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Efficient drug and gene delivery to liver fibrosis:rationale, recent advances, and perspectives

Acta Pharmaceutica Sinica B 2020年第7期10卷 1279-1293页

作者： Somayeh Mahdinloo Seyed Hossein Kiaie Ala Amiri Salar Hemmati Hadi Valizadeh Parvin Zakeri-Milani faculty of pharmacy Tabriz University of Medical ScienceTabriz ***Iran Nano Drug Delivery research center Kermanshah University of Medical SciencesKermanshah ***Iran faculty of Basic Sciences Islamic Azad UniversityScience and Research BranchTehran ***Iran Drug Applied research center Tabriz University of Medical SciencesTabriz ***Iran Drug Applied research center and faculty of pharmacy Tabriz University of Medical SciencesTabriz ***Iran liver and gastrointestinal diseases research center and faculty of pharmacy Tabriz University of Medical SciencesTabriz ***Iran

liver fibrosis results from chronic damages together with an accumulation of extracellular matrix,and no specific medical therapy is approved for that until *** to liver metabolic capacity for drugs,the fragility of drugs,and the presence of insurmountable physiological obstacles in the way of targeting,the development of efficient drug delivery systems for anti-fibrotics seems *** have explored articles with a different perspective on liver fibrosis over the two decades,then collected and summarized the information by providing corresponding in vitro and in vivo *** have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in ***,the critical chemical and herbal anti-fibrotics,biological molecules such as micro-RNAs,siRNAs,and growth factors,which can affect cell division and differentiation,are ***,drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data *** review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

关键词： liver fibrosis Hepatic stellate cell Drug delivery Gene therapy Lipid nanoparticle Viral and non-viral vector Herbal anti-fibrotic

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Efficacy and safety of ivermectin in patients with mild and moderate COVID-19:A randomized controlled trial

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Asian Pacific Journal of Tropical Medicine 2023年第1期16卷 3-8页

作者： Alireza Malektojari Sara Ghazizadeh Mohammad Hamed Ersi Elham Brahimi Soheil Hassanipour Mohammad Fathalipour Mehdi Hassaniazad Evidence Based Medicine center Hormozgan University of Medical SciencesBandar AbbasIran Clinical research Development center of Shahid Mohammadi Hospital Hormozgan University of Medical SciencesBandar AbbasIran Infectious and Tropical diseases research center Hormozgan Health InstituteHormozgan University of Medical SciencesBandar AbbasIran gastrointestinal and liver diseases research center Guilan University of Medical SciencesRashtIran Department of Pharmacology and Toxicology Faculty of PharmacyHormozgan University of Medical SciencesBandar AbbasIran

Objective:To evaluate the effectiveness and safety of ivermectin in patients with mild and moderate ***:This study was a single-center,randomized,open-label,controlled trial with a 2-arm parallel-group design on 68 patients with *** to the 1:1 ratio between the study groups(ivermectin group and standard treatment group),patients were randomly admitted to each intervention ***:The mean age of the participants in the ivermectin group was(48.37±13.32)*** of them were males(54.5%)and the participants in the control group had a mean age of(46.28±14.47)years,with nineteen of them being males(59.4%).As a primary outcome,after 5 days of randomization,there was no significant difference between the ivermectin group and the control group in the length of stay in the hospital(P=0.168).ICU admission(P=0.764),length of stay in ICU(P=0.622),in-hospital mortality(P=0.427),adverse drug reactions,and changes in the mean difference of laboratory data had not any significant difference between the two groups(except for urea change).In addition,the radiologic findings of the two groups of patients were not significantly *** regression analysis showed that for every 10 years increase of age,0.6 day of hospitalization duration was *** was no statistically significant association between other variables and clinical ***:Among adult hospitalized patients with moderate to severe COVID-19,there was no significant relationship between the administration of ivermectin single dose in a five-day course and clinical improvement,and mortality of the participants.

