Acute pancreatitis presented with diffuse ST-segment elevation: A case report and literature review.

INTRODUCTION: Although electrocardiographic changes have been previously reported in patients with acute pancreatitis, diffuse ST-segment elevation without occluded coronary arteries is rarely documented. PATIENT CONCERNS: A 45-year-old man presented to our emergency department due to persistent epigastric pain for 2 hours. However, ECG in the emergency department revealed regular sinus rhythm at 67 beats per minute, peaked T waves in lead V3-5, and upsloping ST-segment elevation in leads II, III, aVF, and V2-6. DIAGNOSIS: He was diagnosed with acute pancreatitis and presented with diffuse ST-segment elevation. INTERVENTIONS: Laboratory workup and computed tomography supported the diagnosis of acute gallstone pancreatitis and endoscopic retrograde cholangiopancreatography was performed. Coronary angiography showed patent coronary arteries finally. OUTCOMES: Endoscopic retrograde cholangiopancreatography and endoscopic papillo-sphincterotomy were performed, and the stone in the common bile duct was removed smoothly without immediate complication. Due to his relatively stable condition, he was discharged on day 7 of admission. CONCLUSION: We presented an uncommon case of acute pancreatitis demonstrating similar features of AMI. This reminds cardiologists and emergency physicians to make the judgment with more caution to avoid jumping to conclusions and providing inappropriate treatment.

Both epicardial and peri-aortic adipose tissue blunt heart rate recovery beyond body fat mass.

Background: Epicardial adipose tissue (EAT) as a marker of metabolic disorders has been shown to be closely associated with a variety of unfavorable cardiovascular events and cardiac arrhythmias. Data on regional-specific visceral adiposity outside the heart and its modulation on autonomic dysfunction, particularly heart rate recovery after exercise, remain obscure. Methods: We studied 156 consecutive subjects (mean age: 49.3 ± 8.0 years) who underwent annual health surveys and completed treadmill tests. Multi-detector computed tomography-based visceral adiposity, including EAT and peri-aortic fat (PAF) tissue, was quantified using dedicated software (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We further correlated EAT and PAF with blood pressure and heart rate (HR) recovery information from an exercise treadmill test. Metabolic abnormalities were scored by anthropometrics in combination with biochemical data. Results: Increased EAT and PAF were both associated with a smaller reduction in systolic blood pressure during the hyperventilation stage before exercise compared to supine status (ß-coefficient (coef.): -0.19 and -0.23, respectively, both p < 0.05). Both visceral adipose tissue mediated an inverted relationship with heart rate recovery at 3 (EAT: ß-coef.: -0.3; PAF: ß-coef.: -0.36) and 6 min (EAT: ß-coef.: -0.32; PAF: ß-coef.: -0.34) after peak exercise, even after adjusting for baseline clinical variables and body fat composition (all p < 0.05). Conclusion: Excessive visceral adiposity, whether proximal or distal to the heart, may modulate the autonomic response by lowering the rate of HR recovery from exercise after accounting for clinical metabolic index. Cardiac autonomic dysfunction may partly explain the increase in cardiovascular morbidity and mortality related to both visceral fats.

Comodulation of NO-Dependent Vasodilation by Erythroid Band 3 and Hemoglobin: A GP.Mur Athlete Study.

