scholarly journals Elimination of Epiplakin by Gene Targeting Results in Acceleration of Keratinocyte Migration in Mice

2006 ◽  
Vol 26 (2) ◽  
pp. 548-558 ◽  
Author(s):  
Mizuki Goto ◽  
Hideaki Sumiyoshi ◽  
Takao Sakai ◽  
Reinhard Fässler ◽  
Shihoka Ohashi ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Epidermal Keratinocytes ◽  
Wild Type ◽  
Wild Mice ◽  
Keratin Filaments ◽  
Explant Cultures ◽  
Skin Explants ◽  
The Difference ◽  
Normal Epidermis ◽  
Keratin 6

ABSTRACT Epiplakin (EPPK) was originally identified as a human epidermal autoantigen. To identify the function of epiplakin, we generated epiplakin “knockout” mice. These mice developed normally, with apparently normal epidermis and hair. Electron microscopy after immunostaining revealed the presence of EPPK adjacent to keratin filaments in wild-type mice, suggesting that epiplakin might associate with keratin. The appearance and localization of keratin bundles in intact epidermal keratinocytes of EPPK−/− mice were similar to those in wild-type mice. Wounds on the backs of EPPK−/− mice closed more rapidly than those on the backs of wild-type and heterozygous mice. The outgrowth of keratinocytes from skin explants from knockout mice was enhanced compared to outgrowth from explants from wild-type mice, even in the presence of mitomycin C, suggesting that the difference in keratinocyte outgrowth might be due to a difference in the speed of migration of keratinocytes. At wound edges in wild-type mice, EPPK was expressed in proliferating keratinocytes in conjunction with keratin 6. In EPPK−/− mice, no similar proliferating keratinocytes were observed, but migrating keratinocytes weakly expressed keratin 6. EPPK was coexpressed with keratin 6 in some keratinocytes in explant cultures from wild mice. We propose that EPPK might be linked functionally with keratin 6.

Attenuated defense response and low basal blood pressure in orexin knockout mice

2003 ◽  
Vol 285 (3) ◽  
pp. R581-R593 ◽  
Author(s):  
Yuji Kayaba ◽  
Akira Nakamura ◽  
Yoshitoshi Kasuya ◽  
Takashi Ohuchi ◽  
Masashi Yanagisawa ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Knockout Mice ◽  
Defense Response ◽  
Adrenergic Blockade ◽  
Wild Type ◽  
Gaba A ◽  
Arterial Blood ◽  
Basal Blood Pressure ◽  
The Difference ◽  
Fight Or Flight Response

The perifornical area of the hypothalamus has been known as the center for the defense response, or “fight or flight” response, which is characterized by a concomitant rise in arterial blood pressure (AP), heart rate (HR), and respiratory frequency (Rf). We examined whether orexin, a recently identified hypothalamic neuropeptide, contributes to the defense response and basal cardiovascular regulation using orexin knockout mice. Microinjection of a GABA-A receptor antagonist, bicuculline methiodide (0.1-1 mM in 20 nl), to the perifornical area in urethane-anesthetized wild-type mice elicited dose-dependent increases in AP, HR, and Rf. Although similar changes were observed in orexin knockout mice, intensities were smaller and duration was shorter than those in wild-type mice. Moreover, in an awake and freely moving condition, telemeter-indwelling orexin knockout mice showed diminished cardiovascular and behavioral responses to emotional stress in the resident-intruder test. We also found that basal AP in orexin knockout mice was significantly lower in both anesthetized (117 ± 8 mmHg in wild type and 92 ± 3 in knockout) and conscious (125 ± 6 mmHg in wild type and 109 ± 2 in knockout) conditions. α-Adrenergic blockade with prazosin or ganglion blockade with hexamethonium canceled the difference in basal AP. HR and cardiac contractile parameters by echocardiography did not differ between the two strains of mice. These results indicate lower sympathetic vasoconstrictor tone in knockout mice. The present study suggests that orexin-containing neurons in the perifornical area play a role as one of the efferent pathways of defense response and also operate as a regulator of AP at basal condition by activating sympathetic outflow.

