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.

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.

Risk factors for hospital readmissions in pneumonia patients: A systematic review and meta-analysis.

BACKGROUND: Factors that are associated with the short-term rehospitalization have been investigated previously in numerous studies. However, the majority of these studies have not produced any conclusive results because of their smaller sample sizes, differences in the definition of pneumonia, joint pooling of the in-hospital and post-discharge deaths and lower generalizability. AIM: To estimate the effect of various risk factors on the rate of hospital readmissions in patients with pneumonia. METHODS: Systematic search was conducted in PubMed Central, EMBASE, MEDLINE, Cochrane library, ScienceDirect and Google Scholar databases and search engines from inception until July 2021. We used the Newcastle Ottawa (NO) scale to assess the quality of published studies. A meta-analysis was carried out with random-effects model and reported pooled odds ratio (OR) with 95% confidence interval (CI). RESULTS: In total, 17 studies with over 3 million participants were included. Majority of the studies had good to satisfactory quality as per NO scale. Male gender (pooled OR = 1.22; 95%CI: 1.16-1.27), cancer (pooled OR = 1.94; 95%CI: 1.61-2.34), heart failure (pooled OR = 1.28; 95%CI: 1.20-1.37), chronic respiratory disease (pooled OR = 1.37; 95%CI: 1.19-1.58), chronic kidney disease (pooled OR = 1.38; 95%CI: 1.23-1.54) and diabetes mellitus (pooled OR = 1.18; 95%CI: 1.08-1.28) had statistically significant association with the hospital readmission rate among pneumonia patients. Sensitivity analysis showed that there was no significant variation in the magnitude or direction of outcome, indicating lack of influence of a single study on the overall pooled estimate. CONCLUSION: Male gender and specific chronic comorbid conditions were found to be significant risk factors for hospital readmission among pneumonia patients. These results may allow clinicians and policymakers to develop better intervention strategies for the patients.

Correlations between hippocampal functional connectivity, structural changes, and clinical data in patients with relapsing-remitting multiple sclerosis: a case-control study using multimodal magnetic resonance imaging.

Multiple sclerosis is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention, memory, and the speed of information processing. The hippocampus, which is a brain important structure involved in memory, undergoes microstructural changes in the early stage of multiple sclerosis. In this study, we analyzed hippocampal function and structure in patients with relapsing-remitting multiple sclerosis and explored correlations between the functional connectivity of the hippocampus to the whole brain, changes in local brain function and microstructure, and cognitive function at rest. We retrospectively analyzed data from 20 relapsing-remitting multiple sclerosis patients admitted to the Department of Neurology at the China-Japan Union Hospital of Jilin University, China, from April 2015 to November 2019. Sixteen healthy volunteers were recruited as the healthy control group. All participants were evaluated using a scale of extended disability status and the Montreal cognitive assessment within 1 week before and after head diffusion tensor imaging and functional magnetic resonance imaging. Compared with the healthy control group, the patients with relapsing-remitting multiple sclerosis had lower Montreal cognitive assessment scores and regions of simultaneously enhanced and attenuated whole-brain functional connectivity and local functional connectivity in the bilateral hippocampus. Hippocampal diffusion tensor imaging data showed that, compared with the healthy control group, patients with relapsing-remitting multiple sclerosis had lower hippocampal fractional anisotropy values and higher mean diffusivity values, suggesting abnormal hippocampal structure. The left hippocampus whole-brain functional connectivity was negatively correlated with the Montreal cognitive assessment score (r = -0.698, P = 0.025), and whole-brain functional connectivity of the right hippocampus was negatively correlated with extended disability status scale score (r = -0.649, P = 0.042). The mean diffusivity value of the left hippocampus was negatively correlated with the Montreal cognitive assessment score (r = -0.729, P = 0.017) and positively correlated with the extended disability status scale score (r = 0.653, P = 0.041). The right hippocampal mean diffusivity value was positively correlated with the extended disability status scale score (r = 0.684, P = 0.029). These data suggest that the functional connectivity and presence of structural abnormalities in the hippocampus in patients with relapse-remission multiple sclerosis are correlated with the degree of cognitive function and extent of disability. This study was approved by the Ethics Committee of China-Japan Union Hospital of Jilin University, China (approval No. 201702202) on February 22, 2017.

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.

Effects of tail docking and/or teeth clipping on behavior, lesions, and physiological indicators of sows and their piglets.

To evaluate effects of tail docking and/or teeth clipping on sows and their piglets, a total of 24 sows and their 302 piglets at 3 days of age were randomly allocated to one of four treatments: teeth clipping and tail docking (TCTD), teeth clipping (TC), tail docking (TD), or intact teeth and tail (Intact). Behavior of piglets and sows, lesions on the body and tail of piglets and sows' teats were inspected. Heart rates of processed piglets were increased (p < .01) during the procedures. Teeth clipping decreased body surface temperature (p < .01) of piglets during and after the procedures but tail docking did not (p > .01). Processed piglets spent more (p < .05) time lying alone and playing/fighting than sham-processed piglets. Tail docked piglets spent less (p < .01) time standing than tail sham-docked piglets. Intact teeth increased (p < .05) the avoidance behaviors of sows. Teeth clipping decreased (p < .05) the lesion scores on the anterior, middle, and posterior teats. Taken together, piglet teeth clipping had more impact on sows and their piglets than tail docking did in the lactation period based on our findings.

Okadaic acid (OA): Toxicity, detection and detoxification.