GP.Mur, a red blood cell (RBC) hybrid protein encoded by glycophorin B-A-B, increases expression of erythroid band 3 (Anion Exchanger-1, SLC4A1). GP.Mur is extremely rare but has a prevalence of 1-10% in regions of Southeast Asia. We unexpectedly found slightly higher blood pressure (BP) among healthy Taiwanese adults with GP.Mur. Since band 3 has been suggested to interact with hemoglobin (Hb) to modulate nitric oxide (NO)-dependent hypoxic vasodilation during the respiratory cycle, we hypothesized that GP.Mur red cells could exert differentiable effects on vascular tone. Here we recruited GP.Mur-positive and GP.Mur-negative elite male college athletes, as well as age-matched, GP.Mur-negative non-athletes, for NO-dependent flow-mediated dilation (FMD) and NO-independent dilation (NID). The subjects were also tested for plasma nitrite and nitrate before and after arterial occlusion in FMD. GP.Mur+ and non-GP.Mur athletes exhibited similar heart rates and blood pressure, but GP.Mur+ athletes showed significantly lower FMD (4.8 ± 2.4%) than non-GP.Mur athletes (6.5 ± 2.1%). NO-independent vasodilation was not affected by GP.Mur. As Hb controls intravascular NO bioavailability, we examined the effect of Hb on limiting FMD and found it to be significantly stronger in GP.Mur+ subjects. Biochemically, plasma nitrite levels were directly proportional to individual band 3 expression on the red cell membrane. The increase of plasma nitrite triggered by arterial occlusion also showed small dependency on band 3 levels in non-GP.Mur subjects. By the GP.Mur comparative study, we unveiled comodulation of NO-dependent vasodilation by band 3 and Hb, and verified the long-pending role of erythroid band 3 in this process.

Variant Aldehyde Dehydrogenase 2 (ALDH2*2) as a Risk Factor for Mechanical LA Substrate Formation and Atrial Fibrillation with Modest Alcohol Consumption in Ethnic Asians.

Aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism is a common genetic variant in Asians that is responsible for defective toxic aldehyde and lipid peroxidation metabolism after alcohol consumption. The extent to which low alcohol consumption may cause atrial substrates to trigger atrial fibrillation (AF) development in users with ALDH2 variants remains to be determined. We prospectively enrolled 249 ethnic Asians, including 56 non-drinkers and 193 habitual drinkers (135 (70%) as ALDH2 wild-type: GG, rs671; 58 (30%) as ALDH2 variants: G/A or A/A, rs671). Novel left atrial (LA) mechanical substrates with dynamic characteristics were assessed using a speckle-tracking algorithm and correlated to daily alcohol consumption and ALDH2 genotypes. Despite modest and comparable alcohol consumption by the habitual alcohol users (14.3 [8.3~28.6] and 12.3 [6.3~30.7] g/day for those without and with ALDH2 polymorphism, p = 0.31), there was a substantial and graded increase in the 4-HNE adduct and prolonged PR, and a reduction in novel LA mechanical parameters (including peak atrial longitudinal strain (PALS) and phasic strain rates (reservoir, conduit, and booster pump functions), p < 0.05), rather than an LA emptying fraction (LAEF) or LA volume index across non-drinkers, and in habitual drinkers without and with ALDH2 polymorphism (all p < 0.05). The presence of ALDH2 polymorphism worsened the association between increasing daily alcohol dose and LAEF, PALS, and phasic reservoir and booster functions (all Pinteraction: <0.05). Binge drinking superimposed on regular alcohol use exclusively further worsened LA booster pump function compared to regular drinking without binge use (1.66 ± 0.57 vs. 1.97 ± 0.56 1/s, p = 0.001). Impaired LA booster function further independently helped to predict AF after consideration of the CHARGE-AF score (adjusted 1.68 (95% CI: 1.06-2.67), p = 0.028, per 1 z-score increment). Habitual modest alcohol consumption led to mechanical LA substrate formation in an ethnic Asian population, which was more pronounced in subjects harboring ALDH2 variants. Impaired LA booster functions may serve as a useful predictor of AF in such populations.

Visceral adiposity index outperforms conventional anthropometric assessments as predictor of diabetes mellitus in elderly Chinese: a population-based study.

