HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

O-GlcNAc of STING mediates antiviral innate immunity.

BACKGROUND: O-GlcNAcylation modification affects multiple physiological and pathophysiolocal functions of cells. Altered O-GlcNAcylation was reported to participate in antivirus response. Stimulator of interferon genes (STING) is an adaptor mediating DNA virus-induced innate immune response. Whether STING is able to be modified by O-GlcNAcylation and how O-GlcNAcylation affects STING-mediated anti-DNA virus response remain unknown. METHODS: Metabolomics analysis was used for detecting metabolic alterations in HSV-1 infection cells. Succinylated wheat germ agglutinin (sWGA), co-immunoprecipitation, and pull-down assay were employed for determining O-GlcNAcylation. Mutagenesis PCR was applied for the generation of STING mutants. WT and Sting1-/- C57BL/6 mice (KOCMP-72512-Sting1-B6NVA) were infected with HSV-1 and treated with O-GlcNAcylation inhibitor for validating the role of STING O-GlcNAcylation in antiviral response. RESULTS: STING was functionally activated by O-GlcNAcylation in host cells challenged with HSV-1. We demonstrated that this signaling event was initiated by virus infection-enhanced hexosamine biosynthesis pathway (HBP). HSV-1 (or viral DNA mimics) promotes glucose metabolism of host cells with a marked increase in HBP, which provides donor glucosamine for O-GlcNAcylation. STING was O-GlcNAcylated on threonine 229, which led to lysine 63-linked ubiquitination of STING and activation of antiviral immune responses. Mutation of STING T229 to alanine abrogated STING activation and reduced HSV-1 stimulated production of interferon (IFN). Application of 6-diazo-5-oxonorleucine (DON), an agent that blocks the production of UDP-GlcNAc and inhibits O-GlcNAcylation, markedly attenuated the removal of HSV-1 in wild type C57BL/6 mice, leading to an increased viral retention, elevated infiltration of inflammatory cells, and worsened tissue damages to those displayed in STING gene knockout mice. Together, our data suggest that STING is O-GlcNAcylated in HSV-1, which is crucial for an effective antiviral innate immune response. CONCLUSION: HSV-1 infection activates the generation of UDP-Glc-NAc by upregulating the HBP metabolism. Elevated UDP-Glc-NAc promotes the O-GlcNAcylation of STING, which mediates the anti-viral function of STING. Targeting O-GlcNAcylation of STING could be a useful strategy for antiviral innate immunity.

Navigation-Guided Nasal Endoscopy to Remove the Cavernous Venous Malformation of the Orbital Apex Through the Sphenoid Approach.

OBJECTIVE: To explore the feasibility of navigation-guided sinus endoscopy to remove the cavernous vascular malformation of the orbital apex through the sphenoid approach. METHODS: A retrospective series of non-control cases were collected. From May 2012 to December 2019, patients with imaging findings of cavernous venous malformation in the orbital apex were collected at the Eye Hospital Affiliated to Nanchang University. All patients underwent navigation guided sinusoscopy through the sphenoid approach to remove the cavernous venous malformation of the orbital apex. Analyze the changes of visual function and postoperative complications before and after operation. RESULTS: Twelve patients were collected, including 3 males and 9 females aged between 32 and 59. In 3 patients without visual impairment, the postoperative visual function was still normal. The remaining 9 patients all had visual impairment. Among them, 3 patients had fully recovered normal visual function after operation, 2 patients had improved visual function compared with preoperative, and 4 patients had no change in postoperative visual acuity. There were no complications in 3 of the 12 patients, and 9 patients had transient limited intraocular rotation with mild limitation of diplopia after operation, and all returned to normal within 1 month after surgery. CONCLUSION: Navigation-guided sinus endoscopy through the sphenoid approach to remove the cavernous venous malformation of the orbital apex is an effective and feasible surgical method.

[Study on biological characteristics: reproduction and viability of Biomphalaria glabrata as an intermediate host of Schistosoma mansoni].

