This work clarified the positive effects of pullulan on dough structure and application properties varied with its molecular weight. Pullulan with different molecular weights were introduced into doug Show more
This work clarified the positive effects of pullulan on dough structure and application properties varied with its molecular weight. Pullulan with different molecular weights were introduced into dough system to explore their intervention effects on structural and technological properties of dough as well as physical and digestion properties of biscuits. Results showed that HPL (pullulan with molecule weight of 100- 300 kDa) could increase the intermolecular collisions, prompt the protein aggregation and limit the water migration in dough system, resulting in an integrate, continuous and dense network structure of the gel with strengthened elasticity and weakened extensibility, which caused an increase in biscuit thickness, hardness and crispness. On the contrary, LPL (pullulan with molecule weight of 3- 100 kDa) could go against the formation of stable and elastic dough through breaking down cross-linkage between protein and starch so as to provide biscuits with decreased hardness and crispness during baking. Both HPL and LPL delayed starch pasting and retrogradation process while HPL had the stronger retarding effect on starch digestibility of biscuits than LPL. These findings dedicated to a better understanding of pullulan function in dough system and provide suggestions for fractionation applications of pullulan in food field. Show less
He Hao, Mingdong Yao, Ying Wang+6 more · 2024 · Proceedings of the National Academy of Sciences of the United States of America · National Academy of Sciences · added 2026-04-24
Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated the impact of G1 phase extension o Show more
Cell phase engineering can significantly impact protein synthesis and cell size, potentially enhancing the production of lipophilic products. This study investigated the impact of G1 phase extension on resource allocation, metabolic functions, and the unfolded protein response (UPR) in yeast, along with the potential for enhancing the production of lipophilic compounds. In brief, the regulation of the G1 phase was achieved by deleting Show less
Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism i Show more
Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism in hepatocellular carcinoma (HCC), however, remains to be further investigated. Bioinformatics approaches were harnessed to scrutinize CBX1's expression profile, its association with tumor staging, and its potential impact on patient outcomes across various cancers. Single-cell RNA sequencing data facilitated the investigation of CBX1 expression patterns at the individual cell level. The CBX1 expression levels in HCC and adjacent non-tumor tissues were quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), and Immunohistochemical analyses. A tissue microarray was employed to explore the relationship between CBX1 levels, patient prognosis, and clinicopathological characteristics in HCC. Various in vitro assays-including CCK-8, colony formation, Transwell invasion, and scratch tests-were conducted to assess the proliferative and motility properties of HCC cells upon modulation of CBX1 expression. Moreover, the functional impact of CBX1 on HCC was further discerned through xenograft studies in nude mice. CBX1 was found to be upregulated in most cancer forms, with heightened expression correlating with adverse patient prognoses. Within the context of HCC, elevated levels of CBX1 were consistently indicative of poorer clinical outcomes. Suppression of CBX1 through knockdown methodologies markedly diminished HCC cell proliferation, invasive capabilities, migratory activity, Epithelial-mesenchymal transition (EMT) processes, and resistance to Tyrosine kinase inhibitors (TKIs). Contrastingly, CBX1 augmentation facilitated the opposite effects. Subsequent investigative efforts revealed CBX1 to be a promoter of EMT and a contributor to increased TKI resistance within HCC cells, mediated via the IGF-1R/AKT/SNAIL signaling axis. The oncogenic activities of CBX1 proved to be attenuable either by AKT pathway inhibition or by targeted silencing of IGF-1R. The broad overexpression of CBX1 in pan-cancer and specifically in HCC positions it as a putative oncogenic entity. It is implicated in forwarding HCC progression and exacerbating TKI resistance through its interaction with the IGF-1R/AKT/SNAIL signaling cascade. Show less
Tongxin Xu, Yuzhe Li, Meijuan Cheng+4 more · 2024 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Competitive endogenous RNAs (ceRNA) theory has been proved in numerous biological processes. Nevertheless, there is a lack of research applying the ceRNA theory to the study of vascular calcification Show more