BACKGROUND: This study assessed the performance of visceral adiposity index and body shape index in predicting diabetes mellitus (DM) risk and compared their predictive ability to that of body mass index and waist circumference. METHODS: Among 8249 consecutive subjects who attended the Nationwide Health Check Up System for Senior Citizens (≥ 65 years) between 2008 and 2018, we examined the associations of several adiposity indices with DM risk and explored gender differences. RESULTS: Among all adiposity indicators, Chinese visceral adiposity index (CVAI) demonstrated the highest discriminatory ability for diabetes mellitus with area under receiver operating characteristic curves (AUC) of 0.65, 0.68, and 0.66 for men, women, and all participants, respectively, and optimal cut-offs set as 126.09 in men and 117.77 in women. Compared with body shape index (ABSI), both CVAI and VAI were strongly associated with baseline DM (adjusted OR: 4.85, 95% CI: 4.05-5.82 and 4.22, 95% CI: 3.53-5.05 for 4th vs 1st quartile groups by CVAI and VAI, P < 0.001), which was more pronounced in older adult women (Pinteraction < 0.05). Over a median of 5.25 years (IQR: 3.07-6.44 years) follow-up, Cox regression models showed higher predictive ability of CVAI and VAI compared to ABSI. Further, both CVAI and VAI independently predicted new-onset DM (adjusted HR: 1.29, 95% CI: 1.22-1.37 and 1.16, 95% CI: 1.11-1.21 by CVAI and VAI) and composite endpoint of new DM and death among those without baseline DM. CONCLUSIONS: Our population-based data demonstrated that Chinese visceral adiposity index may serve as a superior clinical indicator of diabetes when compared with conventional anthropometric indices among older adult Chinese, especially in women.

Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model.

Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression. Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated. Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group. Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.

Epicardial Adiposity in Relation to Metabolic Abnormality, Circulating Adipocyte FABP, and Preserved Ejection Fraction Heart Failure.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Anti-inflammatory effects of Radix Aucklandiae herbal preparation ameliorate intestinal mucositis induced by 5-fluorouracil in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: 5-Fluorouracil (5-FU) is a chemotherapy agent that is widely used in clinical oncologic practice. However, intestinal mucositis is the most frequently occurring side effect of cancer therapy with 5-FU. Based on a literature survey, Radix Aucklandiae herbal preparation potentially ameliorates intestinal mucositis in 5-FU-treated mice. AIM OF THE STUDY: The aim of this study was to investigate the inflammation and gastrointestinal regulation of intestinal mucositis induced by 5-FU, including the intestinal morphology, as well as the reduction in food intake, body weight loss, and diarrhea. MATERIALS AND METHODS: Intestinal mucositis was induced in mice by 5-FU (30 mg/kg, i.p., for 5 consecutive days). The dose-dependent Radix Aucklandiae herbal preparation (0.3, 1, and 3 g/kg/day, p.o.), loperamide (3 mg/kg/day, p.o.) or celecoxib (40 mg/kg/day, p.o.) was concurrently administered until the 7th day. Physical status observation, diarrhea assessment, serum proinflammatory cytokine levels, intestinal villus height and crypt depth, and total goblet cells from tissues were assessed. RESULTS: The dosage regimen of 5-FU administration caused severe intestinal mucositis in mice, including damage to the intestinal morphology, accompanied by a reduction in food intake, body weight loss, and diarrhea. The high-dose Radix Aucklandiae herbal preparation significantly relieves 5-FU-induced intestinal mucositis by enhancing proliferative activity in epithelial crypts; improving anepithymia, body weight loss, and diarrhea; and displaying protective effects on goblet cells in intestinal mucosal epithelia. Activation of NF-κB in the intestinal mucositis model was also suppressed by the Radix Aucklandiae herbal preparation, suggesting that it is a potent inhibitor of NF-κB and proinflammatory cytokines, such as IL-1ß, IL-6, TNF-α, and COX-2. CONCLUSIONS: Our data support the conclusion that the Radix Aucklandiae herbal preparation could effectively ameliorate 5-FU-induced gastrointestinal toxicity and be applied clinically for the prevention of intestinal mucositis during chemotherapy.

Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer.

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

Visceral Adiposity, Pro-Inflammatory Signaling and Vasculopathy in Metabolically Unhealthy Non-Obesity Phenotype.

