Radiotherapy opens the blood-brain barrier and synergizes with anlotinib in treating glioblastoma.

BACKGROUND: Glioblastoma (GBM) has a poor prognosis and lacks effective treatment. Anlotinib is a multitargeted receptor tyrosine kinase inhibitor (TKI) that may have anti-tumor activity in the central nervous system (CNS). This study aimed to determine the therapeutic value of radiotherapy combined with anlotinib in GBM via preclinical research. METHODS: HPLC-MS/MS was used to assess the concentration of anlotinib in blood and brain samples. Cell proliferation assays, flow cytometry, and colony formation assays were performed in vitro. The potential value of anlotinib or in combination with radiotherapy for GBM treatment was estimated in vivo. Western blotting, immunohistochemistry, and immunofluorescent staining were performed to determine the underlying mechanism. RESULTS: Anlotinib effectively inactivated the JAK3/STAT3 pathway to inhibit growth and induce apoptosis in malignant glioma cells (MGCs) independent of MGMT expression. Meanwhile, anlotinib induces MGCs G2/M arrest and sensitizes MGCs to radiation. Radiation down-regulates claudin-5 and weakens the blood-brain barrier (BBB), which contributes to the increased distribution of anlotinib in the CNS by 1.0-2.9 times. Anlotinib restrains tumor growth (PCNA), inhibits tumor microvascular proliferation (CD31), and alleviated intratumor hypoxia (HIF 1α) in vivo. Anlotinib alone or in combination with radiation is effective and safe in vivo evaluation. CONCLUSIONS: We discovered that anlotinib, the original small molecule antiangiogenesis TKI, down-regulates JAK3/STAT3 axis with anti-cancer activity alone or in combination with radiation. Anlotinib combined with radiotherapy might be a promising treatment for newly diagnosed GBM in the clinic.

GBP2 acts as a member of the interferon signalling pathway in lupus nephritis.

Lupus nephritis (LN) is a common and serious clinical manifestation of systemic lupus erythematosus. However, the pathogenesis of LN is not fully understood. The currently available treatments do not cure the disease and appear to have a variety of side effects in the long term. The purpose of this study was to search for key molecules involved in the LN immune response through bioinformatics techniques to provide a reference for LN-specific targeted therapy. The GSE112943 dataset was downloaded from the Gene Expression Omnibus database, and 20 of the samples were selected for analysis. In total, 2330 differentially expressed genes were screened. These genes were intersected with a list of immune genes obtained from the IMMPORT immune database to obtain 128 differentially expressed immune-related genes. Enrichment analysis showed that most of these genes were enriched in the interferon signalling pathway. Gene set enrichment analysis revealed that the sample was significantly enriched for expression of the interferon signalling pathway. Further analysis of the core gene cluster showed that nine genes, GBP2, VCAM1, ADAR, IFITM1, BST2, MX2, IRF5, OAS1 and TRIM22, were involved in the interferon signalling pathway. According to our analysis, the guanylate binding protein 2 (GBP2), interferon regulatory factor 5 and 2'-5'-oligoadenylate synthetase 1 (OAS1) genes are involved in three interferon signalling pathways. At present, we do not know whether GBP2 is associated with LN. Therefore, this study focused on the relationship between GBP2 and LN pathogenesis. We speculate that GBP2 may play a role in the pathogenesis of LN as a member of the interferon signalling pathway. Further immunohistochemical results showed that the expression of GBP2 was increased in the renal tissues of LN patients compared with the control group, confirming this conjecture. In conclusion, GBP2 is a member of the interferon signalling pathway that may have implications for the pathogenesis of LN and serves as a potential biomarker for LN.

In vitro fecal fermentation characteristics of bamboo insoluble dietary fiber and its impacts on human gut microbiota.

