Proteome and Metabolome Profiling of Anticoagulant Disorders Induced by Familial Protein S Deficiency.

Protein S deficiency (PSD) is an autosomal dominant disorder characterized by congenital thrombophilia. Studies on PSD are limited yet, resulting in a lack of clarity about molecular changes during abnormal coagulation. Proteomics and metabolomics analyses were conducted on the plasma of PSD patients based on liquid and gas chromatography-mass spectrometry (LC- and GC-MS). Differential proteins and metabolites of PSD were then filtered by univariate statistical analysis and subjected to network analysis using the ingenuity pathway analysis (IPA) platform. The proteome and metabolome of PSD were obviously disturbed, and the biological pathway of coagulation and complement cascades was the most affected. During PSD, overall levels of anticoagulant protein decreased and negative regulation of thrombin production was reduced, causing the formation of fibrin clots and platelet aggregation. Furthermore, 9 differential proteins correlated significantly with protein S, comprising A2M, AGT, APOE, FGG, GPLD1, IGHV1-69, CFHR5, CPN2, and CA1. The biological networks suggested that the pathways of acute phase response, FXR/RXR activation, serotonin receptor signaling, and p70S6K signaling were associated with PSD, indicating an interaction disorder of inflammatory immune and lipid metabolism. The findings may contribute to knowledge of available functional molecules and biological pathways of familial PSD and help with treatment improvement. Data are available via ProteomeXchange with identifier PXD055111 and MetaboLights with reference number MTBLS2653.

Unravelling the Link between Psychological Distress and Liver Disease: Insights from an Anxiety-like Rat Model and Metabolomics Analysis.

Psychological distress is associated with an increase in liver disease mortality. This association highlights the close relationship between psychological and physical health. The underlying mechanism of this association needs to be elucidated. In this study, a rat model of anxiety was developed via compound stress. Changes in the HPA axis and inflammatory factors in the brains of the rats were evaluated for behavioral tests and liver function, respectively. The liver metabolic profiles of the rats were characterized through liquid chromatography-mass spectrometry (LC-MS). Differential metabolites were screened based on the conditions of p < 0.05 and VIP > 1. A pathway enrichment analysis was performed on the metabolomics data using the Ingenuity Pathway Analysis (IPA). Immunofluorescence (IF), immunohistochemistry (IHC), and Western blotting assays were performed to examine the expression of the screened target epidermal growth factor receptor (EGFR) and to elucidate the pathway associated with the mechanism. The results showed the impairment of liver function among the rats in an anxiety-like state. Additionally, 61 differential metabolites in the control and anxiety groups were screened using metabolomics (p < 0.05, VIP > 1). The results of the IPA analysis showed that the key target was EGFR. We also found that an anxiety-like state in rats may cause liver injury through the EFGR/PI3K/AKT/NF-κB pathway, which can lead to the production of inflammatory factors in the liver. Our results revealed a mechanism by which anxiety-like behavior leads to liver damage in rats. The findings of this study provided new insights into the deleterious effects of psychological problems on physical health.

The Effects of Early-Life Stress on Liver Transcriptomics and the Protective Role of EPA in a Mouse Model of Early-Life-Stress-Induced Adolescent Depression.

Early-life stress (ELS) was found to increase the risk of adolescent depression, and clinical evidence indicated that eicosapentaenoic acid (EPA) was decreased in patients with adolescent depression, but the underlying mechanisms are unclear. Here, we utilized an ELS model of maternal separation with early weaning to explore the protective role of EPA in adolescent depression. We found that that ELS induced depression-like behavior rather than anxiety-like behavior in adolescent mice. RNA-sequencing results showed that ELS changed the transcription pattern in the liver, including 863 upregulated genes and 971 downregulated genes, especially those related to the biosynthesis of unsaturated fatty acids metabolism in the liver. Moreover, ELS decreased the expression of the rate-limiting enzymes, fatty acid desaturases 1/2 (FADS1/2), involved in the biosynthesis of EPA in the liver. Additionally, ELS reduced the levels of EPA in the liver, serum, and hippocampus, and EPA administration improved depression-like behavior-induced by ELS. Our results provide transcriptomic evidence that ELS increases the risk of adolescent depression by reducing the synthesis of unsaturated fatty acids in the liver, especially EPA, and suggest that supplementation with EPA should be investigated as a potential treatment for adolescent depression.