The debate regarding the actual cardiovascular burden in metabolically healthy obese or metabolically unhealthy non-obesity individuals is ongoing. Accumulating data have suggested a unique pathophysiological role of pro-inflammatory cytokines in mediating metabolic and cardiovascular disorders by dysregulated visceral adiposity. To compare the burden of visceral adiposity, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the prevalent atherosclerotic burden in metabolically healthy obese (MHO) or metabolically unhealthy (MU) populations, were compared to those of metabolically healthy non-obesity subjects (MHNO). Coronary artery calcification score (CACS) and visceral fat, including pericardial fat (PCF)/thoracic peri-aortic fat (TAT), were quantified in 2846 asymptomatic subjects using a CT dataset. A cross-sectional analysis comparing CACS, inflammatory marker hs-CRP, and visceral fat burden among four obesity phenotypes (MHNO, metabolically unhealthy non-obesity (MUNO), MHO, and metabolically unhealthy obese (MUO)) was performed. Both MUNO and MUO demonstrated significantly higher hs-CRP and greater CACS than MHNO/MHO (adjusted coefficient: 25.46, 95% confidence interval (CI): 5.29-45.63; 43.55, 95% CI: 23.38-63.73 for MUNO and MUO (MHNO as reference); both p < 0.05). Visceral fat (PCF/TAT) was an independent determinant of MU and was similarly higher in the MUNO/MHO groups than in the MHNO group, with the MUO group having the largest amount. PCF/TAT, obesity, and MU remained significantly associated with higher CACS even after adjustment, with larger PCF/TAT modified effects for MU and diabetes in CACS (both pinteraction < 0.05). MU tightly linked to excessive visceral adiposity was a strong and independent risk factor for coronary atherosclerosis even in lean individuals, which could be partially explained by its coalignment with pathological pro-inflammatory signaling.

Malnutrition in acute heart failure with preserved ejection fraction: clinical correlates and prognostic implications.

AIMS: This study aimed to evaluate the prognostic significance of nutritional status in post-discharge Asians with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We examined the prognostic implications of body mass index (BMI) and nutritional markers among consecutive patients hospitalized for HFpEF. Nutritional metrics were estimated by serum albumin (SA), prognostic nutritional index (PNI), Controlling Nutritional Status (CONUT) score, and geriatric nutritional risk index. Among 1120 patients (mean age: 77.2 ± 12.6 years, 39.4% men), mean SA levels, PNI, CONUT scores, and geriatric nutritional risk index were 3.3 ± 0.6 g/dL, 40.2 ± 8.7, 5.5 ± 2.1, and 95.9 ± 14.5, respectively. Lean body size, higher white blood cell counts and C-reactive protein levels, anaemia, and lack of angiotensin blocker use were independently associated with malnutrition (defined by SA < 3.5 g/dL). Higher SA levels [hazard ratio (HR): 0.67 (95% confidence interval, CI: 0.53-0.85)], higher PNI [HR: 0.97 (95% CI: 0.95-0.99)], and higher geriatric nutritional risk index [HR: 0.98 (95% CI: 0.97-0.99)] (all P < 0.05) were all associated with longer survival, with higher CONUT score [HR: 1.08 (95% CI: 1.02-1.13)] exhibited higher mortality in Cox regression models and with higher SA levels/PNI but not BMI further contributing to the reduced rate of re-hospitalization (both P < 0.05). Categorizing BMI (25 kg/m2 as cut-off) and nutritional status showed significantly higher mortality rates among patients with lower BMI/malnutrition than among those with BMI/better nutrition (SA level, PNI, and CONUT score, all P < 0.01). Restricted cubic spline regression revealed a marked survival benefit of better nutrition with increasing BMI (adjusted Pinteraction for both SA level and PNI: <0.001; adjusted Pinteraction for CONUT score: 0.046). CONCLUSIONS: Malnutrition was frequently and strongly associated with systemic inflammation in Asian patients hospitalized for acute HFpEF. Our findings also indicate that nutrition may play a pivotal role in metabolic protection in this population.

Correction: Thoracic aortic calcification across the clinical dysglycemic continuum in a large Asian population free of cardiovascular symptoms.

[This corrects the article DOI: 10.1371/journal.pone.0207089.].

Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Inflammation contributes to cancer development and inflammatory bowel disease is an important risk factor for CRC. The aim of this study is to assess whether a widely used probiotic Enterococcus faecalis can modulate the NLRP3 inflammasome and protect against colitis and colitis-associated CRC. We studied the effect of heat-killed cells of E. faecalis on NLRP3 inflammasome activation in THP-1-derived macrophages. Pretreatment of E. faecalis or NLRP3 siRNA can inhibit NLRP3 inflammasome activation in macrophages in response to fecal content or commensal microbes, P. mirabilis or E. coli, according to the reduction of caspase-1 activation and IL-1ß maturation. Mechanistically, E. faecalis attenuates the phagocytosis that is required for the full activation of the NLRP3 inflammasome. In in vivo mouse experiments, E. faecalis can ameliorate the severity of intestinal inflammation and thereby protect mice from dextran sodium sulfate (DSS)-induced colitis and the formation of CRC in wild type mice. On the other hand, E. faecalis cannot prevent DSS-induced colitis in NLRP3 knockout mice. Our findings indicate that application of the inactivated probiotic, E. faecalis, may be a useful and safe strategy for attenuation of NLRP3-mediated colitis and inflammation-associated colon carcinogenesis.

High percentage atypical hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs.

Nucleos(t)ide analogs are used for preventing liver cirrhosis in chronic hepatitis B patients, but the risk factors of hepatocellular carcinoma (HCC) in these patients remain unclear. We designed this retrospective cohort study, the aim is to determine the risk factors for HCC development and its image presentation under nucleos(t)ide analogs treatment.In this study, patients were treated with lamivudine (LAM), entecavir 0.5 mg (ETV), or telbivudine (LdT), and followed-up for at least 2 years to detect HCC and its presentation. Assessment of the risk factors for HCC included age, sex, HBeAg, viral load, liver cirrhosis, current and previous medications, and liver function tests.Totally, 396 patients were recruited, and 18 patients developed HCC. The mean time from the treatment to HCC development was 28.5 ±â€Š16.7 months. The clinical characteristics in HCC and no-HCC groups showed significant differences among age (52.8 ±â€Š6.1 vs 47.1 ±â€Š12.6 years, P <.01), baseline alanine transaminase (ALT) levels (161.4 ±â€Š177.3 vs 361.7 ±â€Š496.3, P <.01), and baseline liver cirrhosis (72.2% vs 29.9%, P <.01). In patients aged ≥45 years, the hazard ratio of HCC was 10.2 and liver cirrhosis was 4.1. Majority of HCCs developed in the right liver (14/18), were single numbered (13/18), had tumor size about 1.9 ±â€Š0.7 cm, were classified as T1 (14/18, TNM staging), and the atypical image occupied 88% of the HCC cases.The patients aged ≧45 years on long-term nucleos(t)ide analog therapy, and with baseline liver cirrhosis were at a high risk of HCC. Regular alpha-fetoprotein (AFP) assessment and image study of these patients are the gold standards for early HCC detection in patients with high percentage atypical HCC appearances.

Thoracic aortic calcification across the clinical dysglycemic continuum in a large Asian population free of cardiovascular symptoms.

Thoracic aortic calcification (TAC) is tightly linked to pathological atherosclerosis and associated with certain cardiovascular diseases. While diabetes mellitus (DM) is known as a coronary heart disease equivalent, we examined the presence of TAC across the dysglycemic spectrum of diabetes mellitus (DM). We consecutively studied 3003 asymptomatic ethnic Asians underwent annual cardiovacular health survey, and further categorized them into: 1) 1760 normo-glycemic, 2) 968 pre-diabetic, and 3) 274 overt DM based on dysglycemic indices and medical histories. Several TAC parameters were assessed using non-contrast multi-detector computed tomography (MDCT), and related to dysglycemic indices or diabetes mellitus status. A remarkably graded increases of adjusted total TAC calcium burden, volume and density were seen across Non-diabetes, Pre-diabetes, and diabetes mellitus categories and positively correlated with all dysglycemic profiles (all p<0.001). Multi-variate logistic and linear regression models demonstrated independent associations between greater TAC density and all dysglycemic indices (Coef: 2.5, 1.4, 6.8 for fasting, postprandial sugar and HbA1c) and diabetes mellitus status (all p<0.05). Furthermore, Receiver-operating characteristic curves (ROC) showed fasting sugar and postprandial sugar set at 103mg/dL and 111mg/dL, separately, with HbA1c set at 5.8% all predict the presence of aortic calcification. Dysglycemic status, even without overt diabetes mellitus, were tighly linked to subclinical, pathological thoracic aortic calcification.