OBJECTIVE: To compare the difference of fertility of Biomphalaria glabrata snails between self-fertilization and cross-fertilization and to observe the circadian rhythm of laying eggs, the effect of light on laying eggs and the tolerance of the snail to water and food deficiency, so as to provide the evidence for control and elimination of B. glabrata snails in the field. METHODS: Under laboratory conditions, a single B. glabrata egg for self-fertilization was separated and hatched individually, and young snails were raised in different plastic boxes individually. The eggs for cross-fertilization were hatched and the young snails were fed in the same plastic box. The ability of spawn, the development of the eggs, and the number of snails growing from young to adult snails were compared between the self-fertilization and cross-fertilization. The snails were in the water under four environments, all day illumination, all day without illumination, daytime lighting and night without illumination, and daytime without illumination but night lighting. The eggs were collected and counted daily. The circadian rhythm of spawn and the effect of illumination on spawn were observed. The adult snails were divided into 6 groups and exposed to the environments with relative humidity of 0, 65%, 87% and 100%, respectively. The survival rates of the adult snails exposed to the different environments after different time were observed. The adult snails were placed at 25 °C in the oven to remove water content from the soft body of snails. When the dehydration rates of the soft bodies achieved 10%, 20%, 30%, 40%, 50%, 52%, 55%, 57%, 60%, and 70% respectively, the survival rates of the adult snails exposed to the oven were observed. RESULTS: In the 25 °C water, the average laying egg number for 15 days per snail was (8.77 ± 16.92) eggs/snail in the self-fertilization snail. The average laying egg number for 15 days per snail was (149.71 ± 142.28) eggs/snail in the cross-fertilization snails. There was a significant difference between the self-fertilization snail and cross-fertilization snail (t = 0.999 999, P < 0.01). The hatching rate and reproductive maturation rate of the self-fertilization snails and cross-fertilization snails were 50.1% and 78.9%, and 19.3% and 3.8%, respectively, There was a significant difference (the hatching rate: χ2 = 18.18, P < 0.01, the reproductive maturation rate: χ2 = 11.83, P < 0.01) . In the natural environment of daytime with illumination and nighttime with darkness, the amount of laying 20 eggs of B. glabrata snail was (944.07 ± 392.53) eggs/day during a whole day, among them the amount of laying eggs during daytime account for 10.1% and the amount of laying eggs during nighttime account for 89.9%, and the laying egg was given priority to with the night. The above results suggested that the dark environment was conducive to B. glabrata snails to lay eggs. The above results suggested that light can promote the increase of spawning of B. glabrata. When B. glabrata was exposed to the environments with the relative humidity of 0, 65%, 87% and 100% at 25 °C, respectively, and the longest survival times of snails were 7, 70, 150 d and 100 d, respectively. In the 25 °C water, the snails could survive for 50 days without food. The adult snails were placed at 25 °C in the oven to remove water content from the soft body of snails. When the dehydration rates of the soft bodies achieved 10%, 20%, 30%, 40%, 50%, 52%, 55%, 57%, 60%, and 70% respectively, the survival rates of the adult snails exposed to the oven were 100%, 100%, 100%, 100%, 70%, 30%, 0, 0, 0 and 0, respectively. CONCLUSIONS: B. glabrata can achieve the reproductive process by cross-fertilization or self-fertilization. There is a significant difference in reproductive ability between the cross-fertilization snail and self-fertilization snail, cross-fertilization is stronger than self-fertilization, but the rate of reproduction in the self-fertilization is higher than that in the cross-fertilization. It is indicated that B. glabrata that survive after the dry season plays an important role in the maintenance of local snail populations and transmission of schistosomiasis mansoni.

[Interspecific hybridization of Schistosoma and its significance].

Schistosomiasis is one of zoonoses (diseases that are naturally transmitted between vertebrate animals and human),and it is widespread in tropical and sub-tropical regions. It is one of the important infectious diseases that the World Health Organization plans to eliminate. Hybridization within Genus Schistosoma is an emerging public health concern in our changing world.Schistosoma spp. are dioecious trematode, in which there are lots of species infecting human and animals. Several schistosome species also overlap in their geographical and host range, which allows male and female schistosomes of different species to pair within their definitive hosts. The hybridization among different species and the production of dominant hybrid species and changes of their biological characteristics, such as host selectivity, fertility and infectivity, can lead to the evolution of schistosoma species, regional distribution of the population, the changes of epidemic patterns, and pathogenicity to human and animals, and all of them have an impact on the global schistosomiasis elimination plan.

[Studies on colonization risk and potential geographical distribution of Biomphalaria glabrata as an intermediate host of Schistosoma mansoni in Mainland China].

