Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G­actin signaling cascade.

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G­actin/F­actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)­2/MMP­9, caspase­3/caspase­9/poly(ADP­ribose) polymerase (PARP)/cytochrome c, were determined by western blot analysis to assess the effects of targeting LIMK. The in vitro findings were verified in vivo by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G­actin could be co­transferred to the mitochondria to initiate the mitochondrial­cytochrome c pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.

Upper gastrointestinal hemorrhage and thoracic aortic aneurysm rupture as presenting signs of Behçet disease: A case report.

INTRODUCTION: Behçet disease (BD) is an autoimmune disorder characterized by oral aphthosis, genital aphthosis, ocular lesions, and arthritis. However, other fatal complications are often misdiagnosed, which implies that the early diagnosis of the disease is important for a good prognosis. PATIENT CONCERNS: A 51-year-old man complained of hematemesis for 5 hours and syncope once. DIAGNOSIS: BD as demonstrated by esophageal ulcer and aortic aneurysm rupture. INTERVENTIONS: Surgeries were conducted to repair the thoracic aortic aneurysm, proton-pump inhibitor was used to reduce acid secretion, antibiotics were applied for anti-infective therapy, and immunosuppressor was administered to control the injuries of BD. OUTCOMES: The patient was discharged and his medication dosage was reduced gradually until the minimum maintenance dose. In the follow-ups, the gastric ulcer and vascular aneurysm were not found. CONCLUSION: We presented a rare case of BD with the concurrence of huge esophageal ulcer and thoracic aortic aneurysms rupture, which helped us to diagnose BD at the early stage, while confronting atypical manifestations.

Clinical Characteristics and Outcomes of Pediatric Cerebral Venous Sinus Thrombosis: An Analysis of 30 Cases in China.

Background: Cerebral venous sinus thrombosis (CVST) in children is rare in a clinical setting. The aim of this study was to summarize the etiological, clinical, and imaging characteristics of CVST in children. Methods: We retrospectively analyzed the data of 30 patients with a diagnosis of CVST who were admitted to Children's Hospital of Fudan University from 2008 to 2018. The medical records, including clinical manifestations, laboratory data, neurological findings, treatment, and short-term prognosis were analyzed. Results: Etiologically, the causes of CVST were infection (7/30), tumor (3/30), nephritis or nephrotic syndrome (8/30), traumatic brain injury (1/30), and undefined disease (11/30). All 30 cases were diagnosed with CVST after a neuroimaging examination using brain magnetic resonance imaging (MRI) combined with magnetic angiography venography (MRV). With regard to short-term prognosis, all the patients were treated with anticoagulants, after which 26 cases improved. Conclusions: CVST patients do not typically present with specific clinical manifestations, which leads to a high rate of misdiagnosis and delayed therapy. Increased consideration and prompt MRV checkup plays a key role in achieving an accurate diagnosis. Overall, anticoagulation is a safe and effective treatment for CVST.

[Effects of light intensity on growth and content of active components of Uncaria rhynchophyll].

