Sarcopenia in liver cirrhosis: perspectives from epigenetics and microbiota.

Sarcopenia is characterized by the loss of muscle mass and function. It is well known that sarcopenia is often associated with aging, while in recent years, sarcopenia comorbid with chronic diseases such as cirrhosis has attracted widespread attention, whose underlying molecular mechanisms remain unclear. Since cirrhosis and sarcopenia are assumed to be closely interrelated in terms of pathogenesis, this review innovatively discussed the role of epigenetic modifications and microecological dysregulation in sarcopenia in the context of liver cirrhosis. Here we illustrated the relationship between sarcopenia and cirrhosis in the aspect of epigenetics, dysbiosis, and the crosstalk between gene modifications and intestinal microecology. Furthermore, the alterations in cirrhosis patients with sarcopenia, such as inflammatory response and oxidative stress, are found to present synergistic effects in the pathways of epigenetics and dysbiosis leading to sarcopenia. This review proposes that microbiome-based therapies are promising to break the vicious cycle between epigenetic modification and dysbiosis, providing strong support for the use of intestinal microecological interventions to prevent sarcopenia in cirrhotic patients.

Joint Detection of Serum Vitamin D, Body Mass Index, and Tumor Necrosis Factor Alpha for the Diagnosis of Crohn's Disease.

OBJECTIVE: Vitamin D (VD) deficiency was reported to contribute to the progression of Crohn's disease (CD) and affect the prognosis of CD patients. This study investigated the role of serum VD, body mass index (BMI), and tumor necrosis factor alpha (TNF-α) in the diagnosis of Crohn's disease. METHODS: CD patients (n=76) and healthy subjects (n=76) were enrolled between May 2019 and December 2020. The serum 25-hydroxyvitamin D [25(OH)D] levels, BMI, and TNF-α levels, together with other biochemical parameters, were assessed before treatment. The diagnostic efficacy of the single and joint detection of serum 25(OH)D, BMI, and TNF-α was determined using receiver operating characteristic (ROC) curves. RESULTS: The levels of 25(OH) D, BMI, and nutritional indicators, including hemoglobin, total protein, albumin, and high-density lipoprotein cholesterol, were much lower, and the TNF-α levels were much higher in the CD patients than in the healthy subjects (P<0.05 for all). The areas under the ROC curve for the single detection of 25(OH)D, BMI, and TNF-α were 0.887, 0.896, and 0.838, respectively, with the optimal cutoff values being 20.64 ng/mL, 19.77 kg/m2, and 6.85 fmol/mL, respectively. The diagnostic efficacy of the joint detection of 25(OH)D, BMI, and TNF-α was the highest, with an area under the ROC curve of 0.988 (95%CI: 0.968-1.000). CONCLUSION: The joint detection of 25(OH)D, TNF-α, and BMI showed high sensitivity, specificity, and accuracy in CD diagnosis; thus, it would be effective for the diagnosis of CD in clinical practice.

Causal relationship between asthma and ulcerative colitis and the mediating role of interleukin-18: a bidirectional Mendelian study and mediation analysis.

Objective: Numerous observational investigations have documented a correlation between asthma and ulcerative colitis(UC). In this Mendelian Randomization (MR) study, we utilized extensive summary data from Genome-Wide Association Studies (GWAS) to further estimate the association between adult-onset asthma and the risk of UC, and to investigate the role of Interleukin-18 (IL-18) as a potential mediator. Materials and methods: A two-step, two-sample MR study was conducted through mediation analysis. For this study, we employed a two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, weighted mode, and MR-Egger regression techniques. We utilized publicly accessible summary statistics from a GWAS meta-analysis of adult-onset asthma in the UK Biobank (n=327,253; cases=26,582; controls=300,671) as the exposure factor. The outcomes were derived from GWAS data of individuals with European ancestry (n=26,405; cases=6,687; controls=19,718). GWAS data for IL-18 were obtained from individuals of European ancestry (n=9,785,222; cases=3,636; controls=9,781,586). Results: The MR analysis indicates that adult-onset asthma is associated with an increased risk of UC, with an odds ratio (OR) of 1.019 (95% CI 1.001-1.045, P=0.006). However, there is no strong evidence to suggest that UC significantly impacts the risk of adult-onset asthma. IL-18 may act as a potential mediator in the causal relationship between adult-onset asthma and UC, with a mediation proportion of 3.9% (95% CI, 0.6%-6.9%). Conclusion: In summary, our study established a causal relationship between asthma and UC, in which IL-18 contributes to a small extent. However, the primary factors underlying the influence of asthma on UC remain unclear. Future research should focus on identifying other potential mediators. In clinical practice, it is important to pay greater attention to intestinal lesions in patients with asthma.

