Jejuketomycins A and B,polyketide glycosides with cancer cell migration inhibitory activity from Streptomyces sp. KCB15JA151

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151. Their chemical structures including the absolute configurations were determined by detailed analyses of the NMR and HRMS data and ECD calculations and spectral data. Compounds 1 and 2 possess an unusual 6/6/8 tricyclic ring system. Biological evaluation with the wound healing assay and time-lapse cell tracking analysis revealed that compounds 1 and 2 have significant inhibitory activities against cancer cell migration with low cytotoxicity.

Two new polyketide glycosides jejuketomycins A (1) and B (2), were isolated from a culture of Streptomyces sp. KCB15JA151.     

Antiangiogenic activity of lupeol from Bombax ceiba

In the search for antiangiogenic agents from medicinal plants used in Vietnam, a methanol extract of the stem barks of Bombax ceiba was found to exhibit a significant antiangiogenic activity on in vitro tube formation of human umbilical venous endothelial cells (HUVEC). Bioactivity-guided fractionation and isolation carried out on this extract afforded lupeol as an active principle. At 50 and 30 microg/mL lupeol showed a marked inhibitory activity on HUVEC tube formation while it did not affect the growth of tumor cell lines such as SK-MEL-2, A549, and B16-F10 melanoma.     

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD): A Korean Chronic Kidney Disease Cohort

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Sleep-promoting activity of lotus (Nelumbo nucifera) rhizome water extract via GABAA receptors

ContextThe sleep-promoting activity of Nelumbo nucifera Gaertn. (Nymphaeaceae) alkaloids in leaves or seeds are well known. However, the sleep-promoting activity of the lotus rhizome (LE), which is used mainly as food, has not yet been evaluated.ObjectiveWe investigated the sleep-promoting activity of LE water extract.Materials and methodsInstitute of Cancer Research (ICR) mice (n = 8) were subject to a pentobarbital-induced sleep test to assess changes in sleep latency and duration following the administration of LE (80–150 mg/kg). In addition, electroencephalography analysis was performed to determine the sleep quality after LE treatment as well as the sleep recovery effect of LE using a caffeine-induced insomnia SD rat model. Real-time PCR and western blot analysis were performed to investigate the expression of neurotransmitter receptors, and the GABA_A receptor antagonists were used for receptor binding analysis.ResultsAn oral administration of 150 mg/kg LE significantly increased sleep duration by 24% compared to the control. Furthermore, LE increased nonrapid eye movement (NREM) sleep by increasing theta and delta powers. In the insomnia model, LE increased sleep time by increasing NREM sleep. Moreover, treatment with picrotoxin and flumazenil decreased the sleep time by 33% and 23%, respectively, indicating an involvement of the GABA_A receptor in the sleep-enhancing activity of LE. The expression of GABA_A receptors and the concentration of GABA in the brain were increased by LE.Discussion and conclusionsThe results suggest that the sleep-promoting activity of LE was via the GABA_A receptor. Collectively, these data show that LE may promote sleep.     

Predicting the depressive status using empirical dietary inflammatory index in patients with antineutrophil cytoplasmic antibody‐associated vasculitis

BackgroundThis study investigated whether the empirical dietary inflammatory index (eDII) score is associated with the inflammatory burden as well as the depressive status in patients with antineutrophil cytoplasmic antibody‐associated vasculitis (AAV).MethodsEighty‐four patients with AAV participated in this study. Birmingham vasculitis activity score (BVAS) and short‐form 36‐item Health Survey mental component summary (SF‐36 MCS) were considered as indices assessing the inflammatory burden and depressive status, respectively. The eDII includes 16 food components and consists of three groups: −9 to −2, the low eDII group; −1 to +1, the moderate eDII group; and +2 to +10, the high eDII group. Furthermore, the lower eDII group includes both the low and moderate eDII groups.ResultsThe median age was 64.5 years (36 men). The eDII scores inversely correlated with SF‐36 MCS (r = −0.298, p = 0.006) but not with BVAS. SF‐36 MCS significantly differ between the lower and higher eDII groups (69.7 vs. 56.7, p = 0.016), but not among the low, moderate and high eDII groups. Additionally, when patients with AAV were divided into two groups according to the upper limit of the lowest tertile of SF‐36 MCS of 55.31, patients in the higher eDII group exhibited a significantly higher risk for the lowest tertile of SF‐36 MCS than those in the lower eDII group (RR 3.000).ConclusionWe demonstrated for the first time that the eDII could predict the depressive status by estimating SF‐36 MCS without utilising K‐CESD‐R ≥ 16 in patients with AAV.     

