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1.
China Pharmacy ; (12): 69-74, 2024.
Article in Chinese | WPRIM | ID: wpr-1005216

ABSTRACT

OBJECTIVE To develop a population pharmacokinetic (PPK) model for mycophenolate mofetil active metabolite mycophenolic acid (MPA) in children with primary IgA nephropathy, explore the factors affecting the pharmacokinetic parameters of MPA, and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model; the covariates were tested with a stepwise method. Goodness-of-fit plots, Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model (objective function value of 3 276.31). Covariate analysis suggested that body weight and albumin (ALB) levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows: the central room had a distributed volume of 5.79 L, the clearance rate was 4.06 L/h, the volume of peripheral ventricular distribution was 430.93 L, the clearance rate between compartments was 15.40 L/h, the oral absorption rate constant was 1.29 h-1. After verification, most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration, indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study, identifying body weight and ALB levels are significant factors affecting MPA metabolism.

2.
Acta Pharmaceutica Sinica ; (12): 591-599, 2024.
Article in Chinese | WPRIM | ID: wpr-1016619

ABSTRACT

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

3.
Acta Pharmaceutica Sinica ; (12): 735-742, 2024.
Article in Chinese | WPRIM | ID: wpr-1016617

ABSTRACT

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

4.
Acta Pharmaceutica Sinica ; (12): 764-774, 2024.
Article in Chinese | WPRIM | ID: wpr-1016607

ABSTRACT

italic>Cynanchum wallichii and Cynanchum otophyllum belong to the genus Cynanchum in the family Apocynaceae, and are important medicinal plants. In this study, we sequenced and assembled the chloroplast genomes of C. wallichii and C. otophyllum, and performed a phylogenetic analysis of the structural characteristics of their chloroplast genomes and their phylogenetic positions. The results showed that the chloroplast genomes of both C. wallichii and C. otophyllum had a typical tetrad structure, with 133 genes annotated, and the total GC contents of both were similar. Codon preference analysis showed that the relative synonymous codon usage in the chloroplast genomes of C. wallichii and C. otophyllum differed slightly, but the differences were not significant, and there was a strong A or U preference at the third codon position. In both chloroplast genomes, 91 and 103 simple sequence repeats were detected respectively, and the largest proportion of A/T type repeats. Nucleotide polymorphism analysis showed that the nucleotide diversity of the intergenic sequences in the chloroplast genome of genus Cynanchum were generally higher than those of the common gene sequences. A pair of primers was designed based on the high variation region of the chloroplast genome to identify C. wallichii and C. otophyllum. The phylogenetic analysis showed that the C. wallichii and Cynanchum thesioides were the closest relatives, while the C. otophyllum, Cynanchum bungei and Cynanchum wilfordii formed a stable monophyletic clade within the genus Cynanchum, and the three species were closely related. The comparative analysis of the chloroplast genomic characteristics and phylogeny of C. wallichii and C. otophyllum will provide a theoretical basis for the species identification of the two plants and for the study of genetic diversity and phylogeny of the genus Cynanchum.

