Latest ArticlesHPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection. HPLC-RID:This method was performed on a Kromasil 100-5-NH2 column (250 mm×4.6 mm, 5 μm) with a mobile phase of 0.8 mol·L-1 ammonium sulfate buffer (pH 3.5)-acetonitrile (83:17). The flow rate, column temperature and detector temperature were maintained at 1 mL·min-1, 30℃ and 30℃ respectively. HPIC-CD:This method was performed on an anion exchange column Dionex InPacTM AS11-HC (250 mm×4 mm, 9 μm) with an eluent of 30 mmol·L-1 sodium hydroxide solution. The flow rate was 1.5 mL·min-1, the column temperature was 30℃ and the detector temperature was 35℃. The HPLC-RID method and HPIC-CD method were validated with respects to specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, stability and robustness and met the validation requirements. There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis, both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection. However, the HPLC-CD was better at the following aspects:higher detection sensitivity, simpler sample pretreatment, lower time and money spent, better environmental protection.
A sensitive and simple high-performance liquid chromatographic tandem mass spectrometric (LC-MS/MS) method for the determination of verapamil and norverapamil in human plasma was established and utilized in a pharmacokinetic study in healthy patients. Protein was precipitated by methanol in plasma samples, and the analytes and internal standard were separated on an Agilent Zorbax Eclipse C18 column (50 mm×4.6 mm, 5 μm) with a gradient procedure using methanol-acetonitrile (50:50) as the organic phase and 0.1% formic acid-5% acetonitrile-10 mmol·L-1 ammonium formate solution as the mobile phase at flow rate of 0.5 mL·min-1. Electrospray ionization (ESI) and multiple reaction monitoring (MRM) detection modes were used for quantitative detection of verapamil, norverapamil and verapamil-d6 (IS). In the mode of multiple reaction monitoring of positive-ions, the monitoring ion pairs of verapamil, norverapamil and the verapamil-d6 were m/z 445.0→165.2, m/z 441.0→165.2 and m/z 461.1→165.2, respectively. The quantitative lower limit (LLOQ) for the determination of verapamil and norverapamil concentrations in human plasma can reach 0.1 ng·mL-1 in this assay. The calibration curve concentration ranged from 0.1 to 50 ng·mL-1 with high linearity (r2>0.997). The matrix effect of verapamil and norverapamil was 99.2%-100% and 101%-102%, respectively. The recovery of verapamil and norverapamil was 86.8%-95.9% and 87.4%-94.8%, respectively. This method has good specificity and high sensitivity. The determination of the verapamil and norverapamil was not subject to the matrix effect and stable extraction recovery was achieved in this assay. This method could be used to determine the concentration of verapamil and norverapamil in human plasma and suitable for human pharmacokinetic studies after approved by ethics committee.
In this study, an immunostimulating particulate β-glucan was isolated from a hot alkaline extract of the fruiting bodies of Ganoderma lucidum. The optimum conditions of 8 hours treatment time, 1:20 solid-liquid ratio and 55℃ for the alkaline extract process were obtained after investigating by single-factor experiments and Box-Benhnken design in terms of the Ganoderma lucidum particulate β-glucan (GLG) increment, and these conditions resulted in a GLG yield of 8.57%. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. The result showed that resident macrophages were effectively activated by GLG, such as with the up-regulation of co-stimulatory molecules, the secretion of cytokines and phagocytic uptake. GLG could also promote the proliferation of spleen lymphocytes in mice. In addition, IFN-γ production of spleen CD4+T cells and cytotoxic T lymphocyte (CTL) responses were significantly enhanced on GLG orally treatment, which ultimately resulted in significantly decreased tumor burden. Taken together, these data suggest that GLG might act as an immune stimulator to exert antitumor effects.
To effectively identify the Astragalus and its adulterants based on ITS2 sequence and secondary structure, in this study, 32 portions of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Beg.) Hsiao and Astragalus membranaceus (Fisch.) Bge. collected were conducted ITS2 sequence amplification and bidirectional sequencing, whose results were then spliced by CExpress software remove the 5.8S and 28S sequences at both ends to obtain a complete ITS2 sequence. In addition, 3 ITS2 sequences for each of the adulterants of Astragalus, respectively, Oxytropis coerulea, Caragana sinica, Hedysarum polybotrys, Althaea rosea were downloaded from GenBank. The intra-specific and inter-specific genetic distances were calculated by the software MEGA7 to analyze the difference of each sequence; the Neighbor-joining (NJ) method was used to construct the phylogenetic tree based on ITS2 sequence (primary structure) as well as joint ITS2 sequence and its secondary structure. The results showed that the average ITS2 sequence length of both A. mongolicus and A. membranaceus was 216 bp, and their average GC content was 50.00% and 50.46%, respectively. The similarity of ITS2 sequence length and GC content between the two kind of Astragalus and Oxytropis coerulea was the highest, while the ITS2 sequence length and GC content of Althaea rosea showed great differences with those of Astragalus. The inter-specific distance between Astragalus and Oxytropis coerulea was the smallest, while that between the medicinal Astragalus and Hedysarum polybotrys, Caragana sinica as well as Althaea rosea was great. The phylogenetic trees constructed based on the ITS2 sequence (primary structure) and joint ITS2 sequence and its secondary structure showed that the topological relations of the two phylogenetic trees were basically the same, and both could effectively identify the Astragalus and its adulterants. What's more, the addition of secondary structure information made end branch of the phylogenetic tree become more in its construction, and the distinguish ability and approval rating were also improved, which further reflected the genetic relationship of Astragalus and its adulterants. This provides some scientific basis for classification and accurate identification of Astragalus and its adulterants.
