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Thuy Duong, Nguyen Thi. "SELECTION OF INDIGENOUS STRAINS (Paecilomyces lilacinus) PARASITIZE Meloidogyne spp. ISOLATED FROM BA RIA – VUNG TAU PROVINCE." Vietnam Journal of Science and Technology 55, no. 1A (April 24, 2018): 27. http://dx.doi.org/10.15625/2525-2518/55/1a/12379.
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Twenty two Paecilomyces lilacinus strains were isolated from forest soils and black pepper rhizospheres in Ba Ria –Vung Tau Province. The ability to degrade chitin of PB 3.3, PB 2.9, QT2, and QT5 strains was high. The ability to degrade casein of PB 1.3, PB 2.10, KL5, and KL6 strains was efficient. And then, these strains were parasitized females and egg masses of Meloidogyne spp. in vitro. In female parasitism test, the rates of parasitizing female nematodes reached more than 50 % after treating for 2 days. Four strains of PB 2.10, PB 1.3, KL6 and QT5 belonged to the first group achieved the highest parasitic (> 90 %) effects on female after 3 days of incubation. In egg masses parasitism test, three strains of PB 1.3, PB 2.10 and QT5 exhibited 83.33 %, 75 % and 75 % parasitism on egg masses after 11 days of incubation. The rates of parasitizing female were higher than egg masses. Three selected strains from the experiments were PB 1.3, PB 2.10 and QT5.
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LEIGH, I. M., H. NAVSARIA, P. E. PURKIS, I. A. MCKAY, P. E. BOWDEN, and P. N. RIDDLE. "Keratins (Kl6 and Kl7) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro." British Journal of Dermatology 133, no. 4 (October 1995): 501–11. http://dx.doi.org/10.1111/j.1365-2133.1995.tb02696.x.
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Zhao, Lina, Xinxin Xia, Ting Yuan, Junying Zhu, Zhen Shen, and Min Li. "Molecular Epidemiology of Antimicrobial Resistance, Virulence and Capsular Serotypes of Carbapenemase-Carrying Klebsiella pneumoniae in China." Antibiotics 11, no. 8 (August 13, 2022): 1100. http://dx.doi.org/10.3390/antibiotics11081100.
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This study analyzed genomic data of 4643 strains of carbapenemase-carrying Klebsiella pneumoniae (KPN) in China by using the Kleborate software package. The data showed rich diversity in carbapenemase-carrying KPN genomes, which contain not only 152 sequence types but also 90 capsular serotypes. In 2013, the transfer of carbapenemase to hypervirulent Klebsiella pneumoniae (HvKP) of KL1 and KL2 occurred, and since 2014, the propagation of carbapenemase into mammals, poultry, and insects has been detected. The ST11 capsular serotype had a reversal of the prevalence of KL47 and KL64 in 2016, with KL64 replacing KL47 as the dominant serotype. Colibactin is a very suitable indicator to differentiate KL1-type HvKP and classic Klebsiella pneumoniae. The most prevalent yersiniabactin of KL1 is ybt1 ICEKp10, and that of ST11 carbapenem-resistant KPN(ST11-CRKP) is ybt9 ICEKp3. The virulence genes of KL1 carbapenem-resistant hypervirulent KPN (KL1-CRHvKP), as well as ST65- and ST86-type KL2-CRHvKP, were not lost after carbapenemase was obtained.
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Edd, Shannon N., Patrick Omoumi, Brigitte M. Jolles, and Julien Favre. "Longitudinal Femoral Cartilage T2 Relaxation Time and Thickness Changes with Fast Sequential Radiographic Progression of Medial Knee Osteoarthritis—Data from the Osteoarthritis Initiative (OAI)." Journal of Clinical Medicine 10, no. 6 (March 21, 2021): 1294. http://dx.doi.org/10.3390/jcm10061294.
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This study tested for longitudinal changes in femoral cartilage T2 relaxation time and thickness in fast-progressing medial femorotibial osteoarthritis (OA). From the Osteoarthritis Initiative (OAI) database, nineteen knees fulfilled the inclusion criteria, which included medial femorotibial OA and sequential progression from Kellgren–Lawrence grade (KL) 1 to KL2 to KL3 within five years. Median T2 value and mean thickness were calculated for six condylar volumes of interest (VOIs; medial/lateral anterior, central, posterior) and six sub-VOIs (medial/lateral anterior external, central, internal). T2 value and thickness changes between severity timepoints were tested using repeated statistics. T2 values increased between KL1 and KL2 and between KL1 and KL3 in the medial compartment (p ≤ 0.02), whereas both increases and decreases were observed between the same timepoints in the lateral compartment (p ≤ 0.02). Cartilage thickness decreased in VOI/subVOIs of the medial compartment from KL1 to KL2 and KL3 (p ≤ 0.014). Cartilage T2 value and thickness changes varied spatially over the femoral condyles. While all T2 changes occurred in the early radiographic stages of OA, thickness changes occurred primarily in the later stages. These data therefore support the use of T2 relaxation time analyses in methods of detecting disease-related change during early OA, a valuable period for therapeutic interventions.
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Aoshima, Yoichiro, Yasunori Enomoto, Shigeki Muto, Shiori Meguro, Hideya Kawasaki, Isao Kosugi, Tomoyuki Fujisawa, et al. "Gremlin-1 for the Differential Diagnosis of Idiopathic Pulmonary Fibrosis Versus Other Interstitial Lung Diseases: A Clinical and Pathophysiological Analysis." Lung 199, no. 3 (March 26, 2021): 289–98. http://dx.doi.org/10.1007/s00408-021-00440-y.
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Abstract Purpose The differential diagnosis of interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF) versus other non-IPF ILDs, is important for selecting the appropriate treatment. This retrospective study aimed to explore the utility of gremlin-1 for the differential diagnosis. Methods Serum gremlin-1 concentrations were measured using an ELISA in 50 patients with IPF, 42 patients with non-IPF ILD, and 30 healthy controls. The baseline clinical data, including pulmonary functions, prognosis, and three serum biomarkers (Krebs von den Lungen-6 [KL6], surfactant protein-D [SP-D], and lactate dehydrogenase [LDH]), were obtained through a medical record review for analyzing their associations with serum gremlin-1 concentrations. To evaluate the origin of gremlin-1, we performed immunostaining on lung sections. Results Serum gremlin-1 concentrations were significantly higher in patients with IPF (mean concentration, 14.4 ng/mL), followed by those with non-IPF ILD (8.8 ng/mL) and healthy controls (1.6 ng/mL). The area under the curve for IPF versus non-IPF ILDs was 0.759 (95% confidence interval, 0.661–0.857), which was superior to that of KL6/SP-D/LDH. The sensitivity and specificity for gremlin-1 (cutoff, 10.4 ng/mL) was 72 and 69%, respectively. By contrast, serum gremlin-1 concentrations were not associated with the pulmonary functions nor the prognosis in all patients with ILDs. In immunostaining, the gremlin-1 was broadly upregulated in IPF lungs, particularly at myofibroblasts, bronchiolar/alveolar epithelium, and CD163-positive M2-like macrophages. Conclusions Gremlin-1 may be a useful biomarker to improve the diagnostic accuracy for IPF compared to non-IPF ILDs, suggesting a role of this molecule in the pathogenesis of IPF.
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Zhou, Ying, Chunyang Wu, Bingjie Wang, YanLei Xu, Huilin Zhao, Yinjuan Guo, Xiaocui Wu, et al. "Characterization difference of typical KL1, KL2 and ST11-KL64 hypervirulent and carbapenem-resistant Klebsiella pneumoniae." Drug Resistance Updates 67 (March 2023): 100918. http://dx.doi.org/10.1016/j.drup.2023.100918.
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Ballester, Milara, and Cortijo. "Mucins as a New Frontier in Pulmonary Fibrosis." Journal of Clinical Medicine 8, no. 9 (September 11, 2019): 1447. http://dx.doi.org/10.3390/jcm8091447.
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Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pulmonary disease with a median survival of 3–5 years after diagnosis. Recent evidence identifies mucins as key effectors in cell growth and tissue remodeling processes compatible with the processes observed in IPF. Mucins are classified in two groups depending on whether they are secreted (secreted mucins) or tethered to cell membranes (transmembrane mucins). Secreted mucins (MUC2, MUC5AC, MUC5B, MUC6-8 and MUC19) are released to the extracellular medium and recent evidence has shown that a promoter polymorphism in the secreted mucin MUC5B is associated with IPF risk. Otherwise, transmembrane mucins (MUC1, MUC3, MUC4, MUC12-17 and MUC20) have a receptor-like structure, sensing the external environment and activating intracellular signal transduction pathways essential for mucosal maintenance and damage repair. In this context, the extracellular domain can be released to the external environment by metalloproteinase action, increased in IPF, thus activating fibrotic processes. For example, several studies have reported increased serum extracellular secreted KL6/MUC1 during IPF acute exacerbation. Moreover, MUC1 and MUC4 overexpression in the main IPF cells has been observed. In this review we summarize the current knowledge of mucins as promising druggable targets for IPF.
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Conticini, E., M. D’alessandro, L. Bergantini, D. Castillo, P. Falsetti, P. Cameli, E. Bargagli, L. Cantarini, and B. Frediani. "POS0823 KL-6 IN ANCA-ASSOCIATED VASCULITIS PATIENTS WITH AND WITHOUT ILD: A MACHINE LEARNING APPROACH." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 702.2–703. http://dx.doi.org/10.1136/annrheumdis-2022-eular.480.
