Preparation and osteoinductivity of piezoelectric polyvinylidene fluoride foam-based scaffold / 中国组织工程研究

BACKGROUND:Bone is a remarkable natural material possessing piezoelectric properties.By harnessing the biomimetic piezoelectric effect,tissue engineering materials can be employed to effectively address bone tissue defects and facilitate their repair. OBJECTIVE:Using a solid-phase force chemistry technique,a piezoelectric scaffold with inherent osteogenic properties was meticulously fabricated.This unique scaffold was then assessed for its impact on osteoblast adhesion,proliferation,and osteogenic differentiation. METHODS:Polyvinylidene fluoride(PVDF)powders,along with commercially available NaCl(mass ratios are 60:40,50:50,40:60,and 30:70,respectively),were subjected to solid-phase shear milling technology,resulting in a homogenous mixture.Through a melting process,a substantial material was formed,and subsequent treatment with a pure water solution effectively eliminated the NaCl.Consequently,PVDF piezoelectric foam scaffolds with varying pore sizes were successfully prepared.These materials were categorized as PVDF-40,PVDF-50,PVDF-60,and PVDF-70,denoting the respective mass percentages of NaCl during preparation.The surface morphology,crystal phase composition,thermodynamic behavior,mechanical properties,and piezoelectric properties of each group were meticulously characterized.The four kinds of piezoelectric foam scaffolds were co-cultured with the MG63 osteoblast cell line to evaluate its biocompatibility and potential to promote bone differentiation. RESULTS AND CONCLUSION:(1)The scanning electron microscopy,four groups of scaffolds had multi-level pores.As the NaCl mass fraction in the mixed powder increased,the porosity of the scaffolds increased.X-ray energy dispersion spectrum,X-ray diffraction,Fourier transform infrared spectroscopy,and thermogravimetric analysis collectively revealed the scaffold predominantly comprised the α phase,which inherently lacked piezoelectric properties.However,the application of solid-phase force chemistry successfully stimulated the formation of the β phase,thereby enhancing the scaffold's piezoelectric properties.Notably,the PVDF-60 group exhibited the highest proportion of the β phase among all the tested groups.The results of cyclic compression testing and piezoelectric performance assessment demonstrated that the PVDF-60 group exhibited superior compressive strength and piezoelectric performance compared to the other groups.(2)The findings from scanning electron microscopy and laser confocal microscopy exhibited that MG63 cells adhered well to the surface of the four groups of scaffolds,with good morphology,extended more pseudopods,and secreted a large amount of extracellular matrix.CCK-8 assay revealed that the proliferative absorbance of PVDF-60 cells cultured for 4 days was higher than that of the other three groups(P<0.000 1).Alkaline phosphatase staining and alizarin red staining showed that the expression of alkaline phosphatase and the number of calcified nodules in the PVDF-60 group were higher than those in the other three groups(P<0.01,P<0.000 1).(3)The piezoelectric PVDF foam-based scaffolds demonstrated favorable cytocompatibility.Notably,the PVDF-60 group showed superior mechanical properties,piezoelectric performance,and bone-inducing capabilities.

Compatibility Mechanism of Mineral Medicine Os Draconis in Bupleuri Radix-containing Tri-herbal Medicines Based on Supramolecular Systems / 中国实验方剂学杂志

