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Mechanism of Huashi Xingyu Qingre recipe(化湿行淤清热方)in treating Oral lichen planus based on network pharmacology and clinical trial verification

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Journal of Traditional Chinese Medicine 2022年第2期42卷 304-313页

作者： DENG Qianlan LU Yueting YAN Lijuan LU Hualin JIN Ruizhe XU Yanzhi SONG Jing LIU Tiejun Department of Stomatology the Fourth Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Stomatology Hebei Children's HospitalShijiazhuang 050000China Department of Stomatology Shijiazhuang Third HospitalShijiazhuang 050000China

OBJECTIVE:To identify the main active components and targets of Huashi Xingyu Qingre recipe(化湿行淤清热方,HXQR)and to investigate its mechanism in the treatment of Oral lichen planus(OLP).METHODS:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was searched to identify the active ingredients and corresponding targets of HXQR.Disease genes were obtained from the Gene Cards database,and a“drugdisease regulatory network”was constructed using Cytoscape software and PERL programming language.The STRING database was used to build a protein-protein interaction network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)terms were analyzed using R software with a Bioconducter plugin.Finally,the results and the efficacy of HXQR in treating OLP were validated in a clinical trial that included enzyme-linked immunosorbent assay(ELISA)testing and observations of the post-treatment changes in clinical symptoms.RESULTS:HXQR contained 167 active components and 261 targets,with 391 disease targets.The intersection of these two categories in a Venn diagram revealed 57 drugdisease common targets.A compound-target network was constructed and revealed that the six key pharmaceutical ingredients of HXQR were quercetin,luteolin,wogonin,kaempferol,beta-carotene,and baicalein.The protein-protein interaction network mainly involved core proteins such as ALB,interleukin-6,and AKT1.Drug-disease common targets were enriched in 1628 GO terms and 117 KEGG terms,mainly involving inflammatory responses,viral infections,and tumorrelated pathways.ELISA testing indicated that HXQR inhibited the tumor necrosis factor(TNF)signaling pathway by reducing the expression of interleukin-6,matrix metalloproteinase-9,and intercellular adhesion molecule-1.The clinical symptoms of the patients with OLP were significantly improved after 8 weeks of treatment with HXQR.CONCLUSION:HXQR treats OLP by regulating the TNF signaling pathway,resulting in a marked treatment effect with few adverse effects.

关键词： lichen planus Oral network pharmacology clinical trial Huashi Xingyu Qingre recipe

An update on Oral drug delivery via intestinal lymphatic transport

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Acta Pharmaceutica Sinica B 2021年第8期11卷 2449-2468页

作者： Zichen Zhang Yi Lu Jianping Qi Wei Wu Key Laboratory of Smart Drug Delivery of MOE School of PharmacyFudan UniversityShanghai 201203China Center for Medical Research and Innovation Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China

Orally administered drug entities have to survive the harsh gastrointestinal environment,penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation.Whereas the gastrointestinal stability can be well maintained by taking proper measures,hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism.The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway.Intestinal lymphatic transport is emerging as a promising pathway to this end.In this review,we intend to provide an updated overview on the rationale,strategies,factors and applications involved in intestinal lymphatic transport.There are mainly two pathways for perOral lymphatic transportdthe chylomicron and the microfold cell pathways.The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

关键词： Drug delivery Oral Lymphatic transport Drug absorption Chylomicron Microfold cell Drug carriers Nanoparticles

Effects of a Plantago ovata-based herbal compound in prevention and treatment of Oral mucositis in patients with breast cancer receiving chemotherapy: A double-blind, randomized, controlled crossover trial

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Journal of Integrative Medicine 2020年第3期18卷 214-221页

作者： Fatemeh Sadat Hasheminasab Seyed Mehdi Hashemi Azizallah Dehghan Fariba Sharififar Mohammad Setayesh Pegah Sasanpour Mojtaba Tasbandi Mahboobeh Raeiszadeh Herbal and Traditional Medicines Research Center Kerman University of Medical SciencesKerman ***Iran Department of Traditional Medicine School of Traditional MedicineKerman University of Medical SciencesKerman ***Iran Clinical Immunology Research Center Ali-ebne Abitaleb HospitalZahedan University of Medical SciencesZahedan ***Iran Noncommunicable Diseases Research Center Fasa University of Medical SciencesFasa ***Iran Medical School Zahedan University of Medical SciencesZahedan ***Iran Department of Traditional Pharmacy School of Traditional MedicineKerman University of Medical SciencesKerman ***Iran

