Infusion of Trx-1-Overexpressing hucMSC Prolongs the Survival of Acutely Irradiated NOD/SCID Mice by Decreasing Excessive Inflammatory Injury

A protective reagent for ARI should have the ability to repair injured tissue caused by radiation and prevent continuous damage from secondary risk factors. Trx-1 was explored as a candidate therapy for ARI, as it scavenges reactive oxygen species, regulates cell growth and differentiation, participates in immune reactions, and inhibits apoptosis by acting inside and/or outside cells. Trx-1 can also decrease excessive inflammation in ARI by regulating the creation of inflamed media, by inhibiting the activation of complement, and by reducing the chemotaxis, adhesion, and migration of inflammatory cells. As effectively and stably expressing exogenous genes in the long term and regulating immune inflammation and tissue repair, MSC are a good choice for Trx-1 gene therapy. In this study, Trx-1-overexpressing hucMSC-Trx-1 were obtained by adenoviral vector-mediated infection. We first measured the redox capacity of hucMSC-Trx-1 with an antioxidant capacity (T-AOC) assay, a hydrogen peroxide (H₂O₂) content determination assay in vivo, a H₂O₂-induced oxidation hemolysis assay, and a lipid peroxidation assay in vitro. Then, we measured survival time, the protection of the hematopoietic system, and the regulation of inflammation in important organs in three treatment groups of NOD/SCID mice (treated with hucMSC-Trx-1, with hucMSC, and with saline) that were exposed to 4.5 Gy ⁶⁰Co-γ-ray radiation. The hucMSC-Trx-1 group achieved superior antioxidation results, protecting bone marrow hematopoietic stem cells (Lin⁻CD117⁺: hucMSC-Trx-1 vs. hucMSC, P<0.05; hucMSC-Trx-1 vs. NS, P<0.01), promoting the formation of red blood cells and hemoglobin (hucMSC-Trx-1 vs. hucMSC or NS, P<0.05), reducing inflammation and damage in important organs (Bone marrow and lung: hucMSC-Trx-1 vs. NS, P<0.01; hucMSC-Trx-1 vs. hucMSC, P<0.05. Liver and intestine: hucMSC-Trx-1 vs. NS, P<0.05; hucMSC-Trx-1 vs. hucMSC, P<0.05), and prolonging survival (hucMSC-Trx-1 vs. hucMSC or NS, P<0.01). Therefore, hucMSC-Trx-1 combines the merits of gene and cell therapy as a multifunctional radioprotector for ARI.     

Personality and Dietary Intake – Findings in the Helsinki Birth Cohort Study

Background

Personality traits are associated with health outcomes including non-communicable diseases. This could be partly explained by lifestyle related factors including diet. The personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness are linked with resilience, meaning adaptability in challenging situations. Resilient people usually comply with favorable health behaviors.

Objective

Our objective was to explore the associations between food and nutrient intake, personality traits and resilience.

Design

A validated semi-quantitative food frequency questionnaire was used to measure diet and the NEO-personality inventory to assess personality in 1681 subjects. Linear regression analysis was used to explore diet-personality associations and cluster analysis to define resilient and non-resilient personality profiles.

Results

Adjusting for age, education and energy intake, and applying Bonferroni corrections, openness in men was associated with higher vegetable (14.9 g/d for 1 SD increase in the personality score, P_Bonf <0.01) and lower confectionery and chocolate (−2.8 g/d, P_Bonf <0.01) intakes. In women, neuroticism was associated with lower fish (−4.9 g/d, P_Bonf <0.001) and vegetable (−18.9 g/d, P_Bonf <0.01) and higher soft drink (19.9 g/d, P_Bonf <0.001) intakes. Extraversion, in women, associated with higher meat (5.9 g/d, P_Bonf <0.05) and vegetable (24.8 g/d, P_Bonf<0.001) intakes, openness with higher vegetable (23.4 g/d, P_Bonf <0.001) and fruit (29.5 g/d, P_Bonf <0.01) intakes. Agreeableness was associated with a lower soft drink (−16.2 g/d, P_Bonf <0.01) and conscientiousness with a higher fruit (32.9 g/d, P_Bonf<0.01) intake in women. Comparing resilient and non-resilient subjects, we found resilience in women to be associated with higher intakes of vegetables (52.0 g/d, P<0.001), fruits (58.3 g/d, P<0.01), fish (8.6 g/d, P<0.01) and dietary fiber (1.6 g/d, P<0.01).

