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      • KCI등재SCOPUSSCIE

        PRP4 Kinase Domain Loss Nullifies Drug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells

        Ahmed, Muhammad Bilal,Islam, Salman Ul,Sonn, Jong Kyung,Lee, Young Sup Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.7

        We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

      • KCI등재

        Influence of Financial Literacy and Educational Skills on Entrepreneurial Intent: Empirical Evidence from Young Entrepreneurs of Pakistan

        Muhammad Ahmed BILAL,Hadi Hassan KHAN,Muhammad IRFAN,S.M. Nabeel Ul HAQ,Manzoor ALI,Ali KAKAR,Wahab AHMED,Abdul RAUF 한국유통과학회 2021 The Journal of Asian Finance, Economics and Busine Vol.8 No.1

        This paper attempts to study the impact of Financial Literacy on Youth Entrepreneurial Intent in Pakistan. A closed-ended self-administered structured questionnaire covering financial literacy, computer knowledge, financial attitude, and financial knowledge with Entrepreneurial Intent was collected from young entrepreneurs. The research tried to investigate the education level with computer skill to inspect the effect of financial literateness on young generation Entrepreneurial Intent in the context of Pakistan. The research model was tested using PLS-SEM and authenticating a measurement model through the advanced methodology and their association with Entrepreneurial Intent. Results revealed that financial literacy and its two parts (financial attitude and financial knowledge) have a positive impact on Entrepreneurial Intent. The size of the joint impact of financial literacy and its components on Entrepreneurial Intent was assessed to be adequate. Entrepreneurial Intent is essential for creating new firms to maintain economic development. Furthermore, it is determined in this research that if youth has better financial knowledge and financial attitude, the probability of Entrepreneurial Intent increases. This suggests that if the youth in Pakistan desire to attain a higher limit of Entrepreneurial Intent, they must implement financial literacy models for enhancing and promoting their current Entrepreneurial Intent.

      • KCI등재

        Decursin negatively regulates LPS-induced upregulation of the TLR4 and JNK signaling stimulated by the expression of PRP4 in vitro

        Muhammad Bilal Ahmed,Salman Ul Islam,이영섭 한국통합생물학회 2020 Animal cells and systems Vol.24 No.1

        The current investigation was carried out to analyze the correlation of bacterial lipopolysaccharide (LPS) and pre-mRNA processing factor 4B (PRP4) in inducing inflammatory response and cell actin cytoskeleton rearrangement in macrophages (Raw 264.7) and colorectal (HCT116) as well as skin cancer (B16-F10) cells. Cell lines were stimulated with LPS, and the expression of PRP4 as well as pro-inflammatory cytokines and proteins like IL-6, IL-1β, TLR4, and NF-κB were assayed. The results demonstrated that LPS markedly increased the expression of PRP4, IL-6, IL-1β, TLR4, and NF-κB in the cells. LPS and PRP4 concomitantly altered the morphology of cells from an aggregated, flattened shape to a round shape. Decursin, a pyranocoumarin from Angelica gigas, inhibited the LPS and PRP4-induced inflammatory response, and reversed the induction of morphological changes. Finally, we established a possible link of LPS with TLR4 and JNK signaling, through which it activated PRP4. Our study provides molecular insights for LPS and PRP4-related pathogenesis and a basis for developing new strategies against metastasis in colorectal cancer and skin melanoma. Our study emphasizes that decursin may be an effective treatment strategy for various cancers in which LPS and PRP4 perform a critical role in inducing inflammatory response and morphological changes leading to cell survival and protection against anti-cancer drugs.

      • KCI등재
      • KCI등재

        Mechanical and thermal properties of carboxymethyl fibers (CMF)/PVA based nanocomposite membranes

        Muhammad Bilal Khan Niazi,Zaib Jahan,Arooj Ahmed,Bushra Uzair,Ahmad Mukhtar,Øyvind Weiby Gregersen 한국공업화학회 2020 Journal of Industrial and Engineering Chemistry Vol.90 No.-

        Carboxymethylfibers (CMF) of cellulose are renewable biopolymer and have shown strong reinforcingproperties when added to a compatible polymer matrix. The objective of this study was to investigate theeffect of CMF on the mechanical, thermal and swelling properties of polyvinyl alcohol (PVA) membranes. The PVA/CMF composite membranes with different proportions of CMF ranging from 1 wt.% to 6 wt.%were prepared by solution casting method. The membranes were characterized by SEM, TGA, XRD, FTIRand mechanical testing. The results revealed that at low CMF concentration composite membranesshowed homogenous dispersion of CMF in PVA matrix. The incorporation of CMF enhanced thecrystallinity of composite membranes with increase in relative humidity (RH). Furthermore, themechanical strength and moisture uptake of PVA/CMF nanocomposite membranes were enhanced afterinclusion of CMF. TGA and DSC results revealed that the addition of CMF has no significant impact on thethermal properties. PVA/CMF nanocomposite membranes showed good potential to be applied for gasseparation application particularly for CO2 capture.

