The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.

BACKGROUND: The incidence of non-alcohol fatty liver disease (NAFLD) has been increasing annually with the improvement of living standards. Numerous epidemiological observations have linked sex hormone-binding protein (SHBG) levels to NAFLD. However, evidence of the causal role of SHBG in the development and progression of NAFLD is still absent. Therefore, a systematic assessment of the causal relationship is needed. METHOD: A two-sample Mendelian randomisation (MR) analysis was conducted. Genome-wide association study (GWAS) data for SHBG were obtained online from the IEU database (ebi-a-GCST90012111) as exposure. GWAS data from the NAFLD of the Finngen consortium were used for preliminary analysis, while NAFLD data from another GWAS involving 8434 participants were used for replication and meta-analyses. Causal effects were investigated with inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analyses including Cochran's Q test, leave-one-out analysis and MR-Egger intercept analysis were simultaneously conducted to assess heterogeneity and pleiotropy. RESULTS: After rigorous selection, 179 single-nucleotide polymorphisms (SNPs) were identified as strongly correlated instrumental variables. Preliminary analysis suggested a significant causal relationship between genetically determined serum SHBG levels and NAFLD [odds ratio (OR) IVW = .54, 95% confidence interval (CI) = .30-.98, p = .043], supported by the results of the replication analysis (ORIVW = .61, 95% CI = .46-.81, p = .0006) and further meta-analysis (OR = .59, 95% CI = .46-.77, p < .0001). CONCLUSION: The genetic tendency to high levels of SHBG was causally correlated with a reduced risk of NAFLD, indicating that circulating high levels of SHBG was a protective factor for NAFLD.

Association between preoperative sarcopenia and prognosis of pancreatic cancer after curative-intent surgery: a updated systematic review and meta-analysis.

BACKGROUND: Sarcopenia is associated with poor outcomes in many malignancies. However, the relationship between sarcopenia and the prognosis of pancreatic cancer has not been well understood. The aim of this meta-analysis was to identify the prognostic value of preoperative sarcopenia in patients with pancreatic cancer after curative-intent surgery. METHODS: Database from PubMed, Embase, and Web of Science were searched from its inception to July 2023. The primary outcomes were overall survival (OS), progression-free survival (PFS), and the incidence of major complications. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were used to assess the relationship between preoperative sarcopenia and the prognosis of patients with pancreatic cancer. All statistical analyses were conducted by Review Manager 5.3 and STATA 17.0 software. RESULTS: A total of 23 retrospective studies involving 5888 patients were included in this meta-analysis. The pooled results demonstrated that sarcopenia was significantly associated with worse OS (HR = 1.53, P < 0.00001) and PFS (HR = 1.55, P < 0.00001). However, this association was not obvious in regard to the incidence of major complications (OR = 1.33, P = 0.11). CONCLUSION: Preoperative sarcopenia was preliminarily proved to be associated with the terrible prognosis of pancreatic cancer after surgery. However, this relationship needs to be further validated in more prospective studies.

Identification of Immune Cells and Key Genes associated with Alzheimer's Disease.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive impairment and memory loss, for which there is no effective cure to date. In the past several years, numerous studies have shown that increased inflammation in AD is a major cause of cognitive impairment. This study aimed to reveal 22 kinds of peripheral immune cell types and key genes associated with AD. The prefrontal cortex transcriptomic data from Gene Expression Omnibus (GEO) database were collected, and CIBERSORT was used to assess the composition of 22 kinds of immune cells in all samples. Weighted gene co-expression network analysis (WGCNA) was used to construct gene co-expression networks and identified candidate module genes associated with AD. The least absolute shrinkage and selection operator (LASSO) and random forest (RF) models were constructed to analyze candidate module genes, which were selected from the result of WGCNA. The results showed that the immune infiltration in the prefrontal cortex of AD patients was different from healthy samples. Of all 22 kinds of immune cells, M1 macrophages were the most relevant cell type to AD. We revealed 10 key genes associated with AD and M1 macrophages by LASSO and RF analysis, including ARMCX5, EDN3, GPR174, MRPL23, RAET1E, ROD1, TRAF1, WNT7B, OR4K2 and ZNF543. We verified these 10 genes by logistic regression and k-fold cross-validation. We also validated the key genes in an independent dataset, and found GPR174, TRAF1, ROD1, RAET1E, OR4K2, MRPL23, ARMCX5 and EDN3 were significantly different between the AD and healthy controls. Moreover, in the 5XFAD transgenic mice, the differential expression trends of Wnt7b, Gpr174, Ptbp3, Mrpl23, Armcx5 and Raet1e are consistent with them in independent dataset. Our results provided potential therapeutic targets for AD patients.