Competitive endogenous RNAs (ceRNA) theory has been proved in numerous biological processes. Nevertheless, there is a lack of research applying the ceRNA theory to the study of vascular calcification (VC) in chronic kidney diseases (CKD). In the present study, a ceRNA network was constructed after conducting transcriptome sequencing of differentially expressed genes, followed by experimental validation to identify a new target for the diagnosis and treatment of vascular calcification. Total RNA was extracted from β-glycerophosphate (β-GP) cultured vascular smooth muscle cells (VSMCs) on Day 7. Illumina HiSeq platform was utilized to build sequencing libraries. GO and KEGG analysis was conducted to identify the function of the differentially expressed genes. Protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. A ceRNA network was established based on TargetScan, miRDB, miRWALK, and miRanda database. Western blot and qRT-PCR were used to explore the expression level of protein and RNA, respectively. The direct binding sites were confirmed by dual-luciferase reporter assay. In total, 647 differentially expressed lncRNAs and 289 differentially expressed mRNAs were identified (|log Show less
Underwater noise pollution has become a potential threat to aquatic animals in the natural environment. The main causes of such pollution are frequent human activities creating underwater environmenta Show more
Underwater noise pollution has become a potential threat to aquatic animals in the natural environment. The main causes of such pollution are frequent human activities creating underwater environmental noise, including commercial shipping, offshore energy platforms, scientific exploration activities, etc. However, in aquaculture environments, underwater noise pollution has also become an unavoidable problem due to background noise created by aquaculture equipment. Some research has shown that certain fish show adaptability to noise over a period of time. This could be due to fish's special auditory organ, i.e., their "inner ear"; meanwhile, otoliths and sensory hair cells are the important components of the inner ear and are also essential for the function of the auditory system. Recently, research in respect of underwater noise pollution has mainly focused on adult fish, and there is a lack of the research on the effects of underwater noise pollution on the development process of the auditory system in the embryonic development period. Thus, in this study, we collected embryo-larval samples of the small yellow croaker ( Show less
The study aimed to investigate the change of amyloid precursor protein (APP) processing and amyloid β (Aβ) metabolites in linking periodontitis to Alzheimer's disease (AD). Aβ is one of the main patho Show more
The study aimed to investigate the change of amyloid precursor protein (APP) processing and amyloid β (Aβ) metabolites in linking periodontitis to Alzheimer's disease (AD). Aβ is one of the main pathological features of AD, and few studies have discussed changes in its expression in peripheral tissues or analyzed the relationship between the peripheral imbalance of Aβ production and clearance. A murine model of periodontitis was established by oral infection with Porphyromonas gingivalis (P. gingivalis). Micro-computed tomography (Micro-CT) was used to observe the destruction of the alveolar bone. Nested quantitative polymerase chain reaction (qPCR) was used to measure small quantities of P.gingivalis DNA in different tissues. Behavioral experiments were performed to measure cognitive function in the mice. The mRNA levels of TNF-α, IL-6, IL-8, RANKL, OPG, APP695, APP751, APP770, and BACE1 in the gingival tissues or cortex were detected by RT-PCR. The levels of Aβ1-40 and Aβ1-42 in gingival crevicular fluid (GCF) and plasma were tested by ELISA. P. gingivalis oral infection was found to cause alveolar bone resorption and impaired learning and memory. P.gingivalis DNA was detected in the gingiva, blood and cortex of the P.gingivalis group by nested qPCR (p < .05). The mRNA expression of TNF-α, IL-6, IL-8, RANKL/OPG, and BACE1 in the gingival tissue was significantly higher than that in the control group (p < .05). Similarly, upregulated mRNA levels of APP695 and APP770 were observed in the gingival tissuses and cortex of the P. gingivalis group (p < .05). The levels of Aβ1-40 and Aβ1-42 in the GCF and plasma of the P. gingivalis group were significantly higher than those in the control group (p < .05). P. gingivalis can directly invade the brain via hematogenous infection. The invasion of P. gingivalis could trigger an immune response and lead to an imbalance between Aβ production and clearance in peripheral tissues, which may trigger an abnormal Aβ metabolite in the brain, resulting in the occurrence and development of AD. Show less
Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for Show more
Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis. The two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis. The MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129-2.812, The current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris. Show less
Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate Show more
Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs). Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined. A total of 355 RNAm-SNPs related to m The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD. Show less
The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung Show more
The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention. The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 cells was used to explore the in vivo effect of LRRC45 in lung cancer. Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 cells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis. LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer. Show less
Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-re Show more
Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithmsr. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis. A diagnostic model was developed using random forest algorithm and validated by receiver operating characteristic (ROC) curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by quantitative real-time PCR (qRT-PCR). We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P < 0.0001) and interleukins pathway (R = 0.79, P < 0.0001). Furthermore, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes. Show less
Familial chylomicronemia syndrome (FCS) comprises a group of ultrarare disorders caused by biallelic variants in LPL or, less frequently, by GPIHBP1, APOC2, APOA5, or LMF1. To evaluate the phenotypes Show more
Familial chylomicronemia syndrome (FCS) comprises a group of ultrarare disorders caused by biallelic variants in LPL or, less frequently, by GPIHBP1, APOC2, APOA5, or LMF1. To evaluate the phenotypes and management of eight non-lipoprotein lipase (LPL)-FCS patients. Seven pediatric and one adult patients with non-LPL-FCS were enrolled. Clinical features, treatment outcomes, and genetic profiles were assessed. Among the 33 patients with FCS, 25 (76%) had LPL-FCS and eight (24%) had non-LPL-FCS; five had variants in GPIHBP1, one each in the LMF1, APOC2, and one with composite heterozygous variants in APOA5 and LPL. Twelve non-LPL variants were identified, five of which were novel variants in GPIHBP1 and two in LMF1. In silico predictions indicated that all novel variants might impact protein function. Elevated baseline triglyceride (TG) levels [22.9 (17.4-30.8) mmol/L, 2026.7 (1540.0-2728.5) mg/dL] were observed in all patients. Among the pediatric patients (7/7), chylomicronemia was the most common onset symptom. Acute pancreatitis was observed in only one patient with LMF1-FCS during pregnancy. The frequency of symptoms and lipid levels in the non-LPL-FCS group were slightly lower than those in the LPL-FCS group (P > 0.05). Dietary fat restriction reduced TG levels by 84.0% to 4.21 mmol/L (372.6 mg/dL, P < 0.01). Compared with other non-LPL-FCS patients, GPIHBP1-FCS patients experienced greater challenges in managing TG levels (P < 0.05). This study unveiled the genetic profile of the Chinese FCS cohort and enriched the mutation spectrum of non-LPL-FCS. The clinical characteristics and treatment outcomes of patients with non-LPL-FCS were delineated. Show less
Previous studies have revealed that Propane-2-sulfonic acid octadec-9-enyl-amide(N15) exerts a protective role in the inflammatory response after ischemic stroke and in neuronal damage. However, littl Show more
Previous studies have revealed that Propane-2-sulfonic acid octadec-9-enyl-amide(N15) exerts a protective role in the inflammatory response after ischemic stroke and in neuronal damage. However, little is known about N15 in Alzheimer's disease (AD). The aim of this study was to investigate the effects of N15 on AD and explore the underlying molecular mechanism. AD mice model was established by lateral ventricular injection with Aβ N15 treatment significantly reduced neurocognitive dysfunction, which also significantly activated the expression of PPARα/γ at an optimal dose of 200 mg/kg. Administration of N15 alleviated the formation of Aβ amyloid in the hippocampus of AD mice, enhanced the BDNF mRNA expression, decreased the mRNA and protein levels of PS1 and BACE1, upregulated ADAM10 mRNA and protein levels. N15 exerts its neuroprotective effects through the activation of PPARα/γ and may be a potential drug for the treatment of AD. Show less
Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity. During osteoporosis, bone mesenchymal stem cells (BMSCs) exhibit an incr Show more
