Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complica...Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.展开更多
Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of dementia.Although we have gain...Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of dementia.Although we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to patients.AD is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloid β and hyper-phosphorylated,Tau in addition to neuroinflammation.展开更多
Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard ...Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong survival.Moreover,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)therapies.Trastuzumab,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy.Further,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field.Thus,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.展开更多
AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted m...AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.展开更多
Objective:To identify the prevalence of Cryptosporidium from goats in three types of farm management systems in Terengganu,Malaysia and to determine the Cryptosporidium species infecting goats by using 18 S r RNA.Meth...Objective:To identify the prevalence of Cryptosporidium from goats in three types of farm management systems in Terengganu,Malaysia and to determine the Cryptosporidium species infecting goats by using 18 S r RNA.Methods:A total of 478 fecal samples were randomly collected from goats in three farms;199 samples were collected from intensive farm,179 samples from semi-intensive farm and 100 samples from extensive farm.The samples were processed by using formolether concentration technique and stained by using modified Ziehl–Neelsen.Positive samples were performed by using nested PCR analysis by using 18 S r RNA.Results:Out of 478 goats,207(43.3%) were found to be infected with Cryptosporidium.Goats reared under the intensive farm management system reported the highest prevalence of infection(49.7%),followed by intensive farm management system(41%) and the lowest prevalence was reported in the goats reared under semi-intensive management system(37.4%).Conclusions:The identified species found in goat was Cryptosporidium parvum.Future study on the zoonotic transmission of Cryptosporidium parvum in goats needs to be done in order to find the source of transmission of this parasite.展开更多
Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily of proteins, circulates in a complex with vitronectin. Furthermore, these two proteins are co-localized in the ...Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily of proteins, circulates in a complex with vitronectin. Furthermore, these two proteins are co-localized in the extracellular matrix (ECM) in many different pathophysiological conditions. Though PAI-1 is a well-characterized inhibitor of serine proteases, recent emphasis has also focused on its protease-independent functions. Vitronectin, a multi-domain protein that binds a wide variety of ligands and proteins, exists in the circulation in a preferred monomeric state, while in the extracellular matrix it exists as a multimer resulting from an altered conformation. Though the mechanism for the conformational alterations and compartmentalization in tissues is unknown, there are a number of biomolecules including PAI-1 that appear to cause such changes. Experimental analysis has established that PAI-1 induces association of vitronectin to higher-order species in a concentration-dependent fashion [1]. This report extends our investigations into the mechanism of the interaction between vitronectin and PAI-1 to explore the physiological relevance of these higher-order complexes for cellular adhesion and migration. In this study, we evaluate the effects of the pericellular microenvironment on the functions of the multimeric complexes in a variety of relevant biological settings. Our findings underscore the importance of the variability of components within this microenvironment, including different receptors and ECM components, in governing the way in which the vitronectin/PAI-1 complex mediates cell-matrix interactions.展开更多
Peatlands are unique and complex natural ecosystems that are part of the most important carbon reservoirs on our planet, home to a diversity of microorganisms responsible for fermentation, humification or peat. The ai...Peatlands are unique and complex natural ecosystems that are part of the most important carbon reservoirs on our planet, home to a diversity of microorganisms responsible for fermentation, humification or peat. The aim is to understand chemical and biological indicators of peatland soils. This work aims to determine the physicochemical and bacteriological profile and lipolytic activity of soil bacteria in Bilanko peatlands. The bacterial profile with the production of lipases is carried out by classical microbiology techniques. The results show that the soils are moderately acidic with temperatures of 27.8˚C ± 0.01˚C for Bilanko and 27.1˚C ± 0.57˚C for Ngamakala. The electroconductivity (EC) varies from (9.52 ± 0.002) μS/cm to (39.01 ± 1.4) μS/cm with low turbidity of (2.04 ± 0.66) mg/L to (31.02 ± 0.84) mg/L and low ion concentrations with, however, a richness in phenolic compounds for Bilanko compared to Ngamakala. FMAT diversity ranged from (1.71 ± 0.88)∙104 UFC/g to (2.92 ± 0.07)∙105 UFC/g for Bilanko and (1.30 ± 0.73)∙104 UFC/g to (2.89 ± 0.06)∙104 UFC/g for Ngamakala. Bacillus loads ranged from (5.20 ± 1.40)∙103 CFU/g to (1.22 ± 0.13)∙104 CFU/g and from (1.11 ± 0.13)∙104 CFU/g to (9.20 ± 2.05)∙103 CFU/g;enterobacteria loads from (1.40 ± 0.76)∙103 CFU/g to (8.80 ± 1.73)∙103 CFU/g and from (1.01 ± 0.02)∙103 CFU/g to (9.20 ± 2.05)∙103 CFU/g;in Pseudomonas from 0 to (2.30 ± 0.53)∙102 CFU/g and from 0 to (8.90 ± 2.35)∙102 CFU/g for Bilanko and Ngamakala respectively. These results reveal a variation in bacterial similarity and distribution in the Bilanko and Ngamakala peat bogs.展开更多
