Association of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels with Crohn's disease in Chinese patients.

BACKGROUND AND AIM: The vitamin D receptor (VDR) regulates immune responses and inflammation through binding with 1,25-dihydroxyvitamin D, the active form of vitamin D. The serum 25-hydroxyvitamin D (25(OH)D) level clinically reflects vitamin D status in the human body. We investigated the association of VDR polymorphisms and 25(OH)D levels in Chinese patients with Crohn's disease (CD). METHODS: Vitamin D receptor polymorphisms (FokI, BsmI, ApaI, and TaqI) were genotyped by SNaPshot. Serum 25(OH)D levels were measured by electro-chemiluminescence immunoassay. RESULTS: A total of 297 patients with CD and 446 controls were recruited. Compared with controls, mutant alleles and genotypes of BsmI and TaqI were less prevalent in patients with CD (all P < 0.05/4 = 0.0125). The AAC haplotype formed by BsmI, ApaI, and TaqI was also less prevalent in patients with CD (P = 0.004). Furthermore, 124 patients and 188 controls were randomly selected for measurements of 25(OH)D levels. Average 25(OH)D level was lower in patients with CD than in controls (15.46 ± 8.11 vs 21.64 ± 9.45 ng/mL, P < 0.001) and negatively linked to CD activity index (ß = -0.829, P < 0.001), platelet count (ß = -0.253, P < 0.001) and neutrophil percentage (ß = -0.136, P = 0.005) in patients with CD. The ApaI mutant genotype and vitamin D deficiency (<20 ng/mL) were independently associated with CD (P = 0.009, P < 0.001, respectively). In patients with CD, vitamin D deficiency interacted with FokI, ApaI, and TaqI mutant genotypes (P = 0.027, P = 0.024, and P = 0.040, respectively). CONCLUSIONS: Vitamin D receptor (BsmI, ApaI, and TaqI) mutations and lower 25(OH)D levels are associated with CD in Chinese patients. Moreover, VDR (FokI, ApaI, and TaqI) mutations and vitamin D deficiency may have a combined impact on CD.

Association of vitamin D receptor gene polymorphisms with the susceptibility to ulcerative colitis in patients from Southeast China.

The association studies from different ethnic groups showed that vitamin D receptor (VDR) gene polymorphisms might be connected with the susceptibility to ulcerative colitis (UC); however, the conclusions were less consistent. Our study aimed to analyze the associations of UC with common mutations of VDR in Chinese patients. A total of 382 UC patients and 489 healthy controls were recruited. The genotypes of VDR FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were examined by SNaPshot assays. Haplotype analysis was performed in all study subjects. After Bonferroni correction, the mutant alleles and genotypes of VDR FokI, BsmI, ApaI and TaqI did not statistically differ between UC patients and the controls (all p > 0.0125). However, the mutant allele C and genotype TC + CC of FokI gene were significantly increased in patients with mild and moderate UC compared to those with severe UC (C allele: 54.1% versus 39.3%, OR = 1.83, 95% CI: 1.21-2.75, p = 0.004; TC + CC genotype: 81.6% versus 57.1%, OR = 3.32, 95% CI: 1.83-6.06, p < 0.001, respectively). Haplotype analysis showed that the VDR BsmI, ApaI and TaqI polymorphic loci were in a strong linkage disequilibrium. Furthermore, the frequency of AAC haplotype was statistically lower in UC patients than that in the controls (3.8 versus 5.9%, OR = 0.63, 95% CI: 0.39-1.01, p = 0.039). In conclusion, the mutation of FokI gene influenced severity of the disease in UC patients. Moreover, the AAC haplotype formed by the VDR BsmI, ApaI and TaqI gene might engender a reduced risk of UC attack.

[Association of inflammatory bowel disease with the polymorphisms and haplotypes of fucosyltransferase 3 gene].

