Inulin Inhibits the Inflammatory Response through Modulating Enteric Glial Cell Function in Type 2 Diabetic Mellitus Mice by Reshaping Intestinal Flora.

Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase ß/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.

Leukocyte telomere length predicts overall survival in hepatocellular carcinoma treated with transarterial chemoembolization.

Previous studies have reported that telomere length in peripheral blood leukocytes can predict the clinical outcome of several cancers. However, whether leukocyte telomere length is associated with the prognosis of hepatocellular carcinoma (HCC) remains to be determined. In this study, relative telomere length (RTL) in peripheral blood leukocytes was measured using a real-time PCR-based method for 269 HCC patients treated with transarterial chemoembolization (TACE) from two independent hospitals. The association between RTL and the overall survival (OS) of HCC was analyzed. The immunological function of the HCC patients with different leukocyte RTLs was evaluated. Multivariate analyses indicated that long leukocyte RTL was significantly associated with poor OS of HCC patients, with a hazard ratio of 2.04 (95% confidence interval, 1.46-2.86; P < 0.001). Kaplan-Meier analyses showed a significant difference of median survival time between patients with long and short RTL (log rank P < 0.001). Fluorescence-activated cell sorting analyses showed that the long RTL group had a significantly increased percentage of CD4(+)CD25(+)FOXP3(+) Treg in CD4(+) T cells compared with short RTL group (P = 0.002). In conclusion, our results suggest that leukocyte RTL may serve as an independent prognostic marker for HCC patients treated with TACE.

MiR-23a targets RUNX2 and suppresses ginsenoside Rg1-induced angiogenesis in endothelial cells.

Rg1 is a predominant protopanaxatriol-type of ginsenoside found in Panax ginseng, and it has been shown to have anti-cancer effects in multiple types of cancer cells. However, Rg1 also induces the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF-A), in endothelial cells. Unfortunately, angiogenesis positively correlates with cancer development. In this study, we identified RUNX2 as a regulator of ginsenoside Rg1-induced angiogenesis for the first time. We found that RUNX2 was directly targeted and regulated by miR-23a. Additionally, miR-23a was shown to inhibit angiogenesis in both human umbilical vein endothelial cells (HUVECs) and in zebrafish. Furthermore, a decrease in RUNX2 expression resulted in translational repression of VEGF-A in HUVECs. Taken together, this study identified a MiR-23a/RUNX2/VEGF-A pathway in angiogenesis and shed light on the molecular mechanism of Rg1-induced angiogenesis. Thus, RUNX2 might be a potential therapeutic target in Rg1-mediated angiogenesis in cancer.

Promoter mutations and cellular distribution of telomerase in non-clear cell and clear cell hepatocellular carcinoma.

Reactivation of telomerase is a critical step in the development of hepatocellular carcinoma (HCC). Here we identified the frequency of mutations in telomerase reverse transcriptase (TERT) promoter was 34% in non-clear cell HCC (NCCHCC, n = 259) and 26.3% in clear cell HCC (CCHCC, n = 57). The mutations were independently associated with poor recurrence-free survival of HCCs. Interestingly immunohistochemical analysis demonstrated a higher positive rate of TERT cytoplasmic localization (95%) than nuclear localization (64%) in HCCs. In NCCHCCs, the mutations correlated with higher TERT nuclear expression and increased telomere-dependent telomerase activity. Higher cytoplasmic expression was found in adjacent tissues compared to tumor tissues, and was associated with tumor well-differentiation and lower level of α-fetoprotein. NCCHCCs with low nuclear as well as high cytoplasmic expression correlated with better prognosis. In CCHCCs, elevated TERT cytoplasmic expression was observed in CCHCCs harboring mutations. Higher TERT cytoplasmic expression was found in tumor tissues compared to adjacent tissues, and was associated with multiple numbers of tumors and poor prognosis of CCHCCs. In conclusion, mutations in TERT promoter disclose the significance of both nuclear and cytoplasmic TERT in HCC. Cytoplasmic TERT should also be considered when determining prognosis and treatment of HCCs.

[A case-control study on risk factors for advanced schistosomiasis japonica].

