Pebbles and sand on asteroid (162173) Ryugu: In situ observation and particles returned to Earth.

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.

Inhibitory effects of triterpenoids and sterols on human immunodeficiency virus-1 reverse transcriptase.

Fifty-five triterpenoids consisting of 19 tetracyclic, 32 pentacyclic, and 4 incompletely cyclized triterpenoids, and 2 sterols, mostly isolated from various plant and fungal materials, were examined for their inhibitory effects on a purified human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. Twenty triterpenoids and one sterol showed inhibitory effects with 50% inhibition concentration (IC50) values less than 5.0 microM. Among these cycloartenol ferulate (IC50 = 2.2 microM), 24-methylenecycloartanol ferulate (1.9 microM), lupenone (2.1 microM), betulin diacetate (1.4 microM), and karounidiol 29-benzoate (2.2 microM) inhibited most effectively. Some of the triterpenoids and sterols may be potential new lead compounds to find still more potent HIV-1 reverse transcriptase inhibitors.

Lowered entrainment function in the suprachiasmatic nucleus of Otsuka Long Evans Tokushima Fatty (OLETF) rats.

The entrainment function in the suprachiasmatic nucleus (SCN) of young non-diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats was studied. OLETF rats significantly needed more days for re-entrainment to a new light-dark cycle than control Long Evans Tokushima Otsuka (LETO) rats. We also assessed Fos expression in the SCN induced by dim light exposure. The number of Fos-immunoreactive cells was significantly decreased in 5- to 13-week-old OLETF rats compared with LETO rats. Moreover, the effect of glutamate on neuronal activity in the SCN of OLETF rats were investigated. In young non-diabetic OLETF rats, the phase delay in the SCN neuronal firing rhythm induced by 1 microM glutamate was significantly less than that in LETO rats. These results suggested that the entrainment function is reduced in OLETF rats before the onset of diabetes.

Involvement of glutamate release in substance P-induced phase delays of suprachiasmatic neuron activity rhythm in vitro.

The suprachiasmatic nucleus (SCN) has been identified as a mammalian circadian rhythm clock. Treatment with substance P (SP) at zeitgeber time 13-14 produced phase delays of circadian rhythm in spontaneous neural activity in SCN neurons in vitro. SP-induced phase delays are blocked by treatment with not only SP receptor antagonist, spantide, but N-methyl-D-aspartate receptor antagonist, MK-801. In the biochemical experiment, we demonstrated that SP-induced glutamate release from the SCN slices was observed by the high-performance liquid chromatography assay. The present results suggest that glutamate release may be involved in SP-induced phase delays.

Coexpression of cholesterol sulfate and cytokeratin as tumor markers in well-differentiated squamous cell carcinoma of the human uterine cervix.

The expression of cholesterol sulfate (CS) is known to increase during squamous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the subsequent expression of transglutaminase-1 (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumorigenesis by CS, we examined the concentration and the potential for synthesis of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established from human uterine cervical cancer patients and compared them for the rate of expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expressed in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, cells derived from a keratinizing type of well-differentiated cervical carcinoma demonstrated strong potential for synthesis of CS, stained positive with anti-cytokeratin antibody, and exhibited a higher specific activity of TG-1, whereas the cells without CS did not stain positive with anti-cytokeratin antibody and exhibited a lower specific activity of TG-1. These findings indicate that CS is coexpressed with TG-1 and cytokeratin in the well-differentiated types of squamous cell cancers as a tumor marker.

Sasanquol, a 3,4-seco-triterpene alcohol from sasanqua oil, and its anti-inflammatory effect.

A novel 3,4-seco-triterpene alcohol, named sasanquol, was isolated from the non-saponifiable lipid of sasanqua oil from the seeds of Camellia sasanqua. Its structure was established to be 3,4-seco-D:B-friedobacchara-4,21-dien-3-ol by spectroscopic methods. This is the first example of naturally occurring triterpene with a D:B-friedobaccharane skeleton. The 50% inhibitory dose of this compound against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation (1 microgram per ear) in mice was 0.4 mg per ear.

A T cell activation antigen, Ly6C, induced on CD4+ Th1 cells mediates an inhibitory signal for secretion of IL-2 and proliferation in peripheral immune responses.

