OBJECTIVE: To investigate the safety and efficacy of a new proteasome inhibitor Ixazomib followed by autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of POEMS syndrome. METHODS: The clinical manifestations, diagnosis and treatment process and follow-up results of 4 patients with POEMS syndrome who were treated with Ixazomib-based regimen combined with AHSCT in Wuhan No.1 Hospital from February 2018 to July 2020 were analyzed retrospectively. All patients were male, aged from 37-54 years old, with varying degrees of peripheral neuropathy, organ enlargement (liver, spleen or lymph nodes), circulatory overload (peripheral edema and/or pleural effusion), osteosclerosis, endocrine diseases (thyroid, gonads, etc.), skin changes (pigmentation, hemangioma, white nails, etc.), M protein, papilledema and other clinical manifestations and characteristics at the time of initial treatment. Two patients were pathologically diagnosed as hyaline vascular Castleman disease by lymph node biopsy. Three patients underwent lumbar puncture examinations and all showed elevated cerebrospinal fluid protein. All patients received at least 2 cycles of sequential AHSCT after induction chemotherapy based on ixazomib. The follow-up time was 10-28 months, and the median follow-up time was 16 months. RESULTS: All cases survived. The complications were controllable during the treatment. Moreover, the clinical symptoms related to the disease were improved to a certain extent after the treatment. The levels of vascular endothelial growth factor (VEGF) showed a gradual decline. CONCLUSION Ixazomib combined with AHSCT is safe and effective in the treatment of POEMS syndrome.
Adult ; Boron Compounds ; Glycine/analogs & derivatives* ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; POEMS Syndrome/therapy* ; Retrospective Studies ; Transplantation, Autologous ; Vascular Endothelial Growth Factor A

A stable Zr-based metal-organic framework (MOF, UiO-66-NH2) synthesized via micro-water solvothermal method was used to immobilize amidase by using the glutaraldehyde crosslinking method. The effect of immoblization conditions on enzyme immoblization efficiency was studied. An activity recovery rate of 86.4% and an enzyme loading of 115.3 mg/g were achieved under the optimal conditions: glutaraldehyde concentration of 1.0%, cross-linking time of 180 min, and the weight ratio of MOF to enzyme of 8:1. The optimal temperature and optimal pH of the immobilized amidase were determined to be 40 °C and 9.0, respectively, and the Km, Vmax and kcat of the immoblized amidase were 58.32 mmol/L, 16.23 μmol/(min·mg), and 1 670 s⁻¹, respectively. The immobilized enzyme was used for (S)-4-fluorophenylglycine synthesis and the optimal reaction conditions were 300 mmol/L of N-phenylacetyl-4-fluorophenylglycine, 10 g/L of immobilized enzyme loading, and reacting for 180 min at pH 9.0 and 40 °C. A conversion rate of 49.9% was achieved under the optimal conditions, and the conversion rate can be increased to 99.9% under the conditions of enantiomeric excess. The immobilized enzyme can be repeatedly used, 95.8% of its original activity can be retained after 20 cycles.
Amidohydrolases ; Enzyme Stability ; Enzymes, Immobilized/metabolism* ; Glycine/analogs & derivatives* ; Hydrogen-Ion Concentration ; Metal-Organic Frameworks ; Temperature

Glycine/analogs & derivatives* ; Humans ; Vasculitis, Leukocytoclastic, Cutaneous

Peptide nucleic acid (PNA) is a DNA surrogate in which the phosphate deoxyribose backbone of DNA is replaced by repeating N-(2-aminoethyl)glycine units. PNA can hybridize to the complementary DNA and RNA with higher affinity than their oligonucleotide counterparts. This character of PNA not only makes it a new tool for the studies of molecular biology but also the potential candidate for gene-targeting drugs. The non-ionic backbone of PNA leads to stable hybrids with the nucleic acids, but at the same time, the neutral backbone results in poor cellular uptake. To address this problem, studies on modified PNA progress rapidly in recent years. We reviewed literature reports combined with our study about the delivery methods, including backbone modified PNA and PNA-ligand conjugates, and the cellular uptake of modified PNA. In addition, we summarized the problems and future prospect of the cellular delivery of modified PNA.
DNA, Complementary ; Drug Delivery Systems ; Glycine ; analogs & derivatives ; Humans ; Nucleic Acid Hybridization ; Oligonucleotides ; Peptide Nucleic Acids ; chemistry ; RNA

Metabolism and deposition of exogenous gene and protein from transgenic glyphosate herbicide-tolerant soybean meal in SD rats were studied in the experiment. The transgenic soybean GTS40-3-2 meal and its non-transgenic counterpart (parent A5403) were fed to the generation and the second generation Sprague-Dawley (SD) rats (Rattus norvegicus). The study added the genetically modified (GM) soybean meal and its non-transgenic control soybean meal (parent A5403) in a ratio of 20% respectively to the feeds. By using qualitative, quantitative PCR and ELISA methods to detect transgenic soybean residues of metabolism ingredients in rats, the safety and influence of GM soybean were evaluated. The results showed that the intestinal fecal and cecum contents of rats were detected with residues of GM ingredients, intestinal flora and organs were not found related genes and protein. These results indicated that transgenic glyphosate herbicide-tolerant soybean GTS40-3-2 meal was as safe as its non-GM soybean meal in long-term feeding study.
Animal Feed ; Animal Nutritional Physiological Phenomena ; Animals ; Digestion ; Glycine ; analogs & derivatives ; Herbicide Resistance ; Herbicides ; Plants, Genetically Modified ; Proteolysis ; Rats ; Rats, Sprague-Dawley ; Soybean Proteins ; Soybeans