Conclusion

Personality traits are associated with dietary intake and especially subjects with resilient personality profiles had healthier dietary intakes. These associations were stronger in women than in men.     

Prognostic significance of lncRNA DANCR expression in human cancers: a systematic review and meta-analysis

Several studies demonstrated that lncRNA differentiation antagonizing non-protein coding RNA (lncRNA DANCR) expression might have the potential capacity to predict the cancer prognosis; however, definite conclusion has not been obtained. The aim of this meta-analysis was to evaluate the prognostic value of lncRNA DANCR expression in cancers. PubMed, Web of Science, Scopus, and Embase were comprehensively searched for relevant studies. Studies meeting all inclusion standards were included into this meta-analysis. The analysis of overall survival (OS), disease-free survival (DFS), or clinicopathological features was conducted. Total 11 studies containing 1154 cancer patients were analyzed in this meta-analysis. The results showed, compared with low lncRNA DANCR expression, high lncRNA DANCR expression was significantly associated with shorter OS (hazard ratio [HR] = 1.85; 95% CI = 1.52–2.26; P<0.01) and DFS (HR = 1.82; 95% CI = 1.43–2.32; P<0.01) in cancers. Besides, high lncRNA DANCR expression predicted deeper tumor invasion (P<0.01), earlier lymph node metastasis (P<0.01), earlier distant metastasis (P<0.01), and more advanced clinical stage (P<0.01) compared with low lncRNA DANCR expression in cancer populations. High lncRNA DANCR expression was associated with worse prognosis compared with low lncRNA DANCR expression in cancers. LncRNA DANCR expression could serve as a prognostic factor of human cancers.     

Human Papillomavirus Infection and Vaccination: Awareness and Knowledge of HPV and Acceptability of HPV Vaccine among Mothers of Teenage Daughters in Weihai,Shandong, China

In preparation for the introduction of human papillomavirus (HPV) vaccine, we investigated awareness and knowledge of HPV/HPV vaccine and potential acceptability to HPV vaccine among mothers with a teenage daughter in Weihai, Shandong, China. A cross-sectional survey was conducted in 2013 with a sample of 1850 mothers who had a daughter (aged 9–17 years) attending primary, junior and senior high schools. In the final sample (N = 1578, response rate 85.30%), awareness of HPV was reported by 305 (19.32%) mothers. Awareness varied significantly by daughter’s age (P<0.01), mother’s education level (P<0.01), mother’s occupation (P<0.01), household income (P<0.01) and residence type (P<0.01). Knowledge about HPV/HPV vaccine was poor with a mean total score of 3.56 (SD = 2.40) out of a possible score of 13. Mothers with a higher education level reported higher levels of knowledge (P = 0.02). Slightly more than one-fourth (26.49%) of mothers expressed their potential acceptability of HPV vaccine for their daughters. Acceptability increased along with increased daughters’ age (P<0.01), household income (P<0.01) and knowledge level (P<0.01). House wives and unemployed mothers had the highest acceptability (P<0.01). The most common reasons for not accepting HPV vaccination were “My daughter is too young to have risk of cervical cancer (30.95%)”, “The vaccine has not been widely used, and the decision will be made after it is widely used (24.91%)”, “Worry about the safety of the vaccine (22.85%)”. Awareness and knowledge of HPV/HPV vaccines are poor and HPV vaccine acceptability is low among these Chinese mothers. These results may help inform appropriate health education programs in this population.     