Bamboo contains abundant hemicellulose, cellulose, and lignin, which are a high-quality insoluble dietary fiber (IDF) raw material. To investigate IDF- induced changes in the production of short-chain fatty acids (SCFAs) and the composition of human gut microbiota, IDF was extracted by alkaline hydrogen peroxide (named BIDF), complex enzymatic hydrolysis method (named OIDF) from bamboo, and commercial bamboo fiber BF90. The in vitro fecal fermentation characteristics of BIDF, OIDF, BF90 and its impacts on human gut microbiota were studied for the first time. Results showed that BIDF, OIDF, and BF90 could promote the production of total SCFAs after 24 h fermentation. Additionally, BIDF could alter the composition and microbial diversity of gut microbiota, especially increase the relative abundance of Bacteroides and decrease the ratio of Firmicutes to Bacteroidetes (F/B) value. These results revealed that the IDF from bamboo could be partially utilized by specific bacteria in human intestines and provide a reference for the study of the effects of IDF fermentation on SCFAs production and microbial composition.

Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-ß1/Smad3 pathway.

Radiation-induced lung injury (RILI) mainly contributes to the complications of thoracic radiotherapy. RILI can be divided into radiation pneumonia (RP) and radiation-induced lung fibrosis (RILF). Once RILF occurs, patients will eventually develop irreversible respiratory failure; thus, a new treatment strategy to prevent RILI is urgently needed. This study explored the therapeutic effect of pirfenidone (PFD), a Food and Drug Administration (FDA)-approved drug for (IPF) treatment, and its mechanism in the treatment of RILF. In vivo, C57BL/6 mice received a 50 Gy dose of X-ray radiation to the whole thorax with or without the administration of PFD. Collagen deposition and fibrosis in the lung were reversed by PFD treatment, which was associated with reduced M2 macrophage infiltration and inhibition of the transforming growth factor-ß1 (TGF-ß1)/Drosophila mothers against the decapentaplegic 3 (Smad3) signalling pathway. Moreover, PFD treatment decreased the radiation-induced expression of TGF-ß1 and phosphorylation of Smad3 in alveolar epithelial cells (AECs) and vascular endothelial cells (VECs). Furthermore, IL-4-induced M2 macrophage polarization and IL-13-induced M2 macrophage polarization were suppressed by PFD treatment in vitro, resulting in reductions in the release of arginase-1 (ARG-1), chitinase 3-like 3 (YM-1) and TGF-ß1. Notably, the PFD-induced inhibitory effects on M2 macrophage polarization were associated with downregulation of nuclear factor kappa-B (NF-κB) p50 activity. Additionally, PFD could significantly inhibit ionizing radiation-induced chemokine secretion in MLE-12 cells and consequently impair the migration of RAW264.7 cells. PFD could also eliminate TGF-ß1 from M2 macrophages by attenuating the activation of TGF-ß1/Smad3. In conclusion, PFD is a potential therapeutic agent to ameliorate fibrosis in RILF by reducing M2 macrophage infiltration and inhibiting the activation of TGF-ß1/Smad3.

Construction of chiral chroman scaffolds via catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with 3-vinylindoles.

A catalytic asymmetric (4 + 2) cyclization of ortho-hydroxyphenyl-substituted para-quinone methide derivatives with 3-vinylindoles has been established in the presence of chiral phosphoric acid, which provides a series of chiral chroman derivatives bearing an indole moiety in generally high yields (up to 97%), and with good enantioselectivities (up to 90% ee) and moderate to good diastereoselectivities (up to 95 : 5 dr). This reaction has not only fulfilled the need of developing catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with electron-rich alkenes, but also provided a useful method for constructing chiral chroman scaffolds.

Catalytic Asymmetric Conjugate Addition of Indoles to para-Quinone Methide Derivatives.

A catalytic asymmetric conjugate addition of indoles to o-hydroxyphenyl substituted p-quinone methides has been established in the presence of chiral phosphoric acid, which afforded chiral indole-containing triarylmethanes in generally high yields (54-98%) and good enantioselectivities (90:10-96:4 enantiomeric ratio). The control experiments indicated that o-hydroxyphenyl substituted p-quinone methides had a high possibility to transform into o-quinone methides in the presence of chiral phosphoric acid, and the formation of o-quinone methides might be a necessity for the reaction. This reaction will not only contribute to the research field of catalytic asymmetric transformations of p-quinone methides and o-quinone methides but also provide a useful method for the construction of enantioenriched triarylmethane frameworks.