SK2 channel deletion reduces susceptibility to bupivacaine-induced cardiotoxicity in mouse

2021 ◽  
pp. 096032712110109
Author(s):  
H Chen ◽  
Z Jin ◽  
Z Fu ◽  
F Xia
Keyword(s):  
Regional Anesthesia ◽  
Intravenous Injection ◽  
Postoperative Analgesia ◽  
Knockout Mice ◽  
Qt Interval ◽  
Qrs Complex ◽  
Wild Type ◽  
The Difference

Bupivacaine is frequently used for regional anesthesia and postoperative analgesia. However, an inadvertent intravenous injection can cause severe cardiotoxicity, manifesting as arrhythmia, hypotension, and even cardiac asystole. The mechanism of bupivacaine-mediated cardiotoxicity remains unclear. SK2 knockout mice (SK) and wild-type mice (WT) were divided into four groups, with 12 mice per group. We determined the difference in bupivacaine cardiotoxicity between SK2 knockout and WT mice by measuring the time to the first arrhythmia (Tarrhythmia) and the time to asystole (Tasystole). Secondary indicators of cardiotoxicity were the time from the beginning of bupivacaine infusion to 20% prolongation of the QT interval (TQT) and the time to 20% widening of the QRS complex (TQRS). Tarrhythmia and Tasystole were significantly longer in the SK-bupi group than in the WT-bupi group (both P < 0.05). TQT and TQRS were longer in the SK-bupi group than in the WT-bupi group (all P < 0.05). The time to 25%, 50%, and 75% reduction in HR in the SK-bupi group was significantly longer than in the WT-bupi group (all P < 0.05). Knocking out the SK2 channel can reduce bupivacaine-induced cardiotoxicity in the mouse.

scholarly journals Glycerol Improves Skin Lesion Development in the Imiquimod Mouse Model of Psoriasis: Experimental Confirmation of Anecdotal Reports from Patients with Psoriasis

2021 ◽  
Vol 22 (16) ◽  
pp. 8749
Author(s):  
Vivek Choudhary ◽  
Ismail Kaddour-Djebbar ◽  
Victoria E. Custer ◽  
Rawipan Uaratanawong ◽  
Xunsheng Chen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Knockout Mice ◽  
Severity Index ◽  
Skin Lesions ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Wild Type ◽  
Lesion Development ◽  
Beneficial Effects ◽  
National Psoriasis Foundation

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol’s effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.

scholarly journals Ficolin B in Diabetic Kidney Disease in a Mouse Model of Type 1 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Charlotte Berg Holt ◽  
Jakob Appel Østergaard ◽  
Esben Axelgaard ◽  
Gitte Krogh Nielsen ◽  
Yuichi Endo ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Diabetic Mice ◽  
Wild Type ◽  
Renal Hypertrophy ◽  
Kidney Weight ◽  
Diabetic Kidney ◽  
In The Wild ◽  
The Difference ◽  
Mannan Binding Lectin

Background.The innate immune system may have adverse effects in diabetes and cardiovascular disease. The complement system seems to play a key role through erroneous complement activation via hyperglycaemia-induced neoepitopes. Recently mannan-binding lectin (MBL) was shown to worsen diabetic kidney changes. We hypothesize that mouse ficolin B exerts detrimental effects in the diabetic kidney as seen for MBL.Methods.We induced diabetes with streptozotocin in female wild-type mice and ficolin B knockout mice and included two similar nondiabetic groups. Renal hypertrophy and excretion of urinary albumin and creatinine were quantified to assess diabetic kidney damage.Results.In the wild-type groups, the kidney weighed 24% more in the diabetic mice compared to the controls. The diabetes-induced increase in kidney weight was 29% in the ficolin B knockout mice, that is, equal to wild-type animals (two-way ANOVA,P=0.60). In the wild-type mice the albumin-to-creatinine ratio (ACR) was 32.5 mg/g higher in the diabetic mice compared to the controls. The difference was 62.5 mg/g in the ficolin B knockout mice, but this was not significantly different from the wild-type animals (two-way ANOVA,P=0.21).Conclusions.In conclusion, the diabetes-induced effects on kidney weight and ACR were not modified by the presence or absence of ficolin B.