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BackgroundANCA-associated vasculitis (AAV) are small vessel vasculitis which may variously affect upper and lower respiratory tract. Patients with microscopic polyangiitis (MPA) and, less commonly, granulomatosis with polyangiitis (GPA), especially those who are ANCA-MPO-positive, may suffer from interstitial lung disease (ILD), which is associated with high morbidity and mortality as it is often underdiagnosed and responds poorly to conventional treatmentsObjectivesIn this study, we aimed to assess whether Krebs von den Lungen-6 (KL-6), a marker of fibrotic ILD, may be useful for distinguishing AAV patients with ILD from those without ILD, and whether its changes over time are correlated with disease activity.MethodsWe enrolled all consecutive patients evaluated in the period December 2020 - November 2021. Inclusion criteria were a diagnosis of GPA or MPA, active disease, and eligibility for Rituximab treatment according to EULAR recommendations. All patients underwent concomitant rheumatological and pneumological evaluation, lung function tests, routine blood tests, autoimmunity evaluation and KL-6 assay. Current and previous treatments, Birmingham vasculitis score (BVAS) and vasculitis damage index were also recorded.ResultsA total of 13 patients (Table 1) were enrolled. One was excluded due to a concomitant diagnosis of lung cancer. Higher serum KL-6 were in AAV-ILD compared with those without ILD (972.8±398.5 vs 305.4±93.9, p=0.0040). Area under the Receiver Operating Characteristics curve showed 100% of the diagnostic performance of KL-6 for identifying the ILD involvement (accuracy 91.7%) and the best cutoff value of 368 U/mL (Sensitivity 100% and specificity 87.5%). The decision-tree model showed a 33% improvement in class purity using a cut-off value of 513 U/mL to distinguish AAV patients with and without ILD (Figure 1). Stratifying AAV patients as MPA and GPA with and without ILD considering T0 and T1 KL-6, the model obtained an improvement of 40% for classifying GPA non-ILD with a T0 serum KL-6 cut-off value of 513 U/mL and a T1 KL-6 cut-off of 301 U/mL. A direct correlation was found between serum T0 KL-6 and T0 BVAS (r=0.578, p=0.044).Table 1.Patients’ featuresSex/ageDiagnosisLength of disease * (months)Organs involvedType of lung involvementT0 KL6 levelsT0 BVAST0 VDIT1 KL6 levelsT1 BVAST1 VDIF/83MPA28Lung, kidney, PNSILD, alveolar hemorrhage6258732507M/48GPA1Lung, kidney, nose, eyeNodules35218027920F/55GPA252Lung, skinNodules40115360233F/38MPA1Skin-34760---F/74MPA180Kidney, PNS-36811541405M/77MPA8Lung, kidney, PNS, skinILD, alveolar hemorrhage982241---F/49GPA60Nose, eye-1226211602M/60MPA40Skin, PNS-20591---F/39GPA4Nose-31063---M/71GPA24Lung, eye, jointsNodules, ILD152893---F/64MPA24LungILD7564-10030-F/59GPA72LungNodules3384--0-Figure 1.ROC curve and decision tree modelConclusionOur multicentre study demonstrated KL-6 as a reliable, non-invasive and easy-to-perform marker of ILD in AAV patients and its helpfulness for disease activity assessment. Changes in serum concentrations of KL-6 over time could be useful for monitoring AAV patients. Further study of KL-6 as a marker of response to therapy during long-term follow-up would also be worthwhile.Disclosure of InterestsNone declared
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Milara, Javier, Beatriz Ballester, Paula Montero, Juan Escriva, Enrique Artigues, Manuel Alós, Alfonso Pastor-Clerigues, Esteban Morcillo, and Julio Cortijo. "MUC1 intracellular bioactivation mediates lung fibrosis." Thorax 75, no. 2 (December 4, 2019): 132–42. http://dx.doi.org/10.1136/thoraxjnl-2018-212735.
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BackgroundSerum KL6/mucin 1 (MUC1) has been identified as a potential biomarker in idiopathic pulmonary fibrosis (IPF), but the role of MUC1 intracellular bioactivation in IPF is unknown.ObjectiveTo characterise MUC1 intracellular bioactivation in IPF.Methods and resultsThe expression and phosphorylation of Thr41 and Tyr46 on the intracellular MUC1-cytoplasmic tail (CT) was increased in patients with IPF (n=22) compared with healthy subjects (n=21) and localised to fibroblasts and hyperplastic alveolar type II cells. Transforming growth factor (TGF)-β1 phosphorylated SMAD3 and thereby increased the phosphorylation of MUC1-CT Thr41 and Tyr46 in lung fibroblasts and alveolar type II cells, activating β-catenin to form a phospho-Smad3/MUC1-CT and MUC1-CT/β-catenin nuclear complex. This nuclear complex promoted alveolar epithelial type II and fibroblast to myofibroblast transitions, as well as cell senescence and fibroblast proliferation. The inhibition of MUC1-CT nuclear translocation using the inhibitor, GO-201 or silencing MUC1 by siRNA, reduced myofibroblast transition, senescence and proliferation in vitro. Bleomycin-induced lung fibrosis was reduced in mice treated with GO-201 and in MUC1-knockout mice. The profibrotic lectin, galectin-3, directly activated MUC1-CT and served as a bridge between the TGF-β receptor and the MUC1-C domain, indicating TGF-β1-dependent and TGF-β1-independent intracellular bioactivation of MUC1.ConclusionsMUC1 intracellular bioactivation is enhanced in IPF and promotes fibrotic processes that could represent potential druggable targets for IPF.
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Bentov, Itay, Goutham Narla, Hagit Schayek, Kuhihara Akita, Stephen R. Plymate, Derek LeRoith, Scott L. Friedman, and Haim Werner. "Insulin-Like Growth Factor-I Regulates Krüppel-Like Factor-6 Gene Expression in a p53-Dependent Manner." Endocrinology 149, no. 4 (January 3, 2008): 1890–97. http://dx.doi.org/10.1210/en.2007-0844.
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High-circulating IGF-I concentrations are associated with an increased risk for breast, prostate, and colorectal cancer. Krüppel-like factor-6 (KLF6) is a zinc finger tumor suppressor inactivated in prostate and other types of cancer. We have previously demonstrated that KLF6 is a potent transactivator of the IGF-I receptor promoter. The aim of the present study was to examine the potential regulation of KLF6 gene expression by IGF-I. The human colon cancer cell lines HCT116 +/+ and −/− (with normal and disrupted p53, respectively) were treated with IGF-I. Western blots, quantitative RT-PCR, and transfection assays were used to evaluate the effect of IGF-I on KLF-6 production. Signaling pathway inhibitors were used to identify the mechanisms responsible for regulation of KLF6 expression. Small interfering RNA against p53 and KLF6 was used to assess the role of p53 in regulation of KLF6 expression by IGF-I and to evaluate KLF6 involvement in cell cycle control. Results obtained showed that IGF-I stimulated KLF-6 transcription in cells with normal, but not disrupted, p53, suggesting that KLF6 is a downstream target for IGF-I action. Stimulation of KLF6 expression by IGF-I in a p53-dependent manner may constitute a novel mechanism of action of IGF-I, with implications in normal cell cycle progression and cancer biology.
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Haftek, M., M. J. Staquet, J. Viac, D. Schmitt, and J. Thivolet. "Immunogold labeling of keratin filaments in normal human epidermal cells with two anti-keratin monoclonal antibodies." Journal of Histochemistry & Cytochemistry 34, no. 5 (May 1986): 613–18. http://dx.doi.org/10.1177/34.5.2422248.
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We report on application of the highly sensitive and specific immunogold labeling method for ultrastructural investigation of keratin intermediate filament antigens in human epidermal cell suspensions. Triton X-100 pretreated cells proved accessible to the colloidal gold conjugate, thus enabling keratin filament bundles to be labeled. Anti-keratin KL1 and KL2 monoclonal antibodies were raised in mice after immunization with either human stratum corneum-isolated keratins or keratins extracted from human epidermal cells suspensions, respectively. Immunoelectron microscopy confirmed immunofluorescence and immunoperoxidase results of epidermal keratinocyte staining, and revealed two different antibody reactivity patterns: KL2 reacted with keratin filaments in keratinocytes of all epidermal layers, whereas antigen to KL1 was detected only on keratin of the suprabasal layers, not on the basal keratinocyte tonofilaments. The monoclonal antibody-recognized epitopes were specific for the keratin filaments. Vimentin-rich cells (melanocytes) were not stained in the same epidermal cell suspensions. Additionally, two distinct ultrastructural patterns of keratin filament epitope labeling were observed. KL1 and KL2 monoclonal antibodies react with two different antigenic determinants, depending on the stage of keratinocyte differentiation, and may therefore be used for immunohistochemical studies of various keratin-containing cells in normal and pathologic conditions.
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Ménesguen, Y., M. C. Lépy, Y. Ito, M. Yamashita, S. Fukushima, T. Tochio, M. Polasik, et al. "Structure of single KL0–, double KL1–, and triple KL2 − ionization in Mg, Al, and Si targets induced by photons, and their absorption spectra." Radiation Physics and Chemistry 194 (May 2022): 110048. http://dx.doi.org/10.1016/j.radphyschem.2022.110048.
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Tremblay, Maxime A., Raifish E. Mendoza-Villarroel, Nicholas M. Robert, Francis Bergeron, and Jacques J. Tremblay. "KLF6 cooperates with NUR77 and SF1 to activate the human INSL3 promoter in mouse MA-10 leydig cells." Journal of Molecular Endocrinology 56, no. 3 (April 2016): 163–73. http://dx.doi.org/10.1530/jme-15-0139.
