Evaluation of bi-directional causal association between periodontitis and benign prostatic hyperplasia: epidemiological studies and two-sample mendelian randomization analysis.

Background: Periodontitis and benign prostatic hyperplasia (BPH) are all common chronic diseases with higher incidence in middle-aged and old men. Several studies have indicated a potential association between periodontitis and BPH, although the findings remain inconclusive. However, there is no mendelian randomization (MR) studies to assess this association. Methods: The 40 men who had received health check-ups were included in an epidemiological study. Genetic data of BPH (13118 cases and 72799 controls) and periodontitis (3046 cases and 195395 controls) from FinnGen project was used to perform two-sample MR analysis. The inverse-variance weighted (IVW) model was identified as the primary analytical method, with MR Egger, weighted median, simple mode, and weighted mode serving as additional approaches. Results: The epidemiological analysis demonstrated a lack of statistically significant differences in the prevalence of clinical BPH between severe periodontitis group and non-severe periodontitis group. Similarly, no statistically significant differences were found in the prevalence of severe periodontitis among individuals with clinical BPH compared to those without. Additionally, Among the five models utilized in MR analysis, including the IVW model, no evidence of a causal link between periodontitis and BPH was observed. Conclusion: The findings from our epidemiological investigation and MR analysis do not provide support for a causal relationship between periodontitis and BPH.

Graph neural network model GGDisnet for identifying genes in gastrointestinal cancer and single-cell analysis.

Gastrointestinal cancer, a highly prevalent form of cancer, has been the subject of extensive research resulting in the identification of numerous pathogenic genes. However, validation and exploration of these findings often require traditional biological experiments, which are time-consuming and limit the ability to make extensive assessments promptly. To address this challenge, this paper introduces GGDisnet, a novel model for identifying genes associated with gastrointestinal cancer. GGDisnet efficiently screens human genes, providing a set of genes with a high correlation to gastrointestinal cancer for reference. Comparative analysis with other models demonstrates GGDisnet's superior performance. Furthermore, we conducted enrichment and single-cell analyses based on GGDisnet-predicted genes, offering valuable clinical insights.

Evaluation the relationship between myocardial fibrosis and left ventricular torsion measured by cardiac magnetic resonance feature-tracking in hypertrophic cardiomyopathy patients with preserved ejection fraction.

The relationship between left ventricular (LV) torsion and myocardial fibrosis (MF) in hypertrophic cardiomyopathy (HCM) patients with preserved ejection fraction was still not well understood. New developments in cardiac magnetic resonance (CMR) enable a much fuller assessment of cardiac characteristics. This study sought to assess the impact of HCM on myocardial function as assessed by LV torsion and its relationship with MF. HCM (n = 79) and healthy controls (n = 40) underwent CMR. According to whether there was late gadolinium enhancement (LGE), patients were divided into LGE+ group and LGE- group. LV torsion and torsion rate were measured by CMR feature-tracking (CMR-FT). MF was quantitatively evaluated through LGE imaging. LGE was present in 44 patients (56%). Compared with healthy controls, torsion increased in the LGE- group (P < 0.001). Compared with LGE+ group, torsion was higher in the LGE- group (P < 0.001). There was no significant difference in torsion between LGE+ group and healthy controls. Correlation analysis showed that torsion was correlated with LGE% (r = - 0.443) and LGE mass (r = - 0.435) respectively. On multivariable logistic regression analysis, LV torsion was the only feature that was independently associated with the presence of LGE (OR 0.130; 95% CI 0.040 to 0.420, P = 0.01). The best torsion value associated with MF was 1.91 (sensitivity 60.0%, specificity 77.3%, AUC = 0.733). In HCM patients with preserved ejection fraction, CMR-FT derived LV torsion analysis holds promise for myocardial fibrosis detection.

Functionalized PLGA Microsphere Loaded with Fusion Peptide for Therapy of Bone Defects.

The challenges in the treatment of extensive bone defects are infection control and bone regeneration. Bone tissue engineering is currently one of the most promising strategies. In this study, a short biopeptide with specific osteogenic ability is designed by fusion peptide technology and encapsulated with chitosan-modified poly(lactic acid-glycolic acid) (PLGA) microspheres. The fusion peptide (FP) mainly consists of an osteogenic functional sequence (P-15) and a bone-specific binding sequence (Asp-6), which can regulate bone formation accurately and efficiently. Chitosan-modified PLGA with antimicrobial and pro-healing effects is used to achieve the sustained release of fusion peptides. In the early stage, the antimicrobial and soft tissue healing effects can stop the wound infection as soon as possible, which is relevant for the subsequent bone regeneration process. Our data show that CS-PLGA@FP microspheres have antibacterial and pro-cell migration effects in vitro and excellent pro-wound-healing effects in vivo. In addition, CS-PLGA@FP microspheres promote the expression of osteogenic-related factors and show excellent bone regeneration in a rat defect model. Therefore, CS-PLGA@FP microspheres are an efficient biomaterial that can accelerate the recovery of bone defects.