关键词： COVID-19 Randomized controlled trial Ivermectin Hospitalization Mechanical ventilation Clinical symptoms

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Phytochemical and biological activities of Crataegus sinaica growing in Egypt

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Asian Pacific Journal of Tropical Medicine 2010年第4期3卷 257-261页

作者： Alaa Tawfeek Refaat Abdelaaty Abdelaziz Shahat Nermine Ahmed Ehsan Nemat Yassin Faiza Hammouda Elsayed Abou Tabl Shams Imbabi Ismail Phytochemistry Department National Research CenterEgypt National liver Institute Monofia UniversityEgypt Pharmacology Department National Research CenterEgypt Pharmacognosy Department Faculty of PharmacyCairo UniversityEgypt

Objective:To evaluate the cardiac activity and hepatoprotection of Crataegus sinaica (***).Methods:All the isolated compounds were isolated by open-column liquid chromatography(CC) using sephadex LH-20 as stationary *** of the column was performed with EtOH or *** phytochemical investigation of the young stem of *** for the first time together with the leaves and flowers lead to the isolation and identification of quercetin,hyperoside,vitexin-2"-0-rhamnoside,epicatechin,procyanidin B2 and procyanidins ***:Rats treated with the low and high dose of *** leaves with flowers extract showed 15%and 17%reduction in the heart rate,and reduction in the STsegment by 107%and 57%;*** T-amplitude was decreased by 59%of the high dose *** the other hand,the young steins and leaves with flowers extracts of *** on primary culture of rat hepatocytes monolayer indicated a hepatoprotection for the total extract,ethyl acetate,butanol,and chlor of orm fractions at 100μg/mL,75μg/mL,50μg/mL,and 25μg/mL; ***:The results of these chemical and biological studies suggest the use of *** growing in Egypt as a preventive drug against cardiovascular and hepatic diseases. The chemical studies suggest the use of woody young stems as a newly investigated bioactive *** extraction of unsaturated fatty acids from the seeds of the plant would serve as a good health and nutritive product.

关键词： Crataegus sinaica Cardiovascular Hepatoprotection Flavonoids Proanthocyanidins High performance liquid chromatography

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Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing:A cohort analysis

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World Journal of Gastroenterology 2023年第18期29卷 2864-2874页

作者： Stefania Bunduc Bianca Varzaru Razvan Andrei Iacob Andrei Sorop Ioana Manea Andreea Spiridon Raluca Chelaru Adina Emilia Croitoru Gabriel Becheanu Mona Dumbrava Simona Dima Irinel Popescu Cristian Gheorghe faculty of Medicine Carol Davila University of Medicine and PharmacyBucharest 020021Romania Digestive diseases and liver Transplantation center Fundeni Clinical InstituteBucharest 022328Romania center of Excellence in Translational Medicine Fundeni Clinical InstituteBucharest 022328Romania

BACKGROUND Genetic tests are increasingly performed for the management of unresectable pancreatic *** genotyping aimed samples current guidelines recommend using core specimens,although based on moderate quality ***,in clinical practice among the endoscopic ultrasound(EUS) guided tissue acquisition methods,fine needle aspiration(FNA) is the most widely *** To assess the adequacy for next generation sequencing(NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma(PDAC) *** Between November 2018 and December 2021,105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology *** 22 gauge(G) or 19G FNA needles were *** pass was dedicated to DNA *** concentration and purity(A260/280,A260/230) were assessed by *** assessed the differences in DNA parameters according to needle size and tumor characteristics(size,location) and the adequacy of the extracted DNA for NGS(defined as A260/280 ≥ 1.7,and DNA yield:≥ 10 ng for amplicon based NGS,≥ 50 ng for whole exome sequencing [WES],≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and ttest ***,we compared DNA purity parameters across the different DNA yield *** Our cohort included 49% male patients,aged 67.02 ± 8.38 *** 22G needle was used in 71%of the *** DNA parameters across our samples varied as follows:DNA yield:1289 ng(inter quartile range:534.75-3101),A260/280 = 1.85(1.79-1.86),A260/230 = 2.2(1.72-2.36).DNA yield was > 10 ng in all samples and > 100 ng in 93% of them(one sample < 50 ng).There were no significant differences in the concentration and A260/280 between samples by needle *** size was the only independent predictor of A260/230 which was higher in the 22G samples(P =0.038).NGS adequacy rate was 90% for 19G samples regardless of NGS type,and for 22G samples it reached 89% for WGS adequacy and 91% for WES and