Lactobacillus casei Variety rhamnosus Probiotic Preventively Attenuates 5-Fluorouracil/Oxaliplatin-Induced Intestinal Injury in a Syngeneic Colorectal Cancer Model.

Adjuvant 5-fluorouracil (5-FU)-based chemotherapy, including FOLFOX (5-FU, leucovorin, and oxaliplatin), is recommended for colorectal cancer. However, intestinal mucositis remains a common adverse effect for which no effective preventive strategies are available. To develop a convenient and novel way to alleviate mucositis, we investigated the effect of Lactobacillus casei variety rhamnosus (Lcr35) on FOLFOX-induced mucosal injury. BALB/c mice subcutaneously injected with syngeneic CT26 colorectal adenocarcinoma cells were orally administered Lcr35 daily before, during, and after 5-day injection of FOLFOX regimen, for 14 days. The following methods were used: diarrhea score for toxicity, ELISA for cytokine production, histopathology for intestinal injury, immunohistochemistry for apoptosis/proliferation and regulatory proteins, RT-PCR for cytokine mRNA expression, and DNA sequencing for fecal gut microbiota. FOLFOX administration to colorectal cancer-bearing mice significantly inhibited tumor growth and the accompanying marked diarrhea and intestinal injury histologically characterized by the shortening of villi and destruction of intestinal crypts. Preventive administration of Lcr35 dose-dependently reduced the severity of diarrhea and intestinal mucositis without affecting the anti-tumor effect of FOLFOX. The numbers of apoptotic, NF-κB-, and BAX-activated cells increased after FOLFOX, and these responses were mitigated by Lcr35. TNF-α and IL-6 upregulation by FOLFOX treatment was attenuated by Lcr35. The fecal gut microbiota composition of Firmicutes and Bacteroidetes disturbed by FOLFOX was significantly reversed by Lcr35 toward a preferential profile. In conclusion, the oral probiotic Lcr35 prevented FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism might involve modulation of gut microbiota and proinflammatory responses with suppression of intrinsic apoptosis in intestinal injury.

Cardiac Structural Remodeling, Longitudinal Systolic Strain, and Torsional Mechanics in Lean and Nonlean Dysglycemic Chinese Adults.

BACKGROUND: Diabetes mellitus and pre-diabetes mellitus are associated with lower body mass indices and increased risk of cardiovascular events (including heart failure) at lower glucose thresholds in Chinese compared with Western cohorts. However, the extent of cardiac remodeling and regulation on cardiac mechanics in lean and nonlean dysglycemic Chinese adults is understudied. METHODS AND RESULTS: We studied 3950 asymptomatic Chinese (aged 49.7±10.7 years; 65% male; body mass index: 24.3±3.5 kg/m2) with comprehensive echocardiography including speckle tracking for left ventricular global longitudinal strain/torsion, with plasma sugar, glycosylated hemoglobin (HbA1c), and insulin resistance (homeostasis model assessment of insulin resistance) obtained. Participants were classified as (1) nondiabetic (fasting glucose <100 mg/mL; HbA1c <5.7%; n=1416), prediabetic (fasting glucose 100-126 mg/dL; HbA1c 5.7%-6.4%; n=2029), or diabetic (n=505) and (2) lean (body mass index <23 kg/m2; n=1445) or nonlean (n=2505). Higher sugar, HbA1c, and homeostasis model assessment of insulin resistance were independently associated with higher left ventricular mass, greater mass-to-volume ratio, more impaired diastolic indices, and worse global longitudinal strain even after adjusting for clinical covariates (adjusted coefficient value: 0.28/0.12 for global longitudinal strain per 1 U HbA1c/homeostasis model assessment of insulin resistance increment; both P<0.001), with a consistent trend toward greater torsion (all trend P<0.001). The optimal cutoffs in identifying subclinical systolic dysfunction (global longitudinal strain more impaired than -18%) for lean versus nonlean individuals were 97 versus 106 mg/dL for fasting sugar, 130 versus 135 mg/mL for postprandial sugar, 5.62% versus 6.28% for HbA1c, and 1.81 versus 2.40 for homeostasis model assessment of insulin resistance, respectively. CONCLUSIONS: These data demonstrate the presence of preclinical cardiac remodeling and systolic dysfunction in prediabetic and diabetic Chinese adults, occurring at lower thresholds of glycemic indices than defined by international standards, particularly in lean individuals.

