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Design methods for antimicrobial peptides with improved performance

Zoological Research 2023年第6期44卷 1095-1114页

作者： james mwangi Peter Muiruri Kamau Rebecca Caroline Thuku Ren Lai Key Laboratory of Bioactive Peptides of Yunnan Province Engineering Laboratory of Peptides of Chinese Academy of SciencesKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Centre for Non-Human PrimatesKunming Primate Research CentreNational Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Sino-African Joint Research CentreNew Cornerstone Science InstituteKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650107China Centre for Evolution and Conservation Biology Southern Marine Science and Engineering Guangdong LaboratoryGuangzhouGuangdong 511458China Kunming College of Life Science University of Chinese Academy of SciencesKunmingYunnan 650204China

The recalcitrance of pathogens to traditional antibiotics has made treating and eradicating bacterial infections more difficult.In this regard,developing new antimicrobial agents to combat antibiotic-resistant strains has become a top priority.Antimicrobial peptides(AMPs),a ubiquitous class of naturally occurring compounds with broadspectrum antipathogenic activity,hold significant promise as an effective solution to the current antimicrobial resistance(AMR)crisis.Several AMPs have been identified and evaluated for their therapeutic application,with many already in the drug development pipeline.Their distinct properties,such as high target specificity,potency,and ability to bypass microbial resistance mechanisms,make AMPs a promising alternative to traditional antibiotics.Nonetheless,several challenges,such as high toxicity,lability to proteolytic degradation,low stability,poor pharmacokinetics,and high production costs,continue to hamper their clinical applicability.Therefore,recent research has focused on optimizing the properties of AMPs to improve their performance.By understanding the physicochemical properties of AMPs that correspond to their activity,such as amphipathicity,hydrophobicity,structural conformation,amino acid distribution,and composition,researchers can design AMPs with desired and improved performance.In this review,we highlight some of the key strategies used to optimize the performance of AMPs,including rational design and de novo synthesis.We also discuss the growing role of predictive computational tools,utilizing artificial intelligence and machine learning,in the design and synthesis of highly efficacious lead drug candidates.

关键词： Antimicrobial resistance Antimicrobial peptides Design methods Peptidomimetics Artificial intelligence

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Characterization and Modeling of Mechanical Properties of Additively Manufactured Coconut Fiber-Reinforced Polypropylene Composites

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Advances in Materials Physics and Chemistry 2024年第6期14卷 95-112页

作者： George Mosi Bernard W. Ikua Samuel K. Kabini james W. mwangi Department of Mechatronic Engineering Jomo Kenyatta University of Agriculture and Technology Juja Kenya

In the face of the increased global campaign to minimize the emission of greenhouse gases and the need for sustainability in manufacturing, there is a great deal of research focusing on environmentally benign and renewable materials as a substitute for synthetic and petroleum-based products. Natural fiber-reinforced polymeric composites have recently been proposed as a viable alternative to synthetic materials. The current work investigates the suitability of coconut fiber-reinforced polypropylene as a structural material. The coconut fiber-reinforced polypropylene composites were developed. Samples of coconut fiber/polypropylene (PP) composites were prepared using Fused Filament Fabrication (FFF). Tests were then conducted on the mechanical properties of the composites for different proportions of coconut fibers. The results obtained indicate that the composites loaded with 2 wt% exhibited the highest tensile and flexural strength, while the ones loaded with 3 wt% had the highest compression strength. The ultimate tensile and flexural strength at 2 wt% were determined to be 34.13 MPa and 70.47 MPa respectively. The compression strength at 3 wt% was found to be 37.88 MPa. Compared to pure polypropylene, the addition of coconut fibers increased the tensile, flexural, and compression strength of the composite. In the study, an artificial neural network model was proposed to predict the mechanical properties of polymeric composites based on the proportion of fibers. The model was found to predict data with high accuracy.

