Gut microbiota and risk of coronary heart disease: a two-sample Mendelian randomization study.

Background: The relationship between gut microbiota composition and coronary heart disease (CHD) has been recently reported in several observational studies. However, the causal effect of gut microbiota on coronary heart disease is uncharted. Objective: This study attempted to investigate the effect of gut microbiota on coronary heart disease by Mendelian randomization (MR) analysis. Methods: Through the two-sample MR method, single-nucleotide polymorphisms relevant to gut microbiota were selected as instrument variables to evaluate the causal association between gut microbiota and the risk of CHD. Results: According to the selection criteria of the inverse variance-weighted average method, Class Actinobacteria, Class Lentisphaeria, Family Clostridiales vadinBB60group, Genus Clostridium innocuum group, Genus Bifidobacterium, Genus Butyricicoccus, Genus Oxalobacter, Genus Turicibacter, and Order Victivallales, presented a suggestive association with coronary heart disease. Conclusion: This two-sample Mendelian randomization study found that gut microbiota was causally associated with coronary heart disease. Further randomized controlled trials are needed to clarify the protective effect of probiotics on coronary heart disease and their specific protective mechanisms.

The causal association between COVID-19 and herpes simplex virus: a Mendelian randomization study.

Introduction: The coronavirus disease 2019 (COVID-19) has emerged as a main global public health challenge. Additionally, herpes simplex virus type-1 (HSV-1) and type 2 (HSV-2) are widespread viruses that can cause orolabial herpes and genital herpes. Several clinical case reports have declared a possible association between the two, however, the causal relationship between them has not been clarified. Methods: This study utilized a Mendelian randomization (MR) approach for causality assessment between COVID-19 infection and HSV infection based on the latest public health data and Genome-Wide Association Study (GWAS) data. Multiple causal estimation methods, such as IVW, weighted median, simple mode, and weighted mode, were employed to validate the causal relation between COVID-19 infection and HSV infection, with COVID-19 infection, COVID-19 hospitalization, and severe COVID-19 as exposures, and HSV1/2 infection as the outcome. A reverse MR analysis was subsequently performed. Results: MR analysis exhibited that COVID-19 infection was relevant to a reduced risk of HSV1 infection (p=7.603239e-152, OR=0.5690, 95%CI=0.5455-0.5935, IVW). Regarding the effect of COVID-19 infection on HSV2, MR analysis suggested that COVID-19 infection was correlated with an augmented risk of HSV2 infection (p=6.46735e-11, OR=1.1137, 95%CI=1.0782-1.1502, IVW). The reverse MR analysis did not demonstrate a reverse causal relationship between HSV and COVID-19. Discussion: Altogether, COVID-19 infection might cause a decreased risk of HSV1 infection and an elevated risk of HSV2 infection.

Application of Ag nanoparticles decorated on graphene nanosheets for electrochemical sensing of CEA as an important cancer biomarker.

In this research, a novel biosensing platform is described based on graphene nano-sheets decorated with Ag nano-particles (GNSs@Ag NPs). The designed electrochemical aptasensor was employed to determine carcinoembryonic antigen (CEA), an important cancer biomarker. Inherently, aptasensing interfaces provide high sensitivity for CEA tumor marker because of the high specific surface area and excellent conductivity of the prepared GNSs@Ag NPs composite. The established assay demonstrated a wide linear range from 0.001 pg/mL to 10 pg/mL with a correlation coefficient of 0.9958 and low detection limit (DL) of 0.5 fg/mL based on S/N = 3 protocol. The derived biosensor illustrated acceptable selectivity towards common interfering species including HER2, VEGF, IgG, MUC1 and CFP10. In addition, the aptsensor showed good reproducibility and fast response time. The applicability of the suggested strategy in human serum samples was also examined and compared to the commercial enzyme-linked immunosorbent assay (ELISA). Based on the experimental data, it was found that the discussed sensing platform can be exerted in the monitoring of CEA in different cancers for early diagnosis.

Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study.

Purpose: Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method. Methods: Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP. Results: According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP. Conclusion: The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.

Correlations between schizophrenia and lichen planus: a two-sample bidirectional Mendelian randomization study.

Background: Several existing studies have shown a correlation between schizophrenia and lichen planus (LP). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between schizophrenia and LP. Methods: A two-sample Mendelian randomization (MR) study was carried out to investigate whether schizophrenia is causally related to LP and vice versa, and genetic variants in this study were taken from previous genome-wide association studies. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Our results show that schizophrenia has a protective effect on LP (OR = 0.881, 95%CI = 0.795-0.975, p = 0.015). Conversely, we observed no significant relationship between LP and schizophrenia in reverse MR analysis (OR = 0.934, 95%CI = 0.851-1.026, p = 0.156). Conclusion: Our two-sample Mendelian randomization study supports a significant causal relationship between LP and schizophrenia and finds that schizophrenia can reduce the incidence of LP. This is in contrast to previous findings and provides new insights into the relationship between LP and schizophrenia, but the exact mechanism needs further investigation.