Histatin 1-modified SIS hydrogels enhance the sealing of peri-implant mucosa to prevent peri-implantitis.

Dental implants make it possible to replace teeth in more sophisticated ways. Nevertheless, peri-implantitis is one of the leading causes of implant failure, which can be avoided with proper soft tissue sealing. The aim of this study was to achieve the promotion of the synthesis of peri-implant epithelial hemidesmosome through Histatin 1 and porcine small intestinal submucosa (SIS) hydrogel to form a good peri-implant seal. The results show that hydrogel can improve the biological barrier function around implants by combining antibacterial, promoting soft tissue healing and promoting epithelial bonding. This means that the morphology and anti-infection ability of soft tissue are enhanced, which ensures the long-term stability of the implant.SIS-Hst1 hydrogel has certain clinical application in the prevention and early treatment of peri-implantitis. In conclusion, Hst1-SIS hydrogel, as a local administration system, provides experimental evidence for the prevention of peri-implant disease.

A Bone Targeting Nanoparticle Loaded OGP to Restore Bone Homeostasis for Osteoporosis Therapy.

Restoring bone homeostasis is the key to the treatment of osteoporosis. How to increase osteogenic ability or inhibit osteoclast activity has always been a topic of great concern. In recent years, short peptides with biological activity have received great attention in bone repair. However, the application of short peptides is still limited due to the lack of a stable and targeted delivery system. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by alendronate (AL) to transport osteogenic peptides (OGP) (AL-PLGA@P NPs) are designed. Benefiting from the high affinity of AL for hydroxyapatite, AL-PLGA@P NPs have the ability to target bone. In this delivery system, OGP that promotes osteogenesis synergizes with AL, which inhibits osteoclasts, to regulate bone homeostasis, which gives them more advantages in the treatment of osteoporosis. The data shows that nanoparticles can selectively deliver peptides to the bone surface without systemic toxicity. Moreover, nanoparticles can upregulate osteogenesis-related factors (ALP, Runx-2, and BMP2) and downregulate osteoclast-related factors (TRAP and CTSK) in vitro. With AL-PLGA@P NPs, bone microarchitecture and bone mass are improved in ovariectomized osteoporosis rats. Therefore, this study proposes a novel osteoporosis-based drug system that effectively improves bone density.

An injectable multifunctional thermo-sensitive chitosan-based hydrogel for periodontitis therapy.

Bacteria are recognized as the driving factors of periodontitis. However, excessive reactive oxygen species (ROS) can harm periodontal tissue while also causing an uncontrolled inflammatory response. Hence, eliminating excessive ROS and blocking ROS-induced abnormal inflammatory response by antioxidants are achieving remarkable results in periodontitis therapy. Moreover, influenced by the deep and irregular periodontal pockets, injectable thermo-sensitive chitosan-based hydrogels have attracted a lot of attention. This study aimed to formulate an antibacterial and antioxidant therapeutic regimen by incorporating antimicrobial peptides (Nal-P-113) and/or antioxidants (polydopamine nanoparticles, PDNPs) into chitosan-based hydrogels. The hydrogel was characterized in vitro and finally examined in rats using the experimental periodontitis model. The release kinetics showed that the hydrogel could stably release Nal-P-113 and PDNPs for up to 13 days. The scavenging activity of the hydrogel against DPPH was about 80 % and the antibacterial ratio against Streptococcus gordonii (S. gordonii), Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P. gingivalis) was about 99 %. Importantly, it was examined that the hydrogel had the ability to prevent periodontal tissue damage. Thus, chitosan-based hydrogels may provide a basis for designing multifunctional local drug delivery biomaterials for the treatment of periodontitis.

Adtrp regulates thermogenic activity of adipose tissue via mediating the secretion of S100b.

