Melatonin serves as a novel treatment in bladder fibrosis through TGF-ß1/Smad and EMT.

BACKGROUND: Melatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms. MATERIALS AND METHODS: MEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-ß1 (TGF-ß1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-ß1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed. RESULTS: In vitro, we found that TGF-ß1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-ß1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis. CONCLUSION: Melatonin attenuates bladder fibrosis by blocking the TGF-ß1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

Current applications of nanomaterials in urinary system tumors.

The development of nanotechnology and nanomaterials has provided insights into the treatment of urinary system tumors. Nanoparticles can be used as sensitizers or carriers to transport drugs. Some nanoparticles have intrinsic therapeutic effects on tumor cells. Poor patient prognosis and highly drug-resistant malignant urinary tumors are worrisome to clinicians. The application of nanomaterials and the associated technology against urinary system tumors offers the possibility of improving treatment. At present, many achievements have been made in the application of nanomaterials against urinary system tumors. This review summarizes the latest research on nanomaterials in the diagnosis and treatment of urinary system tumors and provides novel ideas for future research on nanotechnologies in this field.

Targeting MUC1-C reverses the cisplatin resistance of esophageal squamous cell carcinoma in vitro and in vivo.

BACKGROUND: The efficacy of chemotherapeutic treatment of esophageal squamous cell carcinoma (ESCC) is limited by drug resistance during. This severely compromises the long-term survival rate of patients. Therefore, reversing chemotherapy resistance in ESCC may improve the therapeutic outcome. Here, we investigated the molecular mechanism of MUC1-C, the C-terminal transmembrane subunit of MUC1 (a transmembrane heterodimer protein), and its role in the reversal of cisplatin sensitivity in ESCC cells. METHODS: We assessed the efficacy of GO-203, a cell-penetrating peptide, as a chemotherapeutic target of MUC1-C using cell proliferation, colony-forming, and transwell assays. Apoptosis was analyzed in GO-203-treated cells by flow cytometry. Tumor xenograft assay was performed in nude mice to corroborate our in vitro findings. RESULTS: GO-203 treatment inhibited cell proliferation and restrained the migration and invasion of cisplatin-resistant ESCC. Moreover, targeting MUC1 resulted in enhanced apoptosis in GO-203-treated cells. These in vitro pro-apoptotic and anti-proliferative effects of GO-203 in combination with cisplatin were validated by in vivo models. Significantly smaller tumor volumes were observed in ESCCs-xenografted nude mice treated with GO-203 in combination with cisplatin compared with mice treated with monotherapy or their control counterparts. We found that blocking MUC1-C with GO-203 significantly reversed the cisplatin resistance in ESCC via modulating Akt and ERK pathways. CONCLUSIONS: Our findings suggest that GO-203 may hold potential as an ancillary therapeutic molecule and a chemosensitizer to improve the outcomes of cisplatin-based chemotherapy especially in patients with cisplatin-resistant ESCC.

Effects of multiple drilling on the ischemic capital femoral epiphysis of immature piglets.

PURPOSE: This study investigated the effects of multiple drilling on the immature capital femoral epiphysis following ischemic injury in a piglet model. MATERIALS AND METHODS: Ischemic necrosis of capital femoral epiphysis was induced bilaterally in 12 piglets using a cervical ligation method. Three weeks later, medial, central, and lateral 3 drill holes were made on the left femoral head using 0.062" K-wire. At 3, 6, 9, and 12 weeks following the multiple drilling, femoral heads were harvested from each three piglets. On histologic examination, percent of revascularization, percent of osteoblast surface, capital femoral epiphyseal quotient and proximal femoral growth plate height were evaluated. Untreated right femoral heads served as control. RESULTS: While percent of revascularization of left capital femoral epiphysis with multiple drilling was significantly higher than untreated control side (p<0.001), percent of osteoblast surface, capital femoral epiphyseal quotient and proximal femoral growth plate height showed no significant difference. CONCLUSION: This study indicates that multiple drilling could promote revascularization of ischemic capital femoral epiphysis, and multiple drilling does not appear to produce bony physeal bars at short-term, if using small diameter drill. However, multiple drilling alone does not seem to prevent femoral head deformity or to promote new bone formation.

[Survey of studies on adjuvant diagnostic method of stimulating auricular points at home and abroad].

The auricular (including auricular acupoints) adjuvant diagnostic method, besides inspection (including dyeing method), palpation (including thermometric method), tenderness method (including impressing method) and electrical detection, includes the adjuvant diagnostic method of stimulating auricular points as well, it has been mostly studied and used by specialists of western medicine or doctors of integrated Chinese and western medicine. But it hasn't been introduced in the published Chinese monographs of auricular acupuncture yet. This article briefly introduces the adjuvant diagnostic method of stimulating auricular points combined with X-ray radiography; application in fetal heart electronic monitoring and fetal biophysical monitoring; and diagnostic methods of auricle reflex, vascular autonomous signals, and auricle and somatic 7 frequency response regions, which began to be researched abroad 35 years ago. The authors hope it will give some invigoration or illumination to my colleagues in acupuncture, especially those who are interested in auricular acupuncture.

The microrheological changes in the course of erythrocyte senescence after phenylhydrazine injection.

To study the microrheological characteristics of RBCs during erythrocyte senescence in vivo, an anemia model of rabbit induced by phenylhydrazine injection was developed. Measurements of the hematocrit, the deformation indexes, the blood viscosity and the sedimentation, etc. were performed in vivo for more than 60 days in the processes of RBC senescence. Obvious changes in the RBC's rheological characteristics were found in this senescent model. Compared with our previously developed Wen's model [1,2] in which the entire RBC population was nearly synchronously produced following the induction of spherocytic anemia in the rabbit with antibody serum, the changes of RBC microrheological characteristics for this model showed approximately the same tendency, although Wen's model with antibody serum was much better in its ability to simulation of the nearly normal physiological conditions than the present one with phenylhydrazine injection. Hence, the present model can serve as a model of RBC senescence under abnormal physiological conditions.