Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue.
To investigate the association of maternal hyperglycemia exposure during pregnancy with ...obesity and abnormal glucose tolerance in offspring, and the age at occurrence.
We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS).
Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04-0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13-0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18-0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2-5 years old to early adulthood (pooled odds ratio OR, 6.10: 95% CI: 1.23-30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse.
Only observational studies were included, with a few adequately adjusted for covariables.
Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The minimum DNA-binding domain of the transcriptional factor c-Myb R2R3 remarkably fluctuates in the solution. In the present study, we evaluated the protein fluctuation of R2R3 C130I mutant, R2R3*, ...on its DNA-binding and folding thermodynamics. DNA-binding analysis using isothermal titration calorimetry revealed that the heat capacity change determined from the correlation between temperature and binding enthalpy change is highly negative above 35°C, indicating that the fluctuation increases with increasing temperature and elevates the conformational change on DNA binding. The results were in accordance with those of differential scanning calorimetry, which revealed that the heat capacity corresponding to thermal denaturation gradually increased above 35°C, followed by the broad transition peak. In contrast, the transition peak of R2R3* in the DNA-bound state was sharper and larger than that in the DNA-unbound state. The fluctuating form could transform into lesser fluctuating form upon DNA binding, resulting in a larger enthalpy change for denaturation of R2R3* in the DNA-bound state. It should also be noted that R2R3* could specifically bind to DNA around thermal denaturation temperature. This would be due to proteins with numerous fluctuations. Moreover, we discuss specific and non-specific DNA binding accompanied by the conformational change between well-ordered and disordered forms of R2R3* observed around the denaturation temperature.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Although low birth weight in Japan has slightly increased over the past several decades, the association between maternal birth weight and pregnancy outcomes remains poorly understood.
In this ...hospital-based, prospective cohort study conducted at the National Center for Child Health and Development, we obtained information on pregnant women's birth weight via their maternal and child health handbook. We analyzed 944 women born at term after dividing them into five categories according to their birth weight: <2500 g, 2500-2999 g, 3000-3499 g, 3500-3999 g, and ≥4000 g. Multivariate logistic regression analysis and trend analysis were used to elucidate the extent to which maternal birth weight was associated with small-for-gestational-age and low birth weight in offspring, as well as with hypertensive disorders of pregnancy.
Compared with women with a birth weight of 3000-3499 g, those born with a birth weight <2500 g had a significantly higher risk of low birth weight (adjusted odds ratio: 5.39, 95% confidence interval: 2.06-14.1) and small-for-gestational-age (adjusted odds ratio: 9.11, 95% confidence interval: 3.14-26.4) infants. No significant association was found between the incidence of hypertensive disorders of pregnancy and preterm birth. A linear relationship was observed between the lower birth weight categories and a higher risk of low birth weight and small-for-gestational-age (p-values for trends: 0.009 and <0.001, respectively), but no linear relationship was observed for the risk of preterm birth and hypertensive disorders of pregnancy (p-value for trends: 0.317 and 0.157, respectively).
Our findings suggest that lower maternal birth weight is associated with small-for-gestational-age and low birth weight in offspring of women born at term.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The monoclonal antibody G2 specifically recognizes different peptides. The single-chain Fv (scFv) antibodies of G2 covalently linked to antigen peptides, Pep18mer and Pep395, via a flexible linker ...were expressed in Escherichia coli in the insoluble fraction, and were solubilized using guanidine HCl, followed by refolding. We analyzed the folding thermodynamics of the refolded proteins, purified as monomers using size-exclusion chromatography (SEC). The results of the differential scanning calorimetry (DSC) showed that the thermal stabilities of antigen peptide-linked G2 scFvs were higher than those of antigen-free G2 scFv in the absence or presence of antigen peptides. The folding thermodynamics further indicated how the antigen-antibody affinity affect the intramolecular interactions. The combination of SEC and DSC experiments could confirm the folding correctness of antigen peptide-linked G2 scFvs and could be applied for “structural screening” of refolded proteins in the case that the “functional screening” like antigen binding is difficult to apply. The present method to covalently link the peptide would contribute to the stable complex structure, and would be widely applied to other antibodies recognizing peptide antigens.
