Two New Components from an Association of Marine Sponges Poecillastra sp. and Jaspis sp. and Their Inhibitory Effects on Biomarkers for Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH), characterized by the enlargement of the prostate gland and subsequent lower urinary tract symptoms, poses a significant health concern for aging men with increasing prevalence. Extensive efforts encompassing in vitro and in vivo models are underway to identify novel and effective agents for the management and treatment of BPH. Research endeavors are primarily channeled toward assessing the potential of compounds to inhibit cell proliferation, curb inflammation, and display anti-androgenic activity. Notably, through screening aimed at inhibiting 5-alpha reductase type 2 (5αR2) in human prostatic cells, two acyl compounds (1 and 2) were isolated from a bioactive fraction sourced from an association of marine sponges Poecillastra sp. and Jaspis sp. The complete structure of 1 was determined as (Z)-dec-3-enony (2S, 3S)-capreomycidine, ascertained by JBCA and ECD comparison. While the absolute configurations of 2 remained unassigned, it was identified as a linkage of a 2, 7S*-dihydoxy-9R*-methyloctadecanoyl group with the 2-amino position of a tramiprosate moiety referred to as homotaurine. Evaluation of both compounds encompassed the assessment of their inhibitory effects on key biomarkers (5αR2, AR, PSA, and PCNA) associated with BPH in testosterone propionate (TP)-activated LNCap and RWPE-1 cells.

Laser frequency stabilization in the 10 -14 range via optimized modulation transfer spectroscopy on the 87Rb D2 line.

We present a high-performance laser frequency stabilization method using modulation transfer spectroscopy (MTS) on the rubidium 87D2 transition line. A substantial improvement of the laser frequency stability was achieved by searching for the optimal diameter and intensity settings of the probe and pump beam. The frequency instability measured from the beat frequency of two locked external cavity diode lasers (ECDLs) reached a short-term stability of 4.5×10-14/τ and did not exceed 2 × 10-12 until 105 s, which is the best performance reported thus far with a D2 transition. The long-term stability is limited by the offset fluctuations of the baseline induced by the residual amplitude modulation (RAM), which can be further improved by reducing the current temperature variation of about 0.2 K by means of temperature stabilization or through a further reduction of the RAM.

Moving-frame imaging of transiting cold atoms for precise long-range transport.

Transporting cold atoms between interconnected vacuum chambers is an important technique for increasing the versatility of cold atom setups, particularly for those that couple atoms to photonic devices. In this report, we introduce a method where we are able to image the atoms at all points during transport via moving optical dipole trap. Cooled 87Rb atoms are transported ∼50 cm into an auxiliary vacuum chamber while being monitored with a moving-frame imaging system for which in-situ characterization of the atom transport is demonstrated. Precise positioning of the atoms near photonic devices is also tested across several tapered fibers showing an axial positioning resolution of ∼450 µm.

Ovataline: A Polyketide Isolated from the Benthic Dinoflagellate Ostreopsis cf. ovata with 5α-Reductase Inhibitory Activity in RWPE-1 Prostatic Cells.

Ovataline (1), which is a polar metabolite containing a hexahydroquinoline moiety, was isolated from cultures of the marine dinoflagellate Ostreopsis cf. ovata. 1 was characterized as a zwitterionic compound with hexahydroquinoline and tetrahydropyran rings. The configurations of the chiral centers in 1 were established using ROESY correlations, J-based configurational and Mosher reaction analyses, and density functional theory calculations. 1 exhibited a 78% (1 µM) inhibition of type II 5α-reductase in testosterone propionate-induced RWPE-1 human prostatic cells.

Maximized atom number for a grating magneto-optical trap via machine-learning assisted parameter optimization.