Desmodus rotundus and Diphylla ecaudata, both of which are mammals of the order Chiroptera, Desmodontidae family, their diet consisting exclusively of blood. D. rotundus is the main vector and transmitter of the rabie...Desmodus rotundus and Diphylla ecaudata, both of which are mammals of the order Chiroptera, Desmodontidae family, their diet consisting exclusively of blood. D. rotundus is the main vector and transmitter of the rabies virus, which affects human beings as well as several livestock species so the study of this bat species is of high importance within the fields of animal agriculture and public health. The present study describes and compares the histologic characteristics of the urinary system of two hematophagous bat species. A total of 5 bats from each species were captured in the municipalities of Progreso de Obregón, Hidalgo (D. rotundus), and Huayacocotla, Veracruz (D. ecaudata). Organs belonging to the urinary system were extracted: kidneys, ureters, urinary bladder, and urethra;samples were fixed using 10% formalin and processed by the paraffin embedding technique, obtaining sections of 5 µm thickness, which in turn were stained using hematoxylin-eosin (H-E) and Gomori trichrome (GT) stains. From the obtained histologic preparations, a descriptive and comparative analysis of the structural organography of the urinary system of both species was made, and no noteworthy histological differences between samples were noted. The present research is intended to provide a framework for future studies of these species’ currently understudied microscopic anatomy.展开更多
Measles is a highly infectious, vaccine-preventable viral disease. Often forgotten, it is potentially fatal. Its main symptoms are: fever, cough, conjunctivitis, rhinitis and skin rash. Serological diagnoses by ELISA ...Measles is a highly infectious, vaccine-preventable viral disease. Often forgotten, it is potentially fatal. Its main symptoms are: fever, cough, conjunctivitis, rhinitis and skin rash. Serological diagnoses by ELISA test based on the detection of anti-measles virus immunoglobulins M and G (IgM and IgG), are used respectively for the confirmation of suspected cases notified by means of clinical signs of the disease in health structures of the twelve departments of the Republic of Congo involved in the epidemiological surveillance of the disease, and for the evaluation of the immunity conferred by vaccination. During 2021, 459 suspected cases of measles were reported and sampled throughout the country, despite the administration under the Expanded Routine Immunization Program (EPI), of 2 doses of the combined measles-rubella vaccine (RR1 and RR2) in 2020. The notification rate was higher in the south of the country, more precisely in the health structures of the departments of Pointe-Noire (42%) and Brazzaville (11%). During the year 2021, 459 suspected cases of measles were notified and sampled throughout the country with a high notification rate in the south of the country, more precisely in the health structures of the Pointe-Noire departments (42%) and Brazzaville (11%). The samples consisting of human blood (serum) were sent to the National Public Health Laboratory and analyzed by various ELISA tests for the detection of anti-measles immunog-lobulins M and G. The analysis of the results obtained shows that the measles virus circulated in all departments of the country. 154 cases (33.55%) were confirmed positive by IgM ELISA and 98 positive cases (63.63%) were patients vaccinated against measles. Vaccination coverage in RR1 of [50%-95% [(first dose) as well as the lowest RR2 < 50% (second dose) undoubtedly because the COVID-19 pandemic could be the cause of the high frequency of cases positive vaccinated. The non-detection of IgG immunoglobulins in vaccinated patients observed by IgG ELISA tests revealed that 63.26% of vaccinated patients were not immunized against the measles virus. These results confirm those obtained during the Elisa IgM analysis and make it possible to deduce that the quality, the number of doses not properly administered, the individual characteristics of the people as well as the poor conservation of the administered vaccine (non-compliance with the cold chain) would explain the high proportion of positive cases of vaccinated measles observed.展开更多
Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject ...Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.展开更多
Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response ag...Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.展开更多
Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusio...Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusion and agar dilution methods,resistance genes were identified by PCR and sequencing,and molecular typing of isolates was carried out by enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR).Results:Among 125 tested isolates,117(93.6% ) were multidrug-resistant.of which 94(75.2% ) were imipenem resistant.The bla_(ADC)and bla_(OXA-51-like) genes were detected in all isolates,in association with ISAba I sequence in 84% and 8% (imipenem resistant) of isolates,respectively.The bla_(OXA-23-like) and bla_(OXA-24-like)carbapenemase genes were delected in 67.02% and 20.21% of imipenem-resistant isolates,respectively.The bla_(OXA-23-like) gene is linked to ISAba1 or ISAba4 elements.The metallo-β-lactamase NDM-1 gene was found in 10(10.6% ) imipenem-resisianl strains from three hospitals,it is linked to ISAba125 clement in nine strains.Extended spectrum β-lactamases production was not detected.Imipenem and cefotaxime resistance phenolypes could not be transferred to Escherichia coli by conjugation.Outer membrane protein CarO gene was not delected in four imipenem-resisianl isolates.The aac(6')-1b.sul1,sul2,tetA and tetB genes were present in 5.31% .36.17% .77.65% .1.06% and 65.92% of strains,respectively.Class 1 integrons were detected in 23.4% strains.KRIC-PCR typing showed a genetic diversity among bla_(OXA-23-like) and bla_(OXA-24-like) positive strains,while clonality was observed among bla_(NDM-1)positives.Conclusions:This study highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii in Algiers hospitals mediated mainly by bla_(OXA-23-like),bla_(OXA-24-like),and bla_(NDM-1) genes.展开更多
