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Visualization of nasal powder distribution using biomimetic human nasal cavity model

Acta Pharmaceutica Sinica B 2024年第1期14卷 392-404页

作者： Jiawen Su Yan Liu Hongyu Sun Abid Naeem Huipeng Xu Yue Qu Caifen Wang Zeru Li Jianhua Lu Lulu Wang Xiaofeng Wang Jie Wu Lixin Sun Jiwen Zhang Zhigang Wang Rui Yang Li Wu Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China Key Laboratory of Molecular Pharmacology and drug Evaluation School of PharmacyMinistry of EducationYantai UniversityYantai 264005China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201210China Nantong Haimen People’s Hospital Nantong 226199China Yangtze Delta drug Advanced Research Institute Nantong 226126China Shenyang Pharmaceutical University Shenyang 110016China National Institutes for food and drug Control Beijing 100000China Nanjing University of Chinese Medicine Nanjing 210023China

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal ***,no reliable method is currently available to assess its impact on delivery *** this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal *** results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and *** nasal cavity model was modified with dimethicone and validated to be suitable for the deposition *** experimental device produced the most satisfactory results with five spray ***,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,***,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo *** conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

关键词： Nasal drug deposition Nasal drug distribution Nasal drug delivery Biomimetic nasal model Nasal powder Three-dimensional reconstruction Three-dimensional printing Nasal drug distribution

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Prophylactic effects of sialylated glycopeptides from edible bird’s nest on neuroinflammation in lipopolysaccharide-treated mice via the gut-brain axis

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food Science and Human Wellness 2024年

作者： Xiang-Rong Cheng Chen-Xi Zhang Xiao-Yi Zhao Qiu-Shi Li Yu Song Lan Zhang Jia-Hui Ma Yu-Yao Chen Man Yuan Dong-Liang Wang School of food Science and Technology， Jiangnan University State Key Laboratory of food Science and Resources， Jiangnan University Central Nervous System drug Key Laboratory of Sichuan Province Luzhou Hebei Edible Bird's Nest Fresh Stew Technology Innovation Center

Edible bird’s nest (EBN)， abundant in sialic acid (SA) has been recognized as a natural substance beneficial to brain development and cognitive ability. In order to investigate active component of EBN， sialylated glycopeptides (SCP) were extracted from EBN by 60% ethanol after trypsin hydrolysis and its effects on central nervous system was evaluated in lipopolysaccharide (LPS)-induced neuroinflammation mice. EBN， SCP， and SA pretreatment and intervention reduced IL-1β， TNF-α， and IL-6 levels in hippocampus and cortex， meanwhile inhibited the activation of microglia， astrogliosis and neuron apoptosis， which were consistent with the learning and memory improvement and anti-depression effects in behavioral tests. The counts of leukocytes， neutrophils and monocytes， as well as IL-1β， TNF-α， and IL-6 levels in peripheral circulation were significantly reduced by SCP. Results of plasma metabolomics suggested SCP up-regulated energy metabolism， promoted the recovery of primary and secondary bile acid metabolism and indole metabolism， where microbiota may involve. 16S rDNA sequencing of colonic contents showed EBN， SCP and SA repaired dysbacteriosis in LPS-treated mice by significantly up-regulating the anti-inflammatory Muribaculaceae and inhibiting pro-inflammatory related Desulfovibrio and Candidatus＿Saccharimonas. In addition， both EBN and SCP could significantly enrich ***， while SA could specifically enrich Prevotellaceae＿UCG＿001. The gut-brain axis was preliminarily established， and SCP may have the potential to be a functional factor for neuroprotection applied in EBN industry.

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Herb pair of Huangqi-Danggui exerts anti-tumor immunity to breast cancer by upregulating PIK3R1

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Animal Models and Experimental Medicine 2024年第3期7卷 234-258页

作者： Hai-Xin Liu Li Lian Li-Li Hou Cai-Xia Liu Jin-Hong Ren Yuan-Biao Qiao Shi-Yuan Wen Qing-Shan Li College of Traditional Chinese Medicine and food Engineering Shanxi University of Chinese MedicineTaiyuanChina Shanxi Key Laboratory of Innovative drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation College of Traditional Chinese Medicine and Food EngineeringShanxi University of Chinese MedicineTaiyuanChina College of Basic Medical Sciences Shanxi Medical UniversityTaiyuanChina

Background:According to traditional Chinese medicine(TCM),drugs supplementing the vital energy,Qi,can eliminate tumors by restoring host *** objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs,specifically the paired use of Huangqi and ***:Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing *** the MTT assay and a transplanted tumor mice model,the anti-tumor effects of combination TCMs were investigated in vitro and in *** content analysis and flow cytometry were then used to evaluate cellular immunity,followed by network pharmacology and molecular docking to dissect the significant active compounds and potential ***,the anti-tumor activity and the mechanism of the active ingredients were verified by molecular ***:There is an optimal combination of Huangqi and Danggui that,administered as an aqueous extract,can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in *** on network pharmacology analysis,PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and *** docking analysis shows 6 components of the combined Danggui and Huangqi extract(quercetin,jaranol,isorhamnetin,kaempferol,calycosin,and suchilactone)that bind to *** is the most important component against breast *** suchilactone/jaranol combination and,especially,the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the ***:The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.