A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.7 mL · min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng · mL(-1) for sivelestat, and 2.50-1000 ng · mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng · mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers.
Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Glycine ; analogs & derivatives ; blood ; Humans ; Inosine Monophosphate ; blood ; Reproducibility of Results ; Sulfonamides ; blood ; Tandem Mass Spectrometry

This study aims to detect the expression of metabotropic glutamate receptors (mGluRs) in lung carcinoma A549 cells, and to investigate the effects of mGluR8 and mGluR4 activation on the growth of A549 cells in vitro. The mRNA expression levels of the 8 subtypes of mGluRs in A549 cells were determined by real-time PCR. Immunohistochemistry was used to analyze the protein expression of mGluR4 and mGluR8 in A549 cells and lung tissue sections obtained from lung adenocarcinoma patients. To observe the effects of mGluR8 and mGluR4 activation on the growth of A549 cells, the cultured cells were treated with (S)-3,4-DCPG (an agonist of mGluR8) and VU0155041 (an agonist of mGluR4), respectively, and then the cell viability was analyzed by CCK-8 kit, the percentage of DNA synthesis was detected by EdU incorporation, and the apoptosis of the cells was measured by hoechst 33258 staining and flow cytometry. The results showed that there were low expressions of mGluR1, mGluR5, mGluR6, mGluR7 mRNA, no expression of mGluR2 and mGluR3 mRNA, and high expressions of mGluR8 and mGluR4 mRNA in A549 cells. Accordingly, there were also mGluR4 and mGluR8 protein expressions in the A549 cells and the lung adenocarcinoma tissue sections. VU0155041 had no effect on the growth of A549 cells, but (S)-3,4-DCPG significantly decreased the cells' growth in a dose-dependent manner and increased the apoptosis of the cells. The results revealed a role of mGluR8 in the growth and apoptosis of A549 cells and suggested a potential target for clinical treatment of lung cancer.
Anilides ; pharmacology ; Apoptosis ; Benzoates ; pharmacology ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Cyclohexanecarboxylic Acids ; pharmacology ; Glycine ; analogs & derivatives ; pharmacology ; Humans ; Lung Neoplasms ; pathology ; Receptors, Metabotropic Glutamate ; physiology

The purpose of this study is to explore depression metabolic markers in rat hippocampus and to investigate the anti-depressant effect of genipin and its mechanisms using nuclear magnetic resonance (NMR) metabonomics. Chronic unpredictable mild stress (CUMS) procedure was conducted to establish the depressive rat model. At the beginning of the third week, genipin low dose (25 mg x kg(-1)), middle dose (50 mg x kg(-1)), high dose (100 mg x kg(-1)), and venlafaxine (50 mg x kg(-1)) were given to the CUMS rats separately once daily for two weeks except control and model groups. Rat hippocampus was analyzed by 1H NMR based metabonomics after drug administration for 2 weeks. Significant differences in the metabolic profile of rat hippocampus of the CUMS treated group and the control group were observed with metabolic effects of CUMS including decreasing in glycine and N-acetylaspartate, increasing in inositol, glutamate, lactate, glutamine, taurine and alanine. Genipin showed ideal antidepressive effects at a dose of 50 mg x kg(-1) in rats, decrease of inositol, glutamate, lactate, alanine were observed, while glycine and N-acetylaspartate were increased. Important influence has been found on normal nervous system function of these significant changed metabolites, which suggests that the antidepressant effect of genipin may be played by enhancing the activity of neurons in hippocampus, repairing and improving the function of the neuron. The metabonomics approach is an effective tool for the investigation of the anti-depressant effect and pharmacologic mechanisms of genipin.
Alanine ; metabolism ; Animals ; Antidepressive Agents ; isolation & purification ; pharmacology ; Aspartic Acid ; analogs & derivatives ; metabolism ; Behavior, Animal ; drug effects ; Chronic Disease ; Depression ; drug therapy ; metabolism ; physiopathology ; Gardenia ; chemistry ; Glutamic Acid ; metabolism ; Glycine ; metabolism ; Hippocampus ; drug effects ; metabolism ; Inositol ; metabolism ; Iridoids ; isolation & purification ; pharmacology ; Lactic Acid ; metabolism ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

Air Pollution, Indoor ; analysis ; Chromatography, High Pressure Liquid ; Glycine ; analogs & derivatives ; analysis ; Humans ; Workplace

Glycine ; analogs & derivatives ; toxicity ; Herbicides ; toxicity