Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injur...Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injury and affect axon regeneration.A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury.Here,we found that dual specificity phosphatase 2(DUSP2)is a negative regulator of axon regeneration of the Mauthner cell(M-cell).DUSP2 is a phosphatase that mediates the dephosphorylation of JNK.In this study,we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2(-/-)zebrafish had a better regeneration at the early stage after birth(within 8 days after birth),while those of dusp2^(+/-)zebrafish did not.Overexpression of DUSP2 in Tg(Tol 056)zebrafish by single-cell electroporation retarded the regeneration of M-cell axons.Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK.These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons,possibly through enhancing JNK phosphorylation.展开更多
Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assa...Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, lymphomononuclear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing clonal sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence.展开更多
Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despit...Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.展开更多
A significant amount of evidence indicates that micro RNAs(mi RNAs) play an important role in drug addiction. The nucleus accumbens(NAc) is a critical part of the brain's reward circuit and is involved in a variet...A significant amount of evidence indicates that micro RNAs(mi RNAs) play an important role in drug addiction. The nucleus accumbens(NAc) is a critical part of the brain's reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of mi RNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine(0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion) and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered mi RNAs and their putative target m RNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway mapping and Cy Target Linker. We found that 62 mi RNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine(receptor internalization/endocytosis). The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.展开更多
Objective: The structural anisotropy of articular cartilage controls its deformation response. As proteoglycans and collagen vary with depth, simple uniaxial compression results in inhomogeneous deformation with disti...Objective: The structural anisotropy of articular cartilage controls its deformation response. As proteoglycans and collagen vary with depth, simple uniaxial compression results in inhomogeneous deformation with distinct depth-dependent mechanical properties. Investigations into depth-dependent mechanical properties of articular cartilage have previously required tissue modification after specimen isolation. Such modifications include histological processes, freezing, subchondral bone removal, and fluorescent staining that may alter the tissue, limiting in vivo applicability. Design: Using a custom tissue-sectioning device, 0.1 mm thick unfixed, unstained, osetochondral samples were obtained. A customized apparatus loaded samples to 12.5%, 24%, and 29% compression in under a microscope with 10× magnification. Equilibrium load was measured after stress relaxation. Intra-tissue displacement was measured by tracing groups of cells between the different compression levels using a digital imaging program. Cell distance from the subchondral bone was measured to identify intratissue displacement and calculate strain. Results: The results reveal that stress levels and intratissue displacement increased with greater tissue compression (p p in vivo conditions and may provide an important method for analyzing the coordinated changes in cartilage composition and function due to ageing and disease.展开更多
Concurrent infections of malaria and dengue are when both of these mosquito-borne diseases occur simultaneously in an individual. In this review, reported cases with these co-infections in Asia are discussed. The focu...Concurrent infections of malaria and dengue are when both of these mosquito-borne diseases occur simultaneously in an individual. In this review, reported cases with these co-infections in Asia are discussed. The focus is on the overlapping clinical presentations and the difficulties encountered in differential diagnosis. Also, cases reported in some special conditions, viz., pregnancy, foetal infections, and co-infections with one or more other infectious agents are highlighted. Due to similar clinical presentations of malaria and dengue, these co-infections may give rise to an incorrect diagnosis. Moreover, the treatment regimens for these co-infections are not the same as those for mono-infections.Hence, a delay in implementing the appropriate treatment regimen for these concurrent infections due to poor diagnosis can be fatal. The present review is intended to increase awareness about the clinical significance and the importance of these co-infections among clinicians, public health workers and health authorities in the Asian region. Though malaria-dengue concurrent infections are seldom reported from the Asian region, it is probably increasing particularly in the countries known to be endemic for both of the above diseases. A compulsory reporting of the incidences of malaria-dengue concurrent infections is recommended.展开更多
Objective:To elucidate the pharmacological bases of oral administration of Securidaca longepedunculata(S.longepedunculata) root extract as an anthelmintic in folkloric medicine. Methods:Albino mice were infected with ...Objective:To elucidate the pharmacological bases of oral administration of Securidaca longepedunculata(S.longepedunculata) root extract as an anthelmintic in folkloric medicine. Methods:Albino mice were infected with infective third(L3) larval stage of Heligmosomoides polygyrus(H.polygyrus) by esophageal intubation.Following establishment of the adult worms in the intestine,the mice were treated with 0-2 000 mg/kg body weight(bw) of methanolic root extract of S.longepedunculata and 100 mg/kg bw of pyrantel embonate,the reference drug in vivo. Bioactivity and larvicidal effects of the extract were tested by exposing brine shrimps(Artemia salina) to 0.00-1.00 mg/mL and the L3 stage of Heligmosomoides contortus(H.contortus) and H.polygyrus to 0.00-2.50 mg/mL of the extract in vitro.Results:The percentage yield of the extract was 7.13%w/w dry matter.The brine shrimps toxicity bioassay resulted in an LC_(50) of 74.18 μ g/mL.The extract had a significant,dose-dependent larvicidal effect on the L3 stage of H.contortus and H.polygyrus with the terminal effect of 75%and 70%at the highest exposure concentrations,respectively.The extract however,did not affect the number of worm eggs per gram(epg) of fecal materials(P<0.05) and total worm burden(twb) of adult H.polygyrus in infected mice.Treatment with pyrantel embonate significant reduced both the fecal egg count and twb to 0 compared to the untreated control(P<0.05).Conclusions:These results indicate that S.longepedunculata root extract contains potent bioactive compounds and has larvicidal effect on L3 stage of H.contortus and H.polygyrus,substantiating its use as anthelmintic in alternative medicine.展开更多
Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected ...Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P<0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.展开更多
Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can ...Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.展开更多
Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has...Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection (SOI). The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection (POI) where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.展开更多
Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2(PTPN2) with the onset of inflammatory bowel disease(IBD) ...Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2(PTPN2) with the onset of inflammatory bowel disease(IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation.展开更多
Background Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was f...Background Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia.ObjectiveAims To assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms.Methods Cross-sectional studies were applied to(1) compare the levels of plasma leptin between schizophrenia(n=74) and healthy controls(n=50); and(2)investigate the relationship between plasma leptin levels and depressive subscores.Results(1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls.(2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale(PANSS).(3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS.Conclusion Leptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.展开更多
Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there a...Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there are no effective treatments to directly resolve edema within the spinal cord.The aquaporin-4(AQP4) water channel is found on membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid and ependyma around the central canal.Being so locally expressed at the interface between fluid and tissue allow AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma.With the need to better understand the pathophysiology underlying the devastating cellular events in SCI, animal models have become an integral part of exploration.Inevitably, several injury models have been developed(contusion, compression, transection) resulting in difficult interpretation between studies with conflicting results.This is true in the case of understanding the role of AQP4 in the progression and resolution of edema following SCI, whose role is still not completely understood and is highly dependent on the type of edema present(vasogenic vs cytotoxic).Here, we discuss regulation of AQP4 in varying injury models and the effects of potential therapeutic interventions on expression, edema formation and functional recovery.Better understanding of the precise role of AQP4 following a wide range of injuries will help to understand optimal treatment timing following human SCI for prime therapeutic benefit and enhanced neurological outcome.展开更多
The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they ca...The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch;however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers;15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.展开更多
BACKGROUND Cardiovascular diseases(CVD)have been shown to be the greatest cause of death worldwide and rates continue to increase.It is recommended that CVD patients attend cardiac rehabilitation(CR)following a cardia...BACKGROUND Cardiovascular diseases(CVD)have been shown to be the greatest cause of death worldwide and rates continue to increase.It is recommended that CVD patients attend cardiac rehabilitation(CR)following a cardiac event to reduce mortality,improve recovery and positively influence behaviour around CVD risk factors.Despite the recognised benefits and international recommendations for exercisebased CR,uptake and attendance remain suboptimal.A greater understanding of CR barriers and facilitators is required,not least to inform service development.Through understanding current cardiac patients’attitudes and opinions around CR and physical activity(PA)could inform patient-led improvements.Moreover,through understanding aspects of CR and PA that participants like/dislike could provide healthcare providers and policy makers with information around what elements to target in the future.AIM To investigate participants’attitudes and opinions around CR and PA.METHODS This study employed a cross-sectional survey design on 567 cardiac patients.Cardiac patients who were referred for standard CR classes at a hospital in the Scottish Highlands,from May 2016 to May 2017 were sampled.As part of a larger survey,the current study analysed the free-text responses to 5 open-ended questions included within the wider survey.Questions were related to the participants’experience of CR,reasons for non-attendance,ideas to increase attendance and their opinions on PA.Qualitative data were analysed using a 6-step,reflexive thematic analysis.RESULTS Two main topic areas were explored:“Cardiac rehabilitation experience”and“physical activity”.Self-efficacy was increased as a result of attending CR due to exercising with similar individuals and the safe environment offered.Barriers ranged from age and health to distance and starting times of the classes which increased travel time and costs.Moreover,responses demonstrated a lack of information and communication around the classes.Respondents highlighted that the provision of more classes and classes being held out with working hours,in addition to a greater variety would increase attendance.In terms of PA,respondents viewed this as different to the CR experience.Responses demonstrated increased freedom when conducting PA with regards to the location,time and type of exercise conducted.CONCLUSION Changes to the structure of CR may prove important in creating long term behaviour change after completing the rehabilitation programme.展开更多
基金granted by the National Natural Science Foundation of China,No.82071357Ministry of Science and Technology of China,No.2019YFA0405600(both to BH).