Contribution of Baicalin on the Plasma Protein Binding Displacement and CYP3A Activity Inhibition to the Pharmacokinetic Changes of Nifedipine in Rats In Vivo and In Vitro

Baicalin purified from the root of Radix scutellariae is widely used in clinical practices. This study aimed to evaluate the effect of baicalin on the pharmacokinetics of nifedipine, a CYP3A probe substrate, in rats in vivo and in vitro. In a randomised, three-period crossover study, significant changes in the pharmacokinetics of nifedipine (2 mg/kg) were observed after treatment with a low (0.225 g/kg) or high (0.45 g/kg) dose of baicalin in rats. In the low- and high-dose groups of baicalin-treated rats, C _max of total nifedipine decreased by 40%±14% (P<0.01) and 65%±14% (P<0.01), AUC_0–∞ decreased by 41%±8% (P<0.01) and 63%±7% (P<0.01), V_d increased by 85%±43% (P<0.01) and 224%±231% (P<0.01), and CL increased by 97%±78% (P<0.01) and 242%±135% (P<0.01), respectively. Plasma protein binding experiments in vivo showed that C _max of unbound nifedipine significantly increased by 25%±19% (P<0.01) and 44%±29% (P<0.01), respectively, and there was a good correlation between the unbound nifedipine (%) and baicalin concentrations (P<0.01). Furthermore, in vitro results revealed that baicalin was a competitive displacer of nifedipine from plasma proteins. In vitro incubation experiments demonstrated that baicalin could also competitively inhibit CYP3A activity in rat liver microsomes in a concentration-dependent manner. In conclusion, the pharmacokinetic changes of nifedipine may be modulated by the inhibitory effects of baicalin on plasma protein binding and CYP3A–mediated metabolism.     

Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study

Introduction

Disease activity, severity and comorbidity contribute to increased mortality in patients with rheumatoid arthritis (RA). We evaluated the impact of age at disease onset on prognostic risk factors and treatment in patients with early disease.

Methods

In this study, 950 RA patients were followed regularly from the time of inclusion (<12 months from symptom onset) for disease activity (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender and/or swollen joints, Visual Analogue Scale pain and global scores, and Disease Activity Score in 28 joints (DAS28)) and function (Health Assessment Questionnaire (HAQ)). Disease severity, measured on the basis of radiographs of the hands and feet (erosions based on Larsen score), extraarticular disease, nodules, and comorbidities and treatment (disease-modifying antirheumatic drugs (DMARDs), corticosteroids, biologics and nonsteroidal anti-inflammatory drugs) were recorded at the time of inclusion and at 5 years. Autoantibodies (rheumatoid factor, antinuclear antibodies and antibodies against cyclic citrullinated peptides (ACPAs)) and genetic markers (human leucocyte antibody (HLA) shared epitope and protein tyrosine phosphatase nonreceptor type 22 (PTPN22)) were analysed at the time of inclusion. Data were stratified as young-onset RA (YORA) and late-onset RA (LORA), which were defined as being below or above the median age at the time of onset of RA (58 years).

Results

LORA was associated with lower frequency of ACPA (P < 0.05) and carriage of PTPN22-T variant (P < 0.01), but with greater disease activity at the time of inclusion measured on the basis of ESR (P < 0.001), CRP (P < 0.01) and accumulated disease activity (area under the curve for DAS28 score) at 6 months (P < 0.01), 12 months (P < 0.01) and 24 months (P < 0.05), as well as a higher HAQ score (P < 0.01) compared with YORA patients. At baseline and 24 months, LORA was more often associated with erosions (P < 0.01 for both) and higher Larsen scores (P < 0.001 for both). LORA was more often treated with corticosteroids (P < 0.01) and less often with methotrexate (P < 0.001) and biologics (P < 0.001). YORA was more often associated with early DMARD treatment (P < 0.001). The results of multiple regression analyses supported our findings regarding the impact of age on chosen treatment.