Osteoporosis is a common metabolic bone disorder induced by an imbalance between osteoclastic activity and osteogenic activity. During osteoporosis, bone mesenchymal stem cells (BMSCs) exhibit an increased ability to differentiate into adipocytes and a decreased ability to differentiate into osteoblasts, resulting in bone loss. Jumonji domain-containing 1C ( To examine the effect of BMSCs were isolated from mouse bone marrow tissues. Oil Red O staining, Alizarin red staining, alkaline phosphatase staining and the expression of adipogenic and osteogenic-associated genes were assessed to determine the differentiation of BMSCs. Bone marrow-derived macrophages (BMMs) were incubated with receptor activator of nuclear factor-kappa Β ligand to induce osteoclast differentiation, and osteoclast differentiation was confirmed by tartrate-resistant acid phosphatase staining. Other related genes were measured The osteogenic and adipogenic differentiation potential of BMSCs isolated from mouse bone marrow samples was evaluated. The Show less
R-spondins (RSPOs) are secreted signaling molecules that potentiate the Wnt/β-catenin pathway by cooperating with Wnt ligands. RSPO1 is crucial in tissue development and tissue homeostasis. However, t Show more
R-spondins (RSPOs) are secreted signaling molecules that potentiate the Wnt/β-catenin pathway by cooperating with Wnt ligands. RSPO1 is crucial in tissue development and tissue homeostasis. However, the molecular mechanism by which RSPOs activate Wnt/β-catenin signaling remains elusive. In this study, we found that RSPOs could mediate the degradation of Axin through the ubiquitin-proteasome pathway. The results of Co-IP showed that the recombinant RSPO1 protein promoted the interaction between Axin1 and CK1ε. Either knockout of the CK1ε gene or treatment with the CK1δ/CK1ε inhibitor SR3029 caused an increase in Axin1 protein levels and attenuated RSPO1-induced degradation of the Axin1 protein. Moreover, we observed an increase in the number of associations of LRP6 with CK1ε and Axin1 following RSPO1 stimulation. Overexpression of LRP6 further potentiated Axin1 degradation mediated by RSPO1 or CK1ε. In addition, recombinant RSPO1 and Wnt3A proteins synergistically downregulated the protein expression of Axin1 and enhanced the transcriptional activity of the SuperTOPFlash reporter. Taken together, these results uncover the novel mechanism by which RSPOs activate Wnt/β-catenin signaling through LRP6/CK1ε-mediated degradation of Axin. Show less
This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren's Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR Show more
This study aimed to investigate the causal impact of inflammatory cytokines on Sjogren's Syndrome (SS) and to identify potential biomarkers for SS clinical management using Mendelian Randomization (MR). Leveraging GWAS summary data of inflammatory cytokines and SS, we executed the first two-sample MR analysis. Genetic variants from prior GWASs associated with circulating inflammatory cytokines served as instrumental variables (IVs). Data regarding cytokines were analyzed using the Olink Target-96 Inflammation panel, synthesizing data from 14,824 participants. GWAS summary statistics for SS were procured from the UK Biobank, focusing on samples of European ancestry. To discern the causal relationship between inflammatory cytokines and SS, several MR methodologies, including inverse variance weighted (IVW) and MR-Egger regression, were applied. After rigorous IV quality control, 91 cytokines were incorporated into the MR analysis. The IVW analysis identified 8 cytokines with a positive association to SS: Axin-1 (OR 2.56, 95% CI 1.07-6.10), T-cell surface glycoprotein CD5 (OR 1.81, 95% CI 1.08-3.02), CUDP1 (OR 1.61, 95% CI 1.00-2.58), CXCL10 (OR 1.92, 95% CI 1.25-2.95), IL-4 (OR 2.18, 95% CI 1.22-3.91), IL-7 (OR 2.35, 95% CI 1.27-4.33), MCP-2 (OR 1.27, 95% CI 1.05-1.54), and TNFRSF9 (OR 1.83, 95% CI 1.03-3.24), suggesting their potential in increasing SS risk. Our study conducted through MR, identified various inflammatory cytokines associated with SS risk, validating some previous research results and offering some new potential biomarkers for SS. However, these findings necessitate further research for validation and exploration of their precise role in the onset and progression of SS. Show less
Bullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered Show more
Bullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered within the dermatological field, the specific pathogenesis, particularly the molecular mechanisms underlying the pruritus, remains largely unclear. Limited clinical sequencing studies focusing on BP and PN have hindered the identification of pathological mechanisms and the exploration of effective treatment strategies. To address this gap, we collected a total of 23 peripheral blood mononuclear cell samples from BP and PN patients, as well as healthy controls, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the shared immune regulatory networks and pruritus-related mechanisms between BP and PN. Our study identified 161 differentially expressed genes shared between BP and PN, which were primarily enriched in immune activation and neural pathways, providing crucial molecular insights into the pruritus-related