BACKGROUND Adenoviruses pose a serious health risk particularly in the absence of any clinically approved treatment.As adenoviral infections are quite frequent and recent outbreaks manifest more virulent variant strai...BACKGROUND Adenoviruses pose a serious health risk particularly in the absence of any clinically approved treatment.As adenoviral infections are quite frequent and recent outbreaks manifest more virulent variant strains,the need to develop an effective treatment remains a priority.The adenoviral protein,preterminal protein(pTP),is one of the key common products of the viral lifecycle as it is necessary to initiate viral replication and hence the infection process.This makes pTP a potential chemotherapeutic target in the search for and development of an effective treatment for adenoviral induced infections.Here we report,for the first time,that glycosylation of pTP in situ prevents binding to ssDNA in vitro.AIM To explore whether specific structural tailoring of the adenoviral protein pTP,imparts the potential to scupper the viral replication process.METHODS All chemicals used were of reagent grade.Overexpression of pTP was achieved using the‘BAC to BAC’expression system.The presence and relative concentration of the protein was determined throughout the incubation period by the Bradford assay.The pTP was identified by MALDI-TOFF and sodium dodecyl sulphate polyacrylamide gel electrophoresis.For the removal of the aminosugar,a deglycosylase enzyme kit from PROZYME was used.Purification of cloned pTP(6xHis)was done with a ssDNA cellulose column followed by a Ni-NTA column.His-tags were excised with the Tobacco etch virus protease.Protein fractionation was performed with a fraction collector coupled to a UV detector(280 nm)from Pharmacia.RESULTS The pTP overexpressed in insect cells(Spodoptera frugiperda)(>96 hours),is unable to bind to ssDNA in vitro.Treatment of this unbound protein with a deglycosidase enzyme that is specific for the removal of truncated unsubstituted O-linked Galβ(1-3)GalNAc-α1 disaccharides bound to Thr or Ser in a glycoprotein,restores binding to ssDNA.Data is presented as a linegraph for both the glycosylated and the deglycosylated proteins.Each point represents the mean of triplicate experiments(from different batches).Means and standard deviation were calculated and plotted on a line graph(with error bars).CONCLUSION The finding that glycosylation of cloned pTP in situ prevents binding to ssDNA in vitro could aid in the development of an effective treatment of adenoviral infections and/or as an adjunct to complement other antiadenoviral chemotherapeutic strategies.展开更多
AIM： To investigate the effcacy of fu-qi granule （FQG） on carbon tetrachloride （CCl4） induced liver fbrosis in rats and the underlying mechanisms. METHODS： Sixty rats were randomly divided into six groups： norm...AIM： To investigate the effcacy of fu-qi granule （FQG） on carbon tetrachloride （CCl4） induced liver fbrosis in rats and the underlying mechanisms. METHODS： Sixty rats were randomly divided into six groups： normal control group, CCl4 induced liver fbrosis group, AnluoHuaxianWan group and three treatment groups of FQG. Treatment of rats with intraperitoneal injection of carbon tetrachloride solution at 0.3 mL per 100 g body weigh twice a week for 8 wk. The normal control group the rats were given the media （olive oil） at the same time. In the frst 2 wk, rats were raised with feedstuff （80% corn meal, 20% lard, 0.5% cholesterol）. Serum samples were collected for alanine transaminase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein assay and typical histopathological changes was observed in Hematoxylin-eosin staining sections. Smooth muscle alpha actin （α-SMA） was analyzed with immunohistochemistry. Mammalian target of rapamycin （mTOR） and hypoxia-inducible factor-1 （HIF-1α） expressions were detected by Western blot-ting. Tissue inhibitor of matrix metalloproteinases-1 （TIMP-1） and matrix metalloproteinases-9 （MMP-9） were measured with semi-quantitative reverse transcriptase-polymerase chain reaction.RESULTS： FQG significantly reduced the serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and increased the serum contents of albumin, total protein in rats with liver fibrosis. Moreover, FQG promoted extracellular matrix degradation by increasing MMP-9 and inhibiting TIMP-1 and α-SMA. mTOR and HIF-1α expression in liver significantly decreased in the rats treated with FQG. CONCLUSION： The results indicated that FQG signi-fcantly reverse fbrosis induced by CCl4, which should be developed as a new and promising preparation for the prevention of liver fbrosis.展开更多
Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,...Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,for management of hepatitis B reactivation.She developed bleeding diathesis and severe thrombocytopenia was detected on investigations.Bone marrow examination showed normocellular marrow with megakaryocytes.Tenofovir was stopped and she was started on intravenous immunoglobulin,followed by steroids.There was improvement in platlet counts.The case highlights a rare side effect of tenofovir therapy.展开更多
BACKGROUND Using gas chromatography-mass spectrometry(GC/MS)analysis,we examined the composition of volatile components present in the yellow and green fruits,seeds,and jam of the scrambling shrub Capparis cartilagine...BACKGROUND Using gas chromatography-mass spectrometry(GC/MS)analysis,we examined the composition of volatile components present in the yellow and green fruits,seeds,and jam of the scrambling shrub Capparis cartilaginea(C.cartilaginea).These plant samples were collected from Kibbutz Yotvata in Israel.In all the tested samples,isothiocyanates were identified.Utilizing the PASS program,we ascertained the biological activity of these isothiocyanates present in the Capparis genus.The study results highlighted that all isothiocyanates could potentially act as apoptosis agonists,making them strong candidates for antitumor drugs.This information holds significant value for the fields of medicinal chemistry,pharmacology,and practical medicine.AIM To investigate the volatile components present in the yellow and green