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Pan-CDK inhibition augments cisplatin lethality in nasopharyngeal carcinoma cell lines and xenograft models

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Signal Transduction and Targeted Therapy 2018年第1期3卷 237-245页

作者： Nicholas LSyn Pei Li lim Li Ren Kong Lingzhi Wang Andrea Li-Ann Wong Chwee Ming lim Thomas Kwok Seng Loh Gerhard Siemeister Boon cher Goh Wen-Son Hsieh Cancer Science Institute of Singapore National University of SingaporeSingaporeSingapore Department of Haematology-Oncology National University Cancer InstituteSingaporeSingapore Department of Pharmacology Yong Loo Lin School of MedicineNational University Health SystemSingaporeSingapore Department of Otolaryngology-Head and Neck Surgery National University Health SystemSingaporeSingapore Drug Discovery TRG OncologyBayer Pharma AGBerlinGermany

In addition to their canonical roles in regulating cell cycle transition and transcription,cyclin-dependent kinases(CDKs)have been shown to coordinate DNA damage response pathways,suggesting a rational pairing of CDK inhibitors with genotoxic chemotherapeutic agents in the treatment of human ***,we report that roniciclib(BAY1000394),a potent pan-CDK inhibitor,displays promising anti-neoplastic activity as a single agent and potentiates cisplatin lethality in preclinical nasopharyngeal carcinoma(NPC)*** of the NPC cell lines HONE-1,CNE-2,C666-1,and HK-1 was effectively curbed by roniciclib treatment,with IC_(50)values between 11 and 38 nmol/*** anticancer effects were mediated by pleiotropic mechanisms consistent with successful blockade of cell cycle CDKs 1,2,3,and 4 and transcriptional CDKs 7 and 9,ultimately resulting in arrest at G1/S and G2/M,downregulation of the transcriptional apparatus,and repression of anti-apoptotic *** enhanced tumor cell apoptosis was achieved following combined treatment with 10 nmol/L roniciclib and 2.0μmol/L cisplatin;this combination therapy achieved a response over 250%greater than either drug *** roniciclib chemosensitized NPC cells to cisplatin,it did not sensitize untransformed(NP69)*** administration of 0.5 mg/kg roniciclib to BALB/c xenograft mice was well tolerated and effectively restrained tumor growth comparable to treatment with 6 mg/kg cisplatin,whereas combining these two agents produced far greater tumor suppression than either of the *** summary,these data demonstrate that roniciclib has strong anti-NPC activity and synergizes with cisplatin chemotherapy at clinically relevant doses,thus justifying further evaluation of this combinatorial approach in clinical settings.

关键词： cisplatin nasopharyngeal doses

Effect of formulation of alginate beads on their mechanical behavior and stiffness

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Particuology 2011年第3期9卷 228-234页

作者： Eng-Seng Chan Tek-Kaun lim Wan-ping Voo Ravindra Pogaku Beng Ti Tey Zhibing Zhang School of Engineering Monash University Jalan Lagoon Selatan 4~150 Bandar Sunway 5elangor Malaysia Centre of Materials and Minera/s School of Engineering and Information Technology Universiti Malaysia Sabah 88999 Kota Kinabalu Sabah Malaysia Department of Chemical and Environmental Engineering Faculty of Engineering Universiti Putra Malaysia 43400 Serdang Selangor Malaysia School of Chemical Engineering University of Birmingham Edgbaston Birmingham BI5 27Z United Kingdom

The aim of this work was to determine the effect of formulation of alginate beads on their mechanical behavior and stiffness when compressed at high speed. The alginate beads were formulated using different types and concentrations of alginate and gelling cations and were produced using an extrusiondripping method, Single wet beads were compressed at a speed of 40 mm/min, and their elastic limits were investigated, and the corresponding force versus displacement data were obtained. The Young＇s moduli of the beads were determined from the force versus displacement data using the Hertz＇s contact mechanics theory. The alginate beads were found to exhibit plastic behavior when they were compressed beyond 50% with the exception of copper-alginate beads for which yield occured at lower deformation, Alginate beads made of higher guluronic acid contents and gelling cations of higher chemical affinity were found to have greater stiffness. Increasing the concentration of alginate and gelling ions also generated a similar effect. At such a compression speed, the values of Young＇s modulus of the beads were found to be in the range between 250 and 900 kPa depending on the bead formulation.