Background: Oral mucositis(OM) is one of the most common complications of mucotoxic cancer therapy.Mucositis induces clinically significant pain, increases the risk of infections and affects the patients’ quality of life.Objective: This study investigated the effects of an herbal preparation from Plantago ovata hydrocolloid in the prevention and treatment of OM, in breast cancer patients undergoing chemotherapy with a regimen including adriamycin.Design, setting, participants, and interventions: This research was a double-blind, randomized, controlled crossover trial. The herbal compound consisted of a mixture of 500 mg of P. ovate husk in 30 m L water plus three drops of vinegar per dose, which was used as a mouthwash. Phytochemical and physicochemical tests of the compound were also performed. Twenty-eight patients who developed mucositis during the chemotherapy screening cycle were randomized to the herbal compound(n = 14) and placebo(n = 14) groups. They received herbal compound or placebo three times per day during their next chemotherapy cycle(cycle 1 of treatment). Patients were crossed over during cycle 2 of treatment and received the alternative therapy. An Oral care protocol was prescribed to all patients in cycles 1 and 2 of the treatment.Main outcome measures: The patients were visited at baseline, the end of the first and second weeks of the screening cycle, and the end of the first and second weeks of each of two treatment cycles. The degree of mucositis was used as the main treatment outcome. Other indexes, such as the severity of pain, xerostomia grade and the quality of life were also measured.Results: Compared with the placebo, the herbal compound significantly reduced the degree of mucositis,the severity of pain and the xerostomia grade;it also improved the patients’ quality of life(P Oral care protocol had a significant effect in the reduction of OM(P Oral care protocol and the he

关键词： Persian medicine Oral mucositis Plantago ovate Breast cancer Chemotherapy

PEP06 polypeptide 30 is a novel clusterdissociating agent inhibiting αv integrin/FAK/Src signaling in Oral squamous cell carcinoma cells

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1163-1173页

作者： Gulnara Tuguzbaeva Er Yue Xi Chen Lina He Xinlei Li Jiaming Ju Ying Qin Valentin Pavlov Yanjie Lu Wenting Jia Yunlong Bai Yumei Niu Baofeng Yang Central Laboratory of Scientific Research Bashkir State Medical UniversityUfa 450008Russian Federation Department of Pharmacology(State-Province Key Laboratories of BiomedicineePharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbin 150081China Department of Endodontics the First Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Department of Orthopedic Dentistry and Maxillofacial Surgery Bashkir State Medical UniversityUfa 450008Russian Federation

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies.In Oral squamous cell carcinoma(OSCC),av integrin is a crucial mediator of multicellular clustering and collective movement in vitro;however,its contribution to metastatic spread remains to be addressed.According to the emerging therapeutic concept,dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas.This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a clusterdissociating therapeutic agent in vitro.Firstly,we found marked enrichment ofαv integrin in collectivelyinvading multicellular clusters in human OSCCs.Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of av integrin in cancerous lesions.Following PEP06treatment,cell clustering on fibronectin,migration,multicellular aggregation,anchorage-independent survival and colony formation of OSCC were significantly inhibited.Moreover,PEP06 suppressed av integrin/FAK/Sre signaling in OSCC cells.PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC in vitro.Overall,these results suggest that PEP06 polypeptide 30 inhibiting av integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

关键词： Oral squamous cell carcinoma Tumor cell clusters Collective migration Metastasis αv integrin/FAK/RC signaling RGD

Human equivalent dose of Oral 4-aminopyridine differentiates nerve crush injury from transection injury and improves post-injury function in mice

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Neural Regeneration Research 2020年第11期15卷 2098-2107页

作者： Chia George Hsu M A Hassan Talukder Li Yue Loel CTurpin Mark Noble John C.Elfar Center for Orthopaedic Research and Translational Science Penn State Hershey College of MedicineMilton S.Hershey Medical CenterHersheyPAUSA Department of Medicine Aab Cardiovascular Research InstituteUniversity of Rochester School of Medicine and DentistryRochesterNYUSA Department of Orthopedics The Warren Alpert Medical School of Brown University/Rhode Island HospitalProvidenceRIUSA Department of Neuroscience The University of Rochester Medical CenterRochesterNYUSA Department of Biomedical Genetics The University of Rochester Medical CenterRochesterNYUSA