OBJECTIVE: To predict the colonization risk and potential geographical distribution of Biomphalaria glabrata in the Mainland China based on the past period temperature data. METHODS: The survival extreme high temperatures and low temperatures of B. glabrata eggs, young and adult B. glabrata snails and the average effective accumulated temperature of generation development were determined in laboratory conditions. The temperature data in January and July from 1955 to 2010 were collected from the national meteorological monitoring sites in the southern part of China, including Chongqing, Zhejiang, Yunnan, Sichuan, Jiangxi, Hunan, Hainan, Guizhou, Guangdong, Guangxi and Fujian provinces (11 provinces). A database of ambient temperature related to B. glabrata was established based on the Geographic Information System (GIS). The colonization risk and potential geographical distribution of B. glabrata in the southern part of China were analyzed and predicted by ArcGIS 10.1 software. RESULTS: The half lethal low temperatures of B. glabrata eggs, young and adult B. glabrata snails were 6.80, 6.34 ℃ and 6.60 ℃ respectively; the half lethal high temperatures of B. glabrata eggs, young and adult B. glabrata snails were 35.99, 33.59 ℃ and 32.20 ℃, respectively. The developmental threshold temperature was 7.16 ℃; the average effective accumulated temperature of generation development was (1 970.07 ± 455.10) days-degree. The GIS overlay analysis of the half lethal low and high temperatures of B. glabrata showed that the local temperature conditions in all Hainan and part regions in Yunnan, Guangxi, Guangdong and Fujian were conformed to the survival temperature of B. glabrata snails. The regions, where the average effective accumulated temperature was more than the average effective accumulated temperature of generation development of B. glabrata, were Guangdong and Hainan, and part regions of other 9 provinces. The overlay analysis of GIS maps of the survival extreme high temperatures and low temperatures of B. glabrata with the GIS map of the average effective accumulated temperature of generation development in 2010 showed that the whole region of Hainan and part regions of Guangdong, Guangxi, Yunnan and Fujian were potential geographical distribution regions of colonization risk of B. glabrata. The overlay analysis of GIS maps of the survival extreme high temperatures and low temperatures of B. glabrata with the GIS map of the average effective accumulated temperature of generation development from 1955 to 2010 showed that the potential geographical distribution regions of B. glabrata was expanding from the whole region of Hainan and part regions of Guangdong in 1955 to the whole region of Hainan and part regions of Guangdong, Guangxi, Yunnan and Fujian in 2010. CONCLUSIONS: If B. glabrata snails were introduced into the Mainland China, the potential geographical distribution regions would be the whole region of Hainan and part regions of Guangdong, Guangxi and Yunnan. The changes of risk range and risk intensity present the trends of expanding and increasing from the south to the north gradually.

Sesamin Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibition of TLR4 Signaling Pathways.

Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1ß production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways.

[Role of goat in transmission of schistosomiasis japonica III Effect of temperature and humidity on survival of eggs in goat feces and egg survival in natural environments].

OBJECTIVE: To investigate the survival of Schistosoma japonicum eggs in goat feces in natural marshlands and the factors affecting its survival, so as to provide evidences for understanding of the role of eggs in goat feces in the transmission of schistosomiasis and the development of the interventions pertaining to disease control and elimination. METHODS: The goat animals of schistosomiasis japonica were modeled in laboratory, and the feces of infected goat were collected. In laboratory, the effects of environmental temperature and water content in goat feces on egg hatching were evaluated, and in the field, the effect of duration of goat feces on marshland on egg hatching and the effect of direct sunshine on egg survival were evaluated. RESULTS: At 25°C in laboratory, the hatching rate of eggs in goat feces washigh-positively correlated with the water content in goat feces (r = 0.87). If the water content reduced to 7.6% in goat feces, the eggs in goat feces lost the ability to hatch. Under the same water content in goat feces, the hatching rate of eggs gradually decreased with the extension of the duration of exposure of goat feces to -5 °C, which reduced to 0 following 5 h exposure. At 5, 15 and 25 °C, the hatching rates of eggs gradually decreased with the extension of the duration of exposure of goat feces, and themiracidium hatching ratesof eggs were 2.3%, 5% and 0.9% respectively following the exposure for 52 d. At 35°C, the hatching rate of eggs gradually decreased with the extension of the duration of exposure, which reduced to 0 following 13 d exposure. In winter (-2-10 °C), the hatching rate of eggs gradually decreased with the extension of the duration of exposure of goat feces on marshlands, which reduced to 0 after 21 d of exposure, and in spring (16-19 °C), the hatching rate of eggs gradually decreased with the extension of the duration of exposure of goat feces on marshlands, which reduced to 0.9% after 5 d of exposure. At the same time point on the same marshland, the hatching rate of eggs in goat feces exposed to marshlands with direct sunshine was lower than that without direct sunshine. CONCLUSIONS: The survival of S. japonicum eggs in goat feces is associated with environmental temperature and water content (humidity) in goat feces, and the temperature and humidity are major natural factors affecting egg hatching.

