This study investigated the associations between relative telomere length (RTL) and resting metabolic rate (RMR), resting fat oxidation (RFO), and aerobic capacity and whether oxidative stress and ...inflammation are the underlying mechanisms in sedentary women. We also aimed to determine whether the correlations depend on age and obesity. Sixty-eight normal weight and 66 obese women participated in this study. After adjustment for age, energy expenditure, energy intake, and education level, the RTL of all participants was negatively correlated with absolute RMR (RMRAB) and serum high-sensitivity C-reactive protein (hsCRP) concentration, and positively correlated with maximum oxygen consumption (V˙O2max) (all p < 0.05). After additional adjustment for adiposity indices and fat-free mass (FFM), RTL was positively correlated with plasma vitamin C concentration (p < 0.05). Furthermore, after adjustment for fasting blood glucose concentration, RTL was negatively correlated with age and positively correlated with V˙O2max (mL/kg FFM/min). We found that normal weight women had longer RTL than obese women (p < 0.001). We suggest that RTL is negatively correlated with RMRAB and positively correlated with aerobic capacity, possibly via antioxidant and anti-inflammatory mechanisms. Furthermore, age and obesity influenced the associations. We provide useful information for the management of promotion strategies for health-related physical fitness in women.
Opisthorchis viverrini
infection is endemic in the lower Mekong subregion. The liver is an organ that worms are drawn to and cause damage. However, the immune-related susceptibility in the liver is ...poorly understood. In this study, we investigated T helper (Th) cell responses in the liver of BALB/c mice and golden Syrian hamsters during 2–28 days post-infection (DPI). We found that Th cell responses were distinct between mice and hamsters in terms of dynamics and polarization. Mice exhibited the early induction of Th1, Th2, Th17, and regulatory T (Treg) cells responses after the presence of
O. viverrini
worms at 2 DPI. In hamsters, the late induction of Th1/Th17, downregulation of Th2/Treg responses and early elevation of suppressive cytokine interleukin (IL)-10 were found together with swift reduction of Th cell numbers. Interestingly, expressions of IL-4 (Th2 functional cytokine) and Foxp3 (Treg lineage) were completely different between mice and hamsters which elevated in mice but suppressed in hamsters. These results suggest that early induction and well-regulation are related to host resistance. In contrast, late induction of Th cell response might allow immature worms to develop in the host. Our findings provide a greater understanding in Th cell response-related susceptibility in
O. viverrini
infection which would be targeting immunity for the development of immune-based intervention such as vaccine.
Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The interaction between KIRs and their cognate ligands (Human ...leukocyte antigen class I molecules, HLA class I) modulates the immune response of NK cells, in particular through clearance of virus-infected cells. Here, we investigated the effect of
KIRs
and
HLA
ligands on dengue infections and disease severity. The
KIRs
and
HLA
ligands were identified in 235 healthy controls (HC) and 253 dengue patients (DEN) using polymerase chain reaction with sequence specific primer (PCR–SSP); moreover, DEN was classified to 100 dengue fever (DF) and 153 dengue haemorrhagic fever (DHF). Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed
P
value of < 0.05. The Bonferroni correction was applied for multiple comparisons. Twelve significant associations were observed in dengue infections and disease severity; however, two outcomes survived after the Bonferroni correction. Of these,
HLA
-
A11
was associated with an increased risk to develop dengue disease (OR 2.41, 95% CI 1.62–3.60,
P
c
= 0.004), while
KIR3DS1
+
Bw4
was a protective genotype to developing DHF (OR 0.28, 95% CI 0.16–0.48,
P
c
< 0.001). This study revealed an important role of
KIR
and
HLA
ligands in innate immune responses to dengue viral infections and, in particular, their effect on clinical outcomes and disease severity.