A rare case of pemphigus vulgaris disguised as a malignant gingival ulcer.

BACKGROUND: Pemphigus vulgaris (PV) is a kind of rare and severe autoimmune bullous disease. In this case, the specificity of oral PV lies in the clinical manifestations of a single palatal ulcer, and no blisters were found in the oral mucosa. This case provides a powerful reference for dentists diagnosing and treating oral PV with atypical clinical presentations. CASE PRESENTATION: A 54 years old female patient presented with a non-healing palatal gingival ulcer for over three months. By histopathological H&E staining and the direct immunofluorescence (DIF) test, the final diagnosis was oral PV. After topical glucocorticoid therapy, the affected area was cured. CONCLUSIONS: In patients with prolonged erosion of the skin or oral mucosa, even if complete blisters are not visible, the physician should consider autoimmune bullous diseases and pay attention to avoid diagnostic defects.

Multi-disciplinary treatment of severe palatal radicular groove of maxillary lateral incisor: A case report and literature review. / 上颌侧切牙重度畸形舌侧沟多学科联合治疗1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Palatal radicular groove is a developmental malformation of maxillary incisors, lateral incisors in particular, which often causes periodontal destruction. This paper reports a case of combined periodontal-endodontic lesions induced by palatal radicular groove, which was initially misdiagnosed as a simple periapical cyst. After root canal therapy and periapical cyst curettage, the course of disease was prolonged, resulting in the absence of buccal and maxillary bone plates in the affected tooth area. After the etiology was determined, the affected tooth was extracted and guide bone tissue regeneration was performed at the same time, followed by implantation and restoration at the later stage, leading to clinical cure. The palatal radicular groove is highly occult, and the clinical symptoms are not typical. If the abscess of the maxillary lateral incisor occurs repeatedly, and the abscess of the maxillary lateral incisor has not been cured after periodontal and root canal treatment, cone-beam computed tomographic and periodontal flap surgery should be considered.

An Efficient Deep-Subwavelength Second Harmonic Nanoantenna Based on Surface Plasmon-Coupled Dilute Nitride GaNP Nanowires.

High-index semiconductor nanoantennae represent a powerful platform for nonlinear photon generation. Devices with reduced footprints are pivotal for higher integration capacity and energy efficiency in photonic integrated circuitry (PIC). Here, we report on a deep subwavelength nonlinear antenna based on dilute nitride GaNP nanowires (NWs), whose second harmonic generation (SHG) shows a 5-fold increase by incorporating ∼0.45% of nitrogen (N), in comparison with GaP counterpart. Further integrating with a gold (Au) thin film-based hybrid cavity achieves a significantly boosted SHG output by a factor of ∼380, with a nonlinear conversion efficiency up to 9.4 × 10-6 W-1. In addition, high-density zinc blende (ZB) twin phases were found to tailor the nonlinear radiation profile via dipolar interference, resulting in a highly symmetric polarimetric pattern well-suited for coupling with polarization nano-optics. Our results manifest dilute nitride nanoantenna as promising building blocks for future chip-based nonlinear photonic technology.

Low LINC02147 expression promotes the malignant progression of oral submucous fibrosis.