关键词： Pancreatic adenocarcinoma Endoscopic ultrasound guided fine needle aspiration Next generation sequencing DNA yield Needle size Genetic testing

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Transmembrane serine protease 2 and angiotensin-converting enzyme 2 anti-inflammatory receptors for COVID-19/inflammatory bowel diseases treatment

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World Journal of Gastroenterology 2021年第46期27卷 7943-7955页

作者： Naser-Aldin Lashgari Nazanin Momeni Roudsari Saeideh Momtaz Amir Hossein Abdolghaffari Department of Toxicology and Pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehran ***Iran Medicinal Plants research center Institute of Medicinal PlantsACECRKaraj 141554364Iran Toxicology and diseases Group(TDG) Pharmaceutical Sciences Research Center(PSRC)The Institute of Pharmaceutical Sciences(TIPS)Tehran University of Medical SciencesTehran ***Iran Department of Toxicology and Pharmacology Faculty of PharmacyTehran University of Medical SciencesTehran ***Iran gastrointestinal Pharmacology Interest Group(GPIG) Universal Scientific Education and Research Network(USERN)Tehran ***Iran

long-term,and relapsing inflammatory *** may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the *** epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality *** has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral ***,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter *** analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in *** from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.

关键词： Inflammatory bowel diseases COVID-19 Transmembrane serine protease 2 Inflammation Pro-inflammatory Immunological responses

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Effects of herbal medicine in gastroesophageal reflux disease symptoms: a systematic review and meta-analysis

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Traditional Medicine research 2020年第6期5卷 464-475,I0002,I0003页

作者： Fariba Sadeghi Seyed Mohammad Bagher Fazljou Bita Sepehri Laleh Khodaie Hassan Monirifar Mojgan Mirghafourvand Department of Persian Medicine School of Traditional Medicine Tabriz University of Medical Sciences Tabriz Iran liver and gastrointestinal diseases research center Tabriz University of Medical SciencesTabrizIran Department of Traditional pharmacy Faculty of Traditional MedicineTabriz University of Medical SciencesTabrizIran Horticulture and Crops research Department East Azarbaijan Agricultural and Natural Resources Research and Education CenterTabrizIran Social Determinants of Health research center Tabriz University of Medical SciencesTabrizIran

Background: Pyrosis and regurgitation are the cardinal symptoms of gastroesophageal reflux disease. Severalherbs have been used for treating gastrointestinal disorders worldwide. This systematic review was conducted toinvestigate the effects of medicinal herbs on gastroesophageal reflux disease and adverse events. Methods:MEDLINE (via PubMed;The United States National Library of Medicine, USA), Scopus, ScienceDirect,Cochrane Central Register of Controlled Trials, Web of Science, Magiran, and Scientific Information Databasewere systematically searched for human studies, without a time frame, using medical subject heading terms such as“gastroesophageal reflux disease”, “reflux”, “esophagitis” and “herbs”. Manual searches completed the electronicsearches. Results: Thirteen randomized controlled trials were identified, including 1,164 participants from 1,509publications. In comparing herbal medicine to placebo, there were no significant differences in terms of heartburn(P = 0.23 and 0.48), epigastric or abdominal pain (P = 0.35), reflux syndrome (P = 0.12), and effective rate (P =0.60), but there was a significant difference in terms of acid regurgitation (P = 0.01). In comparing herbal medicineto drugs, there was a significant difference in terms of effective rate (P = 0.001), and there was one trial thatreported a significant difference in terms of epigastric pain (P = 0.00001). Also, in comparing herbal medicine todrugs, there were no significant differences in terms of acid regurgitation (P = 0.39). Conclusion: Thismeta-analysis showed that herbal medicines are effective in treating gastroesophageal reflux disease. Furtherstandardized researches with a large-scale, multicenter, and rigorous design are needed.

