumors.
Cuproptosis is a fresh form of the copper-elesclomol-triggered, mitochondrial tricarboxylic acid (TCA) dependent cell death. Yet, the subsumed mechanism of cuproptosis-associated lncRNAs in carcinoma ...is not wholly clarified. Here, We appraised 580 cuproptosis-associated lncRNAs in sarcoma and thereafter construed a module composing of 6 cuproptosis lncRNAs, entitled CuLncScore, utilizing a machine learning methodology. It could outstandingly discern the prognosis of patients in parallel with discriminating tumor immune microenvironment traits. Moreover, we simulate the classification system of cuproptosis lncRNAs by unsupervised learning method to facilitate differentiation of clinical denouement and immunotherapy modality options. Notably, Our Taizhou cohort validated the stability of CuLncScore and the classification system. Taking a step further, we checked these 6 cuproptosis lncRNAs by Quantitative real-time polymerase chain reaction (qRT-PCR) to ascertain their authenticity. All told, our investigations highlight that cuproptosis lncRNAs are involved in various components of sarcoma and assist in the formation of the tumor immune microenvironment. These results provide partial insights to further comprehend the molecular mechanisms of cuproptosis lncRNAs in sarcoma and could be helpful for the development of personalized therapeutic strategies targeting cuproptosis or cuproptosis lncRNAs.
Mammalian cell membranes are decorated by the glycocalyx, which offer versatile means of generating biochemical signals. By manipulating the set of glycans displayed on cell surface, it is vital for ...gaining insight into the cellular behavior modulation and medical and biotechnological adhibition. Although genetic engineering is proven to be an effective approach for cell surface modification, the technique is only suitable for natural and genetically encoded molecules. To circumvent these limitations, non-genetic approaches are developed for modifying cell surfaces with unnatural but functional groups. Here, we review latest development of metabolic glycoengineering (MGE), which enriches the chemical functions of the cell surface and is becoming an intriguing new tool for regenerative medicine and tissue engineering. Particular emphasis of this review is placed on discussing current applications and perspectives of MGE.
Diabetes (DB) is a risk factor for osteoarthritis progression. High glucose (HG) is one of the key pathological features of DB and has been demonstrated to induce apoptosis and senescence in ...chondrocytes. Autophagy is an endogenous mechanism that can protect cells against apoptosis and senescence. The effects of HG on autophagy in cells including chondrocytes have been studied; however, the results have been inconsistent. The current study aimed to elucidate the underlying mechanisms, which could be associated with the contrasting outcomes. The present study revealed that HG can induce apoptosis and senescence in chondrocytes, in addition to regulating autophagy dynamically. The present study demonstrated that HG can cause oxidative stress in chondrocytes and suppress the AMPK pathway in a dose-dependent manner. Elimination of oxidative stress by Acetylcysteine, also called N-acetyl cysteine (NAC), downregulated autophagy and alleviated HG-stimulated apoptosis and senescence, while activation of the AMPK signaling pathway by AICAR not only upregulated autophagy but also alleviated HG-stimulated apoptosis and senescence. A combined treatment of NAC and AICAR was superior to treatment with either NAC or AICAR. The study has demonstrated that HG can suppress autophagy through the AMPK pathway and induce autophagy via oxidative stress in chondrocytes.
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