scholarly journals Distribution and Severity of Placental Lesions Caused by the Chlamydia abortus 1B Vaccine Strain in Vaccinated Ewes

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 543
Author(s):  
Sergio Gastón Caspe ◽  
Javier Palarea-Albaladejo ◽  
Clare Underwood ◽  
Morag Livingstone ◽  
Sean Ranjan Wattegedera ◽  
...  
Keyword(s):  
Disease Outbreaks ◽  
Principal Component ◽  
Placental Pathology ◽  
Wild Type ◽  
Cell Infiltrate ◽  
Chlamydia Abortus ◽  
Vaccine Type ◽  
The Difference ◽  
Enzootic Abortion Of Ewes

Chlamydia abortus infects livestock species worldwide and is the cause of enzootic abortion of ewes (EAE). In Europe, control of the disease is achieved using a live vaccine based on C. abortus 1B strain. Although the vaccine has been useful for controlling disease outbreaks, abortion events due to the vaccine have been reported. Recently, placental pathology resulting from a vaccine type strain (vt) infection has been reported and shown to be similar to that resulting from a natural wild-type (wt) infection. The aim of this study was to extend these observations by comparing the distribution and severity of the lesions, the composition of the predominating cell infiltrate, the amount of bacteria present and the role of the blood supply in infection. A novel system for grading the histological and pathological features present was developed and the resulting multi-parameter data were statistically transformed for exploration and visualisation through a tailored principal component analysis (PCA) to evaluate the difference between them. The analysis provided no evidence of meaningful differences between vt and wt strains in terms of the measured pathological parameters. The study also contributes a novel methodology for analysing the progression of infection in the placenta for other abortifacient pathogens.

scholarly journals A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yağmur Demircan Yalçın ◽  
Taylan Berkin Töral ◽  
Sertan Sukas ◽  
Ender Yıldırım ◽  
Özge Zorlu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Drug Resistant ◽  
Wild Type ◽  
Gene Expressions ◽  
Before And After ◽  
The Difference ◽  
Selection Of ◽  
Resistant Cells

AbstractWe report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Conductivity of the running buffer was matched the conductivity of cytoplasm of wild type K562 and CCRF-CEM cells. Results showed that DEP responses of drug resistant and wild type K562 cells were statistically discriminative (at p = 0.05 level) at 200 mS/m buffer conductivity and at 8.6 MHz working frequency of DEP-D unit. For CCRF-CEM cells, conductivity and frequency values were 160 mS/m and 6.2 MHz, respectively. Our approach enabled discrimination of resistant cells in a group by setting up a threshold provided by the conductivity of running buffer. Subsequent selection of drug resistant cells can be applied to investigate variations in gene expressions and occurrence of mutations related to drug resistance.

scholarly journals Significant Associations of lncRNA H19 Genotypes with Susceptibility to Childhood Leukemia in Taiwan

2021 ◽  
Vol 14 (3) ◽  
pp. 235
Author(s):  
Jen-Sheng Pei ◽  
Chao-Chun Chen ◽  
Wen-Shin Chang ◽  
Yun-Chi Wang ◽  
Jaw-Chyun Chen ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Childhood Leukemia ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Single Nucleotide ◽  
Genotypic Distribution ◽  
Heterozygous Variant ◽  
Significant Difference ◽  
The Difference

The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08–2.14, p = 0.0429) and 1.94 (95%CI, 1.15–3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13–1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.