Rice(Oryza sativa L.)is an important staple food crop worldwide due to its adaptability to different environmental conditions.Because of its great economic and social importance,there is a constant requirement for new...Rice(Oryza sativa L.)is an important staple food crop worldwide due to its adaptability to different environmental conditions.Because of its great economic and social importance,there is a constant requirement for new varieties with improved agronomic characteristics,such as tolerance to different biotic(such as bacterium,fungus,insect and virus)and abiotic stresses(such as salinity,drought and temperature),higher yield and better organoleptic and nutritional value.Among the new genome editing technologies,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)(CRISPR/Cas)system allows precise and specific edition in a targeted genome region.It is one of the most frequently used techniques for the study of the function of new genes and for the development of mutant lines with enhanced tolerance to biotic and abiotic stresses,herbicide resistance or improved yield.The wide varieties of applications for this technology include simple non-homologous end joining,homologous recombination,gene replacement,and base editing.In this review,we analyzed how some of these applications have been used in rice cultivars to obtain rice varieties better adapted to current environmental conditions and market requirements.展开更多
Objective:To study the role of inducible form of heat shock protein 70(Hsp70) in the host tumor regression of rat tumor model.Methods:We examined the role of Hsp70 in host tumorigenicity and in vitro cellular cytotoxi...Objective:To study the role of inducible form of heat shock protein 70(Hsp70) in the host tumor regression of rat tumor model.Methods:We examined the role of Hsp70 in host tumorigenicity and in vitro cellular cytotoxicity using a rat histocytoma.The differential tumor growth and regression kinetics were studied and correlated with the expression of Hsp70,activation of macrophages and natural killer(NK) cells,and circulating or tumor infiltrating immune molecules in the host system.Results:The sub cuteaneous(s.c.) tumor regression was correlated with increased serum cytokines such as IL-12,TNF P,IFNγand Hsp70.Despite of similar increase of Hsp70 in intraperitoneal(i.p.) tumor implanted animals,animals succumb to tumor growth,further,evidently,no immune molecule activation was observed.The viral promoter driven Hsp70 over expression in these tumor cells restrained solid tumor growth,however,failed to inhibit ascites growth.The NK cells from s.c.immunized animals induces cytotoxicity in the presence of anti-tumor antibody,which necessitated CD40-L expression,conversely,NK cells from i.p.immunized animals failed to induce cytotoxicity.The NK cells from s.c.or i.p.implanted animals with Hsp70 positive tumor cells failed to induce such cytotoxicity.The peritoneal macrophages isolated from s.c.tumor implanted animals when co-cultured with parental BC-8 cells lyses tumor cells,nevertheless entail macrophage specific TNFαexpression.On the contrary,Hsp70 expressing BC-8 tumor cells were resistant to peritoneal macrophage induced cytolysis.Conclusions:This study brings out that Hsp70 possibly involved in regulating the host tumor response and cellular cytotoxicity.展开更多
Objective: To investigate the effect of pomegranate peel aqueous extract (PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcus granulosus protoscoleces, and the immunom...Objective: To investigate the effect of pomegranate peel aqueous extract (PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcus granulosus protoscoleces, and the immunomodulatory properties of PGE. Methods: Swiss mice were inoculated intraperitoneally with viable protoscoleces. Then, PGE was orally administered daily during cystic echinococcosis development. Cyst development and hepatic damage were macroscopically and histologically analyzed. The production of nitric oxide and TNF-alpha was assessed in plasma and the hepatic expression of iNOS, TNF-alpha, NF-kappa B and CD68 was examined. Moreover, protoscoleces were cultured and treated with different concentrations of PGE. Results: It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner. In vivo, after treatment of cystic echinococcosis infected mice with PGE, a significant decrease in nitric oxide levels (P<0.000 1) and TNF-alpha levels (P<0.001) was observed. This decline was strongly related to the inhibition of cyst development (rate of hydatid cyst growth inhibition=63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue (P<0.000 1). A significant diminution of iNOS, TNF-alpha and NF-kappa B expression was also observed in liver tissue of treated mice (P<0.000 I). Conclusions: Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE, suggesting its potential therapeutic role against Echinococcus granulosus infection.展开更多
