Objective To know the abnormal expression of the cell cycle-regulated proteins in pancreatic adenocarcinoma and their effect on tumor cell growth. Methods The expression of p16, p21, Rb and p53 protein in 47 cases were investigated by immunohistochemistry with wet autoclave pretreatment for antigen retriaval. Furthermore, tumor growth index were assessed by a novel anti-ki-67 antibody (ki-s5). Results All the expression of p53, p16, p21 and Rb protein were the nuclear stainning. The positive rates of p53, p16, p21 and Rb protein were 55%, 53%, 74% and 98% respectively. There was negative correlation between of p16, p21 or Rb protein expression and ki-67 growth index. No relation of p53 protein stainning and the expression of p21 protein was found. Conclusion In pancreatic adenocarcinoma, the negative expression of p16 protein and p21 protein may play an important role in tumor cell growth, but tumor proliferation caused by abnormality of Rb protein is rare. The expression of p21 protein was not associated with the expression of p53 protein.
Mitochondrial quality control includes mechanisms such as mitochondria-derived vesicles, fusion / fission and autophagy. These processes rely on the collaboration of a variety of key proteins in the inner and outer membranes of mitochondria to jointly regulate the morphological structure and functional integrity of mitochondria, repair mitochondrial damage, and maintain the homeostasis of their internal environment. The imbalance of mitochondrial quality control is associated with leukemia. Therefore, by exploring the mechanisms related to mitochondrial quality control of various leukemia cells and their interactions with immune cells and immune microenvironment, this article sought possible targets in the treatment of leukemia, providing new ideas for the immunotherapy of leukemia.
Objective To elucidate the role of the transcription factor liver activator protein (LAP, a member of the C/EBP family) in the expression of α1(I) collagen gene in activated hepatic stellate cells (HSCs). Methods Rat HSCs were prepared from SD rats by in situ perfusion and singlestep density Nycodenz gradient. Two chimeric luciferase reporter gene plasmids containing the human collagen α1(I) gene promoter fragments (-804～+1 452 or -804～+222) were constructed. Culture-activated HSCs were co-transfected with the reporter gene contructs and mammalian vector expressing LAP using the cationic-liposome mediated method, and the promoter activity was determined by measuring luciferase activity. Results The luciferase reporter gene construct containing the first intron of α1(I) collagen gene (-804～+1 452, was called as PGL3-col) had a higher level of gene expression, as compared with the construct lacking the first intron 〔was called as PGL3-col (△intron)-in activated HSCs (315±45 U/mg protein vs 220±70 U/mg protein, Ｐ＜0.05). Transient transfection of the vector expressing LAP significantly increased basal transcription from PGL3-col and PGL3-col (△intron) reporter gene vectors (587±62 U/mg protein vs 315±45 U/mg protein and 326±52 U/mg protein vs 220±70 U/mg protein respectively, both Ｐ＜0.05). Conclusion The transcription factor LAP transactivates collagen α1(I) gene in activated HSCs, and the first intron is important for α1(I) collagen gene transcription activity in activated HSCs.
Objective To summarize the regulatory effect of non-coding RNA (ncRNA) on type H vessels angiogenesis of bone. Methods Recent domestic and foreign related literature about the regulation of ncRNA in type H vessels angiogenesis was widely reviewed and summarized. ResultsType H vessels is a special subtype of bone vessels with the ability to couple bone formation. At present, the research on ncRNA regulating type H vessels angiogenesis in bone diseases mainly focuses on microRNA, long ncRNA, and small interfering RNA, which can affect the expressions of hypoxia inducible factor 1α, platelet derived growth factor BB, slit guidance ligand 3, and other factors through their own unique ways of action, thus regulating type H vessels angiogenesis and participating in the occurrence and development of bone diseases. ConclusionAt present, the mechanism of ncRNA regulating bone type H vessels angiogenesis has been preliminarily explored. With the deepening of research, ncRNA is expected to be a new target for the diagnosis and treatment of vascular related bone diseases.
Protein post-translational modifications (PTMs) are critical for modulating protein structure and function. Among these, lysine lactylation (Kla) has garnered significant attention in recent years as a newly discovered PTM. Although Kla has been thoroughly investigated in eukaryotic systems, its study in prokaryotes, especially bacteria, remains comparatively limited. Emerging research highlights that bacterial Kla, operating through dynamic modification mechanisms, is pivotal in processes such as growth and metabolism, virulence control, pathogenicity, and host-pathogen interactions. This article provides a comprehensive overview of the latest progress in bacterial Kla research, emphasizing its historical discovery, distinct modification features, and underlying molecular regulatory mechanisms. We further explore the regulatory roles of this modification in bacterial physiological processes and pathogenesis, concluding with a discussion of current research challenges and prospective future developments.