fruits,seeds,and jam of the C.cartilaginea shrub using GC/MS analysis,to detect isothiocyanates in all the analyzed plant samples,and to assess the biological activity of these isothiocyanates utilizing the PASS program.METHODS We utilized two primary methods to analyze the volatile compounds present in the yellow and green fruits,seeds,and jams of the C.cartilaginea,native to Israel.We identified biologically active isothiocyanates in these samples.Their anticipated biological activities were determined using the PASS program,with the most dominant activities being apoptosis agonist,anticarcinogenic,and antineoplastic specifically for genitourinary cancer.RESULTS Fruits,seeds,and jams containing isothiocyanates,which exhibit antineoplastic and anticarcinogenic activities,could be suggested for cancer prevention and management.Specific isothiocyanates,with therapeutic potential in this realm,could be recommended as potent anticancer agents in practical medicine following clinical trials.CONCLUSION The discovery that isothiocyanates exhibit potent antineoplastic and anticarcinogenic activities was unexpected.Additionally,certain isothiocyanates demonstrated antifungal,antiviral(specifically against arbovirus),and antiparasitic properties.展开更多
Small GTP-binding proteins of the ADP-ribosylation fac-tor （Arf） family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prol...Small GTP-binding proteins of the ADP-ribosylation fac-tor （Arf） family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prolif-eration, cytoskeletal remodelling, and migration. The activity of Arfs is tightly regulated. GTPase-activating proteins （GAPs） inactivate Arfs by stimulating GTP hydrolysis, and guanine nucleotide exchange factors （GEFs） stimulate the conversion of inactive GDP-bound Arf to the active GTP-bound conformation. There is increasing evidence that Arf small GTPases contribute to cancer growth and invasion. Increased expression of Arf6 and of Arf-GEPs, or deregulation Arf-GAP functions have been correlated with enhanced invasive capacity of tumor cells and metastasis. The spatiotemporal spe-cifcity of Arf activation is dictated by their GEFs that integrate various signals in stimulated cells. Brefeldin A （BFA）, which inactivates a subset of Arf-GEFs, has been very useful for assessing the function of Golgi-localized Arfs. However, specifc inhibitors to investigate the individual function of BFA-sensitive and insensitive Arf-GEFs are lacking. In recent years, specifc screens have been developed, and new inhibitors with improved se-lectivity and potency to study cell functional responses regulated by BFA-sensitive and BFA-insensitive Arf pathways have been identified. These inhibitors have been instrumental for our understanding of the spa-tiotemporal activation of Arf proteins in cells and dem-onstrate the feasibility of developing small molecules interfering with Arf activation to prevent tumor invasion and metastasis.展开更多
We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of ...We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected)over the past period of time.Tzyh-Chyuan Hour,Ph D,Associate Professor,Institute of Biochemistry,Kaohsiung Medical University,100 Shih-Chuan 1st Road,展开更多
The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the ...The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed.展开更多
Prostatitis comprises of a group of syndromes that affect almost 50% of men at least once in their lifetime and makeup the majority of visits to the Urology Clinics.After much debate, it has been divided into four dis...Prostatitis comprises of a group of syndromes that affect almost 50% of men at least once in their lifetime and makeup the majority of visits to the Urology Clinics.After much debate, it has been divided into four distinct categories by National Institutes of Health namely(1) acute bacterial prostatitis;(2) chronic bacterial prostatitis;(3) chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) which is further divided into inflammatory and non-inflammatory CP/CPPS; and(4)asymptomatic inflammatory prostatitis. CP/CPPS has been a cause of great concern for both patients and physicians because of the lack of presence of thoroughinformation about the etiological factors along with the difficult-to-treat nature of the syndrome. For the presented manuscript an extensive search on PubM ed was conducted for CP/CPPS aimed to present an updated review on the evaluation and treatment options available for patients with CP/CPPS. Several diagnostic criteria's have been established to diagnose CP/CPPS, with prostatic/pelvic pain for at least 3 mo being the major classifying symptom along with the presence of lower urinary tract symptoms and/or ejaculatory pain. Diagnostic tests can help differentiate CP/CPPS from other syndromes that come under the heading of prostatitis by ruling out active urinary tract infection and/or prostatic infection with uropathogen by performing urine cultures, Meares-Stamey Four Glass Test, Preand Post-Massage Two Glass Test. Asymptomatic inflammatory prostatitis is confirmed through prostate biopsy done for elevated serum prostate-specific antigen levels or abnormal digital rectal examination. Researchers have been unable to link a single etiological factor to the pathogenesis of CP/CPPS, instead a cluster of potential etiologies including atypical bacterial or nanobacterial infection, autoimmunity, neurological dysfunction and pelvic floor muscle dysfunction are most commonly implicated. Initially monotherapy with anti-biotics and alpha adrenergic-blockers can be tried, but its success has only been observed in treatment nave population. Other pharmacotherapies including phytotherapy, neuromodulatory drugs and anti-inflammatories achieved limited success in trials. Complementary and interventional therapies including acupuncture, myofascial trigger point release and pelvic floor biofeedback have been employed. This review points towards the fact that treatment should be tailored individually for patients based on their symptoms. Patients can be stratified phenotypically based on the UPOINT system constituting of Urinary, Psychosocial, Organ-specific, Infectious, Neurologic/Systemic and symptoms of muscular Tenderness and the treatment algorithm should be proposed accordingly. Treatment of CP/CPPS should be aimed towards treating local aswell as central factors causing the symptoms. Surgical intervention can cause significant morbidity and should only be reserved for treatment-refractory patients that have previously failed to respond to multiple drug therapies.展开更多
Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Pharmacology.The editors and authors of the articles submitted to the journal ar...Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Pharmacology.The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles(including those published in this issue and those rejected for this issue)during the last editing time period.Tzyh-Chyuan Hour,Ph D,Associate Professor,Institute of Biochemistry,Kaohsiung Medical University,100 Shih-Chuan 1st Road,Kaohsiung 807,Taiwan。展开更多
The therapeutic potential of diet,dietary supplements,herbal remedies,and nutraceuticals for treatment of depression and anxiety is being increasingly explored.In this commentary,we discuss the recent findings on the ...The therapeutic potential of diet,dietary supplements,herbal remedies,and nutraceuticals for treatment of depression and anxiety is being increasingly explored.In this commentary,we discuss the recent findings on the antidepressant potential of silymarin(SILY)in mice and present an alternative approach.We highlight the extensive research on another phytochemical,curcumin,for the treatment of depression and anxiety.Finally,we suggest a future application,which investigates the potential synergistic effects of combined treatment with SILY and curcumin for depression.展开更多
AIM： To examine whether vitamin D is of potential relevance in the healing process of fractures. METHODS： The present narrative review examined the bulk of the evidence based literature on the topic of vitamin D and...AIM： To examine whether vitamin D is of potential relevance in the healing process of fractures. METHODS： The present narrative review examined the bulk of the evidence based literature on the topic of vitamin D and bone healing in key electronic data bases from 1980 onwards using the terms vitamin D and bone healing, callus, fracture healing. All data were examined carefully and categorized according to type of study. A summary of the diverse terms and approaches employed in the research, as well as the rationale for hypothesizing vitamin D has a role in fracture healing was detailed.RESULTS： The results show very few human studies have been conducted to examine if vitamin D is effective at promoting post fracture healing, and the different ani-mal models that have been studied provide no consensus on this topic. The terms used in the related literature, as well as the methods used to arrive at conclusions on this clinical issue are highly diverse, there is no standardization of either of these important terms and methodolo-gies, hence no conclusive statements or clinical guide-lines can be forthcoming. There is a strong rational for continuing to examine if vitamin D supplements should be administered post-fracture, and ample evidence vitamin D is an essential hormone for functioning in general, as well as bone health and muscle as this relates to bone density.CONCLUSION： Whether those with low vitamin D levels can beneft from supplements if their nutritional practices do not cover recommended daily amounts, remains in question.展开更多
Antivirulence therapy inhibits bacterial virulence factors, thus preventing the development of infection without affecting bacterial growth. The development of new antibiotics is complicated by the increasing incidenc...Antivirulence therapy inhibits bacterial virulence factors, thus preventing the development of infection without affecting bacterial growth. The development of new antibiotics is complicated by the increasing incidence of antibiotic resistance in pathogenic bacteria. Antiviru-lence therapy is a promising alternative to traditional an-tibiotic therapy for the treatment of infectious disease, either alone or in combination with antibiotic treatment. In this review, we consider patents concerning inhibition of several bacterial virulence factors： adhesion/colonization, secretion systems, cellular signalling systems and antimicrobial resistance mechanisms. Finally, we emphasize the importance of analyzing new targets and/or molecules in this feld and of considering possible resistance mechanisms.展开更多
Prostate cancer is a major public health concern world-wide, being one of the most prevalent cancers in men. Great improvements have been made both in terms of early diagnosis and therapeutics. However, there is still...Prostate cancer is a major public health concern world-wide, being one of the most prevalent cancers in men. Great improvements have been made both in terms of early diagnosis and therapeutics. However, there is still an urgent need for reliable biomarkers that could overcome the lack of cancer-specifcity of prostate-specifc antigen, as well as alternative therapeutic targets for advanced metastatic cases. Reversible phosphorylation of proteins is a post-translational modifcation critical to the regulation of numerous cellular processes. Phosphoprotein phosphatase 1 （PPP1） is a major serine/threonine phos-phatase, whose specifcity is determined by its interacting proteins. These interactors can be PPP1 substrates, regulators, or even both. Deregulation of this protein-protein interaction network alters cell dynamics and underlies the development of several cancer hallmarks. Therefore, the identification of PPP1 interactome in specific cellular context is of crucial importance. The knowledge on PPP1 complexes in prostate cancer remains scarce, with only 4 holoenzymes characterized in human prostate cancer models. However, an increasing number of PPP1 interactors have been identifed as expressed in human prostate tissue, including the tumor suppressors TP53 and RB1. Efforts should be made in order to identify the role of such proteins in prostate carcinogenesis, since only 26 have yet well-recognized roles. Here, we revise literature and human protein databases to provide an in-depth knowledge on the biological significance of PPP1 complexes in human prostate carcinogenesis and their potential use as therapeutic targets for the development of new therapies for prostate cancer.展开更多