Characterization of Dental Pulp Stem Cell Populations in the Teeth of Patients With Neurofibromatosis Type 1 - Therapeutic Potential for Bone Tissue Engineering.

BACKGROUND/AIM: Neurofibromas (NF) are the most common benign nerve sheath tumors in the tongue, gingiva, major salivary glands, and jaw bones. Nowadays, tissue engineering is a revolutionary technique for reconstructing tissues. To explore the feasibility of using stem cells derived from NF teeth to treat orofacial bone defects, the differences in cell biological properties between an NF teeth group and Normal teeth group. PATIENTS AND METHODS: The intra-dental pulp tissues from each tooth were extracted. The cell survival rates, morphology, proliferation rates, cell activity, and differentiation abilities were contrastively analyzed between the NF teeth group and Normal teeth group. RESULTS: Between the two groups, there were no differences in the primary generation (P0) cells (p>0.05), the cell yield, and the time required for the cells to grow out of the pulp tissue and attach to the culture plate. Furthermore, no differences were found at the first generation (passage) between the two groups in colony formation rate and cell survival rate. The proliferation capacity, cell growth curve, and surface marker expression of dental pulp cells was not altered in the third generation (p>0.05). CONCLUSION: Dental pulp stem cells from NF teeth were successfully obtained and were not different from normal dental pulp stem cells. Although, clinical research using tissue-engineered bone to repair bone defects is still in its infancy, it will eventually enter the clinic and become a routine means of bone defect reconstruction treatment as related disciplines and technologies develop.

Deep learning-based automatic sella turcica segmentation and morphology measurement in X-ray images.

BACKGROUND: Although the morphological changes of sella turcica have been drawing increasing attention, the acquirement of linear parameters of sella turcica relies on manual measurement. Manual measurement is laborious, time-consuming, and may introduce subjective bias. This paper aims to develop and evaluate a deep learning-based model for automatic segmentation and measurement of sella turcica in cephalometric radiographs. METHODS: 1129 images were used to develop a deep learning-based segmentation network for automatic sella turcica segmentation. Besides, 50 images were used to test the generalization ability of the model. The performance of the segmented network was evaluated by the dice coefficient. Images in the test datasets were segmented by the trained segmentation network, and the segmentation results were saved in binary images. Then the extremum points and corner points were detected by calling the function in the OpenCV library to obtain the coordinates of the four landmarks of the sella turcica. Finally, the length, diameter, and depth of the sella turcica can be obtained by calculating the distance between the two points and the distance from the point to the straight line. Meanwhile, images were measured manually using Digimizer. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to analyze the consistency between automatic and manual measurements to evaluate the reliability of the proposed methodology. RESULTS: The dice coefficient of the segmentation network is 92.84%. For the measurement of sella turcica, there is excellent agreement between the automatic measurement and the manual measurement. In Test1, the ICCs of length, diameter and depth are 0.954, 0.953, and 0.912, respectively. In Test2, ICCs of length, diameter and depth are 0.906, 0.921, and 0.915, respectively. In addition, Bland-Altman plots showed the excellent reliability of the automated measurement method, with the majority measurements differences falling within ± 1.96 SDs intervals around the mean difference and no bias was apparent. CONCLUSIONS: Our experimental results indicated that the proposed methodology could complete the automatic segmentation of the sella turcica efficiently, and reliably predict the length, diameter, and depth of the sella turcica. Moreover, the proposed method has generalization ability according to its excellent performance on Test2.

Corrigendum: DCBLD1 Overexpression is associated with a poor prognosis in head and neck squamous cell carcinoma.

[This corrects the article DOI: 10.3389/fimmu.2022.939344.].

DCBLD1 Overexpression Is Associated With a Poor Prognosis in Head and Neck Squamous Cell Carcinoma.

Background: DCBLD1 is highly expressed in several kinds of cancer and plays a potential prognostic factor. However, the prognostic value and immune infiltration in head and neck squamous cell carcinoma remain unclear and need further research. Materials and Methods: DCBLD1 expression and clinical information were obtained from the Cancer Genome Atlas (TCGA) database. The mRNA level in cell lines (SCC25 and CAL27) and gingival fibroblasts were detected using quantitative PCR. Cox regression analysis was used to evaluate the prognostic values of DCBLD1 and clinical data in HNSCC. A nomogram was also established to predict the impact of DCBLD1 on prognosis based on Cox multivariate results. The methylation level of DCBLD1 in HNSC and its prognosis were analyzed in UALACN and MethSurv. Finally, the potential biological functions of DCBLD1 were investigated using gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA). Results: The mRNA and protein expression levels of DCBLD1 were highly expressed in HNSCC tissue and cell lines. The Cox analyses demonstrate that highly expressed DCBLD1 is an independent prognosis marker (p < 0.05). ROC curve analysis showed the performance of DCBLD1 (area under the ROC curve: 0.948, sensitivity: 93.2%, specificity: 84.7%). The methylation was increased in HNSCC patients compared with normal subjects (p < 0.05) and was associated with poor prognosis at sites cg27642470 and cg21104965. Additionally, DCBLD1 expression is poorly associated with immune cell infiltration and immunological checkpoints PD-L1 and TIM-3. Conclusion: In head and neck squamous cell carcinoma, DCBLD1 is overexpressed, associated with poor patient prognosis. The detailed underlying mechanism merits further research.

