Gut Microbiota Disorders in Obesity-Associated Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH), commonly seen in older men, can cause symptoms of discomfort, and may even need surgical intervention. Studies have shown the potential link between gut microbes and BPH, but the molecular association is not fully understood. METHODS: Four-week-old male Sprague-Dawley rats (n = 16) were randomly allocated to normal control diet (ND, 10% fat) and high-fat diet-induced BPH (HFD, 45% fat) groups. Metagenomic analysis was used to examine the abundance and discrepancies in gut microbiota within the two groups after 24 weeks of feeding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted to assess the biological functions of the differentially expressed genes. RESULTS: Rats with HFD-induced obesity exhibited morphological abnormalities in their prostate tissues. Metagenomic analysis of the gut revealed that Firmicutes were the dominant phyla in the HFD group, whereas the ND group had a higher abundance of Spirochaetes. At the genus level, Ruminococcus spp exhibited greater abundance in the HFD group, whereas Treponema spp were more abundant in the ND group. KEGG analysis demonstrated that the differentially expressed genes were mainly enriched in the NOD-like receptor (NLR) signaling, PI3K-Akt signaling, estrogen-signaling, signalings associated with GABAergic synapses, pantothenate and CoA biosynthesis. CONCLUSION: The findings of our study indicated that there was a notable variation in the microbiota abundance within the intestinal tract of obese rats suffering from prostate hyperplasia. It is plausible that these differentially abundant bacteria played a role in the development of pathological alterations in the prostate through the facilitation of inflammatory responses; however, additional research is required to validate the findings.

A novel 450-nm laser-mediated sinoporphyrin sodium-based photodynamic therapy induces autophagic cell death in gastric cancer through regulation of the ROS/PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Photodynamic therapy (PDT) has become an ideal and promising therapeutic method for fighting cancer, but its common application in clinical practice is prevented by the limitations of expensive devices in light sources and phototoxicity in photosensitizers. The aim of this study was to explore the antitumor efficiency of the novel 450-nm blue laser (BL) combined with sinoporphyrin sodium (DVDMS)-mediated PDT against human gastric cancer (GC) in vitro and in vivo, focusing on autophagy pathway. METHODS: Cell viability was detected by Cell Counting Kit-8 and colony formation assays in HGC27, MGC803, AGS, and GES-1 cells. Cell apoptosis was measured by flow cytometry and western blotting. The production of reactive oxygen species (ROS) was measured by fluorescence microscopy and flow cytometry. Autophagy was determined by transmission electron microscopy and western blotting. The antitumor effect of BL-PDT in vivo was detected by a subcutaneous tumor model in nude mice. RESULTS: The novel 450-nm laser-mediated DVDMS-based PDT caused remarkable growth inhibition and apoptosis induction in GC cells in vitro by the production of excessive ROS. Autophagy flux was induced by BL-PDT in GC cells, as determined by LC3 conversion assay, LC3 turnover assay, and mRFP-GFP-LC3 puncta assay. Furthermore, autophagy induction was demonstrated to positively contribute to BL-PDT-induced apoptotic effects on GC cells. Mechanically, ROS/PI3K/Akt/mTOR pathway was identified to involve in the regulation of BL-PDT-induced autophagy as determined by transcriptomic analysis and functional studies. Consistently, xenograft studies confirmed the significant antitumor effect of BL-PDT and its favorable safety in vivo. CONCLUSIONS: The novel 450-nm laser-mediated DVDMS-based PDT may be a safe and effective approach against GC. Our results thus provide compelling evidence for the therapeutic application of BL-PDT in human GC.

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer.