关键词： Additive Manufacturing Artificial Neural Network Mechanical Properties Natural Fibers Polypropylene

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Antimicrobial peptides: new hope in the war against multidrug resistance

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Zoological Research 2019年第6期40卷 488-505页

作者： james mwangi Xue Hao Ren Lai Zhi-Ye Zhang Key Laboratory of Bioactive Peptides of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming Yunnan 650204China Sino-African Joint Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Institutes for Drug Discovery and Development Chinese Academy of SciencesShanghai 201203China KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases Kunming Institute of ZoologyChinese Academy of SciencesKunming Yunnan 650223China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan Hubei 430071China

The discovery of antibiotics marked a golden age in the revolution of human medicine. However,decades later, bacterial infections remain a global healthcare threat, and a return to the pre-antibiotic era seems inevitable if stringent measures are not adopted to curb the rapid emergence and spread of multidrug resistance and the indiscriminate use of antibiotics. In hospital settings, multidrug resistant(MDR) pathogens, including carbapenem-resistant Pseudomonas aeruginosa, vancomycin-resistant enterococci(VRE), methicillin-resistant Staphylococcus aureus(MRSA), and extendedspectrum β-lactamases(ESBL) bearing Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae are amongst the most problematic due to the paucity of treatment options,increased hospital stay, and exorbitant medical costs. Antimicrobial peptides(AMPs) provide an excellent potential strategy for combating these threats. Compared to empirical antibiotics, they show low tendency to select for resistance, rapid killing action, broad-spectrum activity, and extraordinary clinical efficacy against several MDR strains. Therefore, this review highlights multidrug resistance among nosocomial bacterial pathogens and its implications and reiterates the importance of AMPs as next-generation antibiotics for combating MDR superbugs.

关键词： Multidrug resistance Nosocomial infections Antimicrobial peptide Antibiotic alternatives

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Anticarin-β shows a promising antiosteosarcoma effect by specifically inhibiting CCT4 to impair proteostasis

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2268-2279页

作者： Gan Wang Min Zhang Ping Meng Chengbo Long Xiaodong Luo Xingwei Yang Yunfei Wang Zhiye Zhang james mwangi Peter Muiruri Kamau Zhi Daic Zunfu Ke Yi Zhang Wenlin Chen Xudong Zhao Fei Ge Qiumin Lv Mingqiang Rong Dongsheng Li Yang Jin Xia Sheng Ren Lai Key Laboratory of Animal Models and Human Disease Mechanisms Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan ProvinceKIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesNational Resource Center for Non-Human PrimatesKunming Primate Research Centerand National Research Facility for Phenotypic&Genetic Analysis of Model Animals(Primate Facility)Kunming Institute of ZoologyKunming 650107China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China Institutes for Drug Discovery and Development Chinese Academy of SciencesShanghai 201203China Sino-African Joint Research Center Chinese Academy of ScienceWuhan 430074China Department of Pathology First Afﬁliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Orthopaedic Surgery First Afﬁliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Breast Surgery Third Afﬁliated Hospital of Kunming Medical UniversityYunnan Cancer CenterKunming 650118China Department of Breast Surgery First Afﬁliated Hospital of Kunming Medical UniversityKunming 650032China Department of Biosciences University of OsloOslo 0316Norway Key Laboratory of Environment and Health Ministry of Education&Ministry of Environmental ProtectionAnd State Key Laboratory of Environmental HealthSchool of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 434000China Center for Biosafety Mega-Science Chinese Academy of SciencesWuhan 430071China

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex(TRiC) contains eight paralogous subunits(CCT1-8), and assists the folding of as many as 10% of cytosolic proteome.TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma,and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma.Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

关键词： Proteostasis CCT TRiC Osteosarcoma STAT3 Anticarin-β PDX model

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Isolation and Characterization of SARS-CoV-2 in Kenya

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American Journal of Molecular Biology 2024年第2期14卷 66-83页

作者： Albina Makio Robinson Mugasiali Irekwa Matthew Mutinda Munyao Caroline Wangui Njoroge Peter Kipkemboi Rotich Tonny Teya Nyandwaro Joanne Jepkemei Yego Anne Wanjiru mwangi james Hungo Kimotho Ronald Tanui Vincent Rutto Samson Muuo Nzou Center for Traditional Medicine and Drug Research Kenya Medical Research Institute Nairobi Kenya Center for Microbiology Research Kenya Medical Research Institute Nairobi Kenya Production Department Kenya Medical Research Institute Nairobi Kenya Department of Biochemistry and Microbiology Rhodes University Grahamstown South Africa Center for Virus Research Kenya Medical Research Institute Nairobi Kenya