5.
Acta Anatomica Sinica ; (6): 10-16, 2024.
Article in Chinese | WPRIM | ID: wpr-1015148

ABSTRACT

Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

6.
Acta Anatomica Sinica ; (6): 188-194, 2023.
Article in Chinese | WPRIM | ID: wpr-1015238

ABSTRACT

Objective Saiga antelope is a small population inhabiting in desert and semi desert areas of national and world endangered protected animals, its wild population is extremely rare. In order to explore the correlation between hypoxic tolerance and neuroglobin (NGB) in Saiga antelope. A female Saiga antelope died of dystocia was used as the experimental animal, and the tissue samples were sampled repeatedly for 3 times to study the distribution and expression of NGB in brain of Saiga antelope in the process of adapting to hypoxia. Methods The distribution and expression of NGB in the parietal lobe, frontal lobe, temporal lobe, occipital lobe, hypothalamus, hippocampus, pear like leaf, cingulate gyrus, striatum and thalamus of Saiga antelope were detected by immunohistochemistry(IHC) and Real-time PCR. Results The result of IHC showed that NGB was positive in all parts of Saiga antelope brain, and the cells that had positive reactions in the parietal, frontal, temporal and occipital lobes of the cerebral cortex were mostly granular cells and martinotti cells. NGB was found in the granular cell layer, pyramidal cell layer and molecular cell layer in hippocampus, and the positive staining of pyramidal cell layer was the strongest. NGB positive expression in Pear like leaves and hypothalamus mainly occured in multi-type cells. NGB was expressed in the granulocytes and glial cells of cingulate gyrus, mainly in the granular cells. The positive expression of NGB in striatum was mainly located in granular cells, the positive expression of NGB in thalamus could be seen in the polymorphosis and glial cells, and the positive substance of the multi-type cells was obviously colored. The result of Real-time PCR showed that NGB was expressed in different regions of Saiga antelope brain, the highest expression in the frontal lobe of the cerebral cortex, the second in the parietal lobe, and the expression was significantly higher than that in the rest of the brain tissue (P0.05). Conclusion The expression of NGB in different regions of Saiga antelope has some selective differences in the long-term adaptation to hypoxia environment. The frontal and parietal lobes have the highest tolerance to hypoxia, followed by hippocampus, and the striatum is the weakest, which may be related to the specific functions of different regions of brain tissue, but the specific mechanism remains to be further explored.

7.
Acta Physiologica Sinica ; (6): 369-378, 2023.
Article in Chinese | WPRIM | ID: wpr-981013

ABSTRACT

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.


Subject(s)
Mice , Male , Animals , Stress Disorders, Post-Traumatic , Hippocampus , Spatial Learning , GABAergic Neurons
8.
Acta Physiologica Sinica ; (6): 269-278, 2023.
Article in Chinese | WPRIM | ID: wpr-981004

ABSTRACT

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.


Subject(s)
Male , Animals , Humans , Mice , Transcription Factors/genetics , Mammals/metabolism , Cell Differentiation , Neoplasms/genetics
9.
Acta Pharmaceutica Sinica ; (12): 1677-1684, 2023.
Article in Chinese | WPRIM | ID: wpr-978725

ABSTRACT

We constructed and optimized the plasmid DNA (pDNA) Opt-S encoding the gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein, using poly (lactic-co-glycolic acid) copolymer (PLGA) as a delivery carrier for pDNA. PLGA-pDNA NPs were loaded by nanoprecipitation and its properties in vitro were preliminary evaluated. The results showed that the prepared PLGA-pDNA NPs were regular morphology, clear edges, with an average particle size of (184.2 ± 2.4) nm, polydisperse index (PDI) of 0.093 ± 0.013, zeta potential of (-68.10 ± 0.36) mV, and encapsulation rate of (98.92 ± 0.22)%. The PLGA-pDNA NPs were stable at -20 ℃ for 7 months and could protect pDNA against nuclease degradation. And they also exhibited sustained release of pDNA in vitro. The PLGA-pDNA NPs have low cytotoxicity and high safety. In addition, in vitro transfection experiments showed that the SARS-CoV-2 S gene could enter cells and be expressed. These results indicate that PLGA-pDNA NPs non-viral gene vector have simple preparation process and good performance, which are expected to provide a new idea for the research and development of SARS-CoV-2 vaccine.

10.
Acta Pharmaceutica Sinica ; (12): 1577-1585, 2023.
Article in Chinese | WPRIM | ID: wpr-978720

ABSTRACT

In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.

11.
Acta Physiologica Sinica ; (6): 91-98, 2023.
Article in Chinese | WPRIM | ID: wpr-970109

ABSTRACT

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.