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Insulin-like 3 (INSL3), a Leydig cell-specific hormone, is essential for testis descent during foetal life and bone metabolism in adults. Despite its essential roles in male reproductive and bone health, very little is known regarding its transcriptional regulation in Leydig cells. To date, few transcription factors have been shown to activate INSL3 promoter activity: the nuclear receptors AR, NUR77, COUP-TFII and SF1. To identify additional regulators, we have isolated and performed a detailed analysis of a 1.1 kb human INSL3 promoter fragment. Through 5′ progressive deletions and site-directed mutagenesis, we have mapped a 10 bp element responsible for about 80% of INSL3 promoter activity in Leydig cells. This element is identical to the CPE element of the placental-specific glycoprotein-5 (PSG5) promoter that is recognized by the developmental regulator Krüppel-like factor 6 (KLF6). Using PCR and western blotting, we found that KLF6 is expressed in several Leydig and Sertoli cell lines. Furthermore, immunohistochemistry on adult mouse testis revealed the presence of KLF6 in the nuclei of both Leydig and Sertoli cells. KLF6 binds to the 10 bp KLF element at −108 bp and activates the −1.1 kb human, but not the mouse, INSL3 promoter. KLF6-mediated activation of the human INSL3 promoter required an intact KLF element as well as Leydig/Sertoli-enriched factors because KLF6 did not stimulate the human INSL3 promoter activity in CV-1 fibroblast cells. Consistent with this, we found that KLF6 transcriptionally cooperates with NUR77 and SF1. Collectively, our results identify KLF6 as a regulator of human INSL3 transcription.
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Saita, Yoshitomo, Yohei Kobayashi, Hirofumi Nishio, Takanori Wakayama, Shin Fukusato, Sayuri Uchino, Yasumasa Momoi, Hiroshi Ikeda, and Kazuo Kaneko. "Predictors of Effectiveness of Platelet-Rich Plasma Therapy for Knee Osteoarthritis: A Retrospective Cohort Study." Journal of Clinical Medicine 10, no. 19 (September 29, 2021): 4514. http://dx.doi.org/10.3390/jcm10194514.
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There has recently been growing interest worldwide in biological therapies such as platelet-rich plasma injection for the treatment of knee osteoarthritis. However, predicting the effectiveness of platelet-rich plasma therapy remains uncertain. Therefore, this retrospective cohort study was performed to assess a range of predictors for the effectiveness of platelet-rich plasma therapy in treating knee osteoarthritis. The study included 517 consecutive patients who underwent three injections of leucocyte-poor platelet-rich plasma therapy from 2016 to 2019 at a single institution. The treatment outcomes, including patient-oriented outcomes (visual analogue scale score and Knee Injury and Osteoarthritis Outcome Score), were analyzed and compared according to the severity of knee osteoarthritis based on Kellgren–Lawrence (KL) grading using standing plain radiographs. Fisher’s exact test, univariate regression, and multivariate regression were used for data analysis. Patient-oriented outcomes were significantly improved 6 and 12 months after platelet-rich plasma therapy. The overall responder rate in patients who met the Outcome Measures in Rheumatology (OMERACT)–Osteoarthritis Research Society International (OARSI) responder criteria was 62.1%. The responder rate was significantly lower in patients with severe knee osteoarthritis (KL4, 50.9%) than in those with mild (KL2, 75.2%) and moderate (KL3, 66.5%) knee osteoarthritis. The multivariate logistic regression analysis revealed that deterioration of the knee osteoarthritis grade (increased KL grade) was a significant predictor of a worse clinical outcome (odds ratio, 0.58; 95% confidence interval, 0.45–0.75; p < 0.001). The relative risk for non-responders in severe (KL4) KOA was 2.1 (95% CI, 1.5–3.0) at 6 months and 2.3 (1.6–3.2) at 12 months compared with mild-to-moderate (KL2-3) KOA. The efficacy of platelet-rich plasma therapy was not affected by age, sex, body weight, or platelet count. This study revealed that the effectiveness of platelet-rich plasma therapy for the treatment of knee osteoarthritis is approximately 60% and that the effectiveness depends on the severity of knee osteoarthritis. This observation is useful not only for physicians but also for patients with knee osteoarthritis.
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Sahly, Hany, Rainer Podschun, Tobias A. Oelschlaeger, Michael Greiwe, Haralambos Parolis, David Hasty, Jörn Kekow, Uwe Ullmann, Itzhak Ofek, and Shlomo Sela. "Capsule Impedes Adhesion to and Invasion of Epithelial Cells by Klebsiella pneumoniae." Infection and Immunity 68, no. 12 (December 1, 2000): 6744–49. http://dx.doi.org/10.1128/iai.68.12.6744-6749.2000.
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ABSTRACT The adhesion of K21a, K26, K36, and K50 capsulatedKlebsiella strains to ileocecal (HCT-8) and bladder (T24) epithelial cell lines was significantly lower than that of their corresponding spontaneous noncapsulated variants K21a/3, K26/1, K36/3, and K50/3, respectively. Internalization of the bacteria by both epithelial cell lines was also significantly reduced. Similarly, a capsule-switched derivative, K2(K36), that exhibited a morphologically larger K36 capsule and formed more capsular material invaded the ileocecal epithelial cell line poorly compared to the corresponding K2 parent strain. None of the capsulated strains exhibited significant mannose-sensitive type 1 fimbriae, whereas two of the noncapsulated variants K21a/3 and K50/3 exhibited potent mannose-sensitive hemagglutinating activity. Although hemagglutinating activity that could be attributed to mannose-resistantKlebsiella type 3 fimbriae was weak in all strains, in several cases the encapsulated parent strains exhibited lower titers than their corresponding noncapsulated variants. Although the level of adhesion to the ileocecal cells is not different from adhesion to bladder cells, bacterial internalization by bladder cells was significantly lower than internalization by ileocecal cells, suggesting that bladder cells lack components required for the internalization ofKlebsiella.
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Bournazou, Eirini, Jonathan Samuels, Hua Zhou, Svetlana Krasnokutsky, Jyoti Patel, Tianzhen Han, Jenny Bencardino, et al. "Vascular Adhesion Protein-1 (VAP-1) as Predictor of Radiographic Severity in Symptomatic Knee Osteoarthritis in the New York University Cohort." International Journal of Molecular Sciences 20, no. 11 (May 29, 2019): 2642. http://dx.doi.org/10.3390/ijms20112642.
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Background: To investigate the expression of vascular adhesion protein-1 (VAP-1) in joint tissues and serum in symptomatic knee osteoarthritis (SKOA) patients and examine whether VAP-1 levels predict increased risk of disease severity in a cross-sectional study. Methods: Baseline VAP-1 expression and soluble VAP-1 (sVAP-1) levels were assessed in the synovium synovial fluid and in the serum in cohorts of patients with tibiofemoral medial knee OA and healthy subjects. Standardized fixed-flexion poster anterior knee radiographs scored for Kellgren–Lawrence (KL) grade (0–4) and medial joint space width (JSW). KL1/2 vs. KL3/4 scores defined early and advanced radiographic severity, respectively. Biochemical markers assessed in serum or synovial fluids (SF) comprised sVAP-1, interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), soluble receptor for advanced glycation end-products (sRAGE), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 4 (CCL4), cluster of differentiation 163 (CD163), high sensitivity C-reactive protein (hsCRP), and matrix metalloproteinases (MMPs)-1,-3,-9. Associations between biomarkers and radiographic severity KL1/2 vs. KL3/4 (logistic regression controlling for covariates) and pain (Spearman correlation) were evaluated. Results: Elevated levels of sVAP-1 observed in OA synovial fluid and VAP-1 expression in synovium based on immunohistochemical, microarray, and real-time quantitative polymerase chain reaction (qRT-PCR) analyses. However, serum sVAP-1 levels in OA patients were lower than in controls and inversely correlated with pain and inflammation markers (hsCRP and soluble RAGE). Soluble VAP-1 levels in serum were also lower in radiographically advanced (KL3/4) compared with early KL1/2 knee SKOA patients. Conclusion: Local (synovial fluid) semicarbazide-sensitive amine oxidase (SSAO)/sVAP-1 levels were elevated in OA and correlated with radiographic severity. However, systemic (serum) sVAP-1 levels were lower in SKOA patients than normal and inversely correlated with pain and inflammation markers. Serum sVAP-1 levels were higher in early (KL1/2) compared with advanced (KL3/4) SKOA patients.
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Anderson, Mark T., Stephanie D. Himpsl, Lindsay A. Mitchell, Leandra G. Kingsley, Elizabeth P. Snider, and Harry L. T. Mobley. "Identification of distinct capsule types associated with Serratia marcescens infection isolates." PLOS Pathogens 18, no. 3 (March 30, 2022): e1010423. http://dx.doi.org/10.1371/journal.ppat.1010423.