We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of ...We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the展开更多
Inflammatory bowel disease (IBD) has been a worldwide health problem. It is characterized by severe intestinal inflammation due to immune responses against the gut microbes in genetically susceptible individuals. The ...Inflammatory bowel disease (IBD) has been a worldwide health problem. It is characterized by severe intestinal inflammation due to immune responses against the gut microbes in genetically susceptible individuals. The understanding of gut microbiota for its composition and complex interaction in normal and diseased conditions has been assisted by the use of molecular, metagenomics and meta transcriptomics studies. The alteration of intestinal microbiota is the key determinant in the degree of inflammation caused and the prolonged course of disease. The relationship between luminal gut bacteria and innate immunity is also of prime significance. Such developments have further led to the search of specific (including bacteria and fungi) as a causative agent of IBD. Although detailed research has been done for the role of gut microbiota in IBD, molecular mechanisms and related gene expression are still not well understood in this disease, which hampers the generation of effective therapeutic agents for IBD. This paper assessed various factors contributing to IBD, genetic dysbiosis and pathogenic influence in the gut microbiota, interactions such as microbiome-host immune system interaction and microbe-microbe interactions involved in IBD, currently available IBD therapies, followed by a detailed review on bacterial infections that might be involved in IBD, globally and specifically in India.展开更多
The primary objective of this article is to analyze the role of tobacco smoke compounds able to damage the cardiovascular system and, in particular, to interfere with blood pressure. They are products of tobacco plant...The primary objective of this article is to analyze the role of tobacco smoke compounds able to damage the cardiovascular system and, in particular, to interfere with blood pressure. They are products of tobacco plant leaves, like nicotine, thiocyanate and aromatic amines, and a chemical derived from cigarette com-bustion, carbon monoxide. Of the other thousands of chemicals, there is no clear evidence of cardiovascular damage. Nicotine and its major metabolite, cotinine, usually increase blood pressure by a direct action and an action stimulating neuro-humoral metabolites of the body as well as sympathetic stimulation. An indirect mechanism of damage exerted by elevated carboxyhe-moglobin concentrations is mediated by carbon mon-oxide, which, mainly induces arterial wall damage and, consequently, late rising in blood pressure by a toxic direct action on endothelial and blood cells. Thiocya-nate, in turn, reinforces the hypoxic effects determined by carbon monoxide. Aromatic amines, depending on their chemical structure, may exert toxic effects on the cardiovascular system although they have little effect on blood pressure. A rise in blood pressure determined by smoking compounds is a consequence of both their direct toxicity and the characteristics of their chemical chains that are strongly reactive with a large number of molecules for their spatial shape. In addition, a rise in blood pressure has been documented in individuals smoking a cigarette, acutely and chronically, with irre-versible artery wall alterations several years after begin-ning smoking. Since cigarette smoking has a worldwide diffusion, the evidence of this topic meets the interest of both the scientifc community and those individuals aiming to control smoking.展开更多
Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmet...Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.展开更多
Lomatogonium rotatum(L.rotatum)Fries ex Nym,a dry whole grass belonging to the family Gentianaceae,is widely used to treat liver diseases in Mongolian medicine.In Mongolian medicine,L.rotatum Fries ex Nym,also known a...Lomatogonium rotatum(L.rotatum)Fries ex Nym,a dry whole grass belonging to the family Gentianaceae,is widely used to treat liver diseases in Mongolian medicine.In Mongolian medicine,L.rotatum Fries ex Nym,also known as Digeda,is a rare medicinal herb with low yield and widespread clinical use.Currently,it is included in over 25 traditional Mongolian medicine prescriptions that help reduce heat,dispel xieri,enhance stomach function,and heal wounds.Recent studies have shown that L.rotatum Fries ex Nym contains a variety of metabolites,including flavonoids,xanthone compounds,terpenoids,organic acids,steroids,and alkaloids.In addition,its anti-hepatitis B,anti-inflammatory,anti-acute liver injury,and anti-obesity effects have been proven by pharmacological studies.In this review,we summarize the ecological resources,traditional pharmacodynamics,chemical constituents,and pharmacological actions of L.rotatum Fries ex Nym,with an aim to provide a theoretical basis for future applied research and new product development.展开更多
Macular edema such as diabetic macular edema(DME) and diabetic retinopathy are devastating back-of-theeye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior oc...Macular edema such as diabetic macular edema(DME) and diabetic retinopathy are devastating back-of-theeye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static(corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers(bloodretinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.展开更多