Corrigendum: New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease.

[This corrects the article DOI: 10.3389/fped.2022.714054.].

New Insights and Advances in Pathogenesis and Treatment of Very Early Onset Inflammatory Bowel Disease.

Very early onset inflammatory bowel disease (VEO-IBD) is characterized by multifactorial chronic recurrent intestinal inflammation. Compared with elderly patients, those with VEO-IBD have a more serious condition, not responsive to conventional treatments, with a poor prognosis. Recent studies found that genetic and immunologic abnormalities are closely related to VEO-IBD. Intestinal immune homeostasis monogenic defects (IIHMDs) are changed through various mechanisms. Recent studies have also revealed that abnormalities in genes and immune molecular mechanisms are closely related to VEO-IBD. IIHMDs change through various mechanisms. Epigenetic factors can mediate the interaction between the environment and genome, and genetic factors and immune molecules may be involved in the pathogenesis of the environment and gut microbiota. These discoveries will provide new directions and ideas for the treatment of VEO-IBD.

Comparison and recommendation of dietary patterns based on nutrients for Eastern and Western patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD), a non-specific chronic idiopathic inflammatory condition of the digestive system, requires lifelong treatment in which drugs are the mainstay, along with surgery when necessary. In adjuvant therapies, the diet is considered to be an essential, controllable, and economical component. However, the majority of recent nutrition research has focused on the general effects of nutrients on IBD, with little attention given to the advantages and negative aspects of individual foods and dietary combinations. To cover these shortcomings, we surveyed the benefits and drawbacks of typical foods and their chemical compositions on intestinal pathophysiology by comparing nutrients existing in the foods in Eastern and Western countries. Moreover, for Eastern and Western patients with IBD, we innovatively propose a 3-step dietary recommendation based on modified customary eating habits, including lowering the triggering foods, modifying dietary advice to control disease progression, and improving surgery prognosis.

Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence.

The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no "specific drug" available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, "conventional drug in new use" becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the "specific drug". China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.

Risk of skin cancers in thiopurines-treated and thiopurines-untreated patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients. METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity. RESULTS: Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance. CONCLUSION: Exposition of thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.

Conversion therapy and suitable timing for subsequent salvage surgery for initially unresectable hepatocellular carcinoma: What is new?

AIM: To review the conversion therapy for initially unresectable hepatocellular carcinoma (HCC) patients and the suitable timing for subsequent salvage surgery. METHODS: A PubMed search was undertaken from 1987 to 2017 to identify articles using the keywords including "unresectable" "hepatocellular carcinoma", "hepatectomy", "conversion therapy", "resection", "salvage surgery" and "downstaging". Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction. RESULTS: Liver volume measurements [future liver remnant (FLR)/total liver volume or residual liver volume/bodyweight ratio] and function tests (scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing complications, morbidity or mortality. The requirements for performing salvage surgery after transcatheter arterial chemoembolization were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis, and the lack of extrahepatic metastasis. Patients with a standardized FLR (sFLR) > 20% were good candidates for surgery after portal vein embolization, while other predictive parameters like growth rate, kinetic growth rate were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy or yttrium-90 microsphere radioembolization. The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehensively evaluated. CONCLUSION: Conversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subsequent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.

Is a low FODMAP diet beneficial for patients with inflammatory bowel disease? A meta-analysis and systematic review.