ObjectiveBy starting with the combination of Os Draconis， Bupleuri Radix， and Ostreae Concha， the role of mineral medicine Os Draconis in the combination of the Bupleuri Radix-containing tri-herbal medicines was preliminarily explored from the perspective of supramolecular system formation. Method① The appearance and Tyndall phenomenon of single decoction of Os Draconis， Bupleuri Radix， and Ostreae Concha， as well as co-decoction of Bupleuri Radix-Os Draconis， Bupleuri Radix-Os Draconis-Ostreae Concha， and Bupleuri Radix-Ostreae Concha were observed， and the average particle size， dispersion coefficient， and Zeta potential of suspension particles in each decoction were determined. The micromorphology of supramolecular structures was observed by scanning electron microscope （SEM）. ② The pH of different compatibility systems， liquid viscosity coefficient， liquid surface tension， freeze-dried powder yield rate， and other physical properties were determined， and the interaction of different compatibility systems was detected by infrared absorption spectroscopy （FTIR） and UV-visible spectrophotometry （UV-Vis）. ③ The composition and content difference of different compatible systems were determined by high-performance liquid chromatography （HPLC） and ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry （UPLC-Q-TOF-MS）. ResultCompared with the single decoction， the co-decoction had more obvious turbidity and Tyndall phenomenon. The particles in the co-decoction suspension were smaller and more evenly distributed， and the Zeta potential was reduced， indicating a more stable system. Under SEM， Bupleuri Radix was irregularly lamellar， and Bupleuri Radix-Os Draconis and Bupleuri Radix-Os Draconis-Ostreae Concha were mainly spherical nanoparticles. Bupleuri Radix-Ostreae Concha was irregularly lamellar， with a small number of spherical nanoparticles. The pH of the single decoction of Bupleuri Radix and co-decoction increased， and the viscosity coefficient increased. The liquid surface tension decreased. The freeze-dried powder yield rate of the Bupleuri Radix-Os Draconis co-decoction was the highest， followed by Bupleuri Radix-Ostreae Concha decoction and Bupleuri Radix-Os Draconis-Ostreae Concha decoction， and the yield rate of Bupleuri Radix single decoction was the lowest. The main change of FTIR was the stretching vibration of -OH， and the co-decoction moved to the low-frequency direction obviously. UV-Vis showed that the maximum absorption occurred at 295.8 nm for all groups， and the absorption intensity was different （Bupleuri Radix-Os Draconis>Bupleuri Radix-Os Draconis-Ostreae Concha>Bupleuri Radix-Ostreae Concha>Bupleuri Radix）. The components of Bupleuri Radix were used as the indexes， and the content of methanol extract determined by HPLC was higher than that of water extract， and the components of Bupleuri Radix single decoction were mainly saikosaponin a （SSa） and saikosaponin c （SSc）， which were slightly higher after co-decoction compatibility. UPLC-Q-TOF-MS could identify 37 compounds in both single decoction and co-decoction. ConclusionThe combination of Bupleuri Radix， Os Draconis， and Ostreae Concha can form a smaller， more uniform， and stable nano-sized supramolecular system， which is conducive to the dissolution of the main components of Bupleuri Radix， and the Os Draconis contributes the most in this process.

Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Research progress of tralokinumab for the treatment of moderate and severe atopic dermatitis / 中国基层医药

Tralokinumab is a selective interleukin-13 inhibitor developed by LEO Pharma in Denmark. It was granted approval by the US Food and Drug Administration on December 27, 2021, for the treatment of patients aged 18 years or older with moderate to severe atopic dermatitis whose disease is refractory to or cannot be fully controlled by local prescription therapy. This article presents a comprehensive review of the recent research progress in the treatment of moderate to severe atopic dermatitis with tralokinumab.

Interferencia generada por la lipemia en la medición de constituyentes bioquímicos

Introducción. La turbidez por lipemia en las muestras para diagnóstico es una de las principales causas de la aparición de sesgos clínicamente significativos en la medición de magnitudes bioquímicas. Objetivo. Valorar la interferencia por lipemia en la medición de 25 constituyentes bioquímicos en dos analizadores con tecnología de química seca (Vitros 7600®) y química liquida (Atellica® Solution). Métodos. Estudio pre-experimental con pre y posprueba. Se añadieron cantidades crecientes de una emulsión lipídica de nutrición parenteral a siete alícuotas de una mezcla de sueros y se determinó por duplicado la influencia del interferente en 25 constituyentes. Se calculó el porcentaje relativo de desviación de la concentración del constituyente por influencia de la turbidez con respecto a una muestra sin interferente. Se establecieron límites de tolerancia para la interferencia utilizando tres criterios: del distribuidor de reactivos, del error sistemático deseable y del error máximo admisible. Resultados. Los constituyentes que presentaron los mayores sesgos para el analizador de química liquida fueron: fósforo (-84,72%), ALT (+81,25%) y AST (-75,76%), mientras que para la plataforma de química seca los constituyentes: ALT (-79,41%), CK (-28,92%) y lipasa (+24,85%). Se detectó interferencia significativa en diferente número de los constituyentes de acuerdo con el criterio de límite tolerable utilizado. Conclusiones. Los distintos resultados encontrados según la metodología y el analizador utilizado, además de la falta de replicabilidad de los ensayos para la valoración de interferencia por lipemia, origina la necesidad de armonizar los procesos e instaurar límites idénticos de interferencia tolerables entre los laboratorios y proveedores de insumos.