The immotile testicular mammalian spermatozoon gets transformed into a motile spermatozoon during 'epididymal maturation'. During this process, the spermatozoa transit from the caput to the cauda epididymis and unde...The immotile testicular mammalian spermatozoon gets transformed into a motile spermatozoon during 'epididymal maturation'. During this process, the spermatozoa transit from the caput to the cauda epididymis and undergo a number of distinct morphological, biophysical and biochemical changes, including changes in protein composition and protein modifications, which may be relevant to the acquisition of motility potential. The present proteome-based study of the hamster epididymal spermatozoa of caput and cauda led to the identification of 113 proteins spots using Matrix- assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) analysis. Comparison of these 113 protein spots indicated that 30 protein spots (corresponding to 20 proteins) were significantly changed in intensity. Five proteins were increased and eleven were decreased in intensity in the cauda epididymal spermatozoa. In addition, two proteins, glucose-regulated protein precursor (GRP78) and tumor rejection antigen (GP96), were unique to the caput epididymal spermatozoa, while one protein, fibrinogen-like protein 1, was unique to cauda epididymal spermatozoa. A few of the five proteins, which increased in intensity, were related to sperm metabolism and ATP production during epididymal maturation. The changes in intensity of a few proteins such as ERp57, GRP78, GP96, Hsp60, Hsp70, and dihydrolipoamide S-acetyltransferase were validated by immunoblotting. The present study provides a global picture of the changes in protein composition occurring during hamster sperm epididymal maturation, besides being the first ever report on the proteome of hamster spermatozoa.展开更多
Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neurona...Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.展开更多
A new species of the genus Tylototriton is described from eastern Himalaya based on molecular and morphological comparisons. The new species is diagnosable from the closely-related species by having light brown colour...A new species of the genus Tylototriton is described from eastern Himalaya based on molecular and morphological comparisons. The new species is diagnosable from the closely-related species by having light brown colouration in dorsal region in life, flat and blunt snout, greatly separated dorsolateral bony ridges on head and straightthick tailfin. In addition to head morphology, the new species is also morphologically distinguishable from its closelyrelated species Tylototriton shanorum by having 16 dorsal warts and average smaller Snout Vent Length(SVL).展开更多
Today,self-healing graphene-and MXene-based composites have attracted researchers due to the increase in durability as well as the cost reduction in long-time applications.Different studies have focused on designing n...Today,self-healing graphene-and MXene-based composites have attracted researchers due to the increase in durability as well as the cost reduction in long-time applications.Different studies have focused on designing novel self-healing graphene-and MXenebased composites with enhanced sensitivity,stretchability,and flexibility as well as improved electrical conductivity,healing efficacy,mechanical properties,and energy conversion efficacy.These composites with self-healing properties can be employed in the field of wearable sensors,supercapacitors,anticorrosive coatings,electromagnetic interference shielding,electronic-skin,soft robotics,etc.However,it appears that more explorations are still needed to achieve composites with excellent arbitrary shape adaptability,suitable adhesiveness,ideal durability,high stretchability,immediate self-healing responsibility,and outstanding electromagnetic features.Besides,optimizing reaction/synthesis conditions and finding suitable strategies for functionalization/modification are crucial aspects that should be comprehensively investigated.MXenes and graphene exhibited superior electrochemical properties with abundant surface terminations and great surface area,which are important to evolve biomedical and sensing applications.However,flexibility and stretchability are important criteria that need to be improved for their future applications.Herein,the most recent advancements pertaining to the applications and properties of self-healing graphene-and MXene-based composites are deliberated,focusing on crucial challenges and future perspectives.展开更多
Objective:To immunize rabbits with 12 and 16 kDa recombinant subunits of antigen B from Echinococcus granulosus(E.granulosus) and measuring polyclonal antibody and humoral immune response using ELISA and gel diffusion...Objective:To immunize rabbits with 12 and 16 kDa recombinant subunits of antigen B from Echinococcus granulosus(E.granulosus) and measuring polyclonal antibody and humoral immune response using ELISA and gel diffusion.Methods:Two mentioned antigens were cloned and expressed in expression vector and purified by affinity chromatography.Four young rabbits were selected and challenged intradermallt with yielded recombinant antigens.Rabbits’ sera were collected post infection and were tested using ELISA and gel diffusion for polyclonal antibody detection 10 days after last injection.Results:The specific antibody against the recombinant peptides was efficiently produced within 4 weeks post infection.Conclusions: Produced recombinants proteins could induce the immune response of the rabbits successfully. This process might improve the clarification of diagnosis and vaccination as regards hydatidosis.展开更多
文摘Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.
基金funded by U.S.Air Force Office of Scientific Research FA9550-21-1-0096,FONDAP program 15150012,ANID/FONDEF ID1ID22I10120,FONDECY/ANID 1220573the US Army Medical Research Acquisition Activity(USAMRAA)project number AL2201415DoD Award HT9425-23-1-0990,AL220141(to CH)。
文摘Lifestyle and demographics of the world's population are causing serious health problems impacting the brain,increasing the incidence of Alzheimer's disease(AD)and other types of dementia.Although we have gained important insights into the pathogenic mechanisms of AD,only palliative care is available to patients.AD is characterized by the abnormal deposition of protein aggregates in the brain formed by amyloid β and hyper-phosphorylated,Tau in addition to neuroinflammation.