OBJECTIVE: To assess the association of inflammatory bowel disease with polymorphisms and haplotypes of Fucosyltransferase 3 (FUT3) gene. METHODS: A total of 389 patients with ulcerative colitis (UC), 274 patients with Crohn's disease (CD), and 492 controls were collected. Three single nucleotide polymorphisms (SNPs) of the FUT3 gene (rs28362459, rs3745635 and rs3894326) were determined by direct sequencing. Linkage disequilibrium and haplotype analysis were performed using a Haploview 4.2 software. RESULTS: Compared with the controls, the allele and genotype distributions of FUT3 gene did not significantly differ between the UC and CD groups (all P>0.05). By stratified analysis, the mutant allele (A) and genotype (GA+AA) of the FUT3 gene (rs3745635) were significantly increased in the UC group with distal colitis compared with the controls (P<0.01, P<0.05, respectively). The mutant allele (G) and genotype (TG+GG) of the FUT3 gene (rs28362459) as well as the mutant allele (A) of FUT3(rs3745635) were significantly increased in patients with ileocolonic CD and ileal CD as compared with the controls (P<0.05, P<0.01, P<0.05, respectively). The frequency of mutant allele (G) of FUT3(rs28362459) was higher in stricturing CD patients than in the controls (P<0.05). In addition, the three polymorphic loci of FUT3 gene were shown in complete linkage disequilibrium [rs3894326/rs3745635 (D'=1.0, r2=0.017), rs3894326/rs28362459 (D'=0.937, r2=0.311), rs3745635/rs28362459 (D'=0.944, r2=0.448)]. However, the frequency of each haplotype was not significantly different between the UC and CD groups compared with the controls (all P>0.05). CONCLUSION: FUT3 (rs3745635) mutation may increase the risk of distal colitis. FUT3 (rs28362459 and rs3745635) mutations may engender the increased risk of ileocolonic and ileal CD. Moreover, FUT3 (rs28362459) polymorphism may influence the incidence of stricturing CD.

[An analysis of vitamin D receptor gene polymorphisms and serum 25-hydroxyvitamin D levels in patients with Crohn's disease].

OBJECTIVE: To investigate the association of Crohn's disease (CD) with vitamin D receptor (VDR) gene polymorphisms and serum 25-hydroxyvitamin D [25(OH)D] level. METHODS: A total of 297 CD patients and 446 healthy controls were enrolled in our study. Four single nucleosides of VDR (Fok I, Bsm I, Apa I and Taq I) were genotyped by SNaPshot. Serum 25(OH)D levels were tested by electro-chemiluminescence immunoassay in 124 CD patients and 188 matched random controls. RESULTS: By Chi-square test and Bonferroni correction, the frequencies of mutant allele (A) and mutant genotype (GA+AA) of Bsm I were significantly decreased in CD patients compared to controls [3.70% (22/594) vs 7.51% (67/892), 95% CI 0.289-0.776, P=0.002; 7.41%(22/297) vs 14.80% (66/446), 95% CI 0.277-0.765, P=0.002, respectively]. The similar results were seen for the mutant allele (C) and mutant genotype (TC+CC) of Taq I [4.21% (25/594) vs 7.62% (68/892), 95% CI 0.333-0.852, P=0.008; 8.42% (25/297) vs 14.57% (65/446), 95% CI 0.331-0.877, P=0.012]. The analyses of linkage disequilibrium (LD) and haplotype were performed by Haploview 4.2 and R software, respectively. The Bsm I, Apa I and Taq I polymorphic loci were found to be in a strong LD, and the AAC haplotype was significantly reduced in CD patients compared to controls [3.14% vs 6.46%, 95% CI 0.273-0.815, P=0.004]. The further serological analysis showed that average serum 25(OH)D level in CD patients was significantly lower than that of controls [(15.46±8.11) µg/L vs (21.64±9.45) µg/L, P<0.001]. By linear regression analysis, serum 25(OH)D levels in CD patients were negatively correlated to Crohn's disease activity index (ß=-0.829, P<0.001), platelet count (ß=-0.253, P<0.001) and the ratio of neutrophils (ß=-0.136, P=0.005) independently, whereas positively related to erythrocyte sedimentation rate (ß=0.191, P=0.001). Furthermore, logistic regression analysis was applied for establishing the models of gene-environment interaction. In result, both the mutant genotype (CA+AA) of Apa I and vitamin D deficiency (<20 µg/L) were shown to be the independent risk factors for CD (OR=7.580, 95% CI 2.983-19.261, P<0.001; OR=2.842, 95% CI 1.300-6.211, P=0.009, respectively). Besides, vitamin D deficiency in CD patients had multiplicative interactions with the mutant genotype (TC+CC) of Fok I, genotype (CA+AA) of Apa I and genotype (TC+CC) of Taq I, respectively (OR=0.419, 95% CI 0.194-0.906, P=0.027; OR=0.309, 95% CI 0.111-0.855, P=0.024; OR=5.841, 95% CI 1.082-31.538, P=0.040; respectively). CONCLUSIONS: VDR (Bsm I, Apa I and Taq I) polymorphisms and serum 25(OH)D levels are significantly related to CD. Both the mutant genotype (CA+AA) of Apa I and vitamin D deficiency are independent risk factors of CD. The mutations of VDR (Fok I, Apa I and Taq I) and vitamin D deficiency might have a synergistic effect on CD susceptibility.