The sexual brain,genes, and cognition: A machine‐predicted brain sex score explains individual differences in cognitive intelligence and genetic influence in young children

Sex impacts the development of the brain and cognition differently across individuals. However, the literature on brain sex dimorphism in humans is mixed. We aim to investigate the biological underpinnings of the individual variability of sexual dimorphism in the brain and its impact on cognitive performance. To this end, we tested whether the individual difference in brain sex would be linked to that in cognitive performance that is influenced by genetic factors in prepubertal children (N = 9,658, ages 9–10 years old; the Adolescent Brain Cognitive Development study). To capture the interindividual variability of the brain, we estimated the probability of being male or female based on the brain morphometry and connectivity features using machine learning (herein called a brain sex score). The models accurately classified the biological sex with a test ROC–AUC of 93.32%. As a result, a greater brain sex score correlated significantly with greater intelligence (p _fdr < .001, ηp2 = .011–.034; adjusted for covariates) and higher cognitive genome‐wide polygenic scores (GPSs) (p _fdr < .001, ηp2 < .005). Structural equation models revealed that the GPS‐intelligence association was significantly modulated by the brain sex score, such that a brain with a higher maleness score (or a lower femaleness score) mediated a positive GPS effect on intelligence (indirect effects = .006–.009; p = .002–.022; sex‐stratified analysis). The finding of the sex modulatory effect on the gene–brain–cognition relationship presents a likely biological pathway to the individual and sex differences in the brain and cognitive performance in preadolescence.     

Objective Interpretation of the Rapid Urease Test for Helicobacter pylori Infection Using Colorimetry

BackgroundThe rapid urease test (RUT) is a major diagnostic tool for detecting Helicobacter pylori infection. This study aimed to establish an objective method for measuring the color changes in the RUT kit to improve the test’s diagnostic accuracy.MethodsA UV-visible spectrophotometer was selected as the colorimeter; experiments were conducted in three stages to objectively identify the color changes in the RUT kit.ResultsFirst, the urea broth solution showed an identifiable color change from yellow to red as the pH increased by 0.2. The largest transmittance difference detected using the UV-visible spectrophotometer was observed at a 590-nm wavelength. Second, the commercialized RUT kit also showed a gradual color change according to the pH change detected using the UV-visible spectrophotometer. Third, 13 cases of negative RUT results with a biopsy specimen and 16 of positive RUT results were collected. The transmittance detected using the UV-visible spectrophotometer showed a clear division between the positive and negative RUT groups; the largest difference was observed at a 559-nm wavelength. The lowest transmittance in the negative RUT group was 64, while the highest in the positive RUT group was 56, at the 559-nm wavelength. The UV-visible spectrophotometry reading showed a consistency of 92.7% compared with that of manual reading.ConclusionA transmittance of 60 at a 559-nm wavelength detected using UV-visible spectrophotometer can be used as a cutoff value for interpreting RUT results; this will help develop an automatic RUT kit reader with a high accuracy.     

β-Sitosterol Attenuates Dexamethasone-Induced Muscle Atrophy via Regulating FoxO1-Dependent Signaling in C2C12 Cell and Mice Model

Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although β-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of β-sitosterol effect on the catabolic pathway was not well known. β-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. β-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the β-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when β-sitosterol was treated. The muscle loss inhibitory efficacy of β-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. β-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when β-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, β-sitosterol would be a potential treatment agent for aging sarcopenia.     

Phloroglucinol (PG) purified from Ecklonia cava attenuates radiation-induced apoptosis in blood lymphocytes and splenocytes

Phloroglucinol (PG), a polyphenol compound of Eckloniacava known as brown algae abundant in Jeju island, has been proposed to exert the antioxidative and cytoprotective effects against oxidative stress. In this study, we confirmed that PG protected mice from damages caused by ionizing radiation and investigated its protection mechanism in detail. The result showed that PG increased the viability of splenocytes without cytotoxicity. Also, PG significantly enhanced the proliferation of splenocytes by limiting the increment of sub-G₁ DNA contents via the inhibition of reactive oxygen species production in 2 Gy-irradiated splenocytes. In addition, PG significantly decreased DNA damage and the number of apoptotic fragments in lymphocytes against oxidative stress. Also, PG increased the counts of endogenous spleen CFUs, compared with only ionizing radiation-irradiated mice. These results demonstrate the multi-faceted protection mechanisms of PG in mice against oxidative stress caused by ionizing radiation, providing the benefit of inhibiting apoptosis and strengthening hematopoiesis.