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Purpose: Immune infiltration plays a pivotal role in the pathogenesis of mucosal damage in ulcerative colitis (UC). The objective of this study was to systematically analyze and identify genetic characteristics associated with immune infiltration in UC., Patients and Methods: Gene expression data from three independent datasets obtained from the Gene Expression Omnibus (GEO) were utilized. By employing the ssGSEA and CIBERSORT algorithms, we estimated the extent of immune cell infiltration in UC samples. Subsequently, Weighted Correlation Network Analysis (WGCNA) was performed to identify gene modules exhibiting significant associations with immune infiltration, and further identification of hub genes associated with immune infiltration was accomplished using least absolute shrinkage and selection operator (LASSO) regression analysis. The relationship between the identified hub genes and clinical information was subsequently investigated., Results: Our findings revealed significant activation of both innate and adaptive immune cells in UC. Notably, the expression levels of CD44, IL1B, LYN, and ITGA5 displayed strong correlations with immune cell infiltration within the mucosa of UC patients. Immunohistochemical analysis confirmed the significant upregulation of CD44, LYN, and ITGA5 in UC samples, and their expression levels were found to be significantly associated with common inflammatory markers, including the systemic immune inflammation indices, C-reactive protein, and erythrocyte sedimentation rate., Conclusion: CD44, LYN, and ITGA5 are involved in the immune infiltration pathogenesis of UC and may be potential therapeutic targets for UC., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024 Tan et al.)

Background: Most studies have primarily focused on assessing the association between diet or exercise patterns and metabolic dysfunction-associated steatotic liver disease (MASLD). This study adopted a more comprehensive approach by introducing the oxidative balance score (OBS) to evaluate the combined effects of diet and lifestyle on the body's antioxidant ability. Our main objective was to investigate the association between OBS and the burden of MASLD in the United States., Methods: Participants with complete information from 2001 to 2018 were included. In the absence of other definite liver injury factors, the United States fatty liver index (us-FLI) ≥ 30 was used as the diagnostic criterion for MASLD. We first calculated the weighted prevalence for each cycle and stratified it according to demographic and metabolic-related disease characteristics. Subsequently, weighted multiple logistic regression was used to evaluate the relationship between OBS and MASLD. In addition, we explored the body's inflammatory state and the level of insulin resistance (IR) in mediating OBS and MASLD., Results: From 2001 to 2018, the prevalence of MASLD in the U.S. population as a whole increased from 29.76% to 36.04%, and the rate was higher in people with metabolic-related diseases. Notably, OBS exhibited a negative correlation with MASLD. Participants in the highest tertile of OBS had a significantly lower prevalence of MASLD compared to those in the lowest tertile [OR: 0.72, 95%CI: (0.57, 0.92), p < 0.001]. Moreover, a high OBS is associated with a lower inflammatory state and level of IR. The body's inflammatory state and IR level mediated the association between OBS and MASLD by 5.2% and 39.7%, respectively (both p < 0.001)., Conclusions: In this study, we observed an increasing prevalence of MASLD over the years. A higher OBS was associated with a lower risk of MASLD, especially when OBS ≥ 25. The body's inflammatory state and IR level mediate the association between OBS and MASLD, but the mechanism needs to be further investigated.

Background: Lifestyle change plays a crucial role in the prevention and treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). In recent years, diet soft drinks that emphasize "zero sugar and zero calories" have become all the rage, but whether diet soft drink consumption is associated with MASLD is not clear., Methods: This study included data from the National Health and Nutrition Examination Surveys (NHANES) in 2003-2006. The assessment of MASLD status primarily relied on the Fatty Liver Index (FLI). Weighted multiple Logistic regression models were constructed to evaluate the association between diet soft drink consumption and MASLD. Additionally, mediation analysis was performed to examine the mediating effect of body mass index (BMI)., Results: A total of 2,378 participants were included in the study, among which 1,089 individuals had MASLD, and the weighted prevalence rate was 43.64%. After adjusting for variables related to demographic, lifestyle, and metabolic syndrome, excessive diet soft drink consumption (the "always" frequency) remained significantly associated with the occurrence of MASLD (OR = 1.98, 95%CI = 1.36-2.89, P = 0.003). It was estimated that 84.7% of the total association between diet soft drink consumption and MASLD was mediated by BMI (P < 0.001)., Conclusions: Excessive diet soft drink consumption was associated with the occurrence of MASLD. BMI may play a mediating role in the association between diet soft drink consumption and MASLD., (© 2023. The Author(s).)