[The associations of ulcerative colitis with vascular endothelial growth factor (-2578C/A) and (+936C/T) single nucleotide polymorphisms].

OBJECTIVE: To investigate the association of (-2578C/A) and (+936C/T) single nucleotide polymorphism(SNPs) of vascular endothelial growth factor (VEGF) gene with the susceptibility to ulcerative colitis (UC). METHODS: A total of 373 UC patients and 503 healthy controls were recruited. The (-2578C/A) and (+936C/T) polymorphism of VEGF gene were detected using a mini-sequencing technique. RESULTS: By an unconditional logistic regression analysis, the frequencies of the mutant allele T and genotype CT+TT of VEGF gene (+936C/T) were significantly decreased in patients with severe UC compared to the controls (10.4% vs 19.3%, OR = 0.487, 95%CI 0.248-0.954, P = 0.036; 18.8% vs 33.8%, OR = 0.452, 95%CI 0.214-0.955, P = 0.037, respectively). Moreover, patients with severe UC had significant lower rates of mutant allele T and genotype CT+TT compared with patients with mild and moderate UC (10.4% vs 20.5%, OR = 0.452, 95%CI 0.229-0.894, P = 0.022; 18.8% vs 36.9%, OR = 0.394, 95%CI 0.185-0.842, P = 0.016, respectively). The frequencies of mutant allele A and genotype CA+AA of VEGF (-2578C/A) gene were not statistically different between UC patients and the controls. Moreover, they were not significantly associated with the clinicopathologic features in UC patients. CONCLUSIONS: The mutation of VEGF (+936C/T) gene is correlated with the severity of UC. However, the polymorphism of VEGF (-2578C/A) gene is not significantly related to the susceptibility to UC.

Endoscopy-Intravascular Treatment Combination for Duodenal Ulcer Hemorrhages Caused by Small Hepatic Pseudoaneurysms: A Case Report.

Aim: Significant gastrointestinal hemorrhages, resulting from long-term compression of the duodenum by a hepatic pseudoaneurysm (HAPA), is an extremely rare condition. In fact, when the pseudoaneurysm is small in diameter, diagnosis can be particularly challenging. Timely and effective diagnosis and treatment is therefore of great significance, and in this case, endoscopy, combined with intravascular therapy, can provide an effective approach, especially since it removes the need for surgery while yielding favorable outcomes. Case Summary: A 75-year-old old man presented to the hospital's emergency department with hematemesis and black stool. Despite conservative treatments such as "acid suppression, fluid resupply, hemostasis and blood transfusion", no significant improvement was noted. Emergency gastroscopy subsequently revealed an ulcer in the duodenal bulb (Figure 1), with an exposed thrombotic head and active bleeding on the surface. In addition, abdominal computed tomography (Figure 2) showed no obvious HAPA manifestations. After unsuccessful endoscopic hemostasis, angiography was performed (Figure 3) and a pseudotumor-like dilatation measuring 5.56 mm in diameter was found at the distal end of the proximal branch vessel of the common hepatic artery. Following spring coil embolization (Figure 4), the patient's condition improved and he was discharged from the hospital, with a follow-up after six months showing no signs of recurrence or complications. Conclusion: Duodenal ulcer hemorrhages due to small hepatic pseudoaneurysms are very rare, with endoscopic intervention being effective for such cases.

Unraveling the Molecular Regulation of Ferroptosis in Respiratory Diseases.

