One-Minute Preparation of Iron Foam-Drug Implant for Ultralow-Power Magnetic Hyperthermia-Based Combination Therapy of Tumors in Vivo.

The magnetic hyperthermia-based combination therapy (MHCT) is a powerful tumor treatment approach due to its unlimited tissue penetration depth and synergistic therapeutic effect. However, strong magnetic hyperthermia and facile drug loading are incompatible with current MHCT platforms. Herein, an iron foam (IF)-drug implant is established in an ultra-facile and universal way for ultralow-power MHCT of tumors in vivo for the first time. The IF-drug implant is fabricated by simply immersing IF in a drug solution at an adjustable concentration for 1 min. Continuous metal structure of IF enables ultra-high efficient magnetic hyperthermia based on eddy current thermal effect, and its porous feature provides great space for loading various hydrophilic and hydrophobic drugs via "capillary action". In addition, the IF has the merits of low cost, customizable size and shape, and good biocompatibility and biodegradability, benefiting reproducible and large-scale preparation of IF-drug implants for biological application. As a proof of concept, IF-doxorubicin (IF-DOX) is used for combined tumor treatment in vivo and achieves excellent therapeutic efficacy at a magnetic field intensity an order of magnitude lower than the threshold for biosafety application. The proposed IF-drug implant provides a handy and universal method for the fabrication of MHCT platforms for ultralow-power combination therapy.

A Novel 5-HT1B Receptor Agonist of Herbal Compounds and One of the Therapeutic Uses for Alzheimer's Disease.

The serotonin receptor 5-HT1B is widely expressed in the central nervous system and has been considered a drug target in a variety of cognitive and psychiatric disorders. The anti-inflammatory effects of 5-HT1B agonists may present a promising approach for Alzheimer's disease (AD) treatment. Herbal antidepressants used in the treatment of AD have shown functional overlap between the active compounds and 5-HT1B receptor stimulation. Therefore, compounds in these medicinal plants that target and stimulate 5-HT1B deserve careful study. Molecular docking, drug affinity responsive target stability, cellular thermal shift assay, fluorescence resonance energy transfer (FRET), and extracellular regulated protein kinases (ERK) 1/2 phosphorylation tests were used to identify emodin-8-O-ß-d-glucopyranoside (EG), a compound from Chinese medicinal plants with cognitive deficit attenuating and antidepressant effects, as an agonist of 5-HT1B. EG selectively targeted 5-HT1B and activated the 5-HT1B-induced signaling pathway. The activated 5-HT1B pathway suppressed tumor necrosis factor (TNF)-α levels, thereby protecting neural cells against beta-amyloid (Aß)-induced death. Moreover, the agonist activity of EG towards 5-HT1B receptor, in FRET and ERK1/2 phosphorylation, was antagonized by SB 224289, a 5-HT1B antagonist. In addition, EG relieved AD symptoms in transgenic worm models. These results suggested that 5-HT1B receptor activation by EG positively affected Aß-related inflammatory process regulation and neural death resistance, which were reversed by antagonist SB 224289. The active compounds such as EG might act as potential therapeutic agents through targeting and stimulating 5-HT1B receptor for AD and other serotonin-related disorders. This study describes methods for identification of 5-HT1B agonists from herbal compounds and for evaluating agonists with biological functions, providing preliminary information on medicinal herbal pharmacology.

Synthesis and characterization of osmotic pump capsules containing polyoxyethylene and pH modifier to control the release of nifedipine.

The aim of this study was to formulate osmotic pump capsules (OPCs) to control the release of nifedipine (NP). NP solid dispersion was prepared by solvent evaporation method. The prepared mixture of NP solid dispersion and various excipients were filled into the commercial HPMC hard capsule shells and then coated with cellulose acetate (CA) solution to form NP-OPC. The CA coating solution consisted of CA as semi-permeable membrane, and Poloxamer 188 as pore formers. The impact of addition agents, citric acid and pore formers on in vitro drug release were investigated. Furthermore, the study has highlighted the impact of paddle speed and the pH value of release media, on the release and compared the release with the commercial controlled release tablets. The in vitro drug release study indicated that drug release could reach 95% in 24 h with optimal formulation, and interestingly model fitting showed that the drug release behavior was closely followed to zero-order release kinetics. The pharmacokinetic studies were performed in rabbits with commercial controlled release tablets as reference, both preparations showed a sustained release effect. Compared with traditional preparation methods of OPCs, the new preparation process was simplified without the operation of laser drilling and the sealing process of capsule body and cap, which improved the feasibility of industrial production.

