Using probiotics for type 2 diabetes mellitus intervention: Advances, questions, and potential.

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent diseases on earth and several treatments have been developed. However, the current intervention approaches have not been as effective as expected. One promising supplementary strategy is the use of probiotics through direct or indirect approaches. Probiotics are microbial food cultures conferring health-promoting properties. In this review, we summarized the current theories and mechanisms of T2DM intervention using probiotics and hypothesize that probiotics intervene T2DM during its onsetting, developing, and complicating. For the first time, we comprehensively analyzed T2DM intervention in animal models using both wide-type probiotics in different forms and using recombinant probiotics. Then, probiotic intervention in T2DM patients was reviewed and the main results were compared with that obtained from animal studies. Finally yet importantly, remaining questions that are important such as in which form and in which state, as well as the future potential of probiotic intervention in T2DM were discussed from a perspective of food microbiologists. In conclusion, probiotic intervention in T2DM is promising but there are still many important issues unsolved yet. Critical review of the advances, questions, and potential of probiotic intervention in T2DM promotes the development of this approach for further application in humans.

Associations of C-reactive protein and fibrinogen with mortality from all-causes, cardiovascular disease and cancer among U.S. adults.

C-reactive protein (CRP) and fibrinogen are associated with an increased risk of death with suggested differences by gender, diet quality and race/ethnicity. However, the current evidence is limited. We used data including 8646 men and 9880 women from the National Health and Nutrition Examination Survey (NHANES) Linked Morality cohort (1999-2011) to investigate the associations of CRP and fibrinogen with mortality overall and by gender, race/ethnicity and diet quality. Cox-proportional hazard model was used to quantify the associations. With a median follow-up of 6 years, a strong dose-response relationship was observed between CRP levels and mortality risk in men after multivariable adjustment. For subjects who survived the first two years, the adjusted hazard ratios (HRs) for total mortality across quartiles (from lower to higher) of CRP were 1.97 (95% CI: 0.62-6.33), 1.89 (0.59, 6.06) and 6.34 (2.28-17.7) (P for trend <0.001). For cardiovascular disease (CVD) mortality, its association with CRP varied by diet quality. For cancer mortality, its association differed by history of cancer, and positive associations were observed only among subjects with history of cancer. In contrast, no such association of CRP with mortality was found in women. For fibrinogen, we observed its positive association with total mortality and the HRs across quartiles of fibrinogen (from lower to higher) were 1.21 (0.88, 1.67), 1.49 (1.22, 1.82) and 1.99 (1.56, 2.55). The association with CVD mortality differed by diet quality whereas no association was found with cancer mortality. Our findings suggest that higher levels of CRP and fibrinogen were associated with lower survival from total and CVD; the associations of CRP with mortality were more pronounced in men than women. Diet quality is an effect modifier for the association of CRP and fibrinogen with CVD mortality.

Epigenetic regulation of integrin ß6 transcription induced by TGF-ß1 in human oral squamous cell carcinoma cells.

Overexpression of integrin αvß6 is believed to play an important role in the invasion and metastasis of oral squamous cell carcinoma (OSCC). However, little is known about the molecular mechanisms leading to αvß6 upregulation in OSCC. As the integrin ß6 (ITGB6) is the only partner with αv, the expression of αvß6 is dependent on ITGB6, it is, therefore, pivotal to investigate the mechanisms underlying ITGB6 overexpression in OSCC. We previously reported the cloning and characterization of human ITGB6 gene. In the current study, we further investigated the molecular mechanisms of ITGB6 expression and the upregulation by carcinogenesis related cytokine-transforming growth factor-ß1 (TGF-ß1) in OSCC cells. We first demonstrated that TGF-ß1 can induce ITGB6 mRNA and protein express in a time and concentration dependent manner, and the induced-ITGB6 mRNA was not due to increase the mRNA stability, but regulated at transcriptional level. By using a luciferase reporter assay, site-mutation, RNA interference, and chromatin immunoprecipitation assay, we revealed for the first time that JunB, a member of the activator protein-1 (AP-1) family, is involved in the positive regulation to the ITGB6 transcription induced by TGF-ß1 in OSCC cells. Furthermore, our data also demonstrated that histone acetyltransferase (HAT) CBP mediated histone H3 and H4 hyperacetylation, and RNA Polymerase II recruitment to ITGB6 promoter, facilitated the binding of transcription factor JunB to ITGB6 promoter after TGF-ß1 stimulation. Collectively, these findings demonstrate that JunB and CBP-mediated histone hyperacetylation are responsible for TGF-ß1 induced ITGB6 transcription in OSCC cells, suggesting that epigenetic mechanisms are responsible for the active transcription expression of ITGB6 induced by TGF-ß1 in OSCC cells.

