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Substances that enhance the migration of mesenchymal stem cells to damaged sites have the potential to improve the effectiveness of tissue repair. We previously found that ethanol extracts of Mallotus philippinensis bark promoted migration of mesenchymal stem cells and improved wound healing in a mouse model. We also demonstrated that bark extracts contain cinnamtannin B-1, a flavonoid with in vitro migratory activity against mesenchymal stem cells. However, the in vivo effects of cinnamtannin B-1 on the migration of mesenchymal stem cells and underlying mechanism of this action remain unknown. Therefore, we examined the effects of cinnamtannin B-1 on in vivo migration of mesenchymal stem cells and wound healing in mice. In addition, we characterized cinnamtannin B-1-induced migration of mesenchymal stem cells pharmacologically and structurally. The mobilization of endogenous mesenchymal stem cells into the blood circulation was enhanced in cinnamtannin B-1-treated mice as shown by flow cytometric analysis of peripheral blood cells. Whole animal imaging analysis using luciferase-expressing mesenchymal stem cells as a tracer revealed that cinnamtannin B-1 increased the homing of mesenchymal stem cells to wounds and accelerated healing in a diabetic mouse model. Additionally, the cinnamtannin B-1-induced migration of mesenchymal stem cells was pharmacologically susceptible to inhibitors of phosphatidylinositol 3-kinase, phospholipase C, lipoxygenase, and purines. Furthermore, biflavonoids with similar structural features to cinnamtannin B-1 also augmented the migration of mesenchymal stem cells by similar pharmacological mechanisms. These results demonstrate that cinnamtannin B-1 promoted mesenchymal stem cell migration in vivo and improved wound healing in mice. Furthermore, the results reveal that cinnamtannin B-1-induced migration of mesenchymal stem cells may be mediated by specific signaling pathways, and the flavonoid skeleton may be relevant to its effects on mesenchymal stem cell migration.

Two new species of Mallotus (Euphorbiaceae), M. ninhthuanensis V.S.Dang, Bao ＆ Tagane sp. nov. and M. vinhhyensis V.S.Dang, Tagane ＆ Tk.Yamam. sp. nov. from Nui Chua National Park in Ninh Thuan Province, south-central Vietnam, are described and illustrated. Information on their distribution, habitat and ecology, phenology, and vernacular names is provided. Based on the available data, two new species are assigned to Endangered (EN) according to Guidelines for Using IUCN Red List Categories and Criteria.

Capelin are a focal forage species in the Northwest Atlantic ecosystem as they act as an energy conduit from lower to higher trophic levels. Fisheries and Oceans Canada determined that the Newfoundland capelin stock (Northwest Atlantic Fisheries Organization Divisions 2J3KL) suffered an order of magnitude decline in biomass in 1990–1991. This collapse was concomitant with drastic changes observed in the ecosystem during the late 1980s and early 1990s. While the results of more than a dozen studies have supported the capelin stock collapse hypothesis, an alternative non-collapse hypothesis proposed that rather than collapsing in 1990–1991, the capelin stock either (1) changed its migratory patterns while the timing of the spring capelin acoustic survey remained constant, leading to a spatio-temporal mismatch between the spring acoustic survey and the stock, or (2) became less migratory and remained inshore year-round, therefore being largely underestimated by the offshore spring and fall acoustic surveys. The collapse and non-collapse hypotheses were tested using multiple independent data sets, which included both fishery-dependent (inshore commercial catch) and fishery-independent (spring and fall acoustic and fall bottom-trawl surveys, capelin larval indices, aerial surveys, predator diet and behavior) data, and diverse statistical methods. The weight of evidence approach led us to reject the non-collapse hypothesis and conclude that the Newfoundland capelin stock did collapse in 1990–1991 with minimal recovery over the subsequent 3 decades.

