Objective To further comprehend the definition， molecular mechanism， and clinical significance of perineural invasion （PNI） so as to explore new therapy for the tumors. Methods The literatures about the definition， molecular mechanism， and clinical study of PNI were reviewed and analyzed. Results At present， widely accepted definition of PNI was that at least 33% of the circumference of the nerve should be surrounded by tumor cells or tumor cells within any of three layers of the nerve sheath. The newest theory on molecular mechanism of PNI was that PNI was more like infiltration， invasion， not just diffusion. “Path of low-resistance” and “Reciprocal signaling interactions” were the main theories. More recently， the studies had demonstrated that “Reciprocal signaling interactions” could more clearly explain the mechanism of PNI. Stromal elements， including fibroblasts， seemed to play a key role in the complex signaling interactions driving PNI. Neurotrophins and axonal guidance molecules had been implicated in promoting the progress of PNI. PNI was a prognosis index in the cancers of the head and neck， stomach， pancreas， colon and rectum， and prostate， which was positive indicated that the patients would have a poor prognosis and a low 5-year survival rate. Conclusions The mechanism of PNI is very complex， and its clear mechanism is still undefined. Keeping on researching the mechanism of PNI could provide theoretical foundation to disclose the mechanism and the therapy of PNI.
ObjectiveTo explore the mechanism of postoperative recurrence of hepatocellular carcinoma(HCC) and predicting the candidate drug. MethodsThe differently expressed genes of the human gene expression profiles with 35 postoperative recurrence of HCC tissues and 41 no recurrence of HCC tissues were identified. Then enriched these genes with gene ontology(GO) terms and KEGG pathway, and predicting the candidate drugs for suppress the postoperative recurrence using Connectivity Map(cmap) database. ResultsSeveral pathways such as Focal adhesion and MAPK signaling pathway were found involve in postoperative recurrence of HCC. Moreover, two candidate small molecule drugs(bambuterol and lovastatin) were found may suppress and postoperative recurrence of HCC. ConclusionFocal adhesion and MAPK signaling pathway may involve in the postoperative recurrence of HCC, bambuterol and lovastatin may candidate drugs for treat postoperative recurrence of HCC.
ObjectiveTo investigate the molecular mechanism of osteoclast differentiation induced by Staphylococcal peptidoglycan (PGN-sa). MethodsRaw264.7 cells were stimulated with PGN-sa and with PGN-sa+SC75741[a potent inhibitor of nuclear factor κB (NF-κB) activation] in a concentration of 200 ng/mL. The protein expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) was tested at 0, 1, 2, and 3 days; the proteins related to osteoclast differentiation of extracellular regulated protein kinases (ERK), p38, c-Jun N-terminal kinase (JNK), NF-κB, inhibitor of NF-κB (IκB-α), Akt, and the phosphorylation forms of p38, ERK, JNK, Akt, NF-κB were measured at 0, 5, 10, 20, 40, and 60 minutes by Western blot. In addition, Raw264.7 cells were stimulated with PGN-sa in the concentrations of 100 ng/mL (group A), 200 ng/mL (group B), 400 ng/mL (group C), and with PBS (group D) for 1, 2, and 3 days; the expression levels of tumor necrosis factor α (TNF-α), interleukin 1α (IL-1α), and IL-6 were detected by ELISA. ResultsThe results of Western blot showed that the expression of NFATc1 increased gradually with time, showing significant difference between different time points (P<0.05). However, after SC75741 was added, the expression of NFATc1 was inhibited at 2 and 3 days, showing significant difference when compared with no addition of SC75741 (P<0.001). After stimulation of PGN-sa, the expression of IkB-α decreased significantly at 5 and 10 minutes when compared with those at the other time points (P<0.001), and returned to normal at 20 minutes. Meanwhile, the expression of p-NF-κB increased significantly at 5 and 10 minutes when compared with those at the other time points (P<0.001), and returned to normal at 20 minutes; and the expression of p-NF-κB at 5 minutes was significantly higher than that at 10 minutes (P<0.001). After the addition of SC75741, there was no change in the expressions of IκB-α and p-NF-κB, showing no significant difference between different time points P>0.05). Moreover, the expressions of ERK, p38, JNK, NF-κB, Akt, p-p38, p-ERK, p-JNK, and p-Akt showed no significant change between different time points P>0.05). ELISA results showed that there were no expressions of TNF-α and IL-1α in groups A-D at different time points. The expression of IL-6 had an increasing trend with time prolonged in each group, showing significant differences between different time points (P<0.05). Moreover, at 1 day after culture, the expression of IL-6 showed no significant difference among groups P>0.05). At 2 and 3 days after culture, the expression of IL-6 in groups A-C showed an increasing trend and was significantly higher than that in group D, showing significant difference among groups (P<0.05). ConclusionPGN-sa can promote osteoclast differentiation through NF-κB signaling pathway, and IL-6 may play a role in this process.
Angiopoietin-like protein (ANGPTL), a group of secreted glycoproteins, is widely expressed in vivo and is involved in many pathophysiological processes such as glycolipid metabolism, stem cell growth, local inflammation, vascular leakage and angiogenesis. Many kinds of ANGPTL are closely related to the occurrence and development of diabetic retinopathy (DR), especially ANGPTL4, which has gradually become a new hotspot in the field of DR Research. ANGPTL is involved in glucose metabolism and lipid metabolism, promotes increased vascular permeability, pathological angiogenesis, and participates in intraocular inflammation. ANGPTL is a promising molecular target. It can not only be used as a biomarker to predict the occurrence and progression of DR, but also provide new ideas for the treatment of DR by making antibody drugs to interfere with this molecule.
Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that not only impairs vision and quality of life but has also emerged as a leading cause of blindness in working-age individuals. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (LncMALAT1) is a non-coding RNA molecule that regulates gene expression and has been implicated in the pathogenesis and progression of DR. It exerts its effects through the modulation of various pathological processes, including inflammation, oxidative stress, angiogenesis, and apoptosis. Notably, alterations in the expression levels of LncMALAT1 may serve as potential biomarkers for the early diagnosis of DR. Furthermore, interventions targeting LncMALAT1, employing antioxidants, anti-angiogenic agents, traditional Chinese medicine, and gene therapy, present promising avenues for its potential development as an effective therapeutic target for DR.