Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562.

Vitamin D Levels in Pre-frail Older Adults and Its Correlation with Hand Grip Strength.

BACKGROUND: Vitamin D deficiency is frequent in older adults and associated with poor musculoskeletal function. The prevalence of pre-frailty is also high in older persons, who may proceed to a frail state. This study aimed to determine the vitamin D levels in pre-frail older adults and its correlation with hand grip strength. METHODS: A cross-sectional study was conducted on older adults (age > 60 years) with a pre-frail condition who were visiting the outpatient geriatric clinic at Cipto Mangunkusumo Hospital in Jakarta, Indonesia. Serum levels of vitamin D, measured as 25(OH)D, were determined by enzyme-linked immunosorbent assay (ELISA), and hand grip strength was measured using a Jamar hydraulic dynamometer. Correlations between vitamin D levels and hand grip strength were evaluated by Spearman's rank correlation coefficient. Multiple linear regression analysis was carried out to assess contribution of variables that influence hand grip strength. RESULTS: Of 95 pre-frail older adults (mean age 70.08 ± 5.35 years), 67.4% were female,  and the median vitamin D level was 17.91 (interquartile range/IQR 13.68-26.36) ng/mL. Overall, 11.6% of the participants had normal vitamin D levels, whereas 34.7% and 53.7% had insufficient and deficient levels, respectively. Females were more likely to have inadequacy of vitamin D than males.  Those with vitamin D deficiency tended to have a higher body mass index (BMI) and lower vitamin D intake than normal levels. A significant correlation between serum vitamin D levels and hand grip strength was observed (r = 0.283; P = 0.006). After adjusting for age, comorbidities, nutritional status, functional status, BMI, protein intake, and sun exposure score, regression analysis between hand grip strength and vitamin D levels gave standard coefficient beta = 0.255 (P = 0.013). CONCLUSION: In this study, pre-frail older adults had a high proportion of deficient and insufficient vitamin D levels, and a significant correlation was found between serum vitamin D levels and hand grip strength.

Effect of Roselle Flower Extract (Hibiscus sabdariffa Linn.) on Reducing Steatosis and Steatohepatitis in Vitamin B12 Deficiency Rat Model.

Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague-Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&E)-Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.

The Use of Chitosan Nanoparticles for Delivery of CpG ODN in Treatment of Allergic Balb/C Mice.

Background: This study aims to prepare high stability chitosan nanoparticles (CNP) and examine the ability of CNP in CpG-ODN delivery when treating allergic mice model. Methods: Preparation and characterization of CNP were performed by ionic gelation, dynamic light scattering, and zeta sizer. The CNP cytotoxicity and activation ability of CpG ODN delivered with CNP were tested using a cell counting kit-8 and Quanti blue method. Allergic mice were injected intraperitoneal with 10 ug ovalbumin on day 0 and 7, and then treated with intranasal CpG ODN/CpG ODN, delivered with CNP/CNP, on the third week three times per week for three weeks. The ELISA method measured cytokine and IgE profiles in the allergic mice's plasma and spleen. Results: CNP results have sizes 27.73 nm±3.67 dan 188.23 nm±53.47, spherical in shape and non-toxic, and did not alter the NF-κB activation of CpG ODN in RAW-blue cells. The application of CpG ODN delivered by chitosan nanoparticles shows no statistical difference between groups of IFN-γ, IL-10, and IL-13 in Balb/c mice's plasma and spleen, in contrast with IgE level. Conclusions: The results showed that using chitosan nanoparticles as a delivery system for CpG ODN has the potency to safely CpG ODN efficacy.

Increase in transforming growth factor-ß didnot affect trombospondin1 in preeclampsia placentas.