Okadaic acid (OA), a potent polyether marine toxin, accumulates in the digestive glands of marine mollusks and therefore can severely threaten the health of humans after ingestion of contaminated shellfish. In vivo and in vitro studies have revealed that exposure of various cells, including human embryonic amniotic cells, hepatocytes, neuroblastoma cells, to OA induces morphological and functional modifications as well as the death of cells. As the number of reports on OA poisoning has increased, this toxin has gradually attracted the public's attention, and researchers are trying to study it. This review summarizes the current literature on the toxicity effects of OA, in addition to its detection and detoxification.

Simultaneously targeted and untargeted multicomponent characterization of Erzhi Pill by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry.

Large-scale targeted and untargeted metabolites characterization can be achieved by feat of different liquid chromatography/mass spectrometry (LC-MS) platforms by multiple MS experiments or using data-independent acquisition followed by precursor-product ions matching based on certain algorithms. The resulting insufficiency in efficiency and availability greatly restricts the applicability of these strategies in large-scale profiling and identification of various metabolites. A strategy simultaneously enabling both the targeted and untargeted metabolites characterization is established on a Q Exactive hybrid quadrupole-Orbitrap mass spectrometer, by integrating precursor ions list-triggered data-dependent MS2 acquisition (PIL/dd-MS2) of the targeted components and using the "If idle-pick others" (IIPO) function to induce untargeted metabolites fragmentation. A compounds-specific mass defect filter (MDF) algorithm is proposed as a method to generate the PIL. As a proof of concept, this strategy coupled with offline two-dimensional liquid chromatography (2D-LC) was applied to identify the multicomponents of a traditional Chinese medicine formula Erzhi Pill (EZP). A rigid MDF vehicle was elaborated by orthogonal screening of the integer mass and integer mass-dependent dynamic mass defects considering a variation of 20 ppm. The Full MS/dd-MS2 method enabling PIL and IIPO exhibited better performance than Full MS/dd-MS2 and Targeted SIM/dd-MS2 (selected ion monitoring) in respect of the sensitivity in identifying the targeted components and the ability to characterize more untargeted ones. As a consequence, 270 components were separated from EZP, and 146 thereof were selectively characterized. In conclusion, it is a practical, multifaced strategy facilitating the in-depth metabolites profiling and characterization of complex herbal and biological samples.

Cdc45/Mcm2-7/GINS complex down-regulation mediates S phase arrest in okadaic acid-induced cell damage.

Okadaic acid (OA) is one of the most common and widespread marine toxins and causes acute gastrointestinal symptoms known as diarrheic shellfish poisoning (DSP) in humans. Although OA is not classified as a typical neurotoxin, an increasing number of studies have reported its neurotoxic effects. However, most of the available studies have focused on OA-induced inhibition of serine/threonine protein phosphatases, while the molecular mechanism of OA-induced neurotoxicity remains largely unclear. To better understand the potentially toxicological profile of OA, cell cycle arrest, DNA damage and alterations in gene expression in the human neuroblastoma cell line SHSY5Y upon OA exposure were determined using flow cytometry, comet assay, and transcriptome microarray. The results showed that OA could induce cell cycle arrest at S phase and might be involved in significant DNA strand breaks. Gene expression profiling indicated that the differentially expressed genes after OA exposure were significantly enriched in the "DNA replication" and "cell cycle" pathways. Real-time PCR result had further validated that down-regulation of the Cdc45/Mcm2-7/GINS complex might be the major factor regulating those alterations. These findings provide new insight into the molecular mechanisms of OA-induced neurotoxicity, and the current data may also provide a basis for future studies.

[Research Progress of Desialylation in Immune Thrombocytopenia -Review].

Some patients diagnosed as immune thrombocytopenia(ITP) have poor response to common first-line therapy such as corticosteroid and immunoglobulin. Studies in recent years have found a FC-independent platelet clearance pathway exists, which is characterized by desialylation of platelet surface glycoprotein(GP), recognition and phagocytosis by Ashwell-Morell receptor(AMR) on hepatocytes, independent on Fc receptors of the reticuloendothelial system. The up-regulation of neuraminidase-1(Neu1) expression on platelet caused by various factors, such as cold storage of platelet, septicemia and ITP could desialylate GPs. It has been found that ITP with positive anti-GPIbα antibody mostly has a poor response to first-line therapy and indicated that such antibody may lead to FC-independent platelet clearance. It also has been proved that anti-GPIbα antibody could desialylate GPs on platelet in animal experiments. Researchers have tris to use sialidase inhibitor agent to treat ITP and got a persistent response of platelet. Here, the desialylation of platelet and its role in ITP pathogensis and therapy are reviewed.

[Pulsed High-dose Dexamethasone Therapy and Its Application in Children with Immune Thrombocytopenia-Review].

Immune thrombocytopenia (ITP) is the most common immune-mediated acquired bleeding disorders in children. The prognosis of majority of these patient are well, with recent complete remission. However, a few patients are facing the risk of bleeding since they do not respond to the first-line therapy, and need second-line therapy. The present second-line treatments are difficult to be popularized due to their efficacy, side-effects, costs and some other factors. The pulsed high-dose dexamethasone (HDD) therapy with its good effect, small adverse effects and low cost in adults has been used as the first-line therapy in newly diagnosed ITP, which now has attracted the attention of pediatricians. In this review, we briefly summarized the latest progress of pulsed HDD therapy for ITP in children.

Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin.

Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702. Gene expression profiling identified the apoptotic pathway as the major cause of hepatotoxicity induced by TBT. Flow cytometry assays confirmed that medium- and high-dose TBT treatments significantly increased the number of apoptotic cells, and more cells underwent late apoptosis in the high-dose TBT group. The genes encoding heat shock proteins (HSPs), kinases and tumor necrosis factor receptors mediated TBT-induced apoptosis. These findings revealed novel molecular mechanisms of TBT-induced hepatotoxicity, and the current microarray data may also provide clues for future studies.