ABSTRACT
BACKGROUND: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer. METHODS: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques. RESULTS: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells. CONCLUSION: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.
Subject(s)
Urinary Bladder Neoplasms , Male , Humans , Prognosis , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/genetics , Urinary Bladder , Immunotherapy , Cell Culture TechniquesABSTRACT
Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II)-treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.
Subject(s)
Heart Failure , SOXC Transcription Factors , Sirtuin 3 , Animals , Mice , Rats , Angiotensin II/metabolism , Cardiomegaly/metabolism , Heart Failure/pathology , Myocytes, Cardiac/metabolism , Sirtuin 3/metabolism , SOXC Transcription Factors/metabolismABSTRACT
Objective To introduce a new design of interlocking system which is easy in use, makes the distal fracture fragments well aligned and rigidly fixated, reduces exposure to radiation for the surgeon and patient, and allows for a decrease in operating time. Methods The new interlocking system was designed to be a self-locking nail with bevels (b-SLN). According to the bevel principle, the axial force of the nail should be turned into a transverse force so as to control the transverse nail's movement. 10 dry-bone simples were made into the fracture model of the middle-femur to test the prototype nail. The retention of the nail in the intramedullary cavity was evaluated by the radiogram. The mechanical properties of a simulated model of single leg loading were tested on the instron-1342 type MTS. Results The prototype nail performed well as designed. The process was stable and reliable. The retention in the intramedullary cavity was fine. The shearing force between the transverse nail and main nail was enough to cut anything around them. The mechanical properties of b-SLN were similar to those of the Grosse-Kempf nail, better than auto fork compress locked intramedullary nail, and much better than MHUA nail and Ender's nail. Conclusions The structure of b-SLN is simple and reliable. There is no focus-point under stress. Its biomechanic properties are satisfactory. It is easy to use with no need of fluoroscopes in the operating theatre.
ABSTRACT
Rat's osteoblasts cultured in vitro were stimulated by recombinant bovine basic fibroblast growth factor(rb-bFGF). After 1-2 days, the osteoblast grew long protuberance, the numbers of osteoblasts were greater than the control groups', the vitality of osteoblasts was better than that of control groups. After 1 hour, the expression of c-fos in osteoblast increased when compared with that in the control group. After the osteoblasts having been stimulated for 1-2 days, the expression of c-fos increased more conspicuously. These results show that bFGF can boost the osteoblast to grow and proliferate and can enhance the expression of c-fos gene. The increase of c-fos gene's expression may be an important step in the signal transformation process of all kinds of stimulation boosting osteoblast to proliferate.
Subject(s)
Animals , Cattle , Rats , Cell Proliferation , Cells, Cultured , Fibroblast Growth Factor 2 , Pharmacology , Gene Expression Regulation , Genes, fos , Osteoblasts , Cell Biology , Metabolism , Proto-Oncogene Proteins c-fos , Metabolism , Rats, Wistar , Recombinant Proteins , PharmacologyABSTRACT
A new method to reconstruct a thumb was worked out in the past few years. It was achieved by inverting the skin flap of the amputated thumb stump and suturing it to an island-shaped skin flap with nerves and vessels from the dorsum of the index finger. A piece of artificial bone was inserted between the two skin flaps into the first phalanx. The operative procedure was described in detail and the indications, advantages and disadvantages of this method were discussed. It is suggested that this method be used to reconstruct a thumb since it is simple and effective.