关键词： Algioate Young's modulus Elastic limit Deformation Compression Hertz theory

Advances in fabricating spherical alginate hydrogels with controlled particle designs by ionotropic gelation as encapsulation systems

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Particuology 2016年第1期14卷 44-60页

作者： Jun-Yee Leong Weng-Hoong Lam Kiang-Wei Ho Wan-ping Voo Micky Fu-Xiang Lee Hui-Peng lim Swee-Lu lim Beng-Ti Tey Denis Poncelet alan Lagoon Selatan Bandar Sunway Selangor 46150 Malaysia Advanced Engineering Platform Monash University Malaysia Jalan Lagoon Selatan Bandar Sunway Selangor 46150 Malaysia Oniris UMR CNRS 6144 GEPEA rue de la Geraudiere BP82225 Nantes 44322 France

Alginate is a biopolymer that has exceptional gelling properties, which allow easy gel formation under safe and mild conditions. Consequently, it is often used to encapsulate a variety of cargos, such as cells, enzymes, and lipids, and is typically employed as a model to study hydrogel-based encapsulation sys- tems. Since the first use of alginate in the encapsulation field in the 1970s, many methods have been developed to produce alginate hydrogel particles of different sizes, structures, and morphologies. This review provides an overview of the current progress in the fabrication of alginate hydrogels with vari- ous particle designs, including a discussion of dispersion techniques to pre-template alginate particles, gelation mechanisms, considerations in selecting suitable fabrication methods, and future directions.

关键词： Alginate lonotropic gelation Immobilization Encapsulation Hydrogel

Stereotactic radiotherapy and the potential role of magnetic resonance-guided adaptive techniques for pancreatic cancer

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World Journal of Gastroenterology 2022年第7期28卷 745-754页

作者： Tai Ermongkonchai Richard Khor Vijayaragavan Muralidharan Niall Tebbutt Kelvin lim Numan Kutaiba Sweet ping Ng Department of Radiation Oncology Olivia Newton-John Cancer Centre at Austin HealthHeidelberg 3084VictoriaAustralia Department of Surgery Austin HealthHeidelberg 3084VictoriaAustralia Department of Medical Oncology Olivia Newton-John Cancer Centre at Austin HealthHeidelberg 3084VictoriaAustralia Department of Diagnostic Radiology Austin HealthHeidelberg 3084VictoriaAustralia

BACKGROUND Pancreatic cancer is a malignancy with one of the poorest prognoses amongst all *** with unresectable tumours either receive palliative care or undergo various chemoradiotherapy *** techniques are often associated with acute gastrointestinal toxicities,as adjacent critical structures such as the duodenum ultimately limits delivered *** body radiotherapy(SBRT)is an advanced radiation technique that delivers highly ablative radiation split into several fractions,with a steep dose fall-off outside target *** To discuss the latest data on SBRT and whether there is a role for magnetic resonance-guided techniques in multimodal management of locally advanced,unresectable pancreatic *** We conducted a search on multiple large databases to collate the latest records on radiotherapy techniques used to treat pancreatic *** of 1229 total records retrieved from our search,36 studies were included in this *** Studies indicate that SBRT is associated with improved clinical efficacy and toxicity profiles compared to conventional radiotherapy *** dose escalation to the tumour with SBRT is limited by the poor soft-tissue visualisation of computed tomography imaging during radiation planning and treatment *** resonance-guided techniques have been introduced to improve imaging quality,enabling treatment plan adaptation and re-optimisation before delivering each *** Therefore,SBRT may lead to improved survival outcomes and safer toxicity profiles compared to conventional techniques,and the addition of magnetic resonance-guided techniques potentially allows dose escalation and conversion of unresectable tumours to operable cases.

关键词： Magnetic resonance imaging Pancreatic cancer Radiotherapy Stereotactic Adaptive techniques

Advances on ultra-sensitive electrospun nanostructured electrochemical and colori metric sensors for diabetes mellitus detection

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Nano Materials Science 2021年第4期3卷 321-343页

作者： Mohamed Hasaan Hussain lim ping Fook Maria Kana Sanira Putri Huey Ling Tan Noor Fitrah Abu Bakar Norbert Radacsi School of Chemical Bngineering College of Engineering University Teknologi MARA 40450 Shah AlamSelangorMalaysia School of Engineering Institute for Materials and ProcessesThe University of EdinburghRobert Stevenson RoadEdinburghEH93FBUnited Kingdom

Recent developments in the biochemical and medicinal industries have been heavily focused on producing affordable glucose biosensors due to the condi nuous annual increase of diabetic patients *** devel-opment of a fast,accurate,and reliable glucose sensor will increase confidence in controlling di abetes mellitus and its assoclated health complications among the diabetic *** is a versatile method that can produce complex nanofbrous assemblies with attractiwe and functional characteristics from varlous *** nanofibers demonstrated high efficiency in the immobilization of biological molecules,which can improve the sensing performance *** ation of polymer electrospun nanofibers with metal nanoparticles,metal oxde or transition metal in producing nanobiocomposites is also a highly popul ar approach in the past few *** report presents the current progress and research trends of the technique,focusing on varous ma-terials and fabrication strategies used to produce biosensing *** helps readers decide the suitable approach in designing highly sensitive,selective,fast,and inexpensive glucose sensors.