The aim of this study was to study the effects of different light intensity on the growth,biomass accumulation and distribution,chlorophyll content and effective components of Uncaria rhynchophylla seedlings,and explore the suitable light intensity conditions for artificial cultivation of U. rhynchophylla seedlings. Three-year-old U. rhynchophylla seedlings were used as experimental materials. Four light intensity levels( 100%,70%-75%,30%-35%,5%-10%) were set up with different layers of black shading net. With the decrease of light intensity,the results showed that the plant height,basal diameter and biomass( root,stem,leaf and hook) of U.rhynchophylla seedlings exhibited the trend of " increase-decrease". Under 70%-75% light intensity,the plant height,basal diameter,biomass( root,stem,leaf,hook) of U. rhynchophylla seedlings were significantly higher than those of other treatments( P< 0. 05);under 5%-10% light intensity,the plant height,basal diameter and biomass( root,hook) of U. rhynchophylla seedlings were significantly lower than those of other treatments( P<0. 05). With the decrease of light intensity,the chlorophyll content of U. rhynchophylla seedlings increased gradually: under 100% light intensity,the chlorophyll content of U. rhynchophylla seedlings were the smallest,while under 100% light intensity,its chlorophyll content was the highest. With the decrease of light intensity,the contents of rhynchophylline and isorhynchophylline in different organs of U. rhynchophylla seedlings varied: under 30%-35% light intensity,the contents of rhynchophylline and isorhynchophylline in hooks and rhynchophylline content in stems were the highest; under 5%-10% light intensity,the contents of rhynchophylline and isorhynchophylline in leaves and stems of U. rhynchophylla were the highest. In conclusion,70%-75% light intensity is suitable for seedling growth and biomass accumulation,and 30%-35% light intensity is suitable for the accumulation of effective components in U. rhynchophylla seedlings.

Six-month efficacy of the Ketogenic diet is predicted after 3 months and is unrelated to clinical variables.

OBJECTIVE: The aim of this study was to evaluate the 6-month efficacy of a Ketogenic diet (KD) in children with drug-resistant epilepsy and to analyze the associated factors that affect the efficacy of a KD. METHODS: Eighty-seven pediatric patients with drug-resistant epilepsy who followed a KD for at least 6 months were included in this study. The efficacy of a KD was assessed based upon the seizure frequency, as recorded by parents and caregivers. The number of cases and the degree of efficacy in different age ranges were also considered. The effects of gender, age, seizure type, etiology, blood glucose and ketone levels, seizure frequency before the diet, and cognition on the length of time on a KD were analyzed. RESULTS: (1) There was no significant correlation between the length of time on a KD and efficacy (χ(2)=2.31, P=0.51). The 3-month efficacy of a KD was 51%, which did not further increase when the course was extended to 6 months. (2) There was a positive correlation between increased cognition and the efficacy of a KD after 3 months (γ=0.31, P=0.003). (3) The efficacy analysis of 3-month treatment with a KD revealed, with respect to seizure types, that there were 37 patients with multiple seizure phenotypes and 50 patients with a single seizure phenotype. The overall efficacy of a KD in the group with multiple seizure phenotypes was 61%. The efficacy of a KD was not statistically associated with a coexisting syndrome or a type of syndrome; however, the efficacy of a KD had a tendency to be increased in certain types of syndromes. The overall efficacy in the group with a single seizure phenotype was 87%, and the efficacy was not associated with seizure type. (4) The 3-month efficacy of a KD was not correlated with age, gender, etiology, blood glucose or ketone levels, or the seizure frequency before treatment. CONCLUSION: An observation time of 3 months is appropriate for assessing the efficacy of a KD in treating children with drug-resistant epilepsy. The factors that likely influence the efficacy of a KD are unclear, but our study suggests that incorporating more patient samples will help determine whether patients with certain syndromes can benefit from a KD.

[Characteristics of soil mineralizable carbon pool in natural restoration process of Karst forest vegetation].

By the method of taking space instead of time, an incubation test was conducted to study the characteristics of soil mineralizable carbon pool during the natural restoration of Karst forest vegetation in Maolan Nature Reserve, Guizhou Province of Southwest China. It was observed that the contents of soil total organic carbon (TOC) and mineralizable carbon (MC) as well as the carbon mineralization rate decreased with increasing soil depth but increased with the process of vegetation restoration. The amount of cumulative released carbon and the carbon release rate increased with the process of restoration, but the release rate decreased with increasing incubation time. The soil MC/TOC increased with the restoration process but had less change with increasing soil depth, while the qCO2 decreased with increasing soil depth and through the process of restoration. The soil MC had a negative correlation with the existing litter amount (r = -0.796) but positive correlation with the mass loss rate of the litter decomposition (r = 0.924). Soil habitat changed from strong interference at early stages to relative stability at late stages, and soil carbon sequestration changed from small capacity and strong potential at early stages to large capacity and weak potential at late stages.