We present a parameter set for obtaining the maximum number of atoms in a grating magneto-optical trap (gMOT) by employing a machine learning algorithm. In the multi-dimensional parameter space, which imposes a challenge for global optimization, the atom number is efficiently modeled via Bayesian optimization with the evaluation of the trap performance given by a Monte-Carlo simulation. Modeling gMOTs for six representative atomic species - 7Li, 23Na, 87Rb, 88Sr, 133Cs, 174Yb - allows us to discover that the optimal grating reflectivity is consistently higher than a simple estimation based on balanced optical molasses. Our algorithm also yields the optimal diffraction angle which is independent of the beam waist. The validity of the optimal parameter set for the case of 87Rb is experimentally verified using a set of grating chips with different reflectivities and diffraction angles.

Antibiofilm Activity of Phorbaketals from the Marine Sponge Phorbas sp. against Staphylococcus aureus.

Biofilm formation by Staphylococcus aureus plays a critical role in the persistence of chronic infections due to its tolerance against antimicrobial agents. Here, we investigated the antibiofilm efficacy of six phorbaketals: phorbaketal A (1), phorbaketal A acetate (2), phorbaketal B (3), phorbaketal B acetate (4), phorbaketal C (5), and phorbaketal C acetate (6), isolated from the Korean marine sponge Phorbas sp. Of these six compounds, 3 and 5 were found to be effective inhibitors of biofilm formation by two S. aureus strains, which included a methicillin-resistant S. aureus. In addition, 3 also inhibited the production of staphyloxanthin, which protects microbes from reactive oxygen species generated by neutrophils and macrophages. Transcriptional analyses showed that 3 and 5 inhibited the expression of the biofilm-related hemolysin gene hla and the nuclease gene nuc1.

Densazalin, a New Cytotoxic Diazatricyclic Alkaloid from the Marine Sponge Haliclona densaspicula.

Densazalin, a polycyclic alkaloid, was isolated from the marine sponge Haliclona densaspicula collected in Korea. The complete structure of the compound was determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance techniques, high-resolution mass spectrometry, and comparison of the calculated and measured electronic circular dichroism spectra. Densazalin possesses a unique 5,11-diazatricyclo[7.3.1.02,7]tridecan-2,4,6-triene moiety, which is connected by two linear carbon chains. This compound was derived from the biogenetic precursor bis-1,3-dialkylpyridnium. Densazalin exhibited cytotoxic activity on two human tumor cell lines (AGS and HepG2) in the Cell Counting Kit-8 (CCK-8) bioassay, with IC50 values ranging from 15.5 to 18.4 µM.

Chip-Scale Ultra-Low Field Atomic Magnetometer Based on Coherent Population Trapping.

We report a chip-scale atomic magnetometer based on coherent population trapping, which can operate near zero magnetic field. By exploiting the asymmetric population among magnetic sublevels in the hyperfine ground state of cesium, we observe that the resonance signal acquires sensitivity to magnetic field in spite of degeneracy. A dispersive signal for magnetic field discrimination is obtained near-zero-field as well as for finite fields (tens of micro-tesla) in a chip-scale device of 0.94 cm3 volume. This shows that it can be readily used in low magnetic field environments, which have been inaccessible so far in miniaturized atomic magnetometers based on coherent population trapping. The measured noise floor of 300 pT/Hz1/2 at the zero-field condition is comparable to that of the conventional finite-field measurement obtained under the same conditions. This work suggests a way to implement integrated atomic magnetometers with a wide operating range.

Treatment of Hyperammonemia by Transplanting a Symbiotic Pair of Intestinal Microbes.