Introduction. Turbidity due to lipemia in diagnostic samples is one of the main causes of the appearance of clinically significant biases in the measurement of biochemical magnitudes. Objective. To assess the interference by lipemia in the measurement of 25 biochemical constituents in two analyzers with dry chemistry technology (Vitros 7600®) and liquid chemistry (Atellica® Solution). Methods. Pre-experimental study with pre and post test. Increasing amounts of a parenteral nutrition lipid emulsion were added to seven aliquots of pooled sera and the influence of the interferent on 25 constituents was determined in duplicate. The relative percentage deviation of the concentration of the constituent due to the influence of turbidity with respect to a sample without interference, was calculated. Tolerance limits for interference were established using three criteria: reagent distributor, desirable systematic error, and maximum permissible error. Results. The constituents that presented the greatest biases for the liquid chemistry analyzer were: Phosphorus (-84.72%), ALT (+81.25%) and AST (-75.76%), while for the dry chemistry platform the constituents, ALT (-79.41%), CK (-28.92%) and lipase (+24.85%). Significant interference was detected in a different number of constituents according to the tolerable limit criteria used. Conclusions. The different results found according to the methodology and the analyzer used, in addition to the lack of replicability of the tests for the evaluation of interference by lipemia, originates the need to harmonize the processes and establish identical limits of tolerable interference between the laboratories and suppliers of inputs.

Physiochemistry and Microbiological Quality of Surface Water Body around Port Terminals in Southern Nigeria

Anthropogenic activities around the sea ports are capable of causing changes on the physicochemical and microbiological quality of water bodies along the port terminals. Such activities can cause an ecological imbalance in the water quality /ecosystem resulting in extinction of aquatic resources. The aim of this study therefore was to investigate the physicochemical and microbiological quality of surface water along the busy port terminals. Surface water samples were collected from Onne port terminal using sterile containers. The samples were collected during the wet and dry seasons between January to June 2021. The sterile bottles were filled with surface water samples and transported in an ice packed container to the Department of Microbiology Laboratory of the Rivers State University for analyses using standard analytical methods. Statistical analyses were carried out using ANOVA and All pairs tukey-kramer. Results of the physicochemical parameters showed that temperature, total dissolved solids, total suspended solids, nitrate and heavy metals were significantly higher during the dry season than the wet season at P ? 0.05 levels of significance. Seasonal variation with respect to microbial counts shows that Total Heterotrophic Bacteria, Total Heterotrophic Fungi, Total coliforms and Faecal coliforms had a mean value of 3.9±1.77 x 106; 0.8 ±0.05 x 104 ; 7.4 ±1.3 x 104 and 3.6 ±0.17 x 104 colony forming unit per millilitre respectively for wet season while the dry season had 1.6±0.77 x 106 , 0.5 ±0.01 x 104 , 4.6 ±0.17 x 104 and 2.7 ±1.03 x 104 cfu/ml respectively. In this study, the predominant bacterial isolates belonged to the genera of Vibrio, Pseudomonas, Klebsiella, Bacillus, Shigella, Staphylococcus, Salmonella, Proteus, Bacillus and Escherichia. coli. The results of physicochemical and microbiological characteristics including the heavy metals, were detected at concentrations on or below detection limits.. It is therefore suggested that relevant environmental regulatory bodies should maintain regular check to ensure that appropriate standards are maintained around seaports due to beehive of activities.