Outcomes of Trachelectomy vs. Hysterectomy for Early-Stage Cervical Cancer: A Systematic Review and Meta-Analysis.

Objective: To provide updated evidence on comparative efficacy for clinical outcomes of radical trachelectomy and radical hysterectomy in patients with early-stage cervical cancer. Methods: A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews, and Google scholar databases. Studies were done in patients with early-stage cervical cancer that compared the outcomes between radical trachelectomy (RT) and hysterectomy (RH) were considered for inclusion in the review. The outcomes of interest were operative time, the volume of blood loss, need for blood transfusion, any complications, length of hospital stay, risk of recurrence, and survival. The strength of association was presented in the form of pooled relative risk (RR), hazards risk (HR), and weighted mean difference (WMD). Statistical analysis was done using STATA version 16.0. Results: A total of 12 articles were included in the meta-analysis. The majority were retrospective cohort-based studies. Compared to RH, the operative time (in min) was comparatively higher in RT (WMD 23.43, 95% CI: 5.63, 41.24). Patients undergoing RT had blood loss (in ml) similar to those undergoing RT (WMD -81.34, 95% CI: -170.36, 7.68). There were no significant differences in the risk of intra-operative (RR 1.61, 95% CI: 0.49, 5.28) and post-operative complications (RR 1.13, 95% CI: 0.54, 2.40) between the two groups. Patients in the RT group had lesser duration of post-operative hospital stay (in days) (WMD -1.65, 95% CI: -3.22, -0.09). There was no statistically significant difference in the risk of recurrence (HR 1.21, 95% CI: 0.68, 2.18), 5-year overall survival (HR 1.00, 95% CI: 0.99, 1.02), and recurrence-free survival (HR 0.99, 95% CI: 0.96, 1.01) between the two groups. Conclusion: Among the patients with early-stage cervical cancer, RT is similar to RH in safety and clinical outcomes. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.

Analysis of magnetic resonance imaging features of ovarian thecoma.

To investigate the magnetic resonance imaging (MRI) findings in ovarian thecoma and improve preoperative diagnostic accuracy.Retrospective analysis was performed on 45 patients with surgically and pathologically confirmed ovarian thecoma. Patients were grouped into those with maximum lesion diameter ≥5 cm and <5 cm. Diagnostic scores (up to 6 points) were evaluated on the basis of MRI performance.The ≥5 cm group contained 36 cases (cystic necrosis, 32 cases) with the following findings: T1WI: isointense signal, 22 cases; slightly hypointense signal, 14 cases; T2WI: isointense signal, 6 cases; slightly hypointense signal, 21 cases; slightly hyperintense signal, 9 cases; Diffusion-weighted imaging (DWI): hyperintense signal, 23 cases; mixed hyperintense signal, 13 cases; slight enhancement on dynamic enhanced scans; pelvic fluid accumulation, 31 cases. The diagnostic score evaluations yielded 6 points in 31 cases, 5 points in 1 case, 4 points in 2 cases, and 3 points in 2 cases. The <5 cm group contained 9 cases (cystic necrosis, 3 cases) with the following findings: T1WI: isointense signal, 3 cases; slightly hypointense signal, 6 cases; T2WI: isointense signal, 2 cases; slightly hypointense signal, 4 cases; slightly hyperintense signal, 3 cases; DWI, hyperintense signal; slight enhancement in 8 cases and significant enhancement in 1 case; pelvic fluid accumulation, 4 cases. The diagnostic score evaluations yielded 6 points in 3 cases, 5 points in 1 case, 4 points in 4 cases, and 3 points in 1 case. (iii) Incidence of pelvic fluid accumulation and cystic necrosis differed depending on the size of the lesion (P = .007, .000).Larger lesions show hyperintense or mixed hyperintense signals on DWI along with pelvic fluid and cystic necrosis; whereas, smaller lesions show a hyperintense signal on DWI, cystic necrosis is rare. MRI characteristics along with the patient age and laboratory findings can improve the accuracy of preoperative diagnosis of these lesions.