The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected individuals across the world, evolving into the COVID-19 pandemic. Notably, early signs of the virus’s existence were observed in various countries before the initial outbreak in Wuhan. As of 12th of April, the respiratory disease had infected over 762 million people worldwide, with over 6.8 million deaths recorded. This has led scientists to focus their efforts on understanding the virus to develop effective means to diagnose, treat, prevent, and control this pandemic. One of the areas of focus is the isolation of this virus, which plays a crucial role in understanding the viral dynamics in the laboratory. In this study, we report the isolation and detection of locally circulating SARS-CoV-2 in Kenya. The isolates were cultured on Vero Cercopithecus cell line (CCL-81) cells, RNA extraction was conducted from the supernatants, and reverse transcriptase-polymerase chain reaction (RT-PCR). Genome sequencing was done to profile the strains phylogenetically and identify novel and previously reported mutations. Vero CCL-81 cells were able to support the growth of SARS-CoV-2 in vitro, and mutations were detected from the two isolates sequenced (001 and 002). Genome sequencing revealed the circulation of two isolates that share a close relationship with the Benin isolate with the D614G common mutation identified along the S protein. These virus isolates will be expanded and made available to the Kenya Ministry of Health and other research institutions to advance SARS-CoV-2 research in Kenya and the region.

关键词： SARS-CoV-2 COVID-19 Whole Genome Sequencing Phylogenetic Analysis Nucleotide Substitutions Amino Acid Changes

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Purification and characterization of a novel anti-coagulant from the leech Hirudinaria manillensis

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Zoological Research 2019年第3期40卷 205-210页

作者： Ruo-Mei Cheng Xiao-Peng Tang Ai-Lin Long james mwangi Ren Lai Rui-Pu Sun Cheng-Bo Long Zhen-Qing Zhang Department of Pharmaceutical Sciences College of Pharmaceutical SciencesSoocbow UniversitySuzhou Jiangsu 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyKunming Yunnan 650223China Kunming College of Life Science University of Chinese Academy of SciencesKunming Yunnan 650204China Jiangxi Medical College Nanchang UniversityNanchang Jiangxi 330006China

Protease inhibitors have been reported rarely from the leech Hirudinaria manillensis.In this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from H.manillensis.With a molecular weight of 1.4x104,bdellin-HM-2 was also characterized with three intra?molecular disulfide bridges at the N-terminus and multiple HHXDD and HXDD motifs at theC-terminus.cDNAcloning revealed that the putative nucleotide-encoding protein of bdellin-HM-2 contained 132 ami no acids and was encoded by a 399 bp open reading frame(ORF).Sequence alignment showed that bdellin-HM-2 shared similarity with the“non-classical"Kazal-type serine protease inhibitors,but had no inhibitory effect on trypsin,elastase,chymotrypsin,kallikrein,factor Xlla(FXIIa),factor Xia(FXIa),factor Xa(FXa),thrombin,or plasmin.Bdellin-HM-2 showed anticoagulant effects by proIonging the activated partial thromboplastin time(aPTT),indicating a role in enabling H.manillensis to obtain a blood meal from its host.Our results suggest that bdellin-HM丒2 may play a crucial role in blood-sucking in this leech species and may be a pote ntial can didate for the development of clinical anti-thrombotic drugs.