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•We generated single-chain Fv (scFv) antibodies linked to its antigen peptides.•Refolding correctness could be evaluated by folding thermodynamics.•The peptide-scFv linking could contribute to increased stability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cell–cell interactions between cancer cells and neighboring adipose tissue-derived stromal cells (ATSCs) are known to regulate the aggressiveness of cancer cells. In addition, the radiation-induced ...bystander effect is an important modulator of cancer cell kinetics. Radiation therapy is often given for urinary cancer, but the biological effects of the irradiated cancer stroma, including adipose tissue, on urothelial carcinoma (UC) remain unclear. We investigated the bystander effect of irradiated ATSCs on UC using a collagen gel culture method to replicate irradiated ATSC–cancer cell interactions after a single 12-Gy dose of irradiation. Proliferative activity, invasive capacity, protein expression and nuclear translocation of p53 binding protein-1 (53BP1) were analyzed. Irradiated ATSCs significantly inhibited the growth and promoted the apoptosis of UC cells in comparison to non-irradiated controls. The invasiveness of UC cells was increased by irradiated ATSCs, but not irradiated fibroblasts. Nuclear translocation of 53BP1 protein due to the bystander effect was confirmed in the irradiated group. Irradiated ATSCs regulated the expressions of the insulin receptor, insulin-like growth factor-1 and extracellular signal-regulated kinase-1/2 in UC. In conclusion, the bystander effect of irradiated ATSCs is a critical regulator of UC, and the actions differed depending on the type of mesenchymal cell involved. Our alternative culture model is a promising tool for further investigations into radiation therapy for many types of cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
For women with gestational diabetes mellitus (GDM), the evaluation of glucose tolerance (GT) in the early postpartum period is universally recommended. Nevertheless, few studies have evaluated the ...risk factors for T2DM on the basis of GT data obtained during the early postpartum period. We aimed to identify the risk factors for type 2 diabetes mellitus (T2DM) by evaluating GT in the first 12 weeks postpartum (12wPP) in women with GDM and to categorize the risk using a combination of the principal risk factors. This retrospective multicenter observational study included 399 East Asian women with GDM who underwent a 75-g oral glucose tolerance test (OGTT) within 12wPP, which was repeated annually or biennially and used to identify the postpartum development of T2DM. Forty-three women (10.8%) developed T2DM during a median follow-up period of 789 ± 477 days. The independent risk factors for T2DM were pre-pregnancy obesity (BMI ≥25 kg/m2), early postpartum impairment in glucose tolerance (IGT), and an early postpartum glycated hemoglobin (HbA1c) ≥5.7%. The odds ratios (95% confidence intervals) for T2DM were 3.2 (1.3–7.8) in women with either early postpartum IGT or pre-pregnancy obesity, 9.2 (3.0–28.3) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c <5.7%, and 51.4 (16.1–163.9) in those with early postpartum IGT, pre-pregnancy obesity, and HbA1c ≥5.7%, compared with those without obesity or IGT. T2DM risk in East Asian women with GDM should be stratified according to pre-pregnancy obesity and early postpartum IGT, and these patients should be followed up and receive appropriate care for their risk category.
•We analyzed binding thermodynamics of oligonucleotides to form DNA.•The affinity depends on chain length and ionic strength.•The ΔCp changes from negative to positive at a temperature close to Tm.