Extrafloral nectary (EFN)-bearing plants attract ants to gain protection against herbivores. Some EFN-bearing plants possess different types of EFNs, which might have different effects on ants on the plants. Mallotus japonicus (Thunb.) Muell. Arg. (Euphorbiaceae) bears two types of EFNs, including a pair of large EFNs at the leaf base and many small EFNs along the leaf edge. This study aimed to determine the different roles of the two types of EFNs in biotic defense by ants. A field experiment was conducted to investigate the effect of leaf damage on EFN production and on the distribution pattern of ants. After leaf damage, the number of leaf edge EFNs increased in the leaves first-produced. The number of ants on the leaves also increased, and the foraging area of ants extended from the leaf base to the leaf tip. An EFN-covering field experiment revealed that leaf edge EFNs had a greater effect than leaf base EFNs on ant dispersal on leaves. The extended foraging area of ants resulted in an increase of encounter or attack rate against an experimentally placed herbivore, Spodoptera litura. These results suggest that M. japonicus plants control the foraging area of ants on their leaves using different types of EFNs in response to leaf damage, thus achieving a very effective biotic defense against herbivores by ants.

Node and internode explants of Mallotus repandus were precultured on basal medium (BM: Murashige and Skoog (MS) medium with 3 sucrose and 0.55 Agargel) for 0– 18 d before culture on shoot induction Medium (SIM: BM added with 4.44 μ M of benzylaminopurine) for 4 wk. The cultures were subsequently transferred to BM for 4 wk for shoot elongation. Node explants precultured on BM for 14 d before incubation on SIM were at an optimum for shoot regeneration with the response rate of 95 , compared to a 21 response for the control without preculture. Internode explants precultured on BM for 16 d responded with an optimal shoot formation response rate of 69 , whereas the control response rate was 6 . The maximum shoot regeneration rates were 3.1± 0.3 and 2.7± 0.4 shoots/responding explant in node and internode explants, respectively. This study demonstrates for the first time that shoot organogenesis can be induced from internode explants of M. repandus. Furthermore, the results suggest that the explants need to acquire competence before shoot organogenesis. Rooting was obtained by incubation of regenerated shoots on half-strength MS with 10.74 μ M of 1-naphthylacetic acid for a week before culture on half-strength MS for 4 wk. Regenerated plants were successfully transferred to soil.

Node and internode explants of Mallotus repandus were precultured on basal medium (BM: Murashige and Skoog (MS) medium with 3% sucrose and 0.55% Agargel) for 0-18 d before culture on shoot induction Medium (SIM: BM added with 4.44 mu M of benzylaminopurine) for 4 wk. The cultures were subsequently transferred to BM for 4 wk for shoot elongation. Node explants precultured on BM for 14 d before incubation on SIM were at an optimum for shoot regeneration with the response rate of 95%, compared to a 21% response for the control without preculture. Internode explants precultured on BM for 16 d responded with an optimal shoot formation response rate of 69%, whereas the control response rate was 6%. The maximum shoot regeneration rates were 3.1 plus or minus 0.3 and 2.7 plus or minus 0.4 shoots/responding explant in node and internode explants, respectively. This study demonstrates for the first time that shoot organogenesis can be induced from internode explants of M. repandus. Furthermore, the results suggest that the explants need to acquire competence before shoot organogenesis. Rooting was obtained by incubation of regenerated shoots on half-strength MS with 10.74 mu M of 1-naphthylacetic acid for a week before culture on half-strength MS for 4 wk. Regenerated plants were successfully transferred to soil.

Mallotus furetianus is traditionally used as folk medicine on Hainan Island, China. Given the significance of the pharmacokinetic interaction between herbs and drugs, we investigated the effects of Mallotus furetianus ethanol extract (MFE) on CYP3A activity in rats. The major bioactive constituents of MFE, gallic acid (GA) and epigallocatechin gallate (EGCG), were analyzed by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) for MFE standardization. Rats were orally administered 320 mg/10mL/kg MFE or water (control) once a day for 7 days. Two hours after the last MFE treatment, the rats were euthanized, and the livers and small intestines were excised. The activity of CYP3A was measured in hepatic and intestinal microsomes, and the expression in hepatic and intestinal tissues was assessed by qRT-PCR and western blot. In the pharmacokinetics experiment, rats were administered MFE as described above. Two hours after the final dose of MFE, a 15 mg/kg midazolam solution was orally administered. Blood samples were collected before and after midazolam administration. Midazolam plasma concentration and 1-hydroxymidazolam formation in microsomes were measured by LC-MS/MS methods.CYP3A activity in hepatic microsomes exhibited a significant decrease in MFE treatment group, while no change was observed in intestinal microsomes. MFE treatment significantly increased CYP3A1 activity, as well as mRNA and protein expression in the small intestine but reduced these parameters in the liver. However, CYP3A2 remained unaffected by MFE treatment. Pharmacokinetics study showed that administration of MFE for 7 days significantly reduced the Cmax of midazolam from 919 ± 70 ng / mL to 708 ± 91 ng /mL. Conversely, t1/2 was increased from 0.45 ± 0.08 h in the control group to 0.69 ± 0.15 h in the MFE group.Collectively, our study indicated that MFE could modulate CYP3A1 activity and expression of CYP3A1, subsequently changing the metabolism of midazolam in rats.