Conclusion

YORA patients were more frequently ACPA-positive than LORA patients. LORA was more often associated with erosions, higher Larsen scores, higher disease activity and higher HAQ scores at baseline. Nevertheless, YORA was treated earlier with DMARDs, whilst LORA was more often treated with corticosteroids and less often with DMARDs in early-stage disease. These findings could have implications for the development of comorbidities.     

Lactulose and Lactobacillus plantarum,a Potential Complementary Synbiotic To Control Postweaning Colibacillosis in Piglets

The potential of a prebiotic oligosaccharide lactulose, a probiotic strain of Lactobacillus plantarum, or their synbiotic combination to control postweaning colibacillosis in pigs was evaluated using an enterotoxigenic Escherichia coli (ETEC) K88 oral challenge. Seventy-two weanlings were fed four diets: a control diet (CTR), that diet supplemented with L. plantarum (2 × 10¹⁰ CFU · day⁻¹) (LPN), that diet supplemented with 10 g · kg⁻¹ lactulose (LAC), or a combination of the two treatments (SYN). After 7 days, the pigs were orally challenged. Six pigs per treatment were euthanized on days 6 and 10 postchallenge (PC). Inclusion of lactulose improved the average daily gain (ADG) (P < 0.05) and increased lactobacilli (P < 0.05) and the percentage of butyric acid (P < 0.02) in the colon. An increase in the ileum villous height (P < 0.05) and a reduction of the pig major acute-phase protein (Pig-MAP) in serum (P < 0.01) were observed also. The inclusion of the probiotic increased numbers of L. plantarum bacteria in the ileum and colon (P < 0.05) and in the total lactobacilli in the colon and showed a trend to reduce diarrhea (P = 0.09). The concentrations of ammonia in ileal and colonic digesta were decreased (P < 0.05), and the villous height (P < 0.01) and number of ileal goblet cells (P < 0.05) increased, at day 10 PC. A decrease in plasmatic tumor necrosis factor alpha (TNF-α) (P < 0.01) was also seen. The positive effects of the two additives were combined in the SYN treatment, resulting in a complementary synbiotic with potential to be used to control postweaning colibacillosis.     

Prooxidant/Antioxidant Balance in Hypoxia: A Cross-Over Study on Normobaric vs. Hypobaric “Live High-Train Low”

“Live High-Train Low” (LHTL) training can alter oxidative status of athletes. This study compared prooxidant/antioxidant balance responses following two LHTL protocols of the same duration and at the same living altitude of 2250 m in either normobaric (NH) or hypobaric (HH) hypoxia. Twenty-four well-trained triathletes underwent the following two 18-day LHTL protocols in a cross-over and randomized manner: Living altitude (P_IO₂ = 111.9 ± 0.6 vs. 111.6 ± 0.6 mmHg in NH and HH, respectively); training “natural” altitude (~1000–1100 m) and training loads were precisely matched between both LHTL protocols. Plasma levels of oxidative stress [advanced oxidation protein products (AOPP) and nitrotyrosine] and antioxidant markers [ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD) and catalase], NO metabolism end-products (NOx) and uric acid (UA) were determined before (Pre) and after (Post) the LHTL. Cumulative hypoxic exposure was lower during the NH (229 ± 6 hrs.) compared to the HH (310 ± 4 hrs.; P<0.01) protocol. Following the LHTL, the concentration of AOPP decreased (-27%; P<0.01) and nitrotyrosine increased (+67%; P<0.05) in HH only. FRAP was decreased (-27%; P<0.05) after the NH while was SOD and UA were only increased following the HH (SOD: +54%; P<0.01 and UA: +15%; P<0.01). Catalase activity was increased in the NH only (+20%; P<0.05). These data suggest that 18-days of LHTL performed in either NH or HH differentially affect oxidative status of athletes. Higher oxidative stress levels following the HH LHTL might be explained by the higher overall hypoxic dose and different physiological responses between the NH and HH.     