Treatment with endoscopic transnasal resection of hypothalamic pilocytic astrocytomas: a single-center experience.

BACKGROUNDS: Pilocytic astrocytomas (PAs) are World Health Organization (WHO) grade I tumors, which are relatively common, and are benign lesions in children. PAs could originate from the cerebellum, optic pathways, and third ventricular/hypothalamic region. Traditional various transcranial routes are used for hypothalamic PAs (HPAs). However, there are few studies on hypothalamic PAs treated through the endoscopic endonasal approach (EEA). This study reports the preliminary experience of the investigators and results with HPAs via expanded EEAs. METHODS: All patients with HPAs, undergone EEA in our hospital from 2017 to 2019, were retrospectively reviewed. The demographic data, clinical symptoms, complications, skull base reconstruction, prognosis, and endocrinological data were all recorded and analyzed in detail. RESULTS: Finally, five female patients were enrolled. The average age of patients was 28.6 ± 14.0. All patients had complaints about their menstrual disorder. One patient had severe bilateral visual impairment. Furthermore, only one patient suffered from severe headache due to acute hydrocephalus, although there were four patients with headache or dizziness. Four cases achieved gross-total resection, and one patient achieved subtotal resection. Furthermore, there was visual improvement in one patient (case 5), and postoperative worsening of vision in one patient (case 4). However, only one patient had postoperative intracranial infection. None of the patients experienced a postoperative CSF leak, and in situ bone flap (ISBF) techniques were used for two cases for skull base repair. In particular, ISBF combined with free middle turbinate mucosal flap was used for case 5. After three years of follow-up, three patients are still alive, two patients had no neurological or visual symptoms, or tumor recurrence, and one patient had severe hypothalamic dysfunction. Unfortunately, one patient died of severe postoperative hypothalamus reaction, which presented with coma, high fever, diabetes insipidus, hypernatremia and intracranial infection. The other patient died of recurrent severe pancreatitis at one year after the operation. CONCLUSION: Although the data is still very limited and preliminary, EEA provides a direct approach to HPAs with acceptable prognosis in terms of tumor resection, endocrinological and visual outcomes. ISBF technique is safe and reliable for skull base reconstruction.

Variations of Oral Microbiome in Chronic Insomnia Patients with Different Tongue Features.

Chronic insomnia is a disease which brings intense mental pain and disturbing complications to patients worldwide. The oral microbiome exhibits a mechanistic influence on human health. Therefore, it is crucial to understand the oral microbial diversity in insomnia. Tongue diagnosis has been considered a critical basic procedure in insomnia therapeutic decision-making in Traditional Chinese Medicine (TCM). Hence, it is significant to elucidate the various oral microbiome differences in chronic insomnia patients with different tongue features. In this paper, we used 16S rRNA gene sequencing and bioinformatics analysis to investigate dynamic changes in oral bacterial profile and correlations between chronic insomnia patients and healthy individuals, as well as in patients with different tongue coatings. Moreover, the relationship between the severity of insomnia and oral microbiota was explored. Our findings showed that chronic insomnia patients harbored a significantly higher diversity of oral bacteria when compared to healthy controls. More importantly, the results revealed that the diversity and relative abundance of the bacterial community was significantly altered among different tongue coatings in patients but not in healthy individuals. Oral bacteria with a relative abundance [Formula: see text]1% and [Formula: see text] among different tongue groups were considered remarkable bacteria, which included three phyla Proteobacteria, Bacteroidetes, Gracilibacteria, and four genera, Streptococcus, Prevotella_7, Rothia, and Neisseria. Our findings indicate that changes in oral microbiome correlate with tongue coatings in patients with chronic insomnia. Thus, the remarkable microbiome may provide inspiration for further studies on the correlation between tongue diagnosis and oral microbiome in chronic insomnia patients.

Inhibitory and inductive effects of Corydalis saxicola Bunting total alkaloids (CSBTA) on cytochrome P450s in rats.