Background: Dietary fiber is a functional substance with strong antioxidant activity that plays an important role in human health. Dietary fiber has been shown to reduce the risks of many types of cancers, but whether it can reduce the risk of death in cancer survivors remains undetermined., Methods: This study included the dietary data of cancer survivors who participated in the National Health and Nutrition Examination Surveys from 2001 to 2018. Firstly, the relationship between fiber intake and composite dietary antioxidant index (CDAI) was explored by weighted multiple regression and smooth curve. Subsequently, multivariable Cox proportional hazards regression models were used to explore the effects of dietary fiber intake and CDAI level on the risks of all-cause, tumor, and cardiovascular death among cancer survivors., Results: A total of 2077 participants were included in the study, representing approximately 11,854,509 cancer survivors in the United States. The dietary fiber intake of tumor survivors had a nonlinear positive relationship with CDAI levels (β = 0.24, 95% CI: 0.08-0.40, p = 0.004). Multivariable Cox proportional hazards regression models showed that high dietary fiber intake and CDAI levels were associated with reduced risks of all-cause and tumor death in tumor survivors, but were not associated with the risk of cardiovascular death., Conclusion: An increased dietary fiber intake can enhance the body's antioxidant capacity. A higher dietary fiber intake and CDAI level may reduce the risk of all-cause and tumor death in tumor survivors.

Growing evidence suggests that micronutrient status may have some impact on the course of inflammatory bowel disease (IBD). However, micronutrient deficiencies are easily overlooked during the treatment of IBD patients. There have been many studies on micronutrient supplementation, in which several clinical trials have been conducted targeting vitamin D and iron, but the current research is still preliminary for other vitamins and minerals. This review provides an overview of the adjunctive therapeutic effects of micronutrient supplementation in IBD, to summarize the available evidence, draw the attention of clinicians to micronutrient monitoring and supplementation in patients with IBD, and also provide some perspectives for future research directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Liu and Dong.)

Detecting and identifying malignant nodules on chest computed tomography (CT) plays an important role in the early diagnosis and timely treatment of lung cancer, which can greatly reduce the number of deaths worldwide. In view of the existing methods in pulmonary nodule diagnosis, the importance of clinical radiological structured data (laboratory examination, radiological data) is ignored for the accuracy judgment of patients' condition. Hence, a multi-modal fusion multi-branch classification network is constructed to detect and classify pulmonary nodules in this work: (1) Radiological data of pulmonary nodules are used to construct structured features of length 9. (2) A multi-branch fusion-based effective attention mechanism network is designed for 3D CT Patch unstructured data, which uses 3D ECA-ResNet to dynamically adjust the extracted features. In addition, feature maps with different receptive fields from multi-layer are fully fused to obtain representative multi-scale unstructured features. (3) Multi-modal feature fusion of structured data and unstructured data is performed to distinguish benign and malignant nodules. Numerous experimental results show that this advanced network can effectively classify the benign and malignant pulmonary nodules for clinical diagnosis, which achieves the highest accuracy (94.89%), sensitivity (94.91%), and F1-score (94.65%) and lowest false positive rate (5.55%)., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Purpose: Considering that false-positive and true pulmonary nodules are highly similar in shapes and sizes between lung computed tomography scans, we develop and evaluate a false-positive nodules reduction method applied to the computer-aided diagnosis system., Methods: To improve the pulmonary nodule diagnosis quality, a 3D convolutional neural networks (CNN) model is constructed to effectively extract spatial information of candidate nodule features through the hierarchical architecture. Furthermore, three paths corresponding to three receptive field sizes are adopted and concatenated in the network model, so that the feature information is fully extracted and fused to actively adapting to the changes in shapes, sizes, and contextual information between pulmonary nodules. In this way, the false-positive reduction is well implemented in pulmonary nodule detection., Results: Multi-path 3D CNN is performed on LUNA16 dataset, which achieves an average competitive performance metric score of 0.881, and excellent sensitivity of 0.952 and 0.962 occurs to 4, 8 FP/Scans., Conclusion: By constructing a multi-path 3D CNN to fully extract candidate target features, it accurately identifies pulmonary nodules with different sizes, shapes, and background information. In addition, the proposed general framework is also suitable for similar 3D medical image classification tasks., (© 2021. CARS.)