Leaf miner-induced morphological, physiological and molecular changes in mangrove plant Avicennia marina (Forsk.) Vierh.

Avicennia marina (Forsk.) Vierh is a widespread mangrove species along the southeast coasts of China. Recently, the outbreak of herbivorous insect, Phyllocnistis citrella Stainton, a leaf miner, have impacted on the growth of A. marina. Little is reported about the responses of A. marina to leaf miner infection at the biochemical, physiological and molecular levels. Here, we reported the responses of A. marina to leaf miner infection from the aspects of leaf structure, photosynthesis, and antioxidant system and miner responsive genes expression. A. marina leaves attacked by the leaf miner exhibited significant decreases in chlorophyll, carbon and nitrogen contents, as well as a decreased photosynthetic rate. Scanning and transmission electron microscopic observations revealed that the leaf miner only invaded the upper epidermis and destroyed the epidermal cell, which lead to the exposure of salt glands. In addition, the chloroplasts of mined leaves (ML) were swollen and the thylakoids degraded. The maximal net photosynthetic rate, stomatal conductance (Gs), carboxylation efficiency (CE), dark respiration (Rd), light respiration (Rp) and quantum yields (AQE) significantly decreased in the ML, whereas the light saturation point (Lsp), light compensation point (Lcp), water loss and CO2 compensation point (Г) increased in the ML. Moreover, chlorophyll fluorescence features also had been changed by leaf miner attacks. Interestingly, higher generation rate of O2ˉ· and lower antioxidant enzyme expression in the mined portion (MP) were found; on the contrary, higher H2O2 level and higher antioxidant enzyme expression in the non-mined portion (NMP) were revealed, implying that the NMP may be able to sense that the leaf miner attacks had happened in the MP of the A. marina leaf via H2O2 signaling. Besides, the protein expression of glutathione S-transferase (GST) and the glutathione (GSH) content were increased in the ML. In addition, insect resistance-related gene expression such as chitinase 3, RAR1, topless and PIF3 had significantly increased in the ML. Taken together, our data suggest that leaf miners could significantly affect leaf structure, photosynthesis, the antioxidant system and miner responsive gene expression in A. marina leaves.

A novel phloroglucinol and two new phenolic glycosides from Psidium littorale.

One novel phloroglucinol, psidosone A (1), and two new phenolic glycosides, psidoside A (2), and psidoside B (3), together with nine known phenol compounds (4-12), were isolated from the fruits of Psidium littorale Raddi. Their structures were elucidated using data obtained from MS, 1H and 13C NMR spectra, and correlation experiments (HMQC and HMBC), as well as by comparison with published data.

[Flavonoids from leaves of Psidum littorale].

We investigated the chemical constituents of the leaves of Psidum littorale, which include 16 flavonoids, including seven flavonols, six flavonoid glycosides and three flavonones. The compounds were isolated by silica gel column chromatography. Their structures were elucidated on the basis of spectral analysis and by comparison with published data. Seven flavonols were kaempferol (1), isorhamnetin (2), myricetin- 3,7,3'-trimethyl ether(3), laricitrin (4), quercetin (5), myricetin (6) and quercein-3,4'-dimethyl ether (7), six flavonoid glycosides were guaijaverin (8), hyperoside (9), 5,4'-dyhydroxy-3,7,5'-methoxyflavone-3'-O-ß-D- glucoside (10), laricitrin-3-O-xyloside (11), myricetin-3-O-α-L-rhamnopyranoside (12) and myricetin-3-O-ß-D- xyloside (13). Three flavonones were 4'-O-methyldihydroquercetin (14), dihydroapigenin (15) and ampelopsin 4'-O-ß-D-glucopyranoside (16). Compound 10 is a new chemical, compounds 2-4, 7, 10-16 were first isolated from this plant. (1)H NMR and (13)C NMR data of compound 11 were not reported in literature.

