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Targeting LIF/LIFR signaling in cancer

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Genes & Diseases 2022年第4期9卷 973-980页

作者： Suryavathi Viswanadhapalli Kalarickal V.Dileep Kam Y.J.Zhang Hareesh B.Nair ratna K.vadlamudi Department of Obstetrics and Gynecology University of Texas Health San AntonioSan AntonioTX 78229USA Laboratory for Structural Bioinformatics Center for Biosystems Dynamics ResearchRIKENYokohamaKanagawa 230-0045Japan Evestra Inc.San AntonioTX 78245USA Mays Cancer Center University of Texas Health San AntonioSan AntonioTX 78229USA

Leukemia inhibitory factor (LIF), and its receptor (LIFR), are commonly over-expressed in many solid cancers and recent studies have implicated LIF/LIFR axis as a promising clinical target for cancer therapy. LIF/LIFR activate oncogenic signaling pathways including JAK/STAT3 as immediate effectors and MAPK, AKT, mTOR further downstream. LIF/LIFR signaling plays a key role in tumor growth, progression, metastasis, stemness and therapy resistance. Many solid cancers show overexpression of LIF and autocrine stimulation of the LIF/LIFR axis;these are associated with a poorer relapse-free survival. LIF/LIFR signaling also plays a role in modulating multiple immune cell types present in tumor micro environment (TME). Recently, two targeted agents that target LIF (humanized anti-LIF antibody, MSC-1) and LIFR inhibitor (EC359) were under development. Both agents showed effectivity in preclinical models and clinical trials using MSC-1 antibody are in progress. This article reviews the significance of LIF/LIFR pathways and inhibitors that disrupt this process for the treatment of cancer.

关键词： LIF LIFR LIFR inhibitor STAT3 Targeted therapy

Gravity-driven powder flow and the influence of external vibration on flow characteristics

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Particuology 2024年第5期88卷 201-209页

作者： Muhammad Shahid Ansari ratna Kumar Annabattula Sathyan Subbiah Department of Mechanical Engineering Indian Institute of Technology MadrasChennai 600036India

The controlled and homogeneous flow of dry granular powders through hoppers is essential for applications,namely,packaging of food grains,fertilizers and additive manufacturing processes such as directed energy deposition for better product *** of the major issues encountered in the granular flows through hoppers is flow stagnation due to the well-known arching ***-assisted granular flow through hoppers is one of the mechanisms used for better mass flow *** this work,the influence of external mechanical vibration on the powder flow is investigated experimentally and using discrete element ***,the mass flow rate through the hopper increases with an increase in vibration amplitude and then decreases,signifying the existence of an optimal amplitude of *** DEM simulations explained the underlying mechanisms for the existence of an optimal amplitude of vibration corresponding to the maximum mass flow rate.A range of vibration amplitudes from 0 mm to 3.5 mm is used to study the flow behaviour;the maximum flow of around 33 g/s to 35 g/s is observed for 0.75 mm to 1.25 mm vibration amplitude for the hopper-particle combination studied in this *** work also reports the influence of vibration frequency,hopper,and particle dimension on the flow *** research facilitates the effective use of mechanical vibration to enhance powder flow that can further be extended to non-spherical and multi-material particles.

关键词： Discrete element method Flow rate Granular flow Path tracking Vibration intensity

Surgical menopause enhances hippocampal amyloidogenesis following global cerebral ischemia

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Journal of Sport and Health Science 2014年第3期3卷 206-216页

作者： Erin L.Scott Quan-Guang Zhang Yan Dong Dong Han Rui-Min Wang ratna K.vadlamudi Darrell W.Brann University System of Georgia MD/PhD Program Georgia Regents University Institute of Molecular Medicine and Genetics.Georgia Regents University Department of Obstetrics and Gynecology.University of Texas Health Science Center at San Antonio

Background： Prematurely menopausal women have a doubled lifetime risk of dementia and a 5-fold increased risk of mortality from neuro- logical disorders, but the molecular mechanisms underlying these risks remain unclear. We hypothesized that ischemia-induced amyloidogenesis may be enhanced in the hippocampus following prolonged loss of ovarian 17β-estradiol （E2）, which could contribute to these phenomena. Methods： The current study used a rat model of premature surgical menopause （10-week bilateral ovariectomy） with E2 therapy either initiated immediately （short-term E2 deprivation （STED）） or delayed to the end of the ovariectomy period （long-term E2 deprivation （LTED））. One week after continuous, subcutaneous E2 therapy, we subjected animals to 10-min global cerebral ischemia （GCI） to assess the effect of LTED on ischemia-induced amyloidogenesis in the hippocampal CA1. Results： The present study revealed that while hippocampal β-amyloid （Aβ） is not typically enhanced following GCI, there is a rapid, robust elevation of endogenous Aβ in LTED females after GCI. In STED females, we observed that GCI attenuates and E2 maintains A Disintegrin and Metalloprotease 10 （ADAM 10） expression in the hippocampal CA1, and concurrently, GCI increases and E2 decreases BACE1 levels in the same region. Intriguingly, however, we observed a loss of E2 regulation of ADAM 10, ADAM 17, and BACE 1 levels in the hippocampal CA I of LTED females, which provides mechanistic evidence for the enhanced post-ischemic Aβ load following LTED. We also observed loss of E2 regulation of tau hyperphosphorylation in LTED females subjected to GCI. Conclusion： Collectively, these studies partially explain the enhanced risk of dementia and mortality from neurological disorders seen in prematurely menopausal women and support timely initiation of E2 therapy to yield maximum neurological benefit.