mechanisms of both diseases. Furthermore, using the machine learning algorithms of support vector machines and random forest, we pinpoint 7 crucial genes shared between the BP and PN databases. Among these, IL-27 emerged as a potential pivotal gene, as its mRNA expression levels strongly correlated with clinical parameters including pruritus scores, immunoglobulin E levels, and eosinophil counts. Validation experiments conducted on clinical samples from an additional 22 participants confirmed the upregulation of IL-27 expression in both BP and PN lesions. This study is the first to unveil the shared inflammatory and immune pathways common to BP and PN, highlighting the critical role of IL-27 in the pathogenesis of these conditions. Our findings not only enhance the understanding of the intricate relationship between BP and PN, but also provide a foundation for the development of novel therapeutic strategies targeting these two dermatological conditions. Show less
Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focus Show more
Developing strategies for the radiosensitization of cancer cells by the inhibition of genes, which harbor low toxicity to normal cells, will be useful for improving cancer radiotherapy. Here, we focused on a β-site of amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1; β-secretase, memapsin-2). By functional inhibition of this peptidase by siRNA, it has also recently been shown that the DNA strand break marker, γH2AX foci, increased, suggesting its involvement in DNA damage response. To investigate this possibility, we knocked down Show less
Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has Show more
Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host-microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Show less
The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on liver oxidative damage and energy metabolism in immune-stressed broilers. In total, 312 broilers were divided int Show more
The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on liver oxidative damage and energy metabolism in immune-stressed broilers. In total, 312 broilers were divided into 4 groups (saline, LPS, SAEE, and LAEE). Broilers in the saline and LPS groups were fed a basal diet; the SAEE and LAEE groups had an added 0.01% AEE in their diet. Broilers in the LPS and LAEE groups were injected with lipopolysaccharides, while the saline and SAEE groups were injected with saline. Results showed that AEE increased the body weight, average daily gain, and average daily feed intake, as well as decreasing the feed conversion ratio of immune-stressed broilers. AEE protects against oxidative damage in immune-stressed broiler livers by elevating the total antioxidant capacity, superoxide dismutase activity, and glutathione S-transferase alpha 3 ( Show less
Analyzing blood lipid and bile acid profile changes in colorectal cancer (CRC) patients. Evaluating the integrated model's diagnostic significance for CRC. Ninety-one individuals with colorectal cance Show more
Analyzing blood lipid and bile acid profile changes in colorectal cancer (CRC) patients. Evaluating the integrated model's diagnostic significance for CRC. Ninety-one individuals with colorectal cancer (CRC group) and 120 healthy volunteers (HC group) were selected for comparison. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoproteins (Apo) A1, ApoA2, ApoB, ApoC2, and ApoC3 were measured using immunoturbidimetric and colorimetric methods. Additionally, LC-MS/MS was employed to detect fifteen bile acids in the serum, along with six tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, CA19-9, CA242, CA50, and CA72-4. Group comparisons utilized independent sample t-tests and Mann-Whitney U tests. A binary logistic regression algorithm was applied to fit the indicators and establish a screening model; the diagnostic accuracy of individual Indicators and the model was analyzed using receiver operating characteristic (ROC) curves. The CRC group showed significantly lower levels in eight serum lipid indicators and eleven bile acids compared to the HC group (P < 0.05). Conversely, serum levels of TG, CA19-9, and CEA were elevated (P < 0.05). Among the measured parameters, ApoA2 stands out for its strong correlation with the presence of CRC, showcasing exceptional screening efficacy with an area under the curve (AUC) of 0.957, a sensitivity of 85.71%, and a specificity of 93.33%. The screening model, integrating ApoA1, ApoA2, lithocholic acid (LCA), and CEA, attained an impressive AUC of 0.995, surpassing the diagnostic accuracy of individual lipids, bile acids, and tumor markers. CRC patients manifest noteworthy alterations in both blood lipids and bile acid profiles. A screening model incorporating ApoA1, ApoA2, LCA, and CEA provides valuable insights for detecting CRC. Show less
Small extracellular vesicles (sEVs) act as a critical mediator in intercellular communication. Compared to sEVs derived from in vitro sources, tissue-derived sEVs can reflect the in vivo signals relea Show more