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Serratia marcescens is a versatile opportunistic pathogen that can cause a variety of infections, including bacteremia. Our previous work established that the capsule polysaccharide (CPS) biosynthesis and translocation locus contributes to the survival of S. marcescens in a murine model of bacteremia and in human serum. In this study, we determined the degree of capsule genetic diversity among S. marcescens isolates. Capsule loci (KL) were extracted from >300 S. marcescens genome sequences and compared. A phylogenetic comparison of KL sequences demonstrated a substantial level of KL diversity within S. marcescens as a species and a strong delineation between KL sequences originating from infection isolates versus environmental isolates. Strains from five of the identified KL types were selected for further study and electrophoretic analysis of purified CPS indicated the production of distinct glycans. Polysaccharide composition analysis confirmed this observation and identified the constituent monosaccharides for each strain. Two predominant infection-associated clades, designated KL1 and KL2, emerged from the capsule phylogeny. Bacteremia strains from KL1 and KL2 were determined to produce ketodeoxynonulonic acid and N-acetylneuraminic acid, two sialic acids that were not found in strains from other clades. Further investigation of KL1 and KL2 sequences identified two genes, designated neuA and neuB, that were hypothesized to encode sialic acid biosynthesis functions. Disruption of neuB in a KL1 isolate resulted in the loss of sialic acid and CPS production. The absence of sialic acid and CPS production also led to increased susceptibility to internalization by a human monocytic cell line, demonstrating that S. marcescens phagocytosis resistance requires CPS. Together, these results establish the capsule genetic repertoire of S. marcescens and identify infection-associated clades with sialic acid CPS components.
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Jarraya, M., F. Roemer, E. Ashbeck, J. Lynch, C. K. Kwoh, and A. Guermazi. "POS0177 HETEROGENOUS CARTILAGE DAMAGE SEEN ON MRI AMONG KNEES WITH KELLGREN-LAWRENCE 2 & 3 OSTEOARTHRITIS: WHAT ARE THE IMPLICATIONS FOR CLINICAL TRIALS?" Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 319–20. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1882.
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BackgroundThe most recent update of the Global Burden of Disease figures (GBD 2013) estimated that 242 million people were living in the world with symptomatic and activity-limiting OA of the hip and/or knee. Many potential disease-modifying osteoarthritis drugs (DMOADs) have been investigated, but to date no DMOADs that slow or stop disease progression have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA). A potential reason for the lack of demonstrated efficacy may be reliance on radiographs for defining structural inclusion and exclusion criteria for clinical trials, such as use of joint space width and Kellgren-Lawrence (KL) grade as surrogates for cartilage damage.ObjectivesTo estimate the distribution of cartilage damage seen on knee MRI in a sample of knees with radiographic KL 2 and 3 OA that would potentially qualify for a DMOAD trial.MethodsWe selected knees from the Osteoarthritis Initiative (OAI), a longitudinal cohort study of knees with or at risk of developing symptomatic radiographic OA, that met common structural inclusion criteria for DMOAD trial enrollment at OAI baseline: knees with radiographs centrally graded as KL 2 or 3 and medial minimum joint space width (mJSW) ≥ 1.5mm. A musculoskeletal radiologist with 10 years of experience in semi-quantitative MRI assessment scored knee cartilage damage in the medial and lateral tibiofemoral and patellofemoral compartments using WORMS (Whole-Organ Magnetic Resonance Imaging Score). Coronal intermediate weighted (IW) TSE and sagittal fat-suppressed IW TSE sequences on 3T MRI were used. The WORMS cartilage scores, which are based on both the extent and depth of cartilage damage, were collapsed into 4 categories: no cartilage damage (WORMS 0 and 1), focal partial or full-thickness (PT/FT) cartilage damage (WORMS 2 and 2.5), diffuse partial thickness (PT) cartilage damage (WORMS 3 and 4), and diffuse full-thickness (FT) cartilage damage (WORMS 5 and 6). We estimated the prevalence of each category of cartilage damage in KL2 and KL3 knees; 95% confidence intervals (CI) accounted for clustering at the participant-level since some participants contributed two knees to the analysis.ResultsWe identified 2,372 participants contributing 3,446 knees with radiographic OA (KL 2 and 3) and medial mJSW ≥ 1.5mm. There were 2,318 KL2 knees and 1,128 KL3 knees. The distribution of cartilage damage in each compartment by KL grade is presented in Table 1. We found no cartilage damage in any compartments in 9.8% (95%CI: 8.5, 11.1) of KL2 knees and 2.0% (95%CI: 1.1, 2.9) of KL3 knees. Cartilage damage was absent in the medial tibiofemoral compartment in 52.4% (95%CI: 50.1, 54.6) of KL2 knees, and 14.4% (95%CI: 12.2, 16.6) of KL3 knees, versus 61% (95%CI: 58.8, 63.2) of KL2 knees and 53.6% (95%CI: 50.4, 56.7) of KL3 knees in the lateral compartment. When medial and lateral compartments were combined, cartilage damage was absent in 34.8% (95%CI: 32.7, 36.9) of the KL2 knees, and 4.3% (95%CI: 3.0, 5.5) of the KL3 knees. Diffuse FT cartilage lesions in the medial compartment were found in 6.1% (95%CI: 5.0, 7.1) of KL2 knees and 42.5% (95%CI: 39.4, 45.6) of KL3 knees.ConclusionMRI screening prior to clinical trial enrollment may identify a substantial percentage of knees with normal cartilage, as well as knees with diffuse FT cartilage lesions that may not be responsive to DMOADs, depending on the mode of action of a given pharmacological compound.Disclosure of InterestsMohamed Jarraya: None declared, Frank Roemer Shareholder of: Boston Imaging Core Lab, Consultant of: California Institute of Biomedical Research, Erin Ashbeck: None declared, John Lynch: None declared, C. Kent Kwoh Consultant of: Novartis, Regeneron, LG Chem, Kolon Tissue Gene, Avalor, Grant/research support from: Pfizer, Lilly, Cumberland, Ali Guermazi Shareholder of: Stock options in BICL, Consultant of: Pfizer, TissueGene, MerckSerono, Regeneron, Novartis, AstraZeneca
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王, 维. "玄武岩发育区砂岩储层特征及控制因素：渤海南部BZ34-9区与KL6区块对比." Earth Science-Journal of China University of Geosciences 42, no. 4 (2017): 570. http://dx.doi.org/10.3799/dqkx.2017.045.
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Syafruddin, Saiful E., M. Aiman Mohtar, Wan Fahmi Wan Mohamad Nazarie, and Teck Yew Low. "Two Sides of the Same Coin: The Roles of KLF6 in Physiology and Pathophysiology." Biomolecules 10, no. 10 (September 28, 2020): 1378. http://dx.doi.org/10.3390/biom10101378.
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The Krüppel-like factors (KLFs) family of proteins control several key biological processes that include proliferation, differentiation, metabolism, apoptosis and inflammation. Dysregulation of KLF functions have been shown to disrupt cellular homeostasis and contribute to disease development. KLF6 is a relevant example; a range of functional and expression assays suggested that the dysregulation of KLF6 contributes to the onset of cancer, inflammation-associated diseases as well as cardiovascular diseases. KLF6 expression is either suppressed or elevated depending on the disease, and this is largely due to alternative splicing events producing KLF6 isoforms with specialised functions. Hence, the aim of this review is to discuss the known aspects of KLF6 biology that covers the gene and protein architecture, gene regulation, post-translational modifications and functions of KLF6 in health and diseases. We put special emphasis on the equivocal roles of its full-length and spliced variants. We also deliberate on the therapeutic strategies of KLF6 and its associated signalling pathways. Finally, we provide compelling basic and clinical questions to enhance the knowledge and research on elucidating the roles of KLF6 in physiological and pathophysiological processes.
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Miletic, Ivan, Christoph Agten, Reto Sutter, Christian Pfirrmann, and Cynthia Peterson. "Relationship of Radiographic Osteoarthritis Severity with Treatment Outcomes after Imaging-Guided Knee Injections: A Prospective Outcomes Study." RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren 190, no. 02 (June 26, 2017): 134–43. http://dx.doi.org/10.1055/s-0043-112337.
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Introduction To be able to predict which patients are more likely to have a positive treatment outcome, the purpose of this study is 1: To compare outcomes after intra-articular corticosteroid knee injections with the Kellgren and Lawrence (KL) 5 and 3 grading systems for knee osteoarthritis, the Osteoarthritis Research Society International (OARSI) grading system and actual joint space measurements; and 2: To compare the reliability of these grading systems. Materials and Methods Knee radiographs of 117 patients who received intra-articular corticosteroid injections were independently evaluated by two radiologists blinded to the outcome. Evaluation included the KL5, KL3, OARSI systems and actual joint space widths. The numerical rating scale for pain was collected at baseline and along with the Patient’s Global Impression of Change on day 1, in week 1 and in month 1. The number of ‘improved’ patients was compared between the OA grades using the Chi-square test. Logistic regression determined which findings were predictive for improvement. Agreement was assessed using Kappa statistics and the intraclass correlation coefficient (ICC). Results Patients with OARSI grade 2 reported the highest rates of ‘improvement’ at all time points, which was significant on day 1 (p = 0.004). No relationship with improvement was found with KL5, KL3 or actual joint space measurements. Patients with OARSI grade 2 were 8 times more likely to report improvement on day 1 (p = 0.024). Reliability was best for joint space measurements (ICC = 0.812 – 0.882), followed by the OARSI. Conclusion The OARSI for joint space narrowing grade 2 (34 – 66 % narrowing) was linked with a better outcome on day 1 with trends in week 1 and month 1. The reliability of the OARSI was better than the KL5 or KL3 systems. Key Points Citation Format
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Dąbrowski, Mikołaj, Anetta Zioła-Frankowska, Marcin Frankowski, Jacek Kaczmarczyk, and Łukasz Kubaszewski. "Comparison of Bone Tissue Trace Element Content in the Different Radiological Stages of Hip Osteoarthritis." International Journal of Environmental Research and Public Health 18, no. 6 (March 22, 2021): 3260. http://dx.doi.org/10.3390/ijerph18063260.
