Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification

BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.

Unraveling the mechanism of malancao in treating ulcerative colitis:A multi-omics approach

BACKGROUND Malancao(MLC)is a traditional Chinese medicine with a long history of utilization in treating ulcerative colitis(UC).Nevertheless,the precise molecular mechanisms underlying its efficacy remain elusive.This study leveraged ultrahigh-performance liquid chromatography coupled with exactive mass spectrometry(UHPLC-QE-MS),network pharmacology,molecular docking(MD),and gene microarray analysis to discern the bioactive constituents and the potential mechanism of action of MLC in UC management.AIM To determine the ingredients related to MLC for treatment of UC using multiple databases to obtain potential targets for fishing.METHODS This research employs UHPLC-QE-MS for the identification of bioactive compounds present in MLC plant samples.Furthermore,the study integrates the identified MLC compound-related targets with publicly available databases to elucidate common drug disease targets.Additionally,the R programming language is utilized to predict the central targets and molecular pathways that MLC may impact in the treatment of UC.Finally,MD are conducted using AutoDock Vina software to assess the affinity of bioactive components to the main targets and confirm their therapeutic potential.RESULTS Firstly,through a comprehensive analysis of UHPLC-QE-MS data and public database resources,we identified 146 drug-disease cross targets related to 11 bioactive components.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted that common disease drug targets are primarily involved in oxidative stress management,lipid metabolism,atherosclerosis,and other processes.They also affect AGE-RAGE and apoptosis signaling pathways.Secondly,by analyzing the differences in diseases,we identified key research targets.These core targets are related to 11 active substances,including active ingredients such as quercetin and luteolin.Finally,MD analysis revealed the stability of compound-protein binding,particularly between JUNLuteolin,JUN-Quercetin,HSP90AA1-Wogonin,and HSP90AA1-Rhein.Therefore,this suggests that MLC may help alleviate intestinal inflammation in UC,restore abnormal lipid accumulation,and regulate the expression levels of core proteins in the intestine.CONCLUSION The utilization of MLC has demonstrated notable therapeutic efficacy in the management of UC by means of the compound target interaction pathway.The amalgamation of botanical resources,metabolomics,natural products,MD,and gene chip technology presents a propitious methodology for investigating therapeutic targets of herbal medicines and discerning novel bioactive constituents.

Comparative study on emotional behavior and parental job stress of only-child and non-only-child preschool children

BACKGROUND Studies have revealed that Children's psychological,behavioral,and emotional problems are easily influenced by the family environment.In recent years,the family structure in China has undergone significant changes,with more families having two or three children.AIM To explore the relationship between emotional behavior and parental job stress in only preschool and non-only preschool children.METHODS Children aged 3-6 in kindergartens in four main urban areas of Shijiazhuang were selected by stratified sampling for a questionnaire and divided into only and nononly child groups.Their emotional behaviors and parental pressure were compared.Only and non-only children were paired in a 1:1 ratio by class and age(difference less than or equal to 6 months),and the matched data were compared.The relationship between children's emotional behavior and parents'job stress before and after matching was analyzed.RESULTS Before matching,the mother's occupation,children's personality characteristics,and children's rearing patterns differed between the groups(P<0.05).After matching 550 pairs,differences in the children's parenting styles remained.There were significant differences in children's gender and parents'attitudes toward children between the two groups.The Strengths and Difficulties Questionnaire(SDQ)scores of children in the only child group and the Parenting Stress Index-Short Form(PSI-SF)scores of parents were significantly lower than those in the non-only child group(P<0.05).Pearson’s correlation analysis showed that after matching,there was a positive correlation between children's parenting style and parents'attitudes toward their children(r=0.096,P<0.01),and the PSI-SF score was positively correlated with children's gender,parents'attitudes toward their children,and SDQ scores(r=0.077,0.193,0.172,0.222).CONCLUSION Preschool children's emotional behavior and parental pressure were significantly higher in multi-child families.Parental pressure in differently structured families was associated with many factors,and preschool children's emotional behavior was positively correlated with parental pressure.

多色探针熔解曲线法在结核分枝杆菌耐药性检测中的应用

目的评价多色探针熔解曲线法(multicolor melting curve analysis,MMCA)在MTB耐药性检测中的临床应用价值。方法收集235例浓集抗酸杆菌检测阳性和(或)MTB分子检测阳性患者的晨痰,同时用MMCA和分枝杆菌液体培养及比例法药物敏感性试验(简称“药敏试验”)进行耐药性检测,采用Kappa检验比较两方法的一致性。两方法有差别的标本用基因测序的方法进行比较。结果MMCA和比例法药敏试验检测利福平(RFP)、异烟肼(INH)、乙胺丁醇(EMB)、左氧氟沙星(Lfx)、莫西沙星(Mfx)及耐多药结核(MDR-TB)的符合率分别为94.04(221/235)、90.64%(213/235)、80.00%(188/235)、94.89%(223/235)、77.87%(183/235)、89.36%(210/235);RFP、INH、Lfx及MDR-TB两方法比较Kappa值分别为0.88、0.81、0.88、0.77,具有极好的一致性;以上不一致的标本经基因测序技术验证,痰液及培养分离株两种标本类型的MMCA与测序结果总符合率分别为89.80%(132/147)、98.64%(145/147)。结论采用MMCA法直接、快速检测临床患者痰液MTB耐药情况,与金标准比例法药敏试验及参考方法基因测序技术一致性好,且操作简便、快速、准确,在结核病诊断及耐药结核病快速筛查中将发挥重要作用。

Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection

AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.