关键词： anti-tumor Danggui Huangqi immunity

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Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy

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Chinese Chemical Letters 2024年第6期35卷 427-432页

作者： Yihan Zhou Duo Gao Yaying Wang Li Liang Qingyu Zhang Wenwen Han Jie Wang Chunliu Zhu Xinxin Zhang Yong Gan State Key Laboratory of drug Research and Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China

Local delivery of nanoparticles holds promise for colorectal cancer(CRC)***,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment *** is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal ***,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal *** found that the carriers exhibited diverse shapes while maintaining comparable physicochemical *** these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to ***,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in *** findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.

关键词： Worm-like micelles Mucus penetration Shape dependent Transmucosal delivery Colorectal cancer

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Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

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Chinese Chemical Letters 2024年第2期35卷 352-357页

作者： Yingli Zhu Jie Qian Kunqian Yu Jing Hou Yeshuo Ma Fei Chen Jie Dong Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410083China National Engineering Research Center of Rice and Byproduct Deep Processing School of Food Science and EngineeringCentral South University of Forestry and TechnologyChangsha 410004China State Key Laboratory of drug Research Drug Discovery and Design CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Geriatrics Third Xiangya HospitalCentral South UniversityChangsha 410013China

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development,disease diagnosis,and basic theoretical *** N(APN),as a representative tumor biomarker with anti-tumor potential,still lacks a high-precision theranostic probe specifically targeting *** this study,a novel quaternity design strategy for APN theranostic probe was *** proposed strategy utilizes advanced machine learning and molecular dynamics simulations,and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional *** this strategy,a unique“Off-On”theranostic probe,ABTP-DPTB,was ingeniously constructed to light up APN through fluorescence restoration,relying on conformation-induced effects and solvent *** from the common diagnostic probes,the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ *** fabricated probe was used for detecting and inhibiting APN in various environments,with a better in vitro inhibitory than golden-standard drug bestatin.

关键词： Theranostic probe Artificial intelligence Conformational restriction Fluorescence restoration Design strategy

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The MADS-box gene RhAGL6 plays a master role in regulating the receptacle malformation in rose at low temperature

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Horticultural Plant Journal 2024年第5期10卷 1214-1229页

作者： Weikun Jing Shuai Zhang Qingcui Zhao Yang Liu Liangjun Zhao Junping Gao Nan Ma Xiaofeng Zhou Yonghong Li School of food and drug Shenzhen PolytechnicShenzhen 518055China Department of Ornamental Horticulture College of HorticultureChina Agricultural UniversityBeijing 100193China Postdoctoral Innovation Practice Base Shenzhen PolytechnicShenzhen 518055China Flower Research Institute of Yunnan Academy of Agricultural Sciences KunmingYunnan 650205China

Low temperature usually results in the developmental deformity of flower organs,immensely affecting the quality of rose ***,it's largely unknown about the regulatory mechanisms activated by low ***,we used a low temperature-sensitive Rosa hybrida cv.‘Peach Avalanche’to screen a MADS-box gene RhAGL6 via conjoint analysis between RNA sequencing(RNA-seq)and whole-genome bisulfite sequencing(WGBS).Furthermore,we found that low temperature induced the hypermethylation and elevated histone 3 lys-27 trimethylation(H3K27me3)level on the RhAGL6 promoter,leading to decreased RhAGL6 *** addition,RhAGL6 silencing resulted in the formation of abnormal *** also found that the levels of gibberellins(GA3)and abscisic acid(ABA)in the receptacle under low temperature were lower and higher,respectively,than under normal *** activity analysis revealed that GA3 significantly activated RhAGL6 promoter activity,whereas ABA inhibited ***,we propose that RhAGL6 regulates rose receptacle development by integrating epigenetic regulation and phytohormones signaling at low temperature.

关键词： Rosa hybrida Low temperature RhAGL6 Receptacle development DNA methylation H3K27me3 Phytohormone

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Exploring the material basis and mechanism of Moringa oleifera in alleviating slow transit constipation based on network pharmacology and animal models

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food Science and Human Wellness 2024年

作者： Sijin Li Xiaoyu Gao Kaifeng Guo Shuangfeng Liu Weiqian Yang Yan Zhao Jun Sheng Zhongbin Bai Yang Tian College of food Science and Technology， Yunnan Agricultural University Yunnan Key Laboratory of Precision Nutrition and Personalized food Manufacturing， Yunnan Agricultural University Department of Science and Technology， Yunnan Agricultural University College of Veterinary Medicine， Yunnan Agricultural University Engineering Research Center of Development and Utilization of food and drug Homologous Resources， Ministry of Education， Yunnan Agricultural University