...In this study, association of oligonucleotides of length 8-22 bases and their complementary oligonucleotides to form DNA was analyzed using isothermal titration calorimetry. Additionally, dissociation of DNA into its respective oligonucleotides was analyzed using differential scanning calorimetry. The effects of chain length, temperature, and ionic strength on the association and dissociation of DNA were evaluated using thermodynamic analyses. At 25 °C, the association of 10-base oligonucleotides largely depended on ionic strength, however, for oligonucleotides of 12-base and above, association was independent of ionic strength. In oligonucleotides of length 12-, 16-, and 22-bases, both binding enthalpy and entropy changes decreased with increase in chain length around 25 °C, providing similar binding affinity. The highest association constant was approximately 1 × 109 M–1. During association of DNA oligonucleotide of the same chain length, binding enthalpy change gradually decreased with increase in temperature, indicating a negative heat capacity change around 25 °C. As the temperature increased close to the melting temperature, the binding enthalpy change increased, indicating a positive heat capacity change. The temperature-dependent binding enthalpy change was apparently extrapolated to the calorimetric enthalpy change of DNA at the melting temperature. At the melting temperature, the effect of chain length and ionic strength could be observed clearly; the stability of DNA increased with increasing chain length and ionic strength.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The minimum functional unit of c-Myb for specific DNA binding, c-Myb R2R3, fluctuates largely in solution which is critical for its DNA-binding function. The thermal stability of R2R3 increases with ...increasing NaCl concentrations and upon DNA binding as well. The DNA-binding affinity of R2R3 is stringently dependent on NaCl concentration, and decreases both with an increase or decrease in NaCl concentration from the physiological levels. The decreased DNA-binding affinity under low NaCl concentrations is because of the unfavorable entropy change, in contrast to the thermodynamic contribution under high NaCl concentrations. Together with the findings from thermal stability and structure analyses, the results indicate that R2R3 fluctuates more largely under low ionic strength than high ionic strength, resulting in its decreased stability and DNA-binding affinity. Under physiological conditions, R2R3 fluctuates properly to express its DNA-binding ability. The present results clearly show the naïve balance between structural stability and DNA binding.
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•Thermal stability of R2R3 increases with increasing salt concentrations.•DNA-binding affinity of R2R3 decreases in low salt concentrations.•R2R3 adapts its structure suitably for both stability and function.•There exists naïve balance between structural stability and function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Squamous cell carcinoma (SCC) is the most major malignant tumor of the tongue. The tongue exists at the air–liquid interface and is covered with saliva. In addition, the tongue constituent cells and ...tongue cancer are present under fluid flow stimulation due to the abundant capillary network and contraction of muscle tissue. Therefore, replicating both cell–cell interactions (the cellular microenvironment) and the aforementioned physical microenvironment is very important for understanding the kinetics of tongue SCC. To elucidate the effects of the cellular and physical microenvironment on tongue SCC and to investigate the relationships between these factors, we developed a collagen cell disc, with double dish under a rotational culture method to generate cancer–stroma interactions and to create fluid flow stimulation. Mesenchymal cells, NIH-3T3 cells and tongue-derived fibroblasts influenced the proliferative potential. Extracellular signal-regulated kinase and p38 signaling were regulated either synergistically or independently by cellular interactions and fluid flow stimulation, depending on the SCC cell type. The cell–cell interactions and fluid flow stimulation independently, synergistically or contradictorily affected the behavior of tongue SCC. Fluid flow stimulation synergistically enhanced the antiproliferative effect of cis-diamminedichloroplatinum on tongue SCC cells, but mesenchymal cells abolished the synergistic antiproliferative effect related to fluid flow stimulation. In conclusion, a reconstructed model was established to investigate the cellular and physical microenvironments of tongue SCC in vitro. The newly established system is a promising model for the development of further regimes to treat general oral cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The importance of the microenvironment is widely recognized as it regulates not only malignant cell behavior but also drug sensitivity. The cancer cell microenvironment is composed of biological, ...physical and chemical elements, and simultaneous reproduction of these three elements are important conditions investigated in cancer research. In the present study, we focused on the epidemiological and anatomical specificities of endometrioid carcinoma, obesity (biological), fluid flow (physical) and anticancer agents (chemical) to target the specific microenvironmental elements of endometrioid carcinoma. To elucidate the individual effects of these elements on endometrioid carcinoma and to investigate the relationships between these factors, we developed an adipose tissue fragments (ATFs)-embedded cell disc under a rotational culture method to generate carcinoma-stroma interactions and to create fluid flow. ATFs and fluid flow individually or synergistically influenced proliferative cellular behavior and the morphological changes underlying endometrioid carcinoma. ATFs and fluid flow also governed the expression of extracellular signal-regulated kinase and p38 signaling synergistically or individually, depending on the endometrioid carcinoma cell type. Adipose tissue induced chemoresistance to cis-diamminedichloro-platinum (CDDP) in endometrioid cancer, but the resistance effect was abolished by fluid flow. Thus, a simple reconstructed model was established to investigate three elements of the microenvironment of endometrioid carcinoma in vitro. This culture model unequivocally demonstrated the individual and synergistic effects of the three elements on endometrioid carcinoma. This new culture model is a promising tool for elucidating the mechanisms underlying endometrioid carcinoma and for developing further treatment strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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