A T cell activation antigen, Ly6C, is considered to be involved in the autoimmunity of some autoimmune-prone mice; however, the function of Ly6C remains largely unknown. We prepared a rat anti-mouse Ly6C monoclonal antibody (mAb) (S14) that inhibits the proliferation of peripheral T cells stimulated with anti-CD3 mAb in vitro. S14 mAb, the specificity of which is confirmed by a cDNA transfectant, recognizes Ly6C antigen preferentially expressed on a part of CD8+ T cells in peripheral lymphoid organs. The immunohistochemical analysis demonstrates that Ly6C appears on CD8+ T cells in the conventional T cell-associated area of BALB/c but not of nonobese diabetic (NOD) mice, confirming the absence of Ly6C+ T cells in NOD mice. Addition of soluble S14 mAb to the culture does not influence the proliferation of T cells in vitro; however, the S14 mAb coated on the plate clearly inhibits the proliferation and IL-2 production of anti-CD3-stimulated peripheral T cells. The T cells are arrested at the transitional stage from G0/G1 to S+G2/M phases, but they are not induced to undergo apoptotic changes in vitro. This inhibitory signal provided through the Ly6C molecule inhibited IL-2 secretion in a subpopulation of the activated CD4+ T cells. Ly6C is expressed on T cell clones of both Th1 and Th2 cells, but the cytokine secretion from Th1 clones is preferentially inhibited. These results suggest that Ly6C mediates an inhibitory signal for secretion of cytokines from Th1 CD4+ T cells, potentially causing the inhibition of immune response in peripheral lymphoid tissues.

In vitro release of tranilast from oily gels and penetration of the drug into Yucatan micropig skin.

For the transdermal delivery of tranilast (TL), a drug used for the treatment of skin diseases such as keloids and hypertrophic scars, its oily gels were prepared; its in vitro release and penetration into Yucatan micropig skin were evaluated. In the gels that consisted of hydrogenated soybean phospholipids (HSL) and octyl isononanoate (IOIN), a fatty-acid ester, the release of TL from the gels was proportional to the drug content, and the extent of TL released up to 6 h from them was approximately 70% of the amount of applied TL. On the other hand, with the gels consisting of HSL and isocetyl isostearate (ICIS), the release of TL from the gels was about half of that from IOIN gels, even at the same drug concentration. When oily gels were used, the TL skin concentration was rapidly increased compared with the level obtained with suspensions. With 0.1% IOIN gel, a high concentration of TL (ca. 160 microg/g) in the dermis was obtained and continued until at least 48 h. These results suggest that oily gels may be useful for the topical application of TL.

A patient-like orthotopic implantation nude mouse model of highly metastatic human ovarian cancer.

Clinically relevant animal models of human cancer are important for studies of cancer biology, invasion and metastasis, and for investigating new forms of prognostic diagnosis and therapy. An ovarian tumor line (RMG-1: human clear cell carcinoma of the ovary) previously grown subcutaneously was implanted orthotopically as intact tissue into the ovarian capsule of 22 nude mice. The tumors showed progressive growth at the orthotopic site in all animals. Tumor-associated serum galactosyltransferase (GAT) tended to be positive in all nude -mice. The tumors invaded or metastasized to the contralateral ovary, retroperitoneum, mesentery and peritoneum, and omentum, and metastasized to the subcutaneous tissue, lymph nodes and distant organs including the liver, kidney, pancreas, and diaphragm. In striking contrast, subcutaneous transplantation of this tumor resulted in growth in only 2 of 5 animals with local lymph node and kidney involvement but no retroperitoneal or peritoneal involvement. These findings suggest that orthotopic implantation provides a suitable micro-environment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the clinical features of ovarian cancer and is thought to be a useful model for studies of therapy for this cancer.

Inhibitory effect of heliantriol C; a component of edible Chrysanthemum, on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Two hydroxy taraxastane-type triterpenes, faradiol and heliantriol C, have been isolated from the ligulate flowers of Chrysanthemum morifolium Ramat. var. sinense Makino fa. esculentum Makino, the edible Chrysanthemum. These compounds showed strong inhibitory activity against 12-O-tetradecanoyl-phorbol-13-aetate (TPA)-induced inflammation in mice. At 0.2 µmol/mouse, these compounds markedly inhibited the promoting effect of TPA (1 µg/mouse) on skin tumor formation followed by 7,12-dimethylbenz[a]anthracene (50 µg/mouse).