Learning Moiré Pattern Elimination in Both Frequency and Spatial Domains for Image Demoiréing.

Recently, with the rapid development of mobile sensing technology, capturing scene information by mobile sensing devices in the form of images or videos has become a prevalent recording method. However, the moiré pattern phenomenon may occur when the scene contains digital screens or regular strips, which greatly degrade the visual performance and image quality. In this paper, considering the complexity and diversity of moiré patterns, we propose a novel end-to-end image demoiré method, which can learn moiré pattern elimination in both the frequency and spatial domains. To be specific, in the frequency domain, considering the signal energy of moiré pattern is widely distributed in the frequency, we introduce a wavelet transform to decompose the multi-scale image features, which can help the model identify the moiré features more precisely to suppress them effectively. On the other hand, we also design a spatial domain demoiré block (SDDB). The SDDB module can extract moiré features from the mixed features, then subtract them to obtain clean image features. The combination of the frequency domain and the spatial domain enhances the model's ability in terms of moiré feature recognition and elimination. Finally, extensive experiments demonstrate the superior performance of our proposed method to other state-of-the-art methods. The Grad-CAM results in our ablation study fully indicate the effectiveness of the two proposed blocks in our method.

Nitrogen-rich core-shell structured particles consisting of carbonized zeolitic imidazolate frameworks and reduced graphene oxide for amperometric determination of hydrogen peroxide.

Core-shell structured particles were prepared from carbonized zeolitic imidazolate frameworks (ZIFs) and reduced graphene oxide (rGO). The particles possess a nitrogen content of up to 10.6%. The loss of nitrogen from the ZIF is avoided by utilizing the reduction and agglomeration of graphene oxide with suitable size (>2 µm) during pyrolysis. The resulting carbonized ZIF@rGO particles were deposited on a glassy carbon electrode to give an amperometric sensor for H2O2, typically operated at a voltage of -0.4 V (vs. Ag/AgCl). The sensor has a wide detection range (from 5 × 10-6 to 2 × 10-2 M), a 3.3 µM (S/N = 3) detection limit and a 0.272 µA·µM-1·cm-2 sensitivity, much higher than that of directly carbonized ZIFs. The sensor material was also deposited on a screen-printed electrode to explore the possibility of application. Graphical abstract Nitrogen doped carbon (NC) derived from carbonized zeolitic imidazolate frameworks is limited because of low nitrogen content. Here, nitrogen-rich NC@reduced graphene oxide (rGO) core-shell structured particles are described. The NC@rGO particles show distinctly better H2O2 detection performance than NC.

Primary hepatic mucosa-associated lymphoid tissue lymphoma complicated with atrial fibrillation: A case report and literature review.

RATIONALE: Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare malignant primary hepatic lymphoma. The sensible choice of treatment for patients with primary lymphoma combined with atrial fibrillation (AF) is controversial and challenging. PATIENT CONCERNS: The patient presented with both primary hepatic MALT lymphoma and AF, which was difficult to manage. DIAGNOSES: Pathological and immunohistochemical examination are helpful for definitive diagnosis. INTERVENTIONS: Surgical resection and subsequent anticoagulant therapy are main treatment methods, and adjuvant therapy depends on the situation. OUTCOMES: Primary hepatic MALT lymphoma is easy to misdiagnosis due to a lack of typical symptoms and imaging signs. LESSONS: This case highlights for patients with primary hepatic MALT lymphoma combined with AF, toxicity caused by adjuvant chemotherapy should be fully considered, and careful selection should be made based on the general conditions and complications of patients.