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Bone metabolism and the trace element content associated with it change at each stage of degenerative disease. The aim of this study was to find out about the role of the analyzed elements in different stages of hip osteoarthritis. Elements associated with oxidative and enzymatic processes were analyzed depending on the changes in the radiological images of the hip joint. Element content analysis was performed by the inductively coupled plasma mass spectrometry analytical technique. The femoral head in severely osteoarthritic hips (KL3–4) compared to mild grade osteoarthritis (KL2) had a greater content of Cu (median 1.04 vs. 0.04), Sr (median 38.71 vs. 29.59), and Zn (median 75.12 vs. 63.21). There were no significant differences in the content of Mo, Cr, and Fe in the femoral head and neck between the groups. The Cu/Fe correlation was negative in the KL2 group (−0.47) and positive in the KL3–4 groups (0.45). Changes in the content and correlation of trace elements in the hip joint explain the changes in metabolism dependent on the severity of degenerative changes.
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Spadaro, T. "Precision test of the SM with Kl2, Kl3 decays at the KLOE experiment." Nuclear Physics B - Proceedings Supplements 187 (February 2009): 245–52. http://dx.doi.org/10.1016/j.nuclphysbps.2009.01.034.
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Sahly, H., R. Podschun, and U. Ullmann. "Increased antibody responses to Klebsiella serotypes K26, K36, and K50 in patients with ankylosing spondylitis." Rheumatology 38, no. 5 (May 1, 1999): 481–82. http://dx.doi.org/10.1093/rheumatology/38.5.481.
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Alieva, Amina M., Elena V. Reznik, Natalia V. Teplova, Kira V. Voronkova, Elvira Azretalievna Khachirova, Leyla R. Sarakaeva, Ramiz K. Valiev, Irina A. Kotikova, and Igor G. Nikitin. "Klotho protein and atherosclerotic cardiovascular diseases: prolonging the thread of life." Medical Journal of the Russian Federation 28, no. 5 (November 23, 2022): 365–80. http://dx.doi.org/10.17816/medjrf110823.
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To date, the most widely used biomarkers are natriuretic peptides and cardiac troponins. Many other biomarkers have also been identified, but only a few of them have found application in actual clinical practice. This review focuses on the Klotho protein and its role in cardiovascular diseases.
In 1997, a gene that slows down the aging process was identified. It was named Klotho (Greek, ώ, spinning; Latin, Clotho; English, Klotho) in honor of the goddess of ancient Greek mythology, spinning the thread of life and being the personification of the steady, calm course of fate. Mice with an insertional mutation in the region of the Klotho gene promoter were characterized by premature aging processes. Three families of Klotho are known: -Klotho, -Klotho, and -Klotho, and the most studied is -Klotho. The Klotho protein consists of a large extracellular domain and a short C-terminal intracellular region. The extracellular domain consists of two repeat sequences called KL1 and KL2. -Klotho and -Klotho contain the KL1 and KL2 domains, respectively, and -Klotho contains only the KL1 domain. The Klotho gene in humans is located on chromosome 13q12 and consists of five exons. The Klotho protein is mainly expressed in the distal convoluted tubules of the kidneys and the vascular epithelial plexus of the cerebral ventricles. At lower concentrations, the Klotho gene is also found in other organs and tissues, particularly in the heart.
Many studies have demonstrated the protective role of the Klotho protein in cardiovascular pathology. The pleiotropic properties of this protein are reflected in the diversity and interaction of cardioprotective mechanisms. The regulation of the concentrations of the Klotho protein in the blood and its expression in heart cells with the help of drugs can play a significant role in cellular metabolism and represent a promising target for the treatment of heart and vascular pathologies.
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Huang, Zhongting, Haibin He, Feng Qiu, and Hailong Qian. "Expression and Prognosis Value of the KLF Family Members in Colorectal Cancer." Journal of Oncology 2022 (March 19, 2022): 1–13. http://dx.doi.org/10.1155/2022/6571272.
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Krüppel-like factors (KLFs) are some kind of transcriptional regulator that regulates a broad range of cellular functions and has been linked to the development of certain malignancies. KLF expression patterns and prognostic values in colorectal cancer (CRC) have, however, been investigated rarely. To investigate the differential expression, predictive value, and gene mutations of KLFs in CRC patients, we used various online analytic tools, including ONCOMINE, TCGA, cBioPortal, and the TIMER database. KLF2-6, KLF8-10, KLF12-15, and KLF17 mRNA expression levels were dramatically downregulated in CRC tissues, but KLF1, KLF7, and KLF16 mRNA expression levels were significantly elevated in CRC tissues. According to the findings of Cox regression analysis, upregulation of KLF3, KLF5, and KLF6 and downregulation of KLF15 were linked with a better prognosis in CRC. For functional enrichment, our findings revealed that KLF members are involved in a variety of cancer-related biological processes. In colon cancer and rectal cancer, KLFs were also shown to be associated with a variety of immune cells. The findings of this research reveal that KLF family members’ mRNA expression levels are possible prognostic indicators for patients with CRC.
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Moi, Paolo, Giuseppina Maria Marini, Loredana Porcu, Isadora Asunis, Maria Giuseppina Loi, Lisa Anna Cabriolu, and Antonio Cao. "Regulation of the Human α-Globin Genes by GKLF." Blood 112, no. 11 (November 16, 2008): 1867. http://dx.doi.org/10.1182/blood.v112.11.1867.1867.
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Abstract EKLF and related Krueppel-like factors (KLFs) are variably implicated in the regulation of the β- and β-like globin genes. Prompted by the observation that four KLF sites are distributed in the human α-globin promoter, we investigated if any of the β-globin cluster regulating KLFs could also act to modulate the expression of the α-globin genes. We found that, among the globin regulating KLFs (EKLF, LKLF, BKLF, GKLF, KLF6, FKLF and FKLF2), only GKLF and BKLF bound specifically to three out of four KLF sites. In K562 cells, over-expressed GKLF transactivated at high levels a α-globin-luciferase reporter and its action was impaired by point mutations of the KLF sites that disrupted GKLFDNA binding. In K562 cells stably transfected with a Tet-off regulated GKLF expression cassette, GKLF induction stimulated the expression of the endogenous α-globin genes. In a complementary assay in K562 cells, knocking down GKLF expression with small interfering RNAs caused a parallel decrease in the transcription of the α-globin genes. All experiments combined support a main regulatory role of GKLF in the control of α-globin gene expression.
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Volpon, Laurent, Carine Lievre, Michael J. Osborne, Shaifali Gandhi, Pietro Iannuzzi, Robert Larocque, Miroslaw Cygler, Kalle Gehring, and Irena Ekiel. "The Solution Structure of YbcJ from Escherichia coli Reveals a Recently Discovered αL Motif Involved in RNA Binding." Journal of Bacteriology 185, no. 14 (July 15, 2003): 4204–10. http://dx.doi.org/10.1128/jb.185.14.4204-4210.2003.
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ABSTRACT The structure of the recombinant Escherichia coli protein YbcJ, a representative of a conserved family of bacterial proteins (COG2501), was determined by nuclear magnetic resonance. The fold of YbcJ identified it as a member of the larger family of S4-like RNA binding domains. These domains bind to structured RNA, such as that found in tRNA, rRNA, and a pseudoknot of mRNA. The structure of YbcJ revealed a highly conserved patch of basic residues, comprising amino acids K26, K38, R55, K56, and K59, which likely participate in RNA binding.
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Kiang, Juliann G., Phillip D. Bowman, Brian W. Wu, Nyasa Hampton, Andrew G. Kiang, Baiteng Zhao, Yuang-Taung Juang, James L. Atkins, and George C. Tsokos. "Geldanamycin treatment inhibits hemorrhage-induced increases in KLF6 and iNOS expression in unresuscitated mouse organs: role of inducible HSP70." Journal of Applied Physiology 97, no. 2 (August 2004): 564–69. http://dx.doi.org/10.1152/japplphysiol.00194.2004.
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The aim of this study was to determine whether hemorrhage affects the levels of a variety of stress-related proteins and whether changes can be inhibited by drugs reported to provide protection from ischemia and reperfusion injury. Male Swiss Webster mice were subjected to a 40% hemorrhage without resuscitation. Western blot analysis indicated that c-Jun (an AP-1 protein), Kruppel-like factor 6 (KFL6), and inducible nitric oxide synthase (iNOS) were upregulated sequentially in that order. Pretreatment of mice with geldanamycin (GA) 16 h before hemorrhage effectively inhibited the expression of the proteins KLF6 and iNOS, whereas caffeic acid phenethyl ester did not. GA pretreatment increased inducible heat shock protein (HSP) 70 but not HSP90 in both sham and hemorrhagic tissues. The overexpressed inducible HSP70 formed complexes with KLF6 and iNOS. These results suggest that GA may be therapeutically useful for reducing hemorrhage-induced injury when used as a presurgical treatment or when added to resuscitation fluids.
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Iqbal, Ambreen, Haibin Yu, Ping Jiang, and Zhihui Zhao. "Deciphering the Key Regulatory Roles of KLF6 and Bta-miR-148a on Milk Fat Metabolism in Bovine Mammary Epithelial Cells." Genes 13, no. 10 (October 9, 2022): 1828. http://dx.doi.org/10.3390/genes13101828.