文摘Axon regeneration of central neurons is a complex process that is tightly regulated by multiple extrinsic and intrinsic factors.The expression levels of distinct genes are changed after central neural system(CNS)injury and affect axon regeneration.A previous study identified dusp2 as an upregulated gene in zebrafish with spinal cord injury.Here,we found that dual specificity phosphatase 2(DUSP2)is a negative regulator of axon regeneration of the Mauthner cell(M-cell).DUSP2 is a phosphatase that mediates the dephosphorylation of JNK.In this study,we knocked out dusp2 by CRISPR/Cas9 and found that M-cell axons of dusp2(-/-)zebrafish had a better regeneration at the early stage after birth(within 8 days after birth),while those of dusp2^(+/-)zebrafish did not.Overexpression of DUSP2 in Tg(Tol 056)zebrafish by single-cell electroporation retarded the regeneration of M-cell axons.Western blotting results showed that DUSP2 knockout slightly increased the levels of phosphorylated JNK.These findings suggest that knocking out DUSP2 promoted the regeneration of zebrafish M-cell axons,possibly through enhancing JNK phosphorylation.
文摘Recent discovery of occult hepatitis C virus (HCV) infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, lymphomononuclear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing clonal sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence.
基金Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme
文摘Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.
基金funded by the National Research Council of Science & Technology(NST)grant by the Korean government(MSIP)(No.CRC-15-04-KIST)the National Research Foundation of Korea under the grant(No.NRF-2017R1A2B200399Mid-career Researcher Program)
文摘A significant amount of evidence indicates that micro RNAs(mi RNAs) play an important role in drug addiction. The nucleus accumbens(NAc) is a critical part of the brain's reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of mi RNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine(0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion) and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered mi RNAs and their putative target m RNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway mapping and Cy Target Linker. We found that 62 mi RNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine(receptor internalization/endocytosis). The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction.
文摘Objective: The structural anisotropy of articular cartilage controls its deformation response. As proteoglycans and collagen vary with depth, simple uniaxial compression results in inhomogeneous deformation with distinct depth-dependent mechanical properties. Investigations into depth-dependent mechanical properties of articular cartilage have previously required tissue modification after specimen isolation. Such modifications include histological processes, freezing, subchondral bone removal, and fluorescent staining that may alter the tissue, limiting in vivo applicability. Design: Using a custom tissue-sectioning device, 0.1 mm thick unfixed, unstained, osetochondral samples were obtained. A customized apparatus loaded samples to 12.5%, 24%, and 29% compression in under a microscope with 10× magnification. Equilibrium load was measured after stress relaxation. Intra-tissue displacement was measured by tracing groups of cells between the different compression levels using a digital imaging program. Cell distance from the subchondral bone was measured to identify intratissue displacement and calculate strain. Results: The results reveal that stress levels and intratissue displacement increased with greater tissue compression (p p in vivo conditions and may provide an important method for analyzing the coordinated changes in cartilage composition and function due to ageing and disease.
文摘Concurrent infections of malaria and dengue are when both of these mosquito-borne diseases occur simultaneously in an individual. In this review, reported cases with these co-infections in Asia are discussed. The focus is on the overlapping clinical presentations and the difficulties encountered in differential diagnosis. Also, cases reported in some special conditions, viz., pregnancy, foetal infections, and co-infections with one or more other infectious agents are highlighted. Due to similar clinical presentations of malaria and dengue, these co-infections may give rise to an incorrect diagnosis. Moreover, the treatment regimens for these co-infections are not the same as those for mono-infections.Hence, a delay in implementing the appropriate treatment regimen for these concurrent infections due to poor diagnosis can be fatal. The present review is intended to increase awareness about the clinical significance and the importance of these co-infections among clinicians, public health workers and health authorities in the Asian region. Though malaria-dengue concurrent infections are seldom reported from the Asian region, it is probably increasing particularly in the countries known to be endemic for both of the above diseases. A compulsory reporting of the incidences of malaria-dengue concurrent infections is recommended.