      • SCISCIESCOPUS

        Mechanisms of Cr(VI) resistance by endophytic <i>Sphingomonas</i> sp. LK11 and its Cr(VI) phytotoxic mitigating effects in soybean (<i>Glycine max</i> L.)

        Bilal, Saqib,Khan, Abdul Latif,Shahzad, Raheem,Kim, Yoon-Ha,Imran, Muhammad,Khan, Muhammad Jamil,Al-Harrasi, Ahmed,Kim, Tae Han,Lee, In-Jung Elsevier 2018 Ecotoxicology and environmental safety Vol.164 No.-

        <P><B>Abstract</B></P> <P>Chromium Cr(VI) is highly toxic and leads to impaired phenotypic plasticity of economically important crops. The current study assessed an endophytic-bacteria assisted metal bio-remediation strategy to understand stress-alleviating mechanisms in <I>Glycine max</I> L (soybean) plants inoculated with <I>Sphingomonas</I> sp. LK11 under severe Cr(VI) toxicity. The screening analysis showed that high Cr concentrations (5.0 mM) slightly suppressed LK11 growth and metal uptake by LK11 cells, while significantly enhancing indole-3-acetic acid (IAA) production. Endophytic LK11 significantly upregulated its antioxidant system compared to control by enhancing reduced glutathione (GSH), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities to counteract Cr-induced oxidative stress. Cr toxicity induced cell morphological alteration, as shown by SEM-EDX analysis and triggered significant lipid peroxidation. The interaction between LK11 and soybean in Cr-contaminated soil significantly increased plant growth attributes and down-regulated the synthesis of endogenous defense-related phytohormones, salicylic acid and abscisic acid, by 20% and 37%, respectively, and reduced Cr translocation to the roots, shoot, and leaves. Additionally, Cr-induced oxidative stress was significantly reduced in LK11-inoculated soybean, regulating metal responsive reduced GSH and enzymatic antioxidant CAT. Current findings indicate that LK11 may be a suitable candidate for the bioremediation of Cr-contaminated soil and stimulation of host physiological homeostasis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Endophytic LK11 act as an alternative strategy for alleviating chromium stress from soybean. </LI> <LI> IAA producing capability of LK11 was remarkably upregulated Under chromium stress. </LI> <LI> LK11 assoiciation promoted host plant growth attributes and modulated endogenous hormones and antioxidants. </LI> <LI> LK11 Inoculated soybean displayed reduced accumulation of chromium. </LI> </UL> </P>

      • KCI등재

        Additively manufactured nano-mechanical energy harvesting systems: advancements, potential applications, challenges and future perspectives

        Ahmed Ammar,Azam Ali,Wang Yanen,Zhang Zutao,Li Ning,Jia Changyuan,Mushtaq Ray Tahir,Rehman Mudassar,Gueye Thierno,Shahid Muhammad Bilal,Basit Ali Wajid 나노기술연구협의회 2021 Nano Convergence Vol.8 No.37

        Additively manufactured nano-MEH systems are widely used to harvest energy from renewable and sustainable energy sources such as wind, ocean, sunlight, raindrops, and ambient vibrations. A comprehensive study focusing on in-depth technology evolution, applications, problems, and future trends of specifically 3D printed nano-MEH systems with an energy point of view is rarely conducted. Therefore, this paper looks into the state-of-the-art technologies, energy harvesting sources/methods, performance, implementations, emerging applications, potential challenges, and future perspectives of additively manufactured nano-mechanical energy harvesting (3DP-NMEH) systems. The prevailing challenges concerning renewable energy harvesting capacities, optimal energy scavenging, power management, material functionalization, sustainable prototyping strategies, new materials, commercialization, and hybridization are discussed. A novel solution is proposed for renewable energy generation and medicinal purposes based on the sustainable utilization of recyclable municipal and medical waste generated during the COVID-19 pandemic. Finally, recommendations for future research are presented concerning the cutting-edge issues hurdling the optimal exploitation of renewable energy resources through NMEHs. China and the USA are the most significant leading forces in enhancing 3DP-NMEH technology, with more than 75% contributions collectively. The reported output energy capacities of additively manufactured nano-MEH systems were 0.5–32 mW, 0.0002–45.6 mW, and 0.3–4.67 mW for electromagnetic, piezoelectric, and triboelectric nanogenerators, respectively. The optimal strategies and techniques to enhance these energy capacities are compiled in this paper. Graphical Abstract

      • Quantitative Analyses of Esophageal Cancer Research in Pakistan

        Qureshi, Muhammad Asif,Khan, Saeed,Ujjan, Ikram Din,Iqbal, Asif,Khan, Ramsha,Khan, Bilal Ahmed Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.7