Objective To investigate the expression of cell division regulators p16, Rb and cyclin D1 in human early gasric carcinoma tissues and their role in tumor transformation and the correlation among p16, Rb and cyclin D1. MethodsA comparative study was carried out by using immuno-histochemical techniques between the paracarcinomatous intestinal metaplasia of 39 cases of early gatric carcinoma and the non-carcinomatous gastric mucosal intestinal metaplasia tissues of 34 cases.ResultsOver expression of cyclin D1 was determined in 33/39 carcinomatous samples(84.6%) and also in para-carcinomatous intestinal metaplasia tissues. p16 was undetectable in 12 of 39 samples. Interestingly, 15 of 26 Rb positive cancers had no or low p16,while 9 Rb negative cancers showed high levels of p16.Conclusion The over expression of cyclin D1 may be a common molecular abnormality and an early molecular event in early gastric carcinoma. Cyclin D1 over expression and Rb inactivation can co-exist in early gastric carcinoma. However, there is a reciprocity between Rb inactivation and p16 expression in early gastric carcinoma. Thus, abnormality in the negative feedback regulatory pathway of cyclin D1,Rb and p16 may be related to the tumorigenesis in early gastric carcinoma.
For those patients with refractory lower urinary tract dysfunction who are not well treated by traditional therapy such as behavior therapy and drug therapy, neuromodulation technologies have gradually become alternative treatments. Several neuromodulation technologies are also used in animal experimental and clinical scientific research by more and more scholars, in order to find more effective methods and mechanisms of treatment of lower urinary tract dysfunction. This article introduces the principle and advantages of common neuromodulation technologies, which focuses on the application in lower urinary tract dysfunction treatment, and analyzes the direction and the broad prospect of neuromodulation.
Objective To explore the molecular mechanism of LINC00626 regulating malignant progression of lung adenocarcinoma metastasis through JAK1/STAT3/KHSRP axis. Methods Quantitative real-time polymerase chain polymerase chain reaction was used to detect the expression of LINC00626 and KHSRP mRNA in human non-small-cell lung carcinoma cell lines (A549, H1299, H1975, H1437), human normal bronchial epithelial cell line (16HBE) and 144 lung adenocarcinoma tissues. The knockdown LINC00626 lentivirus and the control lentivirus were transferred into H1299 and H1437 cells, and named as sh-LINC00626 group (silencing of LINC00626 by transfecting short hairpin RNA lentiviral vector and sh-NC Group negative control by transfecting short hairpin RNA lentiviral). The overexpressed LINC00626 lentivirus and the control lentivirus were transferred into A549 and H1975 cells and named as LINC00626 group and Vector group. KHSRP vector on the basis of silencing LINC00626 and blank vector on the basis of silencing LINC00626 were added in H1437 cells. Cell counting kit-8 assay and Transwell migration/invasion assay were used to detect cell proliferation, migration and invasion. The expression levels of JAK/STAT and KHSRP in stably transfected cells were detected by Western blot. The effect of LINC00626 in vivo was studied in nude mice. Nuclear-cytoplasmic separation and RNA fluorescence in situ hybridization assay are used to predict the subcellular localization of LINC00626 and KHSRP. RNA pull down and mass spectrometry analysis were used to identify LINC00626 binding proteins. Results The expression levels of LINC00626 and KHSRP in non-small-cell lung carcinoma cell lines were significantly higher than those in normal human bronchial epithelial cells. LINC00626 and KHSRP were highly expressed in lung adenocarcinoma. Compared with the control group, the cell proliferation rate, colony formation, cell migration and invasion of H1437 cells were significantly decreased in knockdown group, while the reverse was true for over-expression. LINC00626 and KHSRP were located in the nucleus. LINC00626 directly binded to the KHSRP protein. Compared with the control group, H1437 cells transfected with knockdown LINC00626 and KHSRP significantly increased cell proliferation rate, cell migration, number of invasions. Compared with the control group, knockdown group showed a significant decrease in tumor volume and weight, cell proliferation rate and proliferation index, and the number of lung metastases. While the overexpression group showed an opposite effect, there were significant differences among the groups (P<0.01). The expression of JAK1 and STAT3 mRNA and protein in sh-LINC00626 group was lower than that in sh-NC Group (P<0.05), and the expression of JAK1 and STAT3 mRNA and protein in sh-LINC00626 group was higher than that in Vector group (P<0.05). Conclusion LINC00626 promotes malignant progression of lung adenocarcinoma metastasis through JAK1/STAT3/KHSRP signaling axis.
ObjectiveTo summarize the regulatory role of long non-coding RNA (lncRNA) in peripheral nerve injury (PNI) and neural regeneration.MethodsThe characteristics and mechanisms of lncRNA were summarized and its regulatory role in PNI and neural regeneration were elaborated by referring to relevant domestic and foreign literature in recent years.ResultsNeuropathic pain and denervated muscle atrophy are common complications of PNI, affecting patients’ quality of life. Numerous lncRNAs are upregulated after PNI, which promote the progress of neuropathic pain by regulating nerve excitability and neuroinflammation. Several lncRNAs are found to promote the progress of denervated muscle atrophy. Importantly, peripheral nerve regeneration occurs after PNI. LncRNAs promote peripheral nerve regeneration through promoting neuronal axonal outgrowth and the proliferation and migration of Schwann cells.ConclusionAt present, the research on lncRNA regulating PNI and neural regeneration is still in its infancy. The specific mechanism remains to be further explored. How to achieve clinical translation of experimental results is also a major challenge for future research.