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MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of their target genes involved in many cellular functions at the post-transcriptional level. Previously, bta-miR-148a showed significantly high expression in bovine mammary epithelial cells (BMECs) of Chinese Holstein cows producing high milk fat compared to those with low milk fat content. Here, we investigated the role of bta-miR-148a through targeting Krüppel-like factor 6 (KLF6) and further analyzed the role of KLF6 in regulating fat metabolism through targeting PPARA, AMPK/mTOR/PPARG, and other fat marker genes in BMECs of Chinese Holstein. The bioinformatics analysis showed that the 3’ UTR of KLF6 mRNA possesses the binding sites for bta-miR-148a, which was further verified through dual-luciferase reporter assay. The BMECs were transfected with bta-miR-148a-mimic, inhibitor, and shNC, and the expression of KLF6 was found to be negatively regulated by bta-miR-148a. Moreover, the contents of triglyceride (TG), and cholesterol (CHO) in BMECs transfected with bta-miR-148a-mimic were significantly lower than the contents in BMECs transfected with bta-miR-148a-shNC. Meanwhile, the TG and CHO contents were significantly increased in BMECs transfected with bta-miR-148a-inhibitor than in BMECs transfected with bta-miR-148a-shNC. In addition, the TG and CHO contents were significantly decreased in BMECs upon the down-regulation of KLF6 through transfection with pb7sk-KLF6-siRNA1 compared to the control group. Contrarily, when KLF6 was overexpressed in BMECs through transfection with pBI-CMV3-KLF6, the TG and CHO contents were significantly increased compared to the control group. Whereas, the qPCR and Western blot evaluation of PPARA, AMPK/mTOR/PPARG, and other fat marker genes revealed that all of the genes were considerably down-regulated in the KLF6-KO-BMECs compared to the normal BMECs. Taking advantage of deploying new molecular markers and regulators for increasing the production of better-quality milk with tailored fat contents would be the hallmark in dairy sector. Hence, bta-miR-148a and KLF6 are potential candidates for increased milk synthesis and the production of valuable milk components in dairy cattle through marker-assisted selection in molecular breeding. Furthermore, this study hints at the extrapolation of a myriad of functions of other KLF family members in milk fat synthesis.
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van Loon, Ellen P. M., Wilco P. Pulskens, Eline A. E. van der Hagen, Marla Lavrijsen, Marc G. Vervloet, Harry van Goor, René J. M. Bindels, and Joost G. J. Hoenderop. "Shedding of klotho by ADAMs in the kidney." American Journal of Physiology-Renal Physiology 309, no. 4 (August 15, 2015): F359—F368. http://dx.doi.org/10.1152/ajprenal.00240.2014.
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The anti-aging gene klotho plays an important role in Ca2+ and phosphate homeostasis. Membrane-bound klotho is an essential coreceptor for fibroblast growth factor-23 and can be cleaved by proteases, including a disintegrin and metalloproteinase (ADAM)10 and ADAM17. Cleavage of klotho occurs at a site directly above the plasma membrane (α-cut) or between the KL1 and KL2 domain (β-cut), resulting in soluble full-length klotho or KL1 and KL2 fragments, respectively. The aim of the present study was to gain insights into the mechanisms behind klotho cleavage processes in the kidney. Klotho shedding was demonstrated using a Madin-Darby canine kidney cell line stably expressing klotho and human embryonic kidney-293 cells transiently transfected with klotho. Here, we report klotho expression on both the basolateral and apical membrane, with a higher abundance of klotho at the apical membrane and in the apical media. mRNA expression of ADAM17 and klotho were enriched in mouse distal convoluted and connecting tubules. In vitro ADAM/matrix metalloproteinase inhibition by TNF484 resulted in a concentration-dependent inhibition of the α-cut, with a less specific effect on β-cut shedding. In vivo TNF484 treatment in wild-type mice did not change urinary klotho levels. However, ADAM/matrix metalloproteinase inhibition did increase renal and duodenal mRNA expression of phosphate transporters, whereas serum phosphate levels were significantly decreased. In conclusion, our data show that renal cells preferentially secrete klotho to the apical side and suggest that ADAMs are responsible for α-cut cleavage.
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Ma, Zengyu, Baozhen Qu, Shenjie Zhong, Lan Yao, Zhan Gao, and Shicui Zhang. "Subtle Difference Generates Big Dissimilarity: Comparison of Enzymatic Activity in KL1 and KL2 Domains of Lancelet Klotho." Marine Biotechnology 21, no. 4 (May 3, 2019): 448–62. http://dx.doi.org/10.1007/s10126-019-09891-0.
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Tran, Tung Dang Xuan, Chi-Ming Wu, Navneet Kumar Dubey, Yue-Hua Deng, Chun-Wei Su, Tu Thanh Pham, Phuong Bich Thi Le, Piero Sestili, and Win-Ping Deng. "Time- and Kellgren–Lawrence Grade-Dependent Changes in Intra-Articularly Transplanted Stromal Vascular Fraction in Osteoarthritic Patients." Cells 8, no. 4 (April 3, 2019): 308. http://dx.doi.org/10.3390/cells8040308.
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Knee osteoarthritis (OA) is one of the most prevalent disorders in elderly population. Among various therapeutic alternatives, we employed stromal vascular fraction (SVF), a heterogeneous cell population, to regenerate damaged knee cartilage. OA patients were classified on the basis of age, gender, body mass index (BMI), and x-ray-derived Kellgren–Lawrence (KL) grade. They were treated with SVF and followed-up for 24 months. Visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index were used to determine treatment efficacy. Cartilage healing was assessed using the MRI-based Outerbridge score (OS) and evaluation of bone marrow edema (BME) lesions, while a placebo group was used as a control. Time- and KL-dependent changes were also monitored. We observed a decreasing trend in VAS score and WOMAC index in the SVF-treated group up to 24 months, as compared with the placebo group. Besides, a significant increase and decrease in Lysholm and OS, respectively, were observed in the treatment group. Compared with the values before treatment, the greatly reduced WOMAC scores of KL3 than KL2 groups at 24 months, indicate more improvement in the KL3 group. Highly decreased BME in the treated group was also noted. In conclusion, the SVF therapy is effective in the recovery of OA patients of KL3 grade in 24 months.
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Chen, Zhuxiang, Zhimin Zhang, and Zhang Zhao. "Circular RNA circ-ABCB10 Promotes Proliferation and Inhibits Apoptosis of Laryngeal Carcinoma by Inhibiting KLF6." Computational and Mathematical Methods in Medicine 2022 (June 15, 2022): 1–8. http://dx.doi.org/10.1155/2022/7754931.
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Objective. To explore the effect of circular RNA circ-ABCB10 on the proliferation and apoptosis of laryngeal carcinoma via inhibiting KLF6. Methods. RT-qPCR assay was adopted to detect the expression of circ-ABCB10 and KFL6 in laryngeal carcinoma tissues and cell lines. Cell counting kit-8 (CCK-8) and clone formation assay were employed to detect laryngeal cancer cell viability and proliferation when circ-ABCB10 was silenced or upregulated. In this study, the apoptosis rate was detected by flow cytometry and the protein expression was detected by Western blotting. Wound healing and cross-hole invasion were used to study the migration and invasion of laryngeal cancer cells when circ-ABCB10 was silenced or upregulated. Results. The results of RT-qPCR detection indicated that the expression of circ-ABCB10 in all three laryngeal carcinoma cells was downregulated by 3.2 times compared with that of HaCat cells. There is low expression of circ-ABCB10 in most laryngeal carcinoma tissues, the diagnostic cutoff value of circ-ABCB10 is 0.0008, the area under the curve is 0.718, the sensitivity is 0.981, and the specificity is 0.556. The expression level of KLF6 in laryngeal carcinoma is on the rise, which is significantly higher compared to healthy tissues ( P < 0.05 ); 48 hours after transfection, RT-qPCR analysis confirmed the transfection efficiency, and upregulation of circ-ABCB10 could significantly promote cell proliferation. Compared with the control group, silencing circ-MTCL1 could inhibit cell proliferation, overexpression of circ-ABCB10 promoted cell migration, and downregulation of circ-ABCB10 significantly inhibited cell movement ( P < 0.001 ). Upregulation of circ-ABCB10 significantly enhanced the invasiveness and motility of laryngeal cancer cells, while downregulation of circ-ABCB10 was the opposite. Compared with the KLF6 NC group, KLF6 level increased significantly in the KLF6 group, while cell viability, colony formation, scratch healing rate, invasive cell number, and Bcl-2 expression level decreased significantly in the KLF6 group, while apoptosis rate and Bax expression level increased significantly ( P < 0.05 ). KLF6 level in the si-circ-ABCB10+anti-KLF6 group was significantly lower than that in the si-circ-ABCB10+anti-KLF6-NC group ( P < 0.05 ). Meanwhile, the cell activity, colony formation number, cell scratch healing rate, number of invaded cells, and Bcl-2 all indicated an upward trend, while the cell apoptosis rate and Bax expression indicated a downward trend ( P < 0.05 ). Conclusion. The expression of circ-ABCB10 in laryngeal carcinoma was significantly higher compared to that in paracancerous tissues. Silencing circ-ABCB10 could significantly inhibit the growth and proliferation of laryngeal adenocarcinoma cells, while overexpression of circ-ABCB10 could significantly promote the growth of laryngeal adenocarcinoma cells, probably by inhibiting KLF6 to enhance the proliferation of laryngeal carcinoma and inhibit apoptosis.