[Role of goat in transmission of schistosomiasis japonica III Environmental contamination by goat feces and prediction of environments at high risk of S. japonicum infection].

OBJECTIVE: To quantitatively estimate the range and area of environmental contamination by the feces of Schistosoma japonicum-infected that were freely grazed, so as to provide the theoretical evidence for the scientific assessment of the role of the freely grazed goat in the transmission of schistosomiasis japonica and development of control strategy. METHODS: All the fecal samples excreted by the infected goat at daytime (12 h) were collected by using a self-made goat fecal collector, weighed and counted. The quantity and dispersal of the feces excreted by the freely grazed goat at daytime under a natural condition were investigated, and the walking route and speed of the freely grazed goat at daytime were recorded with a multifunction GPS data logger. The maximum range and area of the environment contaminated by the feces of the freely grazed goat at daytime were estimated, and the maximum range and area of the Oncomelania hupensis snails that may be infected by the schistosome miracidium released from the eggs in the fecal samples of the freely graze goat at daytime were calculated. RESULTS: During the walking along the marshland at daytime (12 h), the quantity of the feces execrated by the freely grazed infected goat was (232.8 ± 39.8) g per goat, and the fecal samples were composed of (819.2 ± 152.1) pellets. The goat had a mean walking speed of (0.522 7 ± 0.099 7) km/h, and the longest distance, largest radius and largest range of walking activity were (6.272 4 ± 1.195 8) km, 3.136 2 km and (3 191.113 0 ± 1 189.709 4) hm2 at daytime, respectively. The area of the snails that may be infected by the miracidium released from the eggs in the fecal samples of the freely graze goat (range of key regions for infected snails detection and control) at daytime was estimated to be (3 210.717 5 ± 1 190.907 3) hm2. CONCLUSIONS: The intensity of environmental contamination by the eggs in the fecal samples of the freely grazed goat is linked to the number of infected goat. The contamination range caused by the feces of the freely grazed goat with fixed fences is relatively stably kept within the walking range at day-time, and the range and area of goat fecal contamination is associated with the number of households that breed goat and the distribution of goat fence. The area of the snails that may be infected by the miracidium released from the eggs in the fecal samples of the freely graze goat is larger than the area of setting contaminated by the eggs in the goat feces, indicating that the range of infected snail examination and control is larger than the range of goat feces detected.

[Role of goat in transmission of schistosomiasis japonica III Development of goat feces collector and optimization of fecal hatching technique].

OBJECTIVE: To develop a simple, feasible goat feces collector to improve the collection accuracy and integrity of goat fecal samples without pollution, and to modify the miracidium hatching test with a plastic tube to achieve simple, standard and comparative procedures, so as to provide technical support for pathogenic diagnosis and scientific research of goat schistosomiasis japonica. METHODS: According to the body features of goat in marshland regions, a goat fecal collector, which was made of coarse fabric cottons, was devised, which was able to be fixed onto the goat buttocks and avoid urine pollution. Prior to miracidium hatching test, the goat fecal samples were pieced by using a mechanical method instead of the conventional artificial piecing method, and the effect of mechanical piecing treatment on miracidium hatching was evaluated. A filter membrane was added between the tube and rubbery ring to block the floater in fecal residues into the tube. The effects on miracidium hatching by using thin fat-free cotton, thick fat-free cotton, nylon gauze at 100 pores/25.4 mm2 and 150 pores/25.4 mm2 were compared. RESULTS: The goat feces collector was composed of foreleg fixing garment, hindleg fixing garment and stool bag. The functions of the fixing garment were as a fixed collector to allow non-shift and tolerance of weight during goat activity, while the major function of stool bag was in storage of stool. The goat activity did not affect by the use of collector, and all fecal samples were excreted to the bag. This collector was easy to perform and could avoid urine pollution, which was reusable after cleaning. Prior to miracidium hatching, the goat fecal samples, together with water, were pieced at 18000 to 23000 r/min for successive three times in a cooking machine, of 10 s each time at an interval of 5 s. Mechanical piecing had no clear-cut effect on miracidium hatching of eggs in fecal samples. A total of 541, 620, 344 and 211 miracidia were detected by using the miracidium hatching test with nylon gauze at 100 pores/25.4 mm2 and 150 pores/25.4 mm2, thin fat-free cotton and thick fat-free cotton respectively, indicating a better detection efficacy by using nylon gauze at 100 pores/25.4 mm2 and 150 pores/25.4 mm2. CONCLUSIONS: The goat fecal collector is a easy-to-perform, accurate, unpolluted and reusable device to collect goat feces, which is suitable for pathogenic diagnosis of goat schistosomiasis. Mechanical piecing and use of nylon gauze at 150 pores/25.4 mm2 allow a simple, accurate and stable technique for parasitological diagnosis of schistosomiasis japonica, which provides a reliable tool for schistosomiasis control and research.