Hyperammonemia is a deleterious and inevitable consequence of liver failure. However, no adequate therapeutic agent is available for hyperammonemia. Although recent studies showed that the pharmabiotic approach could be a therapeutic option for hyperammonemia, its development is clogged with poor identification of etiological microbes and low transplantation efficiency of candidate microbes. In this study, we developed a pharmabiotic treatment for hyperammonemia that employs a symbiotic pair of intestinal microbes that are both able to remove ammonia from the surrounding environment. By a radioactive tracing experiment in mice, we elucidated how the removal of ammonia by probiotics in the intestinal lumen leads to lower blood ammonia levels. After determination of the therapeutic mechanism, ammonia-removing probiotic strains were identified by high-throughput screening of gut microbes. The symbiotic partners of ammonia-removing probiotic strains were identified by screening intestinal microbes of a human gut, and the pairs were administrated to hyperammonemic mice to evaluate therapeutic efficacy. Blood ammonia was in a chemical equilibrium relationship with intestinal ammonia. Lactobacillus reuteri JBD400 removed intestinal ammonia to shift the chemical equilibrium to lower the blood ammonia level. L. reuteri JBD400 was successfully transplanted with a symbiotic partner, Streptococcus rubneri JBD420, improving transplantation efficiency 2.3×103 times more compared to the sole transplantation while lowering blood ammonia levels significantly. This work provides new pharmabiotics for the treatment of hyperammonemia as well as explains its therapeutic mechanism. Also, this approach provides a concept of symbiotic pairs approach in the emerging field of pharmabiotics.

In Situ Magnetic Control of Macroscale Nanoligand Density Regulates the Adhesion and Differentiation of Stem Cells.

Developing materials with remote controllability of macroscale ligand presentation can mimic extracellular matrix (ECM) remodeling to regulate cellular adhesion in vivo. Herein, we designed charged mobile nanoligands with superparamagnetic nanomaterials amine-functionalized and conjugated with polyethylene glycol linker and negatively charged RGD ligand. We coupled negatively a charged nanoligand to a positively charged substrate by optimizing electrostatic interactions to allow reversible planar movement. We demonstrate the imaging of both macroscale and in situ nanoscale nanoligand movement by magnetically attracting charged nanoligand to manipulate macroscale ligand density. We show that in situ magnetic control of attracting charged nanoligand facilitates stem cell adhesion, both in vitro and in vivo, with reversible control. Furthermore, we unravel that in situ magnetic attraction of charged nanoligand stimulates mechanosensing-mediated differentiation of stem cells. This remote controllability of ECM-mimicking reversible ligand variations is promising for regulating diverse reparative cellular processes in vivo.

Administration of encapsulated L-tryptophan improves duodenal starch digestion and increases gastrointestinal hormones secretions in beef cattle.

OBJECTIVE: This study investigated the effects of oral administration of rumen-protected L-tryptophan (RPL-T) on duodenal starch digestion and gastrointestinal hormones (GIH) secretions using Hanwoo beef steers as the animal models. METHODS: Four steers (423±24 kg) fitted with ruminal and duodenal cannulas were employed in a crossover design replicated twice. Treatments were control (basal diet) and RPL-T (basal diet+191.1 mg/kg body weight [BW]) group. Blood and duodenal samples were collected to measure serum GIH levels and pancreatic α-amylase activity at day 0, 1, 3, and 5 (-30, 30, 90, 150, and 210 min) of the study. Samples from each segment of the gastrointestinal tract were collected via ruminal and duodenal cannulas and were used to determine soluble protein and the starch digestion rate at days 6 (-30, 180, 360, and 540 min) and 8 (-30, 90, 270, and 450 min) of the experiment. RESULTS: No significant difference in ruminal pH, NH3-N, and total volatile fatty acid including the levels of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, and the acetate-to-propionate ratio was observed between groups (p>0.05). Crude protein uptake was higher and feces starch content was lower in RPL-T group than the control group (p<0.05). The D-glucose contents of feces in RPL-T group decreased at day 5 compared to those in the control group (p<0.05), however, no change was found at day 0, 1, or 3 compared to the control group (p>0.05). Serum cholecystokinin (CCK), melatonin, duodenal pancreatic α-amylase activity, and starch digestion were significantly higher in RPL-T group than the control group (p<0.05). CONCLUSION: Taken together, oral administration of RPL-T at the rate of 191.1 mg/kg BW consistently increased CCK concentration, pancreatic α-amylase activity in duodenal fluids, and starch digestion rate in the small intestine and thus found to be beneficial.