文摘Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in 2008.In the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong survival.Moreover,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)therapies.Trastuzumab,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy.Further,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field.Thus,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.
基金Supported by the Grant from Calling for Tenders by Key Subject of Jiangsu Province, No. WK200221
文摘AIM: To study the effectiveness and mechanisms of anti-human vascular endothelial growth factor (hVEGF) hairpin ribozyme on angiogenesis,oncogenicity and tumor growth in a hepatocarcinoma cell line and a xenografted model. METHODS: The artificial anti-hVEGF hairpin ribozyme was transfected into hepatocarcinoma cell line SMMC-7721 and,subsequently,polymerase chain reaction (PCR) and reverse transcription polymerase chain reaction (RT-PCR) were performed to confirm the ribozyme gene integration and transcription. To determine the effects of ribozyme ,VEGF expression was detected by semiquantitative RT-PCR and enzyme liked immunosorbent assay (ELISA). MTT assay was carried out to measure the cell proliferation. Furthermore,the transfected and control cells were inoculated into nude mice respectively,the growth of cells in nude mice and angiogenesis were observed. RESULTS: VEGF expression was down-regulated sharply by ribozyme in transfected SMMC-7721 cells and xenografted tumor. Compared to the control group,the transfected cells grew slower in cell cultures and xenografts,and the xenograft formation was delayed as well. In addition,the microvessel density of the xenografted tumor was obviously declined in the transfected group. As demonstratedby microscopy,reduction of VEGF production induced by ribozyme resulted in a significantly higher cell differentiation and less proliferation vigor in xenografted tumor. CONCLUSION: Anti-hVEGF hairpin ribozyme can effectively inhibit VEGF expression and growth of hepatocarcinoma in vitro and in vivo. VEGF is functionally related to cell proliferation,differentiation and tumori-genesis in hepatocarcinoma.
基金Supported by IIUM Research Initiative Grant,RIGS grant no.16-301-0465
文摘Objective:To identify the prevalence of Cryptosporidium from goats in three types of farm management systems in Terengganu,Malaysia and to determine the Cryptosporidium species infecting goats by using 18 S r RNA.Methods:A total of 478 fecal samples were randomly collected from goats in three farms;199 samples were collected from intensive farm,179 samples from semi-intensive farm and 100 samples from extensive farm.The samples were processed by using formolether concentration technique and stained by using modified Ziehl–Neelsen.Positive samples were performed by using nested PCR analysis by using 18 S r RNA.Results:Out of 478 goats,207(43.3%) were found to be infected with Cryptosporidium.Goats reared under the intensive farm management system reported the highest prevalence of infection(49.7%),followed by intensive farm management system(41%) and the lowest prevalence was reported in the goats reared under semi-intensive management system(37.4%).Conclusions:The identified species found in goat was Cryptosporidium parvum.Future study on the zoonotic transmission of Cryptosporidium parvum in goats needs to be done in order to find the source of transmission of this parasite.
文摘Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) superfamily of proteins, circulates in a complex with vitronectin. Furthermore, these two proteins are co-localized in the extracellular matrix (ECM) in many different pathophysiological conditions. Though PAI-1 is a well-characterized inhibitor of serine proteases, recent emphasis has also focused on its protease-independent functions. Vitronectin, a multi-domain protein that binds a wide variety of ligands and proteins, exists in the circulation in a preferred monomeric state, while in the extracellular matrix it exists as a multimer resulting from an altered conformation. Though the mechanism for the conformational alterations and compartmentalization in tissues is unknown, there are a number of biomolecules including PAI-1 that appear to cause such changes. Experimental analysis has established that PAI-1 induces association of vitronectin to higher-order species in a concentration-dependent fashion [1]. This report extends our investigations into the mechanism of the interaction between vitronectin and PAI-1 to explore the physiological relevance of these higher-order complexes for cellular adhesion and migration. In this study, we evaluate the effects of the pericellular microenvironment on the functions of the multimeric complexes in a variety of relevant biological settings. Our findings underscore the importance of the variability of components within this microenvironment, including different receptors and ECM components, in governing the way in which the vitronectin/PAI-1 complex mediates cell-matrix interactions.