文摘Objective:To elucidate the pharmacological bases of oral administration of Securidaca longepedunculata(S.longepedunculata) root extract as an anthelmintic in folkloric medicine. Methods:Albino mice were infected with infective third(L3) larval stage of Heligmosomoides polygyrus(H.polygyrus) by esophageal intubation.Following establishment of the adult worms in the intestine,the mice were treated with 0-2 000 mg/kg body weight(bw) of methanolic root extract of S.longepedunculata and 100 mg/kg bw of pyrantel embonate,the reference drug in vivo. Bioactivity and larvicidal effects of the extract were tested by exposing brine shrimps(Artemia salina) to 0.00-1.00 mg/mL and the L3 stage of Heligmosomoides contortus(H.contortus) and H.polygyrus to 0.00-2.50 mg/mL of the extract in vitro.Results:The percentage yield of the extract was 7.13%w/w dry matter.The brine shrimps toxicity bioassay resulted in an LC_(50) of 74.18 μ g/mL.The extract had a significant,dose-dependent larvicidal effect on the L3 stage of H.contortus and H.polygyrus with the terminal effect of 75%and 70%at the highest exposure concentrations,respectively.The extract however,did not affect the number of worm eggs per gram(epg) of fecal materials(P<0.05) and total worm burden(twb) of adult H.polygyrus in infected mice.Treatment with pyrantel embonate significant reduced both the fecal egg count and twb to 0 compared to the untreated control(P<0.05).Conclusions:These results indicate that S.longepedunculata root extract contains potent bioactive compounds and has larvicidal effect on L3 stage of H.contortus and H.polygyrus,substantiating its use as anthelmintic in alternative medicine.
文摘Objective:To investigate the wound healing properly of Napoleona vogelii leaf extract in folkloric medicine.Methods:Roth sexes of adult albino rats(n=25) were used in this study and another group(n=30) were subjected to acute toxicity test(LD_(50)) of the plant extract.For the LD_(50),three randomized groups of 5 rats were first treated with 10,100,1 000 mg/kg body weight(bw),orally.This w as followed by a second treatment of 1500,3000,and 5 000 mg/kg bw of the leaf extract with continual monitoring of the animals for mortality or non-mortality.Incision wounds(1.3cm) were created on the skin of five groups of 5 rals using surgical blade under anesthesia.The first group was topically treated with petroleum jelly alone,group 2 was topically applied 400 mg/mL w/v of the reference drug,Neobaein,while group 3-5 were topically treated with 5-50 mg/mL w/v of the plant extract,respectively.Results:The percentage yield of the extract was 49.80%w/w dry matter.The phytochemical analysis revealed several bioactive constituents including glycosides,tannins,alkaloids,perpenoids.saponins,steroids,proteins,and carbohydrates.The LD_(50) was beyond our experimental limit and was not determined.Increased concentrations(5,20,and 50mg/mL w/v) of the extract had significant(ANOVA,P<0.05) healing effect on the incision wounds giving rise to 125%-140% while treatmentawith Neobacin resulted in 150% healing effect on the third treatment regimen compared to the control(100%).Conclusions:These data indicate that Napoleona vogelii leaf extract contains potent bioactive compounds containing wound healing activity,substantiating its use as a wound healer in folkloric medicine.
文摘Exposure to toxic chemicals, especially chemotherapeutic drugs, may induce several DNA lesions, including DNA interstrand crosslinks. These crosslinks are considered toxic lesions to the dividing cells since they can induce mutations, chromosomal rearrangements, and cell death. Many DNA interstrand crosslinks lesions can be generated by platinum-based chemotherapeutic agents. Satraplatin is a novel orally administered platinum-based chemotherapeutic agent. In the present study, we investigated DNA interstrand crosslinks lesions induced by oxaliplatin and satraplatin in lymphocytes obtained from colorectal cancer patients and healthy volunteers. Satraplatin demonstrated an increase in interstrand crosslinks in a dose-dependent manner in the Comet assay (p in vitro. Here, to the best of our knowledge we report for the first time evidence of DNA double strand breaks formation as a possible molecular mechanism of action for satraplatin.