关键词： Hirudinaria manillensis Bdellin-HM-2 "Non-classical"Kazal inhibitors Blood sucking Anticoagulant Anti-thrombotic drugs

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Antimicrobial peptide LL-37 forms complex with bacterial DNA to facilitate blood translocation of bacterial DNA and aggravate ulcerative colitis

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Science Bulletin 2018年第20期63卷 1364-1375页

作者： Zilei Duan Yaqun Fang Yang Sun Ning Luan Xue Chen Mengrou Chen Yajun Han Yizhu Yin james mwangi Junkun Niu Kunhua Wang Yinglei Miao Zhiye Zhang Ren Lai Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute .of ZoologyKunming 650223China Life Sciences College of Nanjing Agricultural University Nanjing 210095China Department of Gastroenterology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032China Department of General Surgery The First Affiliated Hospital of Kunming Medical UniversityKunming 650032China Kunming College of Life Science University of Chinese Academy of SciencesKunming 650204China Sino-African Joint Research Center Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China

Bacterial DNA(bacDNA) is frequently found in serum of patient with ulcerative colitis(UC) and Crohn's disease, even blood bacterial culture is negative. How bacDNA evades immune elimination and is translocated into blood remain unclear. Here, we showed that bacDNA avoids elimination and disables bacteriakilling function of antimicrobial peptide LL-37(Cramp in mice) by forming complex with LL-37, which is inducible after culture with bacteria or bacterial products. Elevated LL-37-bacDNA complex was found in plasma and lesions of patients with UC. LL-37-bacDNA promoted inflammation by inducing Th1, Th2 and Th17 differentiation and activating toll-like receptor-9(TLR9). The complex also increased paracellular permeability, which possibly combines its inflammatory effects to promote local damage and bacDNA translocation into blood. Cramp-bacDNA aggravated mouse colitis severity while interference with the complex ameliorated the disease. The study identifies that inflammatogenic bacDNA utilizes LL-37 as a vehicle for blood translocation and to evade immune elimination. Additionally, bacteria may make a milieu by releasing bacDNA to utilize and resist host antimicrobial peptides as a ‘trojan horse'.

关键词： Ulcerative colitis Bacterial DNA LL-37 Immune elimination Chronic inflammation

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Characterization of Forest Degradation beyond Canopy Cover Change in Mau Forest, Kenya

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Open Journal of Forestry 2022年第4期12卷 393-407页

作者： Merceline Awuor Ojwala Felix Mutua mwangi james Kinyanjui Department of Geomatic Engineering and Geospatial Information Systems Jommo Kenyatta University of Agriculture and Technology Nairobi Kenya Directorate of Resource Surveys and Remote Sensing Nairobi Kenya School of Natural Resources and Environmental Studies Karatina University Karatina Kenya

Monitoring Forest degradation is evidence enough to show a country’s commitment to monitor the forest trend both for national and local decision-making and international reporting processes. Unlike deforestation which is easier to point out, monitoring forest degradation is quite a challenge since there is no universal definition and thus no clear monitoring methods apart from the canopy cover change. This research, therefore, sought to look at the degradation trends in the Mau forest complex between 1995-2020 with the aim of finding out whether monitoring canopy density changes over time and quantifying these changes in terms of biomass loss could be a good approach in monitoring forest degradation. Forest Canopy Density (FCD) model was adopted focusing on using vegetation indices describing biophysical conditions of Vegetation, Shadow and Bareness to monitor changes in canopy density as a parameter for describing forest degradation in the forest blocks of Maasai Mau and Olpusimoru in Mau forest complex. Results indicated how different vegetation indices responded to changes in the vegetation density and eventually changes in the canopy density values which were converted in terms of biomass loss. The forest Canopy Density model proved to be a good tool for monitoring forest degradation since it combines different biophysical indices with different characteristics capturing what is happening below the canopy.

关键词： Forest Degradation Canopy Density Vegetation Indices Biomass Loss Monitoring

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Development and Evaluation of Recycled Polypropylene and Bean Pod Powder Composite Biomaterial for Fused Filament Fabrication

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Advances in Materials Physics and Chemistry 2023年第3期13卷 31-48页

作者： Felix Sotohou james W. mwangi james M. Mutua Erick K. Ronoh Pan African University Institute for Basic Sciences Technology and Innovation Juja Kenya Department of Mechatronic Engineering Jomo Kenyatta University of Agriculture and Technology Juja Kenya Department of Mechanical Engineering Jomo Kenyatta University of Agriculture and Technology Juja Kenya Department of Agricultural and Biosystems Engineering Jomo Kenyatta University of Agriculture and Technology Juja Kenya