RBPs in the development and progression of BC remains unclear. Here, we elucidated the role of RBPs in predicting the survival of patients with BC. Clinical information and RNA sequencing data of the training and validation cohorts were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Survival-related differentially expressed RBPs were identified using Cox regression analyses. A total of 113 upregulated and 54 downregulated RBPs were observed, with six showing prognostic values (AHNAK, MAP1B, LAMA2, P4HB, FASN, and GSDMB). In both the GSE32548 and GSE31684 datasets, patients with low-risk scores in survival-related six RBPs-based prognostic model showed longer overall survival than those with high-risk scores. AHNAK, MAP1B, P4HB, and FASN expression were significantly upregulated in both BC tissues and cell lines. BC tissues from high-risk group showed higher proportions of naive CD4+ T cells, M0 and M2 macrophages, and neutrophils and lower proportions of plasma cells, CD8+ T cells, and T-cell follicular helper compared to low-risk group. AHNAK knockdown significantly inhibited the proliferation, invasion, and migration of BC cells in vitro and inhibited the growth of subcutaneous tumors in vivo. We thus developed and functionally validated a novel six RBPs-based prognostic model for BC.

Tensile creep mechanical behavior of periodontal ligament: A hyper-viscoelastic constitutive model.

OBJECTIVE: In orthodontic treatment, the biomechanical response of periodontal ligament (PDL) induces tooth movement. Coupling modeling of PDL can effectively reflect its biomechanical response. The nonlinear creep mechanical behavior of PDL was studied by uniaxial tensile creep test and a new hyper-viscoelastic constitutive model. Two coupling modeling methods with limitations were excluded. METHODS: PDL specimens were prepared from the central incisors of pig mandible. The theoretical step function was replaced by static loading with a total loading time of 1 s. The creep loading with the constant stresses of 0.05, 0.1, and 0.15 MPa was selected and kept unchanged for 1000 s. The instantaneous hyperelastic mechanical behavior and time-dependent nonlinear viscoelastic mechanical behavior of PDL were characterized by coupled instantaneous third-order Ogden hyperelastic and time-dependent nonlinear creep models. RESULTS: The results showed that the instantaneous elastic curve of PDL increases in the form of hyperelastic index. The creep strain and creep compliance curves increase rapidly before 200s, and then increase slowly in steady state. The creep strain increased with an increase in the constant stress; conversely, the creep compliance decreased with an increase in the constant stress. The results showed that the experimental data were highly consistent with the hyper-viscoelastic constitutive model (R2>0.97). SIGNIFICANCE: We normalize the framework of hyper-viscoelastic coupling modeling (Instantaneous hyperelastic model + time-dependent nonlinear viscoelastic model). Which can be extended to other nonlinear viscoelastic biomaterials.

A new perspective: Periodontal ligament is a viscoelastic fluid biomaterial as evidenced by dynamic shear creep experiment.

Currently, Periodontal ligament (PDL) is considered as a viscoelastic solid biomaterial. However, we observed the steady-state rheological behavior of PDL through long time loading experiments, and suggested the theoretical definition of PDL as a viscoelastic fluid biomaterial. PDL specimens were prepared from the middle area of the mandibular central incisors in pigs. Dynamic force loading with frequencies of 0 (static load), 2, 5, and 10 Hz and amplitudes of 0.01, 0.02, and 0.03 MPa was adopted. The shear strain-time curve at the equilibrium position of PDL was obtained by a dynamic shear creep experiment. The results showed that the shear strain increased exponentially at first and then inclined toward an oblique line. The results showed that the PDL has viscoelastic fluid characteristics, independent of frequency and amplitude. The shear strain decreased with an increase in frequency and amplitude. To further analyze the viscoelastic characteristics of PDL, a 50000-s static shear creep experiment was re-designed. PDL exhibited viscoelastic fluid biomaterial characteristics according to the three aspects of the algebraic fitting, geometric characteristics, and physical results. For the first time, a viscoelastic fluid constitutive model was established to characterize the mechanical properties of PDL with high fitting accuracy. Furthermore, the shear viscosity coefficient of the dynamic load was larger than that of the static load, increasing with an increase in frequency and amplitude; compared with the static force, the dynamic force improved the viscosity of PDL, enhancing its function of fixing teeth, and introducing the new medical knowledge of "No tooth extraction after a meal."