Brown and beige adipose tissues dissipate chemical energy in the form of heat to maintain your body temperature in cold conditions. The impaired function of these tissues results in various metabolic diseases in humans and mice. By bioinformatical analyses, we identified a functional thermogenic regulator of adipose tissue, Androgen-dependent tissue factor pathway inhibitor [TFPI]-regulating protein (Adtrp), which was significantly overexpressed in and functionally activated the mature brown/beige adipocytes. Hereby, we knocked out Adtrp in mice which led to multiple abnormalities in thermogenesis, metabolism, and maturation of brown/beige adipocytes causing excess lipid accumulation in brown adipose tissue (BAT) and cold intolerance. The capability of thermogenesis in brown/beige adipose tissues could be recovered in Adtrp KO mice upon direct ß3-adrenergic receptor (ß3-AR) stimulation by CL316,243 treatment. Our mechanistic studies revealed that Adtrp by binding to S100 calcium-binding protein b (S100b) indirectly mediated the secretion of S100b, which in turn promoted the ß3-AR mediated thermogenesis via sympathetic innervation. These results may provide a novel insight into Adtrp in metabolism via regulating the differentiation and thermogenesis of adipose tissues in mice.

Deletion of Letmd1 leads to the disruption of mitochondrial function in brown adipose tissue.

Human cervical cancer oncogene (HCCR-1), also named as LETMD1, is an LETM-domain containing outer mitochondrial membrane protein which plays an important role in carcinogenesis. The present study found that the loss of Letmd1 in mice led to severe abnormities, such as brown adipose tissue (BAT) whitening, impaired thermogenesis of both BAT and beige fat, cold intolerance, diet-induced obesity, glucose intolerance and insulin resistance. Mechanically, the deletion of Letmd1 in BAT caused decreased level of both mitochondrial and intracellular Ca2+. The reduced intracellular Ca2+ could suppress the fission of mitochondria and ultimately lead to the disruption of BAT thermogenesis by regulating mitochondrial structures and functions. This study indicates that LETMD1 played a crucial role in BAT thermogenesis and energy homeostasis through regulating mitochondrial structures and functions, which provides a novel insight into therapeutic target exploration from oncogenes for metabolic disorders.

Research on the Development of Urban Parks Based on the Perception of Tourists: A Case Study of Taihu Park in Beijing.

With the development of the economy and society, the derivative needs beyond the basic survival needs of citizens are constantly expanding. The emergence of urban parks caters to the needs of citizens to relax, playing an important role in improving the ecological environment, providing leisure and recreation places, and having a good prospect of development. This paper takes Taihu Park in Beijing as an example, from the perspective of tourists. The influence factors are analyzed with the structural equation model, the influence of factors, and drawn up to a degree. The tourists' satisfaction and loyalty were positively related to the change; the tourists' satisfaction and complaints about change had a negative correlation and were put forward to strengthen the construction of infrastructure to park development. It is suggested to improve the functional level of the park and increase the selling point of commodities in the park.

Comprehensive analysis of expression signature and immune microenvironment signature of biomarker Endothelin Receptor Type A in stomach adenocarcinoma.

Background: EDNRA (Endothelin Receptor Type A) is closely associated with tumor progression in many tumor types. However, the functional mechanism of EDNRA in stomach adenocarcinoma (STAD) remains to be elucidated. Methods: ENDRA expression levels in STAD were assessed. A Receiver Operating Characteristic (ROC) curve was constructed to measure the diagnostic value of EDNRA. The correlation between ENDRA expression levels and patient clinical-pathological characteristics was analyzed. The survival and prognostic significance were validated using Kaplan-Meier and Cox regression and confirmed by the immunohistochemistry cohorts. Differentially expressed genes of EDNRA in STAD were determined, and EDNRA related functional enrichment and biological pathways involved in STAD were obtained by Gene-Set Enrichment Analysis (GSEA). The correlation between EDNRA expression in STAD and immune cell infiltration was assessed using the CIBERSORT and Spearman correlation analysis, and the correlation between EDNRA and TMB, MSI, IC50, and immune checkpoints was examined. Results: EDNRA expression was significantly higher in STAD than in normal tissues (P < 0.001) and associated with worse overall survival (OS). EDNRA expression was significantly associated with T stage, histological type, histologic grade, and TP53 status. Cox regression analysis revealed that primary therapy outcome, age, tumor status, and EDNRA were independent prognostic factors for OS. Multivariate analysis revealed that EDNRA expression, tumor status, age, and primary therapy outcome influenced patient prognosis. GSEA was significantly enriched in several pathways and biological processes, which include Immunoregulatory, Hedgehog, WNT, PI3K-AKT.NK cells, Tem, macrophages, and mast cells were substantially positively correlated with EDNRA expression in the STAD microenvironment. Notably, high EDNRA expression may promote M2 macrophages to block PD-1-mediated immunotherapy and induce immunosuppression. In addition, patients with high expression of EDNRA might be resistant to the treatment of several anti-tumor drugs. Conclusion: Our results suggest that EDNRA was closely related to clinicopathologic characteristics, poor prognosis, and promoted macrophage differentiation and synergistic role in immunosuppression.

