MRI comparative study of diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered.

PURPOSE: The MRI features of Diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered were compared and analyzed, and the changes in the apparent diffusion coefficient (ADC) of the two groups were quantitatively analyzed. METHODS: The MRI images of 35 patients with Diffuse midline gliomas, H3 K27-altered and gliomas in the midline without H3 K27-altered were analyzed retrospectively. The location, edge, signal, peritumoral edema and enhancement characteristics of the lesions were observed, and the changes in ADC values were analyzed. RESULTS: In the H3 K27-altered group, 85.7% (12/14) of the tumors were located in the thalamus and brainstem compared with 28.6% (6/21) in the no H3 K27-altered group. In the H3 K27-altered group, for tumors only located in the midline area, only 14.3% (1/7) had irregular shapes and unclear boundaries, while for tumors also invaded the extramidline tissues 85.7% (6/7) had irregular shapes and unclear boundaries.The"basilar artery wrapped sign" was found in 6 patients with tumors located in the pons in the H3 K27-altered group, but none in the no H3 K27-altered group had this sign. In the H3 K27-altered group, only 14.3% (1/7) of the tumors confined to the midline area had small cystic degeneration and necrosis, while for tumors also invaded the extramidline tissues, 100% (7/7) of the tumors had cystic degeneration and necrosis, and the cystic degeneration and necrosis only located in the extramidline region of the tumor in 6 cases.A total of 78.6% (11/14) of tumors in the H3 K27-altered group showed mild to moderate enhancement, while 47.6% (10/21) of tumors in the no H3 K27-altered group showed mild to moderate enhancement. The average peritumoral edema index was 1.13 in the H3 K27-altered group and 1.75 in the no H3 K27-altered group. The average ADC value of tumor in the H3 K27-altered group was 7.83 × 10- 4 mm2/s, and the ratio to normal brain tissue was 0.844, while the values in the no H3 K27-altered group were 13.5 × 10- 4 mm2/s and 1.75, respectively. CONCLUSION: Compared with gliomas in the midline without H3 K27-altered, The MRI findings and ADC value of Diffuse midline gliomas, H3K27-altered have some characteristics, which can help improve the diagnosis and differential diagnosis.

NRPS substrate promiscuity leads to more potent antitubercular sansanmycin analogues.

Sansanmycins, members of the uridyl peptide antibiotics, are assembled by nonribosomal peptide synthetases (NRPSs), the substrate promiscuity of which results in the diversity of products. Further exploration of the NRPSs' substrate promiscuity by reinvestigating sansanmycin producer strain led to the isolation and structural elucidation of eight new uridyl peptides, sansanmycins H-O (1-8). Among them, sansanmycin L, containing a 6-OH-bicyclic residue and Phe3 first found at the position AA3, exhibited activity against M. tuberculosis H37Rv with an MIC value of 2 µg/mL, 8-fold more potent than that of the major compound, sansanmycin A (MIC = 16 µg/mL).

Effect of peritumoral injection of boanmycin hydrochloride within temperature-sensitive in situ gel using Hep-G2 hepatoma nude mice model.

BACKGROUND: Boanmycin hydrochloride, a new antitumor agent, has a short half-life and fast clearance speed in vivo. The aim of this research was to investigate the effectiveness of peritumor injection of boanmycin hydrochloride within temperature-sensitive gel in situ using Hep-G2 hepatoma nude mice model. METHODS: Nude mice with human Hep-G2 tumor in right flank were randomly divided into four groups: normal saline group, in situ gel only group, boanmycin hydrochloride in situ saline group, and boanmycin hydrochloride in situ gel group, and were treated with injection of corresponding agents into peripheral tissue of the tumor. The volume of the tumor and the body weight of the mice were regularly measured, and tumor growth curve was generated. The size, internal echo, and blood flow of the tumors were observed by color Doppler ultrasonography. Histopathologic changes of the tumor after treatment were observed under both optical and transmission electron microscopy. RESULTS: The tumor growth was significantly inhibited by peritumoral therapy in boanmycin hydrochloride in situ gel group with the tumor inhibitory rate of 86.76%. The blood flow of the tumor was still seen in both normal saline group and in situ gel only group on color Doppler ultrasound. Punctate calcification and dotted blood flow were seen in boanmycin hydrochloride group; however, there was massive calcification and no blood flow in the tumor in the boanmycin hydrochloride in situ gel group. Large areas of necrosis and apoptotic cells were shown by microscopic observation in boanmycin hydrochloride in situ gel group. CONCLUSION: Temperature-sensitive boanmycin hydrochloride in situ gel can effectively delay the release of boanmycin hydrochloride and increase its anticancer effects for liver cancer in animal model.