Ferroptosis, a type of programmed cell death that relies on iron, is distinct in terms of its morphological, biochemical and genetic features. Unlike other forms of cell death, such as autophagy, apoptosis, necrosis, and pyroptosis, ferroptosis is primarily caused by lipid peroxidation. Cells that die due to iron can potentially trigger an immune response which intensifies inflammation and causes severe inflammatory reactions that eventually lead to multiple organ failure. In recent years, ferroptosis has been identified in an increasing number of medical fields, including neurological pathologies, chronic liver diseases and sepsis. Ferroptosis has the potential to cause an inflammatory tempest, with many of the catalysts and pathological indications of respiratory ailments being linked to inflammatory reactions. The growing investigation into ferroptosis in respiratory disorders has also garnered significant interest to better understand the mechanism of ferroptosis in these diseases. In this review, the recent progress in understanding the molecular control of ferroptosis and its mechanism in different respiratory disorders is examined. In addition, this review discusses current challenges and prospects for understanding the link between respiratory diseases and ferroptosis.

Mesenchymal Stem Cell-Derived Exosomes in Various Chronic Liver Diseases: Hype or Hope?

Chronic liver conditions are associated with high mortality rates and have a large adverse effect on human well-being as well as a significant financial burden. Currently, the only effective treatment available for the effects of liver failure and cirrhosis resulting from the progression of several chronic liver diseases is liver transplantation carried out at the original location. This implies that developing novel and effective treatments is imperative. Regenerative medicine has long been associated with stem cell therapy. Mesenchymal stem cells (MSCs), a type of cell with great differentiation potential, have become the preferred source for stem cell therapy. According to recent studies, MSCs' paracrine products-rather than their capacity for differentiation-play a significant therapeutic effect. MSC exosomes, a type of extracellular vesicle (MSC-EV), came into view as the paracrine substances of MSCs. According to research, MSC exosomes can maintain tissue homeostasis, which is necessary for healthy tissue function. All tissues contain them, and they take part in a variety of biological activities that support cellular activity and tissue regeneration in order to preserve tissue homeostasis. The outcomes support the use of MSCs and the exosomes they produce as a therapeutic option for a range of diseases. This review provides a brief overview of the source of MSC-EVs and outlines their physiological roles and biochemical capabilities. The elucidation of the role of MSC-EVs in the recovery and repair of hepatic tissues, as well as their contribution to maintaining tissue homeostasis, is discussed in relation to different chronic liver diseases. This review aims to provide new insights into the unique roles that MSC-EVs play in the treatment of chronic liver diseases.

Inflammation unleashed: The role of pyroptosis in chronic liver diseases.

Pyroptosis, a newly identified form of programmed cell death intertwined with inflammatory responses, is facilitated by the Gasdermin family's pore-forming activity, leading to cell lysis and the release of pro-inflammatory cytokines. This process is a double-edged sword in innate immunity, offering protection against pathogens while risking excessive inflammation and tissue damage when dysregulated. Specifically, pyroptosis operates through two distinct signaling pathways, namely the Caspase-1 pathway and the Caspase-4/5/11 pathway. In the context of chronic liver diseases like fibrosis and cirrhosis, inflammation emerges as a central contributing factor to their pathogenesis. The identification of inflammation is characterized by the activation of innate immune cells and the secretion of pro-inflammatory cytokines such as IL-1α, IL-1ß, and TNF-α. This review explores the interrelationship between pyroptosis and the inflammasome, a protein complex located in liver cells that recognizes danger signals and initiates Caspase-1 activation, resulting in the secretion of IL-1ß and IL-18. The article delves into the influence of the inflammasome and pyroptosis on various liver disorders, with a specific focus on their molecular and pathophysiological mechanisms. Additionally, the potential therapeutic implications of targeting pyroptosis for liver diseases are highlighted for future consideration.

Association Between Serum Vitamin C and Non-alcoholic Fatty Liver Disease: A Cross-sectional Study.