Seasonality in the adverse outcomes in weight loss surgeries.

BACKGROUND: Weight loss surgery is a common procedure in the United States. OBJECTIVE: As weight loss surgery is largely an elective procedure for which patients and physicians can choose the timing, it could be helpful to explore the seasonality pattern of its perioperative adverse outcomes to help decide the timing of this surgery. SETTING: United States. METHODS: We used an obese adult sample (age ≥20 yr) of patients who underwent weight loss surgeries from the Premier Healthcare Database from 2011 to 2014. The International Classification of Diseases, Ninth Revision Clinical Modification procedure codes were used to identify weight loss surgery cases. Binary variables are used for 4 adverse outcomes, including hospital mortality, sepsis, deep vein thrombosis (DVT), and pulmonary embolism. The associations between the adverse outcomes and season of surgery were examined using logistic regressions, adjusting for age, sex, race, marital status, surgery types, body mass index, the Charlson co-morbidity index, and region. RESULTS: A total of 69,365 weight loss surgeries were identified for the analytic sample. The overall rate was .27% for hospital mortality, .16% for DVT, .10% for pulmonary embolism, and .20% for sepsis. For DVT, adjusted odds ratio for the fall was 2.68 (95% confidence interval: 1.39-5.19) and the odds ratio for the winter was 2.26 (95% confidence interval: 1.09-4.27) compared with the summer. For sepsis, adjusted odds ratio for the spring was 1.83 (95% confidence interval: 1.07-3.12) compared with that of the summer. The seasonality pattern was not statistically significant for hospital mortality and pulmonary embolism. CONCLUSION: DVT and sepsis are more likely to occur in colder seasons compared with the summer season, although the crude rates of these adverse events were low.

Changes in utilization and peri-operative outcomes of bariatric surgery in large U.S. hospital database, 2011-2014.

BACKGROUND: With the epidemic of morbid obesity, bariatric surgery has been accepted as one of the most effective treatments of obesity. OBJECTIVE: To investigate recent changes in the utilization of bariatric surgery, patients and hospital characteristics, and in-hospital complications in a nationwide hospital database in the United States. SETTING: This is a secondary data analysis of the Premier Perspective database. METHODS: ICD-9 codes were used to identify bariatric surgeries performed between 2011 and 2014. Descriptive statistics were computed and regression was used. RESULTS: A total of 74,774 bariatric procedures were identified from 436 hospitals between 2011 and 2014. During this time period, the proportion of gastric bypass (from 44.8% to 31.3%; P for trend < 0.0001) and gastric banding (from 22.8% to 5.2%; P for trend < 0.0001) decreased, while the proportion of sleeve gastrectomy (from 13.7% to 56.9%; P for trend < 0.0001) increased substantially. The proportion of bariatric surgery performed for outpatients decreased from 17.15% in 2011 to 8.11% in 2014 (P for trend < 0.0001). The majority of patients undergoing surgery were female (78.5%), white (65.6%), younger than 65 years (93.8%), and insured with managed care (53.6%). In-hospital mortality rate and length of hospital stay remained stable. The majority of surgeries were performed in high-volume (71.8%) and urban (91.6%) hospitals. CONCLUSIONS: Results based on our study sample indicated that the popularity of various bariatric surgery procedures changed significantly from 2011 to 2014. While the rates of in-hospital complications were stable, disparities in the use of bariatric surgery regarding gender, race, and insurance still exist.

A proper triage for detecting women with high-risk human papillomavirus genotypes other than HPV16/18.