文摘Peatlands are unique and complex natural ecosystems that are part of the most important carbon reservoirs on our planet, home to a diversity of microorganisms responsible for fermentation, humification or peat. The aim is to understand chemical and biological indicators of peatland soils. This work aims to determine the physicochemical and bacteriological profile and lipolytic activity of soil bacteria in Bilanko peatlands. The bacterial profile with the production of lipases is carried out by classical microbiology techniques. The results show that the soils are moderately acidic with temperatures of 27.8˚C ± 0.01˚C for Bilanko and 27.1˚C ± 0.57˚C for Ngamakala. The electroconductivity (EC) varies from (9.52 ± 0.002) μS/cm to (39.01 ± 1.4) μS/cm with low turbidity of (2.04 ± 0.66) mg/L to (31.02 ± 0.84) mg/L and low ion concentrations with, however, a richness in phenolic compounds for Bilanko compared to Ngamakala. FMAT diversity ranged from (1.71 ± 0.88)∙104 UFC/g to (2.92 ± 0.07)∙105 UFC/g for Bilanko and (1.30 ± 0.73)∙104 UFC/g to (2.89 ± 0.06)∙104 UFC/g for Ngamakala. Bacillus loads ranged from (5.20 ± 1.40)∙103 CFU/g to (1.22 ± 0.13)∙104 CFU/g and from (1.11 ± 0.13)∙104 CFU/g to (9.20 ± 2.05)∙103 CFU/g;enterobacteria loads from (1.40 ± 0.76)∙103 CFU/g to (8.80 ± 1.73)∙103 CFU/g and from (1.01 ± 0.02)∙103 CFU/g to (9.20 ± 2.05)∙103 CFU/g;in Pseudomonas from 0 to (2.30 ± 0.53)∙102 CFU/g and from 0 to (8.90 ± 2.35)∙102 CFU/g for Bilanko and Ngamakala respectively. These results reveal a variation in bacterial similarity and distribution in the Bilanko and Ngamakala peat bogs.
文摘Desmodus rotundus and Diphylla ecaudata, both of which are mammals of the order Chiroptera, Desmodontidae family, their diet consisting exclusively of blood. D. rotundus is the main vector and transmitter of the rabies virus, which affects human beings as well as several livestock species so the study of this bat species is of high importance within the fields of animal agriculture and public health. The present study describes and compares the histologic characteristics of the urinary system of two hematophagous bat species. A total of 5 bats from each species were captured in the municipalities of Progreso de Obregón, Hidalgo (D. rotundus), and Huayacocotla, Veracruz (D. ecaudata). Organs belonging to the urinary system were extracted: kidneys, ureters, urinary bladder, and urethra;samples were fixed using 10% formalin and processed by the paraffin embedding technique, obtaining sections of 5 µm thickness, which in turn were stained using hematoxylin-eosin (H-E) and Gomori trichrome (GT) stains. From the obtained histologic preparations, a descriptive and comparative analysis of the structural organography of the urinary system of both species was made, and no noteworthy histological differences between samples were noted. The present research is intended to provide a framework for future studies of these species’ currently understudied microscopic anatomy.
文摘Measles is a highly infectious, vaccine-preventable viral disease. Often forgotten, it is potentially fatal. Its main symptoms are: fever, cough, conjunctivitis, rhinitis and skin rash. Serological diagnoses by ELISA test based on the detection of anti-measles virus immunoglobulins M and G (IgM and IgG), are used respectively for the confirmation of suspected cases notified by means of clinical signs of the disease in health structures of the twelve departments of the Republic of Congo involved in the epidemiological surveillance of the disease, and for the evaluation of the immunity conferred by vaccination. During 2021, 459 suspected cases of measles were reported and sampled throughout the country, despite the administration under the Expanded Routine Immunization Program (EPI), of 2 doses of the combined measles-rubella vaccine (RR1 and RR2) in 2020. The notification rate was higher in the south of the country, more precisely in the health structures of the departments of Pointe-Noire (42%) and Brazzaville (11%). During the year 2021, 459 suspected cases of measles were notified and sampled throughout the country with a high notification rate in the south of the country, more precisely in the health structures of the Pointe-Noire departments (42%) and Brazzaville (11%). The samples consisting of human blood (serum) were sent to the National Public Health Laboratory and analyzed by various ELISA tests for the detection of anti-measles immunog-lobulins M and G. The analysis of the results obtained shows that the measles virus circulated in all departments of the country. 154 cases (33.55%) were confirmed positive by IgM ELISA and 98 positive cases (63.63%) were patients vaccinated against measles. Vaccination coverage in RR1 of [50%-95% [(first dose) as well as the lowest RR2 < 50% (second dose) undoubtedly because the COVID-19 pandemic could be the cause of the high frequency of cases positive vaccinated. The non-detection of IgG immunoglobulins in vaccinated patients observed by IgG ELISA tests revealed that 63.26% of vaccinated patients were not immunized against the measles virus. These results confirm those obtained during the Elisa IgM analysis and make it possible to deduce that the quality, the number of doses not properly administered, the individual characteristics of the people as well as the poor conservation of the administered vaccine (non-compliance with the cold chain) would explain the high proportion of positive cases of vaccinated measles observed.
文摘Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
文摘Inflammatory bowel diseases(IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor(TNF)-α, interleukin(IL)-1b, IL-8, and IL-17A], anti-inflammatory cytokines(IL-4 and IL-13), and immunoregulatory cytokines(IL-10 and transforming growth factors b) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide(NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase(iN OS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iN OS. A positive correlation between NO production and increased pro-inflammatory cytokine levels(TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.