Evaluación del aceite de hierbaluisa ecuatoriana como inhibidor de algunos patógenos orales / Evaluation of Ecuadorian lemongrass oil as an inhibitor of some oral pathogens

Introducción: El aceite esencial de hierbaluisa tiene propiedades antibacterianas y antifúngicas que merecen ser estudiadas para usarse como alternativa a los fármacos. Objetivo: Determinar el efecto inhibitorio del aceite esencial de hierbaluisa, procedente del oriente (provincia de Pastaza) y la costa (provincia de los Ríos) ecuatoriana al 25, 50, 75 y 100 por ciento a las 24, 48 y 72 horas sobre el Porphyromona gingivalis, Enterococcus faecalis, Staphylococcus aureus y Candida albicans. Métodos: Estudio experimental, in vitro. Para medir el efecto inhibitorio se usaron las cepas de P. gingivalis, E. faecalis, S. aureus y C. albicans incubadas en 20 cajas Petri para cada microorganismo (10 para el aceite de la costa y 10 para el oriente). En cada caja se colocaron los discos con la concentración del aceite esencial de hierbaluisa, el control positivo (clorhexidina al 0,12 por ciento para las bacterias y nistatina para C. albicans) y el control negativo (suero fisiológico). Se midieron los halos de inhibición a las 24, 48 y 72 horas. Resultados: El aceite esencial de hierbaluisa del oriente al 100 por ciento a las 24 horas obtuvo los halos de inhibición más altos que fueron de 8,90 mm para la C. albicans; 19,10 mm para el S. aureus; 11,90 mm para el E. faecalis y 8,00 mm para la P. gingivalis. Hubo una sensibilidad media para S. aureus, límite para E. faecalis y nula para C. albicans y P. gingivalis. Conclusiones: El aceite de hierbaluisa de la costa y el oriente ecuatoriano inhibió el S. aureus(AU)

Introduction: The essential oil of lemongrass has antibacterial and antifungal properties that deserve to be studied for using as an alternative to drugs. Objective: To determine the inhibitory effect of the essential oil of lemon verbena from the east (Pastaza province) and the coast (Los Rios province) of Ecuador at 25 percent, 50 percent, 75 percent and 100 percent at 24, 48 and 72 hours on Porphyromona gingivalis, Enterococcus faecalis, Staphylococcus aureus and Candida albicans. Methods: Experimental study, in vitro. To measure the inhibitory effect, P. gingivalis, E. faecalis, S. aureus and C. albicans strains were incubated in 20 Petri dishes for each microorganism (10 for coastal oil and 10 for eastern). In each box were placed the disks with the concentration of the essential oil of lemon verbena, the positive control (chlorhexidine 0.12 percent for bacteria and nystatin for C. albicans) and the negative control (physiological serum). Inhibition halos were measured after 24, 48 and 72 hours. Results: Eastern lemongrass essential oil at 100 percent at 24 hours obtained the highest inhibition halos which were 8.90 mm for C. albicans; 19.10 mm for S. aureus; 11.90 mm for E. faecalis and 8.00 mm for P. gingivalis. There was medium sensitivity for S. aureus, borderline for E. faecalis and null for C. albicans and P. gingivalis. Conclusions: Herbal lemongrass oil from coastal and eastern Ecuador inhibited S. aureus(AU)

Pharmacological properties and mechanisms of Notoginsenoside R1 in ischemia-reperfusion injury / 中华创伤杂志(英文版)

Panax notoginseng is an ancient Chinese medicinal plant that has great clinical value in regulating cardiovascular disease in China. As a single component of panax notoginosides, notoginsenoside R1 (NGR1) belongs to the panaxatriol group. Many reports have demonstrated that NGR1 exerts multiple pharmacological effects in ischemic stroke, myocardial infarction, acute renal injury, and intestinal injury. Here, we outline the available reports on the pharmacological effects of NGR1 in ischemia-reperfusion (I/R) injury. We also discuss the chemistry, composition and molecular mechanism underlying the anti-I/R injury effects of NGR1. NGR1 had significant effects on reducing cerebral infarct size and neurological deficits in cerebral I/R injury, ameliorating the impaired mitochondrial morphology in myocardial I/R injury, decreasing kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in renal I/R injury and attenuating jejunal mucosal epithelium injury in intestinal I/R injury. The various organ anti-I/R injury effects of NGR1 are mainly through the suppression of oxidative stress, apoptosis, inflammation, endoplasmic reticulum stress and promotion of angiogenesis and neurogenesis. These findings provide a reference basis for future research of NGR1 on I/R injury.

Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

Chemistry-led investigations into the mode of action of NAMPT activators, resulting in the discovery of non-pyridyl class NAMPT activators

The cofactor nicotinamide adenine dinucleotide (NAD+) plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+ levels is an established approach to enhancing healthy aging. Recently, several classes of nicotinamide phosphoribosyl transferase (NAMPT) activators have been shown to increase NAD+ levels in vitro and in vivo and to demonstrate beneficial effects in animal models. The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors, however the basis for the switch from inhibitory activity to activation is not well understood. Here we report an evaluation of the structure activity relationships of NAMPT activators by designing, synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known activators. The results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site, resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead, which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

Establishment an aggregation-induced emission vesicle material based on supramolecular host-guest chemical assembly for siRNA delivery and study on its toxicity to tumor cells / 国际生物医学工程杂志

Objective:To establish an aggregation-induced emission vesicle material based on supramolecular host-guest chemical assembly (AIE-HG-Vesicle) for siRNA delivery and fluorescence imaging, and to explore its uptake effect by tumor cells and siRNA-based cell killing effect.Methods:By synthesizing β-cyclodextrin modified with polyethyleneimine dendrimer (H-β-CD-dendrimer) as a host compound and a Bola type adamantane containing tetrastyrene AIE group (G-Ada-AIE) as a guest compound, the nanovesicle material was prepared by a supramolecular host-guest self-assembly process for loading siRNA. The morphology and size of the materials were tested by transmission electron microscopy and the dynamic light scattering method. The aggregation-induced luminescence properties of the materials were investigated by fluorescence spectrophotometry. The loading effect of the material on siRNA was investigated by gel retardation experiments. The delivery effect of siRNA-loaded AIE-HG-Vesicle vesicles in tumor cells was observed by a confocal laser scanning microscope. The killing effect of siRNA-loaded AIE-HG-Vesicle vesicles on tumor cells was tested by an MTT assay.Results:The prepared host-guest compounds can be assembled into vesicles with a size of about 100 nm and wall thickness of 9 nm in solution, and the positively charged vesicles on the surface can efficiently load siRNA. The siRNA-loaded AIE-HG-Vesicle vesicles can deliver siRNA into HeLa tumor cells and can be observed through aggregation-induced luminescence. The siRNA-loaded vesicles have an obvious killing effect on HeLa tumor cells.Conclusions:A vesicle material with aggregation-induced luminescence properties was prepared by a method based on supramolecular host-guest chemical assembly, which can be used to deliver siRNA. The material has fluorescence imaging and siRNA-based tumor cytotoxic effects and is expected to be applied to tumor treatment in vivo.

Significance of BRAFV600E protein and gene detection in benign,malignant and borderline thyroid diseases / 临床外科杂志

Objective To investigate the significance of BRAFV600Ein the detection of benign,malignant and borderline thyroid lesions.Methods A total of 273 formalin fixed and paraffin-embedded specimens of papillary thyroid carcinoma(PTC)were selected for study from January 2010 to December 2018.There were 254 cases of classical variant of papillary carcinoma(CVPTC)and 19 cases of follicular variant of papillary carcinoma(FVPTC).30 benign lesions were made into tissue microarray(TMA),and 17 uncertain borderline lesions diagnosed by HE.Polymerase chain reaction(PCR)was used to detect 17 cases of CVPTC 12 cases of FVPTC 17 cases of borderline lesions and 13 cases of benign lesions.BRAFV600E gene mutation and protein expression were observed.Results The positive expression rates of BRAFV600E protein in CVPTC,FVPTC,borderline lesion and benign lesion were 86.6％,15.9％,23.5％and 26.7％,respectively.Mutation rates of BRAFV600E gene in CVPTC,FVPTC,borderline lesions and benign lesions were 82.4％,41.7％,23.5％and 0,respectively.There were significant differences in expression of BRAFV600E protein in CVPTC,FVPTC,borderline lesions and benign lesions(P＜0.05).There was statistically significant difference between BRAFV600E gene mutation in CVPTC and FVPTC and borderline diseases(P＜0.05).The coincidence coefficient between BRAFV600E gene mutation and protein expression in CVPTC was K=0.821,P＜0.05.It was statistically significant.The positive expression of BRAFV600E protein in PTC was not correlated with gender,age,tumor size and lymph node metastasis(P＞0.05),but was correlated with tissue type and capsule invasion(P＜0.05).Conclusion BRAFV6001 has reference value in the diagnosis and differential diagnosis of benign and malignant thyroid and borderline thyroid lesions.