scholarly journals IL-17F depletion accelerates chitosan conduit guided peripheral nerve regeneration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Feixiang Chen ◽  
Weihuang Liu ◽  
Qiang Zhang ◽  
Ping Wu ◽  
Ao Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Knockout Mice ◽  
Inflammatory Markers ◽  
Nerve Repair ◽  
Peripheral Nerve Regeneration ◽  
Wild Type ◽  
Anti Inflammatory

AbstractPeripheral nerve injury is a serious health problem and repairing long nerve deficits remains a clinical challenge nowadays. Nerve guidance conduit (NGC) serves as the most promising alternative therapy strategy to autografts but its repairing efficiency needs improvement. In this study, we investigated whether modulating the immune microenvironment by Interleukin-17F (IL-17F) could promote NGC mediated peripheral nerve repair. Chitosan conduits were used to bridge sciatic nerve defect in IL-17F knockout mice and wild-type mice with autografts as controls. Our data revealed that IL-17F knockout mice had improved functional recovery and axonal regeneration of sciatic nerve bridged by chitosan conduits comparing to the wild-type mice. Notably, IL-17F knockout mice had enhanced anti-inflammatory macrophages in the NGC repairing microenvironment. In vitro data revealed that IL-17F knockout peritoneal and bone marrow derived macrophages had increased anti-inflammatory markers after treatment with the extracts from chitosan conduits, while higher pro-inflammatory markers were detected in the Raw264.7 macrophage cell line, wild-type peritoneal and bone marrow derived macrophages after the same treatment. The biased anti-inflammatory phenotype of macrophages by IL-17F knockout probably contributed to the improved chitosan conduit guided sciatic nerve regeneration. Additionally, IL-17F could enhance pro-inflammatory factors production in Raw264.7 cells and wild-type peritoneal macrophages. Altogether, IL-17F may partially mediate chitosan conduit induced pro-inflammatory polarization of macrophages during nerve repair. These results not only revealed a role of IL-17F in macrophage function, but also provided a unique and promising target, IL-17F, to modulate the microenvironment and enhance the peripheral nerve regeneration.

scholarly journals A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4743
Author(s):  
Romain Duroux ◽  
Anne Mandeau ◽  
Gaelle Guiraudie-Capraz ◽  
Yannick Quesnel ◽  
Estelle Loing
Keyword(s):  
Physiological Role ◽  
Olfactory Receptors ◽  
Major Constituent ◽  
Epidermal Keratinocytes ◽  
Functional Assay ◽  
Skin Explants ◽  
Stress Mediators ◽  
Double Blinded ◽  
Split Face

Olfactory receptors (ORs) are expressed and active in various human tissues, including the skin. Although the sense of smell plays an important physiological role in the regulation of mood and stress, a link between olfactive compounds, ORs, and skin stress has yet to be established. This study aims to investigate the role of newly identified skin ORs and agonists in the modulation of skin stress. Screening for odorant molecules was done with cAMP functional assay to identify OR agonists. RT-qPCR and immunofluorescence microscopy were conducted to identify and quantify ORs in epidermal keratinocytes (NHEKs) and human skin explants, as well as to evaluate specific markers (G6PDH, loricrin, and γH2AX) of stress-induced skin alterations. A randomized double-blinded, split-face clinical study was performed on a panel of stressed women to measure the benefits of OR agonist treatment for skin. Three new ORs (OR10A6, OR2AG2, and OR11H4) were identified in skin. A specific Rose extract and its major constituent (phenylethyl alcohol) were found to activate these ORs. The extract composition was revealed by both GC/FID and GC/MS analyses simultaneously and showed the presence of 34 volatiles molecules. Moreover, epinephrine induces a skin stress response characterized by increased expression of G6PD, loricrin, and γH2AX biomarkers, and a decrease of OR expression. These effects were prevented in the presence of rose extract and its benefits were confirmed clinically by a decrease in the appearance of under-eye dark circles. Altogether, our findings suggest that ORs may represent a new, promising way to treat stress-associated skin disorders.

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