Identification and prognostic analysis of candidate biomarkers for lung metastasis in colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent types of malignant tumors. It's vital to explore new biomarkers and potential therapeutic targets in CRC lung metastasis through adopting integrated bioinformatics tools. Multiple cohort datasets and databases were integrated to clarify and verify potential key candidate biomarkers and signal transduction pathways in CRC lung metastasis. DAVID, STRING, UALCAN, GEPIA, TIMER, cBioPortal, THE HUMAN PROTEIN ATLAS, GSEA 4.3.2, FUNRICH 3.1.3, and R 4.2.3 were utilized in this study. The enriched biological processes and pathways modulated by the differentially expressed genes (DEGs) were determined with Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. The search tool Retrieval of Interacting Genes and Cytoscape were used to construct a protein-protein interaction network among DEGs. Four hundred fifty-nine colorectal primary cancer and lung metastatic gene expression profiles were screened from 3 gene expression profiles (GSE41258, GSE68468, and GSE41568). Forty-one upregulated genes and 8 downregulated genes were identified from these 3 gene expression profiles and verified by the transcriptional levels of hub genes in other GEO datasets and The Cancer Genome Atlas database. Two pathways (immune responses and chemokine receptors bind chemokines), 13 key DEGs, 6 hub genes (MMP3, SFTPD, ABCA3, CLU, APOE, and SPP1), and 2 biomarkers (APOE, SPP1) with significantly prognostic values were screened. Forty-nine DEGs were identified as potential candidate diagnostic biomarkers for patients with CRC lung metastasis in present study. Enrichment analysis indicated that immune responses and chemokine receptors bind chemokines may play a leading role in lung metastasis of CRC, and further studies are needed to validate these findings.

Molecularly imprinted solid-phase extraction combined with non-ionic hydrophobic deep eutectic solvents dispersed liquid-liquid microextraction for efficient enrichment and determination of the estrogens in serum samples.

Hormonal drugs in biological samples are usually in low concentration and highly intrusive. It is of great significance to enhance the sensitivity and specificity of the detection process of hormone drugs in biological samples by utilizing appropriate sample pretreatment methods for the detection of hormone drugs. In this study, a sample pretreatment method was developed to effectively enrich estrogens in serum samples by combining molecularly imprinted solid-phase extraction, which has high specificity, and non-ionic hydrophobic deep eutectic solvent-dispersive liquid-liquid microextraction, which has a high enrichment ability. The theoretical basis for the effective enrichment of estrogens by non-ionic hydrophobic deep eutectic solvent was also computed by simulation. The results showed that the combination of molecularly imprinted solid-phase extraction and deep eutectic solvent-dispersive liquid-liquid microextraction could improve the sensitivity of HPLC by 33∼125 folds, and at the same time effectively reduce the interference. In addition, the non-ionic hydrophobic deep eutectic solvent has a relatively low solvation energy for estrogen and possesses a surface charge similar to that of estrogen, and thus can effectively enrich estrogen. The study provides ideas and methods for the extraction and determination of low-concentration drugs in biological samples and also provides a theoretical basis for the application of non-ionic hydrophobic deep eutectic solvent extraction.

Characteristics of quiescent adult neural stem cells induced by the bFGF/BMP4 combination or BMP4 alone in vitro.