This study aimed to assess the effect of Vitamin C on blood pressure (BP), and subsequently on oxidative stress and nitric oxide (NO) release, following the low-intensity exercise in the patients. ...This study included 24 patients with type 2 diabetes mellitus (T2D) (age, 53 ± 7 years; hemoglobin A1c, 10.1% ± 0.9%) randomized into two 6-week daily arms based on the consumption of either placebo or 1000 mg Vitamin C. The crossover trial occurred after a 6-week washout. Before and after both supplementation arms, all patients performed cycling exercise at 33% of peak oxygen consumption for 20 min. BP was measured before, immediately, and 60 min after the exercise. Blood samples were drawn immediately before and after the exercise to determine plasma ascorbate, malondialdehyde (MDA), F
-isoprostanes (F
-IsoPs), and NO concentrations. Data showed significant lower BP in the Vitamin C arm when compared with the placebo arm (systolic BP SBP P < 0.001 at every time point, diastolic BP DBP P < 0.001 except at immediately after exercise, P < 0.05). Plasma ascorbate concentration (P < 0.05 at every time point) and plasma NO (at resting P < 0.001, immediately after exercise P < 0.05) were significantly increased in the Vitamin C arm than in the placebo arm. Plasma MDA (P < 0.05 at every time point) and F
-IsoPs (P < 0.05 at every time point) concentrations were significantly lower in the Vitamin C arm than in the placebo arm. In addition, data showed significantly lower SBP (P < 0.001 at every time point), DBP (P < 0.001 except at immediately after exercise P < 0.05), plasma MDA (P < 0.001 at every time point), and F
-IsoPs (P < 0.05 at every time point) at post-supplementation than at pre-supplementation. Besides, there were significantly higher plasma ascorbate (P < 0.05 at every time point) and NO (at rest P < 0.01, immediately after exercise P < 0.05) concentrations at post-supplementation than at pre-supplementation. This is in contrast to the placebo treatment arm which demonstrated no statistical difference in all outcomes throughout the experiment. This study suggests that 6-week Vitamin C supplementation decreased preexercise and postexercise BPs, possibly due to improved oxidative stress and NO release. However, exercise had no effect on any outcome measures.
Genetic involvement of Killer Immunoglobulin-like Receptor (KIR) polymorphisms and Human Immunodeficiency Virus (HIV)-exposed seronegative (HESN) compared to HIV-infected (HIVI) individuals has been ...reported. However, inconsistency of the outcomes reduces precision of the estimates. A meta-analysis was applied to obtain more precise estimates of association.
A multi-database literature search yielded thirteen case-control studies. Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P-value of ≤ 0.05. We used two levels of analyses: (1) gene content that included 13 KIR polymorphisms (2DL1-3, 2DL5A, 2DL5B, 2DS1-3, 2DS4F, 2DS4D, 2DS5, 3DL1 and 3DS1); and (2) 3DL1/S1 genotypes. Subgroup analysis was ethnicity-based (Caucasians, Asians and Africans). Outlier treatment was applied to heterogeneous effects which dichotomized the outcomes into pre-outlier (PRO) and post-outlier (PSO). Multiple comparisons were addressed with the Bonferroni correction.
We generated 52 and 18 comparisons from gene content and genotype analyses, respectively. Of the 70 comparisons, 13 yielded significant outcomes, two (indicating reduced risk) of which survived the Bonferroni correction (Pc). These protective effects pointed to the Caucasian subgroup in 2DL3 (OR 0.19, 95% CI 0.09, 0.40, Pc < 10-3) and 3DS1S1 (OR 0.37, 95% CI 0.24, 0.56, Pc < 10-3). These two PSO outcomes yielded effects of increased magnitude and precision, as well as raised significance and deemed robust by sensitivity analysis. Of the two, the 2DL3 effect was improved with a test of interaction (Pc interaction < 10-4).
Multiple meta-analytical treatments presented strong evidence of the protective effect (up to 81%) of the KIR polymorphisms (2DL3 and 3DS1S1) among Caucasians. The Asian and African outcomes were inconclusive due to the low number of studies.
In this study, a key issue to be addressed is the safe disposal of hybridoma instability. Hybridoma technology was used to produce anti-O. viverrini monoclonal antibody. Previous studies have shown ...that antibody production via antibody phage display can sustain the hybridoma technique. This paper presents the utility of antibody phage display technology for producing the phage displayed KKU505 Fab fragment and using experiments in concomitant with molecular simulation for characterization. The phage displayed KKU505 Fab fragment and characterization were successfully carried out. The KKU505 hybridoma cell line producing anti-O. viverrini antibody predicted to bind to myosin was used to synthesize cDNA so as to amplify the heavy chain and the light chain sequences. The KKU505 displayed phage was constructed and characterized by a molecular modeling in which the KKU505 Fab fragment and -O. viverrini myosin head were docked computationally and it is assumed that the Fab fragment was specific to -O. viverrini on the basis of mass spectrometry and Western blot. This complex interaction was confirmed by molecular simulation. Furthermore, the KKU505 displayed phage was validated using indirect enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry. It is worthy to note that ELISA and immunohistochemistry results confirmed that the Fab fragment was specific to the -O. viverrini antigen. Results indicated that the approach presented herein can generate anti-O. viverrini antibody via the phage display technology. This study integrates the use of phage display technology together with molecular simulation for further development of monoclonal antibody production. Furthermore, the presented work has profound implications for antibody production, particularly by solving the problem of hybridoma stability issues.