Moringa oleifera(M. oleifera) have laxative effects， but their active compositions and mechanisms are not very clear thus far. To this end， we systematically explored the active components and mechanism of M. oleifera leaves in relieving constipation by using the slow transit constipation (STC) mouse model and network pharmacology. The results of animal experiments showed that M. oleifera aqueous extract (MOA) had good laxative activity， and its 70% alcohol soluble part (ASP) also showed significant laxative activity(P < 0.01). Network pharmacological prediction results suggested that L-phenylalanine (Phe) was the key compound of ASP， and it might relieve constipation through tachykinin receptor 1 (TACR1) and three kinds of adrenergic receptors， including alpha-1a (ADRA1A)， alpha-2a (ADRA2A)， and alpha-2b (ADRA2B). Further animal experiment results showed that Phe significantly promoted gastrointestinal motility. Phe may relieve STC by enhancing the release of substance P (SP) and upregulating the mRNA expression of TACR1 in the ileum. Importantly， Phe may also promote intestinal movement by downregulating ADRA2A and ADRA2B and upregulating calmodulin and the mRNA and protein expression of myosin light chain 9 (MYL9) in the ileum， thereby activating the GPCR-MLC signaling pathway. These results lay a foundation for the application of M. oleifera and Phe in constipation.

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Degradation Rate Assessment of Biodegradable Magnesium Alloys

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Materials Sciences and Applications 2024年第8期15卷 245-252页

作者： Bianmei Cao Limei Cao David F. Kallmes Department of Radiology Mayo Clinic Rochester MN USA National Institutes for food and drug Control Beijing China

Biodegradable magnesium alloys have been widely used in medical implants. But safety concerns were put forward for the high degradation rate of biodegradable magnesium alloy. The optimal biodegradable magnesium alloys that give rise to the desired degradation rate hasn’t yet to be defined. Assessing the degradation rate of biodegradable magnesium alloys involves in vitro testing, in vivo testing, numerical modeling, understanding the factors influencing their degradation in physiological environments, biocompatibility testing, and clinical studies. It is important to standardize analytical tools aimed at assessing the degradation rate of biodegradable magnesium alloys. It is advisable to identify the threshold for safe degradation rate of biodegradable magnesium alloys in biomedical applications.

关键词： Magnesium Alloys Biomedical Application Biodegradation Degradation Rate Biocompatibility

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Antibacteria Activity of Peganum harmala and Haloxylon salicornicum Leaves Extracts

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Advances in Microbiology 2024年第2期14卷 122-136页

作者： Naif M. Alhawiti Agnes K. Nthenge Waeel H. Alramadhan William Boadi Abdulrahman F. Alqahtani Elber-Lewis Myles CAHFS University of California Davis USA Department of Agricultural and Environmental Sciences College of Agriculture Tennessee State University Nashville USA Department of Biological Science Tennessee State University Nashville USA Department of Chemistry Tennessee State University Nashville USA Saudi food and drug authority Riyadh Saudi Arabia

The use of antibiotics in humans and animals has been marked as a significant step in health due to their effectiveness in controlling and treating bacterial infections. The misuse and overuse of antibiotics have been identified as risk factors for bacterial resistance since microorganisms adapt and develop mechanisms to defend against antibiotics. According to the Centers for Disease Protection and Control (CDC), around 23,000 individuals die every year in the United States due to antibiotic resistance complications. As a result, a demand for alternative treatments has been a goal for scientists as the microbes adapt to selective pressure. The aim of this study is to test the antibacterial activity of leaf extracts of Peganum harmala and Haloxylon salicornicum on both Gram-positive and Gram-negative bacteria on various mediums. The results of the study showed that both P. harmala and H. salicornicum inhibited the bacterial growth in two different media. The results were also compared with different common antibiotics used in both human’s and animal’s fields and showed a promising outcome as alternative antibiotics.

关键词： Peganum harmala Haloxylon salicornicum Antibiotics Resistance Medicinal Plants Gram-Positive Gram-Negative

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Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3643-3660页

作者： Jie Wang Zilong Zhang Yan Zhuo Zhuan Zhang Rongrong Chen Li Liang Xiaohe Jiang Di Nie Chang Liu Zhiwen Zou Xiang Li Jiaxin Li Bingqi Wang Rui Wang Yong Gan Miaorong Yu School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China State Key Laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Jiangxi Medical College Nanchang UniversityNanchang 330006China School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients National Institutes for Food and Drug ControlBeijing 100050China

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum(ER)presents an opportunity to amplify the synergistic effects of chemotherapy and *** this study,we initially validated celastrol(CEL)as an inducer of immunogenic cell death(ICD)by promoting ER stress and autophagy in colorectal cancer(CRC)***,an ER-targeted strategy was posited,involving the codelivery of CEL with PD-L1 small interfering RNAs(siRNA)using KDEL peptide-modified exosomes derived from milk(KME),to enhance chemoimmunotherapy *** findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER *** to their non-targeting counterparts,KME exhibited a significant augmentation of the CEL-induced ICD ***,it facilitated the release of danger signaling molecules(DAMPs),thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the ***,the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression,consequently fostering the proliferation and activity of CD8^(+)T ***,the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in ***,a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

关键词： Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress Immunogenic cell death siRNA Chemoimmunotherapy Targeted drug delivery Endoplasmic reticulum Endoplasmic reticulum stress Immunogenic cell death siRNA

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