Small extracellular vesicles (sEVs) act as a critical mediator in intercellular communication. Compared to sEVs derived from in vitro sources, tissue-derived sEVs can reflect the in vivo signals released from specific tissues more accurately. Currently, studies on the role of sEVs in the cochlea have relied on studying sEVs from in vitro sources. This study evaluates three cochlear tissue digestion and cochlear tissue-derived sEV (CDsEV) isolation methods, and first proposes that the optimal approach for isolating CDsEVs using collagenase D and DNase І combined with sucrose density gradient centrifugation. Furthermore, it comprehensively investigates CDsEV contents and cell origins. Small RNA sequencing and proteomics are performed to analyze the miRNAs and proteins of CDsEVs. The miRNAs and proteins of CDsEVs are crucial for maintaining normal auditory function. Among them, FGFR1 in CDsEVs may mediate the survival of cochlear hair cells via sEVs. Finally, the joint analysis of single CDsEV sequencing and single-cell RNA sequencing data is utilized to trace cellular origins of CDsEVs. The results show that different types of cochlear cells secrete different amounts of CDsEVs, with Kölliker's organ cells and supporting cells secrete the most. The findings are expected to enhance the understanding of CDsEVs in the cochlea. Show less
Anlotinib hydrochloride is a potent oral multitargeted tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4, and PDGFR α/β, demonstrating significant antiangiogenic activity. Transcatheter arteria Show more
Anlotinib hydrochloride is a potent oral multitargeted tyrosine kinase inhibitor that targets VEGFR1-3, FGFR1-4, and PDGFR α/β, demonstrating significant antiangiogenic activity. Transcatheter arterial chemoembolization (TACE) is considered the effective treatment for intermediate/advanced hepatocellular carcinoma (HCC), which remains a major global health challenge. This study evaluated the relative efficacy and safety of combining anlotinib with TACE against the standard TACE monotherapy among patients with intermediate or advanced HCC. This phase II randomized controlled trial included 38 patients diagnosed with intermediate or advanced HCC. Patients were randomly assigned to receive either TACE in combination with anlotinib or TACE alone. The primary endpoint of the study was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. This trial aimed to determine whether the addition of anlotinib could extend PFS and improve other clinical outcomes compared to TACE alone. The median PFS for patients treated with TACE and anlotinib was significantly longer at 11.04 months compared to 6.87 months in the TACE-alone group [hazard ratio (HR) 0.46; P=0.02], indicating a robust enhancement in disease management. Although the median OS was not reached at the time of analysis, early trends suggest potential improvement. Both treatment groups had comparable ORR and DCR, demonstrating effective disease control. The safety profile of the combined treatment was manageable, with side effects similar in nature to those observed with TACE alone but not significantly more severe, thus maintaining patient quality of life. The addition of anlotinib to TACE appears to provide a safe and effective therapeutic benefit for patients with intermediate or advanced-stage HCC. However, longer follow-up is needed for a more comprehensive efficacy assessment. ClinicalTrials.gov NCT04066543. Show less
This study aimed to investigate the possible mechanisms by which ANGPTL4 is involved in the pathogenesis of choroidal neovascularization (CNV) and subretinal fibrosis. Differentially expressed genes i Show more
This study aimed to investigate the possible mechanisms by which ANGPTL4 is involved in the pathogenesis of choroidal neovascularization (CNV) and subretinal fibrosis. Differentially expressed genes in retinal pigmented epithelium (RPE)-choroid-sclera complex tissues from nAMD patients and control individuals were identified via the GEO database, followed by GO and KEGG analyses. A Venn diagram was used to identify EndMT-related DEGs. A logistic regression model was constructed to screen for prognostic genes. Laser-induced CNV mouse models were established and validated with FFA and OCTA. The expression of ANGPTL4 and EndMT-related markers in the RPE-choroid-sclera complex was measured via RT‒qPCR and Western blotting. TGF-β2-induced HUVECs were used as EndMT cell models, and specific siRNAs targeting ANGPTL4 (si-ANGPTL4) were designed and screened. The effects of ANGPTL4 knockdown on the migration and invasion of HUVECs were also examined. Laser-induced CNV mouse models were constructed, and an intravitreal injection of cholesterol-modified si-ANGPTL4 was used to knock down ANGPTL4. FFA, OCTA and immunofluorescence staining were used to observe CNV formation and subretinal fibrosis, and the expression of ANGPTL4 and EndMT-related markers was determined. ANGPTL4 expression was significantly increased in mice with CNV and colocalized with IB4. In TGF-β2-induced EndMT, ANGPTL4 was also upregulated, and its knockdown led to the inhibition of EndMT and cell migration and invasion, while its overexpression promoted the EndMT process. ANGPTL4 knockdown reduced the formation of CNV and subretinal fibrosis in mice with CNV by suppressing EndMT. ANGPTL4 may promote CNV and subretinal fibrosis through EndMT, suggesting that ANGPTL4 may be a novel potential target for nAMD therapy. Show less