Bone morphogenetic protein-4 (BMP4) is involved in regulation of neural stem cells (NSCs) proliferation, differentiation, migration and survival. It was previously thought that the treatment of NSCs with BMP4 alone induces astrocytes, whereas the treatment of NSCs with the bFGF/BMP4 combination induces quiescent neural stem cells (qNSCs). In this study, we performed bulk RNA sequencing (RNA-Seq) to compare the transcriptome profiles of BMP4-treated NSCs and bFGF/BMP4-treated NSCs, and found that both NSCs treated by these two methods were Sox2 positive qNSCs which were able to generate neurospheres. However, NSCs treated by those two methods exhibited different characteristics in state and the potential for neuronal differentiation based on transcriptome analysis and experimental results. We found that BMP4-treated NSCs tended to be in a deeper quiescent state than bFGF/BMP4-treated NSCs as the percentage of ki67-positive cells were lower in BMP4-treated NSCs. And after exposure to differentiated environment, bFGF/BMP4-treated NSCs generated more DCX-positive immature neurons and MAP2-positive neurons than BMP4-treated NSCs. Our study characterized qNSCs treated with BMP4 alone and bFGF/BMP4 combination, providing a reference for the scientific use of BMP4 and bFGF/BMP4-induced qNSCs models.

Identification of immune cells infiltrating in hippocampus and key genes associated with Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia and is primarily associated with memory impairment and cognitive decline, but the etiology of AD has not been elucidated. In recent years, evidence has shown that immune cells play critical roles in AD pathology. In the current study, we collected the transcriptomic data of the hippocampus from gene expression omnibus database, and investigated the effect of immune cell infiltration in the hippocampus on AD, and analyzed the key genes that influence the pathogenesis of AD patients. The results revealed that the relative abundance of immune cells in the hippocampus of AD patients was altered. Of all given 28 kinds of immune cells, monocytes were the important immune cell associated with AD. We identified 4 key genes associated with both AD and monocytes, including KDELR1, SPTAN1, CDC16 and RBBP6, and they differentially expressed in 5XFAD mice and WT mice. The logistic regression and random forest models based on the 4 key genes could effectively distinguish AD from healthy samples. Our research provided a new perspective on immunotherapy for AD patients.

Defining nomograms for predicting prognosis of early and late recurrence in gastric cancer patients after radical gastrectomy.

There are few studies on the predictive factors of early recurrence (ER) and late recurrence (LR) of advanced gastric cancer (GC) after curative surgery. Our study aims to explore the independent predictors influencing the prognosis between ER and LR in patients with advanced GC after curative intent surgery respectively. And we will further develop nomograms for prediction of post recurrence survival (PRS). Data of patients with GC who received radical gastrectomy was retrospectively collected. Recurrence was classified into ER and LR according to the 2 years after surgery as the cutoff value. Multivariate Cox regression analyses were used to explore significant predictors in our analysis. Then these significant predictors were integrated to construct nomograms. The 1-, 2- and 3-year probabilities of PRS in patients with ER were 30.00%, 16.36% and 11.82%, respectively. In contrast, the late group were 44.68%, 23.40%, and 23.30%, respectively. Low body mass index (hazard ratio [HR] = 0.86, P = .001), elevated monocytes count (HR = 4.54, P = .003) and neutrophil-lymphocyte ratio (HR = 1.03, P = .037) at the time of recurrence were risk factors of PRS after ER. Decreased hemoglobin (HR = 0.97, P = .008) and elevated neutrophil-lymphocyte ratio (HR = 1.06, P = .045) at the time of recurrence were risk factors of PRS after LR. The calibration curves for probability of 1-, 2-, and 3-year PRS showed excellent predictive effect. Internal validation concordance indexes of PRS were 0.722 and 0.671 for ER and LR respectively. In view of the different predictive factors of ER and LR of GC, the practical predictive model may help clinicians make reasonable decisions.

Is endoscopic radiofrequency ablation plus stent placement superior to stent placement alone for the treatment of malignant biliary obstruction? A systematic review and meta-analysis.