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Yasuda, Tatsuya, Daisuke Togawa, Tomohiko Hasegawa, Yu Yamato, Sho Kobayashi, Go Yoshida, Tomohiro Banno, et al. "Relationship between Knee Osteoarthritis and Spinopelvic Sagittal Alignment in Volunteers over 50 Years of Age." Asian Spine Journal 14, no. 4 (August 31, 2020): 495–501. http://dx.doi.org/10.31616/asj.2018.0266.
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Study Design: Large cohort study of volunteers.Purpose: The purpose of this study was to investigate the relationship between the severity of knee osteoarthritis, assessed using the Kellgren-Lawrence (KL) grading scale, and spinopelvic sagittal alignment in older adult volunteers.Overview of Literature: The relationship between spinopelvic alignment in the sagittal plane and knee osteoarthritis in the coronal plane is unclear.Methods: Volunteers over 50 years of age underwent radiographic analysis. Radiographic parameters including pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), thoracic kyphosis, and sagittal vertical axis (SVA) were measured. The the three Scoliosis Research Society-Schwab sagittal modifiers (PT, SVA, PI–LL) were categorized and the KL grade was assessed. Differences in spinopelvic parameters and Oswestry Disability Index (ODI) scores among KL grades were evaluated.Results: A total of 396 volunteers (160 men, 236 women; mean age, 74.4 years) were analyzed. PI–LL and PT in KL4 were significantly higher compared to that in the other KL grades. However, there were no significant group differences in SVA. In women, but not in men, higher frequencies of the worst modifier grade (++) were observed for PI–LL and PT in the KL3 and KL4 groups compared to those for the other KL grades. In women, the ODI score in KL4 was worse compared to that in the other KL grades.Conclusions: Individuals over 50 years of age with severe knee osteoarthritis had poor lumbo-pelvic sagittal alignment. Moreover, the progression severity of knee osteoarthritis had more impact onstronger relationship with lumbo-pelvic malalignment and disability-related low back pain in women than in men.
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Yudanin, Naomi, and Donna Farber. "Transcriptome analysis of lung resident compared to spleen memory CD4 T cells reveals differential expression of genes controlling tissue egress (P5083)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 129.6. http://dx.doi.org/10.4049/jimmunol.190.supp.129.6.
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Abstract Memory T cells, generated after pathogen encounter, persist in diverse tissue sites, including lymphoid and mucosal tissues. We previously identified a population of memory CD4 T (CD4TM) cells that were retained in the lung, and mediated optimal protective responses to respiratory virus infection. Spleen-derived CD4 TM cells circulated in multiple sites and were not protective. Here, we investigated potential mechanisms for these differential migration patterns by whole transcriptome analysis of lung and spleen CD4 TM cells. We isolated RNA from lung and spleen CD4 TM generated in vivo for subsequent RNAseq analysis. Our analysis revealed a set of genes that are differentially expressed in lung compared to spleen CD4 TM cells. Using unbiased gene ontology clustering (GO), functional pathway analysis (KEGG), and gene interaction network mapping (STRING9.0) we identified a cohesive gene interaction pathway that functions in cell motility and tissue retention. Along with other genes involved in cell adhesion and migration, the selected candidates included Sphingosine-1-phosphate receptor (S1PR1), CD69, Kruppel-like factor (KLF)-2, and KLF6, all known to regulate lymphocyte egress from tissues. Upon re-activation, lung CD4TM upregulated CD69 and KLF6, and downregulated S1PR1 and KLF2 compared to spleen CD4TM. These findings suggest that the upregulation of these genes in lung but not in spleen memory CD4 T cells may contribute to their tissue-specific retention in the lung.
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GROSBY, Steven. "RM KLH." ARAM Periodical 7, no. 2 (December 1, 1995): 337–52. http://dx.doi.org/10.2143/aram.7.2.2002234.
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Li, Bing An. "Kl4 Decays." International Journal of Modern Physics A 16, supp01a (October 2001): 172–74. http://dx.doi.org/10.1142/s0217751x01006401.
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An effective theory of large NC QCD of mesons has been used to study six Kl4 decay modes. PCAC is satisfied. A relationship between three form factors of axial-vector current has been found. ρ → ππ plays important role. the decay rates are calculated in the chiral limit. There is no adjustable parameter.
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An Li, Bing. "Kl4 decays." European Physical Journal A 10, no. 2 (April 2001): 237–44. http://dx.doi.org/10.1007/s100500170135.
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Cai, Qing, Sen-Miao Tong, Wei Shao, Sheng-Hua Ying, and Ming-Guang Feng. "Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in Beauveria bassiana." Cellular Microbiology 20, no. 7 (April 6, 2018): e12839. http://dx.doi.org/10.1111/cmi.12839.
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Kenyon, Johanna J., Nikolay P. Arbatsky, Emma L. Sweeney, Alexander S. Shashkov, Mikhail M. Shneider, Anastasia V. Popova, Ruth M. Hall, and Yuriy A. Knirel. "Production of the K16 capsular polysaccharide by Acinetobacter baumannii ST25 isolate D4 involves a novel glycosyltransferase encoded in the KL16 gene cluster." International Journal of Biological Macromolecules 128 (May 2019): 101–6. http://dx.doi.org/10.1016/j.ijbiomac.2019.01.080.
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Nakamura, S., N. Nakazawa, H. Mawatari, and S. Satō. "KL0 → 2π and KL0 → π0e+e− without CP violation." Nuclear Physics A 577, no. 1-2 (September 1994): 463–68. http://dx.doi.org/10.1016/0375-9474(94)90897-4.
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Bradner, N. R., R. D. Simpson, and A. A. Hadlock. "Nattoking K86 soybean." Canadian Journal of Plant Science 71, no. 3 (July 1, 1991): 855–56. http://dx.doi.org/10.4141/cjps91-120.
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NattoKing K86 is a Maturity Group 00 soybean (Glycine max (L.) Merr.) cultivar having higher yield performance, smaller seed size, and later maturity than Canatto. Key words: Glycine max, NattoKing K86 cultivar, cultivar description, soybean
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Martinez, Alejandro Morales, Francesco Caliva, Valentina Pedoia, Drew Lansdown, and Nikan Namiri. "Poster 242: Deep Learning for Identifying Patellofemoral Measurements Associated with Cartilage Lesions on MRI." Orthopaedic Journal of Sports Medicine 10, no. 7_suppl5 (July 1, 2022): 2325967121S0080. http://dx.doi.org/10.1177/2325967121s00803.
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Objectives: Magnetic resonance imaging (MRI) enables patellofemoral joint (PFJ) geometric measurements that may guide metrics of operative treatments, such as anteromedialization osteotomy, offloading stress on PFJs with chondral defects. However, utilization of MRI is limited due to expense required in manual image annotation. Preliminary work in small cohorts has suggested differences in PFJ measurements involving the anterior tibia and trochlea among symptomatic and control patients. Recently, deep learning (DL) has been used to perform accurate, automated segmentation of knee MRI. Herein, our aim was to develop a DL algorithm to segment the bony structures in knee MRIs and determine the relationship between PFJ geometries and cartilage lesions in a large, longitudinal cohort. Methods: Subjects: We obtained data from the Osteoarthritis Initiative (OAI), a multi-institutional study conducted between 2005 and 2006, consisting of 4796 participants aged 45 to 80 years (NCT#00080171, on ClinicalTrials.gov). Eligible participants had osteoarthritis (OA) or elevated risk of OA in at least one knee at baseline. Each participant was assessed yearly with questionnaires, radiographs, and MRI. MRI sequences: MRIs were obtained using 3T scanners (Siemens Trio, Germany) on both right and left knees. From the OAI database, we accessed 3D sagittal double echo steady-state volumes with the following parameters: resolution=0.365×0.456×0.7mm, field of view=14cm, repetition time/echo time=16.2/4.7ms, matrix=384×307×160, bandwidth=62.5kHz. Radiologist grading: A subset of knee MRIs from OAI were graded according to MRI Osteoarthritis Knee Score (MOAKS) as part of several previous studies and shared publicly. A centralized group performed the grading through direct supervision of two musculoskeletal radiologists with more than nine years of training in grading knee OA with semi-quantitative scoring systems. Clinical data and case-control status were not made available to the radiologists during grading. In total, 2653 unique participants received imaging at either or both of two visits (baseline and 4 years), resulting in gradings for 4413 knee MRIs from 3117 unique knees. Automated segmentation: We built a DL segmentation model to determine the locations of patella, femur, and tibia within the double echo steady-state MRIs. The model utilized a 3D V-Net architecture, and training was performed on 40 manually annotated MRIs. We then used the trained model to segment femur, tibia, and patella bone from the radiologist MOAKS-graded subset of the OAI. Geometric measurements: We measured the tibial tubercle-trochlear groove (TTTG) length, sagittal tibial tubercle-trochlear groove (sTTTG) length, trochlear sulcus angle, trochlear dysplasia, Caton-Deschamps index, and flexion angle using the bone segmentations of the MOAKS-graded cohort. The trochlea was chosen using the axial slice of the segmentation with the largest femur width. The tibial tubercle was chosen using the anterior-most point of the axial cut 13.8mm superior to the inferior-most axial cut of the segmentation. This axial cut of the tibia was chosen using the average axial location of the tibial tubercle in 15 randomly selected segmentations. Statistical analysis: Dice score determined accuracy of the segmentation model on the holdout set of manually segmented images. Kruskal-Wallis H-test compared differences in demographics, radiographic findings, and geometric measurements between subjects without and with PFJ OA. PFJ OA was defined as having a MOAKS score greater than 2 in one or more of the following articular surfaces of the PFJ: anterior medial femur, anterior lateral femur, medial patella, lateral patella. Controls with no PFJ OA were classified as MOAKS score less than or equal to 2 in all four PFJ articular surfaces. Two-tailed p-values less than 0.05 were considered statistically significant. Statistical analyses were performed in Python (version 3.6.5; Python Software Foundation, Beaverton, Ore); important packages included numpy, pandas, and scipy. Results: Baseline demographics for all subjects were as follows: women=1868, men=1243, age (mean(SD))=62.7(8.9), BMI=28.7(4.8). Kellgren-Lawrence (KL) grades of the knees were KL0=1106, KL1=590, KL2=695, KL3=493, KL4=194. Dice scores of the model on the holdout test set were 97.2% (95% confidence interval (CI): 96.6-97.7%), 97.3% (95% CI: 96.6-97.9%), and 96.0% (95% CI: 95.2-96.7%) for femur, tibia, and patella, respectively. A total of 2051 knees did not have PFJ OA, while 1060 knees possessed PFJ OA (Table 1). Subjects with PFJ OA were older, had greater female predominance, greater BMI, greater KL scores, greater pain levels, and greater proportion of total knee replacement at 8 years. Knees without PFJ OA had a greater sTTTG (-8.2(5.7) mm) compared to subjects with PFJ OA (-9.8(5.8) mm) (p<0.001), indicating a more anteriorly-positioned tibial tubercle for those subjects without PFJ OA. There were no differences in TTTG (9.2(4.2) mm v. 9.4(4.9) mm, p=0.12) and sulcus angle (145.7(9.1) degrees v. 146.0(9.6) degrees, p=0.41) among knees without and with PFJ OA. Conclusions: We used DL to segment bony structures within knee MRIs and compare PFJ geometric measurements with presence of OA. Knees with PFJ OA were associated with a more posteriorly positioned tibial tubercle; however, we found no differences in TTTG and sulcus angle in knees with and without OA. This relationship of the tibial tubercle and trochlea in the sagittal plane is consistent with prior smaller case series, though the methodology of this study allows for evaluation of these measurements on a much broader scale in this large cohort. Understanding the geometric measurements of knees without chondral defects may serve as metrics for correctional chondral deformity operations. [Table: see text]
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Walkowiak, Magdalena, Marcin Matuszczak, Stanisław Spasibionek, Alina Liersch, and Katarzyna Mikołajczyk. "Cleaved Amplified Polymorphic Sequences (CAPS) Markers for Characterization of the LuFAD3A Gene from Various Flax (Linum usitatissimum L.) Cultivars." Agronomy 12, no. 6 (June 15, 2022): 1432. http://dx.doi.org/10.3390/agronomy12061432.