Sisi Zheng, Sitong Feng, Nan Song+8 more · 2024 · The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · Taylor & Francis · added 2026-04-24
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor- Show more
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD. Show less
Foot-and-mouth disease virus (FMDV), a member of picornavirus, can enter into host cell via macropinocytosis. Although it is known that receptor tyrosine kinases (RTKs) play a crucial role in FMDV mac Show more
Foot-and-mouth disease virus (FMDV), a member of picornavirus, can enter into host cell via macropinocytosis. Although it is known that receptor tyrosine kinases (RTKs) play a crucial role in FMDV macropinocytic entry, the specific RTK responsible for regulating this process and the intricacies of RTK-mediated downstream signaling remain to be elucidated. Here, we conducted a screening of RTK inhibitors to assess their efficacy against FMDV. Our findings revealed that two compounds specifically targeting fibroblast growth factor receptor 1 (FGFR1) and FMS-like tyrosine kinase 3 (FLT3) significantly disrupted FMDV entry. Furthermore, additional evaluation through gene knockdown and overexpression confirmed the promotion effect of FGFR1 and FLT3 on FMDV entry. Interestingly, we discovered that the increasement of FMDV entry facilitated by FGFR1 and FLT3 can be ascribed to increased macropinocytic uptake. Additionally, in-depth mechanistic study demonstrated that FGFR1 interacts with FMDV VP3 and undergoes phosphorylation during FMDV entry. Furthermore, the FGFR1 inhibitor inhibited FMDV-induced activation of p21-activated kinase 1 (PAK1) on Thr212 and Thr423 sites. Consistent with these findings, the ectopic expression of FGFR1 resulted in a concomitant increase in phosphorylation level of PAK1 on Thr212 and Thr423 sites. Taken together, our findings represent the initial exploration of FGFR1's involvement in FMDV macropinocytic entry, providing novel insights with potential implications for the development of antiviral strategies. Show less
Circular RNAs (circRNAs) are engaged in various types of cancers. This study aimed to investigate the roles of circ₀₀₀₆₇₄₃ (circ_JMJD1C) in breast cancer. The downstream of circ_JMJD1C and their inte Show more
Circular RNAs (circRNAs) are engaged in various types of cancers. This study aimed to investigate the roles of circ₀₀₀₆₇₄₃ (circ_JMJD1C) in breast cancer. The downstream of circ_JMJD1C and their interaction network was determined by bioinformatic analyses. Gene expression were analyzed through western blot and qRT-PCR assays. Functional assays were conducted in vitro and in vivo to verify circ_JMJD1C role in BC. FISH and confocal analysis indicated the cellular distribution of circ_JMJD1C. Luciferase reporter, RNA immune-precipitation (RIP) assays, as well as Pearson's correlation analysis, were implemented to test the relation of miR-182-5p, JMJD1C and circ_JMJD1C. Circ_JMJD1C and JMJD1C expression were both elevated, and their expression was positively correlated in BC. Circ_ JMJD1C knockdown hindered BC cell proliferation, invasion, and migration, along with epithelial-mesenchymal transition (EMT) in vitro and in vivo. Circ_JMJD1C facilitated BC progression by the miR-182-5p-JMJD1C axis. Circ_JMJD1C epigenetically upregulated SOX4. Circ_JMJD1C promotes the aggressiveness of BC via regulating miR-182-5p/JMJD1C/SOX4 axis. This may provide a novel and promising therapy targeting BC. Show less
The MACF1 gene, found on chromosome 1p34.3, is vital for controlling cytoskeleton dynamics, cell movement, growth, and differentiation. It consists of 101 exons, spanning over 270 kb. The 16p13.11 mic Show more