Objective: The abnormalities of the placental growth process are a theory causing pre-eclampsia. Antiangiogenic factors contributed to it, such as thrombospondin-1 (TSp-1) that could stimulate transforming growth factor-beta (TGF-ß), or vice versa. Some research showed that an increase in TGF-ß did not always figurized its signaling. Therefore, we conducted a study to examine the TGF-ß signaling proteins through its receptors and TSp-1 expression in preeclampsia placentas. Materials and Methods: This observational study used 33 normal and 33 pre-eclampsia placental storaged samples, for examination of TGF-ß and TGF-ßR 1 and 2, SMAD2 using ELISA, and SMAD2 and TSp-1 mRNA using the reverse transcription polymerase chain reaction method. Data were analyzed using SPSS version 20.0, normality test by Kolmogorov-Smirnov, and significancy was analyzed using nonparametric Mann-Whitney test, or t-test for parametric, with confidence interval 95%. Spearman correlation was used for non-parametric data, besides the Pearson correlation for parametric data. Results: Results showed that there were significant differences between preeclampsia and normal placenta in TGF-ß, its receptors, SMAD2, and TSp-1 mRNA. Normal-TGF-ß=1.19 (0.713-2.051) pg/mg; preeclampsia-TGFB=2.69 (0.906-10.252) pg/mg; p=0.001; normal-TGFBR1=1.025 (0.622-1.402) ng/mg; preeclampsia-TGFBR1=1.223 (0.372-2.553) ng/mg; p=0.004; Normal-TGF-ßR2=0.959 (0.644-1.634) pg/mg; preeclampsia-TGFBR2=1.490 (0.775-3.645) pg/mg; p=0.0001; normal-SMAD2=2.087 (1.279-4.300) ng/mg; preeclampsia-SMAD2=3.508 (1.842-22.489) ng/mg; p=0.0001. The SMAD2 mRNA relative expression (Livax) in the normal placenta was=0.71 (0.03-7.25); pre-eclampsia placenta (PE)=0.49 (0.01-40.71); p=0.075, the normal TSp-1 mRNA expression=1.08 (0.09-5.31); PE=0.21 (0.002-24.06); p=0.002. The correlation test showed a strong correlation between TGF-ß with TGFBR1 and 2 in the normal placenta, conversely, there was no correlation in the preeclampsia placenta. There was also no correlation between SMAD2 and TSp-1 mRNA in both normal and pre-eclampsia. Conclusion: TGF-ß signaling in the preeclampsia placenta was changed due to the increased of the protein signaling it self without correlation between TGF-ß to its receptors and TSp-1 relative expression.

Increasing of LDH Specific Activity and PEPCK Level Play a Role on Activation of Gluconeogenesis Pathway in Early Onset Pre-Eeclampsia Placenta.

Background: Recent advancement on experiment concluded that etiology of pre-eclampsia (PE) could be explained by the "two-stage" theory. The theory of which explained that pre-eclampsia occurs due to abnormalities in spiral arteries development and release of inflammatory response. Failure of spiral arteries development, the lesion of damage could be due to ischemia-reperfusion or hypoxia-reoxygenation. Hypoxia in pre-eclamptic placenta leads to metabolic change to anaerobic in glycolysis. Lactate dehydrogenase (LDH) has important role in anaerobic glycolysis that catalyzes the conversion of lactate to pyruvate during hypoxia. On the other hand, phosphoenolpyruvate carboxy kinase (PEPCK) is merely an enzyme of gluconeogenesis. This research conduct to reveal that in early onset pre-eclampsia the placenta still hypoxic and undergoes gluconeogenesis even after delivery, through metabolic enzyme of LDH and PEPCK level. Methods: This cross-sectional study compared early onset PE (< 34 weeks) with normal term placenta. We measured LDH enzyme activity using colorimetric assay and PEPCK protein using ELISA method. Results: Result show that placental LDH specific activity was increased significantly in PE with median 2.750 (0.030 - 5.680) U/mg compared to normal term placenta 0.255 (0.032 - 1.194) U/mg (Mann-Whitney, p< 0.001). PEPCK level was significantly increased in PE 8.998 (1.737-44.914) ng/mg compared to normal term placenta 1.552 (0.741-8.832) ng/mg (Mann-Whitney, p< 0.001). Conclusion: We conclude that anaerobic glycolysis and gluconeogenesis pathway are increased in early onset PE placenta as adaptation mechanism to hypoxic condition.

Diagnostic role of urine specific gravity to detect kidney impairment on heat-exposed workers in a shoe factory in Indonesia: a cross-sectional study.

OBJECTIVES: Globally, there are increasing cases of chronic kidney disease of unknown origin among heat-exposed workers. We aimed to see the kidney damages of indoor heat-exposed workers and whether urine specific gravity can predict any kidney damages. DESIGN: A cross-sectional study. SETTING: A shoe-making factory in West Java, Indonesia. PARTICIPANTS: 119 subjects were included. Minimum total sample size was 62. Subjects were indoor heat-exposed workers who were exposed to occupational wet-bulb globe temperature (WBGT) of 28°C-30°C for 8 hours daily with 1 hour break, 5 days a week. The inclusion criterion was healthy subjects according to the result from annual medical check-up in 2019. The exclusion criteria were subjects who were taking vitamins and/or supplements that might cause disturbance in urine specific gravity and/or hydration status, pregnant and fasting. PRIMARY AND SECONDARY OUTCOME MEASURES: Area under the curve (AUC), sensitivity and specificity of urine specific gravity for the detection of urinary nephrin and urinary kidney injury molecule-1 (KIM-1) were analysed. Estimated glomerular filtration rate (eGFR) and quantitative albuminuria were also measured. RESULTS: WBGT in the work area of the subject was 28°C-30°C. There were 15 (12.6%) subjects who had eGFR <90 mL/min, but ≥60 mL/min. High serum vasopressin levels were found in 79 subjects with a mean of 6.54 (95% CI 5.94 to 7.14) ng/mL. Most subjects had nephrinuria (87.4%) with preserved renal function (87.4%). Several subjects had elevated urinary KIM-1 (10.9%) and albuminuria (7.6%). AUC of urine specific gravity for increased urinary nephrin was 81.7% (95% CI 68.8% to 94.6%) and statistically significant (p<0.001). Cut-off value of ≥1.018 for urine specific gravity has sensitivity of 71.2% and specificity of 80% for detecting elevation of urinary nephrin levels. CONCLUSION: Urine specific gravity with a cut-off value of ≥1.018 could be used to detect nephrinuria among heat-exposed workers.