BACKGROUND & AIMS: To assess the current evidence regarding the benefit of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diet in the treatment of patients with inflammatory bowel disease (IBD). METHODS: Databases such as PubMed, Web of Science, Medline were comprehensively searched for relevant studies through January 2017. The pooled odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were used to analyze the dichotomous variables (diarrhea response, abdominal pain and bloating, etc.) and the continuous variables. Random- and fixed-effects models were chosen according to heterogeneity. RESULTS: Two RCTs and four before-after studies with a total of 319 patients (96% in remission) were identified. Except for the constipation response, there was a significant improvement in other symptoms: diarrhea response (OR: 0.24, 95% CI: 0.11-0.52, p = 0.0003), satisfaction with gut symptoms (OR: 26.84, 95% CI: 4.6-156.54, p < 0.00001), abdominal bloating (OR: 0.10, 95% CI: 0.06-0.16, p < 0.00001), abdominal pain (OR: 0.24, 95% CI: 0.16-0.35, p < 0.00001), fatigue (OR: 0.40, 95% CI: 0.24-0.66, p = 0.0003) and nausea (OR: 0.51, 95% CI: 0.31-0.85, p = 0.009). CONCLUSIONS: The present meta-analysis offers proof to support that a low FODMAP diet is beneficial for reducing gastrointestinal symptoms in patients with quiescent IBD. With the inherent limitations, the findings of this analysis remain to be confirmed and updated by further high-volume, well-designed and long-term follow-up studies.

Decreased CD8+CD28+/CD8+CD28- T cell ratio can sensitively predict poor outcome for patients with complicated Crohn disease.

Crohn disease (CD) with complications such as penetrating, stricturing, and perianal disease is called complicated CD. The aim of this study is to test the efficiency with which the CD8CD28/CD8CD28 cell balance can predict a subsequent active stage in patients with newly diagnosed complicated CD.Seventeen patients with complicated CD and 48 CD patients with no complications were enrolled. Blood CD8 T cells were tested from all of the 65 newly diagnosed CD patients upon enrollment. The potential risk factors were compared between the 2 groups. A 30-week follow-up was performed, and the efficiency of the CD8 cell balance at predicting active CD was analyzed using receiver-operating characteristic curves. The cumulative remission lasting rates (CRLRs) were analyzed using the Kaplan-Meier method.Compared with the control CD group, patients with complicated CD were predominantly male and younger in age; they also had lower body mass indices (BMIs), higher Crohn disease activity indices (CDAIs), higher immunosuppressant and steroid prescription rates, and significantly higher surgical rates. The CD8CD28/CD8CD28 balance was associated with BMI, CDAI, steroids, and surgery. The CD8CD28/CD8CD28 ratios were significantly lower at week 0 and on the 6th, 22nd, and 30th week during follow-up with a shorter lasting time of remission for the complicated CD patients. The CD8CD28/CD8CD28 ratio could accurately predict the active stage for the patients with complicated CD, and the highest sensitivity (89.2%) and specificity (85.3%) were found when the ratio was 1.03. Treatment with steroids and surgery, along with a significantly lower CD8CD28/CD8CD28 ratio and lower CRLRs, was closely related to a worse outcome for the patients with complicated CD.Patients requiring steroids and surgery experience more severe disease activity and thus a disequilibrated immunological balance, which could be the main reason for a decreased CD8CD28/CD8CD28 ratio. This ratio can sensitively predict the active stage for patients with complicated CD, and more care should be taken when this ratio is <1.03.

CD8+CD28+/CD8+CD28- T cell equilibrium can predict the active stage for patients with inflammatory bowel disease.