OBJECTIVE: To investigate risk factors for the development of advanced schistosomiasis. METHODS: The case-control study was designed with a match of 1:1 and 1:2. Healthy persons and chronic schistosomiasis patients were used as control. Each group was composed of 213 cases. Items investigated included: history of schistosomiasis and treatment, exposure to the contaminated water, social-economical condition and nutritional status, other concomitant diseases. Cellular and humoral immunity, HBVMs and ABO blood groups were also detected. Statistical analysis was performed by 1:1 and 1:2 matched single and stepwise conditional logistic regression analysis with SAS software. RESULTS: By stepwise conditional logistic regression analysis, it was revealed that number of schistosomiasis examination (OR = 1.168-1.311), interval from first infection to last treatment(OR = 1.142), interval from first infection to this investigation (OR = 1.089), HBsAg+ (OR = 4.683-10.759), HBcAb+ (OR = 2.873), HBsAg+ + HBeAb+ + HBcAb+ (OR = 7.64) were risk factors of developing advanced schistosomiasis. The average living space and cellular immunity were lower in advanced schistosomiasis patients than others. No association was found between advanced schistosomiasis and ABO blood groups. CONCLUSION: The development of advanced schistosomiasis is associated with repeated infections, and delayed or incomplete treatment. Combined infection with hepatitis B, poor socio-economic conditions and impaired cellular immunity may increase the pathogenetic risk of schistosomiasis.

A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats.

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA¹:¹), or low n-3/n-6 PUFA ratio (1∶4, PUFA¹:4). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA¹:¹ diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA¹:¹ compared with SFA; however, PUFA¹:4 diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA¹:¹ diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines.

Effects of dietary fish oil on learning function and apoptosis of hippocampal pyramidal neurons in streptozotocin-diabetic rats.

Previous research has demonstrated that diabetes induces learning and memory deficits. However, the mechanism of memory impairment induced by diabetes is poorly understood. Dietary fatty acids, especially polyunsaturated fatty acids, have been shown to enhance learning and memory and prevent memory deficits in various experimental conditions. The present study investigated the effects of fish oil supplementation on the neuron apoptosis in the hippocampus of streptozotocin (STZ)-induced diabetes rats. The effects of diabetes and fish oil treatment on the spatial learning and memory were also evaluated using the Morris Water Maze. Diabetes impaired spatial learning and memory of rats. Diabetes increased the expression of Bax and caspase-3, which led the apoptosis of the CA1 pyramidal neurons, and further contributed to the deficits in learning and memory processing. Fish oil dietary supplementation in diabetic rats conducts neuron-protective function through an anti-apoptotic pathway and significantly improves the ability of learning and memory. These results partially explain the mechanism of the effect of diabetes and fish oil treatment on learning and memory, supporting a potential role for fish oil as an adjuvant therapy for the prevention and treatment of diabetic complications.

Effect of hypoxia on the proliferation of murine cornea limbal epithelial progenitor cells in vitro.

AIM: To investigate the effect of hypoxia on the proliferation of mouse corneal epithelial cells in vitro. METHODS: Mouse corneal epithelial cells(MCEs) were cultured in normoxia (210mL/L O(2) and 50mL/L CO(2)) and hypoxia (20mL/L O(2) and 50mL/L CO(2)), respectively. Colony forming efficiency (CFE) and cell proliferation were determined. The expression of corneal epithelial progenitor cell marker p63 and K19 was investigated by immunostaining. RESULTS: Normoxic colonies were smaller compared with colonies formed in hypoxia. CFE was (12.50±1.50)% in hypoxic cultures, which was similar compared with normoxia cultures [(11.13±1.86)%, P>0.05)]. Cell proliferation was enhanced in hypoxia. Progenitor markers p63 and K19 were expressed in most cells under both normoxic and hypoxic conditions. CONCLUSION: Murine limbal epithelial progenitor cells can be efficiently expanded in hypoxic conditions.

Effect of calcium on the proliferation and differentiation of murine corneal epithelial cells in vitro.

