Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity

Journal of Natural Medicines - Pulsatilla species are known as “Yargui”, and their flowers are traditionally used in Mongolia as a tonic and for the treatment of inflammatory diseases....     

Lactose-riched Mongolian mare's milk improves physical fatigue and exercise performance in mice

Fatigue may cause the efficiency of the organ in human body to decrease, which may affect the daily life and exercise performance of the general people and athletes. Mare''s milk powder (MMP) is a lactose rich supplement. The research of the study is to evaluate the whether MMP has anti-fatigue effect. Forty male ICR mice were randomly divided into four group to receive vehicle or MMP by oral gavage at 0 (Vehicle), 0.27 (MMP-1X), 0.54 (MMP-2X), 1.35 (MMP-5X) g/kg/day for 14 days. The forelimb grip of the MMP-2X, and MMP-5X group were significantly higher than the vehicle group. The swim-to-exhaustion times of the MMP-1X, MMP-2X, and MMP-5X group were significantly greater than the vehicle group. Glycogen levels in liver and muscle were significantly larger in the MMP-1X, MMP-2X, and MMP-5X groups than the vehicle group. Receive MMP supplement for 14 days can promoting exercise performance and amelioration of exercise-induced fatigue.     

Novel chemoembolization using calcium‐phosphate ceramic microsphere incorporating TNP‐470, an anti‐angiogenic agent

The purpose of the present study was to develop a new method of chemoembolization to improve the therapeutic effectiveness and safety profile of cancer treatment. A chemoembolization approach was designed for human solid tumors using resorbable calcium‐phosphate ceramic microspheres loaded with an agent anti‐angiogenic to tumor vasculature in vivo. The human uterine sarcoma cell line FU‐MMT‐3 was used in this study because this tumor is aggressive and also exhibits a poor response to radiotherapy or any chemotherapy currently used. The calcium‐phosphate ceramic microspheres loaded with TNP‐470, an anti‐angiogenic agent, were injected into FU‐MMT‐3 xenografts in nude mice three times per week for 8 weeks. The treatment using TNP‐470‐loaded microspheres suppressed tumor growth, compared to treatment with TNP‐470 alone, microspheres alone, and the control. The mean tumor weight after treatment using TNP‐470‐loaded microspheres was significantly lower than that after treatment with microspheres alone. These ceramic microspheres were remarkably embolized in tumor microvessels as well as in the feeding arteries and a significant reduction of intratumoral vascularity was also demonstrated following treatment with TNP‐470‐loaded microspheres. Severe loss of body weight was not observed in any mice treated with the TNP‐470‐loaded microspheres, compared to treatment with TNP‐470 alone. These results suggest that targeting tumor vasculature in human uterine sarcoma using calcium‐phosphate microspheres might be more effective and safer than the treatment that employs anti‐angiogenic agent alone. This new chemoembolization method incorporating an anti‐angiogenic agent may contribute to the effective treatment of locally advanced or recurrent solid tumors. (Cancer Sci 2010; 101: 984–990)     

Timing outweighs magnitude of rainfall in shaping population dynamics of a small mammal species in steppe grassland

Climate change–induced shifts in species phenology differ widely across trophic levels, which may lead to consumer–resource mismatches with cascading population and ecosystem consequences. Here, we examined the effects of different rainfall patterns (i.e., timing and amount) on the phenological asynchrony of population of a generalist herbivore and their food sources in semiarid steppe grassland in Inner Mongolia. We conducted a 10-y (2010 to 2019) rainfall manipulation experiment in 12 0.48-ha field enclosures and found that moderate rainfall increases during the early rather than late growing season advanced the timing of peak reproduction and drove marked increases in population size through increasing the biomass of preferred plant species. By contrast, greatly increased rainfall produced no further increases in vole population growth due to the potential negative effect of the flooding of burrows. The increases in vole population size were more coupled with increased reproduction of overwintered voles and increased body mass of young-of-year than with better survival. Our results provide experimental evidence for the fitness consequences of phenological mismatches at the population level and highlight the importance of rainfall timing on the population dynamics of small herbivores in the steppe grassland environment.