18F-FDG PET/CT helps rule out malignancy in lipomatous hypertrophy of the interatrial septum with atypical MRI manifestations, to avoid unnecessary surgical treatment.

Lipomatous hypertrophy of the interatrial septum (LHIS) is a rare benign heart disease characterized by excessive deposition of adipose tissue in the atrial septum with sparing fossa ovalis, which demonstrates a characteristic hourglass/dumbbell configuration. We reported a case of LHIS with inhomogenous characteristic on CMR and persistently no FDG uptake on 18F-FDG PET-CT, which is contrary to a few previous cases. This single case report suggests that in case LHIS present in-homogenous characteristic on CMR, metabolic PET imaging could be used as a complementary imaging model to decrease the concern of lipomatous neoplasms, thereby avoid unnecessary surgical therapy.

Rapid determination and origin identification of total polysaccharides contents in Schisandra chinensis by near-infrared spectroscopy.

In this study, a classification model was established based on near-infrared spectroscopy and random forest method to accurately distinguish three samples of Schisandra chinensis from different habitats. At the same time, the feasibility of fast and effective prediction of polysaccharide contents in Schisandra chinensis by near-infrared spectroscopy combined with chemometrics was evaluated. In this paper, phenol sulfuric acid method was used to determine the content of total polysaccharides in samples, and partial least squares regression algorithm was used to link the spectral information with the reference value. Different spectral pretreatment methods were used to optimize the model to improve its predictability and stability. The results showed that random forest could distinguish these samples accurately, with an accuracy of 97.47%. In the established prediction model, the RMSEC of the optimal model calibration set is 0.0012, and the coefficient of determination R is 0.9976. The RMSEP of prediction set is 0.0024, the coefficient of determination R is 0.9922, and the RPD is 11.36. In general, the method has good stability and applicability, which provides a new analytical method for the identification of Schisandra chinensis origin and quality evaluation.

High Expression of ERK-related RASGRF2 predicts Poor prognosis in patients with Stomach Adenocarcinoma and correlates with M2 macrophage.

Background: The role of RASGRF2 has been verified in the development of various cancers. However, its roles in stomach adenocarcinoma (STAD) are still under investigation. Methods: RASGRF2 transcript-level data and the associated clinical information from patients with STAD were extracted from The Cancer Genome Atlas (TCGA). Diagnostic and prognostic values of RASGRF2 were analyzed using receiver-operator characteristics (ROC) analysis, correlation analysis, and survival analysis in conjunction with a prognostic model. In addition, gene expression profiles, differentially-expressed genes for co-varying expression, and a differential expressed genes (DEG) protein-protein interaction network for influential nodes were also analyzed. To identify the molecular role of RASGRF2 in STAD, gene ontology (GO) term, Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway, and gene set enrichment analysis (GSEA)-mediated functional module enrichment analyses were conducted. The relationship between RASGRF2 and gene signature-based predicted immune cell infiltration patterns were also investigated. To validate the bioinformatic findings, RASGRF2 protein expression was investigated in vitro using western blot and immunohistochemistry. Furthermore, relationships among RASGRF2 protein expression, clinicopathologic characteristics, and patient survival were analyzed. Results: Bioinformatic analysis revealed a significantly higher RASGRF2 transcript level in STAD tissue, which was positively associated with the T stage, histological type, histological grade, and TP53 status. Moreover, the RASGRF2 transcript level indicated poor overall survival in STAD patients (hazard ratio = 1.47, P = 0.023). Multivariate Cox regression analysis showed that primary therapy outcome, age, and RASGRF2 transcript level were independent prognostic factors for survival, and the C-index of a nomogram was 0.695. Additionally, 159 genes were differentially expressed according to RASGRF2 transcript levels; 15 exhibited co-varying expression, and 13 were identified as influential nodes. The DEG-list was significantly enriched for several GO terms, biological pathways, and functional modules, including MAPK, RAS, ERK, and immunoregulatory pathways. RASGRF2 transcript levels were significantly positively correlated with infiltration levels of Tem, Macrophages, pDCs, and NK cells. Validation analysis showed similar results for the RASGRF2 protein expression level in both in vitro analyses. Conclusion: Bioinformatic predictions combined with in vitro validation suggest that RASGRF2 plays diagnostic and prognostic roles and serves as a negative protective molecular factor in STAD patients.