Subject(s)
Female , Animals , Histone Code , Histones , Protein Processing, Post-Translational , Ovary , Oocytes , Mammals
12.
Acta Pharmaceutica Sinica ; (12): 86-94, 2023.
Article in Chinese | WPRIM | ID: wpr-964290

ABSTRACT

Polymer self-healing is mainly based on the molecular structure and interaction of polymers, and some need external stimulation, such as light, heat, pH, etc. In recent years, many studies have found that the self-healing properties of polymers can prolong the life of materials, while maintaining the mechanical properties of polymers after healing. According to the different action modes of polymer materials, it can be divided into autonomous self-healing and non-autonomous self-healing. Among them, autonomous self-healing mainly works through reversible covalent bonds (Schiff base bond, Diels-Alder reaction, hydrazide bond), reversible non-covalent bonds (hydrogen bond, metal-ligand coordination bond, electrostatic interaction, π-π stacking interaction, hydrophobic interaction) and a combination of the two interactions. Drug carriers with unique self-healing properties play an important role in the encapsulation and stable release of biomacromolecules. In this review, the self-healing mechanism of polymers and their applications in the field of biomedicine were briefly summarized and discussed.

13.
Chinese Journal of Pediatrics ; (12): 642-647, 2023.
Article in Chinese | WPRIM | ID: wpr-985923

ABSTRACT

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.


Subject(s)
Humans , Male , Infant , Acidosis, Lactic , Brain , Brain Stem , Dystonia , Dystonic Disorders , Mitochondrial Diseases
14.
Acta Pharmaceutica Sinica ; (12): 3108-3115, 2023.
Article in Chinese | WPRIM | ID: wpr-999048

ABSTRACT

Based on the dual needs of analgesia and anti-inflammation in trauma treatment, this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology. Due to the complexity of the 3D printing process, there is an interaction between the various parameters. Through the optimization of the process, the relationship between the key process parameters can be determined more intuitively. In this study, the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release. The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors. The optimal extended-release process parameters were obtained by the response optimizer: the inkjet quantity of the printing ink was 10 (about 13.8 pL), the powder thickness was 180 μm, and the running speed was 360 mm·s-1. The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model. The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size, and the dissolution of the immediate release layer within 15 min was greater than 85%. The internal pore size of the extended release layer is large, but it can still release slowly for up to 8 h, the mechanism may be related to the extended release of HPMC gelation. On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets, this study also provides a theoretical basis for the preparation of 3D printing complex preparations.

15.
Acta Pharmaceutica Sinica ; (12): 2811-2817, 2023.
Article in Chinese | WPRIM | ID: wpr-999024

ABSTRACT

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

16.
Chinese Journal of Biotechnology ; (12): 2485-2501, 2023.
Article in Chinese | WPRIM | ID: wpr-981213

ABSTRACT

Amino acids are the basic building blocks of protein that are very important to the nutrition and health of humans and animals, and widely used in feed, food, medicine and daily chemicals. At present, amino acids are mainly produced from renewable raw materials by microbial fermentation, forming one of the important pillar industries of biomanufacturing in China. Amino acid-producing strains are mostly developed through random mutagenesis- and metabolic engineering-enabled strain breeding combined with strain screening. One of the key limitations to further improvement of production level is the lack of efficient, rapid, and accurate strain screening methods. Therefore, the development of high-throughput screening methods for amino acid strains is very important for the mining of key functional elements and the creation and screening of hyper-producing strains. This paper reviews the design of amino acid biosensors and their applications in the high-throughput evolution and screening of functional elements and hyper-producing strains, and the dynamic regulation of metabolic pathways. The challenges of existing amino acid biosensors and strategies for biosensor optimization are discussed. Finally, the importance of developing biosensors for amino acid derivatives is prospected.