基金supported by grants from National Fund for the Research and National Agency for the Development of Research in Health(Algeria)
文摘Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusion and agar dilution methods,resistance genes were identified by PCR and sequencing,and molecular typing of isolates was carried out by enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR).Results:Among 125 tested isolates,117(93.6% ) were multidrug-resistant.of which 94(75.2% ) were imipenem resistant.The bla_(ADC)and bla_(OXA-51-like) genes were detected in all isolates,in association with ISAba I sequence in 84% and 8% (imipenem resistant) of isolates,respectively.The bla_(OXA-23-like) and bla_(OXA-24-like)carbapenemase genes were delected in 67.02% and 20.21% of imipenem-resistant isolates,respectively.The bla_(OXA-23-like) gene is linked to ISAba1 or ISAba4 elements.The metallo-β-lactamase NDM-1 gene was found in 10(10.6% ) imipenem-resisianl strains from three hospitals,it is linked to ISAba125 clement in nine strains.Extended spectrum β-lactamases production was not detected.Imipenem and cefotaxime resistance phenolypes could not be transferred to Escherichia coli by conjugation.Outer membrane protein CarO gene was not delected in four imipenem-resisianl isolates.The aac(6')-1b.sul1,sul2,tetA and tetB genes were present in 5.31% .36.17% .77.65% .1.06% and 65.92% of strains,respectively.Class 1 integrons were detected in 23.4% strains.KRIC-PCR typing showed a genetic diversity among bla_(OXA-23-like) and bla_(OXA-24-like) positive strains,while clonality was observed among bla_(NDM-1)positives.Conclusions:This study highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii in Algiers hospitals mediated mainly by bla_(OXA-23-like),bla_(OXA-24-like),and bla_(NDM-1) genes.
文摘Rice(Oryza sativa L.)is an important staple food crop worldwide due to its adaptability to different environmental conditions.Because of its great economic and social importance,there is a constant requirement for new varieties with improved agronomic characteristics,such as tolerance to different biotic(such as bacterium,fungus,insect and virus)and abiotic stresses(such as salinity,drought and temperature),higher yield and better organoleptic and nutritional value.Among the new genome editing technologies,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)(CRISPR/Cas)system allows precise and specific edition in a targeted genome region.It is one of the most frequently used techniques for the study of the function of new genes and for the development of mutant lines with enhanced tolerance to biotic and abiotic stresses,herbicide resistance or improved yield.The wide varieties of applications for this technology include simple non-homologous end joining,homologous recombination,gene replacement,and base editing.In this review,we analyzed how some of these applications have been used in rice cultivars to obtain rice varieties better adapted to current environmental conditions and market requirements.
文摘Objective:To study the role of inducible form of heat shock protein 70(Hsp70) in the host tumor regression of rat tumor model.Methods:We examined the role of Hsp70 in host tumorigenicity and in vitro cellular cytotoxicity using a rat histocytoma.The differential tumor growth and regression kinetics were studied and correlated with the expression of Hsp70,activation of macrophages and natural killer(NK) cells,and circulating or tumor infiltrating immune molecules in the host system.Results:The sub cuteaneous(s.c.) tumor regression was correlated with increased serum cytokines such as IL-12,TNF P,IFNγand Hsp70.Despite of similar increase of Hsp70 in intraperitoneal(i.p.) tumor implanted animals,animals succumb to tumor growth,further,evidently,no immune molecule activation was observed.The viral promoter driven Hsp70 over expression in these tumor cells restrained solid tumor growth,however,failed to inhibit ascites growth.The NK cells from s.c.immunized animals induces cytotoxicity in the presence of anti-tumor antibody,which necessitated CD40-L expression,conversely,NK cells from i.p.immunized animals failed to induce cytotoxicity.The NK cells from s.c.or i.p.implanted animals with Hsp70 positive tumor cells failed to induce such cytotoxicity.The peritoneal macrophages isolated from s.c.tumor implanted animals when co-cultured with parental BC-8 cells lyses tumor cells,nevertheless entail macrophage specific TNFαexpression.On the contrary,Hsp70 expressing BC-8 tumor cells were resistant to peritoneal macrophage induced cytolysis.Conclusions:This study brings out that Hsp70 possibly involved in regulating the host tumor response and cellular cytotoxicity.
文摘Objective: To investigate the effect of pomegranate peel aqueous extract (PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcus granulosus protoscoleces, and the immunomodulatory properties of PGE. Methods: Swiss mice were inoculated intraperitoneally with viable protoscoleces. Then, PGE was orally administered daily during cystic echinococcosis development. Cyst development and hepatic damage were macroscopically and histologically analyzed. The production of nitric oxide and TNF-alpha was assessed in plasma and the hepatic expression of iNOS, TNF-alpha, NF-kappa B and CD68 was examined. Moreover, protoscoleces were cultured and treated with different concentrations of PGE. Results: It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner. In vivo, after treatment of cystic echinococcosis infected mice with PGE, a significant decrease in nitric oxide levels (P<0.000 1) and TNF-alpha levels (P<0.001) was observed. This decline was strongly related to the inhibition of cyst development (rate of hydatid cyst growth inhibition=63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue (P<0.000 1). A significant diminution of iNOS, TNF-alpha and NF-kappa B expression was also observed in liver tissue of treated mice (P<0.000 I). Conclusions: Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE, suggesting its potential therapeutic role against Echinococcus granulosus infection.