Identification of a novel mutation gene signature HAMP for cholangiocarcinoma through comprehensive TCGA and GEO data mining.

Cholangiocarcinoma (CHOL), the second most common malignant liver tumor, is clinically heterogeneous. In this study, we used gene expression profiles of CHOL obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to identify novel mutation signatures in CHOL. Hepcidin antimicrobial peptide (HAMP) was identified as a novel diagnostic biomarker for CHOL using the intersection of mutation analysis and receiver operating characteristic (ROC) analysis. We then explored the expression signatures of HAMP in CHOL. HAMP-related differentially expressed genes (DEGs) were selected for the identification of hub genes related to HAMP and for prognostic prediction model analysis. Gene set enrichment analysis (GSEA) showed that the HAMP-related DEGs were mainly enriched for signaling pathways related to cholangiocarcinoma development. Through immunohistochemistry validation, clinical cohorts analysis, and TCGA analysis, we investigated the association between HAMP and clinical parameters and found that decreased HAMP expression was correlated with advanced pathological grade and poor prognosis. Besides, we estimated the immune infiltration level in CHOL and its relationship with HAMP expression. The proportion of tumor-infiltrating cells revealed that gamma delta T cells and monocytes were positively correlated with HAMP expression. Besides, HAMP was also correlated with chemokine, CCL16. This evidence suggested that HAMP might contribute to immune activation in the CHOL microenvironment. Therefore, HAMP may play a synergistic role with these immune cells and chemokines to inhibit CHOL development. HAMP serves as a valuable biomarker in CHOL and is closely correlated with its progression.

Cyanidin-3-o-Glucoside Pharmacologically Inhibits Tumorigenesis via Estrogen Receptor ß in Melanoma Mice.

Expression patterns of estrogen receptors [ERα, ERß, and G-protein associated ER (GPER)] in melanoma and skin may suggest their differential roles in carcinogenesis. Phytoestrogenic compound cyanidin-3-o-glucoside (C3G) has been shown to inhibit the growth and metastatic potential of melanoma, although the underlying molecular mechanism remains unclear. The aim of this study was to clarify the mechanism of action of C3G in melanoma in vitro and in vivo, as well as to characterize the functional expressions of ERs in melanoma. In normal skin or melanoma (n = 20/each), no ERα protein was detectable, whereas expression of ERß was high in skin but weak focal or negative in melanoma; and finally high expression of GPER in all skin vs. 50% melanoma tissues (10/20) was found. These results correspond with our analysis of the melanoma survival rates (SRs) from Human Protein Atlas and The Cancer Genome Atlas GDC (362 patients), where low ERß expression in melanoma correlate with a poor relapse-free survival, and no correlations were observed between SRs and ERα or GPER expression in melanoma. Furthermore, we demonstrated that C3G treatment arrested the cell cycle at the G2/M phase by targeting cyclin B1 (CCNB1) and promoted apoptosis via ERß in both mouse and human melanoma cell lines, and inhibited melanoma cell growth in vivo. Our study suggested that C3G elicits an agonistic effect toward ERß signaling enhancement, which may serve as a potential novel therapeutic and preventive approach for melanoma.

Pharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model.

Cannabidiol (CBD) exhibits significant efficacy in mental and inflammatory diseases. Several studies have recently reported on the rapid antidepressant-like effects of CBD, suggesting that CBD is a potential anti-depressant or anti-stress drug. However, CBD is mainly administered orally or by inhalation with poor bioavailability, resulting in high costs. We aim to explore the efficacy of long-term periodic administration of CBD in chronic mild stress (CMS) via two routes and its pharmacokinetics. We treated ICR mice with CBD administered orally and intravenously and then determined the kinetic constants. A single bolus intravenous injection of CBD resulted in a half-life of 3.9 h, mean residence time of 3.3 h, and oral bioavailability of about 8.6%. The antidepressant-like effects of periodically administered CBD on the chronic mild stress mouse model are evaluated. Results demonstrated that such treatment at a high dose of 100 mg/kg CBD (p.o.) or a low dose of 10 mg/kg CBD (i.v.), elicited significant antidepressant-like behavioral effects in forced swim test, following increased mRNA expression of brain-derived neurotrophic factor (BDNF) and synaptophysin in the prefrontal cortex and the hippocampus. Our findings are expected to provide a reference for the development of intravenous antidepressant formulations of CBD.