[Changes of foliar delta13C value of Quercus fabric in different root underground habitat types in Karst area].

Selecting the dominant tree species Quercus fabric in three root underground habitat types (the dolomites of low oblique occurrence with multilayer space, middle oblique occurrence with multilayer space, and high oblique occurrence with multilayer space) in Karst area as test object, this paper studied the foliar delta13C value and its correlations with habitat soil conditions, and the plant water use efficiency. There existed remarkable differences in the foliar delta13C value of Q. fabric among the three habitat types, being decreased in the order of low oblique occurrence with multilayer space type (-26.35 per thousand) > high oblique occurrence with multilayer space type (-26.66 per thousand) > middle oblique occurrence with multilayer space type (-27.07 per thousand). Accordingly, the plant water use efficiency decreased in the same order. The foliar delta13C value had significant correlation with habitat soil moisture content, but less correlation with habitat soil elements contents. The delta13C value increased with the decrease of soil moisture content and soil fertility.

[Characteristics of soil microbial biomass carbon and soil water soluble organic carbon in the process of natural restoration of Karst forest].

By the method of taking space instead of time, an incubation test was conducted to study the characteristics of soil microbial biomass carbon and water soluble organic carbon in the process of natural restoration of Karst forest in Maolan Nature Reserve, Guizhou Province of Southwest China. The soil microbial biomass carbon content and soil basal respiration decreased with increasing soil depth but increased with the process of the natural restoration, soil microbial quotient increased with increasing soil depth and with the process of restoration, and soil water soluble organic carbon content decreased with increasing soil depth. In the process of the natural restoration, surface soil water soluble organic carbon content increased, while sublayer soil water soluble organic carbon content decreased after an initial increase. The ratio of soil water soluble organic carbon to total soil organic carbon increased with increasing soil depth but decreased with the process of restoration. Soil quality increased with the process of restoration. Also, the quality and quantity of soil organic carbon increased with the process of restoration, in which, soil microbial biomass carbon content had the greatest change, while soil water soluble organic carbon content had less change.

Influence of drought intensity on the response of six woody karst species subjected to successive cycles of drought and rewatering.

Tolerance to the effects of drought and subsequent recovery after a rainfall appear to be critical for plants in the karst regions of southwestern China, which are characterized by frequent but temporary drought events. This study investigated the effects of drought intensity and repetition on photosynthesis and photoprotection mechanisms of karst plants during successive cycles of drought and subsequent recovery. Leaf water potential, gas exchange, chlorophyll fluorescence and several associated metabolic processes were studied in six plant species, including Pyracantha fortuneana (PF), Rosa cymosa (RC), Broussonetia papyrifera (BP), Cinnamomum bodinieri (CB), Platycarya longipes (PL) and Pteroceltis tatarinowii (PT) during three cycles of drought treatments at four different intensities. The four treatments were: well-watered, mild drought, moderate drought and severe drought, each followed by rewatering events. We found that limitations to CO(2) diffusion accounted for photosynthetic declines under mild and moderate drought treatments, while metabolic limitations dominated the response to severe drought. Repetition of drought did not intensify the impairment of photosynthetic metabolism regardless of drought intensity in the six species studied. Repetition of severe drought delayed the photosynthetic recoveries in PF, RC and CB after rewatering. Repetition of drought increased thermal dissipation in PF, CB and BP, as well as superoxide dismutase (EC 1.15.1.1) activity in RC and CB. Enhanced photosynthetic performance, measured as increased intrinsic water use efficiency, photosynthetic performance per unit of photosynthetic pigment, maintenance of high thermal dissipation and high ratios of carotenoids to chlorophylls, was observed during the rewatering periods. This enhanced photosynthetic performance allowed for the complete recovery of the six karst species from successive intermittent drought events.