4-Aminopyridine(4-AP), an FDA-approved drug for the symptomatic treatment of multiple sclerosis, is used to improve neuromuscular function in patients with diverse demyelinating disorders. We recently demonstrated that local, transdermal or injectable forms of 4-AP improve myelination, nerve conduction velocity, muscle atrophy, and motor function after traumatic peripheral nerve injury in mice. While Oral 4-AP is most commonly used in the clinic, it is unknown whether human equivalent Oral doses of 4-AP have effects on traumatic peripheral nerve injury differentiation, myelination, muscle atrophy, functional recovery, and post-injury inflammatory processes in animals. Mice with sciatic nerve crush or denervation injury received Oral or intraperitoneal 4-AP(10 μg) or vehicle alone and were examined for pharmacokinetics, motor function, muscle mass, intrinsic muscle force, nerve morphological and gene expression profiles. 4-AP showed linear pharmacokinetics and the maximum plasma 4-AP concentrations were proportional to 4-AP dose. Acute single dose of Oral 4-AP administration induced a rapid transient improvement in motor function that was different in traumatic peripheral nerve injury with or without nerve continuity, chronic daily Oral 4-AP treatment significantly enhanced post crush injury motor function recovery and this effect was associated with improved myelination, muscle mass, and ex vivo muscle force. Polymerase chain reaction array analysis with crushed nerve revealed significant alterations in gene involved in axonal inflammation and regeneration. These findings provide convincing evidence that regardless of the route of administration, 4-AP can acutely differentiate traumatic peripheral nerve injury with or without nerve continuity and can enhance in vivo functional recovery with better preservation of myelin sheaths, muscle mass, and muscle force. The animal experiments were approved by the University Committee on Animal Research(UCAR) at the University of Rochester(UCAR-2009-019) on March 31, 2017.

关键词： 4-aminopyridine electron microscopy of nerves functional recovery gene expression muscle force muscle mass Oral administration pharmacokinetics sciatic nerve crush injury sciatic nerve denervation injury

Single-stage tubular urethral reconstruction using Oral grafts is an alternative to classical staged approach for selected penile urethral strictures

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Asian Journal of Andrology 2020年第2期22卷 134-139页

作者： Felix Campos-Juanatey Simon Bugeja Mariya Dragova Anastasia V Frost Stella L Ivaz Daniela E Andrich Anthony R Mundy Reconstructive Urology Unit Institute of UrologyUniversity College London HospitalsLondon W1G 8PHUK Department of Urology Marques de Valdecilla University HospitalInstitute of Investigation Valdecilla(IDIVAL)Santander 39008Spain Urology Unit Mater Dei HospitalMsida MSD 2090Malta

Penile urethral strictures have been managed by a staged surgical approach.In selected cases,spongiofibrosis can be excised,a neo-urethral plate created using buccal mucosa graft(BMG)and tubularized during the same procedure,performing a“twoin-one”stage approach.We aim to identify stricture factors which indicate suitability for this two-in-one stage approach.We assess surgical outcome and compare with staged reconstruction.We conducted an observational descriptive study.The data were prospectively collected from two-in-one stage and staged penile urethroplasties using BMG in a single center between 2007 and 2017.The minimum follow-up was 6 months.Outcomes were assessed clinically,radiologically,and by flow-rate analysis.Failure was defined as recurrent stricture or any subsequent surgical or endoscopic intervention.Descriptive analysis of stricture characteristics and statistical comparison was made between groups.Of 425 penile urethroplasties,139 met the inclusion criteria:59 two-in-one stage and 80 staged.The mean stricture length was 2.8 cm(single stage)and 4.5 cm(staged).Etiology was lichen sclerosus(LS)52.5%(single stage)and 73.8%hypospadias related(staged).40.7%of patients had previous failed urethroplasties in the single-stage group and 81.2%in the staged.The most common stricture locations were navicular fossa(39.0%)and distal penile urethra(59.3%)in the single-stage group and mid or proximal penile urethra(58.7%)in the staged group.Success rates were 89.8%(single stage)and 81.3%(staged).A trend toward a single-stage approach for select penile urethral strictures was noted.We conclude that a single-stage substitution penile urethroplasty using BMG as a“two-in-one”approach is associated with excellent functional outcomes.The most suitable strictures for this approach are distal,primary,and LS-related strictures.