The MACF1 gene, found on chromosome 1p34.3, is vital for controlling cytoskeleton dynamics, cell movement, growth, and differentiation. It consists of 101 exons, spanning over 270 kb. The 16p13.11 microduplication syndrome results from the duplication of 16p13.11 chromosome copies and is associated with various neurodevelopmental and physiological abnormalities. Both MACF1 and 16p13.11 microduplication have significant impacts on neural development, potentially leading to nerve damage or neurological diseases. This study presents a unique case of a patient simultaneously experiencing a de novo MACF1 mutation and a hereditary 16p13.11 microduplication, which has not been reported previously. In this report, we describe a Chinese preterm newborn girl exhibiting the typical characteristics of 16.13.11 microduplication syndrome. These features include developmental delay, respiratory issues, feeding problems, muscle weakness, excessive joint movement, and multiple congenital abnormalities. Through whole-exome sequencing, we identified a disease-causing mutation in the MACF1 gene (c.15266T > C / p. Met5089Thr). Additionally, after microarray analysis, we confirmed the presence of a 16p13.11 microduplication (chr16:14,916,289 - 16,315,688), which was inherited from the mother. The patient's clinical presentation, marked by muscle weakness and multiple birth defects, may be attributed to both the de novo MACF1 mutation and the 16p13.11 duplication, which could have further amplified her severe symptoms. Genetic testing for individuals with complex clinical manifestations can offer valuable insights for diagnosis and serve as a reference for genetic counseling for both patients and their families. Show less
N6-methyladenosine (m6A) modification is the most prevalent mRNA modification in carcinogenesis and it plays a crucial role. WTAP, an m6A RNA methyltransferase, is functionally significant in various Show more
N6-methyladenosine (m6A) modification is the most prevalent mRNA modification in carcinogenesis and it plays a crucial role. WTAP, an m6A RNA methyltransferase, is functionally significant in various cancers; however, the specific role and functional mechanism in colorectal cancer (CRC) remain poorly understood. In this study, we utilized Gene Expression Profiling Interactive Analysis (GEPIA) to compare WTAP expression in CRC and normal tissues. Functional assays including colony formation assay and transwell assay were conducted to assess the impact of WTAP on cell viability and migration. RNA dot blot and MeRIP-PCR assays were used to investigate WTAP's role in m6A modification. WTAP expression was elevated in CRC tissues. Colony formation and transwell assays showed that WTAP promoted proliferation and migration of CRC cells in vitro. Mechanistically, MeRIP-PCR analysis demonstrated that WTAP knockdown inhibited SNAI1 expression by reducing m6A modification of SNAI1 in CRC cells. Supporting this, analysis of data from GEPIA and cBioPortal revealed a positive correlation between WTAP and SNAI1 expression. WTAP may act as an oncogene in CRC by regulating SNAI1 expression. Show less
Reducing the levels of dietary protein is an effective nutritional approach in lowering feed cost and nitrogen emissions in ruminants. The purpose of this study was to evaluate the effects of dietary Show more
Reducing the levels of dietary protein is an effective nutritional approach in lowering feed cost and nitrogen emissions in ruminants. The purpose of this study was to evaluate the effects of dietary Lys/Met ratio in a low protein diet (10%, dry matter basis) on the growth performance and hepatic function (antioxidant capacity, immune status, and glycolytic activity) in Tibetan lambs. Ninety two-month-old rams with an average weight of 15.37 ± 0.92 kg were randomly assigned to LP-L (dietary Lys/Met = 1:1), LP-M (dietary Lys/Met = 2:1) and LP-H (dietary Lys/Met = 3:1) treatments. The trial was conducted over 100 d, including 10 d of adaption to the diets. Hepatic phenotypes, antioxidant capacity, immune status, glycolytic activity and gene expression profiling was detected after the conclusion of the feeding trials. The results showed that the body weight was higher in the LP-L group when compared to those on the LP-M group (P < 0.05). In addition, the activities of the catalase (CAT) and glutathione peroxidase (GSH-Px) in the LP-L group were significantly increased compared with the LP-M group (P < 0.05), while the malondialdehyde (MDA) levels in LP-H group were significantly decreased (P < 0.05). Compared with LP-H group, both hepatic glycogen (P < 0.01) and lactate dehydrogenase (LDH) (P < 0.05) were significantly elevated in LP-L group. For the LP-L group, the hepatocytes were arranged radially with the central vein in the center, and hepatic plates exhibited tight arrangement. Transcriptome analysis identified 29, 179, and 129 differentially expressed genes (DEGs) between the LP-M vs. LP-L, LP-H vs. LP-M, and LP-H vs. LP-L groups, respectively (Q-values < 0.05 and |log2Fold Change| > 1). Gene Ontology (GO) and correlation analyses showed that in the LP-L group, core genes (C1QA and JUNB) enriched in oxidoreductase activity were positively correlated with antioxidant indicators, while the MYO9A core gene enriched in the immune response was positively associated with immune indicators, and core genes enriched in molecular function (PDK3 and PDP2) were positively correlated with glycolysis indicators. In summary, low-protein diet with a low Lys/Met ratio (1:1) could reduce the hepatic oxidative stress and improve the glycolytic activity by regulating the expression of related genes of Tibetan sheep. Show less