关键词： Amyloid Dementia Estrogen Ischemia Surgical menopause

EC330, a small-molecule compound, is a potential novel inhibitor of LIF signaling

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Journal of Molecular Cell Biology 2020年第6期12卷 477-480页

作者： Xuetian Yue Fangnan Wu Jianming Wang Kaitlin Kim Bindu Santhamma Kalarickal VDileep Kam YJZhang Suryavathi Viswanadhapalli ratna Kvadlamudi Gulzar Ahmed Zhaohui Feng Klaus Nickisch Wenwei Hu Rutgers Cancer Institute of New Jersey Rutgers UniversityNew BrunswickNJ 08903USA Evestra Inc.San AntonioTX 78245USA Laboratory for Structural Bioinformatics Center for Biosystems Dynamics ResearchRIKENYokohama 230-0045Japan Department of Obstertrics and Gynecology University of Texas Health San AntonioSan AntonioTX 78229USA

Dear Editor,LIF,a multi-functional cytokine,is frequently overexpressed in many human cancers,including breast,colorectal,and pancreatic cancers(Liu et al.,2013;Li et al.,2014;Yu et al.,2014;Pascual-Garcia et al.,2019;Shi et al.,2019;Wang et al.,2019).LIF overexpression is frequently associated with poor prognosis in human cancers(Liu et al.,2013;Li et al.,2014;Yu et al.,2014).LIF functions through binding to LIF receptor complex composed of LIF receptor(LIF-R)and glycoprotein gp130(Taga and Kishimoto,1997;Heinrich et al.,2003;Watanabe et al.,2006).LIF overexpression induces activation of several oncogenic signaling pathways in a cell/tissue type-specific manner,including STAT3,PI3K/AKT,and mTOR,which in turn promotes proliferation,metastasis,and therapeutic resistance of cancer cells(Liu et al.,2013;Li et al.,2014;Yu et al.,2014;Shi et al.,2019).Recent studies have suggested that LIF is a potential important target for cancer therapy,especially for cancers with LIF *** neutralization antibodies(LIF neu Abs)have been reported to block LIF signaling and largely abolish the promoting effect of LIF on cancer progression(Li et al.,2014;Yue et al.,2016;Shi et al.,2019).

关键词： PI3K/AKT STAT3 metastasis

Tumor cell-intrinsic PD-L1 promotes tumor-initiating cellgeneration and functions in melanoma and ovarian cancer

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Signal Transduction and Targeted Therapy 2016年第1期1卷 1-9页

作者： Harshita B Gupta Curtis A Clark Bin Yuan Gangadhara Sareddy Srilakshmi Pandeswara Alvaro S Padron Vincent Hurez Jose Conejo-Garcia ratna vadlamudi Rong Li Tyler J Curiel Department of Medicine University of Texas Health Science CenterSan AntonioTXUSA The Graduate School of Biomedical Sciences University of Texas Health Science CenterSan AntonioTXUSA Department of Molecular Medicine University of Texas Health Science CenterSan AntonioTXUSA Department of Obstetrics and Gynecology University of Texas Health Science CenterSan AntonioTXUSA Tumor Microenvironment and Metastasis Program The Wistar InstitutePhiladelphiaPAUSA Cancer Therapy and Research Center University of Texas Health Science CenterSan AntonioTXUSA Department of Microbiology and Immunology University of Texas Health Science CenterSan AntonioTXUSA