关键词： anterior urethral stricture hypospadias lichen sclerosus Oral mucosa reconstructive surgical procedures tissue transplants

Superior safety of direct Oral anticoagulants compared to Warfarin in patients with atrial fibrillation and underlying cancer: a national veterans affairs database study

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Journal of Geriatric Cardiology 2019年第9期16卷 706-709页

作者： Abhishek C Sawant Arnav Kumar Wilmon Mccray Sheldon Tetewsky Linda Parone Srilekha Sridhara Meghana Prakash Hiriyur Prakash Gary Tse Tong LIU Nidhi Kanwar Aishwarya Bhardwaj Sahoor Khan Christopher Manion Ankush Lahoti Ashish Pershad Peter Elkin John Corbelli Banner University Medical Center Phoenix Arizona USA Andreas Gruentzig Cardiovascular Center Emory University School of Medicine Cardiovascular Medicine Atlanta GA USA Western New York Healthcare System Buffalo VA Medical Center Buffalo NY USA Department of Medicine and Therapeutics Faculty of Medicine Chinese University of Hong Kong Hong Kong SAR China Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease Department of Cardiology Tianjin Institute of Cardiology Second Hospital of Tianjin Medical University Tianjin China

Background Studies evaluating safety of warfarin and direct Oral anticoagulants(DOACs) for prevention of stroke in patients with atrial fibrillation(AF) are lacking. Methods & Results All patients(n = 196,521) receiving care at veteran’s affairs with active cancer and AF from 2010–2015 were included. One-year mortality was significantly higher in unadjusted analysis with warfarin(44.9%) compared to dabigatran(25%, P < 0.001), rivaroxaban(24.4%, P < 0.001) and apixaban(30%, P < 0.001) and after adjusting for age, sex and type of cancer mortality(OR = 2.66, 95% CI: 2.52–2.82, P < 0.001). Risk of ischemic stroke(13.5% vs. 11.1%, 12.0%, 14.0%) was similar, however risk of hemorrhagic stroke was significantly higher among patients receiving warfarin(1.2%) compared to patients receiving dabigatran(0.5%), rivaroxaban(0.7%) and apixaban(0.8%) respectively, P = 0.04. Conclusions We demonstrated the superior safety profile of DOACs compared to warfarin among patients with underlying cancer and AF. Warfarin was associated with higher mortality, similar ischemic stroke risk but higher risk of hemorrhagic stroke.

关键词： Atrial fibrillation Cancer Oral anticoagulation

Adapting liposomes for Oral drug delivery

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Acta Pharmaceutica Sinica B 2019年第1期9卷 36-48页

作者： Haisheng He Yi Lu Jianping Qi Quangang Zhu Zhongjian Chen Wei Wu Key Laboratory of Smart Drug Delivery of MOE and PLA School of Pharmacy Fudan University Shanghai Dermatology Hospital

Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes,Oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract,difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for Oral drug delivery. This review provides an overview of the challenges and current approaches toward the Oral delivery of liposomes.

关键词： Liposomes Oral Drug delivery Stability Absorption Bioavailability

Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats

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Biomedical and Environmental Sciences 2019年第7期32卷 508-519页

作者： KULAS Jelena NINKOV Marina TUCOVIC Dina POPOV Aleksandrov Aleksandra UKROPINA Mirela CAKIC MILOSEVIC Maja MUTIC Jelena KATARANOVSKI Milena MIKROV Ivana Immunotoxicology group Department of Ecology Institute for Biological Research 'Sinisa Stankovic ' University of Belgrade 142 Bulevar despota Stefana Belgrade 11000 Serbia Institute of Zoology Faculty of Biology University of Belgrade 16 Studentskitrg Belgrade 11000 Serbia Innovation center of the Faculty of Chemistry University of Belgrade 12-16 Studentskitrg 11000 Belgrade Serbia Institute of Physiology and Biochemistry Faculty of Biology University of Belgrade 16 Studentskitrg Belgrade 11000 Serbia

Objective The aim of this study is to investigate the effects of Oral cadmium(Cd) ingestion on the pulmonary immune response. Methods Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day Oral Cd administration(5 and 50 mg/L). Antioxidant enzyme defense(superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor(TNF) and interferon(IFN)-γ, as well as the activity of myeloperoxidase(MPO), nitric oxide(NO), and various cytokines [interleukin(IL)-1β, IL-6, IL-10, and IL-17] were investigated. Results Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. Conclusion The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.

关键词： Rats Oral cadmium administration Lungs Cytokine response