Killer-cell immunoglobulin-like receptor (KIR) 3DL3 is a framework gene present in all human KIR haplotypes. Although the structure of KIR3DL3 is suggestive of an inhibitory receptor, the function of ...KIR3DL3 has not been demonstrated and cognate ligands have not been identified. KIR3DL3 has been shown to be constitutively expressed at a low RNA level in peripheral blood mononuclear cell (PBMC) and decidual natural kill (NK) cells, but cell surface expression of KIR3DL3 cannot be detected. Accordingly, post-transcriptional regulation of KIR3DL3 should exist. Using bioinformatics analysis, we identified three candidate micro ribonucleic acids (miRNAs; miR-26a-5p, -26b-5p and -185-5p) that potentially regulate KIR3DL3 expression. Luciferase reporter assays utilizing constructs with mutated miRNA-binding sites of miR-26a-5p, -26b-5p and -185-5p in the 3'-untranslated region (3' UTR) of KIR3DL3 resulted in up-regulation of luciferase activity demonstrating a potential mechanism of gene regulation. Furthermore, knockdown of the same endogenous miRNAs using silencing ribonucleic acid (siRNA) led to induced surface expression of KIR3DL3. In conclusion, we provide a novel mechanism of functional regulation of KIR3DL3 via miRNAs. These findings are relevant in understanding the generation of KIR repertoire and NK cell clonality.
This work demonstrates the ability of the Ion-Sensitive Field-Effect Transistor (ISFET)-based immunosensor to detect antibodies against the human leukocyte antigen (HLA) and the major ...histocompatibility complex class-I-related chain A (MICA). The sensing membrane of the ISFET devices was modified and functionalized using an APTES-GA strategy. Surface properties, including wettability, surface thickness, and surface topology, were assessed in each module of the modification process. The optimal concentrations of HLA and MICA proteins for the immobilization were 10 and 50 μg/mL. The dose-response curve showed a detection range of 1.98–40 µg/mL for anti-HLA and 5.17–40 µg/mL for anti-MICA. The analytical precision (%CV) was found to be 10.69% and 8.92% for anti-HLA and -MICA, respectively. Moreover, the electrical signal obtained from the irrelevant antibody was considerably different from that of the specific antibodies, indicating the specific binding of the relevant antibodies without noise interference. The sensitivity and specificity in the experimental setting were established for both antibodies (anti-HLA: sensitivity = 80.00%, specificity = 86.36%; anti-MICA: sensitivity = 86.67%, specificity = 88.89%). Our data reveal the potential of applying the ISFET-based immunosensor to the detection of relevant anti-HLA and -MICA antibodies, especially in the field of kidney transplantation.
Vitamin C is an essential element required for normal metabolic function. We investigated the effect of vitamin C supplementation on circulating miRNA (miR) expression in subjects with poorly ...controlled type 2 diabetes mellitus (T2DM). Changes in miR expression were also correlated with clinical measures of disease.
Pre- and post-vitamin C supplementation samples from five participants who had increased vitamin C levels, improved oxidative status and polymorphonuclear (PMN) function after receiving 1,000 mg of vitamin C daily for six weeks were screened for miRNA expression using the NanoString miRNA assay. Differences in miRNA expression identified from the miRNA screen were validated by qRT-PCR.
Four miRNAs showed significantly different expression post-vitamin C supplementation relative to baseline, including the down-regulation of miR-451a (-1.72 fold change (FC),
= 0.036) and up-regulation of miR-1253 (0.62 FC,
= 0.027), miR-1290 (0.53 FC,
= 0.036) and miR-644a (0.5 FC,
= 0.042). The validation study showed only miR-451a expression was significantly different from baseline with vitamin C supplementation. MiR-451a expression was negatively correlated with vitamin C levels (
= - 0.497,
= 0.049) but positively correlated with levels of malondialdehyde (MDA) (
= 0.584,
= 0.017), cholesterol (
= 0.564,
= 0.022) and low-density lipoproteins (LDL) (
= 0.522,
= 0.037). Bioinformatics analysis of the putative target genes of miR-451a indicated gene functions related to signaling pathways involved in cellular processes, such as the mammalian target of rapamycin (mTOR) signaling pathway.
Vitamin C supplementation altered circulating miR-451a expression. The results from this pilot study suggest that miRNAs could be used as biomarkers to indicate oxidative status in subjects with T2DM and with poor glycemic control and could lead to a novel molecular strategy to reduce oxidative stress in T2DM.
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