Draft genome sequence of Streptomyces sp. strain SS, which produces a series of uridyl peptide antibiotic sansanmycins.

Streptomyces sp. SS produces a series of uridyl peptide antibiotic sansanmycins. Here, we present a draft genome sequence of Streptomyces sp. SS containing the biosynthetic gene cluster for the antibiotics. The identification of the biosynthetic gene cluster of sansanmycins may provide further insight into biosynthetic mechanisms for uridyl peptide antibiotics.

Biomechanical analysis of the impact of fibular osteotomies at tibiotalar joint: A cadaveric study.

BACKGROUND: Osteotomy of the fibula is a common orthopedic procedure performed for various indications, including harvesting fibula for grafting purposes. The effect of fibular osteotomy and need for tibiofibular syndesmotic fixation fusion at different levels on tibiotalar joint is matter of debate. We performed a biomechanical analysis of the impact of fibular osteotomies at different levels and whether the fixation of distal tibiofibular joint mitigates instability caused by the osteotomy. MATERIALS AND METHODS: Six lower limb specimens from fresh adult cadavers were used to prepare leg-foot models. The specimens were assigned to six status according to the level of osteotomy and whether fixation of distal tibiofibular joint was performed or not. Each specimen was then loaded axially to 700 N by the material testing machine, and the tibiotalar joint contact area and peak pressure were measured using an electronic pressure sensor. RESULTS: The contact area and the pressure of tibiotalar joint showed significant changes when compared to the normal specimen. All osteotomy specimens had a decreased tibiotalar contact area and an increased peak pressure. This positively correlated with proximity of level of osteotomy to the lateral malleolus. CONCLUSIONS: Through this study, we found that fibular osteotomy had an adverse effect in terms of decreasing the contact surface of tibiotalar joint that led to increased peak pressure in the joint. However, bone fusion and screw fixation of the distal tibiofibular joint reduced these adverse effects.

[In vivo distribution of FITC-labeled boanmycin hydrochloride in situ gel].

This study is to evaluate the sustained-release effect of the thermosensitive in situ gel for injection of boanmycin hydrochloride (BAM) by bioluminescence imaging in nude mice. BAM was labeled with fluorescein isothiocyanate (FITC). The FITC-labeled BAM (FITC-BAM) was purified by dialysis and Sephadex G25 gel column, and then was identified by matrix-assisted laser desorption ionization/time of flight (MALDI-TOF). The model of experimental hepatoma HepG-2 nude mice was established, and the optical imaging system was applied to evaluate the distribution of FITC-BAM in vivo. Results of MALDI-TOF proved that the major molecular ratio of BAM : FITC was 1 : 1 or 1 : 2. Bioluminescence imaging showed that the diffusion of FITC-BAM in situ gel group was significantly delayed compared with the negative control group. This study demonstrated that the thermosensitive in situ gel can effectively delay the release of boanmycin hydrochloride, and extend the retention time in vivo.

Synthesis and in vitro antitubercular evaluation of novel sansanmycin derivatives.

Tuberculosis (TB) is a major health problem worldwide. A series of novel sansanmycin derivatives were designed, semi-synthesized and evaluated for their activity against drug-susceptible Mycobacterium tuberculosis strain H(37)Rv with sansanmycin A (SSA) as the lead. Among these analogs tested, compound 1d possessing an isopropyl group at the amino terminal afforded an increased antimycobacterial activity with a MIC value of 8 µg/mL in comparison with SSA. Importantly, it was active for rifampicin- and isoniazid-resistant M. tuberculosis strain isolated from patients in China. These promising results offer an opportunity for further exploration of this novel class of analogs as antitubercular agents.

[Thermosensitive in situ gel of boanmycin hydrochloride for injection].