There is no specific drug that has been approved for 2019-nCoV. There are a number of factors that pose major challenges in their development. Approaches to the development of anti-2019-nCoV include screening existing broad-spectrum antiviral drugs, repositioning of readily available clinical compounds, and de novo development of novel and specific agents for 2019-nCoV. Candidate compounds can be developed either to inhibit virus-based targets, such as RNA proteases, polymerase, spike glycoproteins, and viral envelop and membrane proteins, or to inhibit host-based targets, such as receptors and proteases that are utilized by virus for viral entry and endocytosis. Recently, the RNA polymerase remdesivir had demonstrated clinical efficacy in one patient with severe novel coronavirus pneumonia (NCP). The broad-spectrum viral protease inhibitor Kaletra® is also recommended in the current NCP clinical practice. Both drugs had lately been proceeded into multiple controlled phase Ⅲ clinical trials to test their safety and efficacy in NCP. Combinational therapies consisting of multiple drugs provide other viable options against 2019-nCoV, based on scientific and clinical rationales. Using bioinformatics and database analysis, we have identified 75 clinically compounds, including 20 marketed compounds, that are efficacious in inhibiting key targets in virus- and host-based approaches, which may facilitate the development of new therapeutic options for 2019-nCoV.
Hepatic selective insulin resistance refers to that insulin fails to suppress hepatic glucose production but continues to promote hepatic lipogenesis in insulin resistance. Therefore, type 2 diabetes mellitus is characterized with dyslipidemia apart from hyperglycemia. This review highlights the roles and molecular mechanisms of the key hepatic lipogenesis factors such as sterol regulatory factor binding protein 1c (SREBP1c), mammalian rapamycin target complex 1 (mTORC1), endoplasmic reticulum stress (ER stress), FoxO1, lipid synthesis substrate, etc.
Depression is a common mental illness with mood disorders as the main clinical feature. In recent years numerous studies have shown that mitochondrial function and structure are abnormal in patients with depression, and changes in mitochondrial ultrastructure can lead to energy metabolism disorders in the body. It is suggested that 'mitochondrial energy metabolism disorder' may be the pathogenesis of depression. This paper reviews the intrinsic association of mitochondrial energy metabolism with depression and notes potential mechanisms from the standpoint of mitochondrial structure and function on the molecular level. We provide a reference for understanding the pathogenesis of depression and identifying the possible targets of antidepressant drugs.
Neuropathic pain (NP), as a kind of chronic pain syndrome, seriously endangers the quality of life of patients, and the pathogenesis is complex, clinical treatment is limited, and it is easy to relapse. More and more reports have found that Wnt signaling pathway is closely related to the occurrence and development of neuropathic pain. Therefore, further study of the Wnt signaling pathway may provide useful ideas for exploring the pathogenesis of NP and discovering effective treatment methods. This article reviews the role and mechanism of Wnt signaling pathway in neuropathic pain.
Cerebral malaria (CM) is the deadliest complication of Plasmodium falciparum infection and even with effective anti-malarial treatment the mortality of children can be as high as 18%; up to one-third of CM survivors are left with neurological and cognitive deficits. The pathophysiology of CM is not completely understood, but mechanical obstruction and immunopathology are its mainstream theories. Adjuvant therapy aims to improve clinical outcomes and/or reduce mortality, as well as preventing long-term neurocognitive deficits. Improving survival and reducing neurological damage to survivors are new goals for new antimalarials and adjuvant therapies. Herein, we discussed what is known about the disease mechanism of CM and systematically summarize the progress of adjuvant therapy research in protecting the vascular endothelium, reducing adhesion formation, regulating immune balance, interfering with malarial metabolism, protecting nerves, improving nitric oxide bioavailability, improving energy metabolism and alleviating inflammation, with the aim of exploiting this understanding to reduce the neurological damage to children with CM. This work also highlights some preclinical studies which may be candidate strategies in future clinical trials.
Following small molecules and monoclonal antibodies, oligonucleotides are expected to overcome the rare and refractory human diseases. It has been attracted the attention of the pharmaceutical industry since the approval of six oligonucleotides in recent years because of their unique mechanism of regulating disease gene transcription at the RNA level. As a new class of drug molecules, oligonucleotides are highly polar, charged, and need to be improved by means of chemical modification and drug delivery systems. And therefore, they have different clinical pharmacology properties compared with chemical molecules and monoclonal antibodies, which pose new challenges for early clinical development. This paper reviews the characteristics of oligonucleotides from the perspective of technological development, mechanism of action, human pharmacokinetics, efficacy and safety.
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