Approximately 450 million tons of plastic and agricultural waste are produced each year in the world. Only a small portion of this plastic waste is recycled, and a small portion of this agricultural waste is used as fuel or fertilizer, and the rest of this waste is left in the environment or is burned, resulting in environmental and air pollution. For proper disposal, plastic and agricultural waste can be used in the manufacture of composites as raw materials. In this study, we had evaluated the use of bean pod powder (BPp) was used as natural reinforcing filler in recycled polypropylene (rPP) based composites. BPp/rPP composite filaments were developed using the extrusion method and the samples were printed by Fused Filament Fabrication (FFF). Composites with rPP matrix containing different weight fractions of BPp (5%, 10% and 15%) were fabricated to observe and compare the mechanical properties (tensile, flexural, and compressive strength) of the filament composites. In addition, the filament surface was analyzed for roughness and particle size of bean pod powder. The results established that BPp/rPP composites exhibited better tensile, flexural, and compressive strength than rPP and pure PP. By adding 5 wt% BPp, the tensile strength of rPP increased from 20.4 MPa to 22.8 MPa. The highest flexural strength (15.05 MPa) was obtained at 5 wt% BPp among all composites and the highest compressive strength (24.5 MPa), was obtained at 10 wt% BPp. Therefore, it can be concluded that by carefully selecting the ratio of BPp to bean pod powder, it is therefore possible to positively influence the mechanical properties of the resulting composite.

关键词： Pollution Composite Fused Filament Fabrication Mechanical Properties

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Optimization of Extrusion Process Parameters of Recycled High-Density Polyethylene-Thermoplastic Starch Composite for Fused Filament Fabrication

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复合材料期刊(英文) 2023年第4期13卷 69-86页

作者： Grace Njeri Wamuti james Wamai mwangi Samuel Kabini Karanja Leif Micke Henning Zeidler Pan African University Institute of Basic Sciences Technology and Innovation Nairobi Republic of Kenya Department of Mechatronic Engineering Jomo Kenyatta University of Agriculture and Technology Nairobi Republic of Kenya Chair of Additive Manufacturing Technische Universit&aumlt Bergakademie Freiberg Freiberg Germany

High-density poly-ethylene (HDPE) is a nonbiodegradable recyclable plastic which is widely utilized in single use packaging applications. Consequently, it constitutes a significant amount of plastic waste found in landfills. From literature, it has been shown that parts produced using composites of HDPE with carbohydrate-based polymers, such as thermoplastic starch (TPS), experience mechanical degradation through hydrolytic degradation process. The possible utilization of recycled-HDPE (rHDPE) and TPS composite in nonconventional manufacturing processes such as Fused filament fabrication (FFF) has however not been explored. This study explores the potential application of rHDPE and TPS composites in FFF and optimizes the extrusion process parameters used in rHDPE-TPS filament production process. Taguchi method was utilized to analyze the extrusion process. The extrusion process parameters studied were the spooling speed, extrusion speed and the extrusion temperatures. The response variable studied was the filament diameter. In this research, the maximum TPS content achieved during filament production was 40 wt%. This filament was however challenging to use in FFF printers due to frequent nozzle clogging. Printing was therefore done with filaments that contained 0 - 30 wt% TPS. The experimental results showed that the most significant parameter in extrusion process was the spooling speed, followed by extrusion speed. Extrusion temperature had the least significant influence on the filament diameter. It was observed that increase in TPS content resulted in reduced warping and increased rate of hydrolytic degradation. Mechanical properties of printed parts were investigated and the results showed that increasing TPS content resulted in reduction in tensile strength, reduction in compression strength and increase in stiffness. The findings of this research provide valuable insights to plastic recycling industries and researchers regarding the utilization of recycled HDPE and TPS composites as substitute materials in

关键词： Additive Manufacturing (AM) Fused Filament Fabrication (FFF) High Density Polyethylene (HDPE) Thermoplastic Starch (TPS) Bio-Composite

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