Objective: To assess the association of tag single nucleotide polymorphisms (tag SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from Yunnan, China., Methods: A case-control study was carried out. Four tag SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients with essential hypertension and 312 healthy controls using polymerase chain reaction - restriction fragment length polymorphism(PCR-RFLP) method., Results: No significant difference in genotypic and allelic distributions of the four polymorphisms was detected between the two groups(P>0.05), and the same results existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype constructed with rs1956921 and rs5244 were greater in male patients compared with male controls(P<0.01)., Conclusion: The rs1956921 C allele of the CMA1 gene and the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for essential hypertension in ethnic Yi males from Yunnan.

Objectives: The interval harboring a quantitative trait locus for blood pressure (BP), C18QTL3, contains β-2 adrenergic receptor (Adrb2) and neural precursor cell expressed, developmentally downregulated 4-like (Nedd4l) genes. None of the other genes in the C18QTL3-residing interval is known to affect BP. The identification of C18QTL3 might uncover a brand new gene that could prosper into a novel diagnostic and/or therapeutic target for essential hypertension, if neither Adrb2 nor Nedd4l could be upheld as candidate genes., Methods: Congenic fine resolution was combined with gene analyses., Results: The gene encoding α-kinase 2 (Alpk2) contains a three base-pair deletion and multiple nonconserved mutations in its coding region in Dahl salt-sensitive (DSS) rats. In contrast, the gastrin-releasing peptide gene (Grp) possesses two nonconserved mutations, designated as single nucleotide polymorphisms 1 and 2 (i.e. SNP1 and SNP2), but could not be supported as a candidate gene because the C18S.L14 congenic strain displayed a homozygous DSS genotype at both SNP1 and SNP2. Furthermore, Adrb2 and Nedd4l could not account for the BP-diminishing effect of Lewis alleles in C18S.L14, as their DSS alleles bear functionally identical domains as those of Lewis, and no evidence of differential expression and splicing was evident. No significant nucleotide variations were found in 13 other genes closely linked to Alpk2., Conclusion: Alpk2 emerged as a strong candidate gene for C18QTL3. The present study is the first to implicate Alpk2 in the genetics of polygenic hypertension and paves the way for novel gene discovery.

Based on the theory of constitution of Traditional Chinese Medicine (TCM), the human population is divided into nine constitutions including one balanced constitution (Normality) and eight unbalanced constitutions (Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution). Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms (SNPs) in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Pro12Ala in Yin-deficiency and PPARD rs2076167, APM1 rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotype13 (Hap13) of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hap14 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes of PPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM., (Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.)