关键词： Herbal medicine Gastroesophageal reflux disease Randomized controlled trial Acid regurgitation Effective rate Epigastric pain

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Glutaminolysis-ammonia-urea Cycle Axis,Non-alcoholic Fatty liver Disease Progression and Development of Novel Therapies

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 356-362页

作者： Ángela Rojas María Rosario García-Lozano Antonio Gil-Gómez Manuel Romero-Gómez Javier Ampuero Department of Unit of Digestive diseases Virgen del Rocío University HospitalSevilleSpain Seliver group at the Insti-tute of Biomedicine of Seville(IBIS) Virgen del Rocío University Hospital/CSIC/University of SevilleSevilleSpain center for the Study of liver and gastrointestinal diseases(CIBERehd) Carlos III National Institute of HealthMadridSpain De-partment of Organic and Medicinal Chemistry Faculty of PharmacyUniversity of SevilleE-41071SevilleSpain

The prevalence of non-alcoholic fatty liver disease(NAFLD)is increasing worldwide,reflecting the current epidemics of obesity,insulin resistance,type 2 diabetes mellitus,and metabolic *** is characterized by the accumulation of fat in the liver,and is known to be a cause of *** many pathways have been proposed,the cause of NAFLD-linked fibrosis progression is still unclear,which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular *** is associated with activation of hepatic stellate cells(HSC)and accumulation of excess extracellular matrix proteins,and inhibiting the activation of HSCs would be expected to slow the progression of *** molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC *** mechanisms are plausible antifibrotic targets in NASH,as the activation of HSCs the proliferation of myofibroblasts depend on those *** review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression,and shows how the axis could be a novel therapeutic target.

关键词： Non-alcoholic fatty liver disease Cirrhosis Fibrosis Glutaminoly-sis Ammonia Urea

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Interventions of natural and synthetic agents in inflammatory bowel disease, modulation of nitric oxide pathways

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World Journal of Gastroenterology 2020年第24期26卷 3365-3400页

作者： Aida Kamalian Masoud Sohrabi Asl Mahsa Dolatshahi Khashayar Afshari Shiva Shamshiri Nazanin Momeni Roudsari Saeideh Momtaz Roja Rahimi Mohammad Abdollahi Amir Hossein Abdolghaffari Department of Medicine Tehran University of Medical SciencesTehran ***Iran Students'Scientific research center Tehran University of Medical SciencesTehran ***Iran Department of Traditional pharmacy School of Persian MedicineTehran University of Medical SciencesTehran ***Iran Department of Toxicology and Pharmacology Faculty of PharmacyTehran Medical SciencesIslamic Azad UniversityTehran ***Iran Medicinal Plants research center Institute of Medicinal PlantsACECRTehran ***Iran Toxicology and diseases Group(TDG) Pharmaceutical Sciences Research Center(PSRC)The Institute of Pharmaceutical Sciences(TIPS)and Department of Toxicology and PharmacologySchool of PharmacyTehran University of Medical SciencesTehran ***Iran gastrointestinal Pharmacology Interest Group Universal Scientific Education and Research NetworkTehran ***Iran Department of Toxicology and Pharmacology Faculty of PharmacyTehran University of Medical SciencesTehran ***Iran

