Plant-derived nanovesicles: Further exploration of biomedical function and application potential

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Interpretation and thinking of indicators of pharmaceutical administration in National Tertiary Public Hospitals Performance Evaluation Operational Manual （2022 edition） / 中国药房

OBJECTIVE To interpret the revision of the in dicators o f pharmaceutical administration in National Tertiary Public Hospitals Performance Evaluation Operational Manual （2022 edition）[hereinafter referred to as the Mannual（2022 edition）]，and to provide reference for the implementation of a new round of performance appraisal in tertiary public hospitals. METHODS The contents and revision details of the indicators of pharmaceutical administration in the Mannual（2022 edition）were described briefly，and the revised contents were interpreted and relevant suggestions were put forward. RESULTS & CONCLUSIONS The Manual（2022 edition）continued the scope of performance evaluation ，indicators’structure and sequence in the Manual（2020 edition），which focused on rational drug use and drug cost control. The Manual （2022 edition） placed more emphasis on strengthening the provision and use of essential medicines and selected drugs in the centralized drug procurement ，and further reducing the burden of medical costs in patients. It is suggested that tertiary public hospitals scientifically set indicators for the use of essential medicines ，selected drugs in the centralized drug procurement ，auxiliary drugs and antibacterial drugs in clinical departments，and improve relevant incentive mechanisms and performance assessment systems ；strengthen the interpretation of policies about essential medicines and drug centralized procurement ，as well as the training of rational drug use ；optimize in-hospital drug catalog and formulary ；formulate medication standards ，strengthen prescription review ，rational medication review and assessment ；establish and improve the drug use monitoring and evaluation and early warning system so as to standardize clinical drug use behavior by information technology ；strengthen the use of essential drugs and centrally purchase selected drugs on the basis of ensuring rationality ；control the unreasonable gradually reduce the increase in average drug costs.

Effects of RNA binding protein RNPC1 on biological function of renal cell carcinoma cells / 医学研究生学报

Objective RNPC1 may act as an oncogene or suppressor gene in human tumors and its role in human renal cell carcinoma (RCC) remains unclear.The objective of this study was to investigate the role of RNPC1 in the development of RCC.Methods Over-expression of RNPC1 gene group (RNPC1 group) and short hairpin RNA interfering RNPC1 gene expression (shRNPC1 group) were respectively built in RCC CAKI-1 and CAKI-2.The blank control group (NC group) and negative control group (SCR group) were built as well.The qRT-PCR and western blot (WB) were used to detect the expression levels of RNPC1 mRNA and RNPC1 protein in RCC cells.Lentivirus infection was applied to establish stable expressed RCC cell lines of RNPC1 over-expression and interference.Detection was made on mRNA and protein expression levels in RNPC1 stable RCC cell lines.The effects of RNPC1 on cell proliferation, colony formation assay, migration, and invasion were detected by CCK-8 cell differentiation test, clone test, scratch test, and migration and invasion test.WB was applied to detect the change of protein expression in the EMT path of RNPC1 stable RCC cell lines and explore the molecular mechanism of RNPC1 effect on the biological function of RCC cells.Results The expression levels of RNPC1 mRNA and protein were found lower in shRNPC1 group than those in SCR group, while the expression levels of RNPC1 mRNA and protein in SCR group were higher than those NC group (P<0.05).The capability of proliferation in shRNPC1 group was stronger than that in SCR group, while the capability of proliferation in shRNPC1 group was weaker than that in NC group (P<0.05).The capabilities of cell migration and invasion were stronger in shRNPC1 group than those in SCR group, while the capabilities of cell migration and invasion in RNPC1 group were weaker than those in NC group (P<0.05).RNPC1 could inhibit the proliferation capability of RCC cells and might up-regulate the protein expression of E-cadherin and down-regulate the protein expression of β-catenin and vimentin, thus inhibiting EMT path and the capabilities of migration and invasion off RCC cells (P<0.05).Conclusion RNPC1 acts as a tumor suppressor in RCC and has the potential for the prediction of RCC prognosis.