关键词： Glucose sensor Electrospinning Nanofiber Electrochemical sensing Colorimetric sensing

Genetic diversity of the S-type small subunit ribosomal RNA gene of Plasmodium knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia

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Asian Pacific Journal of Tropical Medicine 2024年第2期17卷 84-90页

作者： Eric Tzyy Jiann Chong Joveen Wan Fen Neoh Tiek Ying Lau Kek Heng Chua Yvonne Ai-Lian lim ping-Chin Lee Biotechnology Research Institute Universiti Malaysia SabahJalan UMS88400 Kota KinabaluSabahMalaysia Department of Biomedical Science Faculty of Medicine BuildingUniversity of Malaya50603 Kuala LumpurMalaysia Centre of Excellence for Research in AIDS(CERiA) University of Malaya50603 Kuala LumpurMalaysia Faculty of Science and Natural Resources Universiti Malaysia SabahJalan UMS88400 Kota KinabaluSabahMalaysia

Objective:To determine the genetic diversity of Plasmodium(P.)knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia,targeting the S-type SSU rRNA gene and including aspects of natural selection and ***:Thirty-nine blood samples infected with *** were collected in Sabah,Malaysian Borneo and Peninsular *** S-type SSU rRNA gene was amplified using polymerase chain reaction,cloned into a vector,and *** natural selection and haplotype of the S-type SSU rRNA gene sequences were determined using DnaSP v6 and illustrated using NETWORK *** study's 39 S-type SSU rRNA sequences and eight sequences from the Genbank database were subjected to phylogenetic analysis using MEGA ***:Overall,the phylogenetic analysis showed no evidence of a geographical cluster of *** isolates from different areas in Malaysia based on the S-type SSU rRNA gene *** S-type SSU rRNA gene sequences were relatively conserved and with a purifying *** sharing of the S-type SSU rRNA gene was observed between the *** isolates in Sabah,Malaysian Borneo,but not between Sabah,Malaysian Borneo and Peninsular ***:This study suggests that the S-type SSU rRNA gene of *** isolates in Sabah,Malaysian Borneo,and Peninsular Malaysia has fewer polymorphic sites,representing the conservation of the *** features make the S-type SSU rRNA gene suitable for comparative studies,such as determining the evolutionary relationships and common ancestry among *** species.

关键词： Plasmodium knowlesi S-type small subunit ribosomal RNA Genetic diversity Natural selection Haplotype

Forensic examination of plastic drinking straws based on their physical characteristics and manufacturing marks

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Forensic Sciences Research 2020年第1期5卷 64-73页

作者： Alaric C.W.Koh Suat ping Oh Shing Min lim Sok Yee Yew Jean Chen Vicky Y.S.Chow Forensic Chemistry and Physics Laboratory Health Sciences AuthoritySingapore

This work highlights the evidential value of examining plastic drinking straws to establish linkages between multiple sources for forensic intelligence,investigative or prosecution *** drinking straws are commonly encountered in drug cases,either as inhalational paraphernalia or as packaging ***,to the best of our knowledge,systematic studies on the evidential value of straws have not previously been carried *** this study,over 80 packets of clear and colourless straws—most of which were visually similar—were purchased from various commercial outlets in *** physical characteristics(viz.,polarizing patterns,thickness,circumference and mass per unit length)and the manufactur-ing marks of these straws were examined to assess their potentials for discriminating straws from different *** of polarizing patterns yielded a discrimination of approximately 69%,while thickness,circumference,and mass per unit length measurements resulted in lower *** microscopy of manufacturing marks was found to be the most discriminating among all techniques employed herein,with a discrimination of about 95%,even among straws with similar polarizing patterns.