文摘The immotile testicular mammalian spermatozoon gets transformed into a motile spermatozoon during 'epididymal maturation'. During this process, the spermatozoa transit from the caput to the cauda epididymis and undergo a number of distinct morphological, biophysical and biochemical changes, including changes in protein composition and protein modifications, which may be relevant to the acquisition of motility potential. The present proteome-based study of the hamster epididymal spermatozoa of caput and cauda led to the identification of 113 proteins spots using Matrix- assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) analysis. Comparison of these 113 protein spots indicated that 30 protein spots (corresponding to 20 proteins) were significantly changed in intensity. Five proteins were increased and eleven were decreased in intensity in the cauda epididymal spermatozoa. In addition, two proteins, glucose-regulated protein precursor (GRP78) and tumor rejection antigen (GP96), were unique to the caput epididymal spermatozoa, while one protein, fibrinogen-like protein 1, was unique to cauda epididymal spermatozoa. A few of the five proteins, which increased in intensity, were related to sperm metabolism and ATP production during epididymal maturation. The changes in intensity of a few proteins such as ERp57, GRP78, GP96, Hsp60, Hsp70, and dihydrolipoamide S-acetyltransferase were validated by immunoblotting. The present study provides a global picture of the changes in protein composition occurring during hamster sperm epididymal maturation, besides being the first ever report on the proteome of hamster spermatozoa.
基金supported by Comisión Nacional de Investigación Cientifica y Tecnologica-Chile Fondecyt 12011668(to ARA)Fondecyt 1190334(to SZ)+6 种基金Fondecyt 11200592(to MJY)Fondef ID21/10347(to ARA andSZ)Fondef D10E1077(to ARA and SZ)CARE-UCAFB 170005(to ARA)MSCA-RISE-2016-Lysomod-734825 European Union's Horizon 2020Research and Innovation Program under the Marie Sklodowska-Curie grant agreement N°953489(to SZ)Millennium Science Initiative Program-ICN09_016/ICN 2021_045(to ARA)。
文摘Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.
基金supported by the world academy of sciences(TWAS)CAS-TWAS president fellowship programthe National Natural Sciences Foundation of China(NSFC-31201702 granted to Bin Wang and NSFC-31471964 granted to Jianping Jiang)
文摘A new species of the genus Tylototriton is described from eastern Himalaya based on molecular and morphological comparisons. The new species is diagnosable from the closely-related species by having light brown colouration in dorsal region in life, flat and blunt snout, greatly separated dorsolateral bony ridges on head and straightthick tailfin. In addition to head morphology, the new species is also morphologically distinguishable from its closelyrelated species Tylototriton shanorum by having 16 dorsal warts and average smaller Snout Vent Length(SVL).
文摘Today,self-healing graphene-and MXene-based composites have attracted researchers due to the increase in durability as well as the cost reduction in long-time applications.Different studies have focused on designing novel self-healing graphene-and MXenebased composites with enhanced sensitivity,stretchability,and flexibility as well as improved electrical conductivity,healing efficacy,mechanical properties,and energy conversion efficacy.These composites with self-healing properties can be employed in the field of wearable sensors,supercapacitors,anticorrosive coatings,electromagnetic interference shielding,electronic-skin,soft robotics,etc.However,it appears that more explorations are still needed to achieve composites with excellent arbitrary shape adaptability,suitable adhesiveness,ideal durability,high stretchability,immediate self-healing responsibility,and outstanding electromagnetic features.Besides,optimizing reaction/synthesis conditions and finding suitable strategies for functionalization/modification are crucial aspects that should be comprehensively investigated.MXenes and graphene exhibited superior electrochemical properties with abundant surface terminations and great surface area,which are important to evolve biomedical and sensing applications.However,flexibility and stretchability are important criteria that need to be improved for their future applications.Herein,the most recent advancements pertaining to the applications and properties of self-healing graphene-and MXene-based composites are deliberated,focusing on crucial challenges and future perspectives.
基金supported financially by Tehran University of Medical Sciencesimplemented in Cellular and Molecular Biology Research Center of Shahid Beheshti University of Medical Sciences,Tehran,Iran
文摘Objective:To immunize rabbits with 12 and 16 kDa recombinant subunits of antigen B from Echinococcus granulosus(E.granulosus) and measuring polyclonal antibody and humoral immune response using ELISA and gel diffusion.Methods:Two mentioned antigens were cloned and expressed in expression vector and purified by affinity chromatography.Four young rabbits were selected and challenged intradermallt with yielded recombinant antigens.Rabbits’ sera were collected post infection and were tested using ELISA and gel diffusion for polyclonal antibody detection 10 days after last injection.Results:The specific antibody against the recombinant peptides was efficiently produced within 4 weeks post infection.Conclusions: Produced recombinants proteins could induce the immune response of the rabbits successfully. This process might improve the clarification of diagnosis and vaccination as regards hydatidosis.