Application of ALK antibody clone 1A4 in the diagnosis of non-small cell lung cancer with ALK fusion / 临床与实验病理学杂志

Purpose The aim of this study is to explore the application value of ALK(1A4)in ALK fused non-small cell lung cancer(NSCLC).Methods A total of 1 035 NSCLC specimens were collected.The expression of ALK(1A4)and ALK(D5F3)antibodies was detected by immunohistochemical(IHC)staining,and their consistency was analyzed.FISH and next-generation sequencing(NGS)were used to detect ALK positive,and the sensitivity and specificity of ALK in the two groups were evaluated.Results ALK fused NSCLC patients accounted for about 5.4％(56/1 035).The positive rate of ALK(1A4)was 7.2％(75/1 035),and that of ALK(D5F3)was 5.7％(59/1 035).The consistency between them was high,with a Kappa value of 0.874.The consistency of ALK(1A4)and ALK(D5 F3)antibodies with FISH was high,with Kappa values of 0.845 and 0.954,respectively.The consisten-cy of ALK(1A4)and ALK(D5F3)with NGS was also high,with Kappa values of 0.836 and 0.988,respectively.According to the FISH results,the sensitivities of ALK(1A4)and ALK(D5F3)antibodies were 100％and 98.2％,and the specifici-ties were 98.1％and 99.6％,respectively.Conclusion ALK(1A4)antibody has high sensitivity and slightly low specificity,and can be used for clinical screening of ALK fused NSCLC.

Research Process of Polysaccharide and Triterpenoids in Large Varieties of Poria cocos with Homology of Medicine and Food / 世界科学技术-中医药现代化

Poria cocos is a classic Chinese medicine with homology of food and medicine,which is beneficial to water infiltration,spleen and stomach,calming the heart and calming the mind,etc.It is known as"nine Poria cocos in ten prescriptions".Poria cocos contains polysaccharide,triterpenoids and steroids,among them polysaccharide and triterpenoid are considered as the main active components.Modern studies have shown that Poria cocos polysaccharide triterpenes display pharmacological activities such as anti-tumor,immunomodulatory and anti-oxidation.The dissolution rate of poria cocos and triterpenes was low in the traditional decocting process,and the oral absorption rate of poria cocos was low,but the activity of poria cocos and triterpenes was still very good,indicating the high activity of poria cocos and triterpenes.Therefore,this paper systematically reviews the extraction and separation,structural identification,content determination,structural modification,biosynthesis,pharmacological activity and potential product development value of Poria cocos polysaccharide and triterpenoids,in order to provide literature reference for the development of Poria cocos grand health industry.

Click chemistry-based enrichment strategy for tracing cellular fatty acid metabolism by LC-MS/MS / 药物分析学报

Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling molecules.Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events.Inspired by the advances in click chemistry for protein enrichment,we herein established a click chemistry-based enrichment(CCBE)strategy for tracing the cellular metabolism of eicosapentaenoic acid(EPA,20:5 n-3)in neural cells.Terminal alkyne-labeled EPA(EPAA)used as a surrogate was incubated with N2a,mouse neuroblastoma cells,and alkyne-labeled metabolites(ALMs)were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment.After removing unlabeled metabolites,ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry(LC-MS)analysis.The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices.In addition,this method can overcome current detection limits by enhancing MS sensitivity of targets,improving the chromatographic separation of sn-position glycerophospholipid regioisomers,facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature,and providing versatile fluorescence detection of ALMs for cellular distribution.This CCBE strategy might be expanded to trace the metabolism of other FAs,small molecules,or drugs.