As tumor PD-L1 provides signals to anti-tumor PD-1^(+)T cells that blunt their functions,αPD-1 andαPD-L1 antibodies have been developed as anti-cancer immunotherapies based on interrupting this signaling ***,tumor cell-intrinsic PD-L1 signals also regulate immune-independent tumor cell proliferation and mTOR signals,among other important ***-initiating cells(TICs)generate carcinomas,resist treatments and promote *** show here that in murine B16 melanoma and ID8agg ovarian carcinoma cells,TICs express more PD-L1 versus *** PD-L1 in B16 and ID8agg cells by shRNA(‘PD-L1lo’)reduced TIC numbers,the canonical TIC genes nanog and pou5f1(oct4),and functions as assessed by tumorosphere development,immune-dependent and immune-independent tumorigenesis,and serial transplantability in ***,tumor PD-L1 sensitized TIC to interferon-γand rapamycin in ***-intrinsic PD-L1 similarly drove functional TIC generation,canonical TIC gene expression and sensitivity to interferon-γand rapamycin in human ES2 ovarian cancer ***,tumor-intrinsic PD-L1 signals promote TIC generation and virulence,possibly by promoting canonical TIC gene expression,suggesting that PD-L1 has novel signaling effects on cancer pathogenesis and treatment responses.

关键词： melanoma interferon initiating

Investigating the future study area on VR technology implementation in safety training: A systematic literature review

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Journal of Safety Science and Resilience 2024年第2期5卷 235-248页

作者： Adithya Sudiarno ratna Sari Dewi Retno Widyaningrum Ahmad Murtaja Dzaky Ma'arij Aldi Yustisia Supriatna Industrial and Systems Engineering Department Institut Teknologi Sepuluh NopemberSurabaya60111Indonesia Occupational Safety and Health Councilof East Java Province(Dewan K3 Provinsi Jawa Timur) Surabaya60234Indonesia

Safety training is the exercise normally conducted for all the current and future employees of a company to identify and recognize occupational hazards and diseases as well as determine the appropriate controlling ***,virtual reality(VR)is a technology developed to virtually simulate the surrounding envi-ronment to ensure immersive experience and interaction through artificial three-dimensional(3D)*** devices have been developed to be more compact,easy to use,and affordable to enable people to enjoy immersive virtual experiences and provide interactive and realistic *** has made technology one of the most popular forms of media for different kinds of training,such as safety-related ***,this study aimed to review the use of VR in safety training through the systematic literature review(SLR)*** process focused on developing 4 primary questions(PQs)classified into 11 systematic research questions(SRQs)for discussion points concerning current developments in VR technology *** were further combined with the preferred reporting items for systematic reviews and meta-analyses(PRISMA)flow diagrams in selecting the relevant *** questions were also used to investigate the scenarios,methods,objectives,and outcomes of previous *** results showed the need for further studies on the application of VR technology in safety training in other fields such as firefighting,chemical industry,maritime,***,several scenarios such as construction design,disaster response,rescue procedures,and others need to be *** study also provides information on the gaps for future study,including the exploration of a broader range of industries and VR scenarios.

关键词： Virtual reality Safety training VRfuture development Systematic literaturereview

Impact of applying the theory of human becoming and self-care deficit theory of nursing on insomnia in after stroke urinary incontinence patients

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Frontiers of Nursing 2024年第3期11卷 259-266页

作者： Heltty Heltty ratna Sitorus Haryanto Haryanto Medical Surgical Nursing Department Faculty of Health ScienceUniversitas Mandala WaluyaKendariSulawesi Tenggara 93121Indonesia Medical Surgical Nursing Department Nursing FacultyUniversitas IndonesiaDepokJawa Barat 16424Indonesia Medical Surgical Nursing and Wound Management Department Nursing FacultyWest Kalimantan Muhammadiyah Institute of Technology and HealthKalimantan Barat 78122Indonesia

Objective:To determine the impact of applying the theory of human becoming and self-care deficit theory of nursing in overcoming insomnia in patients of urinary incontinence(UI)after *** is a sleep disorder experienced by UI patients after stroke which can exacerbate problems related to brain damage and can complicate the recovery ***:This study was a quasi-experimental conducted in 4 ***-six patients were selected by convenience sampling and divided into 2 groups(the intervention and control group).Participants in the intervention group received“applying the theory of Human becoming and self-care deficit theory of nursing,”starting when the patient is about to go home from the hospital and continuing at the *** of insomnia is done using the Pittsburgh Sleep Quality Index(PSQI).Results:The mean insomnia scores of participants from both groups increased in the first and third *** second and third insomnia measurements found a significant difference(P<0.001).This intervention decreased the average score of insomnia by 4.11 times in the second measurement and 5.82 times in the third *** most important item that decreased in the third measurement of insomnia was sleep ***:Applying the theory of human becoming and self-care deficit theory of nursing in this study significantly decreased the insomnia score of post-stroke UI *** can be used as a guide for nurses,patients,and families in managing *** addition,the application of nursing theory in nursing practice can systematize nursing care plans and organize the knowledge of professionals into a conceptual framework,as well as provide effective guidance for nurses on what to do.