Oxidative Stress Induced Damage and Early Senescence in Preterm Placenta.

INTRODUCTION: Senescent cells have been demonstrated to release High Mobility Group Box 1 (HMGB1) which induces labor through an inflammatory pathway. This research is aimed at demonstrating whether telomere shortening, proinflammatory HMGB1, and oxidative damage marker 8-OHdG play a role in the placenta of preterm birth in comparison to term birth. METHOD: A cross-sectional study on 67 full thickness of the placenta obtained from mothers with term and preterm birth. Mothers with clinical signs of infection (fever > 38°C, leukocytosis > 18000/µL, or abnormal vaginal discharge) and other pregnancy complications were excluded. Real-time polymerase chain reaction was performed to measure T/S ratio and ELISA quantification to measure the amount of HMGB1 and 8-OHdG. RESULT: A total of 34 placentas from preterm and 33 placentas from term birth were examined. Maternal characteristics were comparable between the two groups. There were no statistical difference of T/S ratio (p = 0.181), HMGB1 (p = 0.119), and 8-OHdG (p = 0.144) between the preterm and term groups. HMGB1 was moderately correlated with 8-OHdG (r = 0.314). Telomere T/S ratio of the placenta did not differ between preterm and term labor despite difference in gestational age, suggesting earlier shortening in the preterm group. It is possible that critical telomere length has been achieved in both term and preterm placenta that warrants labor through senescence process. The result of our study also showed that HMGB1 was not correlated to telomere length, due to the fact that HMGB1 is not upregulated until the critical length of telomere for senescence is exhibited. CONCLUSION: Similar telomere length might be exhibited due to early telomere shortening in preterm birth that mimics the term placenta. The relationship between placental telomere shortening and HMGB1 release remains to be uncovered. Further research is needed to discover the factors leading to early telomere shortening in the placenta of preterm birth.

The formula for calculating the predicted value of cardiorespiratory endurance using a foot rest-based cardiorespiratory exercise device.

This study developed a formula for calculating the predicted VO2 max value using a prototype model of foot-based cardiorespiratory exercise. Forty sedentary workers (20 men and 20 women) were enrolled via consecutive sampling. They underwent direct measurement of VO2 max using spiroergometry as the gold standard; the predicted VO2 max value was calculated using a prototype model of foot-based cardiorespiratory exercise, which was performed on consecutive days. Multivariate linear regression analysis was used to formulate the equation for the predicted VO2 max value by including potential contributing variables: gender, body height, body weight and heart rate. Bland-Altman test was used for assessing the agreement level for the predicted VO2 max value. The equation for the predicted VO2 max value was formulated as 3.2 + 0.15 optimal exercise heart rate -5.5 sexes (0 for men, 1 for women). The agreement level for the formula was acceptable in all measurement result ranges. The formula developed in this study can be used to measure the predicted VO2 max value with an acceptable agreement level.

SEMA3B but Not CUL1 as Marker for Pre-Eclampsia Progression.

BACKGROUND: An imbalance between pro- and anti-angiogenic factors contributes to impaired trophoblast invasion during pregnancy, leading to failure of uterine spiral artery remodeling, blood vessel ischemia, and pre-eclampsia (PE). Anti-angiogenic semaphorin 3B (SEMA3B) and pro-angiogenic cullin 1 (CUL1) are expressed in both the placenta and maternal blood. The present study investigated correlations between serum and placental SEMA3B as well as CUL1 levels in late-onset PE. METHODS: This cross-sectional study included 50 patients with late-onset (≥ 32 weeks gestation) PE. Maternal serum was obtained before delivery, and placentas were obtained immediately after delivery. SEMA3B and CUL1 levels were evaluated by ELISA. Results were statistically analysed by Spearman correlation test, with a P < 0.05 considered statistically significant. RESULTS: While elevated serum SEMA3B levels significantly correlated with increased placental SEMA3B levels in late-onset PE (R = 0.620, P = 0.000), alteration of serum CUL1 levels did not correlate with alteration of placental CUL1. CONCLUSION: Alteration of circulating maternal SEMA3B, but not CUL1, levels can potentially be used to monitor PE progression during pregnancy.