Deacetylphylloketal, a New Phylloketal Derivative from a Marine Sponge, Genus Phyllospongia, with Potent Anti-Inflammatory Activity in In Vitro Co-Culture Model of Intestine.

The inflammatory bowel diseases (IBD) cause chronic inflammation of the gastrointestinal tract and include ulcerative colitis (UC) and Crohn's disease (CD). The prevalence of IBD has been increasing worldwide, and has sometimes led to irreversible impairment of gastrointestinal structure and function. In the present study, we successfully isolated a new phylloketal derivative, deacetylphylloketal (1) along with four known compounds from the sponge genus Phyllospongia. The anti-inflammatory properties of deacetylphylloketal (1) and phyllohemiketal A (2) were evaluated using an in vitro co-culture system that resembles the intestinal epithelial environment. A co-culture system was established that consisted of human epithelial Caco-2 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophage cells. The treatment of co-cultured THP-1 cells with compounds 1 or 2 significantly suppressed the production and/or gene expression of lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), Interleukin-6 (IL-6), IL-1ß and Tumor Necrosis Factor alpha (TNF-α). The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 were down-regulated in response to inhibition of NF-kB translocation into the nucleus in cells. In addition, we observed that 1 and 2 markedly promoted the nuclear translocation of Nrf2 and subsequent increase in the expression of heme oxygernase (HO)-1. These findings suggest the potential use of sponge genus Phyllospongia and its metabolites as a pharmaceutical aid in the treatment of inflammation-related diseases including IBD.

(10Z)-Debromohymenialdisine from Marine Sponge Stylissa sp. Regulates Intestinal Inflammatory Responses in Co-Culture Model of Epithelial Caco-2 Cells and THP-1 Macrophage Cells.

Crohn's disease (CD) and ulcerative colitis (UC), collectively referred to as inflammatory bowel disease (IBD), are autoimmune diseases characterized by chronic inflammation within the gastrointestinal tract. Debromohymenialdisine is an active pyrrole alkaloid that is well known to serve as a stable and effective inhibitor of Chk2. In the present study, we attempted to investigate the anti-inflammatory properties of (10Z)-debromohymenialdisine (1) isolated from marine sponge Stylissa species using an intestinal in vitro model with a transwell co-culture system. The treatment with 1 attenuated the production and gene expression of lipopolysaccharide (LPS)-induced Interleukin (IL)-6, IL-1ß, prostaglandin E2 (PGE2), and tumor necrosis factor-α in co-cultured THP-1 macrophages at a concentration range of 1-5 µM. The protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were down-regulated in response to the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) translocation into the nucleus in cells. In addition, we observed that 1 markedly promoted the nuclear translocation of nuclear factor erythroid 2 related factor 2 (Nrf2) and subsequent increase of heme oxygenase-1 (HO-1) expression. These findings suggest the potential use of 1 as a pharmaceutical lead in the treatment of inflammation-related diseases including IBD.

Intravenous administration of L-tryptophan stimulates gastrointestinal hormones and melatonin secretions: study on beef cattle.

This study aimed to determine the effective dose of intravenous administration of L-tryptophan (L-T) on gastrointestinal hormones (GIH) secretions and melatonin using Hanwoo cattle. Three steers (362 ± 23 kg) fitted with indwelling jugular vein catheters were assigned in a 3 × 3 Latin square design. Treatments were intravenous administration of saline (control), 28.9 mg L-T/kg body weight (BW; low) and 57.8 mg L-T/kg BW (high) L-T for 1 day with 7 days of adaptation. Samples were collected after adaptation period at -60, 0, 30, 60, 90, 120, 150, 180, 240, and 300 min of sampling day. The levels of serum cholecystokinin (CCK) and secretin were higher (p < 0.05) in the high L-T group than those in the other groups. Serum Melatonin (MEL) levels were increased upon L-T administration (p < 0.05) in the high L-T group. Taken together, the effective dose of L-T administration was defined at 57.8 mg L-T/kg BW in order to stimulate increase of GIH and MEL.