BACKGROUND/AIM: The balance of blood CD8+CD28+/CD8+CD28- T cells has been verified to be vital for patients with ulcerative colitis (UC), but their role in inflammatory bowel disease (IBD) remains unknown. This investigation aimed to evaluate the efficiency of the balance in predicting the active stage in IBD patients. METHODS: Fifty-three IBD subjects, including 31 UC and 22 Crohn's disease (CD) patients, were enrolled, and their peripheral blood CD8+CD28+ and CD8+CD28- T cell levels were tested using flow cytometry. The risk factors related to prognosis were compared between UC and CD patients. A 1-year follow-up was performed for all the IBD patients, and the CD8+ T cells and their ratio were compared at the 3rd, 6th, 9th, and 12th months during follow-up. The sensitivity and specificity of the CD8+ T cell level and balance were analyzed through receiver operator characteristic (ROC) curves. The cumulative remission lasting rates (CRLRs) under the different factors were analyzed using the Kaplan-Meier method. RESULTS: Higher prescription rates of immunosuppressants, steroids, probiotics, and biological agents (BAs) were found in CD subjects in comparison to UC subjects (P=0.005, 0.024, 0.034, and 0.001), as was a higher active rate during follow-up (95.5% of CD patients vs 67.7% of UC patients, P=0.035). The CD8+CD28+ T cell level and the CD8+CD28+/CD8+CD28- T cell ratio were significantly higher in UC patients than in CD patients, but the reverse was true for CD8+CD28- T cells during follow-up at the 9th and 12th month (all P<0.05). The diagnostic models of the initial CD8+CD28+ and CD8+CD28- T cell numbers and the CD8+CD28+/CD8+CD28- T cell ratio in predicting the active stage were found to be significant, with areas under the curves (AUCs) of 0.883, 0.098, and 0.913 for UC subjects (with 95% CI: 0.709-0.940, 0.009-0.188, and 0.842-1.003; P=0.001, 0.00, and 0.000) and 0.812, 0.078, and 0.898 for CD subjects (with 95% CI: 0.683-0.957, 0.003-0.158, and 0.837-0.998; P=0.003, 0.00, and 0.000). The cut-off values showed that when the ratios were 1.30 for UC and 1.22 for CD patients, the best sensitivity and specificity were observed, with 91.6% and 89.0% for UC and 88.5% and 85.1% for CD, respectively. The CRLRs were significantly higher in female, non-BA-treated, non-surgical IBD subjects when compared to male, BA-treated, surgical subjects (P=0.031, 0.000, and 0.000). The number of CD8+CD28+ and CD8+CD28- T cells and the CD8+CD28+/CD8+CD28- T cell ratio were correlated with BA treatment and surgery (all P<0.05). CONCLUSION: The CD8+CD28+/CD8+CD28- T cell balance, expected to be a novel immunologic marker, presented a satisfactory efficiency with high sensitivity and specificity in predicting the active stage in UC and CD patients, and the balance was closely related to the use of BAs and surgery.

[Effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion injury in rats].

OBJECTIVE: To observe the effect of different time windows and interventions on skin pressure ulcers and ischemia-reperfusion (I/R) injury in rats. METHODS: Sixty?eight SD rats were randomly divided into blank control group (n=4) and model group (n=64). The rats in the model group were randomly divided into group A (n=32) without intervention and group B (n=32) with post?conditioning. The degree of skin compression, neutrophil infiltration and serum levels of free radicals were observed in the rats after compression for 2, 4, 6, and 8 h (8 rats at each time point). RESULTS: A significant difference was found in the severity of skin damage among the control group, group A, and group B (P=0.001), and the injury was milder in group B than in group A. Severe skin lesions occurred in 2 rats after skin compression for 6 h, as compared with 6 after compression for 8 h (P=0.043), but in none of the rats after compression for 2 or 4. Seventeen rats in group B and 15 in group A showed grade 1 neutrophil infiltration in the skin lesions, and 8 rats in group B and 10 in group A showed grade II neutrophil infiltration (P=0.002). Neutrophil infiltration was the mildest in rats with a 2?h compression, and exacerbated progressively and significantly as the compression time extended (P=0.027). With the prolongation of the intervention time, the rats in both groups A and B showed decreased SOD and increased MDA and NO levels, and overall the I/R injury was milder in 2? and 4?h compression groups than in 6? and 8?h compression groups. The level of serum SOD was significantly higher and MDA and NO levels were significantly higher in group B than in group A (P<0.05). CONCLUSION: Ischemic post?conditioning can relieve I/R injury in acute pressure ulcer in rats. The effective time window for intervention is within 6 h of ischemia, and the effect of ischemic post-conditioning is optimal within 2 h. Ischemic post?conditioning can alleviate free radical injury and inflammation caused by I/R injury.

[Immunological balance of CD8+CD28+/CD8+CD28- T lymphocytes can predict gastrointestinal hemorrhage in patients with inflammatory bowel disease].