Maternal Hypoxia Decreases Capillary Supply and Increases Metabolic Inefficiency Leading to Divergence in Myocardial Oxygen Supply and Demand

Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO₂=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. ¹⁴C-labelled glucose and ³H-palmitate were provided as substrates and metabolism quantified from recovery of ¹⁴CO₂ and ³H₂O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve local PO₂, minimising regions of hypoxia and hence maximising the area of myocardium able to preserve cardiac output following maternal hypoxia.     

Increased Circulating Cathepsin K in Patients with Chronic Heart Failure

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the “lowLVEF” group) and the 90 patients showing LVEF values ≥ 40% (the “highLVEF” group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = −0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84–0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.     

Suppression of TGF-β1/Smad Signaling Pathway by Sesamin Contributes to the Attenuation of Myocardial Fibrosis in Spontaneously Hypertensive Rats

This study investigated the effect of sesamin on myocardial fibrosis in spontaneously hypertensive rats (SHRs) and the possible mechanisms involved. Twenty-eight male SHRs were randomly allocated to SHR group, Ses160 group (sesamin 160 mg/kg), Ses80 group (sesamin 80 mg/kg) and Cap30 group (captopril 30 mg/kg). Seven male WKY rats were used as control. Sesamin and captopril were administered intragastrically for 12 weeks. Captopril significantly reduced systolic blood pressure and angiotensin II (Ang II) levels in SHRs, accompanied by a marked attenuation of left ventricular hypertrophy (LVH) and collagen deposition (P <0.05 or P <0.01). Though sesamin had no significant influence on Ang II levels, and the hypotensive effect was also significantly inferior to that of captopril (P <0.05 or P <0.01), however, the improvement of LVH and collagen deposition was similar to that in captopril group. Sesamin markedly reduced transforming growth factor-β₁ (TGF-β₁) content in cardiac tissues, with Smad3 phosphorylation decreased and Smad7 protein expression increased notably (P <0.05 or P <0.01). Protein expression of type I collagen and type III collagen, target genes of Smad3, was down-regulated markedly by sesamin (P <0.05 or P <0.01). In addition, sesamin significantly increased total antioxidant capacity and superoxide dismutase protein in cardiac tissues (P <0.05 or P <0.01), while the expression of NADPH oxidase subunit p47phox and malondialdehyde content were reduced markedly (P <0.05 or P <0.01). In vitro studies also demonstrated that sesamin was able to suppress Ang II induced phosphorylation of Smad3 and secretion of TGF-β₁ and type I and type III collagen in cultured rat cardiac fibroblasts. These data suggest that sesamin is capable of attenuating hypertensive myocardial fibrosis through, at least partly, suppression of TGF-β₁/Smad signaling pathway.     

The natural organosulfur compound dipropyltetrasulfide prevents HOCl-induced systemic sclerosis in the mouse

Introduction

The aim of this study was to test the naturally occurring organosulfur compound dipropyltetrasulfide (DPTTS), found in plants, which has antibiotic and anticancer properties, as a treatment for HOCl-induced systemic sclerosis in the mouse.

Methods

The prooxidative, antiproliferative, and cytotoxic effects of DPTTS were evaluated ex vivo on fibroblasts from normal and HOCl mice. In vivo, the antifibrotic and immunomodulating properties of DPTTS were evaluated in the skin and lungs of HOCl mice.

Results

H₂O₂ production was higher in fibroblasts derived from HOCl mice than in normal fibroblasts (P < 0.05). DPTTS did not increase H₂O₂ production in normal fibroblasts, but DPTTS dose-dependently increased H₂O₂ production in HOCl fibroblasts (P < 0.001 with 40 μM DPTTS). Because H₂O₂ reached a lethal threshold in cells from HOCl mice, the antiproliferative, cytotoxic, and proapoptotic effects of DPTTS were significantly higher in HOCl fibroblasts than for normal fibroblasts. In vivo, DPTTS decreased dermal thickness (P < 0.001), collagen content in skin (P < 0.01) and lungs (P < 0.05), αSMA (P < 0.01) and pSMAD2/3 (P < 0.01) expression in skin, formation of advanced oxidation protein products and anti-DNA topoisomerase-1 antibodies in serum (P < 0.05) versus untreated HOCl mice. Moreover, in HOCl mice, DPTTS reduced splenic B-cell counts (P < 0.01), the proliferative rates of B-splenocytes stimulated by lipopolysaccharide (P < 0.05), and T-splenocytes stimulated by anti-CD3/CD28 mAb (P < 0.001). Ex vivo, it also reduced the production of IL-4 and IL-13 by activated T cells (P < 0.05 in both cases).