he majority of cancer drugs entering clinical trials fail to reach the market due to poor efficacy. Preclinical efficacy has been traditionally tested using subcutaneous xenograft models that are cheap, fast and easy ...he majority of cancer drugs entering clinical trials fail to reach the market due to poor efficacy. Preclinical efficacy has been traditionally tested using subcutaneous xenograft models that are cheap, fast and easy to perform. However, these models lack the correct tumor microenvironment, leading to poor clinical predictivity. Selecting compounds for clinical trials based on efficacy results obtained from subcutaneous xenograft models may therefore be one important reason for the high failure rates. In this review we concentrate in describing the role and importance of the tumor microenvironment in progression of breast and prostate cancer, and describe some breast and prostate cancer cell lines that are widely used in preclinical studies. We go through different preclinical efficacy models that incorporate the tissue microenvironment and should therefore be clinically more predictive than subcutaneous xenografts. These include three-dimensional cell culture models, orthotopic and metastasis models, humanized and transgenic mouse models, and patient-derived xenografts. Different endpoint measurements and applicable imaging techniques are also discussed. We conclude that models that incorporate the tissue microenvironment should be increasingly used in preclinical efficacy studies to reduce the current high attrition rates of cancer drugs in clinical trials.展开更多
文摘BACKGROUND Adenoviruses pose a serious health risk particularly in the absence of any clinically approved treatment.As adenoviral infections are quite frequent and recent outbreaks manifest more virulent variant strains,the need to develop an effective treatment remains a priority.The adenoviral protein,preterminal protein(pTP),is one of the key common products of the viral lifecycle as it is necessary to initiate viral replication and hence the infection process.This makes pTP a potential chemotherapeutic target in the search for and development of an effective treatment for adenoviral induced infections.Here we report,for the first time,that glycosylation of pTP in situ prevents binding to ssDNA in vitro.AIM To explore whether specific structural tailoring of the adenoviral protein pTP,imparts the potential to scupper the viral replication process.METHODS All chemicals used were of reagent grade.Overexpression of pTP was achieved using the‘BAC to BAC’expression system.The presence and relative concentration of the protein was determined throughout the incubation period by the Bradford assay.The pTP was identified by MALDI-TOFF and sodium dodecyl sulphate polyacrylamide gel electrophoresis.For the removal of the aminosugar,a deglycosylase enzyme kit from PROZYME was used.Purification of cloned pTP(6xHis)was done with a ssDNA cellulose column followed by a Ni-NTA column.His-tags were excised with the Tobacco etch virus protease.Protein fractionation was performed with a fraction collector coupled to a UV detector(280 nm)from Pharmacia.RESULTS The pTP overexpressed in insect cells(Spodoptera frugiperda)(>96 hours),is unable to bind to ssDNA in vitro.Treatment of this unbound protein with a deglycosidase enzyme that is specific for the removal of truncated unsubstituted O-linked Galβ(1-3)GalNAc-α1 disaccharides bound to Thr or Ser in a glycoprotein,restores binding to ssDNA.Data is presented as a linegraph for both the glycosylated and the deglycosylated proteins.Each point represents the mean of triplicate experiments(from different batches).Means and standard deviation were calculated and plotted on a line graph(with error bars).CONCLUSION The finding that glycosylation of cloned pTP in situ prevents binding to ssDNA in vitro could aid in the development of an effective treatment of adenoviral infections and/or as an adjunct to complement other antiadenoviral chemotherapeutic strategies.
基金Supported by The National Natural Sciences Foundation,No.81173571National Basic Research Program of China,No.2007CB512607The Major Projects of the National Science and Technology,No.2012ZX10005010-002-002
文摘AIM： To investigate the effcacy of fu-qi granule （FQG） on carbon tetrachloride （CCl4） induced liver fbrosis in rats and the underlying mechanisms. METHODS： Sixty rats were randomly divided into six groups： normal control group, CCl4 induced liver fbrosis group, AnluoHuaxianWan group and three treatment groups of FQG. Treatment of rats with intraperitoneal injection of carbon tetrachloride solution at 0.3 mL per 100 g body weigh twice a week for 8 wk. The normal control group the rats were given the media （olive oil） at the same time. In the frst 2 wk, rats were raised with feedstuff （80% corn meal, 20% lard, 0.5% cholesterol）. Serum samples were collected for alanine transaminase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein assay and typical histopathological changes was observed in Hematoxylin-eosin staining sections. Smooth muscle alpha actin （α-SMA） was analyzed with immunohistochemistry. Mammalian target of rapamycin （mTOR） and hypoxia-inducible factor-1 （HIF-1α） expressions were detected by Western blot-ting. Tissue inhibitor of matrix metalloproteinases-1 （TIMP-1） and matrix metalloproteinases-9 （MMP-9） were measured with semi-quantitative reverse transcriptase-polymerase chain reaction.RESULTS： FQG significantly reduced the serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and increased the serum contents of albumin, total protein in rats with liver fibrosis. Moreover, FQG promoted extracellular matrix degradation by increasing MMP-9 and inhibiting TIMP-1 and α-SMA. mTOR and HIF-1α expression in liver significantly decreased in the rats treated with FQG. CONCLUSION： The results indicated that FQG signi-fcantly reverse fbrosis induced by CCl4, which should be developed as a new and promising preparation for the prevention of liver fbrosis.
文摘Tenofovir disoproxil fumarate is used in the management of hepatitis B and human immunodeficiency virus infection.We present a 50 years old lady,post liver transplant,who was switched over from entecavir to tenofovir,for management of hepatitis B reactivation.She developed bleeding diathesis and severe thrombocytopenia was detected on investigations.Bone marrow examination showed normocellular marrow with megakaryocytes.Tenofovir was stopped and she was started on intravenous immunoglobulin,followed by steroids.There was improvement in platlet counts.The case highlights a rare side effect of tenofovir therapy.
