scholarly journals miR-217 Is a Useful Diagnostic Biomarker and Regulates Human Podocyte Cells Apoptosis via Targeting TNFSF11 in Membranous Nephropathy

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Li ◽  
Bin Liu ◽  
Hen Xue ◽  
Qiao Qiao Zhou ◽  
Ling Peng
Keyword(s):  
Membranous Nephropathy ◽  
Target Gene ◽  
In Vitro Experiments ◽  
Diagnostic Biomarker ◽  
Diagnostic Biomarkers ◽  
Cutoff Value ◽  
Pathological Mechanism ◽  
Opposite Change ◽  
And Control

Background. MicroRNAs have recently been verified as useful diagnostic biomarkers in various diseases. In this study, we investigated whether miR-217 is a useful diagnostic biomarker and the possible pathological mechanism of miR-217 in this disease. Methods. Patients with focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and diabetic nephropathy (DN) and control patients were enrolled in this study. The miR-217 inhibitor and mimics were transfected into human podocyte cells to investigate the pathological mechanism of miR-217 in this disease. Relevant indicators were detected and tested. Results. Compared with control patients, miR-217 was significantly downregulated and TNFSF11 was significantly upregulated in MN. Then, miR-217 had obvious separation between patients with MN and control patients, with an AUC of 0.941, a cutoff value of <750.0 copies/ul, and sensitivity and specificity of 88.9% and 75.9%. In addition, the TNFSF11 was confirmed to be the target gene of miR-217. Finally, in in vitro experiments, the upregulation of miR-217 could decrease the expression of TNFSF11 and not induce human podocyte cells apoptosis; however, the downregulation of miR-217 could bring about an opposite change. Conclusions. miR-217 is a useful diagnostic biomarker and is involved in human podocyte cells apoptosis via targeting TNFSF11 in membranous nephropathy.

scholarly journals Reversible Gene Expression Control inYersinia pestisby Using an Optimized CRISPR Interference System

2019 ◽  
Vol 85 (12) ◽  
Author(s):  
Tong Wang ◽  
Min Wang ◽  
Qingwen Zhang ◽  
Shiyang Cao ◽  
Xiang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Throughput ◽  
Biofilm Formation ◽  
Prevention And Control ◽  
Target Gene ◽  
Gene Knockdown ◽  
Content Type ◽  
Short Palindromic Repeat ◽  
And Control

ABSTRACTMany genes in the bacterial pathogenYersinia pestis, the causative agent of three plague pandemics, remain uncharacterized, greatly hampering the development of measures for plague prevention and control. Clustered regularly interspaced short palindromic repeat interference (CRISPRi) has been shown to be an effective tool for gene knockdown in model bacteria. In this system, a catalytically dead Cas9 (dCas9) and a small guide RNA (sgRNA) form a complex, binding to the specific DNA target through base pairing, thereby impeding RNA polymerase binding and causing target gene repression. Here, we introduce an optimized CRISPRi system usingStreptococcus pyogenesCas9-derived dCas9 for gene knockdown inY. pestis. Multiple genes harbored on either the chromosome or plasmids ofY. pestiswere efficiently knocked down (up to 380-fold) in a strictly anhydrotetracycline-inducible manner using this CRISPRi approach. Knockdown ofhmsH(responsible for biofilm formation) orcspB(encoding a cold shock protein) resulted in greatly decreased biofilm formation or impaired cold tolerance inin vitrophenotypic assays. Furthermore, silencing of the virulence-associated genesyscBorailusing this CRISPRi system resulted in attenuation of virulence in HeLa cells and mice similar to that previously reported foryscBandailnull mutants. Taken together, our results confirm that this optimized CRISPRi system can reversibly and efficiently repress the expression of target genes inY. pestis, providing an alternative to conventional gene knockdown techniques, as well as a strategy for high-throughput phenotypic screening ofY. pestisgenes with unknown functions.IMPORTANCEYersiniapestisis a lethal pathogen responsible for millions of human deaths in history. It has also attracted much attention for potential uses as a bioweapon or bioterrorism agent, against which new vaccines are desperately needed. However, manyY. pestisgenes remain uncharacterized, greatly hampering the development of measures for plague prevention and control. Clustered regularly interspaced short palindromic repeat interference (CRISPRi) has been successfully used in a variety of bacteria in functional genomic studies, but no such genetic tool has been reported inY. pestis. Here, we systematically optimized the CRISPRi approach for use inY. pestis, which ultimately repressed target gene expression with high efficiency in a reversible manner. Knockdown of functional genes using this method produced phenotypes that were readily detected byin vitroassays, cell infection assays, and mouse infection experiments. This is a report of a CRISPRi approach inY. pestisand highlights the potential use of this approach in high-throughput functional genomics studies of this pathogen.

scholarly journals Mesenchymal stem cell-derived exosomes inhibit Aβ1-42 induced microglia polarization by TLR2/MYD88/NF-κB pathway

2021 ◽  
Author(s):  
Zhenyu Yin ◽  
Mengtian Guo ◽  
Dong Wang ◽  
Zhaoli Han ◽  
Tianpeng Hu ◽  
...  
Keyword(s):  
Target Gene ◽  
Research Evidence ◽  
Treated Group ◽  
In Vitro Experiments ◽  
Microglial Polarization ◽  
Microglia Polarization ◽  
Key Factor ◽  
The Brain

Abstract Background In recent years, more and more research evidence indicates that the causes of various neurodegeneration diseases are related to neuroinflammation in the brain, Aβ1–42 may be a key factor in the development of neuroinflammation in neurodegenerative diseases. Therefore, it is urgent to find an effective and targeted alleviation of neuroinflammation caused by Aβ1–42. Methods Our study found that exogenous administration of Aβ1–42 has a very obvious polarizing effect on microglia in the brain compared with the PBS-treated group. After the intervention of Aβ1–42, we obtained the mesenchymal stem cells derived exosome by ultracentrifugation. Microglia were treated with MSC-Exo in vivo and in vitro. Results The MSC-Exo were found have the effect of inhibiting microglial polarization in vivo and in vitro experiments. It was further found that its target gene was TLR2 on the surface of microglial cells to inhibit the expression of the downstream protein MYD88/NF-κB and inhibit the microglia polarization and the development of neuroinflammation. Conclusion MSC-Exo can significantly inhibited the Aβ1–42 induced microglia polarization by TLR2/MYD88/NF-κb pathway.

