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Natural products are primal and have been a driver in the evolution of organic chemistry and ultimately in science. The chemical structures obtained from marine organisms are diverse, reflecting biodiversity of genes, species and ecosystems. Biodiversity is an extraordinary feature of life and provides benefits to humanity while promoting the importance of environment conservation. This review covers the literature on marine natural products (MNPs) discovered in Indonesian waters published from January 1970 to December 2017, and includes 732 original MNPs, 4 structures isolated for the first time but known to be synthetic entities, 34 structural revisions, 9 artifacts, and 4 proposed MNPs. Indonesian MNPs were found in 270 papers from 94 species, 106 genera, 64 families, 32 orders, 14 classes, 10 phyla, and 5 kingdoms. The emphasis is placed on the structures of organic molecules (original and revised), relevant biological activities, structure elucidation, chemical ecology aspects, biosynthesis, and bioorganic studies. Through the synthesis of past and future data, huge and partly undescribed biodiversity of marine tropical invertebrates and their importance for crucial societal benefits should greatly be appreciated.

Pathological hyperpermeability is a morbidity involved in various systemic diseases, including sepsis. The endothelial glycocalyx layer (GCX) plays a key role in controlling vascular permeability and could be a useful therapeutic target. The purpose of the present study was to analyze the functional role of the GCX in vascular permeability and to elucidate its role in pathological conditions. First, male C57BL/6J wild-type mice were used as in vivo models to study the effects of sepsis and the pharmacological digestion of glycosaminoglycans (GAGs) on the GCX. Vascular permeability was evaluated using fluorescein isothiocyanate (FITC)-labeled dextran. Second, the changes in gene expression in vascular endothelial cells after GAGs digestion were compared between a control and a septic model using RNA sequencing. In the in vivo study, the glycocalyx was depleted in both the septic model and the group with pharmacological GAGs digestion. FITC-labeled dextran had leaked into the interstitium in the septic group, but not in the other groups. In the in vitro study, histamine decreased the transendothelial electrical resistance (TEER), indicating an increase in permeability. GAGs digestion alone did not change the TEER, and the effect of histamine on the TEER was not enhanced by GAGs digestion. The gene expression profiles after GAGs digestion differed from the control condition, indicating the initiation of signal transduction. In conclusion, we demonstrated that the structural barrier of the GCX does not solely determine the fluid permeability of the endothelial layer, since enzymatic depletion of the GCX did not increase the permeability. The gene expression findings suggest that the digestion of GAGs alone did not induce hyperpermeability either in vitro or in vivo , although sepsis did induce hyperpermeability. While GAGs degradation by itself does not appear to induce hyperpermeability, it may play an important role in initiating signal transductions.

Organoids generated from pluripotent stem cells are used in the development of organ replacement regenerative therapy by recapitulating the process of organogenesis. These processes are strictly regulated by morphogen signalling and transcriptional networks. However, the precise transcription factors involved in the organogenesis of exocrine glands, including salivary glands, remain unknown. Here, we identify a specific combination of two transcription factors (Sox9 and Foxc1) responsible for the differentiation of mouse embryonic stem cell-derived oral ectoderm into the salivary gland rudiment in an organoid culture system. Following orthotopic transplantation into mice whose salivary glands had been removed, the induced salivary gland rudiment not only showed a similar morphology and gene expression profile to those of the embryonic salivary gland rudiment of normal mice but also exhibited characteristics of mature salivary glands, including saliva secretion. This study suggests that exocrine glands can be induced from pluripotent stem cells for organ replacement regenerative therapy. Functional salivary glands have not been generated from embryonic stem cells (mESCs) to date. Here the authors demonstrate directed in vitro differentiation of mESCs to oral ectoderm and salivary gland rudiments that form mature, functional salivary glands after orthotopic transplantation.

Okichromanone ( 1 ), a new chromanone, was isolated from the culture extract of a sponge-derived actinomycete Microbispora , along with known 1-hydroxyphenazine ( 2 ). Compound 1 was elucidated to exist as a mixture of two isomeric structures ( 1a and 1b ) at a ratio of nearly 3:2. Compounds 1 and 2 showed anti HSV-I activity with IC 50 values 40 and 86 μM, respectively, and anti HSV-II activity with IC 50 values 59 and 123 μM, respectively.

Salivary glands act as virus reservoirs in various infectious diseases and have been reported to be targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms underlying infection and replication in salivary glands are still enigmatic due to the lack of proper in vitro models. Here, we show that human induced salivary glands (hiSGs) generated from human induced pluripotent stem cells can be infected with SARS-CoV-2. The hiSGs exhibit properties similar to those of embryonic salivary glands and are a valuable tool for the functional analysis of genes during development. Orthotopically transplanted hiSGs can be engrafted at a recipient site in mice and show a mature phenotype. In addition, we confirm SARS-CoV-2 infection and replication in hiSGs. SARS-CoV-2 derived from saliva in asymptomatic individuals may participate in the spread of the virus. hiSGs may be a promising model for investigating the role of salivary glands as a virus reservoir. Tanaka et al. generate human induced pluripotent stem cell-derived salivary gland organoids that serve as a model for salivary gland development and SARS-CoV-2 infection.