Conclusions

The natural organosulfur compound DPTTS prevents skin and lung fibrosis in the mouse through the selective killing of diseased fibroblasts and its immunomodulating properties. DPTTS may be a potential treatment for systemic sclerosis.     

High Incidence of Preharvest Colonization of Huanglongbing-Symptomatic Citrus sinensis Fruit by Lasiodiplodia theobromae (Diplodia natalensis) and Exacerbation of Postharvest Fruit Decay by That Fungus

Huanglongbing (HLB), presumably caused by the bacterium “Candidatus Liberibacter asiaticus,” is a devastating citrus disease associated with excessive preharvest fruit drop. Lasiodiplodia theobromae (diplodia) is the causal organism of citrus stem end rot (SER). The pathogen infects citrus fruit under the calyx abscission zone (AZ-C) and is associated with cell wall hydrolytic enzymes similar to plant enzymes involved in abscission. By means of DNA sequencing, diplodia was found in “Ca. Liberibacter asiaticus”-positive juice from HLB-symptomatic fruit (S) but not in “Ca. Liberibacter asiaticus”-negative juice. Therefore, the incidence of diplodia in fruit tissues, the impact on HLB-related postharvest decay, and the implications for HLB-related preharvest fruit drop were investigated in Hamlin and Valencia oranges. Quantitative PCR results (qPCR) revealed a significantly (P < 0.001) greater incidence of diplodia in the AZ-C of HLB-symptomatic (S; “Ca. Liberibacter asiaticus” threshold cycle [C_T] of <30) than in the AZ-C of in asymptomatic (AS; “Ca. Liberibacter asiaticus” C_T of ≥30) fruit. In agreement with the qPCR results, 2 weeks after exposure to ethylene, the incidences of SER in S fruit were 66.7% (Hamlin) and 58.7% (Valencia), whereas for AS fruit the decay rates were 6.7% (Hamlin) and 5.3% (Valencia). Diplodia colonization of S fruit AZ-C was observed by scanning electron microscopy and confirmed by PCR test and morphology of conidia in isolates from the AZ-C after surface sterilization. Diplodia C_T values were negatively correlated with ethylene production (R = −0.838 for Hamlin; R = −0.858 for Valencia) in S fruit, and positively correlated with fruit detachment force (R = 0.855 for Hamlin; R = 0.850 for Valencia), suggesting that diplodia colonization in AZ-C may exacerbate HLB-associated preharvest fruit drop.     

Worst case scenario match analysis and contextual variables in professional soccer players: a longitudinal study

This study aimed to describe the worst-case scenarios (WCS) of professional soccer players by playing position in different durations and analyse WCS considering different contextual variables (match half, match location and match outcome). A longitudinal study was conducted in a professional soccer team. Data were collected from different WCS durations in the total distance (TD), high-speed running distance (HSRD), and sprinting distance (SPD). A mixed analysis of variance was performed to compare different WCS durations between playing positions and contextual variables, making pairwise comparisons by Bonferroni post hoc test. Positional differences were found for TD (p < 0.01, ω_p² = 0.02), HSRD (p < 0.01, ω_p² = 0.01) and SPD (p < 0.01, ω_p² = 0.02). There was a significant interaction when comparing WCS by match half in TD (F = 6.1, p < 0.01, ω_p² = 0.07) but no significant differences in HSRD (p = 0.403, ω_p² = 0) or SPD (p = 0.376, ω_p² = 0). A significant interaction was identified when comparing WCS by match location in TD (F = 51.5, p < 0.01, ω_p² = 0.14), HSRD (F = 19.15, p < 0.01, ω_p² = 0.05) and SPD (F = 8.95, p < 0.01, ω_p² = 0.01) as well as WCS by match outcome in TD (F = 36.4, p < 0.01, ω_p² = 0.08), HSRD (F = 13.6, p < 0.01, ω_p² = 0.04) and SPD (F = 7.4, p < 0.01, ω_p² = 0.02). Positional differences exist in TD, HSRD, and SPD in match-play WCS, and contextual variables such as match half, match location and match outcome have a significant impact on the WCS of professional soccer players.     