BACKGROUND: Key lncRNAs associated with the malignant progression of oral submucous fibrosis (OSF) to oral squamous cell carcinoma (OSCC) were identified. METHODS: Key lncRNAs with sequential changes from normal oral mucosa (NOM) to OSF to OSCC were identified based on the GEO database. Kaplan-Meier analysis was used to screen lncRNAs related to OSCC prognosis. Cox regression analysis was used to validate the independent prognostic value. qPCR was used to confirm the expression of the candidate lncRNAs. Gene set enrichment analysis (GSEA), nucleocytoplasmic separation assay, fluorescence in situ hybridization, RNA knockdown, western blot, and cell viability assay were performed to investigate the biological functions of the candidate lncRNA. A nomogram was constructed to quantitatively predict OSCC prognosis based on TCGA. RESULTS: Bioinformatics methods indicated that LINC02147 was sequentially downregulated from NOM to OSF to OSCC, as confirmed by clinical tissues and cells. Meanwhile, low LINC02147 expression, as an independent prognostic factor, predicted a poor prognosis for OSCC. GSEA and in vitro studies suggested that low LINC02147 expression promoted OSF malignant progression by promoting cell proliferation and differentiation. A LINC02147 signature-based nomogram successfully quantified each indicator's contribution to the overall survival of OSCC. CONCLUSIONS: Low LINC02147 expression promoted OSF malignant progression and predicted poor OSCC prognosis.

Comparative molecular analysis of oral submucous fibrosis and other organ fibrosis based on weighted gene co-expression network analysis. / åŸºäºŽåŠ æƒåŸºå› å ±è¡¨è¾¾ç½‘ç»œåˆ†æžçš„å£è ”é»è†œä¸‹çº¤ç»´åŒ–ä¸Žå ¶ä»–å™¨å®˜çº¤ç»´åŒ–çš„æ¯”è¾ƒåˆ†å­åˆ†æžï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: There is currently a lack of economic and suitable animal models that can accurately recapitulate the oral submucous fibrosis (OSF) disease state for indepth study. This is one of the primary reasons for the limited therapeutic methods available for OSF. Based on the underlying logic of pan-cancer analysis, this study systematically compares OSF and the other four types of organ fibrosis from the aspects of molecules, signaling pathways, biological processes, etc. A comprehensive analysis of the similarities and differences between OSF and other organ fibrosis is helpful for researchers to discover some general rules of fibrosis disease and may provide new ideas for studying OSF. METHODS: Microarray data of the GSE64216, GSE76882, GSE171294, GSE92592, and GSE90051 datasets were downloaded from GEO. Differentially expressed mRNAs (DEmRNAs) of each type of fibrosis were identified by Limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify each type of fibrosis-related module. The similarities and differences of each fibrosis-related-module genes were analyzed by function and pathway enrichment analysis. RESULTS: A total of 6 057, 10 910, 27 990, 10 480, and 4 801 DEmRNAs were identified in OSF, kidney intestinal fibrosis (KIF), liver fibrosis (LF), idiopathic pulmonary fibrosis (IPF), and skin fibrosis (SF), respectively. By using WGCNA, each type of fibrosis-related module was identified. The co-expression networks for each type of fibrosis were constructed respectively. Except that KIF and LF have 5 common hub genes, other fibrotic diseases have no common hub genes with each other. The common pathways of OSF, KIF, LF, IPF, and SF mainly focus on immune-related pathways. CONCLUSIONS: OSF and the other 4 types of fibrotic diseases are tissue- and organ-specific at the molecular level, but they share many common signaling pathways and biological processes, mainly in inflammation and immunity.