Erratum to: Impacts of whey protein on starch digestion in rumen and small intestine of steers.

[This corrects the article DOI: 10.5187/jast.2019.61.2.98.].

Impacts of whey protein on starch digestion in rumen and small intestine of steers.

Four Korean native steers (511 ± 17.2 kg; 2 × 2 replicated crossover design) fitted with duodenal cannulas were used to investigate the influence of oral administration of soluble whey protein (WP; 82.29% crude protein) on ruminal fermentation, gastrointestinal (GI) hormone secretion in the blood, pancreatic α-amylase activity in the duodenum, and disappearance rate in each segment of the GI tract. Steers were orally fed the basal diet (control; TMR [total mixed ration] 9 kg/d) or the basal diet with enriched WP (400 g/d) for 14 days. The apparent crude protein disappearance rate in the rumen of the WP was higher than in control (p < 0.05). However, no difference between groups was observed in the apparent crude protein disappearance rate in the intestine and the apparent starch disappearance rates in the rumen, GI tract. The level of cholecystokinin, secretin, and ghrelin in serum and pancreatic α-amylase activity in the duodenum of the WP also did not change. The changes in the level of blood urea nitrogen related to protein metabolism were higher in the WP than in the control (p < 0.05). However, the levels of total protein, lipid, carbohydrate and mineral metabolites did not change. Consequently, we suggest that the oral administration of WP in steers assisted in ruminal fermentation due to the population increase of microbes in the rumen but did not improve the starch digestion rate in the small intestine because GI hormone secretion in the blood and pancreatic α-amylase activity did not change.

Optical phase-locking of two extended-cavity diode lasers by serrodyne modulation.

We report the optical phase-locking of two extended-cavity diode lasers with a frequency difference of 6.9 GHz by serrodyne modulation. The bandwidth of the phase-locking loop is extended up to 9.5 MHz. The residual phase noise of the two phase-locked lasers reaches -130 dBrad2/Hz in the offset frequency range of 1.5 kHz to 9 kHz and below -120 dBrad2/Hz in the range of 150 Hz to 350 kHz, respectively. It is expected that the sensitivity limit of atom interferometers will be enhanced when the phase-locked lasers are used.

Relative Configurational Assignment of 4-Hydroxyprorocentrolide and Prorocentrolide C Isolated from a Benthic Dinoflagellate ( Prorocentrum lima).

Herein, we clarify the structure and relative configurations of two prorocentrolide analogues (1 and 2) isolated from the benthic marine dinoflagellate Prorocentrum lima. The results of NMR spectroscopy show that 1 is prorocentrolide substituted by a hydroxy group at C-4, while the newly isolated compound 2 can be thought of as 1 lacking one ether ring and having one extra double bond. The relative configurations of all stereogenic centers and the configurations of the double bonds in 1 and 2 were determined utilizing ROESY correlations and J-based configuration analysis. Furthermore, 2 was shown to exhibit cytotoxicity against HCT-116 and Neuro-2a cells (IC50 2.2 and 5.2 µM, respectively.

Limaol: A Polyketide from the Benthic Marine Dinoflagellate Prorocentrum lima.

Limaol (1), along with a dinophysistoxin 1 derivative and an okadaic acid (OA) derivative, was isolated from the large-scale cultivation of the benthic marine dinoflagellate Prorocentrum lima. The structure of 1 was determined by a combination of NMR spectroscopy and mass spectrometry and contained tetrahydropyran, 1,3,5,7-tetra(methylene)heptane, and octahydrospiro[pyran-2,2'-pyrano[3,2-b]pyran] moieties. The absolute configuration of 1 was completely elucidated on the basis of ROESY correlations, J-based configuration analysis, and modified Mosher's ester analysis. Limaol showed moderate cytotoxicity when compared to OA against three cancer cell lines.