The Earth is facing a great challenge from accelerated climate change. The global surface air temperature has increased by about 1° during the past century and is projected to exceed 1.5 to 2 °C by the end of the 21st century (1). Climate change has caused profound impacts on the Earth’s ecosystems, such as local extinctions (2), range shifts (3), and population fluctuations (4, 5) of many species. Many organisms have advanced the timing of phenological events in response to climate warming, such as earlier leaf-out in plants, earlier emergence of insects, or accelerated egg hatching dates for birds (6). For consumers, phenological events are timed to match peak food resources for breeding; however, the direction of consumer’s phenological response to climate change may differ from the response of species occupying lower trophic levels, leading to asynchrony between resources and consumers (7, 8). With respect to climate change, numerous studies have focused on the impact of temperature and its role in driving phenological asynchrony (9–11) since this is especially critical for species population dynamics and ecosystem functioning. However, relatively little is known about how rainfall mediates asynchrony between resources and consumers and its potential demographic consequences, especially in arid environments.Shifts in rainfall patterns have been greatly affected by climate warming (12) and play a key role in regulating vertebrate population dynamics (13), the species composition of communities, and ecosystem functions and services (14). Both the timing and the amount of rainfall are recognized as distinct but major components that synergistically influence the timing of vegetation phenology, e.g., the timing of plant germination and seed ripening (15, 16). However, it remains unclear whether changes in the timing or the amount of rainfall play the more dominant role in the processes of phenological asynchrony between interacting species despite their distinct effects on aboveground annual net primary productivity (17). It is therefore important to disentangle the independent effects of rainfall timing and amount if we are to predict responses of species’ populations and ecosystems to global climate change.Among small herbivores, rainfall is well recognized to induce a bottom-up increase in abundance via increasing food availability, as observed in Phyllotis darwini and Octodon degus in South America (18, 19), Pseudomys hermannsburgensis and Mus domesticus in Australia (20, 21), Spermophilus dauricus (22) and Cricetulus barabensis (23) in East Asia, Dipodomys merriami in North America (24), and Mastomys natalensis in Africa (25). However, these observations are all based on the correlation between rodent abundance and precipitation; the mechanism underlying the bottom-up effects of precipitation on rodents through plant productivity is often assumed but has been rarely investigated by manipulative experiments. While valuable in their own right, most previous studies have been unable to elucidate fully the role of rainfall as a potential proximate cue in regulating phenology. In natural environments, many biotic factors (e.g., predation and interspecific competition) and abiotic factors (e.g., flooding of burrows) may interact to influence how phenological processes can affect population dynamics. To understand the effects of rainfall on the role of phenological asynchrony in the population dynamics of target species, including the effects of rainfall amount and timing, it is therefore necessary to exclude or control for confounding factors. Conducting more tightly controlled manipulative experiments is a requirement when assessing the fitness consequences of phenological asynchrony (6, 7), although it is very challenging for small rodents owing to the need for large field enclosures that prevent immigration/emigration of individuals and impacts by predators.We conducted a 10-y, large-scale, manipulative experiment to examine the bottom-up effects of changes in rainfall regime (including timing and amount; SI Appendix, Fig. S1) on the phenological asynchrony between plants and herbivores, demographic parameters, and population dynamics of Brandt’s voles Lasiopodomys brandtii. In our study region in Inner Mongolia, an increase in annual rainfall, especially during the early growing season, can markedly enhance annual net primary productivity (26), with more rain increasing the biomass of rye grass Leymus chinensis (27, 28), a major and favored food source for Brandt’s voles (29). Additional rainfall in the early growing season can provide a match between the peak food resources and peak food requirements of young voles. Therefore, we hypothesized that rainfall would change the population density of voles by mediating the timing and peak amount of preferred foods and that rainfall timing (in the early growing season) would be of vital importance in triggering population increases, or outbreaks, of voles in arid steppe grassland.     

CD133+ cancer stem cell-like cells derived from uterine carcinosarcoma (malignant mixed Müllerian tumor)

Cancer stem cells (CSCs) that display tumor-initiating properties have recently been identified. CD133, a surface glycoprotein linked to organ-specific stem cells, has been described as a marker of CSCs in different tumor types. We herein identify and characterize CSCs in human uterine carcinosarcoma (malignant mixed Müllerian tumor), which is one of the most aggressive and therapy-resistant gynecological malignancies and is considered to be of mesodermal origin. The CD133(+) population was increased in uterine carcinosarcoma, and this population showed biphasic properties in the primary tumor. CD133(+) cells predominantly formed spheres in culture and were able to differentiate into mesenchymal lineages. CD133(+) cells were more resistant to cisplatin/paclitaxel-induced cytotoxicity in comparison with CD133(-) cells. A real-time polymerase chain reaction analysis of the genes implicated in stem cell maintenance revealed that CD133(+) cells express significantly higher levels of Oct4, Nanog, Sox2, and Bmi1 than CD133(-) cells. Moreover, CD133(+) cells showed a high expression level of Pax2 and Wnt4, which are genes essential for Müllerian duct formation. These CD133(+) cells form serially transplantable tumors in vivo and the resulting CD133(+) tumors replicated the EpCAM, vimentin, and estrogen and progesterone receptor expression of the parent tumor, indicating that CSCs likely differentiated into cells comprising the uterine carcinosarcoma tissue. Moreover, strong CD133 expression in both epithelial and mesenchymal elements in primary tumor demonstrated significant prognostic value. These findings suggest that CD133(+) cells have the characteristics of CSCs and Müllerian mesenchymal progenitors.     

Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities

Two new xanthone glycosides, corymbiferin 3-O-beta-D-glucopyranoside (1) and swertiabisxanthone-I 8'-O-beta- d-glucopyranoside (2), were isolated from Gentianella amarella ssp. acuta, along with eight known xanthones: triptexanthoside C, veratriloside, corymbiferin 1-O-glucoside, swertianolin, norswertianolin, swertiabisxanthone-I, bellidin, and bellidifolin, four of them identified for the first time in G. amarella ssp. acuta. The isolation was conducted mainly by centrifugal partition chromatography, and the structures of the isolated compounds were established on the basis of spectrometric data including 2D NMR and mass spectrometry. Xanthones were weakly active against acetylcholinesterase (AChE), except triptexanthoside C, which inhibited AChE with an IC(50) of 13.8 +/- 1.6 microM. Some compounds were active against monoamine oxidases (MAO): bellidin and bellidifolin showed interesting inhibitory activity of MAO A, while swertianolin, the 8-O-glucopyranoside form of bellidifolin, gave 93.6% inhibition of MAO B activity at 10(-5) M.     

Metronomic irinotecan chemotherapy combined with ultrasound irradiation for a human uterine sarcoma xenograft

Metronomic chemotherapy is the frequent administration of low doses of chemotherapeutic agents targeting tumor-associated endothelial cells. We examined the efficacy of metronomic irinotecan combined with low-intensity ultrasound (US) in human uterine sarcoma and evaluated its antiangiogenesis mechanism by measuring the circulating endothelial progenitor cells (CEP), a surrogate marker of angiogenesis. A human uterine sarcoma cell line, FU-MMT-3, was used in the present study because this tumor is one of the most malignant neoplasms of human solid tumors and it also has a high angiogenesis property. The combination of low-dose irinotecan and US irradiation significantly inhibited the tube formation of HUVEC and vascular endothelial growth factor expression of tumor cells in vitro. The FU-MMT-3 xenografts in nude mice were treated using US at a low intensity (2.0 w/cm(2), 1 MHz) for 4 min three times per week each after the intraperitoneal administration of irinotecan; this treatment was continued for 5 weeks. The tumor vascularity was assessed by contrast-enhanced color Doppler US in real time. The combination treatment significantly inhibited the mobilization of CEP and intratumoral vascularity compared with the control. This combination therapy showed a significant reduction in tumor volume, resulting in a significant prolongation of survival, in comparison with each treatment alone. These results suggest that the effect of metronomic chemotherapy for human uterine sarcoma was accelerated by US irradiation in vivo and this combination might therefore be potentially effective for new cancer therapy.     

11-Acetyl-1,19-epoxydenudatine: A New Alkaloid from Aconitum barbatum

A new diterpenoid alkaloid was isolated from the overground parts of ACONITUM BARBATUM Pers. (Ranuncluaceae). Its structure was elucidated by spectroscopic methods as 11-acetyl-1,19-epoxydenudatine.     

Metronomic doxifluridine chemotherapy combined with the anti-angiogenic agent TNP-470 inhibits the growth of human uterine carcinosarcoma xenografts

Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Metronomic chemotherapy is accepted as a new approach for cancer treatment, and its underlying mechanism seems to involve the suppression of angiogenesis. However, the efficacy of metronomic and anti-angiogenic therapies against uterine carcinosarcoma is unknown. The anti-angiogenic effect of doxifluridine was assessed in vitro using human umbilical vein endothelial cells (HUVEC) co-cultured with FU-MMT-1 human uterine carcinosarcoma cells. The antitumor and anti-angiogenic effects of metronomic doxifluridine (delivered via oral gavage) in combination with TNP-470 were evaluated in vivo. Tumor vascularity was assessed by contrast-enhanced color Doppler ultrasound, laser Doppler and microvessel density staining. Doxifluridine suppressed tube formation of HUVEC and vascular endothelial growth factor production by FU-MMT-1 cells. Metronomic doxifluridine alone significantly suppressed tumor growth compared with the untreated (control) group, while metronomic doxifluridine in combination with TNP-470 significantly inhibited tumor growth compared with each treatment alone. A significant reduction of intratumoral vascularity was observed in FU-MMT-1 xenografts following treatment with metronomic doxifluridine in combination with TNP-470, as compared with each treatment alone. Intestinal bleeding was only observed when the maximum tolerated dose of doxifluridine was administered in combination with TNP-470. Metronomic doxifluridine chemotherapy in combination with TNP-470 might be effective for uterine carcinosarcoma without marked toxicity, possibly acting via its potent anti-angiogenic effects. Clinical studies are needed to evaluate the safety and efficacy of this treatment in humans.