Pathological investigations and correlation research of microfibrillar-associated protein 4 and tropoelastin in oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF), distinguished by abnormal collagen deposition, is a potentially malignant disorder with 4.2% (95% CI 2.7-5.6%) of malignant transformation and rising global prevalence. However, the precise pathogenesis and effective treatment remain elusive and controversial despite the abundance of literature on this topic. Therefore, it is crucial to explore the clinicopathological characteristics and potential markers for the diagnosis and prognosis of OSF. The objective of this study was to evaluate the influence and correlation of Microfibrillar-associated protein 4 (MFAP4) and tropoelastin (TE) in the development of OSF patients. MATERIAL AND METHODS: Clinicopathological factors, hematoxylin-eosin (HE) and Masson trichome staining, immunohistochemical characteristics and the correlation between MFAP4 and TE were recorded and compared among different stages of OSF progression among cases (n = 60) and controls (n = 10). Student's t test, ANOVA analysis, and the chi-square test were performed to compare the categorical variables for clinicopathological characteristics and the expression level of MFAP4 and TE between the fibrotic and normal tissues. Correlation analysis of MFAP4 and TE was performed using Pearson's correlation test and linear regression. RESULTS: MFAP4 and TE proteins are upregulated and increased gradually in patients with varying stages of OSF, relative to the control group. Furthermore, statistical analyses revealed that the expression level of MFAP4 was positively associated with TE, with a Pearson correlation coefficient of 0.3781 (p = 0.0048). Clinically, we found that OSF affected more males than females, with a ratio of 29:1. The age range was 16-60 years, and the mean age was 36.25 ± 10.25 years. In patients younger than 40 years, the positive expression rate of MFAP4 and TE was higher than in those over 40 years. All OSF cases had chewed areca nut, with 51.67% smoking tobacco. CONCLUSIONS: Our study elucidates that the accumulation of MFAP4 and TE proteins may play a vital role in the occurrence and development of OSF and may be promising candidate moleculars for prevention, diagnosis, and treatment strategies for OSF in the future.

A case of delayed allergic reaction caused by local injection of triamcinolone acetonide. / å±€éƒ¨æ³¨å°„é†‹é ¸æ›²å®‰å¥ˆå¾·è‡´è¿Ÿå‘è¿‡æ•ååº”1例.

Glucocorticoid is a commonly used anti-inflammatory and anti-allergic drug in clinic. Allergic reactions caused by glucocorticoids are rare in clinic. Glucocorticoid allergy is a type of allergic reaction caused by glucocorticoid as an allergen, and its clinical manifestations of hypersensitivity are not specific. Here we reported a case of an allergic reaction in patients with oral lichen planus who received submucosal injection of triamcinolone acetonide in the tongue. The patient showed local erosion, bleeding, and pain in the mucous membrane of the tongue in the Xiangya Stomatological Hospital, Central South University. The allergic symptoms were relieved after the patient was given diclofenac sodium sustained-release tablets, sodium bicarbonate injection for gargle, and Kangfuxin liquid.It is the clinical need to further deepen the understanding of glucocorticoid allergy. The allergens should be cut off as soon as possible, and the corresponding treatment is performed according to the type of hypersensitivity reaction, thereby improving the therapeutic effect.

Elliptical Airy beam.

We found a new type of noncircular symmetrical Airy beam called an elliptical Airy beam (EAB). Using a simple single-pixel checkerboard hologram method, we achieved the EAB in an experiment. We observed its unique property of double focusing and the ability of the energy to flow towards the endpoints of the long axis during propagation. These particular properties will have some potential applications.

[Recent advances in miR-200c and fibrosis in organs].

In the fibrosis and pterygium of lung, liver, kidney, peritoneum or skin, miR-200c was aberrantly expressed. It has been shown that the regulatory effect of miR-200c on fibrosis in organ was involved in TGF-ß-mediated epithelial-mesenchymal transition. The abnormal level of miR-200c in serum may be a basis for early diagnosis of lung fibrosis. Furthermore, miRNA mimics, miRNA agomir, and miRNA inhibitor are potential therapeutic tools for fibrosis. In present review, we summarize the recent progress in relevant studies on the expression and regulatory function of miR-200c and focus on its role in diagnosis, treatment, and prognosis of fibrosis in organ.

XRCC1 Arg399Gln polymorphism is not associated with oral cancer risk: evidence from a meta-analysis.