OBJECTIVE: Malignant biliary obstruction (MBO) is a rare disease with a poor prognosis. Recent studies have shown that endoscopic radiofrequency ablation (ERFA) may improve survival. We conducted a systematic review and meta-analysis of the efficacy of ERFA in combination with biliary stent placement for the treatment of MBO. METHODS: The study was registered in INPLASY (number 202340096). The PubMed, Cochrane Library, Web of Science, and Embase databases were searched from inception to April 2023. We selected studies comparing the efficacy of ERFA plus stent placement with stent placement alone. The primary outcomes were pooled hazard ratios (HRs) for overall survival and stent patency; the secondary outcomes were the odds ratios (ORs) for adverse events. RESULTS: Eleven studies (four randomized controlled trials and seven observational studies) were included in the meta-analysis. Pooled analysis showed a difference in survival time between the two groups (HR 0.65, 95% confidence interval [CI] 0.58-0.73, I2 = 40%). However, there were no differences in the duration of stent patency or the incidence of adverse events (HR 1.04, 95% CI 0.84-1.29, I2 = 46%; OR 1.41, 95% CI 1.02-1.96, I2 = 29%). CONCLUSIONS: ERFA has a significant survival benefit for MBO, but does not increase the risk of adverse events.

Laparoscopic pancreaticoduodenectomy versus open pancreaticoduodenectomy for carcinoma of the ampulla of Vater in a medium-volume center: a propensity score matching analysis.

OBJECTIVE: To compare the efficacy of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in a medium-volume medical center. METHODS: Data for patients who underwent OPD or LPD for carcinoma of the ampulla of Vater (VPC) between January 2017 and June 2022 were acquired retrospectively. Propensity score-matching (PSM) analysis was performed to balance the baseline characteristics between the groups. The primary outcome was disease-free survival (DFS). Cox regression analysis was used to explore the independent risk factors for DFS. RESULTS: A total of 124 patients with pathologically diagnosed VPC were included. After 1:1 matching, there were 23 cases each in the OPD and LPD groups. Kaplan-Meier survival analyses showed that the median DFS in the OPD and LPD groups was identical (16.0 months vs 16.0 months, respectively). Multivariate Cox regression analysis showed that low levels of alkaline phosphatase and γ-glutamyl transpeptidase, positive surgical margin, and lymph node enlargement were independent risk factors for DFS. CONCLUSION: LPD in medium-volume centers with acceptable technical conditions may approach or even achieve the efficacy of LPD in large-volume centers.

Dummy-template Pickering emulsion imprinted microspheres online pretreatment and analysis for the estrogens in cosmetics.

Estrogens are a class of steroid hormone with strong physiological activity. Due to the pronounced beauty effect, such drugs are highly susceptible to illegal addition and cause other adverse effects. To avoid template leakage and the negative impacts on the environment caused by the estrogens, diosgenin was selected as the dummy template due to its similar skeleton structure. The Pickering emulsion polymerization was used to obtain the dummy-template molecularly imprinted polymers (dt-MIPs). Scanning electron microscopy, optical microscopy, specific surface area testing, Fourier transform infrared spectroscopy and adsorption experiments were used to characterize the apparent morphology and the recognition performance of the microspheres. Then, the prepared microspheres and commercial fillers were used to construct an on-line solid phase extraction (on-line SPE) analytical system coupled with HPLC via a two-position switching valve. On-line solid phase extraction-HPLC analytical methods were established and verified, for the simultaneous determination of four estrogens in cosmetic samples. The accuracy and precision RSDs for the established methods using the imprinted sorbents were 92.00-104.02% and less than 9.12%, respectively. All four estrogens exhibited good linearity in the range of 0.05 to 5 µg/mL with a coefficient of determination R2 greater than 0.9810. The method comparison results suggest that the established analytical method is simple in pre-treatment, easy to automate, and has excellent sensitivity to meet the analytical requirements of complex samples.

Irisin exhibits neuroprotection by preventing mitochondrial damage in Parkinson's disease.