文摘BACKGROUND Using gas chromatography-mass spectrometry(GC/MS)analysis,we examined the composition of volatile components present in the yellow and green fruits,seeds,and jam of the scrambling shrub Capparis cartilaginea(C.cartilaginea).These plant samples were collected from Kibbutz Yotvata in Israel.In all the tested samples,isothiocyanates were identified.Utilizing the PASS program,we ascertained the biological activity of these isothiocyanates present in the Capparis genus.The study results highlighted that all isothiocyanates could potentially act as apoptosis agonists,making them strong candidates for antitumor drugs.This information holds significant value for the fields of medicinal chemistry,pharmacology,and practical medicine.AIM To investigate the volatile components present in the yellow and green fruits,seeds,and jam of the C.cartilaginea shrub using GC/MS analysis,to detect isothiocyanates in all the analyzed plant samples,and to assess the biological activity of these isothiocyanates utilizing the PASS program.METHODS We utilized two primary methods to analyze the volatile compounds present in the yellow and green fruits,seeds,and jams of the C.cartilaginea,native to Israel.We identified biologically active isothiocyanates in these samples.Their anticipated biological activities were determined using the PASS program,with the most dominant activities being apoptosis agonist,anticarcinogenic,and antineoplastic specifically for genitourinary cancer.RESULTS Fruits,seeds,and jams containing isothiocyanates,which exhibit antineoplastic and anticarcinogenic activities,could be suggested for cancer prevention and management.Specific isothiocyanates,with therapeutic potential in this realm,could be recommended as potent anticancer agents in practical medicine following clinical trials.CONCLUSION The discovery that isothiocyanates exhibit potent antineoplastic and anticarcinogenic activities was unexpected.Additionally,certain isothiocyanates demonstrated antifungal,antiviral(specifically against arbovirus),and antiparasitic properties.
基金Supported by A Grant from the Canadian Institutes of Health Research(MOP-14790)to Bourgoin SG
文摘Small GTP-binding proteins of the ADP-ribosylation fac-tor （Arf） family control various cell functional responses including protein transport and recycling between different cellular compartments, phagocytosis, prolif-eration, cytoskeletal remodelling, and migration. The activity of Arfs is tightly regulated. GTPase-activating proteins （GAPs） inactivate Arfs by stimulating GTP hydrolysis, and guanine nucleotide exchange factors （GEFs） stimulate the conversion of inactive GDP-bound Arf to the active GTP-bound conformation. There is increasing evidence that Arf small GTPases contribute to cancer growth and invasion. Increased expression of Arf6 and of Arf-GEPs, or deregulation Arf-GAP functions have been correlated with enhanced invasive capacity of tumor cells and metastasis. The spatiotemporal spe-cifcity of Arf activation is dictated by their GEFs that integrate various signals in stimulated cells. Brefeldin A （BFA）, which inactivates a subset of Arf-GEFs, has been very useful for assessing the function of Golgi-localized Arfs. However, specifc inhibitors to investigate the individual function of BFA-sensitive and insensitive Arf-GEFs are lacking. In recent years, specifc screens have been developed, and new inhibitors with improved se-lectivity and potency to study cell functional responses regulated by BFA-sensitive and BFA-insensitive Arf pathways have been identified. These inhibitors have been instrumental for our understanding of the spa-tiotemporal activation of Arf proteins in cells and dem-onstrate the feasibility of developing small molecules interfering with Arf activation to prevent tumor invasion and metastasis.
文摘We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the articles(either published or rejected)over the past period of time.Tzyh-Chyuan Hour,Ph D,Associate Professor,Institute of Biochemistry,Kaohsiung Medical University,100 Shih-Chuan 1st Road,
文摘The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration,especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal,dynamic and static ocular barriers. Also,therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades,ocular drug delivery research acceleratedly advanced towards developing a novel,safe and patient compliant formulation and drug delivery devices/techniques,which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also,it includes development of conventional topical formulations such as suspensions,emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand,for posterior ocular delivery,research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreo-retinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topicaldrops. Also,these novel devices and/or formulations are easy to formulate,no/negligibly irritating,possess high precorneal residence time,sustain the drug release,and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also,recent developments with other ocular drug delivery strategies employing in situ gels,implants,contact lens and microneedles have been discussed.
文摘Prostatitis comprises of a group of syndromes that affect almost 50% of men at least once in their lifetime and makeup the majority of visits to the Urology Clinics.After much debate, it has been divided into four distinct categories by National Institutes of Health namely(1) acute bacterial prostatitis;(2) chronic bacterial prostatitis;(3) chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS) which is further divided into inflammatory and non-inflammatory CP/CPPS; and(4)asymptomatic inflammatory prostatitis. CP/CPPS has been a cause of great concern for both patients and physicians because of the lack of presence of thoroughinformation about the etiological factors along with the difficult-to-treat nature of the syndrome. For the presented manuscript an extensive search on PubM ed was conducted for CP/CPPS aimed to present an updated review on the evaluation and treatment options available for patients with CP/CPPS. Several diagnostic criteria's have been established to diagnose CP/CPPS, with prostatic/pelvic pain for at least 3 mo being the major classifying symptom along with the presence of lower urinary tract symptoms and/or ejaculatory pain. Diagnostic tests can help differentiate CP/CPPS from other syndromes that come under the heading of prostatitis by ruling out active urinary tract infection and/or prostatic infection with uropathogen by performing urine cultures, Meares-Stamey Four Glass Test, Preand Post-Massage Two Glass Test. Asymptomatic inflammatory prostatitis is confirmed through prostate biopsy done for elevated serum prostate-specific antigen levels or abnormal digital rectal examination. Researchers have been unable to link a single etiological factor to the pathogenesis of CP/CPPS, instead a cluster of potential etiologies including atypical bacterial or nanobacterial infection, autoimmunity, neurological dysfunction and pelvic floor muscle dysfunction are most commonly implicated. Initially monotherapy with anti-biotics and alpha adrenergic-blockers can be tried, but its success has only been observed in treatment nave population. Other pharmacotherapies including phytotherapy, neuromodulatory drugs and anti-inflammatories achieved limited success in trials. Complementary and interventional therapies including acupuncture, myofascial trigger point release and pelvic floor biofeedback have been employed. This review points towards the fact that treatment should be tailored individually for patients based on their symptoms. Patients can be stratified phenotypically based on the UPOINT system constituting of Urinary, Psychosocial, Organ-specific, Infectious, Neurologic/Systemic and symptoms of muscular Tenderness and the treatment algorithm should be proposed accordingly. Treatment of CP/CPPS should be aimed towards treating local aswell as central factors causing the symptoms. Surgical intervention can cause significant morbidity and should only be reserved for treatment-refractory patients that have previously failed to respond to multiple drug therapies.