Previous studies regarding the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and oral cancer risk were contradictory. We performed a meta-analysis to derive a more precise estimation of the association. The PubMed and Web of Science were searched for eligible studies. Odds ratio (OR) with its 95% confidence interval (95% CIs) was used to assess the strength of the association. Nine individual studies with a total of 3,244 subjects were finally included into the meta-analysis. Overall, there was no association between XRCC1 Arg399Gln polymorphism and oral cancer risk under all genetic models (Gln versus Arg: OR = 1.09, 95% CI 0.86-1.37, P = 0.46; GlnGln versus ArgArg: OR = 1.11, 95% CI 0.69-1.79, P = 0.66; GlnGln versus ArgArg/ArgGln: OR = 1.04, 95% CI 0.68-1.61, P = 0.84; and GlnGln/ArgGln versus ArgArg: OR = 1.13, 95% CI 0.88-1.44, P = 0.34). After excluding studies on oral leukoplakia, there was still no association between XRCC1 Arg399Gln polymorphism and oral cancer risk under all genetic models. Subgroup analysis by ethnicity suggested that there was no association between XRCC1 Arg399Gln polymorphism and oral cancer risk in both Asians and Caucasians. In conclusion, the data from the meta-analysis suggests that XRCC1 Arg399Gln polymorphism is not associated with oral cancer risk.

[Changes of miRNA after oral submucous fibrosis co-cultured with Salvia and low-dose prednisolone].

OBJECTIVE: To explore and analyze the the expression change of miRNA associated with oral submucous fibrosis (OSF) treated by the Salvia combined with law-dose prednisolone. METHODS: Ten pairs of tissues from patients with typical early or advanced stage clinical pathological features of OSF and their paired normal tissues (internal control), were selected respectively. The miRNA expression profiles between the OSF and its paired controls were compared by the Affymetrix analysis. The primary normal oral mucous cells were cultured in arecoline (50 µg/mL) for 3, 6, 12 d (0 d ser ved as cont rol), and the primary OSF-fibroblast cells were cultured with Salvia (90 mg/mL) combined with low-dose prednisolone for 12, 24, 36 h (0 h served as control). The differential expression of miRNA was detected. RESULTS: Arecoline induced the expression changes of miRNAs in normal mucosal cells. Salvia combined with low doses of prednisolone reversed the related miRNA expression. CONCLUSION: MiRNAs play an essential role in the occurrence and development of OSF. Salvia combined with low-dose prednisolone can reverse the expression of related miRNAs in OSF cells.

Role and new insights of microfibrillar-associated protein 4 in fibrotic diseases.

Fibrosis is one of the most worrisome complications of chronic inflammatory diseases, leading to tissue damage, organ failure, and ultimately, death. The most notable pathological characteristic of fibrosis is the excessive accumulation of extracellular matrix (ECM) components such as collagen and fibronectin adjacent to foci of inflammation or damage. The human microfibrillar-associated protein 4 (MFAP4), an important member of the superfamily of fibrinogen-related proteins, is considered to have an extremely important role in ECM transformation of fibrogenesis. This review summarizes the structure, characteristics, and physiological functions of MFAP4 and the importance of MFAP4 in various fibrotic diseases. Meanwhile, we elaborated the underlying actions and mechanisms of MFAP4 in the development of fibrosis, suggesting that a better understand of MFAP4 broadens novel perspective for early screening, diagnosis, prognostic risk assessment, and treatment of fibrotic diseases.

Metabolomics reveals that chronic restraint stress alleviates carbon tetrachloride-induced hepatic fibrosis through the INSR/PI3K/AKT/AMPK pathway.