Gut microbiome changes in overweight male adults following bowel preparation.

BACKGROUND: Human gut microbiome has an essential role in human health and disease. Although the major dominant microbiota within individuals have been reported, the change of gut microbiome caused by external factors, such as antibiotic use and bowel cleansing, remains unclear. We conducted this study to investigate the change of gut microbiome in overweight male adults after bowel preparation, where none of the participants had been diagnosed with any systemic diseases. METHODS: A total of 20 overweight, male Taiwanese adults were recruited, and all participants were omnivorous. The participants provided fecal samples and blood samples at three time points: prior to bowel preparation, 7 days after colonoscopy, and 28 days after colonoscopy. The microbiota composition in fecal samples was analyzed using 16S ribosome RNA gene amplicon sequencing. RESULTS: Our results demonstrated that the relative abundance of the most dominant bacteria hardly changed from prior to bowel preparation to 28 days after colonoscopy. Using the ratio of Prevotella to the sum of Prevotella and Bacteroides in the fecal samples at baseline, the participants were separated into two groups. The fecal samples of the Type 1 group was Bacteroides-dominant, and that of the Type 2 group was Prevotella-dominant with a noticeable presence Bacteroides. Bulleidia appears more in the Type 1 fecal samples, while Akkermensia appears more in the Type 2 fecal samples. Of each type, the gut microbial diversity differed slightly among the three collection times. Additionally, the Type 2 fecal microbiota was temporarily susceptible to bowel cleansing. Predictive functional analysis of microbial community reveals that their activities for the mineral absorption metabolism and arachidonic acid metabolism differed significantly between the two types. Depending on their fecal type, the variance of triglycerides and C-reactive protein also differed between the two types of participants. CONCLUSIONS: Depending upon the fecal type, the microbial diversity and the predictive functional modules of microbial community differed significantly after bowel preparation. In addition, blood biochemical markers presented somewhat associated with fecal type. Therefore, our results might provide some insights as to how knowledge of the microbial community could be used to promote health through personalized clinical treatment.

Membrane Proteomics of Impaired Energetics and Cytoskeletal Disorganization in Elderly Diet-Induced Diabetic Mice.

Diabetic cardiomyopathy is a well-recognized complication of diabetes, but its pathophysiology is unclear. We aimed to investigate the mechanisms underlying cardiac dysfunction in an elderly type 2 diabetic (T2DM) mouse model, using membrane proteomic analyses. Elderly mice were fed a high fat diet for 12 weeks to induce T2DM, and myocardial structure and function were assessed by echocardiography. Cardiomyocytes were isolated by Langendorff perfusion and subjected to iTRAQ-based quantitative membrane proteomic profiling, immunoblotting, and real-time quantitative reverse-transcriptase polymerase chain reaction. Compared to controls, elderly T2DM mice showed worse systolic function, more myocardial fibrosis and up-regulation of several heart failure markers (all p < 0.05). Cardiomyocyte membrane proteomic profiling revealed that 417 proteins had differential expressions related to perturbations in several biological processes in T2DM mice compared with the control. The most up-regulated proteins were involved in oxidative phosphorylation, whereas many down-regulated proteins were involved in cytoskeletal regulation. Differential protein expression correlated with myocardial systolic velocity by tissue Doppler. In addition, cardiomyocyte immunofluorescence staining showed greater disorganization of thick/parallel F-actin stress fibers and marked reduction in F-to-G-actin ratio in T2DM vs control (p < 0.05), which paralleled worsened myocardial systolic velocity. We concluded that cardiac contractile dysfunction in elderly T2DM mice was associated with impaired energetics and cytoskeletal disorganization.