Accumulation of advanced glycation end products (AGEs) plays an important role in diabetes, immunoinflammation, and cardiovascular and neurodegenerative diseases. Since AGEs mediate their pathological effects through interaction with receptor for AGEs (RAGE), RAGE antagonists would provide a useful therapeutic option for various health disorders. Therefore, in this study, we aimed to identify phytochemicals that would inhibit binding of AGEs to RAGE, which may help develop new drug leads and/or nutraceuticals for AGE–RAGE-related diseases. On screening ethanol extracts obtained from 700 plant materials collected in Myanmar, we found that the ethanol extract from the leaves of Mallotus philippensis inhibited the binding of AGEs to RAGE. We also found that the leaves of M. japonicus , which belongs to the same genera and distributes abundantly in Japan, exhibited the inhibitory activity similar to M. philippensis. Activity-guided fractionation and LC/MS analysis of the ethanol extract of M. japonicus helped identify pheophorbide a (PPBa) as a major component in the active fraction, along with some other pheophorbide derivatives. PPBa exhibited potent inhibitory activity against AGE–RAGE binding, with an IC 50 value (0.102 μM) comparable to that of dalteparin (0.084 μM). PPBa may be a valuable natural product for use as a therapeutic agent and/or a nutraceutical against various health complications arising from activation of the AGE–RAGE axis.

Using histology to examine ovarian structures in Pacific capelin for the first time, we found biological evidence that captive, age‐1, female Pacific capelin Mallotus catervarius are capable of iteroparity (41% of mature females). Evidence of the potential to spawn over multiple years included more than one oocyte cohort, including primary growth and vitellogenic oocytes in maturing fish, or primary growth and post ovulatory follicles in spent fish.The data on iteroparity rates provide a better understanding of how fish might respond to variable or extreme environments, as a population with mixed or flexible parities may have more flexibility in spawning frequency, reproductive output, and survival.

Mallotus paniculatus (Lam.), a member of the Euphorbiaceae Juss family, is a little tree or shrub that has long been used in folk medicine to cure ailments like fever, wound healing, and postpartum recuperation. In this study, Swiss albino mice were used to evaluate the analgesic, antipyretic, and antidiarrheal properties of the acetone extract of M. paniculatus (AMP). Standard screening techniques were used to identify the phytochemical ingredients. Three models were used to evaluate analgesic activity: the tail immersion test, formalin‐induced paw licking, and acetic acid–induced writhing. Antipyretic activity was assessed using a fever model induced by brewer′s yeast. At the same time, antidiarrheal effects were evaluated by castor oil–induced diarrhea, and gastrointestinal motility was studied using a charcoal meal marker. Furthermore, in silico analyses—such as molecular docking, ADME profiling, toxicity prediction, and PASS analysis—were conducted using online tools. The results indicated that AMP at a lower dose (200 mg/kg) produced significant analgesic effects across all pain models compared with the control group. In the antipyretic evaluation, AMP administered at 400 mg/kg illustrated the most pronounced reduction in body temperature after 4 h, which was statistically significant ( p < 0.01). The same higher dose (400 mg/kg) also significantly reduced diarrheal episodes and slowed gastrointestinal motility in both the castor oil–induced diarrhea and charcoal meal transit tests. Molecular docking analysis further corroborated these pharmacological effects, revealing that AMP compounds exhibited strong binding affinity toward key target receptors associated with pain, inflammation, and gastrointestinal activity. Collectively, these results indicate that AMP has promising potential as a natural multitarget therapeutic agent for the treatment of pain, fever, and diarrhea.