A comparative study on the secretion of various cytokines by pulp stem cells at different passages and their neurogenic potential.

AIMS: By measuring the extent of cytokines secreted by human dental pulp stem cells (hDPSCs) from passages 2 through 10, the optimal passage of hDPSCs was determined. This offers a potential theoretical basis for the treatment of neurological disorders. METHOD: After isolation and culture of hDPSCs from human teeth, the morphological features of the cells were observed under an inverted microscope. hDPSCs were identified by their immunophenotypes and their multiple differentiation capability. Cytokine concentrations secreted in the supernatants at passages 2-10 were detected by ELISA. RESULTS: hDPSCs were viewed as fusiform or polygonal in shape, with a bulging cell body, homogenized cytoplasm, and a clear nucleus. Moreover, they could differentiate into neuroblasts in vitro. hDPSCs at passage 3 were positive for CD29 (91.5%), CD73 (94.8%) and CD90 (96.7%), but negative for the hematopoietic markers CD34 (0.13%). ELISA results showed that hDPSCs at passage 3 had the highest secretion levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF), with the highest secretion level of Neurotrophin-3 (NT-3) being at passage 2. CONCLUSION: hDPSCs have steady biological features of stem cells and exhibit optimal proliferation potential. hDPSCs at different passages have different capacities in the secretion of VEGF, BDNF, NGF, and NT-3. In conclusion cytokines secreted by hDPSCs may prove to be appropriate in the treatment of neurological diseases.

Evaluation of the Effects of Human Dental Pulp Stem Cells on the Biological Phenotype of Hypertrophic Keloid Fibroblasts.

OBJECTIVE: Despite numerous existing treatments for keloids, the responses in the clinic have been disappointing, due to either low efficacy or side effects. Numerous studies dealing with preclinical and clinical trials have been published about effective therapies for fibrotic diseases using mesenchymal stem cells; however, no research has yet been reported to scientifically investigate the effect of human dental pulp stem cells (HDPSCs) on the treatment of keloids. The objective is to provide an experimental basis for the application of stem cells in the treatment of keloids. METHODS: Human normal fibroblasts (HNFs) and human keloid fibroblasts (HKFs) were cultured alone and in combination with HDPSCs using a transwell cell-contact-independent cell culture system. The effects of HDPSCs on HKFs were tested using a CCK-8 assay, live/dead staining assay, quantitative polymerase chain reaction, Western blot and immunofluorescence microscopy. RESULTS: HDPSCs did not inhibit the proliferation nor the apoptosis of HKFs and HNFs. HDPSCs did, however, inhibit their migration. Furthermore, HDPSCs significantly decreased the expression of profibrotic genes (CTGF, TGF-ß1 and TGF-ß2) in HKFs and KNFs (p < 0.05), except for CTGF in HNFs. Moreover, HDPSCs suppressed the extracellular matrix (ECM) synthesis in HKFs, as indicated by the decreased expression of collagen I as well as the low levels of hydroxyproline in the cell culture supernatant (p < 0.05). CONCLUSIONS: The co-culture of HDPSCs inhibits the migration of HKFs and the expression of pro-fibrotic genes, while promoting the expression of anti-fibrotic genes. HDPSCs' co-culture also inhibits the synthesis of the extracellular matrix by HKFs, whereas it does not affect the proliferation and apoptosis of HKFs. Therefore, it can be concluded that HDPSCs can themselves be used as a tool for restraining/hindering the initiation or progression of fibrotic tissue.

[Experimental study on the anti-tumor effect of monocytes/macrophages against Tca8113 cells and the secretion of vascular endothelial growth factor in acid microenvironment].