Flavonoids from leaves of Psidum littorale / 药学学报

We investigated the chemical constituents of the leaves of Psidum littorale, which include 16 flavonoids, including seven flavonols, six flavonoid glycosides and three flavonones. The compounds were isolated by silica gel column chromatography. Their structures were elucidated on the basis of spectral analysis and by comparison with published data. Seven flavonols were kaempferol (1), isorhamnetin (2), myricetin-3,7,3'-trimethyl ether (3), laricitrin (4), quercetin (5), myricetin (6) and quercein-3,4'-dimethyl ether (7), six flavonoid glycosides were guaijaverin (8), hyperoside (9), 5,4'-dyhydroxy-3,7,5'-methoxyflavone-3'-O-β-D-glucoside (10), laricitrin-3-O-xyloside (11), myricetin-3-O-α-L-rhamnopyranoside (12) and myricetin-3-O-β-D-xyloside (13). Three flavonones were 4'-O-methyldihydroquercetin (14), dihydroapigenin (15) and ampelopsin 4'-O-β-D-glucopyranoside (16). Compound 10 is a new chemical, compounds 2-4, 7, 10-16 were first isolated from this plant. 1H NMR and 13C NMR data of compound 11 were not reported in literature.

Designed synthesis of size-tunable Ag2S nanoclusters via distinguishable C-S bond cleavage reaction of alkyl- and aryl-thiolates.

We report herein the synthesis of two different silver clusters of aryl- and alkyl-thiolates. These two cluster complexes exhibited biased C-S bond cleavage reaction rates upon removing protective hexamethylazacalix[6]pyridine (Py[6]) ligands, which was applied in the fabrication of silver sulfide nanoclusters with variable and controllable sizes.

[Mini-open trans-spatium intermuscular versus percutaneous short-segment pedicle fixation for the treatment of thoracolumbar mono-segmental vertebral fractures].

OBJECTIVE: To compare the clinical effects and radiographic outcomes of mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits. METHODS: From August 2009 and August 2012, 95 patients with thoracolumbar mono-segmental vertebral fractures without neurological deficits were treated with short-segment pedicle fixation through mini-open trans-spatium intermuscular or percutaneous approach. There were 65 males and 30 females, aged from 16 to 60 years old with an average of 42 years. The mini-open trans-spatium intermuscular approach was used in 58 cases (group A) and the percutaneous approach was used in 37 cases (group B). Total incision length, operative time, intraoperative bleeding, fluoroscopy, hospitalization cost were compared between two groups. Visual analog scale (VAS) and radiographic outcomes were compared between two groups. RESULTS: All patients were followed up from 12 to 36 months with an average of 19.6 months. No complications such as incision infection, internal fixation loosening and breakage were found. In group A, fluoroscopy time was short and hospitalization cost was lower than that of group B (P<0.05). But the total incision length in group B was smaller than that of group A (P<0.05). There was no significant differences in operative time, intraoperative bleeding, postoperative VAS and radiographic outcomes between two groups (P>0.05). Postoperative VAS and radiographic outcomes were improved than that of preoperative (P<0.05). CONCLUSION: The mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation have similar clinical effects and radiographic outcomes in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits. However, in this study, the mini-open trans-spatium intermuscular approach has a short learning curve and more advantages in hospitalization cost and intraoperative radiation exposure times, and is recommendable.

[Quality control of Maca (Lepidium meyenii)].

To control the quality of Maca, the quality standard was established in this study. According to the methods recorded in the Appendix of Chinese Pharmacopoeia (2010 Edition), the water, extract, total ash, acid insoluble substance, and heavy metals inspections in Lepidium meyenii were carried out. N-benzyl-9Z, 12Z-octadecadienamide in L. meyenii was identified by TLC, and it was determined by HPLC. The results showed that the N-benzyl-9Z, 12Z-octadecadienamide identification of TLC was a strong mark and specificity. In content determination experiment, the linearity of N-benzyl-9Z, 12Z-octadecadienamide was in the range of 0.01-2 microg (r = 0.9998), and the average recovery (n=9) was 99.27% (RSD 2.0%). The methods were simple, accurate, with good reproducibility. It is suitable for quality control L. meyenii.