OBJECTIVE: To evaluate the effect of human papillomavirus (HPV) L1 capsid protein detection in cervical exfoliated cells as a proper triage for women with high-risk human papillomavirus (hrHPV) genotypes other than HPV 16/18. STUDY DESIGN: From January 2013 to June 2015, a total of 513 women aged 30-65 years infected with non-16/18 hrHPV were enrolled into the study. Primary HPV testing, HPV 16/18 genotyping and Papanicolaou (Pap) test were performed in all eligible women. HPV L1 capsid protein was detected by immunocytochemistry in cervical exfoliated cells. All hrHPV positive women underwent colposcopy and further biopsy if indicated. Relationships between HPV L1 capsid protein expression and histologic diagnosis, as well as cytology were analyzed. RESULTS: The positive expression rate of HPV L1 capsid protein in CIN2+ group was significantly lower than that in CIN1 or better group (16.3% vs. 66.7%, P=0.000). Compared with the Pap test, HPV L1 detection achieved higher sensitivity (83.7% vs. 51.2%, P=0.000), higher negative predictive value (NPV) (95.3% vs. 88.6%, P=0.002), and significant lower specificity (66.7% vs.76.1%, P=0.002) while identifying CIN2+. Compared with the Pap test, HPV L1 detection achieved higher sensitivity (89.7% vs. 51.7%, P=0.008), higher NPV (99.0% vs. 96.2%, P=0.043), and significant lower specificity (61.2% vs.73.8%, P=0.000) while identifying CIN3+. CONCLUSION: Because of its higher sensitivity and NPV than that of Pap test, HPV L1 capsid protein detection in cervical exfoliated cells reduces the missed identification of high-grade cervical intraepithelial neoplasia (CIN) in women with hrHPV genotypes other than HPV 16/18. HPV L1 capsid protein detection could be a potential triage for women with non-16/18 hrHPV infection.

Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its mechanism of action.

The aim was to investigate the suppressive effect of bicyclol on hepatic fibrosis induced by dimethylnitrosamine (DMN) in mice and the mechanism of its action. Hepatic fibrosis was established by intraperitoneal injection of 8 mg kg(-1) day(-1) on three consecutive days of each week for 4 or 5 weeks. In the prophylactic experiment, bicyclol (100 and 200mg.kg(-1)) was administered by gavage in association with DMN injection. For the therapeutic experiment, mice were firstly injected with DMN for 5 weeks as in the prophylactic experiment, and then the mice in drug groups were orally administered bicyclol (100 and 200mg.kg(-1)) once daily for 5 weeks. As a result, the levels of alanine aminotransferase (ALT), total bilirubin, hydroxyproline (Hyp), prolidase, tumor necrosis factor-alpha (TNFalpha), transforming growth factor beta-1 (TGFbeta(1)), type I collagen in serum and the score of liver fibrosis all significantly increased in the hepatic fibrosis model group in comparison with those in control group. The treatment with bicyclol markedly reduced all the above criteria. Bicyclol also attenuated the decrease of body weight of mice, serum total protein and albumin. In addition, bicyclol treatment inhibited liver TGFbeta(1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) mRNA expression in the prophylactic experiment. Similarly, bicyclol reduced TIMP-1 levels in liver and serum and increased collagenase activity in the liver in the therapeutic experiment. The result suggest that bicyclol attenuates DMN-induced hepatic fibrosis in mice. Its mechanisms of action may be related to the hepatoprotective and anti-inflammation properties, the down-regulation of liver TGFbeta(1) and TIMP-1 expression and the increase of net collagenase activity in liver.

Gender differences in the association between food insecurity and insulin resistance among U.S. adults: National Health and Nutrition Examination Survey, 2005-2010.

PURPOSE: To examine gender-specific associations between food insecurity and insulin resistance in a representative U.S. METHODS: Data on 5533 adults of 20 years of age or more (2742 men and 2791 women) without diabetes from the 2005-2010 National Health and Nutrition Examination Survey were analyzed. Respondents were categorized as having full, marginal, low, or very low food security using a validated scale. Insulin-resistant individuals were defined as those with a homeostasis model assessment of insulin resistance value 2.5 or more. RESULTS: Insulin resistance was higher in both normal-weight (P = .001) and overweight or obese (P < .001) women with lower food security, but no linear trend was found in men. In multiple logistic regression analyses, however, very low food security-compared with full food security-was associated with insulin resistance in normal-weight men (odds ratio, 3.99; 95% confidence interval, 1.71-9.33), and marginal food insecurity was associated with insulin resistance in overweight or obese men (odds ratio, 2.07; 95% confidence interval, 1.18-3.64) after adjusting for potential confounders. In women, the association between food insecurity and insulin resistance was no longer significant after adjustment. CONCLUSIONS: Food insecurity is associated with insulin resistance in adults without diabetes, and this effect varies by gender in normal-weight and overweight or obese populations. Improving food security status may help reduce insulin resistance, an underlying risk factor for diabetes and cardiovascular disease.