Sema4C is a transmembrane protein that belongs to axon guidance molecules of semaphorin family. Previous reports have shown that Sema4C could interact with postsynaptic protein PSD95, etc, but the expression and the role of Sema4C in neurogenesis remains unknown. In this study, whole-mount in situ hybridization result showed that Sema4C was expressed abundantly in the areas of lateral ventricle, the striatum, the wall of midbrain, and the pons/midbrain junction of E11.5 embryos brain. Neural stem/progenitor cells (NSPs) obtained from E13.5 embryonic rat midbrain are also positive for Sema4C immunoreactivity. Sema4C expression was dramatically downregulated during induction of NSP differentiation. In order to confirm the involvement of Sema4C in neurogenesis, we used the rat global cerebral ischemia model to make adult neurogenesis in vivo. The robust proliferative NSPs were monitored by labeling with bromodeoxyuridine (BrdU) within the subventricular zone and dentate gyrus that continues for at least 2 weeks. Immunohistochemistry and Western blot analysis showed that Sema4C expression was dramatically upregulated during neurogenesis after cerebral ischemia-perfusion injury. Double immunostaining and stereologic counting analysis indicated that a high proportion of BrdU-positive proliferative cells were Nestin-positive NSPs, and also, Sema4C was highly expressed in these proliferative populations at specific stages after ischemic injury. These observations provide the evidence to support a putative role of Sema4C during neurogenesis both in vivo and in vitro.

DIXDC1 is a Dishevelled-Axin (DIX) domain-containing protein involved in neural development and Wnt signaling pathway. Besides the DIX domain, DIXDC1 also contains a coiled-coil domain (MTH domain), which is a common feature of centrosomal proteins. We have demonstrated that exogenously expressed GFP-tag fused DIXDC1 co-localize with gamma-tubulin both at interphase and mitotic phase in HEK293 cells. By immunostaining with anti-DIXDC1 and anti-gamma-tubulin antibody, endogenous DIXDC1 was also co-localized with gamma-tubulin at the centrosomes in HEK293 cells. We confirmed this interaction of DIXDC1 with gamma-tubulin by co-immunoprecipitation. The findings suggest that DIXDC1 might play an important role in chromosome segregation and cell cycle regulation.

CPNE5 is one of the ubiquitous Ca(2+)-dependent, phospholipid-binding proteins that are highly conserved in animals. It was cloned in the fetal human brain with no exact functions identified yet. We have examined the distribution pattern of CPNE5 mRNA and protein in the developing murine brain by using in situ hybridization, western blotting and immunocytochemistry. Expression of CPNE5 mRNA remains high from embryonic day 9.5 (E9.5) to E15.5 in the developing murine brain. Whole-mount in situ hybridization with the E11.5 and E12.5 embryos showed the strong positive signals in the central nervous system. Western-blot analysis showed that CPNE5 protein is expressed in the developing but not in the adult murine brain. In situ hybridization and immunohistochemistry analysis on the embryonic brain sections indicated that both at RNA and protein levels CPNE5 is mainly expressed in frontal cortex, medial nasal prominence, ganglionic eminence and medulla, particularly in the ventricular zones. Further investigation revealed the co-localization of CPNE5 with Tuj1 and Nestin on embryonic brain sections. In addition to the slight expression in primary cultured neural progenitor cells, CPNE5 is found in soma and neurite projections of primary cultured neurons where Tuj1 is co-localized. Our results demonstrate that CPNE5 is expressed in both neural progenitor cells and the differentiated neurons during the neural development, which suggests that CPNE5 might play an important role in the development of murine central nervous system.

Sema4C is a member of transmembrane semaphorin proteins which regulate axonal guidance in the developing nervous system. The expression of Sema4C was dramatically induced not only during differentiation of C2C12 mouse myoblasts, but also during injury-induced skeletal muscle regeneration. C2C12 cells stably or transiently expressing Sema4C both showed increased myogenic differentiation reflected by accelerated myotube formation and expression of muscle-specific proteins. Overexpression of Sema4C elicited p38 phosphorylation directly, and the effects of Sema4C during myogenic differentiation could be abolished by the p38alpha-specific inhibitor SB203580. Knockdown of Sema4C by siRNA transfection during C2C12 myoblasts differentiation could suppress the phosphorylation of p38 followed by dramatically diminished myotube formation. Sema4C could activate the myogenin promoter during myogenic differentiation. This activation could be abolished by p38 inhibitor SB203580. Taken together, these observations reveal novel functional potentialities of Sema4C which suggest that Sema4C promotes terminal myogenic differentiation in a p38 MAPK-dependent manner.