BACKGROUND: The association between vitamin C and the risk of developing non-alcoholic fatty liver disease remains controversial. The aim of the present study is to examine any correlation between serum vitamin C and the risk of non-alcoholic fatty liver disease. METHODS: Our study enrolled 3374 participants aged ≥ 20 years from the National Health and Nutritional Survey (2003-2006). Nonalcoholic fatty liver disease was defined as the US Fatty Liver Index ≥ 30 in the absence of other chronic liver disease. Multivariate logistic regression and the fitted smoothing curves were adopted for analyzing the correlation between serum vitamin C levels and the risk of developing non-alcoholic fatty liver disease. RESULTS: After adjusting for all the covariates, it was discovered that serum vitamin C was negatively correlated with the risk of nonalcoholic fatty liver disease (odds ratio: 0.664, 95% CI: 0.512-0.860, P = .002). Through smooth curve fitting, it was further noticed that the relationship between serum vitamin C and the risk of non-alcoholic fatty liver disease was non-linear. The inflection point was 0.92, and to its left, a negative correlation was seen between vitamin C and non-alcoholic fatty liver disease (odds ratio: 0.451, 95% CI: 0.288- 0.706, P = .001). To the right of the inflection point, however, the correlation between vitamin C and non-alcoholic fatty liver disease was not found to be significant. CONCLUSION: The correlation was non-linear between serum vitamin C levels and the risk of developing non-alcoholic fatty liver disease. Serum vitamin C was negatively correlated with the risk of non-alcoholic fatty liver disease when its level was less than 0.92 mg/dL.

Appendiceal bleeding: A case report.

BACKGROUND: Acute lower gastrointestinal bleeding is common in clinical practice, and the colon is responsible for the majority of cases. However, appendiceal bleeding is an extremely rare cause. Appendiceal bleeding due to vascular diseases, such as angiodysplasia and Dieulafoy's lesion, may result in massive lower gastrointestinal bleeding. Appendectomy is a reliable and effective option for treatment. CASE SUMMARY: A 32-year-old male presented to our hospital with hematochezia that had lasted for 6 h, with approximately 600-800 mL bloody stools and loss of consciousness for a few seconds. Persistent bleeding from the orifice of the appendix was observed by colonoscopy. Following the new diagnosis of appendiceal bleeding, the patient was treated by an emergency laparoscopic appendectomy. Finally, the patient was pathologically diagnosed with appendiceal Dieulafoy's lesion. The patient was uneventfully discharged, and follow-up 2 wk later showed no evidence of rebleeding. CONCLUSION: Although appendiceal bleeding is a rare cause of acute lower gastrointestinal bleeding, clinicians should consider it during differential diagnosis.

Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China.

OBJECTIVES: Dysbiosis of intestinal microbiota has been implicated in ulcerative colitis (UC). Fucosyltransferase (FUT) 2 and FUT3 determine expression of histo-blood group antigens in the gut and may affect the intestinal microbiota. We investigated the association between FUT2 and FUT3 polymorphisms and UC in Chinese patients. METHODS: We genotyped FUT2 (rs281377, rs1047781 and rs601338) and FUT3 (rs28362459, rs3745635 and rs3894326) in 485 UC patients and 580 healthy controls using SNaPshot. We also evaluated expression of Lewis a and b antigens in the sigmoid colon of 7 UC patients and 7 patients with benign colonic polyps. RESULTS: The frequencies of mutant allele (A) and genotype (GA+AA) in FUT3 (rs3745635) were higher in UC patients than controls (P = 0.016, 95%CI: 1.339-1.699; P = 0.038, 95%CI: 1.330-1.742, respectively). Stratified analyses revealed that the frequencies of mutant allele (G) and genotype (TG+GG) of FUT3 (rs28362459) were significantly lower in patients with extensive colitis than those with distal colitis (P<0.001, 95%CI: 0.503-0.742; P = 0.001, 95%CI: 0.567-0.786, respectively). Similar conclusions were drawn for the mutant allele (A) and genotype (GA+AA) of FUT3 (rs3745635) in patients with extensive colitis compared to those with distal colitis (P = 0.006, 95%CI: 0.553-0.845; P = 0.011, 95%CI: 0.621-0.900, respectively). Although expression of Lewis b antigen in the sigmoid colon did not differ between UC patients and controls, Lewis a antigen expression was higher in the cryptic epithelium of both inflammatory and non-inflammatory sigmoid colon of UC patients than controls (P = 0.028). CONCLUSIONS: Our findings indicated that polymorphisms in FUT3 and its intestinal expression might be associated with UC pathogenesis.