Exploration of Specification Rationality of Capsules Commonly Used in Children by Capsule Application Analysis in a Children's Hospital / 中国药师

Objective: To study the dosages of capsules commonly used in children to provide reference for the addition of capsule specification for children.Methods: According to the application situation of capsule dosages commonly used for the inpatients in one children's hospital from January 1, 2013 to September 1, 2016, and combined with the usage rates of various drugs with different dosages, the addition of the minimum dosage of capsules was proposed.Results: Totally 10 species of commonly used capsules were selected from the children's hospital, and among them, 4 ones met the requirements of clinics, and the other 8 ones needed the specification addition, including clostridium butyricum capsules (210 mg) and polysaccharide ferric complex capsules (25 mg).Conclusion: The existing capsule specification can not fully meet the clinical requirements in the children's hospital.Therefore, appropriate dosage adjustments are still needed.

Optimizing Effect of PDCA Cycle on Emergent Medicine Management of Inpatient Area Based on JCI / 中国药师

Objective: To establish the standardized management mode for emergent medicines of inpatient area based on JCI. Methods:The expiry verification data of emergent medicines in hospital wards were collected from 2013 to 2015. The number and the amount of emergent medicines expired in the last three months in each calendar month during the three years were analyzed, the exist-ing problems in the management mode were found out and gradually optimized using PDCA cycle. Results:From 2013 to 2015, the re-placement amount of emergent medicines expired in the next month was 3497. 37 yuan. The number of emergent medicines expired in current month was 62. A total of 420 times of emergent medicines didn' t meet the requires of expiry verification from 2013 to 2015. After the check-in form redesign for emergent medicines and the standardization of replacement process, the number of expired medi-cines in the rescue carts was reduced, and the validity and quantity of drugs in all the rescue vehicles could be clearly shown in the new form. Conclusion:The standardization of emergent medicine management model can guarantee the safety of emergent medicines used in patients.

Exploration of a training mode for professional-degree postgraduates of clinical pharmacy / 医学研究生学报

Balanced emphasis on theory and clinical practice is essential to the training of professional-degree postgraduates of clinical pharmacy. In this article, the author explores a training mode for professional-degree postgraduates of clinical pharmacy in such aspects as establishing a pharmacy-clinic double-tutor system, designing applied theoretical courses, combining theoretical courses with clinical practice, offering gradual in-depth clinical practice, and cultivating clinical practice-based abilities of scientific research.

Correlation between Empty Bottle Volume, Negative Pressure and Gas Production Volume of Freeze-dried Powder Commonly Used in Children / 中国药师

Objective: To study the correlation between the empty bottle volume, negative pressure and gas production of the freeze-dried powder in the out-patient pharmacy intravenous admixture center of a children' s hospital in order to provide reference for the drug production. Methods:20 ml Syringes were used to measure the volume of empty bottles, negative pressure and produced gas. The relationship between the theoretical drug dissolution volume and the actual dissolution volume was compared, and the precautions for the drug production were put forward. Results:Among the tested 30 drugs, 6 ones were with the actual dissolution volume half of the theoretical dissolution volume, 8 ones were with negative pressure in the bottles, and 3 ones were with produced gas after dissol-ving. It was appropriate that the empty bottle volume be 4 ml larger than the theoretical dissolution volume, and it was appropriate that the negative pressure volume of drugs was slightly larger than the theoretical dissolution volume. Negative pressure should be still kept in the bottles after the gas production. Conclusion:The design of part of freeze-dried powder injection needle shows defects resulting in drug mixing difficulties to a certain extent.