OBJECTIVE: To evaluate the sensitivity and specificity of CD8+CD28+/CD8+CD28- T lymphocyte balance in predicting the gastrointestinal hemorrhage (GH) in patients with inflammatory bowel disease (IBD). METHODS: Forty-nine IBD patients, including 30 with ulcerous colitis (UC) and 19 with Crohn's disease (CD), were enrolled to test peripheral blood CD8+CD28+ and CD8+CD28- T cells using flow cytometry. All the patients were followed up for one year. The receiver-operating characteristic (ROC) curves were used to test the efficiency of CD8+CD28+/CD8+CD28- T lymphocyte balance to predict GH. The differences in lasting time of remission (LTR) under different factors were compared using Kaplan-Meier survival analysis, and the correlation between CD8+ T lymphocytes and the factors were analyzed. RESULTS: The utilization rates of immunosuppressant, steroids, and biological agent (BA) were significantly higher in CD patients than in UC patients (P=0.003, 0.043 and 0.002, respectively). The frequencies of CD8+CD28+T cells were obviously higher in UC patients than those in CD patients (t=3.022, P=0.004). CD8+CD28+T cells, CD8+CD28- T cells, and especially CD8+CD28+/CD8+CD28- ratio (area under curve of 0.977, P=0.000; cut-off value of 1.14 [13.95%/12.24%] with a sensitivity of 93.3% and a specificity of 91.2%) showed good efficiencies in predicting GH (P<0.01). The mean and median of LTR of IBD patients who did not receive BA or surgical treatment were significantly longer (Χ2=9.730, P=0.002; Χ2=15.981, P=0.000). CD8+CD28+/CD8+CD28- ratio was significantly related to both BA (P=0.009) and surgery (P=0.038). CONCLUSION: Both decreased CD8+CD28+T cells and elevated CD8+CD28-T cells are closely correlated with GH, and their ratio can predict the occurrence of GH with a high sensitivity and specificity and is correlated with BA and surgery at the cut-off value of 1.14.

Baicalin attenuates TNBS-induced colitis in rats by modulating the Th17/Treg paradigm.

Baicalin, a flavonoid, has a wide range of pharmacological properties, including immunomodulation. The objective of this study was to investigate the effect of baicalin on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in a colitis model. The rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Baicalin (10 ml/kg, each) or mesalazine (positive control) was then administered orally for 7 days. Inflammatory and immunological responses were evaluated by pathology, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, western blot analysis, and flow cytometry. Our study showed that baicalin not only significantly attenuated TNBS-induced colitis by reducing the disease activity index as well as macroscopic and microscopic scores, but it also improved the weight loss and shortening of the colon. Baicalin treatment also induced a significant decrease in the levels of inflammatory mediators, including the myeloperoxidase activity, the levels of tumor necrosis factor α, IL-1ß, and Th1-related cytokines IL-12 and IFN-γ. Furthermore, the beneficial effects of baicalin seem to be associated with regulation of the Th17 and Treg paradigm. We found that administration of baicalin significantly downregulated the number of Th17 cells and the levels of Th17-related cytokines (IL-17 and IL-6) and retinoic acid receptor-related orphan receptor γt. In contrast, there was an increase in Treg cells numbers, Treg-related cytokines transforming growth factor-ß and IL-10, and forkhead box P3. Our results suggest that the anti-inflammatory effect of baicalin may be linked to modulation of the balance between Th17 and Treg cells in TNBS-induced ulcerative colitis.

Association of the interleukin-22 genetic polymorphisms with ulcerative colitis.

BACKGROUND: Interleukin-22 (IL-22) is a member of the IL-10 family of anti-inflammatory cytokines that mediates epithelial immunity. IL-22 expression was found to be increased in patients with ulcerative colitis (UC). Whether genetic polymorphisms of IL-22 also influence UC risk is still unknown. The purpose of this study was to investigate the association between the IL-22 gene polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) and the risk of UC in Chinese Han patients. METHODS: This hospital-based case-control study comprised 180 patients with UC and 180 age- and gender-matched controls. Genotypes of 3 common polymorphisms of the IL-22 gene were determined by fluorogenic 5' exonuclease assays (TaqMan). RESULTS: Patients with UC had a significantly higher frequency of IL-22 -429 TT genotype [odds ratio (OR) =2.43, 95% confidence interval (CI) =1.35, 4.37; P=0.003] and -429 T allele (OR =1.54, 95% CI=1.14, 2.07; P=0.004) than controls. The findings are still emphatic by the Bonferroni correction. The IL-22+1046 T/A and IL-22+1995 A/C gene polymorphisms were not associated with a risk of UC. When stratifying by clinical type, location and disease severity of UC, no significant differences were found in any groups. CONCLUSION: This is the first study to provide evidence for an association of IL-22 -429 C/T gene polymorphisms with UC risk. Additional well-designed large studies were required for the validation of our results. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_183.

Balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes is vital for patients with ulcerative colitis.

BACKGROUND: Immune balances are important for many diseases including ulcerative colitis (UC). This study aimed to explore the role of the balance between CD8+ CD28+ and CD8+ CD28- T lymphocytes for the immunological pathogenesis of UC. METHODS: Sixteen patients with UC, 16 patients with irritable bowel syndrome (IBS) and 15 healthy volunteers were enrolled. The frequencies of CD8+ CD28+ and CD8+CD28- T lymphocytes in peripheral blood and colon tissue were tested using flow cytometry and immunofluorescent, respectively. The cytokines of the two lymphocytes were detected by protein chips and ELISA. The expression of the signal transducers, the JAK3 and STAT6, as well the transcription factors, the NFATc2 and GATA3, was all detected by both western blot and immunohistochemistry. RESULTS: For UC patients, the frequencies of CD8+ CD28+ T lymphocytes, together with the ratios of CD8+ CD28+ / CD8+ CD28- T lymphocytes in blood and colon tissue, were significantly lower than those in both IBS patients and healthy volunteers. But the frequencies of CD8+ CD28- T lymphocytes in blood and colon tissue of the UC patients were significantly higher than the other two groups. The concentration of IL-7 and -13, and the expression of JAK3 and STAT6 in UC patients, were significantly lower when compared with the other two groups. Conversely, the concentration of IL-12p40 and -15, and the expression of GATA3 and NFATc2 in UC patients, were significantly higher than both IBS and control group. CONCLUSIONS: The balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes plays a vital role in UC, while the balance tilt towards CD8+ CD28+ T lymphocytes is beneficial for patients with UC.

Baicalin down-regulates the expression of macrophage migration inhibitory factor (MIF) effectively for rats with ulcerative colitis.

The purpose of this study was to investigate whether baicalin, a Chinese herbal extract, down-regulates the expression of macrophage migration inhibitory factor (MIF), an inflammatory factor that regulates the function of macrophages (MΦ), in rats with trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis (UC). The results showed that baicalin simultaneously down-regulated the expression of MIF, the quantity of MΦs and the amount of MΦ-related cytokines, including macrophage chemotactic factor-1 (MCP-1, CCL2) and macrophage inflammatory protein-3α (MIP-3α, CCL20), in rats with UC. There was no statistical difference between baicailin and mesalazine in down-regulating the expression of MIF. Our study demonstrated that baicalin, an inexpensive but effective monomer, could be a new and alternative pharmaceutical for UC.

[Huangqin decoction lowers the number of mast cells in ulcerative colitis in rats with dampness and heat syndrome].

OBJECTIVE: To explore the role of mast cells in the pathogenesis of ulcerative colitis in rats with dampness and heat syndrome, and observe the regulatory effect of Huangqin decoction on the mast cells. METHODS: Rat models of dampness and heat syndrome were established by feeding with high-fat and-sugar chow, maintenance of a hot and humid environment, and intrarectal administration of 2,4,6-trinitro-benzene-sulfonic acid. The model rats were then randomized into the model group (n=12), Huangqin decoction group (n=13) and mesalazine group (n=12). After a one-week treatment, the inflammatory cell infiltration was observed using HE staining, and the number of mast cells was determined using toluidine blue staining. Immunohistochemistry was used to detect the expression of tryptase, and serum IL-4 and IL-6 levels were measured using ELISA. RESULTS: Compared with the normal control rats (n=15), the rats in the model group showed obvious inflammatory cell infiltration at the lesion site with significantly increased mast cells and serum IL-6 level (P<0.05). Huangqin and mesalazine significantly lessened inflammatory cell infiltration and decreased the mast cell number and serum IL-6 level after a one-week treatment. CONCLUSION: The intestinal mucosal immune cells such as the mast cells play an important role in the pathogenesis of ulcerative colitis associated with dampness and heat syndrome. Huangqin decoction can ameliorate the inflammation, decrease mast cell number and tryptase release, and inhibit IL-6 secretion for treatment of ulcerative colitis in rats with dampness and heat syndrome.