基金operating research grants from the Canadian Institutes of Health Research, Canada and the Canada Research Chair Program, and the Canada Foundation for Innovation
文摘Hepatitis B virus (HBV) is a highly pathogenic virus that causes chronic liver diseases in millions of people globally. In addition to a symptomatic, serologically evident infection, occult persistent HBV carriage has been identified since nucleic acid amplification assays of enhanced sensitivity became introduced for detection of hepadnaviral genomes and their replicative intermediates. Current evidence indicates that occult HBV infection is a common and long-term consequence of resolution of acute hepatitis B. This form of residual infection is termed as secondary occult infection (SOI). The data from the woodchuck model of HBV infection indicate that exposure to small amounts of hepadnavirus can also cause primary occult infection (POI) where virus genome, but no serological makers of exposure to virus, are detectable, and the liver may not be involved. However, virus replicates at low levels in the lymphatic system in both these forms. We briefly summarize the current understanding of the nature and characteristics of occult hepadnaviral persistence as well as of its documented and expected pathological consequences.
基金Supported by Grants from the Swiss National Science Foundation(SNF)to MSGrant No.314730-146204 and No.CRSII3_154488/1(to Rogler G)+2 种基金Grant No.310030-120312the Swiss IBD CohortGrant No.3347CO-108792
文摘Genome wide association studies have associated single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase non-receptor type 2(PTPN2) with the onset of inflammatory bowel disease(IBD) and other inflammatory disorders. Expression of PTPN2 is enhanced in actively inflamed intestinal tissue featuring a marked up-regulation in intestinal epithelial cells. PTPN2 deficient mice suffer from severe intestinal and systemic inflammation and display aberrant innate and adaptive immune responses. In particular, PTPN2 is involved in the regulation of inflammatory signalling cascades, and critical for protecting intestinal epithelial barrier function, regulating innate and adaptive immune responses, and finally for maintaining intestinal homeostasis. On one hand, dysfunction of PTPN2 has drastic effects on innate host defence mechanisms, including increased secretion of pro-inflammatory cytokines, limited autophagosome formation in response to invading pathogens, and disruption of the intestinal epithelial barrier. On the other hand, PTPN2 function is crucial for controlling adaptive immune functions, by regulating T cell proliferation and differentiation as well as maintaining T cell tolerance. In this way, dysfunction of PTPN2 contributes to the manifestation of IBD. The aim of this review is to present an overview of recent findings on the role of PTPN2 in intestinal homeostasis and the impact of dysfunctional PTPN2 on intestinal inflammation.
基金supported by grants from the National Key R&D Program of China(2017YFC0909200)the National Science Foundation of China(NSFC+4 种基金81171266,81271481,81671336 and 81500976)the China and National Key Research and Development Program(2017YFC0909200)the Shanghai Key Laboratory of Psychotic Disorders(13dz2260500)the Shanghai Municipal Planning Commission of Science and Research Fund(20154Y0194)the Canadian Institutes of Health Research(project grant PJT-156116)
文摘Background Depressive symptoms are often seen in schizophrenia. The overlap in presentation makes it difficult to distinguish depressive symptoms from the negative symptoms of schizophrenia. The adipokine leptin was found to be altered in both depression and schizophrenia. There are few studies focusing on the prediction of leptin in diagnosis and evaluation of depressive symptoms in schizophrenia.ObjectiveAims To assess the plasma leptin level in patients with schizophrenia and its relationships with depressive symptoms.Methods Cross-sectional studies were applied to(1) compare the levels of plasma leptin between schizophrenia(n=74) and healthy controls(n=50); and(2)investigate the relationship between plasma leptin levels and depressive subscores.Results(1) Plasma leptin levels were significantly higher in patients with schizophrenia than in healthy controls.(2) Correlation analysis revealed a significant negative association between leptin levels and the depressed factor scores on the Positive and Negative Syndrome Scale(PANSS).(3) Stepwise multiple regression analyses identified leptin as an influencing factor for depressed factor score on PANSS.Conclusion Leptin may serve as a predictor for the depressive symptoms of chronic schizophrenia.