Subject(s)
Animals , Humans , Amino Acids , Biosensing Techniques , Metabolic Engineering , High-Throughput Screening Assays , China
17.
Chinese Journal of Neurology ; (12): 715-722, 2022.
Article in Chinese | WPRIM | ID: wpr-957959

ABSTRACT

Objective:To summarize clinical features, outcome and prognosis of anti-myelin oligodendrocyte glycoprotein IgG associated disorders (MOGAD) in children, and to explore the markers of recurrent MOGAD.Methods:The clinical features, imaging, serum and cerebrospinal fluid immune markers, treatments and outcomes were analyzed and compared between children with monophasic and recurrent MOGAD, who were hospitalized in the Department of Neurology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics from January 2019 to February 2020.Results:A total of 22 children were included, of whom 8 patients (36.4%) had a recurrent course and 14 patients (63.6%) had a monophasic course. There was no statistically significant difference in sex, age of onset, clinical symptoms, modified Rankin Scale score, location of lesions and serum anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) titer, overall duration of total immunotherapy, positive antinuclear antibody and history of precursory infection between the two groups ( P>0.05). The serum MOG-IgG titer in the recurrent course group was more likely to remain unchanged or increased, and even increased after treatment, while there was no increase in the serum MOG-IgG titer in the monophasic course group, and the proportion of the patients with serum MOG-IgG titer decreased was higher in the monophasic course group (the monophasic course group: 6/8, the recurrent course group: 2/8), and there was statistically significant difference between the two groups ( P=0.030). The positive rate of MOG-IgG in cerebrospinal fluid in the recurrent course group was significantly higher than that in the monophasic course group at the first attack, the difference being statistically significant (the monophasic course group: 1/10, the recurrent course group: 4/6, P=0.036). The both groups were effecive to first-line immunotherapy, and the clinical symptoms and imaging were completely or partially recovered compared to the acute phase. Seven of 8 patients with recurrent MOGAD were treated with mycophenolate mofetil, and the recurrence rate decreased significantly [annual recurrence rate before treated with mycophenolate mofetil: 2.06 (1.36, 2.34) times/year, annual recurrence rate after treated with mycophenolate mofetil: 0 (0, 0) time/year, Z=-3.26, P=0.001]. The humoral immune status of children treated with mycophenolate mofetil was monitored regularly, and no obvious adverse reactions were found during the follow-up. Conclusions:At least one third of children with MOGAD were recurrent, and the serum MOG-IgG titer of children with recurrent MOGAD continued to be high, and even increased after treatment. Positive MOG-IgG in cerebrospinal fluid at the first attack was found to be a high risk factor for recurrence. The maintenance treatment of mycophenolate mofetil in patients with recurrent MOGAD can significantly reduce the annual recurrence rate and was well tolerated.

18.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 990-998, 2022.
Article in Chinese | WPRIM | ID: wpr-1015773

ABSTRACT

O⁃GlcNAcylation is an O⁃linked⁃β⁃N⁃acetylglucosamine modification attached to the hydroxyl group of serine or threonine residue within the nuclear or cytoplasmic proteins. O⁃GlcNAcylation profoundly influences important biological events, including kinase activity, transcription and translation, and protein degradation. However, there are few summarized reviews on how O⁃GlcNAcylation modulates signaling pathways associated with inflammatory responses. Due to the attachment and removal of the sugar group catalyzed by O⁃GlcNAc transferase and O⁃GlcNAcase, O⁃GlcNAcylation cycles rapidly with a short half⁃life time (within minutes). Therefore, O⁃GlcNAcylation plays a crucial role in various signaling pathways via intricate cross⁃talking with other post⁃translational modifications of protein, such as phosphorylation, acetylation, ubiquitylation, and methylation. Currently, most researchers focused on the Toll⁃like receptor (TLR)⁃initiated NF⁃κB signaling when it comes to the relationship between O⁃GlcNAcylation and inflammation. Evidence has shown that O⁃GlcNAcylation at T352 or at T305 on p65 promotes its nuclear translocation activity, while O⁃GlcNAcylation at S536 blocks the activation of p65 by competing with phosphorylation. Meanwhile, O⁃GlcNAcylation modulates upstream and downstream regulators of NF⁃κB and then governs the polarization of M1/ M2 macrophage and the progress of inflammation reactions. Furthermore, O⁃GlcNAcylation indirectly participates in the kinase activation of MAPKs by interfering with the proteins at the upper reaches (i. e. MEK2 and Ras proteins). Besides, O⁃GlcNAcylation has a profound influence on multiple kinases of PI3K/ AKT signaling. Nevertheless, O⁃GlcNAcylation manipulates inflammation⁃associated transcriptional factors on the JAK/ STAT pathway. Comparatively, the involved signaling transduction for the inflammatory response in vivo is far more complicated and multidimensional than that in vitro. And O⁃GlcNAcylation is widely involved with the onset and development of inflammatory diseases located at the pancreas, liver, lung, gut, and adipose tissues. Novel research has firstly found that gut bacteria expressing O⁃GlcNAcase⁃like hydrolases exert potent prevention on mouse colitis induced by different chemical drugs, which indicates the mediating role of O⁃GlcNAcylation in mutual interactions between gut microbiota and host inflammation. In summary, recent findings provided a novel strategy for preventing and treating inflammatory diseases by targeting O⁃GlcNAcylation.