The junctional epithelium (JE) is an epithelial component that attaches directly to the tooth surface and performs the unique function of protecting against bacterial infections; its destruction causes inflammation of the periodontal tissue and loss of alveolar bone. A recent study that used the single-color lineage tracing method reported that JE is maintained by its stem cells. However, the process by which individual stem cells form the entire JE around a whole tooth remains unclear. Using a 4-color lineage tracing method, we performed a detailed examination of the dynamics of individual stem cells that constitute the entire JE. The multicolor lineage tracing method showed that single-color areas, which were derived from each cell color, replaced all the constituent JE cells 168 d after the administration of tamoxifen. The horizontal section of the first molar showed that the single-color areas in the JE expanded widely. We detected putative stem cells at the external basal layer farthest from the enamel. In this study, JE cells that were supplied from different stem cells were visualized as individual monochromatic regions, and the JE around the first molar was maintained by several JE-specific stem cells. These findings indicated that the JE consisted of several cell populations that were supplied from their multiple stem cells and could help to explore the mechanisms involved in periodontal tissue homeostasis.

A new, rare trinor-dolabellane diterpenoid, sangiangol A (1), and one new dolabellane diterpenoid, sangiangol B (2), together with known cembranes and dolabellanes (3–8), were isolated from the ethyl acetate layer of an extract of an Indonesian marine soft coral, Anthelia sp. Compounds 1–8 exhibited moderate cytotoxicity against an NBT-T2 cell line (0.5–10 µg/mL). The structures of the new compounds were determined by analyzing their spectra and a molecular modelling study. A possible biosynthetic pathway for sangiangols A (1) and B (2) is presented. Cytotoxicity requires two epoxide rings or a chlorine atom, as in 4 (stolonidiol) and 5 (clavinflol B).

In Japan, high-yielding indica rice cultivars such as ‘Habataki’, ‘Takanari’, and ‘Hokuriku 193’ have been bred, and many genes related to the high-yield traits have been isolated from these and other indica cultivars. Many such genes are expected to be effective in increasing the yield of japonica rice, including those that increase sink size. It has been expected that high-yielding japonica rice could be bred by introducing sink-size genes into the genetic background of japonica cultivars such as ‘Koshihikari’, which show strong cold tolerance, have good taste characteristics, and fetch a high price. However, the corresponding near-isogenic lines did not necessarily produce high yields when tested in the field. In this review, we summarize information on the major high-yield-related rice genes and discuss pyramiding strategies to further increase the yield of japonica rice. In parallel with increasing sink size, source capacity needs to be increased by increasing photosynthetic rate per unit leaf area (single leaf photosynthesis), improving canopy structure, and increasing translocation capacity during the ripening stage. To implement these strategies, innovative breeding methodologies that efficiently produce the combinations of desired alleles are required.

Myoepithelial (ME) cells in exocrine glands exhibit both epithelial and mesenchymal features, contributing to fluid secretion through contraction. However, the regulation mechanism of behind this unique phenotype in salivary glands remains unclear. We established a flow cytometry-based purification method using cell surface molecules, epithelial cell adhesion molecule (EpCAM) and alpha 6 integrin (CD49f), to characterize ME cells. EpCAM+CD49fhigh cells showed relatively high expression of ME cell-marker genes, such as alpha-smooth muscle actin (α-SMA). For lineage tracing and strict isolation, tdTomato+EpCAM+CD49fhigh-ME cells were obtained from myosin heavy chain 11 (Myh11) -CreERT2/tdTomato mice. Transcriptome analysis revealed that expression of genes involved in the epithelial-mesenchymal transition, including Snai2, were upregulated in the ME cell-enriched subset. Snai2 suppression in stable ME cells decreased α-SMA and increased Krt14 expression, suggesting that ME cell features may be controlled by the epithelial-mesenchymal balance regulated by Snai2. In contrast, ME cells showed reduced ME properties and expressed the ductal markers Krt18/19 under sphere culture conditions. Notch signaling was activated under sphere culture conditions; excessive activation of Notch signaling accelerated Krt18/19 expression, but reduced α-SMA and Snai2 expression, suggesting that the behavior of Snai2-expressing ME cells may be controlled by Notch signaling.

The present study was carried out to clarify the role of noradrenergic systems in the mediation of drinking response to angiotensin II (ANG II) in the rat subfornical organ (SFO). Microinjection of ANG II (10 pmol, 50 nl) into the SFO caused a robust drinking response (water volume, 1.8–8.7 ml for 20 min). Injections of either noradrenaline (NA; 0.1, 1 and 10 nmols, 50 nl) into the SFO did not produce a significant water intake. Phenylephrine (Phen; 0.1, 1, 10 nmols, 50 nl), an α 1 -adrenoceptor agonist, injected into the SFO elicited little drinking in the rats tested (water volume, 0.4–1.5 ml for 20 min). Previous injections of NA (0.1 and 1 nmols) or Phen (0.1, 1 and 10 nmols) significantly enhanced the water intake elicited by the injection of ANG II into the SFO. Neither the α 2 -adrenoceptor agonist clonidine (Clon; 10 nmol, 50 nl) nor the β-adrenoceptor agonist isoprenaline (Isop; 10 nmol, 50 nl) into the SFO caused a significant water intake. Previous injections of Clon (0.1, 1 and 10 nmol, 50 nl) into the SFO were without effect on the water intake produced by the ANG II injection into the SFO. Pretreatment with Isop (1 and 10 nmols), on the other hand, significantly attenuated the drinking response to ANG II. Vehicle (artificial cerebrospinal fluid, 50 nl) had no effect on the ANG II-induced water intake. These results suggest that both α1-(facilitatory) and β-(inhibitory) adrenoceptor mechanisms may be implicated in the control of drinking response induced by angiotensinergic activation of SFO neurons.