High atherogenic index of plasma and cardiovascular risk factors among Ghanaian breast cancer patients

Comorbidities impact negatively on breast cancer prognosis, especially in developing countries where cases are usually presented to clinics at advanced stages. This study aimed to determine the atherogenic index of plasma (AIP) and cardiovascular risk factors among Ghanaian women diagnosed with breast cancer. A total of 52 breast cancer patients were age-matched with 52 healthy controls. Sociodemographics of participants were obtained using a well-structured questionnaire. Pathological data of patients were obtained from medical records, and all clinical and anthropometric measurements were done using standard instruments. Lipid profile was determined from serum using enzymatic assays, and cardiovascular risk factors were calculated from estimated lipid parameters. Blood pressure, AIP, total cholesterol (T. chol), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) were significantly elevated (P < 0.05) in the breast cancer patients compared to the controls, but the reverse was observed for high-density lipoprotein cholesterol (HDL-c) (P < 0.01). Obesity (odds ratio [OR] = 2.51, P = 0.015), hypertension (OR = 4.04, P < 0.001), AIP (OR = 10.44, P < 0.001), and dyslipidemia (P < 0.01) were significantly associated with breast cancer. AIP correlated positively with age (r = 0.244, P < 0.05), body mass index (r = 0.225, P < 0.05), blood pressure (P < 0.01), T. chol (r =0.418, P< 0.01), and TG (r = 0.880, P < 0.01), but inversely correlated with HDL-c (r = −0.460, P < 0.01). A greater proportion (88%) of the patients presented with advanced breast cancer. AIP and cardiovascular risk factors were high in the breast cancer patients. Considering that AIP and cardiovascular disease risk factors are of interest in breast cancer patients, further studies are needed to understand the effect of AIP and cardiovascular risk factors on breast cancer outcomes.     

HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies

Background

HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive.

Methodology/Principal Findings

A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association.HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96; P _{heterogeneity} = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6; P _{heterogeneity} < 0.01), dominant model (1772C/T: TT/CT vs. CC: OR = 1.27, 95% CI: 1.04, 1.55; P _{heterogeneity} < 0.01, 1790G/A: AA/GA vs. GG: OR = 1.65, 95% CI: 1.05, 2.60; P _{heterogeneity} < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70; P _{heterogeneity} < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96; P _{heterogeneity} < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism.

Conclusions

HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk.     

The Effect of ShenQi FuZheng Injection in Combination with Chemotherapy versus Chemotherapy Alone on the Improvement of Efficacy and Immune Function in Patients with Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To evaluate the effect of ShenQi FuZheng Injection (SFI) on cellular immunity and clinical efficacy in patients with advanced non small cell lung cancer(NSCLC) when combined with chemotherapy.

Methods

Electronic databases including EMBASE, PUBMED, the conference proceedings of the American Society of Clinical Oncology (ASCO), Cochrane, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biological Medical disc(CBM) were searched, until July, 2015. The randomized controlled clinical studies reporting results of efficacy and immune function were collected according to the inclusion criteria. Cochrane handbook 5.1.0 was applied to assess the quality of included trials and Revman 5 software was used for data analysis.