Poloxamer F127, poloxamer F68 and hydroxypropyl methylcellulose K4M were used to prepare the thermosensitive in situ gel of boanmycin hydrochloride for injection. Its gelation temperature, rheological behavior, texture characteristics, scanning electron microscopy, in vitro and in vivo drug release were evaluated. These results showed that the formulation was a fluid solution at room temperature, which could become semisolid at the temperature of 37 degrees C, and the thermally induced sol-gel transition allowed to be injectable and in situ setting. The formulation was constructed into a tridimensional network at gelation temperature. The drug release was controlled by the diffusion of the drug and the erosion of the gelmatrix. The pharmacokinetics indicated that the drug could be released slowly for up to 48 hours after subcutaneous administration in rats.

Potent antitumor actions of the new antibiotic boningmycin through induction of apoptosis and cellular senescence.

Boningmycin, a new antibiotic of the bleomycin family, is isolated from the fermentation broth of Streptomyces verticillus var. pingyangensis n.sp. This study aimed to evaluate its antitumor actions and mechanism. The results showed that boningmycin exhibited potent inhibitory effects on several human solid tumor cells and that it was stronger than bleomycin. The administration of boningmycin inhibited the growth of human hepatoma HepG2 xenografts in nude mice, with more efficacy than that of bleomycin. Boningmycin led to an increase of the reactive oxygen species involving iron and caused G2/M phase accumulation in the HepG2 and human breast cancer MCF-7 cells. Two types of cell death, apoptosis and senescence, were detected after exposure to boningmycin. The accumulation of sub-G1 phase cells, an index of apoptosis, and the activation of caspase apoptotic pathways were detected after treatment with higher concentrations of boningmycin. Low concentrations of boningmycin led to a senescent phenotype with an increase in senescence-associated ß-galactosidase activity and the time-dependent increase of p21, p27, and p53 expressions from 48 to120 h. Taken together, the results showed that boningmycin exhibits potent antitumor actions through the induction of apoptosis and cellular senescence.

[Characteristics of boningmycin induced cellular senescence of human tumor cells].

Cellular senescence is one of the important steps against tumor. This study was to observe the characteristics of boningmycin induced senescence of human tumor cells. MIT method and clone formation assay were used to detect the growth-inhibitory effect. Cellular senescence was detected with senescence-associated beta-galactosidase staining. Cell cycle distribution and accumulation of intracellular reactive oxygen species (ROS) were analyzed with flow cytometry. Protein expression was detected by Western blotting. The results showed that the growth-inhibitory effect of boningmycin was obviously stronger on human oral epithelial carcinoma KB cells than that on non-small cell lung cancer A549 cells. Comparison to the similar action of doxorubicin, that boningmycin induced the features of cellular senescence in both cell lines, its due to the arrest at G2/M phase and an increase of ROS level. The molecular senescence marker P21 increased significantly after boningmycin treatment at a dosage of 0.1 micromol x L(-1), whereas a higher concentration of it induced apoptosis. The results indicated that cellular senescence induced by boningmycin was one of its mechanisms in tumor suppression.

Mechanisms of the antitumor action of the new antibiotic NC0604, a member of the bleomycin family.

NC0604, the new antibiotic of the bleomycin family, was isolated from the fermentation broth of Streptomyces verticillus var. pingyangensis n.sp. In this study, we investigated its mechanisms of antitumor action in vitro and in vivo. The results showed that the colony formation inhibition of NC0604 was 2-10 times higher than that of bleomycin to several tumor cell types. In comparison to bleomycin, a better antitumor efficacy of NC0604 was observed in the BALB/c mice loading mouse hepatoma H22 tumors. Flow cytometry assay detected an increase of intracellular reactive oxygen species and arrest at G2/M phase in human hepatoma HepG2 cells after exposure to NC0604. The comet of DNA damage was also observed in the NC0604-treated cells using single cell gel electrophoresis assay. The chromatin condensation appeared in the NC0604-induced apoptotic cells. The activation of apoptotic caspase pathway and increase of apoptosis-modulated protein expression, such as p53, Bax, were also detected by Western blot analysis. Taken together, the anti-tumor actions of NC0604 involve activation of the apoptotic pathway and it is valuable for further drug development.

Effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm.

OBJECTIVE: To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. METHODS: Micro-dilution method was used to determine the minimal inhibitory concentrations (MICs) of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PA1 and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PA1 and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin. RESULTS: The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PA1 and PA27853 strains through biofilms. PA1 and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin. CONCLUSION: Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.

Sansanmycins B and C, new components of sansanmycins.