Quality control of Maca (Lepidium meyenii) / 中国中药杂志

To control the quality of Maca, the quality standard was established in this study. According to the methods recorded in the Appendix of Chinese Pharmacopoeia (2010 Edition), the water, extract, total ash, acid insoluble substance, and heavy metals inspections in Lepidium meyenii were carried out. N-benzyl-9Z, 12Z-octadecadienamide in L. meyenii was identified by TLC, and it was determined by HPLC. The results showed that the N-benzyl-9Z, 12Z-octadecadienamide identification of TLC was a strong mark and specificity. In content determination experiment, the linearity of N-benzyl-9Z, 12Z-octadecadienamide was in the range of 0.01-2 microg (r = 0.9998), and the average recovery (n=9) was 99.27% (RSD 2.0%). The methods were simple, accurate, with good reproducibility. It is suitable for quality control L. meyenii.

Mini-open trans-spatium intermuscular versus percutaneous short-segment pedicle fixation for the treatment of thoracolumbar mono-segmental vertebral fractures / 中国骨伤

<p><b>OBJECTIVE</b>To compare the clinical effects and radiographic outcomes of mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits.</p><p><b>METHODS</b>From August 2009 and August 2012, 95 patients with thoracolumbar mono-segmental vertebral fractures without neurological deficits were treated with short-segment pedicle fixation through mini-open trans-spatium intermuscular or percutaneous approach. There were 65 males and 30 females, aged from 16 to 60 years old with an average of 42 years. The mini-open trans-spatium intermuscular approach was used in 58 cases (group A) and the percutaneous approach was used in 37 cases (group B). Total incision length, operative time, intraoperative bleeding, fluoroscopy, hospitalization cost were compared between two groups. Visual analog scale (VAS) and radiographic outcomes were compared between two groups.</p><p><b>RESULTS</b>All patients were followed up from 12 to 36 months with an average of 19.6 months. No complications such as incision infection, internal fixation loosening and breakage were found. In group A, fluoroscopy time was short and hospitalization cost was lower than that of group B (P<0.05). But the total incision length in group B was smaller than that of group A (P<0.05). There was no significant differences in operative time, intraoperative bleeding, postoperative VAS and radiographic outcomes between two groups (P>0.05). Postoperative VAS and radiographic outcomes were improved than that of preoperative (P<0.05).</p><p><b>CONCLUSION</b>The mini-open trans-spatium intermuscular and percutaneous short-segment pedicle fixation have similar clinical effects and radiographic outcomes in treating thoracolumbar mono-segmental vertebral fractures without neurological deficits. However, in this study, the mini-open trans-spatium intermuscular approach has a short learning curve and more advantages in hospitalization cost and intraoperative radiation exposure times, and is recommendable.</p>

[Seagrass ecosystems: contributions to and mechanisms of carbon sequestration].

The ocean's vegetated habitats, in particular seagrasses, mangroves and salt marshes, each capture and store a comparable amount of carbon per year, forming the Earth's blue carbon sinks, the most intense carbon sinks on the planet. Seagrass meadows, characterized by high primary productivity, efficient water column filtration and sediment stability, have a pronounced capacity for carbon sequestration. This is enhanced by low decomposition rates in anaerobic seagrass sediments. The carbon captured by seagrass meadows contributes significantly to the total blue carbon. At a global scale, seagrass ecosystems are carbon sink hot spots and have profound influences on the global carbon cycle. This importance combined with the many other functions of seagrass meadows places them among the most valuable ecosystems in the world. Unfortunately, seagrasses are declining globally at an alarming rate owing to anthropogenic disturbances and climate change, making them also among the most threatened ecosystems on the Earth. The role of coastal systems in carbon sequestration has received far too little attention and thus there are still many uncertainties in evaluating carbon sequestration of global seagrass meadows accurately. To better assess the carbon sequestration of global seagrass ecosystems, a number of scientific issues should be considered with high priorities: 1) more accurate measurements of seagrass coverage at national and global levels; 2) more comprehensive research into species- and location-specific carbon sequestration efficiencies; 3) in-depth exploration of the effects of human disturbance and global climate change on carbon capture and storage by seagrass ecosystems.