关键词： human becoming theory insomnia self-care deficit theory stroke urinary incontinence

Hydrocarbon Potential of the Triassic-Jurassic Sediments in Southeast Sulawesi, Indonesia, Based on Lithofacies and Geochemical Analysis

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Open Journal of Geology 2024年第8期14卷 723-745页

作者： Muhammad Sulhuzair Burhanuddin Shun Chiyonobu Takuto Ando Anggi Yusriani ratna Husain Suryawan Asfar Graduate School of International Resources Sciences Akita University Akita Japan Geological Department of Hasanuddin University Makassar Indonesia Geoservices Laboratory South Jakarta Indonesia Geological Department of Haluoleo University Kendari Indonesia

Triassic-Jurassic carbonates widely distributed in Eastern Indonesia are believed as oils source rock. The Mesozoic Tokala Formation exhibit source rock potential, as evidenced by high contents of organic matter. Recent exploration has been conducted in southeastern Sulawesi, targeting the Mesozoic intervals. Therefore, in this study, we attempted to determine source rock potential of Tokala Formation outcropped in southeastern Sulawesi area and its capability to generate hydrocarbon. Five distinct lithofacies were delineated, emphasizing lithological and mineralogical features: foraminifera wackestone (FW), lime mudstone (LM), massive bioturbated calcareous-argillaceous shale (MBCAS), weakly laminated argillaceous-calcareous shale (WLACS), and strongly laminated calcareous-argillaceous shale (SLCAS). Subsequent analyses showed that carbonate-rich samples (FW and LM facies, >50% CaO) had poor source rock potential. Conversely, shale facies with moderate carbonate content (WLACS, MBCAS, and SLCAS, 15% - 50% CaO) had good to excellent source rock characteristics, qualifying them as preferable source rock. In addition, levels of SiO2 and Al2O3 should not be neglected, as these constituents play important roles in clay mineral adsorption. Laminated shale facies with moderate CaO content tended to be more promising as source rock than bioturbated facies. The shale facies of Tokala Formation indicate prospective source rock horizon.

关键词： Source Rock Triassic-Jurassic Source Rock Lithofacies Southeastern Sulawesi Tokala Formation

Application of Pomegranate Rind Extract for Improvement of Functional Properties of Various Materials—A Critical Review

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Open Journal of Composite Materials 2024年第2期14卷 71-90页

作者： Habeebunissa Nooman Narayanan Gokarneshan Murugan Umamaheswari Muthumani Dhiliphan Kumar Usha Kumari ratna Jayagopal Lavanya Senthamarai Kannan Umamageshwari Sona Mohandas Anton Zahurudeen Shahanaz Venkatesan Sathya David Piriadarshani Chokkanathan Kayalvizhi Department of Knitwear Design National Institute of Fashion Technology Chennai India Department of Textile Chemistry SSM College of Engineering Komarapallayam India Department of Management Studies Dr. SNS Rajalakshmi College of Arts and Science Coimbatore India Department of Business Administration Kalasalingam Business School Kalasalingam Academy of Research and Education Srivilliputhur India Department of Textiles and Clothing Avinashi Lingam Institute for Home Science and Higher Education for Women Coimbatore India Department of Fashion Design SRM Institute of Science and Technology (Kattankalathur) Chennai India Department of Fashion Design Hindustan Institute of Technology and Science Chennai India Department of Fashion Design SRM Institute of Science and Technology (Ramapuram) Chennai India Department of Mathematics Hindustan Institute of Technology and Science Chennai India Department of Textile Technology Jaya Engineering College Tiruninravur India

Pomegranate rind is abundantly available as a waste material. Pomegranate Rind Extract (PRE) can be applied to cotton fabrics for its natural colours, as a mordanting agent and also for imparting certain functional properties such as fire retardancy and antimicrobial properties. This paper reviews the feasibility of Pomegranate Rind Extract to improve the functional properties of cellulosic fabrics. Studies show that varying concentrations and higher temperatures that were used to apply the extract on the fabric, resulted in enhanced functional properties. At a particular concentration, the treated fabric showed a 15 times lower burning rate in comparison with the control fabric. Also, antimicrobial efficacy has been observed against Gram-positive and Gram-negative bacteria. Due to the natural colouring material, it can be used as a natural dye on cotton material. The fire retardancy of pomegranate rind extract was tested on jute material under varying alkalinity. Research has indicated that pomegranate rind extract could be used to dye polyamide as well. The rubbing and wash fastness of the finished fabrics is good. The light fastness was fair, and its antibacterial efficiency against tested bacteria was good.

关键词： Natural Polymers Synthetic Polymers Pomegranate Rind Extract (PRE) Dyeing Functional Property