19.
Acta Pharmaceutica Sinica ; (12): 2503-2511, 2022.
Article in Chinese | WPRIM | ID: wpr-937042

ABSTRACT

In order to meet the clinical needs of long-acting sustained-release thienorphine, injectable thienorphine loaded microspheres were developed, and the accelerated stability study was carried out to explore the suitable storage and transportation conditions of the microspheres. Using poly(lactic-co-glycolic acid) (PLGA) as carrier material, 3 batches of microspheres were prepared in pilot scale with emulsion solvent evaporation method. By investigating the in vitro release of thienorphine loaded microspheres at 37, 45, 52, and 60 ℃, and applying the Arrhenius equation, the linear relationship between the release rate constant (lgk) and the temperature (1/T) was established to obtain the equation: lgk = -8.073/T + 24.35 (R2 = 0.985 3), which showed that the release of microspheres at high temperature can be used to predict the release in vitro at 37 ℃, and 52.0 ± 0.5 ℃ was selected as the accelerated release condition in vitro. The quality research methods were established to investigate the changes of critical quality attributes such as microsphere morphology, drug loading, particle size and distribution, polymer molecular weight, and the related substances under accelerated conditions. The difference factor f1 and similarity factor f2 were used to assess the similarity of release behavior under accelerated conditions. The results showed that under the accelerated experimental conditions of 25 ± 2 ℃ and relative humidity (RH) 60% ± 5%, the critical quality attributes of injectable thienorphine loaded microspheres had no significant change in 6 months, suggesting that the long-term storage condition could be 5 ± 3 ℃.

20.
Acta Pharmaceutica Sinica ; (12): 2512-2519, 2022.
Article in Chinese | WPRIM | ID: wpr-937033

ABSTRACT

In this study, the reverse engineering technology was used to analyze the prescription and process of Doppelherz® Energy DIRECT, based on the composition of the prescription on the official website of the product, the detection method of composition is established according to the pharmacopoeia and literature information, combined with gravimetric analysis to complete prescription analysis. The prescription composition of the reference listed drug was determined to be composed of caffeine, taurine, vitamin B, anhydrous glucose, citric acid, sorbitol, sucralose, magnesium salts of fatty acids, in which the glucose content was 71.4%, the citric acid content was 7.0% and the magnesium salts of fatty acids content was < 5.8%. According to patent inquiry, Raman imaging and other technologies, the preparation process of the marketed preparation has been basically obtained, and the development of the self-made preparation has been completed on this basis. The study was approved by the Ethics Committee of the Academy of Military Medical Sciences. Combined with the results of the taste evaluation experiment and the caffeine dissolution test of the preparation in 1 min, the hot-melt extrusion technology was screened out as the taste-masking technology of the self-made preparation, the parameters of the hot-melt extrusion process were screened by differential scanning calorimetry analysis, and finally a product with good taste and qualified quality was obtained, which provided a reference method for the research and development of related preparations.

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