Research on Biomechanical Compatibility for the Artificial Anal Sphincter Based on Improved Actuator

2021 ◽  
Vol 15 (3) ◽  
Author(s):  
Peng Zan ◽  
Qiao Ding ◽  
Banghua Yang ◽  
Guofu Zhang ◽  
Yingjie Xue ◽  
...  
Keyword(s):  
Finite Element Analysis ◽  
Anal Sphincter ◽  
In Vitro Experiments ◽  
Artificial Anal Sphincter ◽  
Element Analysis ◽  
Biomechanical Compatibility ◽  
Bowel Movements ◽  
Defecation Disorders ◽  
And Control

Abstract Anal incontinence, also known as fecal incontinence, refers to the loss of the body's ability to accumulate and control the liquid, solid, and gas contents in the rectum, increasing the frequency of bowel movements. It is a symptom of defecation disorders. The artificial anal sphincter provides a new solution for clinical treatment. In this paper, in order to solve the problem of biomechanical compatibility of the actuator of the artificial anal sphincter system, the original actuator was improved. The model of the rectum and the actuator was constructed by ANSYS. The mechanical finite element analysis of the clamping mechanism was carried out by simulating sphincter behavior, and the displacement cloud diagram and stress cloud diagram of the clamping rectum were obtained. in vitro experiments were carried out using pig intestine to simulate the rectum, which verified the effectiveness of the actuator. The results of the experiment show that the successful rate of holding the rectum reached 96% under the condition of ensuring the normal blood supply to the rectum. It fully proves that the actuator has good biomechanical compatibility.

An Earthworm-Like Microrobot for Colonoscopy

2006 ◽  
Vol 40 (6) ◽  
pp. 471-478 ◽  
Author(s):  
K. D. Wang ◽  
G. Z. Yan
Keyword(s):  
Minimally Invasive Surgery ◽  
Control System ◽  
Minimally Invasive ◽  
Invasive Surgery ◽  
Viscoelastic Model ◽  
Research Topic ◽  
In Vitro Experiments ◽  
And Control ◽  
Acting Force

Abstract Miniature robotics for colonoscopy has become a hot research topic with the development of minimally invasive surgery (MIS). In this paper, a novel microrobot for colonoscopy that operates based on a simulation of the squirming motion of the earthworm is described. The robot uses a unique driving unit called a linear electromagnetic driver. The prototype measures 9.5 mm in diameter and 120 mm in length. It is driven by a linear direct current (DC) motor designed and manufactured by the authors. This paper describes the prototype, locomotion principle, and control system in detail. It then describes two models that were built to study the robot's ability to move in the viscoelastic colon environment. A slope model of motion was developed and some mathematical evaluations of locomotion conditions were conducted. Experiments to test the creeping ability of the prototype on a slope were performed to verify these expressions. From the viscoelastic model relative to acting force between the robot and the colon, a transcendent equation about locomotive efficiency of the critical squirm step was deduced and solved to instruct the design of the robot. Last, in vitro experiments in the fresh colon of a pig were performed. The results show that this kind of microrobot can propel itself freely and reliably in the soft viscoelastic colon. Finally, future areas of research are noted.

Chemogenomics Mapping of Potential Drugs and Targets for Treatment of Multiple Myeloma

2021 ◽  
Author(s):  
Shifan Ma ◽  
Xiang-Qun Xie
Keyword(s):  
Multiple Myeloma ◽  
Gene Signature ◽  
Therapeutic Interventions ◽  
Data Sets ◽  
Diagnostic Biomarkers ◽  
Risk Of Death ◽  
Pathological Mechanism ◽  
Search Data ◽  
Drug Reposition

Abstract Multiple myeloma (MM) is the second common hematological malignancy affecting about 352,000 worldwide. Some subgroups of MM patients still cannot benefit from the currently available anti-MM drugs and therefore are at high risk of death. The pathological mechanism of MM remains to be unraveled. The identification of a global gene signature for MM might lead toward development of novel diagnostics and therapeutic interventions. Here, we identified common differentially expressed genes (DEGs) shared by 30 MM microarray data sets and compared the common DEGs with those induced by genetic or chemical perturbations. We found some potential therapeutic targets for MM treatment, for example RARA, FGFR1, PML, ROR1, SLAMF7, MTDH and Daxx. as modulating them can reverse the MM-induced gene signature. Based on our analysis results, we also predicted and validated some drug reposition, such as Imatinib, Decitabine, Dexamethasone, Vincristine, Paclitaxel, as well as Bortezomib plus Bafilomycin A1 combination for MM treatment by a literature search, data mining, and in vitro bioassays. This study could provide guidance and indications for the development of MM specific diagnostic biomarkers, indication predictors and therapeutic treatment.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

2049-P: The Chd4 Helicase of the Nucleosome Remodeling and Deacetylase Complex Modulates Pdx1 Target Gene Expression In Vitro

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2049-P
Author(s):  
REBECCA K. DAVIDSON ◽  
NOLAN CASEY ◽  
JASON SPAETH
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Nucleosome Remodeling ◽  
Target Gene Expression

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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