Inflammatory bowel disease(IBD)refers to a group of disorders characterized by chronic inflammation of the gastrointestinal(GI)*** elevated levels of nitric oxide(NO)in serum and affected tissues;mainly synthesized by the inducible nitric oxide synthase(iNOS)enzyme;can exacerbate GI inflammation and is one of the major biomarkers of GI *** natural and synthetic agents are able to ameliorate GI inflammation and decrease iNOS expression to the extent comparable with some IBD ***,the purpose of this study was to gather a list of natural or synthetic mediators capable of modulating IBD through the NO *** databases including Google Scholar and PubMed were searched from 1980 to May *** found that polyphenols and particularly flavonoids are able to markedly attenuate NO production and iNOS expression through the nuclear factorκB(NF-κB)and JAK/STAT signaling *** and probiotics can also alter the GI microbiota and reduce NO expression in IBD models through a broad array of mechanisms.A number of synthetic molecules have been found to suppress NO expression either dependent on the NF-κB signaling pathway(i.e.,dexamethasone,pioglitazone,tropisetron)or independent from this pathway(i.e.,nicotine,prednisolone,celecoxib,β-adrenoceptor antagonists).Co-administration of natural and synthetic agents can affect the tissue level of NO and may improve IBD symptoms mainly by modulating the Toll like receptor-4 and NF-κB signaling pathways.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease Nitric oxide Nuclear factor-κB Natural or synthetic mediators

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Real-time sono-elastography in the diagnosis of diffuse liver diseases

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World Journal of Gastroenterology 2010年第14期16卷 1720-1726页

作者： Dan Ionut Gheonea Adrian S ǎftoiu Tudorel Ciurea Florin Gorunescu Sevastita Iordache Gabriel Lucian Popescu Smaranda Belciug Marina Gorunescu Larisa Sǎndulescu research center of Gastroenterology and Hepatology University of Medicine and Pharmacy Craiova 200349 Romania Department of Biostatistics and Informatics University of Medicine and Pharmacy Craiova 200349 Romania IT Department University of Medicine and Pharmacy Craiova 200349 Romania faculty of Mathematics of Computer Science University of Craiova Craiova 200585 Romania

AIM: To analyze whether computer-enhanced dynamic analysis of elastography movies is able to better characterize and differentiate between different degrees of liver fibrosis. METHODS: The study design was prospective. A total of 132 consecutive patients with chronic liver diseases and healthy volunteers were examined by transabdominal ultrasound elastography. All examinations were done by two ***: Due to the limitations of the method, we obtained high-quality elastography information in only 73.48% of the patients. The κ-means clustering method was applied to assess the inter-observer diagnosis varia- bility, which showed good variability values in accordance with the experience of ultrasound examination of every observer. Cohen’sκ test indicated a moderate agreement between the study observers (κ = 0.4728). Furthermore, we compared the way the two observers clustered the patients, using the test for comparing two proportions (t value, two-sided test). There was no statistically significant difference between the two physicians, regardless of the patients’ real status. CONCLUSION: Transabdominal real-time elastography is certainly a very useful method in depicting liver hard- ness, although it is incompletely tested in large multicenter studies.

关键词： Elastography Ultrasonography liver steato- sis Viral hepatitis liver cirrhosis

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Serum immunoglobulin A concentration is a reliable biomarker for liver fibrosis in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2014年第35期20卷 12566-12573页

作者： Iradj Maleki Mahmood Reza Aminafshari Tarang Taghvaei Vahid Hosseini Alireza Rafiei Zhila Torabizadeh Maryam Barzin Elahe Orang Inflammatory diseases of Upper gastrointestinal Tract research center Mazandaran University of Medical Sciences Department of Immunology Mazandaran University of Medical Sciencesfaculty of Medicine Department of Pathology Mazandaran University of Medical SciencesImam Khomeini Hospital Department of Radiology Mazandaran University of Medical SciencesImam Khomeini Hospital

AIM: To evaluate the diagnostic accuracy of serum Immunoglobulin A (IgA) for differentiating early stage nonalcoholic fatty liver disease (NAFLD) from nonalcoholic steatohepatitis (NASH).

关键词： Non-alcoholic Fatty liver Disease Biological Markers Immunoglobulin A liver Cirrhosis Fibrosis

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