[Role of goat in transmission of schistosomiasis japonica â £ Schistosome development in goat and egg count and distribution in goat feces].

OBJECTIVE: To describe the growth and development of Schistosoma japonicum in goat and the intensity and temporal distribution of eggs excreted by goat feces, so as to provide baseline data for the control and elimination of the role of goat in the transmission of schistosomiasis. METHODS: The goat animal models of schistosomiasis were established, and stool samples were collected for parasitological examinations. The number of adult worms recovered, variation of schistosomes in goat at different time points post-infection, number of eggs in schistosomes, variation in number and temporal profiles of eggs excreted from goat feces were observed. RESULTS: Of the 6 schistosome-infected goat, 415 adult worms were recovered, with a mean adult worm recovery of 34.58% (range, 23.00% to 45.50%). Among the 5 goat infected with 200 cercariae each, 47, 93, 77, 74 and 73 adult worms were recovered 2, 5, 8, 11 and 14 months post-infection, respectively. There were (200.00±42.33), (226.20±45.88), (168.20±25.85), (183.80±55.13) and (190.80±53.53) eggs detected in female schistosomes. The mean prepatent period of eggs excreted by 10 infected goat was (37.7±3.02) d. From 2 to 14 months post-infection, 7 batches of goat feces were hatched, and there were 30, 23, 14, 1 and 2 times for miracidium intensity of "++++", "+++", "++", "+" and "-", respectively, with 42.86%, 32.86%, 20.00%, 1.43% and 2.86% constituent ratios of miracidium intensity. CONCLUSIONS: Approximately 1/3 S. japonicum cercariae may develop to adults in goats post-infection, and the prepatent period of eggs is (37.7±3.02) d. There is no remarkable decrease seen in the number of adult worms, eggs in female schistosomes and eggs in goat feces within 14 months post-infection. Our findings suggest a long duration for infected goat in the transmission of schistosomiasis, and there is no evidence to prove the "self-cure" phenomenon in goat, indicating that goat is an important source of infection for schistosomiasis japonica.

[Role of goat in transmission of schistosomiasis japonica IV Goat breeding in endemic regions and role of goat in schistosomiasis transmission].

This review describes the major species, number, breeding pattern, ratio of fenced to freely grazed goat, susceptibility to Schistosoma japonicum, pattern of S. japonicum infection, infection rate, intensity of infection, fecal contamination of goat that were bred in 5 marshland and lake provinces of Hunan, Hubei, Jiangxi, Anhui and Jiangsu, and two mountainous provinces of Yunnan and Sichuan, and demonstrates the associations of infected goat distribution with the distribution of infected Oncomelania hupensis snails and humans. Considering the huge number of goat which were predominantly grazed freely in marshland and lake endemic regions of China, the high infection rate, numerous environmental pollution by goat feces, as well as the close correlation between the infected goat distribution and infected snail distribution, goat is considered as a major infectious source for schistosomiasis japonica in China, and to play a critical role in the transmission of the disease. Since the control of schistosomiasis in animals is critical to schistosomiasis interruption and elimination, it is suggested that the integrated management of goat schistosomiasis should be included in the national schistosomiasis control program of China.

Changes in protein composition of epidermal mucus in turbot Scophthalmus maximus (L.) under high water temperature.

To explore the skin mucous of juvenile turbot (Scophthalmus maximus) protein under thermo-treatment in different temperatures (20, 23, 25, and 27 °C), the corresponding proteome maps were constructed by two-dimensional gel electrophoresis (2-DE), from which the peptide mass map with MALDI-TOF-TOF was obtained, and a novel protein of polypeptide was identified by database retrieval. Results show that the proteome maps varied remarkably with temperature, indicating the increase or decrease in protein spot. Totally, 209 protein spots were matched in five maps in temperature using ImageMaster 2D Platinum 6.0. In addition, six unique protein spots were selected and identified with MALDI-TOF-TOF. By searching database for protein identification and function prediction, five proteins were confirmed, of which lectin and cytokeratin are highly potential as protein marker for further research. The information should be useful for better understanding the role of mucus as a component of innate immune system and for identifying genotypes that suit best to the aquiculture environment. These proteins could be used as potential biomarkers to environmental stressors in mucus for providing early warning when fish suffers in a dangerous situation.