        Background: Health-care research is a neglected discipline in Pakistan and research related to esophageal cancer (ranks 9th in Pakistani males and 5th in females) is no exception in this regard. Particularly, there are no data available to delineate the overall status of esophageal cancer epidemiological studies in Pakistan. This study describes the first ever effort to make a systematic quantification, in an attempt to provide a road-map to all stakeholders for designing appropriate epidemiological, diagnostic and therapeutic strategies. Materials and Methods: International (PubMed, ISI Web of Knowledge) and local (PakMedinet) scientific databases as well as Google search engine were searched using specified keywords to extract relevant publication. Well-defined inclusion criteria were implemented to select publications for final analyses. All data were recorded by at least 3 authors and consensus data were entered into and analyzed for descriptive statistics (such as frequencies, percentages and annual growth rates) using Microsoft Excel and SPSS software. Results: A total of 79 publications fulfilled the inclusion criteria including 20 publications for which full texts were not available. Of the 79 publications, 59 (74.6%) were original/research publications, 5 (6.3%) were case reports, 4 (5.1%) were research communications, 2 (2.5%) were review articles, 1 was (1.2%) correspondence and 8 (10.1%) were undefined categories. Only 13 (<20%) cities of Pakistan contributed towards the 79 publications. On average, only 1.9 relevant publications/year were published from 1976 (year of first publication) to the present. Alarmingly, a decline in the annual growth at -4.1% was recorded in the last six years. Conclusions: Esophageal cancer research is largely unfathomed in Pakistan. Urgent/dramatic steps are required by all concerned to address this common (and under reported) cancer of Pakistan.

      • PRP4 kinase induces actin rearrangement and epithelial-mesenchymal transition through modulation of the actin-binding protein cofilin

        Islam, Salman Ul,Ahmed, Muhammad Bilal,Lee, Su Jin,Shehzad, Adeeb,Sonn, Jong Kyung,Kwon, Oh-Shin,Lee, Young Sup Elsevier 2018 Experimental cell research Vol.369 No.1

        <P><B>Abstract</B></P> <P>Cell actin cytoskeleton is primarily modulated by Rho family proteins. RhoA regulates several downstream targets, including Rho-associated protein kinase (ROCK), LIM-Kinase (LIMK), and cofilin. Pre-mRNA processing factor 4B (PRP4) modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition. In this study, we discovered that PRP4 over-expression in HCT116 colon cancer cells induces cofilin dephosphorylation by inhibiting the Rho-ROCK-LIMK-cofilin pathway. Two-dimensional gel electrophoresis, and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF MS) analysis indicated increased expression of protein phosphatase 1A (PP1A) in PRP4-transfected HCT116 cells. The presence of PRP4 increased the expression of PP1A both at the mRNA and protein levels, which possibly activated cofilin through dephosphorylation and subsequently modulated the cell actin cytoskeleton. Furthermore, we found that PRP4 over-expression did not induce cofilin dephosphorylation in the presence of okadaic acid, a potent phosphatase inhibitor. Moreover, we discovered that PRP4 over-expression in HCT116 cells induced dephosphorylation of migration and invasion inhibitory protein (MIIP), and down-regulation of E-cadherin protein levels, which were further restored by the presence of okadaic acid. These findings indicate a possible molecular mechanism of PRP4-induced actin cytoskeleton remodeling and epithelial-mesenchymal transition, and make PRP4 an important target in colon cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PRP4 is involved in pre-mRNA splicing and cell signalling. </LI> <LI> PRP4 modulates the actin cytoskeleton of cancer cells via RhoA activity inhibition. </LI> <LI> PRP4 induces cofilin dephosphorylation by inhibiting the Rho-ROCK-LIMK-cofilin pathway in HCT116 cells. </LI> <LI> Dephosphorylation of cofilin results in F-actin stabilization, re-distribution of cytoplasmic actin, formation of actin stress fibers, and inhibition of cell motility. </LI> <LI> PRP4 over-expression induces the expressions of PP1A, which directly or indirectly dephosphorylates cofilin, resulting in actin cytoskeleton rearrangement, downregulation of E-cadherin, and EMT induction. Cofilin activation may be associated with EMT properties, and promotes the progression of human colon cancer. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P> <B>Proposed model for PRP4-induced cofilin and MIIP dephosphorylation and epithelial-mesenchymal transition (EMT) induction</B>. PRP4 over-expression results in cofilin and MIIP dephosphorylation, causing actin dynamics to increase, which may lead to EMT. Another proposed pathway for EMT induction by dephosphorylated MIIP is illustrated in the black-dotted panel. MIIP may inhibit the Rac1 signaling pathway through PAK1 (Rac1 downstream target) binding competition, which results in reduced lamellipodia formation and, finally, EMT.</P> <P>[DISPLAY OMISSION]</P>

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