Two new antibiotics, sansanmycins B and C, were isolated from Streptomyces sp. SS. Their structures were elucidated by extensive 1D and 2D NMR and MS spectral analyses. Sansanmycins B and C exhibited inhibitory activity against our test strain of Pseudomonas aeruginosa with MIC values of 8.0 and 16 microg/ml, respectively. Sansanmycin B also exhibited inhibitory activity against Mycobacterium tuberculosis H37Rv and multidrug-resistant Mycobacterium tuberculosis, with the MIC values ranging from 8.0 to 20 microg/ml.

Isolation and characterization of antibiotic NC0604, a new analogue of bleomycin.

NC0604, a new analogue of bleomycin, was isolated from fermentation broth of Streptomyces verticillus var. pingyangensis n.var. The structure of NC0604 was elucidated by spectroscopic analyses. NC0604 had the same kernel structure as bleomycin, but a different terminal amine moiety determined as amidepropyl spermidine. NC0604 exhibited antibacterial activity against a wide range of bacterial species and showed cytotoxicity in vitro against human HepG(2), KB, MCF-7, HCT116, BGC-823 and MCF-7/DOX cells with IC(50) values of 1.18, 1.21, 1.41, 1.83, 2.02, 1.45 muM, respectively. The antitumor activity of NC0604 against these cells was 3~9 times higher than that of bleomycin; and the pulmonary toxicity of NC0604 was much lower than that of bleomycin.

[In vitro studies on asexual embryos and regenerated plantlets obtained from leaf organ of Panax notoginseng].

OBJECTIVE: To study and improve the tissue culture technology of Panax notoginseng. METHOD: Using the callus of leaf blade and leafstalk of P. notogingseng as explants, MS + 2, 4-D 1.5 mg x L(-1) as basal medium, the formation of asexual embryos was induced by added LFS, BA, KT or ZT 0.5 mg x L(-1), and cultured in dark. It cultured then in 2000 lx of illumination for 10-12 h x d(-1) to induce the asexual embryos germinating and developing to be the regenerated-plantlet. RESULT AND CONCLUSION: Only the medium added with LFS could induce the formation of asexual embryos, and made it developed to be regenerated-plantlet. The inducing ratio of asexual embryos reached about 85%, and 30% of asexual embryos could grow and develop as robust regenerated-plantlets.

A new nucleosidyl-peptide antibiotic, sansanmycin.

A new nucleosidyl-peptide antibiotic, sansanmycin, was isolated from an unidentified Streptomyces sp SS. The structure of sansanmycin was elucidated by analyses of its alkaline hydrolysate and spectroscopic analyses. Sansanmycin exhibits antibacterial activity against Mycobacterium tuberculosis H(37)Ra and Pseudomonas aeruginosa with MIC values of 10 and 12.5 mug/ml, respectively.

[Effects of angustmycin on callus occurrence and proliferation of Panax notogingseng in vitro].

In order to explore quick, efficient inducement and proliferation of Panax notogingseng callus, the stem sections were taken as explants in the following 5 groups of medium: 1. MS + 2,4-D 2 mg/L (CK), 2. MS + 2,4-D 2 mg/L + N6-BA 2 mg/L, 3. MS + 2,4-D 2 mg/L + KT 2 mg/L, 4. MS + 2,4-D 2 mg/L + ZT 2 mg/L, 5. MS + 2,4-D 2 mg/L + LFS 2 mg/L. The results showed: 1. LFS (Lingfasu, a new kind of CTK) was able to promote the callus formation earlier 1-2 week than CK and to raise the rate of induced callus as high as 81%, higher 30% than that on other 4 mediums; 2. On medium 5, the fresh weight of callus increased 360.2% after being cultured 40 d, on other 4 mediums increased only 13.4%-21.8%. At the same time, 1 g callus cultured 40 d could obtain dry material 81.5 mg on medium 5, but on other 4 mediums only 21.5-25.9 mg; 3. The callus cultured on medium 5. continual generation to generation could live as long as more than 3 years, on other 4 mediums the callus hardened and aged quickly.

[Treatment of 48 cases of frozen shoulder with manual therapy under brachial plexus anesthesia through a retained tube].

Manual therapy was adopted for treatment of 48 patients with frozen shoulder, under brachial plexus block through a tube that was not withdrawn until 1 to 2 weeks after the initiation of the treatment course. Satisfactory results were achieved in most of the patients after the treatment, indicating the safety and feasibility of brachial plexus block for pain relief through long-term retention of the tube.