Decreased level of light-induced Fos expression in the suprachiasmatic nucleus of diabetic rats.

We assessed light-induced Fos-immunoreactive cells in the suprachiasmatic nucleus of diabetic rats. The number of Fos-immunoreactive cells significantly decreased in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats as compared with control Long-Evans Tokushima Otsuka (LETO) rats. In contrast there was no decrease in the number of Fos-immunoreactive cells in young OLETF rats which have not yet developed diabetes. Two months after the administration of streptozotocin (STZ) to Wistar rats, the number of Fos-immunoreactive cells significantly decreased, although 1 week after the administration of STZ, the number had not yet changed in these STZ-induced diabetic rats. These results suggest that chronic diabetic (hyperglycemic) conditions may affect the light entraining responses in the suprachiasmatic nucleus (SCN).

Evaluation of Yucatan micropig skin for use as an in vitro model for skin permeation study.

Skin permeation rates of five non-steroidal anti-inflammatory drugs, three of them lipophilic (ibuprofen, indomethacin and ketoprofen) and two hydrophilic (sodium diclofenac and antipyrine), through Yucatan hairless micropig (YMP) full-thickness skin were determined in vitro using Franz-type diffusion cells, and the usefulness of YMP skin as an animal model skin was investigated. Five-month-old YMP skin showed small variation with respect to drug permeation rates, if the region of skin site was the same. But skin from 6-month-old YMPs showed faster and varied permeation rates due to skin defects. In the case of hydrophilic drugs, no effects on permeation due to the region from which the skin was obtained were observed, although higher permeation rates were observed through the flank than through dorsal skin in the case of ibuprofen and ketoprofen. For YMP skin, the permeation coefficients of drugs were lower than those for hairless rat skin, especially for hydrophilic drugs. Compared with reported human data on permeation coefficients, the permeation coefficients of drugs through YMP skin were 1/2-1/8 of those through human skin, regardless of whether the drugs were hydrophilic or lipophilic. YMP skin could be used as an in vitro animal skin model because of the reproducibility of the permeation rate of drugs through this skin and its similarity to human skin.

Triterpene alcohols from camellia and sasanqua oils and their anti-inflammatory effects.

The nonsaponifiable lipids of camellia and sasanqua oils from the seeds of Camellia japonica L. and C. sasanqua THUNB., respectively, were investigated for their triterpene alcohol constituents. This led to the isolation of twenty-seven triterpene alcohols of which seven were novel naturally occurring compounds, tirucalla-5,7,24-trien-3 beta-ol (1), lemmaphylla-7,21-dien-3 beta-ol (2), isoeuphol (3), isotirucallol (4), (24R)-24,25-epoxybutyrospermol (5) and its 24S-epimer (6), and isoaglaiol (7). The structures were determined by spectroscopic and chemical methods. The inhibitory effects of 3, 4 a mixture of 5 and 6, a mixture of 7 and its 24S-epimer (aglaiol), and eight known triterpene alcohols isolated in this study were evaluated in ear inflammation in mice induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The 50% inhibitory dose of these triterpenes for TPA-induced inflammation (1 microgram per ear) was 0.2-0.9 mg/ear.

Triterpene alcohols from the flowers of compositae and their anti-inflammatory effects.

Eleven tabular and nine ligulate flowers from 15 species of Compositae plants were investigated for their triterpene alcohol constituents. This led to the isolation and identification of 11 triterpene alcohols as follows: heliaol, taraxasterol, psi-taraxasterol, alpha-amyrin, beta-amyrin, lupeol, taraxerol, cycloartenol, 24-methyl-enecycloartanol, tirucalla-7,24-dienol and dammaradienol. The tabular flowers of Calendula officinalis, Carthamus tinctorius, Cosmos bipinnatus, Chrysanthemum morifolium, Helianthus annuus and Matricaria matricarioides showed a characteristic feature by containing helianol as the most predominant component (29-86%) in the triterpene alcohol fractions. The triterpene alcohols from Compositae flowers were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation (1 microgram per ear) in mice. All of these showed marked inhibitory activity, and their 50% inhibitory dose was 0.1-0.8 mg per ear.

Involvement of 5-HT1A receptor mechanisms in the inhibitory effects of methamphetamine on photic responses in the rodent suprachiasmatic nucleus.