Hepatic fibrosis (HF) could be developed into liver cirrhosis or even hepatocellular carcinoma. Stress has an important role in the occurrence and development of various considerable diseases. However, the effect of a certain degree stress on HF is still controversial. In our study, stress was simulated with regular chronic restraint stress (CRS) and HF model was induced with CCl4 in mice. We found that CRS was able to attenuate CCl4-induced liver injury and fibrosis in mice. Surprisingly, behavioral analysis showed that the mice in the HF group exhibited depression-like behavior. Further, the metabolomic analysis revealed that 119 metabolites and 20 metabolic pathways were altered in mice liver, especially the betaine metabolism pathway. Combined with the results of Ingenuity Pathway Analysis (IPA), the key proteins INSR, PI3K, AKT, and p-AMPK were identified and verified, and the results showed that CRS could upregulate the protein levels and mRNA expression of INSR, PI3K, AKT, and p-AMPK in liver tissues of HF mice. It suggested that CRS alleviated CCl4-induced liver fibrosis in mice through upregulation of the INSR/PI3K/AKT/AMPK pathway. Proper stress might be a potential therapeutic strategy for the treatment of chronic liver disease, which provided new insights into the treatment of HF. KEY MESSAGES: Chronic restraint stress mitigated CCl4-induced liver injury and hepatic fibrosis. CCl4-induced liver fibrosis could cause depression-like behavior. Chronic restraint stress altered metabolomic profiles in hepatic fibrosis mice, especially the betaine metabolism pathway. Chronic restraint stress increased betaine levels in liver tissue. Chronic restraint stress regulated the INSR/PI3K/AKT/AMPK signaling pathway in hepatic fibrosis mice.

A Bibliometric and Visualised Analysis of Proliferative Verrucous Leucoplakia From 2003 to 2023.

BACKGROUND: Proliferative verrucous leucoplakia (PVL) is a rare but slow-growing, aggressive leucoplakia lesion associated with the highest malignant transformation rate in oral potentially malignant disorders (OPMDs). With increasing attention paid to PVL, it is urgent for us to analyse and summarise the publications globally using comprehensive bibliometric studies to help researchers propose possible future research directions and guide them to further conduct relevant studies in the domain. OBJECTIVES: The purpose of the study was to evaluate global academic productivity, impact, and collaboration of potentially malignant oral disorder PVL utilising bibliometrics based on annual number of publications, countries and regions, institution, authors, journals, citations and co-occurrences of author keywords over the last 20 years. METHODS: This study searched publications pertaining to proliferative verrucous leucoplakia in the Web of Science Core Collection, spanning from 2003 to 2023. Utilizing VOSviewer, R software, Bibliometric online analysis platform, CiteSpace software, and Microsoft Excel, we conducted a bibliometric and visualised analysis of PVL. RESULTS: The quantity of pertinent publications in this research domain displays a fluctuating but overall upward trend. In aggregate, there are 148 articles and 61 reviews, encompassing research contributions from 44 countries, 45 institutions, and involving 831 authors. Among these publications, the USA, Spain, and UK emerged as the predominant contributing nations. Predominantly, articles found their publication venue in "Pathology Research and Practice." Notably, the author with the highest number of publications and most influence is Warnakulasuriya S. The top 3 keywords include "Proliferative Verrucous Leucoplakia," "Squamous-Cell Carcinoma," "Oral Leucoplakia," and "Potentially Malignant Disorders." CONCLUSION: In this investigation, statistical analysis and network visualisation were conducted to reveal the research progress, trends, and trending topics on PVL via a thorough bibliometric analysis. We found that current publications comprise mainly case reports, there is a significant research need to explore the molecular mechanisms, specific diagnostic criteria, and effective management options for PVL. Our work should serve as a key reference and a directional guide for future research in this domain.

Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut ß-GUS.

BACKGROUND: Irinotecan (CPT-11, Camptosar@) is a first-line drug for metastatic colorectal cancer. CPT-11-induced diarrhea, which is closely related to the concentrations of ß-glucuronidase (ß-GUS) and SN-38 in the gut, largely limits its clinical application. PURPOSE: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for ß-GUS from the gut microbiota. METHODS: First, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of ß-GUS in intestine were examined. We also resolved the 3D structure of ß-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit ß-GUS. RESULTS: In XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of ß-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of ß-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT. CONCLUSIONS: Overall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.