AIM: To investigate the effect of calcium on the proliferation and differentiation of murine corneal epithelial cells in vitro. METHODS: Mouse corneal epithelial cells were cultured in serum-free low-Ca(2+) medium (KSFM) and KSFM supplemented with 0.9mmol/L Ca(2+). Population doublings (PDs) were determined. The expression of corneal epithelial cell markers p63, keratin 19 (K19) and involucrin was investigated by RT-PCR analysis and semiquantitative analysis of Western blotting. RESULTS: Cells in KSFM were stably subcultured over 25 passages, however, none of the cell lines could pass P4 in KSFM with Ca(2+). In KSFM, the cells was were homogeneous and small cells with typical cobblestone appearance; and expressed p63, K19 and involucrin. After medium was supplemented with calcium, cells became a heterogeneous mix of small and large cells. Furthermore, semiquantitative analysis of Western blotting showed that the expression of involucrin was increased significantly. CONCLUSION: Calcium has the effect of inhibiting proliferation and triggering differentiation on mouse corneal epithelial cells.

Effect of microkeratome suction duration on corneal flap thickness and diameter in pigs.

AIM: To determine the effect of suction duration on thickness and diameter of corneal flap created by microkeratome in porcine eyes in laser in situ keratomileusis (LASIK). METHODS: SIXTY PORCINE EYES WERE RANDOMLY ASSIGNED TO THREE GROUPS ACCORDING TO DIFFERENT SUCTION DURATIONS: group 1 (10 seconds), group 2 (20 seconds), and group 3 (30 seconds). A Moria M2 microkeratome (Moria, France) with a 160µm head was used to create a corneal flap. Corneal flap thickness was measured by automated ultrasonic pachymetry, and the flap diameter was measured by a vernier caliper. RESULTS: The flap thickness of group 1, group 2 and group 3 was (146.05±13.46)µm, (157.35±18.95)µm and (169.25±21.02)µm, respectively. There was a statistically significant difference among three groups (P=0.001). The mean flap diameter in groups 1, 2 and 3 was(8.63±0.19)mm, (8.89±0.24)mm and (9.06±0.18)mm, respectively. A statisti-cally significant difference was found among groups (P<0.01). CONCLUSION: In LASIK in porcine eyes, an increase in suction duration resulted in a thicker and greater flap.

[Multi-factorial analysis on the flap thickness influenced by laser operation in situ keratomileusis].

OBJECTIVE: To investigate the various factors that influencing the flap thickness after laser operation in situ keratomileusis (LASIK). METHODS: 369 LASIK eyes (192 cases; among them, 15 patients for surgery monocular) with M2 130 microkeratome heads, grouped by left or right eye were analyzed by Chi-square test and logistic regression analysis based on age, sex, occupation, family history of myopia and ophthalmologic examination results before and after LASIK. The result of analysis of one-way variance which P < 0.05 as the variance to described with logistic regression analysis. RESULTS: Results from logistic regression analysis showed that the flap thickness after LASIK of right eye group was related to two factors: the preoperative refractive power (P = 0.017, OR = 0.832,95% CI: 0.715-0.968), and the corneal thickness (P = 0.000, OR = 1.023, 95% CI: 1.011-1.036) while left eye group was related to three factors: the preoperative astigmatism power (P = 0.044, OR = 2.094, 95% CI: 1.021-4.294), negative pressure suction time (P = 0.019, OR = 1.418, 95% CI: 1.059-1.898) and the corneal thickness (P = 0.000, OR = 1.049, 95% CI: 1.025-1.073). CONCLUSION: Corneal thickness, the preoperative astigmatism power and the negative pressure suction time tended to make the flap thicker while the preoperative refractive power tended to make the flap thinner. Results showed that the flap thickness performed at the first time was more obvious than at the second time.

[Investigation and management of wound on head and neck from the disaster area in Wenchuan earthquake].