Exercise has been proposed as an effective non-pharmacological management for Parkinson's disease (PD) patients. Irisin, a recently identified myokine, is increased by exercise and plays pivotal roles in energy metabolism. However, it remains unknown whether irisin has any protective effects on PD. Here, we found that serum irisin levels of PD patients were markedly elevated after 12-week regular exercise, which had a positive correlation with improved balance function scored by Berg Balance Scale. Treatment with exogenous irisin could improve motor function, and reduce dopaminergic neurodegeneration in PD models. Meanwhile, irisin could reduce cell apoptosis by renovating mitochondrial function in PD models, which was reflected in decreased oxidative stress, increased mitochondrial complex I activity and mitochondrial content, increased mitochondrial biogenesis, and repaired mitochondrial morphology. Furthermore, irisin regulated the aforementioned aspects by upregulating downstream Akt signaling pathway and ERK1/2 signaling pathway through integrin receptors rather than directly targeting mitochondria. With the use of small-molecule inhibitors, it was found that irisin can reduce apoptosis, restore normal mitochondrial biogenesis, and improve mitochondrial morphology and dynamic balance in PD models by activating Akt signaling pathway and ERK1/2 signaling pathway. And irisin reduced oxidative stress via activating ERK1/2 signaling pathway. The results revealed that exogenous irisin conferred neuroprotection relieving apoptosis and oxidative stress, restraining mitochondrial fragmentation, and promoting mitochondrial respiration and biogenesis in PD models, and irisin exerted the aforementioned effects by activating Akt signaling pathway and ERK1/2 signaling pathway. Thus, peripherally delivered irisin might be a promising candidate for therapeutic targeting of PD.

Promotion of Wound Healing Using Nanoporous Silk Fibroin Sponges.

Wound dressings are important for wound repair. The morphology of the biomaterials used in these dressings, and in particular, the pore structure affects tissue regeneration by facilitating attachment and proliferation of cells due to the hierarchical multiscale, water absorbance, and nutrient transport. In the present study, silk fibroin (SF) sponges with walls containing nanopores (SFNS) were prepared from SF nanoparticles generated during the autoclaving of SF solutions, followed by leaching the SF nanoparticles from the freeze-dried sponges of SF. The nano/microporous structure, biofluid absorbance, and porosity of the SF sponges with and without nanopores were characterized. In vitro cell proliferation, in vivo biocompatibility, and wound healing were evaluated with the sponges. The results demonstrated that SFNS had significantly increased porosity and water permeability, as well as cell attachment and proliferation when compared with SF sponges without the nanopores (SFS). Wound dressings were assessed in a rat skin wound model, and SFNS was superior to SFS in accelerating wound healing, supported by vascularization, deposition of collagen, and increased epidermal thickness over 21 days. Hence, such a dressing material with a hierarchical multiscale pore structure could promote cell migration, vascularization, and tissue regeneration independently without adding any growth factor, which would offer a new strategy to design and engineer better-performed wound dressing.

Single-Cell Transcriptomics Reveals Splicing Features of Adult Neural Stem Cells in the Subventricular Zone.

The central nervous system has enormously complex cellular diversity with hundreds of distinct cell types, yet alternative splicing features in single cells of important cell types at neurogenic regions are not well understood. By employing in silico analysis, we systematically identified 3,611 alternative splicing events from 1,908 genes in 28 single-cell transcriptomic data of adult mouse ependymal and subependymal regions, and found that single-cell RNA-seq has the advantage in uncovering rare splicing isoforms compared to bulk RNA-seq at the population level. We uncovered that the simultaneous presence of multiple isoforms from the same gene in a single cell is prevalent, and quiescent stem cells, activated stem cells, and neuroblast cells exhibit high heterogeneity of splicing variants. Furthermore, we also demonstrated the existence of novel bicistronic transcripts in quiescent stem cells.

Role of Mitochondria in Neurodegenerative Diseases: From an Epigenetic Perspective.

