AIM:To examine and compare the effects of several ARBs that are widely used in clinics , on the ACE-Ang II-AT1 receptor and the ACE2-Ang(1-7)-Mas axis during the development of cardiac remodeling after pressure overload .METHODS: All of the mice used in the study underwent transverse aortic constriction (TAC) or sham operation for 2 or 4 weeks.A solution of either ARBs or sa-line was administered through a stomach tube 3 days before the operation .Meanwhile , to eliminate the influence of Ang II , a recombi-nant adenovirus expressing small interfering RNAs targeting angiotensinogen ( Ad-ATG siRNA) was injected via the tail vein .The sur-gery was then performed and the drug was administered as mentioned above .Cardiac function and remodeling were evaluated by echo-cardiography , hemodynamic measurements and cardiac histology .Western blotting was used to determine the protein expression levels . Meanwhile , we performed similar experiments using ARBs with or without ATG siRNA in cardiomyocytes induced by mechanical stretch.RESULTS:Although all of the six ARBs , none of which repressed the elevation of left ventricular pressure after TAC , attenu-ated the development of cardiac hypertrophy and heart failure in the wild-type mice, the degree of attenuation by Olmesartan , Candesar-tan and Losartan tended to be larger than that of the other three drugs tested .Additionally , the degree of downregulation of the ACE-Ang II-AT1 axis and upregulation of the ACE2-Ang(1-7)-Mas axis was higher in response to Olmesartan, Candesartan and Losartan administration in vivo and in vitro.Additionally, Olmesartan had a larger influence when administered long term .However, the expres-sion of ACE was not influenced by the administration of ARBs in vivo and in vitro.Moreover, in angiotensinogen-knockdown mice, TAC-induced cardiac hypertrophy and heart failure were inhibited by Olmesartan , Candesartan and Losartan but not by Telmisartan , Valsartan and Irbesartan administration .Furthermore , only Olmesartan and Candesartan could downregulate the ACE-Ang II-AT1 axis and upregulate the ACE2-Ang(1-7)-Mas axis in vitro.CONCLUSION: Olmesartan, Candesartan and Losartan could effectively in-hibit pressure overload-induced cardiac remodeling even when with knockdown of Ang II , possibly through upregulation of the expres-sion of the ACE2-Ang(1-7)-Mas axis and downregulation of the expression of the ACE-Ang II-AT1 axis.In contrast, Telmisartan, Valsartan and Irbesartan only played a role in the presence of Ang II , and Losartan had no effect in the presence of Ang II in vitro.

BACKGROUND:Although there is a certain progress in the preparation of tissue-engineered bone tissue using a variety of materials, some deficiencies have appeared such as mismatching between scaffold degradation rate and new bone formation rate, slow tissue growth, toxic metabolites.
OBJECTIVE:To build a new type of inducible bone repair composite scaffold with bionic bone structurematerials and to evaluate its physicochemical and biological properties.
METHODS: Icarin encapsulated by chitosan was used to prepare drug-loaded microspheres, and the drug release rate of the microspheres was detected. Chitosan microspheres were mixed with colagen to build the core part of scaffold materials. Hydroxyapatite (HA), polycaprolactone (PCL) and colagen were mixed in hexafluoride isopropanol (HFIP) to prepare the HA/PCL/colagen outer part of composite scaffold material at the rate of 0:3:3, 1:3:3, 2:3:3, 3:3:3. Each proportional electrospinning was used for one layer, and finaly the 4-layer outer tube of the scaffold was produced. The tube core and outer tube were crosslinked by 1% genipin. Universal material testing machine, surface contact angle meter, infrared spectroscopy, scanning electron microscope, water absorption, permeability, porosity,in vitro degradation tests for cross-linked and uncross-linked were used to observe the structure and characteristics of tubular materials. Bone marrow mesenchymal stem cels were seeded on the surface of cross-linked and uncross-linked bone repair materials to evaluate the biocompatibility of the scaffolds. Cross-linked and uncross-linked bone repair materials were implanted subcutaneously into Wistar rats to evaluate the histocompatibility of the scaffolds.
RESULTS AND CONCLUSION:The drug in the scaffold had a suitable release; the bone scaffold material had good uniformity, and cross-linked scaffolds materials had better mechanical properties, water absorption and permeability than the uncross-linked(P < 0.05). The degradation rate of the cross-linked group was significantly lower than that of the uncross-linked group (P< 0.05). Hematoxylin-eosin staining showed that the bone marrow mesenchymal stem cels could adhere wel to the cross-linked and uncross-linked materials. No inflammatory reactions occurred after subcutaneous implantation of cross-linked and uncross-linked materials. These findings indicate that the cross-linked scaffold for inducible bone tissue engineering has good biocompatibility and mechanical properties.

Objective To explore the clinical characteristics and the cause of misdiagnosis of child suffering from cerebral parago-nimiasis with intracranial hemorrhage as initial symptom,and to improve the diagnosis and treatment level of cerebral paragonimiasis.Methods The clinical data of the children who suffered from cerebral paragonimiasis with intracranial hemorrhage as initial symptom were collected from January 2011 to December 2015 in Affiliated Hospital of Zunyi Medical College.The clinical manifestation,imageology and laboratory tests,outcome of therapy were analyzed and then the effect of treatment and the prognosis were followed up.Results There were 7 patients meeting the inclusion criteria for cerebral paragonimiasis,including 4 male and 3 female.They were from 6 to 13 years old with the average age of 9.3 years old.All patients presented with headache and vomiting,and showed intracranial hemorrhage through CT or MRI of brain.All of the 7 patients were misdiagnosed as cerebrovascular malformation by the neurosurgeons.Three of them showed typical imaging pattern including tunnel sign and the ring-like shape of cerebral paragonimiasis.Five of these cases were attacked by pulmonary distomiasis at the same time.Six of them had an increasing eosinophil,and the paragonimus antibody was positive.They were treated with Praziquantel.Six patients recovered completely,and 1 patient had the dysfunction of left extremities.Conclusions The childhood cerebral paragonimiasis has strong clinical heterogeneity and diversity in manifestation.Intracranial hemorrhage may be the initial symptom,which should be paid more attention to.Cerebral paragonimiasis can be diagnosed and treated early according to the clinical characteristics,the increase of eosinophil,the typical changes in imageology and the specific antibody test.

AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.

Background: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. Objectives: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. Methods: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. Results: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4 + T cells were observed in mice immunized with VLPs. Conclusions The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

Rapid and accurate detection technologies are crucial for disease prevention and control. In particular, the COVID-19 pandemic has posed a great threat to our society, highlighting the importance of rapid and highly sensitive detection techniques. In recent years, CRISPR/Cas-based gene editing technique has brought revolutionary advances in biotechnology. Due to its fast, accurate, sensitive, and cost-effective characteristics, the CRISPR-based nucleic acid detection technology is revolutionizing molecular diagnosis. CRISPR-based diagnostics has been applied in many fields, such as detection of infectious diseases, genetic diseases, cancer mutation, and food safety. This review summarized the advances in CRISPR-based nucleic acid detection systems and its applications. Perspectives on intelligent diagnostics with CRISPR-based nucleic acid detection and artificial intelligence were also provided.
Humans ; CRISPR-Cas Systems/genetics* ; COVID-19/genetics* ; Pandemics ; Artificial Intelligence ; Nucleic Acids

CRISPR-Cas Systems ; Embryo, Mammalian ; Gene Editing ; methods ; HEK293 Cells ; Humans ; Polycomb Repressive Complex 1 ; genetics ; Zygote