OBJECTIVE: To investigate and analyze the wounded's state of ear, nose, throat, neck and head injury in Wenchuan earthquake. METHODS: The 206 wounded cases, who was treated in No. 452 Hospital of People's Liberation Army, were investigated specially with emphasis on injury cause, severity and treatment. RESULTS: The injured 165 cases among the 206 were in hospital, while the cases who related to the injury of ear, nose and throat were 37 cases (22.4%). Among the inpatients, the trauma of otorhinolaryngology and head and neck included: ear injuries totally 13 cases (including hemotympanum 2 cases), extraneous matter 4 cases, haemorrhagic 4 cases, nasalis and the fracture of nasal bone and nasal sinuses 7 cases (including cerebrospinal rhinorrhea 1 case), zygomatic abscess 1 case, fracture of mandible 4 cases, lip injuries 2 cases and hoarse 2 cases. The inpatients were wounded mostly because of falling and stepping. All the inpatients recovered well after properly management by ENT doctors. CONCLUSIONS: Maxillofacial injury of the wounded those were medical evacuation in the earthquake area, was ignored more readily comparing to the injury of other spots, so specialist should examine early and treat properly the people as soon as possible.

[Particle trajectory model desulfurization spray tower used in numerical simulation of flue gas].

The commercial computational fluid dynamics (CFD) software FLUENT is used to predict the two-phase flow in a flue gas desulfurization (FGD) spray tower. The Euler-Lagrange method is used, in which the gas flow is described with standard k-epsilon turbulence model, and the motion of the liquid droplets is described with the particle trajectory model. The procedure of model definition, including force analysis of liquid particle, gas turbulent dispersion and the gas-liquid coupling method, is presented. The results show that the uniformity of axial gas velocity in the spray tower is satisfactory, and the hollow spray nozzle used in the tower can efficiently prevent short-circuiting of the flue gas. The concentration of liquid droplets in the central region is higher than near the wall, and this problem can be solved by optimizing the arrangement of the spray nozzles near the wall. Model predictions for particle trajectory are shown to be in good agreement with experimental results, and the particle trajectory model can predict the two-phase flow in the spray tower successfully.

[Reactivity of the limestone in wet flue gas desulfurization].

On the basis of the analysis of chemical components of the natural limestones from different deposits in China, the pore structures of the typical limestones, with the different CaCO3 content, were examined. The reactivity of the limestones was investigated by sulfuric acid titration and gas-liquid absorption methods. The research results showed that the specific surface area of the natural limestones studied in this work was about 1.8 m2/g. It was seen that the pH of the limestone slurry rapidly decreased and then back up when the sulfuric acid was added. The higher the CaCO3 content was, or the smaller the particle size was, the larger the pH back-up rate was, and similarly the faster the SO2 concentration of the reactor outlet increased. The Reactivity of the limestone obtained by the sulfuric acid titration had the same features as that obtained by the gas liquid absorption. Compared with the specific surface area, the CaCO3 content had more effect on the reactivity of the limestones. The particle size of the limestones had a significant effect on the reactivity when the particle size was relatively large, that is less than 300-360 mesh, vice versa.

[Multifactor analysis of the reasons causing undercorrection after laser in situ keratomileusis].

OBJECTIVE: To investigate the relationship between various factors and the undercorrection after laser in situ keratomileusis (LASIK). METHODS: Of 1 391 eyes (696 cases), the undercorrection eyes grouped by left or right eye were analyzed by Chi-square test and logistic regression analysis based on age, sex, occupation, address, family history of myopia and all ophthalmologic examination results before and after LASIK. RESULTS: The results of logistic regression analysis showed that the undercorrection after LASIK of both groups was related to four factors: the duration of myopia (left eye OR = 1.076, 95% CI: 1.030 - 1.124; right eye OR = 1.093, 95% CI: 1.046 - 1.142), preoperative refractive power (left eye OR = 7.799, 95% CI: 1.755 - 34.654; right eye OR = 28.823, 95% CI: 5.750 - 144.467), preoperative best corrected vision (left eye OR = 0.000, 95% CI: 0.000 - 0.262; right eye OR = 0.000, 95% CI: 0.000 - 0.144) and the corneal thickness (left eye OR = 0.976, 95% CI: 0.965 - 0.987; right eye OR = 0.975, 95% CI: 0.964 - 0.986). CONCLUSION: Longer duration of myopia and the more refractive power seemed to be the risk factors, while the better corrected vision and the thicker thickness of cornea the protect factors of undercorrection after LASIK.