Protein expression of mesenchymal stem cells after transfection of pcDNA3.1⁻-hVEGF165 by ultrasound-targeted microbubble destruction.

Ultrasound-targeted microbubble destruction (UTMD) has been proposed as a new technique for organ-specific gene transfer and drug delivery. This study was performed to investigate the effect of UTMD on marrow mesenchymal stem cells (MSCs) transfected with pcDNA3.1⁻-hVEGF165.pcDNA3.1⁻-hVEGF165 were transfected into the third passage of MSCs, with or without UTMD under different ultrasound conditions. Protein expression was quantified by hVEGF165-ELISA kit after transfection for 24, 48, and 72 hours. UTMD-mediated transfection of MSCs yielded a significant protein expression. UTMD of mechanic index (MI) 0.6 for 90 seconds led to the highest level of protein expression.

PTK-pathways and TGF-beta signaling pathways in schistosomes.

Schistosome parasites have co-evolved an intricate relationship with their human and snail hosts as well as a novel interplay between the adult male and female parasites. Drug-induced suppression of female schistosome sexual maturation is an auspicious strategy to combat schistosomiasis since the eggs are the causative agent. Studies on signaling in schistosomes opens a new era for investigation of host-parasite and male-female interactions. We review the role of the TGF-beta signaling pathway in parasite development, host-parasite interactions and male-female interactions. This review also summarizes recent studies suggesting tyrosine kinases as important factors for the regulation of female gonad development. In this context, cytoplasmatic tyrosine kinases of the Src class seem to play especially dominant roles. Moreover, experimental data and theoretical concepts are provided supporting a crosstalk between tyrosine kinase and TGF-beta signaling in the production of vitellocytes. Finally, we take advantage of the schistosome genome project to propose a model for the regulation of vitelline-cell production and differentiation.

The influence of St John's Wort on CYP2C19 activity with respect to genotype.

Induction of cytochrome p450 isozymes is the major cause for clinical drug interactions of St. John's wort. The relationships of St. John's wort to cytochrome p450 isoforms have been fully investigated, but its effect on CYP2C19 is lacking. Thus, the aim of the present study was to observe the effect of St. John's wort on CYP2C19 activity using CYP1A2 as a control. Twelve healthy adult men-6 extensive metabolizers of CYP2C19 (2C19(*)1/2C19(*)1) and 6 poor metabolizers (4 2C19(*)2/2C19(*)2 and 2 2C19(*)2/2C19(*)3)-were enrolled in a two-phase, randomized, crossover manner. All subjects took a 300-mg St. John's wort tablet or placebo three times daily for 14 days, and then the activities of CYP2C19 and CYP1A2 were measured using mephenytoin and caffeine. It was found that St. John's wort treatment significantly increased CYP2C19 activity in CYP2C19 wild-genotype subjects, with urinary 4'-hydroxymephenytoin excretion raised by 151.5% +/- 91.9% (p = 0.0156), whereas no significant alteration was observed for CYP2C19 poor metabolizers. Repeated St. John's wort administration did not affect the CYP1A2 phenotypic ratio for both CYP2C19 genotype subjects. In conclusion, St. John's wort is an inducer to the human CYP2C19, and clinicians should pay great attention when St. John's wort is added to or withdrawn from an existing drug regimen containing substrates for such enzymes.

[Effect of N, P, K on rhizome yield and diosgenin content of Dioscorea zingiberensis].

OBJECTIVE: A field experiment was conducted to investigate the different effects of various applying ratios of nitrogen (N), potassium (K) and phosphate (P) on diosgenin content and Rhizoma yield of Dioscorea zingiberensis. METHOD: Experiment was conducted with both one factor and orthogonal design, and data was analyzed statistically on SPSS 11. 5. RESULTS: Compared with the control groups,the yield of rhizome was significantly increased by N (P < 0.01), K (P < 0.01) , P (P <0.05). The content of diosgenin has no obvious increase (P > 0.05) by individual application of N, P and K, while changed significantly (P < 0.05) by the combination of proper levels of N, P, K. CONCLUSION: The degree of effect on diosgenin content was ranged with N > K > P, while on output of dioscorea rhizome was K > N > P, and the combination of N, K, P2 was superior to others.