Results

Fifteen studies including 1006 cases of advanced NSCLC were included based on the inclusion criteria. The results of meta-analysis showed that there were significant differences in percentages of CD₃⁺ cells (SMD = 13.48; 95%CI: 8.11–18.85; p<0.01), CD₄⁺ cells (SMD = 10.78; 95%CI, 6.38–15.18; p<0.01), NK [WMD = 8.59, 95% CI(3.97, 13.21), p = 0.003], and ratio of CD₄⁺/ CD₈⁺ (SMD = 0.32; 95%: 0.28–0.36; p<0.01) between SFI combination group and control group, whereas the difference was not significant in CD₈⁺ (SMD = -1.44; 95%CI, -4.53–1.65; p = 0.36). Funnel plot, Begg''s rank correlation test and Egger''s linear regression analysis indicated that there was significant publication bias across studies.

Conclusion

SFI is effective to improve the efficacy of chemotherpay and function of cellular immunity in NSCLC patients, however, high quality RCTs are needed to further confirm the findings.     

Pectin- Derived Acidic Oligosaccharides Improve the Outcome of Pseudomonas aeruginosa Lung Infection in C57BL/6 Mice

The administration of prebiotics as oligosaccharides (OS), by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS) could modulate the outcome of pulmonary P. aeruginosa (PA) infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P<0.05). This improvement correlated with a better control of the inflammatory response with a lower neutrophil count on day 1 (P<0.05), a sustained neutrophil and macrophage recruitment on days 2 and 3 (P<0.01) a greater and sustained IL-10 release in lung (P<0.05) and a reduction of the Th1 response and M1 activation with a lower IFN-γ/IL-4 (P<0.01) and nos2/arg1 (P<0.05) ratios. These results coincided with a modulation of the intestinal microbiota as shown by an increased butyric acid concentration in feces (P<0.05). Moreover, pAOS decreased the bacterial load (P<0.01) in mice reinfected 2 weeks after the first infection, suggesting that pAOS could reduce pulmonary exacerbations. In conclusion, pAOS improved the outcome of PA infection in C57BL/6 mice by modulating the intestinal microbiota and the inflammatory and immune responses.     

Predictors of Acute Respiratory Distress Syndrome in Patients with Paraquat Intoxication

Introduction

Paraquat poisoning is characterized by acute lung injury, pulmonary fibrosis, respiratory failure, and multi-organ failure, resulting in a high rate of mortality and morbidity. The objectives of this study were to identify predictors of acute respiratory distress syndrome (ARDS) in cases of paraquat poisoning and determine the association between these parameters.

Materials and Methods

In total, 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and Acute Kidney Injury Network (AKIN) scores were collected, and predictors of ARDS were analyzed.

Results

The overall mortality rate for the entire population was 54% (101/187). Furthermore, the mortality rate was higher in the ARDS patients than in the non-ARDS patients (80% vs. 43.80%, P<0.001). Additionally, the ARDS patients not only had higher AKIN_48-h scores (P<0.009), SOFA_48-h scores (P<0.001), and time to ARDS/nadir PaO₂ (P=0.008) but also suffered from lower nadir PaO₂ (P<0.001), nadir AaDO₂ (P<0.001), and nadir eGFR (P=0.001) compared to those in the non-ARDS patients. Moreover, pneumomediastinum episodes were more frequent in the ARDS patients than in the non-ARDS patients (P<0.001). A multivariate Cox regression model revealed that blood paraquat concentrations (P<0.001), SOFA_48-h scores (P=0.001), and steroid and cyclophosphamide pulse therapies (P=0.024) were significant predictors of ARDS. The cumulative survival rates differed significantly (P<0.001) between patients with SOFA_48-h scores <3 and SOFA_48-h scores ≥3, with a sensitivity of 95.8%, specificity of 58.4%, and overall correctness of 67.6%. Finally, the area under the receiver operating characteristic (AUROC) analysis showed that SOFA_48-h scores (P<0.001) had a better discriminatory power than blood paraquat concentrations (P=0.01) for predicting ARDS.

Conclusions

The analytical results indicate that SOFA_48-h scores, blood paraquat concentrations, and steroid and cyclophosphamide pulse therapies are significantly associated with ARDS complications after paraquat intoxication.