[Impacts of digging Phascolosoma esculenta on the growth of mangrove Avicennia marina seedlings: a simulation study].

Digging Phascolosoma esculenta to increase income is one of the main causes leading to the degradation of China mangroves. In order to understand the impact mechanisms of digging P. esculenta on the mangrove growth and to select indicators to evaluate the mangrove health, a simulative study was conducted to clarify the impacts of digging depth, radian, and frequency on the growth of 1-year old Avicennia marina seedlings, with the indices seedling height, basal diameter, single leaf area, specific leaf area, total biomass, and dead root dry mass measured. The results showed that digging activities decreased the increment of seedling height and basal diameter, single leaf area, specific leaf area, and total biomass significantly, and increased the dead root dry mass markedly. Digging depth and radian had obvious effects on the growth of A. marina seedlings, but digging frequency had minor effects. When the digging depth was < 5 cm, digging radian was < 240 degrees, and digging frequency was < 2 times per month, the damage to the seedlings was slighter; but when the digging depth was > 5 cm, the damage was quite serious.

Comparative pharmacokinetic and bioavailability studies of three salvianolic acids after the administration of Salviae miltiorrhizae alone or with synthetical borneol in rats.

Salviae miltiorrhizae is one of the most commonly used herbal plants in the treatment of numerous ailments including cardiovascular diseases for hundreds of years. According to the theory of traditional Chinese herbal medicine, S. miltiorrhizae is always used in combination with borneol to obtain better pharmacological effects. The purpose of this study was to investigate the effects of borneol on the pharmacokinetic and bioavailability of S. miltiorrhizae. The pharmacokinetics studying on rosmarinic acid, salvianolic acid A and salvianolic acid B which are the main active compounds of S. miltiorrhizae in rat plasma, was achieved using a optimal high-performance liquid chromatographic technique coupled with liquid-liquid extraction method. After administration of either single salvianolic acids or salvianolic acids in combination with borneol, plasma concentrations of rosmarinic acid, salvianolic acid A and salvianolic acid B of male Sprague-Dawley rats were determined at different time points (5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min). In comparison with salvianolic acid extract alone, there were statistically significant differences in pharmacokinetic parameters of rosmarinic acid, salvianolic acid B and salvianolic acid A, and the bioavailability of the three salvianolic acids increased by different degrees when the salvianolic acid extract and borneol were administered together. These results indicated that borneol could enhance the intestinal absorption, decrease the distribution and inhibit the metabolism of salvianolic acids.

Reduction of CD47 on monocytes correlates with MODS in burn patients.

Alternation of surface markers on monocytes is associated with the development of inflammation. The goals of the present study were to detect CD47 expression on monocytes by flow cytometry and explore its relationship with disease severity and MODS in burned patients. The results show CD47 expression on monocytes from all burned patients (n = 21) was lower than that from the healthy population (n = 21) for 24 days after burn. There was a significant difference in CD47 expression on monocytes between the patients with differing burn severity in the first 7 days after injury (P < 0.05). Considering the relationship between CD47 expression and MODS, we found the CD47 expression on monocytes from patients with MODS was lower (P < 0.05) in the first 3 days after injury than that from patients without MODS. In conclusion, diminished CD47 expression on monocytes is associated with burn severity and the occurrence of MODS in burn patients.

Treatment of tracheal stenosis with an extended tracheal cannula in a patient with extensive burn.

Burn-induced tracheal stenosis is rare. This article reports an extensive burn patient who developed severe tracheomalacia and stenosis before wound healing. Given the ineffectiveness of the conventional techniques available for the treatment of tracheal stenosis, we used an extended tracheal cannula to dilate the narrowed part of the trachea successfully. As a result, the extensive burn wound was repaired, and the symptoms of tracheal stenosis were eventually relieved. No serious restenosis was observed during a 2-year follow-up period.