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Depending on the variety, flax (Linum usitatissimum L.) provides an oil rich in omega-3 acids (especially 50% α-linolenic acid) with proven health properties, and is used as a raw industrial material. Alpha-linolenic acid is a polyunsaturated fatty acid easily subject to oxidative transformation. The auto-oxidation of α-linolenic acid is the main process contributing to off-flavor, color loss, and change in the nutritional value of flax oil. We used six flax genotypes differing in fatty acid content in our research. For all the DNA samples extracted from the leaf tissue of the studied flax, the new, cleaved amplified polymorphic sequences (CAPS) markers specific to the LuFAD3A desaturase gene were applied. A specific PCR product from the LuFAD3A flax gene comprising fragments of exon 5, exon 6, and the intron between these exons was digested using six various restriction enzymes. These experiments could differentiate between some of the studied varieties of flax. We also proved that the LuFAD3A gene mutation previously detected by other authors in the low-linolenic forms of flax (solin line 593–708) was absent in the low-linolenic forms of flax that we studied (Linola KLA and Linola KLB).
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Tema, E. "Detailed archaeomagnetic study of a ceramic workshop at Kato Achaia: New directional data and archaeomagnetic dating in Greece." Bulletin of the Geological Society of Greece 47, no. 3 (December 21, 2016): 1279. http://dx.doi.org/10.12681/bgsg.10903.
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New archaeomagnetic results from two ancient kilns excavated at Kato Achaia, southern Greece, are presented. According to archaeological evidence, both kilns were part of a bigger ceramic workshop, probably used for the production of bricks or ceramics. Systematic archaeomagnetic sampling was carried out collecting 9 brick samples from the first kiln (KL3) and 12 brick samples from the second kiln (KL5). Magnetic mineralogy measurements have been carried out in order to determine the main magnetic carrier of the samples and to check their thermal stability. Standard thermal demagnetization procedures have been used to determine the archaeomagnetic direction registered by the bricks during their last firing. The direction of the Characteristic Remanent Magnetization (ChRM) has been obtained from principal component analysis and the kilns mean directions were calculated using Fisher statistics. The archaeomagnetic ages of both kilns were determined using the most recent developments in data elaboration and were calculated after comparison of the kilns declination and inclination with the reference curves produced by the SCHA.DIF.3K European regional geomagnetic field model. Dating results are in good agreement with archaeological evidence of the site and suggest that both kilns were in use during Hellenistic times.
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Alder, Jonathan K., Robert W. Georgantas, Richard L. Hildreth, Xiaobing Yu, and Curt I. Civin. "Kruppel-Like Factor 4 Upregulates p21 and Downregulates Proliferation of Human and Mouse HSPCs, but Is Not Essential for Mouse HSPC Repopulation." Blood 108, no. 11 (November 16, 2006): 1317. http://dx.doi.org/10.1182/blood.v108.11.1317.1317.
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Abstract Several Kruppel-like factor family members, including KLF1, KLF2, KLF3, and KLF6 have pivotal roles in hematopoiesis. Experiments in zebrafish have suggested that KLF4 may play a similar role. Here we found that enforced expression of KLF4 in hematopoietic cells induced cell cycle arrest without triggering apoptosis. Based on the high levels of expression of KLF4 in mouse and human hematopoietic stem-progenitor cells (HSPCs), we hypothesized and demonstrated that KLF4 regulates proliferation of these cells through regulation of p21cip1/waf1 (p21). Nevertheless, KLF4−/− mouse fetal liver cells had normal numbers of all mature lineages and provided radioprotection, similar to wild type (wt) controls. Furthermore, in long-term competitive repopulation assays, KLF4−/− mouse HSPCs demonstrated hematopoietic potency equivalent to wt. We found that KLF2 is expressed at higher levels than KLF4 in mouse HSPCs and is a more potent activator of p21, suggesting that KLF2 (and/or other KLF family members) may play a compensatory role in KLF4−/− HSPCs. Thus, although is not essential for their normal development and function, KLF4 expression is sufficient to induce p21-mediated cell cycle arrest in hematopoietic cells.
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Zeng, Binbin, Jiaxin Lin, Xingdong Cai, Li Che, Wei Zeng, and Shengming Liu. "Krüppel-Like Factor 6 Downregulation Is Connected with a Poor Prognosis and Tumor Growth in Non-Small-Cell Lung Cancer." Computational and Mathematical Methods in Medicine 2022 (January 30, 2022): 1–11. http://dx.doi.org/10.1155/2022/3193553.
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Purpose. Research in this article was performed to explore the biological role and clinical significance of Krüppel-like transcription factor 6 (KLF6) in non-small-cell lung cancer (NSCLC). Methods. KLF6 expression in NSCLC cell lines was analyzed using reverse transcription PCR and Western blot. The expressed KLF6 protein was examined in 50 surgical NSCLC tissues using immunohistochemistry. Statistical analyses were employed for clinical association examinations. CCK8 assay and Annexin V/PI analysis were used to execute cell proliferation and apoptosis in KLF6-overexpression cell lines and the control groups. Cleaved caspase-3 expression was also detected in KLF6-overexpression cells and NSCLC tissues. KLF6 expression correlation with cleaved caspase-3 was also examined. Results. It was discovered that downregulation of KLF6 was seen in human NSCLC cell lines. Low KLF6 expression in NSCLC tissues was correlated with poor patient prognosis ( P < 0.005 ); patients with less KLF6 expression possessed a lower cumulative 5-year survival rate. Multivariate analysis showed KLF6 expression as an independent prognostic indicator for NSCLC individuals. Expression levels of KLF6 were associated with NSCLC tumor size ( P = 0.041 ). Overexpression of KLF6 inhibited cell proliferation and stimulated A549 and H322 cell line apoptosis. Cleaved caspase-3 protein had higher expression levels in KLF6-overexpressed cells than in the control group. The KLF6 expression levels were positively related to the cleaved caspase-3 protein expression in NSCLC tissues ( r = 0.689 , P = 0.001 ). Conclusions. The results indicate that downregulation of KLF6 is a significant NSCLC progression marker. KLF6 prevents cell growth and promotes cell apoptosis, possibly caspase-3 activations.
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Edwards, Jessica K. "KLF6 protects injured podocytes." Nature Reviews Nephrology 11, no. 4 (March 10, 2015): 197. http://dx.doi.org/10.1038/nrneph.2015.29.
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Aichinger, Michael C., Martina Ortbauer, Siegfried Reipert, Wolfgang Zauner, Péter Bogner, Elisabeth Froschauer, Karin Nowikovsky, et al. "Unique membrane-interacting properties of the immunostimulatory cationic peptide KLKL5 KLK (KLK)." Cell Biology International 32, no. 11 (November 2008): 1449–58. http://dx.doi.org/10.1016/j.cellbi.2008.08.024.
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