文摘Edema formation is a major problem following traumatic spinal cord injury(SCI) that acts to exacerbate secondary damage.Severity of edema correlates with reduced neurological outcome in human patients.To date, there are no effective treatments to directly resolve edema within the spinal cord.The aquaporin-4(AQP4) water channel is found on membranes of astrocytic endfeet in direct contact with blood vessels, the glia limitans in contact with the cerebrospinal fluid and ependyma around the central canal.Being so locally expressed at the interface between fluid and tissue allow AQP4 channels to play an important role in the bidirectional regulation of water homeostasis under normal conditions and following trauma.With the need to better understand the pathophysiology underlying the devastating cellular events in SCI, animal models have become an integral part of exploration.Inevitably, several injury models have been developed(contusion, compression, transection) resulting in difficult interpretation between studies with conflicting results.This is true in the case of understanding the role of AQP4 in the progression and resolution of edema following SCI, whose role is still not completely understood and is highly dependent on the type of edema present(vasogenic vs cytotoxic).Here, we discuss regulation of AQP4 in varying injury models and the effects of potential therapeutic interventions on expression, edema formation and functional recovery.Better understanding of the precise role of AQP4 following a wide range of injuries will help to understand optimal treatment timing following human SCI for prime therapeutic benefit and enhanced neurological outcome.
文摘The incidence of familial adenomatous polyposis (FAP) is one in 7,000 to 12,000 live births. Virtually, all surgically untreated patients with FAP inevitably develop colorectal-cancer in their lifetime because they carry the adenomatous polyposis coli gene. Thus prophylactic proctocolectomy is indicated. Surgical treatment of FAP is still controversial. There are however, four surgical options: ileorectal anastomosis, restorative proctocolectomy with ileal pouch-anal anastomosis, proctocolectomy with ileostomy, and proctocolectomy with continent-ileostomy. Conventional proctocolectomy options largely lie between colectomy with ileorectal anastomosis or ileal pouch-anal anastomosis. Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis because of better functional results and quality of life. The functional outcome of total colectomy with ileorectal anastomosis is undoubtedly far superior to that of the ileoanal pouch;however, the risk for rectal cancer is increased by 30%. Even after mucosectomy, inadvertent small mucosal residual islands remain. These residual islands carry the potential for the development of subsequent malignancy. We reviewed the literature (1975-2012) on the incidence, nature, and possible etiology of subsequent ileal-pouch and anal transit zone adenocarcinoma after prophylactic surgery procedure for FAP. To date there are 24 studies reporting 92 pouch-related cancers;15 case reports, 4 prospective and 5 retrospective studies. Twenty three of 92 cancers (25%) developed in the pouch mucosa and 69 (75%) in anal transit zone (ATZ). Current recommendation for pouch surveillance and treatment are presented. Data suggest lifetime surveillance of these patients.
文摘BACKGROUND Cardiovascular diseases(CVD)have been shown to be the greatest cause of death worldwide and rates continue to increase.It is recommended that CVD patients attend cardiac rehabilitation(CR)following a cardiac event to reduce mortality,improve recovery and positively influence behaviour around CVD risk factors.Despite the recognised benefits and international recommendations for exercisebased CR,uptake and attendance remain suboptimal.A greater understanding of CR barriers and facilitators is required,not least to inform service development.Through understanding current cardiac patients’attitudes and opinions around CR and physical activity(PA)could inform patient-led improvements.Moreover,through understanding aspects of CR and PA that participants like/dislike could provide healthcare providers and policy makers with information around what elements to target in the future.AIM To investigate participants’attitudes and opinions around CR and PA.METHODS This study employed a cross-sectional survey design on 567 cardiac patients.Cardiac patients who were referred for standard CR classes at a hospital in the Scottish Highlands,from May 2016 to May 2017 were sampled.As part of a larger survey,the current study analysed the free-text responses to 5 open-ended questions included within the wider survey.Questions were related to the participants’experience of CR,reasons for non-attendance,ideas to increase attendance and their opinions on PA.Qualitative data were analysed using a 6-step,reflexive thematic analysis.RESULTS Two main topic areas were explored:“Cardiac rehabilitation experience”and“physical activity”.Self-efficacy was increased as a result of attending CR due to exercising with similar individuals and the safe environment offered.Barriers ranged from age and health to distance and starting times of the classes which increased travel time and costs.Moreover,responses demonstrated a lack of information and communication around the classes.Respondents highlighted that the provision of more classes and classes being held out with working hours,in addition to a greater variety would increase attendance.In terms of PA,respondents viewed this as different to the CR experience.Responses demonstrated increased freedom when conducting PA with regards to the location,time and type of exercise conducted.CONCLUSION Changes to the structure of CR may prove important in creating long term behaviour change after completing the rehabilitation programme.