Clinical application of positive urobilirubin as a rule of microscopic review of urinalysis / 中华检验医学杂志

Objective:To study the correlation between urobilirubin and urine cast, and further assess the accuracy of positive urobilirubin as a new microscopic review rule for urinalysis.Methods:505 inpatients′ urine samples were selected from Wuhan Union Hospital during October 2021 and April 2022, including 339 males and 166 females with an age range of 51.45±16.64 years. 202 samples with positive urobilirubin were selected as study objects and were divided into two groups, one group includes 70 samples with positive urine protein and another group includes 132 samples with negative urine protein. According to the clinical departments′ distribution of the study objects, 40 samples from the corresponding clinical departments with negative urobilirubin were selected as a control group. 200 samples were selected for verification test one without consideration of the clinical department distribution and the urinalysis results and another 63 samples with positive urobilirubin and negative positive urine protein were selected for verification test two. After the IQC of each instrument was passed, the liver and renal functions were detected and the urine samples were detected by dry chemical analysis, automated sediment analyzer, microscope exam after centrifugation, and urine β 2-MG and RBP quantitative detections. Two microscope review rules were defined, rule one: if any of WBC, RBC, PR0/CAST were different between the dry chemical system and urine sediments analyzer and the urine protein was positive by dry chemical analysis. Rule two: positive urobilirubin plus rule one. We estimated the accuracies of the two rules by Mann-Whitney U test and χ 2 test. Results:①The positive rates of the cast of study objects and patients with negative urine protein were 58.42% (118/202)and 55.30%(73/132) respectively, both higher than that of the control group(20%,8/40) (χ 2=19.74,15.36, P<0.01), and on univariate analysis, positive urobilirubin was found to be a significant predictor of urine cast when the urine protein was negative by dry chemical system[OR(95% CI):5.619(2.466-12.806), P<0.01].②Four protocols were used: positive urine protein by dry chemical method, positive cast result by UF-5000i, rule one and rule two. As for the study group, the total review rates of each protocol were 34.65%(70/202), 30.69%(62/202), 60.89%(123/202), and 100% (202/202)respectively, and the false negative rates of the cast were 35.64%(72/202), 30.20%(61/202), 12.87%(26/202)and 0 respectively. As for patients with positive urobilirubin and negative urine protein, the total review rates of each protocol were 0, 22.73%(30/132), 40.15%(53/132), and 100%(132/132) respectively and the false negative rates of the cast were 54.55%(72/132), 34.85%(46/132), 19.70%(26/132)and 0 respectively.③The results of verification test one showed there were no significant differences between the total review rates(50.50% vs 52.50%, χ 2=0.16, P>0.05) and the false negative rates of cast detection(4.50% vs 2.50%, χ 2=1.15, P>0.05)of rule one and rule two. The results of verification test two showed the total review rates of rule two was higher than that of rule one(100% vs 46.03%, χ 2=46.57, P<0.01), and the false negative rates of cast detection of rule two was significantly lower than that of rule one(0 vs 14.29%, χ 2=9.69, P<0.01). Conclusions:Positive urobilirubin can be used to predict urine cast when urine protein was negative by dry chemical method. And we recommended that positive urobilirubin should be considered as a rule of microscopic review of urinalysis to decrease the false negative rate of cast detection of samples with positive urobilirubin and negative urine protein dry chemical method.

Advances in research on small molecule regulators targeting HBV cccDNA generation and transcription / 药学学报

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Recent advances of antiviral drugs based on multispecific binding strategy / 药学学报

To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

Modern Pharmacological Effect of Zhishi Xiebai Guizhitang： A Review / 中国实验方剂学杂志

Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B2 （TXB2）， prostacyclin I2（PGI2） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.