Levels of IL-18, IL-16, IL-8, eotaxin and the chymase activity in the sputum of asthmatics / 中国病理生理杂志

AIM: To investigate the levels of IL-18, IL-16, IL-8, eotaxin and the chymase activity in the sputum of asthmatics. METHODS: IL-18, IL-16, IL-8 and eotaxin levels were detected with sandwich ELISA procedures and chymase activity was determined spectrophotometrically (410 nm) by the rate of hydrolysis of N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide (SAAPP). RESULTS: The specific chymase activities in the severe and moderate asthmatics were higher than that in controls. Native protease inhibitors ?_1-antitrypsin (?_1-AT) and soybean trypsin inhibitor (SBTI) inhibited 71.9% and 72.1% enzymatic chymase activity, respectively. The levels of IL-18, IL-16, IL-8 and eotaxin were significantly elevated in the sputum of patients with acute asthma. There were correlations between the levels of IL-8 and IL-16 (r=0.55, P

Induction of histamine release from human mast cells by Chinese cobra snake venom metalloproteinase / 中国病理生理杂志

AIM: To investigate the ability of Chinese cobra snake venom-metalloproteinase(MT) to induce the histamine release from human mast cells and its potential mechanisms.METHODS: MT was purified from the snake venom by using heparin agarose and Superdex75 chromatography.Mast cells were dispersed from human lung, colon and tonsil tissues after digestion with collagenase and hyaluronidase.The dispersed mast cells were then challenged with MT,stimulus and control in LP4 tubes for 15 min at 37 ℃.A glass fibre-based fluorometric assay was used to measure histamine in the supernatants of dispersed mast cells.RESULTS: MT induced a dose-dependent release of histamine from human colon,lung and tonsil mast cells.As low as 0.03(mg/L) of MT was able to stimulate significant histamine release from human colon mast cells,but a minimum of 0.3 or 30 mg/L of MT was required to stimulate a similar level of histamine release from lung or tonsil mast cells,respectively.The release of histamine from colon and lung mast cells in response to MT was maximized at 12 min following the addition of the stimulus.This was quite different from the picture of the peak histamine release from tonsil mast cells,in which histamine release was maximized at 8 min following the addition of MT.Pretreatment of cells with metabolic inhibitors and pertussis toxin reduced dramatically histamine release from human colon,lung and tonsil mast cells by MT.In exogenous Ca~(2+) and Mg~(2+) free experiments,the release of histamine induced by MT was significantly decreased.CONCLUSION: Cobra snake venom MT induces human mast cells to release histamine through a G-protein-related mechanism,which may contribute to the pathogenesis of venomous snake bite.

The apoptosis of HUVCE cell line induced by L-amino acid oxidase from snake of bungarus fasciatus / 中国病理生理杂志

AIM: To investigate the effect of purifried L-amino acid oxidase (LAO) from bungarus fasciatus snake venom on apoptosis and growth of HUVCE cell line. METHODS: The L-amino acid oxidase was purified by SP-sepharose HP column followed by Heperin-Sepharose (FF) column. The homogeneity of the preparation was examined by SDS-PAGE and the molecular weight of LAO was determined by SDS-PAGE and high performance liquid chromatography (HPLC) gel-filtration. The MTT assay was used to detect the viability of cells. Flow cytometry and laser confocal microscopy were used to identiyfy the cell cycle and apoptotic morphology after cells treated with LAO. RESULTS: An L-amino acid oxidase (BF-LAO) was successfully purified from the venom of bungarus fasciatus. It showed a single band in SDS-PAGE under both reduced and non-reduced conditions. The apparent molecular weight was determined to be 60 kD by SDS-PAGE and 70 kD by HPLC gel filtration. LAO inhibited growth and induced apoptosis of HUVCE cell line in a dose-dependent manner after 12 h incubation, with the 50% inhibitory concentration (IC_ 50 ) being of 2.8 mg/L. Flow cytometry and laser confocal microscope showed a typical apoptotic peak and morphological changes of these cells. CONCLUSION: The L-amino acid oxidase from bungarus fasciatus snake venom could inhibit the HUEVC cell growth and induce the cell apoptosis.