OBJECTIVE: To investigate the anti-tumor effect of monocytes/macrophages against Tca8113 cells and the secretion of vascular endothelial growth factor (VEGF) in acid microenvironment in vitro. METHODS: Peripheral blood mononuclear cells were extracted from healthy person's blood and cultivated to transform into monocytes/macrophages. The monocytes/macrophages were cultured with Tca8113 in acid microenvironment (pH6.6 and pH6.8) and in normal microenvironment (pH7.2). The anti-tumor effect of monocytes/macrophages against Tca8113 cells were examined by MTT assay. The expression of VEGF was detected by enzyme-link immunoassay (ELISA). RESULTS: The anti-tumor effect of monocytes/macrophages against Tca8113 cells in acid environment was lower than in normal environment (P < 0.05). VEGF excreted by mononuclear/macrophage was significantly higher in acid microenvironment than in normal microenvironment. CONCLUSION: Due to acid microenvironment inside tumor, the anti-tumor effect of monocytes/macrophages against tumor cell was decreased, but the secretion of VEGF was gradually increased. However, the function of monocytes/macrophages on anti-tumor need more research.

[Multiple-deformities with congenital cleft lip, ala nasi cleft, face horizontal cleft, accessory ear and inguinal hernia: a case report].

A 10-month-old boy suffering from a rare multiple-deformities with congenital cleft lip, ala nasi cleft, face horizontal cleft, alveolar cleft, accessory ear and inguinal hernia. All of the above-mentioned multiple-deformities have been cured by surgical operations, during which the bleeding was prevented strictly. According to the principle of asepsis, the hernial sac was ligatured firstly, the accessory ears were cut off, the ala nasi cleft, cleft lip and facial transversal cleft were repaired in turn. After the operation, the wound were completely healed up in time and the deformities were corrected.

[Expression and significance of angiopoietin-1 and angiopoietin-2 in oral squamous cell cacinoma].

BACKGROUND & OBJECTIVE: Recently, Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) have been identified as potential angiogenic factors. The local balance between them and other angiogenic factors determines the growth, stableness, or regression of blood vessels. This study was to investigate the correlations of Ang-1 and Ang-2 expression to clinicopathologic features, microvessel density (MVD), and vessel maturation index (VMI) of oral squamous cell cacinoma (OSCC), and evaluate the significance of Ang-1 and Ang-2 coexpression in tumor angiogenesis and vessel maturation. METHODS: The expression of Ang-1 and Ang-2 in 41 specimens of OSCC, 30 specimens of adjacent noncancerous oral tissues, and 10 specimens of normal oral mucosa was detected by immunohistochemistry. MVD and VMI were assessed with double-labeling immunohistochemical staining against CD34 and alpha-smooth muscle actin (alpha-SMA). RESULTS: The positive rate of Ang-1 was significantly lower in OSCC than in adjacent noncancerous oral tssues and normal oral mucosa (41.46% vs. 90.00% and 90.0%, P < 0.05); the positive rate of Ang-2 was significantly higher in OSCC than in adjacent noncancerous oral tssues and normal oral mucosa (51.22% vs. 26.67% and 0, P < 0.05). The differences in Ang-1 and Ang-2 expression between adjacent noncancerous oral tssues and normal oral mucosa were not significant (P > 0.05). The positive rate of Ang-1 was significantly higher in highly differentiated tumor than in moderately differentiated tumor (56.00% vs. 18.75%, P < 0.05); the positive rate of Ang-2 was significantly higher in tumor with lymph node metastasis than in tumor without lymph node metastasis (84.62% vs. 35.71%, P < 0.01). Ang-1 and Ang-2 expression were closely correlated with angiogenesis and vessel maturation of tumor (P < 0.05). Ang-1 and Ang-2 had antagonistic effect on the regulation of tumor vessel maturation. CONCLUSION: The down-regulation of Ang-1 and up-regulation of Ang-2 are closely related to tumor angiogenesis and vessel maturation.

[Correlation between expression of vascular endothelial growth factor-C in tumor-associated macrophages and lymphatic metastasis in oral cancer].

BACKGROUND & OBJECTIVE: Previous study shows that both vascular endothelial growth-C (VEGF-C) and tumor-associated macrophages (TAMs) are related to lymphatic metastasis. This study aimed to explore the correlation between the expression of VEGF-C in TAMs and lymphatic metastasis in human oral squamous-cell carcinoma (OSCC). METHODS: After immunohistochemical staining, light microscope was used for counting macrophages and automated image analysis quantification was used to determine VEGF-C expression,which was reflected by positive index (PI). In addition,the double staining was also used to determine VEGF-C expression in TAMs. RESULTS: VEGF-C expression was higher in lymphatic metastasis group (PI=12.169+/-2.778) than in no-metastasis group (PI=8.498+/-2.674, P< 0.05). TAMs counts was related to VEGF-C expression in OSCC (r=0.370, P< 0.05). The result of double staining indicated that macrophage with positive VEGF-C expression accounted for about 22.8% of the total. CONCLUSION: Not only tumor cells but also TAMs secrete the VEGF-C in OSCC, and TAMs may play a major role in peritumoral lymphatic neoangiogenesis and lymphatic metastasis.