We examined the role of serotonin 1A (5-HT1A) receptors in the inhibitory effects of methamphetamine (MA) on photic entrainment to the circadian pacemaker in the suprachiasmatic nucleus (SCN) of rodents. MA inhibited optic nerve stimulation-evoked field potential in the SCN, light-induced Fos expression in the SCN and light-induced phase shift of hamster wheel-running rhythm. NAN-190, a 5-HT1A receptor antagonist, eliminated the inhibitory effects of MA. NAN-190 has also been reported to antagonize alpha 1 adrenergic receptors. However, prazosin, which selectively antagonizes alpha 1 adrenergic receptors, did not affect the inhibitory action of MA on light-induced Fos expression. In addition, parachloroamphetamine, which is known to be a 5-HT releaser, dose-dependently inhibited light-induced phase shift of wheel-running rhythm. These findings suggest that elevation of endogenous 5-HT levels by MA inhibits the photic entraining responses of the circadian pacemaker in the SCN via 5-HT1A receptor stimulation of the 5-HT released by MA.

Inhibitory effect of Di- and trihydroxy triterpenes from the flowers of compositae on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation in mice.

Ten dihydroxy- and trihydroxy triterpenes, viz., four taraxastanes: faradiol, heliantriol B0, heliantriol C and arnidiol; two lupanes: calenduladiol and heliantriol B2; two oleananes: maniladiol and longispinogenin; and two ursanes: brein and uvaol, isolated from the nonsaponifiable lipids of the flower extracts of Compositae plants were evaluated with respect to their anti-inflammatory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. All the triterpenes were found to possess marked inhibitory activity. The 50% inhibitory dose of these compounds with respect to TPA-inflammation (1 microgram) was 0.03-0.2 mg/ear.

Inhibitory effect of taraxastane-type triterpenes on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

Two taraxastane-type hydroxy triterpenes, taraxasterol and faradiol, isolated from the flowers of Compositae plants Cynara scolymus (artichoke) and Chrysanthemum morifilolium (chrysanthemum), respectively, showed strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. At 2.0 mumol/mouse, these compounds inhibited markedly the tumor-promoting effect of TPA (1 microgram/mouse) on skin tumor formation following initiation with 7,12-dimethylbenz[alpha]anthracene (50 micrograms/mouse).

Inhibitory effect of oral administration of Monascus pigment on tumor promotion in two-stage carcinogenesis in mouse skin.

Monascus pigment was extracted from red malted rice, Monascus anka. It has been used as coloring matter for foodstuffs in Japan and certain Asian countries. Oral administration of Monascus pigment suppressed the tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in mice following initiation by 7,12-dimethylbenz[a]anthracene.

[An autopsy case of fungal (Mucor) cerebral aneurysm].

An autopsy of rupture of Mucor cerebral aneurysm, not diagnosed during the patient's life, was experienced. A 63-year-old female was admitted to our hospital with the chief complaint of disturbance of consciousness and high fever. Her past histories were diabetes mellitus, liver cirrhosis and nasal sinusitis. The remarkable findings on admission were moderate inflammatory data, high blood sugar level in serum and ascites. Brain CT film revealed a non-enhanced low-density area in the frontal region. The cerebrospinal fluid showed bloody color and white blood cell counts were 3300/microliter (mostly neutrophils). Under our suspected of bacterial encephalomeningitis, intravenous cefotaxime and ampicillin therapy was started immediately. Cultures of cerebrospinal fluid for bacteria were negative. The disturbance of her consciousness gradually improved under general treatment. However, her conscious level suddenly became a coma on the 6th hospital day and she died on the 9th hospital day. An autopsy revealed Mucor at the site of the rupture of the cerebral aneurysm.

Some lupane-type triterpenes inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

We have found that several lupane-type triterpenes, including lupeol, its acetate, betulin and betulinic acid, inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, and that betulinic acid inhibits tumor promotion in two-stage carcinogenesis in mice. Among seven lupane-type triterpenes assayed, these compounds inhibited the inflammatory activity induced by TPA in mice. The 50 % inhibitory dose of these compounds for TPA-induced inflammation was 0.4-4.0 µmol. Furthermore, topical application of lupeol, lupeol 3-acetate and betulin markedly suppressed the tumor-promoting effect of TPA (1 µg/mouse) in mouse skin initiated with 7,12-dimethyl-benz[a]anthracene (50 µg/mouse), at a grade corresponding to that of betulinic acid.