Mitochondria, the centers of energy metabolism, have been shown to participate in epigenetic regulation of neurodegenerative diseases. Epigenetic modification of nuclear genes encoding mitochondrial proteins has an impact on mitochondria homeostasis, including mitochondrial biogenesis, and quality, which plays role in the pathogenesis of neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. On the other hand, intermediate metabolites regulated by mitochondria such as acetyl-CoA and NAD+, in turn, may regulate nuclear epigenome as the substrate for acetylation and a cofactor of deacetylation, respectively. Thus, mitochondria are involved in epigenetic regulation through bidirectional communication between mitochondria and nuclear, which may provide a new strategy for neurodegenerative diseases treatment. In addition, emerging evidence has suggested that the abnormal modification of mitochondria DNA contributes to disease development through mitochondria dysfunction. In this review, we provide an overview of how mitochondria are involved in epigenetic regulation and discuss the mechanisms of mitochondria in regulation of neurodegenerative diseases from epigenetic perspective.

Lycopene Aggravates Acute Gastric Injury Induced by Ethanol.

Lycopene is an important natural red pigment with strong singlet oxygen and peroxide free radical quenching ability. Ethanol directly destroys the epithelial cells of gastric mucosa, causing oxidative damage and inflammation. To evaluate the effect of lycopene on the ethanol induced gastric injury, 112 adult male Kunming mice were randomly divided into normal control, lycopene control, gastric injury control, omeprazole (20 mg/kg) positive control, and lycopene experimental groups (at doses of 10, 50, 100, and 150 mg/kg body weight) in this study. The general and pathological evaluation, gastric secretion, as well as the levels of antioxidant and inflammatory factors were detected. In lycopene experimental groups, the amount of gastric juice were lower than that in the gastric injury control group; the levels of T-SOD, and the levels of MDA and inflammatory factors (MMP-9 and MCP-1) decreased. However, general and pathological evaluation of gastric tissues revealed that lycopene (especially at high doses) could aggravate acute gastric mucosal injury induced by ethanol. Therefore, lycopene (especially at high doses) aggravates acute gastric mucosal injury caused by ethanol, but this was not due to oxidative stress or inflammatory factors. In lycopene control group, the levels of MTL, T-SOD, and NO increased, but the levels of ALT and AST decreased, indicating that lycopene has a protective effect on the stomach and liver when ethanol wasn't taken. It reminds us that, when alcohol is consumed in large quantities, consumption of lycopene products should be carefully considered.

Immune Profiling of Parkinson's Disease Revealed Its Association With a Subset of Infiltrating Cells and Signature Genes.

Parkinson's disease (PD) is an age-related and second most common neurodegenerative disorder. In recent years, increasing evidence revealed that peripheral immune cells might be able to infiltrate into brain tissues, which could arouse neuroinflammation and aggravate neurodegeneration. This study aimed to illuminate the landscape of peripheral immune cells and signature genes associated with immune infiltration in PD. Several transcriptomic datasets of substantia nigra (SN) from the Gene Expression Omnibus (GEO) database were separately collected as training cohort, testing cohort, and external validation cohort. The immunoscore of each sample calculated by single-sample gene set enrichment analysis was used to reflect the peripheral immune cell infiltration and to identify the differential immune cell types between PD and healthy participants. According to receiver operating characteristic (ROC) curve analysis, the immunoscore achieved an overall accuracy of the area under the curve (AUC) = 0.883 in the testing cohort, respectively. The immunoscore displayed good performance in the external validation cohort with an AUC of 0.745. The correlation analysis and logistic regression analysis were used to analyze the correlation between immune cells and PD, and mast cell was identified most associated with the occurrence of PD. Additionally, increased mast cells were also observed in our in vivo PD model. Weighted gene co-expression network analysis (WGCNA) was used to selected module genes related to a mast cell. The least absolute shrinkage and selection operator (LASSO) analysis and random-forest analysis were used to analyze module genes, and two hub genes RBM3 and AGTR1 were identified as associated with mast cells in the training cohort. The expression levels of RBM3 and AGTR1 in these cohorts and PD models revealed that these hub genes were significantly downregulated in PD. Moreover, the expression trend of the aforementioned two genes differed in mast cells and dopaminergic (DA) neurons. In conclusion, this study not only exhibited a landscape of immune infiltrating patterns in PD but also identified mast cells and two hub genes associated with the occurrence of PD, which provided potential therapeutic targets for PD patients (PDs).