Corydalis saxicola Bunting, a well-known traditional Chinese medicine in south China, has been widely used for the treatment of various hepatic diseases. Its active ingredients are Corydalis saxicola Bunting total alkaloids (CSBTA), which primarily include dehydrocavidine, palmatine, and berberine. These representative alkaloids could be metabolized by hepatic CYP450s. Hence, it is necessary to investigate the potential influences of CSBTA on CYP450s to explore the possibility of herb-drug interactions. In present study, in vitro inhibition and in vivo induction studies were performed to evaluate the potential effects of CSBTA extract on CYP450s in rats. Inhibition assay illustrated that CSBTA exerted inhibitory effects on CYP1A2 (IC50 , 38.08 µg/ml; Ki , 14.3 µg/ml), CYP2D1 (IC50 , 20.89 µg/ml; Ki , 9.34 µg/ml), CYP2C6/11 (IC50 for diclofenac and S-mephenytoin, 56.98 and 31.59 µg/ml; Ki, 39.0 and 23.8 µg/ml), and CYP2B1 (IC50 , 48.49 µg/ml; Ki , 36.3 µg/ml) in a noncompetitive manner. Induction study showed CSBTA had obvious inhibitory rather than inductive effects on CYP1A2 and CYP2C6/11. Interestingly, neither inhibition nor induction on CYP3A was observed for CSBTA. In conclusion, CSBTA-drug interactions might occur through CYP450s inhibition, particularly CYP1A and CYP2D. Further studies are still needed to elucidate the underlying mechanisms of inhibition.

RNA-Seq transcriptomic analysis of the Morus alba L. leaves exposed to high-level UVB with or without dark treatment.

Ultraviolet-B (UVB) irradiation induces oxidative stress in plant cells due to the generation of excessive reactive oxygen species. Morus alba L. (M. abla) is an important medicinal plant used for the treatment of human diseases. Also, its leaves are widely used as food for silkworms. In our previous research, we found that a high level of UVB irradiation with dark incubation led to the accumulation of secondary metabolites in M. abla leaf. The aim of the present study was to describe and compare M. alba leaf transcriptomics with different treatments (control, UVB, UVB+dark). Leaf transcripts from M. alba were sequenced using an Illumina Hiseq 2000 system, which produced 14.27Gb of data including 153,204,462 paired-end reads among the three libraries. We de novo assembled 133,002 transcripts with an average length of 1270bp and filtered 69,728 non-redundant unigenes. A similarity search was performed against the non-redundant National Center of Biotechnology Information (NCBI) protein database, which returned 41.08% hits. Among the 20,040 unigenes annotated in UniProtKB/SwissProt database, 16,683 unigenes were assigned 102,232 gene ontology terms and 6667 unigenes were identified in 287 known metabolic pathways. Results of differential gene expression analysis together with real-time quantitative PCR tests indicated that UVB irradiation with dark incubation enhanced the flavonoid biosynthesis in M. alba leaf. Our findings provided a valuable proof for a better understanding of the metabolic mechanism under abiotic stresses in M. alba leaf.

Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus.

Ginsenosides, the secondary plant metabolites produced by Panax ginseng are responsible for the enhancing effects on learning observed following treatment with Panax ginseng. A number of studies have provided correlational evidence that cell proliferation and survival are closely associated with hippocampal-dependent learning tasks. In this study, to investigate the beneficial effects of ginsenoside Rh1 on hippocampal cells and learning, mice (6 months old) were administered ginsenoside Rh1 at a dose of 5 and 10 mg/kg/day for a period of 3 months. Saline-treated mice were used as controls. The enhancement of memory and learning in the mice was evaluated by hippocampal-dependent tasks (passive avoidance tests and Morris water maze tests) and the immunohistochemical marker of cell proliferation, bromodeoxyuridine (BrdU). In addition, the levels of brain-derived neurotrophic factor (BDNF) were measured following treatment. Based on our data, the Rh1-treated group (5 and 10 mg/kg) showed a significantly improved learning and memory ability in the passive avoidance tests compared with the control group; however, only treatment with 10 mg/kg ginsenoside Rh1 significantly promoted spatial learning ability in the Morris water maze test. Ginsenoside Rh1 significantly enhanced cell survival in the dentate gyrus of mice, although it did not enhance hippocampal cell proliferation. In addition, ginsenoside Rh1 upregulated the expression of BDNF. These findings address the potential therapeutic significance of ginsenoside Rh1 as a nutritional supplement in memory loss and neurodegenerative diseases.

[Establishment and application of TLR2 receptor-based cell screening model].

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.