关键词： Forensic sciences drug packaging plastics manufacturing marks tool marks straw discrimination

Repeated exposure to moxa-burning smoke: its acute and chronic toxicities in rats

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Journal of Traditional Chinese Medicine 2018年第1期38卷 67-75页

作者： Han Li Liu Changxi Liu ping Hu Hai Yang Jia Cai Hong lim Minyee Zhu Maoxiang Pan Xiujie Huang Jian Cui Yingxue Lao Lixing Zhao Baixiao Shool of Chinese medicine Beijing University of Chinese Medicine Healthcare Management Center Beijing Electric Power Hospital Department of Acupunture Beijing Hospital of Acupuncture and Moxibustion Shool of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine Department of Traditional Chinese Medicine Chongqing Yubei District Hospital of Traditional Chinese Medicine Institute of Radiation Medicine China Academy of Military Medical Science Department of Acupunture Beijing Dong Fang Hospital Department of Acupunture Beijing Hospital of Traditional Chinese Medicine School of Chinese Medicine The University of Hong Kong

OBJECTIVE： To assess toxicities of the air in Chinese medicine clinics polluted by moxa-burning smoke due to moxibustion-derived burning products （MBP）. METHODS： Both acute and chronic toxicity studies were conducted. For the acute toxicity study, five groups of Wistar rats （n = 16/group, male： female = 1 ： 1） were exposed to five different concentrations （95%, 90%, 85%, 80% and 75%, respectively） of MBP for 2 h. For the chronic toxicity study, another three groups of male rats （n = 21/group） were ex- posed to MBP in three concentrations （10%, 40% and 70%, respectively） and one control group ex- posed to clean air 20 min/d for 144 d. Routine ex- aminations were performed and analyzed by analy- sis of variance and dose-response relationship. RESULTS： In the acute toxicity study, the number of dead rats in the 95%, 90%, 85%, 80% and 75% groups were 16, 13, 7, 6 LDS0 of 86.274% after or and 3, respectively, with during the 2 h exposure. In the chronic toxicity study, MBP exposure induced a decline in activity of the rats. Rats in the 10% group showed no signs of toxicity, while those in the 40% MBP group showed toxicity effects on the body weights （P 〈 0.05） and lung. Rats in the 70% MBP group also presented with reversible damage in the blood coagulation system （P 〈 0.05）. CONCLUSION： Exposure to 10% MBP, which is equivalent to 27.45 mg/m^3 was under the critical threshold for male rats＇safety. Exposure to MBP above that limit induced lung damage. MBP in clinics need to be reduced to a safe level with enhanced ventilation.

关键词： Smoke Moxibustion Environmental exposure Toxicity tests

Entamoeba histolytica acetyl-CoA synthetase:biomarker of acute amoebic liver abscess

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Asian Pacific Journal of Tropical Biomedicine 2014年第6期4卷 446-450页

作者： lim Boon Huat Alfonso Olivos Garcia Tan Zi Ning Wong Weng Kin Rahmah Noordin Siti shafiqah Anaqi Azham Lee zhi Jie Guee cher Ching Foo Phiaw Chong Pim Chau Dam Biomedicine Programme.School of Health Sciences Universiti Sains Malaysia Departmento de Medicina Experimental Facultad de MedicinaUniversidad Nacional Autonoma de Mexico Department of Medicine Allianze University College of Medical Sciences Institute for Research in Molecular Medicine 11800 University Sains Malaysia

Objective:To characterize the Entamoeba histolytica(***)antigen(s)recognized by moribound amoebic liver abscess ***:Crude soluble antigen of *** was probed with sera of moribund hamsters in 1D-and 2D-Westem blot *** antigenic protein was then sent for tandem mass spectrometry *** corresponding gene was cloned and expressed in Escherichia coli BL21-AI to produce the recombinant *** ADP-forming acetyl-CoA synthetase(EhACS)protein.A customised ELISA was developed to evaluate the sensitivity and specificity of the recombinant ***:A^75 kDa protein band with a pl value of 5.91-6.5 was found to be antigenic;and not detected by sera of hamsters in the control *** mass spectrometry analysis revealed the protein to be the 77 kDa *** ADP-forming acetyl-CoA synthetase(EhACS).The customised ELISA results revealed 100%sensitivity and 100%specificity when tested against infected(n=31)and control group hamsters(n=5)serum samples,***:This rinding suggested the significant role of EhACS as a biomarker for moribund hamsters with acute amoebic liver abscess(ALA)*** is deemed pertinent that future studies explore the potential roles of EhACS in better understanding the pathogenesis of ALA;and in the development of vaccine and diagnostic tests to control ALA in human populations.

关键词： Entamoeba histolytica Amoebic liver abscess Biomarker Acetyl-CoA synthetase Recombinant EhACS Western blot