Research progress of polysaccharide nanocarriers based on traditional Chinese medicine Thallus japonica

In the last few years,the overall incidence of malignant tumors has been increasing in the country.In order to find effective anti-tumor drugs,the development and modification of natural drugs have become the focus of domestic and international researchers.Thallus japonica,composed of polysaccharides,minerals,amino acids,natural proteins,and lipids,is a traditional Chinese medicine with the functions of eliminating phlegm and disinhibiting water.At the same time,it has the edible and medicinal efficacy.There are a lot of active components that have been demonstrated to possess diverse biological activities including anti-tumor,anti-viral,anti-coagulant,and anti-bacterial,and so on in thallus japonica.Laminarin,composed of glucose,galactose,fucose and so on,is a common and high molecular weight heteropolysaccharide in brown algae(such as thallus japonica,kelp),and it is a potential anti-tumor drug.However,the lack of biological activity of natural polysaccharides limits the application of polysaccharides,so it is necessary to modify the structure or physical and chemical properties of it to enhance the anti-tumor activity of polysaccharides.In recent years,in order to improve the biological activity of laminarin,domestic and international researchers have introduced some groups on the surface of it.Moreover,use the function of modified groups to cause the changes in physicochemical property,spatial structure,substituent group and molecular weight to improve the anti-tumor activity in vitro and in vivo.Therefore,the structural modification has become the main and powerful means to improve the activity of polysaccharides.

π-π堆叠构建钙钛矿光伏高效电荷通道

Perovskite solar cells(PSCs)have emerged as strong potential candidates for future photovoltaic technologies.The power conversion efficiency(PCE)of PSCs has already surpassed 26%,approaching their theoretical limit[1].The commonly used device structure for PSCs is ITO/SnO_(2)/perovskite/2,2',7,7'-tetrakis-(N,N-di-4-methox yphenylamino)-9,9'-spirobifluorene(spiro-OMeTAD)/Au[2].

Chelation strategy induced blue-shift for efficient deep-blue perovskite light-emitting diodes

Metal halide perovskite, regarded as a potential material for next-generation display and lighting applications, has attracted great attention [1,2]. The development of blue perovskite light-emitting diodes (Pe LEDs) remains stagnant compared with their green and red counterparts in recent years [3–8].

CsPbBrI perovskites with low energy loss for high-performance indoor and outdoor photovoltaics

Over the years,the efficiency of inorganic perovskite solar cells(PSCs)has increased at an unprecedented pace.However,energy loss in the device has limited a further increase in efficiency and commercialization.In this work,we used(NH4)2C2O4·H2O to treat CsPbBrI2 perovskite film during spin-coating.The CsPbBrI2 underwent secondary crystallization to form high quality films with micrometer-scale and low trap density.(NH4)2C2O4·H2O treatment promoted charge transfer capacity and reduced the ideal factor.It also dropped the energy loss from 0.80 to 0.64 eV.The resulting device delivered a power conversion efficiency(PCE)of 16.55%with an open-circuit voltage(Voc)of 1.24 V,which are largely improved compared with the reference device which exhibited a PCE of 13.27%and a Voc of 1.10 V.In addition,the optimized treated device presented a record indoor PCE of 28.48%under a fluorescent lamp of 1000 lux,better than that of the reference device(19.05%).

A General Synthetic Approach of Organic Lateral Heterostructures for Optical Signal Converters in All-Color Wavelength

Organic heterostructures with precisely defined compositions,architectures,and interfaces are considered promising building blocks for integrated optoelectronic devices.However,it remains a great challenge to rationally design and synthesize a heterostructure with tunable performance for promising applications such as optoelectronic devices.Herein,we report a universal strategy for the synthesis of organic lateral heterostructures(OLHs)with tunable function and optical properties.We fabricated cocrystals based on the tunable intermolecular distance(dπ–πfrom 3.33 to 3.48Å)ofBenzo[ghi]perylene(BGP)-based driven by arene-perfluoroarene interaction or charge transfer interaction;these different components were selectively constructed into organic solid solution microwires or OLHs.Importantly,the solid solution microwires obtained could be epitaxially grown on the BGP-tetrabromophthalicanhydride trunk microwire to construct a series of OLHs microwires,which led to the successful demonstration of both photonic signal conversion and optical logic gate in all-color wavelength.This work gives a new insight into the fine synthesis of heterostructures with tunable structures/performances,providing predictable synthetic pathways to multifunctional organic heterostructures for the future realization of integrated optoelectronics.

Smelting recrystallization of CsPbBrI_(2)perovskites for indoor and outdoor photovoltaics

A smelting multiple recrystallization strategy and its effects on the morphology,composition,and defects of CsPbBrI_(2)film were investigated.An optimal number(n=2)of recrystallization cycles improved the crystallinity and phase purity,minimized the grain boundaries,and optimized the crystal structure,yielding a high-quality perovskite film with significantly reduced defects density.The corresponding photovoltaic devices exhibited a champion efficiency of 16.02%under AM 1.5 G illumination and presented an even higher indoor efficiency of 33.50%under an LED(2956 K,P_(in):334.41𝜇W/cm^(2)).This recrystallization method offers a promising strategy for developing high-performance indoor and outdoor photovoltaics.Direct recrystallization in the cells was also explored to achieve enhanced stability and longer lifetime in humid conditions.