文摘Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Pharmacology.The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles(including those published in this issue and those rejected for this issue)during the last editing time period.Tzyh-Chyuan Hour,Ph D,Associate Professor,Institute of Biochemistry,Kaohsiung Medical University,100 Shih-Chuan 1st Road,Kaohsiung 807,Taiwan。
文摘The therapeutic potential of diet,dietary supplements,herbal remedies,and nutraceuticals for treatment of depression and anxiety is being increasingly explored.In this commentary,we discuss the recent findings on the antidepressant potential of silymarin(SILY)in mice and present an alternative approach.We highlight the extensive research on another phytochemical,curcumin,for the treatment of depression and anxiety.Finally,we suggest a future application,which investigates the potential synergistic effects of combined treatment with SILY and curcumin for depression.
文摘AIM： To examine whether vitamin D is of potential relevance in the healing process of fractures. METHODS： The present narrative review examined the bulk of the evidence based literature on the topic of vitamin D and bone healing in key electronic data bases from 1980 onwards using the terms vitamin D and bone healing, callus, fracture healing. All data were examined carefully and categorized according to type of study. A summary of the diverse terms and approaches employed in the research, as well as the rationale for hypothesizing vitamin D has a role in fracture healing was detailed.RESULTS： The results show very few human studies have been conducted to examine if vitamin D is effective at promoting post fracture healing, and the different ani-mal models that have been studied provide no consensus on this topic. The terms used in the related literature, as well as the methods used to arrive at conclusions on this clinical issue are highly diverse, there is no standardization of either of these important terms and methodolo-gies, hence no conclusive statements or clinical guide-lines can be forthcoming. There is a strong rational for continuing to examine if vitamin D supplements should be administered post-fracture, and ample evidence vitamin D is an essential hormone for functioning in general, as well as bone health and muscle as this relates to bone density.CONCLUSION： Whether those with low vitamin D levels can beneft from supplements if their nutritional practices do not cover recommended daily amounts, remains in question.
基金Supported by Instituto de Salud Carlos III FEDER,Spanish Network for the Research in Infectious Diseases,No.REIPIRD12/0015the Spanish Ministry of Health and FEDER funding,No.FIS PI10/00056-PI13/02390(to Tomás M) and PI12/00552(to Bou G)the Miguel Servet Programme(C.H.U.A.Coruna and ISCIII)(to Tomás M)
文摘Antivirulence therapy inhibits bacterial virulence factors, thus preventing the development of infection without affecting bacterial growth. The development of new antibiotics is complicated by the increasing incidence of antibiotic resistance in pathogenic bacteria. Antiviru-lence therapy is a promising alternative to traditional an-tibiotic therapy for the treatment of infectious disease, either alone or in combination with antibiotic treatment. In this review, we consider patents concerning inhibition of several bacterial virulence factors： adhesion/colonization, secretion systems, cellular signalling systems and antimicrobial resistance mechanisms. Finally, we emphasize the importance of analyzing new targets and/or molecules in this feld and of considering possible resistance mechanisms.
基金Supported by Fundao para a Ciência e Tecnologia(FCT)(PTDC/QUI-BIQ/118492/2010)Fundo Europeu de Desenvolvimento Regional(FEDER)(FCOMP-01-0124-FEDER-020895),Portugal
文摘Prostate cancer is a major public health concern world-wide, being one of the most prevalent cancers in men. Great improvements have been made both in terms of early diagnosis and therapeutics. However, there is still an urgent need for reliable biomarkers that could overcome the lack of cancer-specifcity of prostate-specifc antigen, as well as alternative therapeutic targets for advanced metastatic cases. Reversible phosphorylation of proteins is a post-translational modifcation critical to the regulation of numerous cellular processes. Phosphoprotein phosphatase 1 （PPP1） is a major serine/threonine phos-phatase, whose specifcity is determined by its interacting proteins. These interactors can be PPP1 substrates, regulators, or even both. Deregulation of this protein-protein interaction network alters cell dynamics and underlies the development of several cancer hallmarks. Therefore, the identification of PPP1 interactome in specific cellular context is of crucial importance. The knowledge on PPP1 complexes in prostate cancer remains scarce, with only 4 holoenzymes characterized in human prostate cancer models. However, an increasing number of PPP1 interactors have been identifed as expressed in human prostate tissue, including the tumor suppressors TP53 and RB1. Efforts should be made in order to identify the role of such proteins in prostate carcinogenesis, since only 26 have yet well-recognized roles. Here, we revise literature and human protein databases to provide an in-depth knowledge on the biological significance of PPP1 complexes in human prostate carcinogenesis and their potential use as therapeutic targets for the development of new therapies for prostate cancer.
文摘We acknowledge our sincere thanks to our reviewers.Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of our World Series Journals.Both the editors of the journals and authors of the manuscripts submitted to the journals are grateful to the following reviewers for reviewing the
文摘Inflammatory bowel disease (IBD) has been a worldwide health problem. It is characterized by severe intestinal inflammation due to immune responses against the gut microbes in genetically susceptible individuals. The understanding of gut microbiota for its composition and complex interaction in normal and diseased conditions has been assisted by the use of molecular, metagenomics and meta transcriptomics studies. The alteration of intestinal microbiota is the key determinant in the degree of inflammation caused and the prolonged course of disease. The relationship between luminal gut bacteria and innate immunity is also of prime significance. Such developments have further led to the search of specific (including bacteria and fungi) as a causative agent of IBD. Although detailed research has been done for the role of gut microbiota in IBD, molecular mechanisms and related gene expression are still not well understood in this disease, which hampers the generation of effective therapeutic agents for IBD. This paper assessed various factors contributing to IBD, genetic dysbiosis and pathogenic influence in the gut microbiota, interactions such as microbiome-host immune system interaction and microbe-microbe interactions involved in IBD, currently available IBD therapies, followed by a detailed review on bacterial infections that might be involved in IBD, globally and specifically in India.
文摘The primary objective of this article is to analyze the role of tobacco smoke compounds able to damage the cardiovascular system and, in particular, to interfere with blood pressure. They are products of tobacco plant leaves, like nicotine, thiocyanate and aromatic amines, and a chemical derived from cigarette com-bustion, carbon monoxide. Of the other thousands of chemicals, there is no clear evidence of cardiovascular damage. Nicotine and its major metabolite, cotinine, usually increase blood pressure by a direct action and an action stimulating neuro-humoral metabolites of the body as well as sympathetic stimulation. An indirect mechanism of damage exerted by elevated carboxyhe-moglobin concentrations is mediated by carbon mon-oxide, which, mainly induces arterial wall damage and, consequently, late rising in blood pressure by a toxic direct action on endothelial and blood cells. Thiocya-nate, in turn, reinforces the hypoxic effects determined by carbon monoxide. Aromatic amines, depending on their chemical structure, may exert toxic effects on the cardiovascular system although they have little effect on blood pressure. A rise in blood pressure determined by smoking compounds is a consequence of both their direct toxicity and the characteristics of their chemical chains that are strongly reactive with a large number of molecules for their spatial shape. In addition, a rise in blood pressure has been documented in individuals smoking a cigarette, acutely and chronically, with irre-versible artery wall alterations several years after begin-ning smoking. Since cigarette smoking has a worldwide diffusion, the evidence of this topic meets the interest of both the scientifc community and those individuals aiming to control smoking.
文摘Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.
基金National Natural Science Foundation of China,No.81803845Natural Science Foundation of Inner Mongolia Autonomous Region,No.2018MS08040+1 种基金Construction Project of"Inner Mongolia Autonomous Region Mongolian Medicine and Food Source Protection and Utilization Innovation Team",No.190301Graduate Research Project of Inner Mongolia Minzu University,No.NMDBS1901.
文摘Lomatogonium rotatum(L.rotatum)Fries ex Nym,a dry whole grass belonging to the family Gentianaceae,is widely used to treat liver diseases in Mongolian medicine.In Mongolian medicine,L.rotatum Fries ex Nym,also known as Digeda,is a rare medicinal herb with low yield and widespread clinical use.Currently,it is included in over 25 traditional Mongolian medicine prescriptions that help reduce heat,dispel xieri,enhance stomach function,and heal wounds.Recent studies have shown that L.rotatum Fries ex Nym contains a variety of metabolites,including flavonoids,xanthone compounds,terpenoids,organic acids,steroids,and alkaloids.In addition,its anti-hepatitis B,anti-inflammatory,anti-acute liver injury,and anti-obesity effects have been proven by pharmacological studies.In this review,we summarize the ecological resources,traditional pharmacodynamics,chemical constituents,and pharmacological actions of L.rotatum Fries ex Nym,with an aim to provide a theoretical basis for future applied research and new product development.
文摘Macular edema such as diabetic macular edema(DME) and diabetic retinopathy are devastating back-of-theeye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static(corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers(bloodretinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.
基金Supported by Eurostars program of Eureka(project acronym"D-SIST")
文摘he majority of cancer drugs entering clinical trials fail to reach the market due to poor efficacy. Preclinical efficacy has been traditionally tested using subcutaneous xenograft models that are cheap, fast and easy to perform. However, these models lack the correct tumor microenvironment, leading to poor clinical predictivity. Selecting compounds for clinical trials based on efficacy results obtained from subcutaneous xenograft models may therefore be one important reason for the high failure rates. In this review we concentrate in describing the role and importance of the tumor microenvironment in progression of breast and prostate cancer, and describe some breast and prostate cancer cell lines that are widely used in preclinical studies. We go through different preclinical efficacy models that incorporate the tissue microenvironment and should therefore be clinically more predictive than subcutaneous xenografts. These include three-dimensional cell culture models, orthotopic and metastasis models, humanized and transgenic mouse models, and patient-derived xenografts. Different endpoint measurements and applicable imaging techniques are also discussed. We conclude that models that incorporate the tissue microenvironment should be increasingly used in preclinical efficacy studies to reduce the current high attrition rates of cancer drugs in clinical trials.
