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Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

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Oncology research 2024年第1期32卷 101-125页

作者： ROGHAYEH GHORBANI MAHMOUD GHARBAVI ALI SHARAFI ELHAM RISMANI HAMED REZAEEJAM YOUSEF MORTAZAVI BEHROOZ JOHARI Department of Medical biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Nanotechnology research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Zanjan pharmaceutical biotechnology research Center Zanjan University of Medical SciencesZanjanIran Department of pharmaceutical biotechnology School of PharmacyZanjan University of Medical SciencesZanjanIran Molecular Medicine Department Biotechnology Research CenterPasteur Institute of IranPasteur AvenueTehranIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer *** decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics *** were loaded on the synthesized Se@BSA@Chi-MTX *** physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis ***,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell *** results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,*** results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of *** results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/*** ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic *** targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the *** results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP *** nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

关键词： Chemoradiotherapy Combination therapy Decoy oligodeoxynucleotides Myc transcription factor Selenium nanoparticle Prostate cancer

Piperazine-derived ionizable lipids for enhanced mRNA delivery and cancer immunotherapy

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Nano research 2024年第8期17卷 7357-7364页

作者： Kai Xu Yujia Xu Jin Sun Xinwei Cheng Chenxi Lu Wenzhong Chen Bingfang He Tianyue Jiang School of pharmaceutical Sciences Nanjing Tech UniversityNanjing 211816China Department of Nano Formulation Nanjing GeneLeap BiotechnologyNanjing 210061China

Messenger ribonucleic acid(mRNA)-based therapeutics hold great prospects in disease treatment and lipid nanoparticles(LNPs)are the most extensively applied non-viral platform for RNA delivery in *** the clinical success of LNPs as vehicles have been achieved,developing LNPs with enhanced mRNA transmembrane delivery and transfection efficiency in a non-toxic manner is highly desirable and *** this study,we designed a series of new ionizable amino lipids with piperazinederived headgroups and constructed a group of LNPs to promote the transfection activity of mRNA *** them,LNP formulated with lipid 10(L10-LNP)can efficiently package mRNA and perform superior transfection efficiency both in vitro and in vivo,which is mainly attributed to the improved intracellular uptake and effective endosomal *** verified that a single administration of L10-LNP packaging interleukin(IL)-12 mRNA induced tumor shrink and even regression by robust activation of immune effector CD8^(+)T cells and stimulating the generation of IFN-γwithout causing systemic toxicity,which provides a promising platform for clinical cancer immunotherapy.

关键词： ionizable lipid lipid nanoparticle piperazine-derived lipid mRNA therapeutics cancer immunotherapy

Changes in Metabolites and Allelopathic Effects of Non-Pigmented and Black-Pigmented Lowland Indica Rice Varieties in Phosphorus Deficiency

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Rice science 2024年第4期31卷 434-448,I0025,I0026页

作者： Liyana SARA Sompop SAEHENG Panupong PUTTARAK Lompong KLINNAWEE division of Biological Science Faculty of SciencePrince of Songkla UniversitySongkhla 90110Thailand division of Health and Applied Sciences Faculty of SciencePrince of Songkla UniversitySongkhla 90110Thailand Plant Cell and Physiology for Sustainable Agriculture research Unit Faculty of SciencePrince of Songkla UniversitySongkhla 90110Thailand Department of Pharmacognosy and pharmaceutical Botany Faculty of Pharmaceutical SciencesPrince of Songkla UniversitySongkhla 90110Thailand Phytomedicine and pharmaceutical biotechnology Excellence Center Prince of Songkla UniversitySongkhla 90110Thailand

Phosphorus(P) levels alter the allelopathic activity of rice seedlings against lettuce seeds. In this study, we investigated the effect of P deficiency on the allelopathic potential of non-pigmented and pigmented rice varieties. Rice seedlings of the white variety Khao Dawk Mali(KDML105, non-pigmented) and the black varieties Jao Hom Nin(JHN, pigmented) and Riceberry(RB, pigmented) were cultivated under high P(HP) and low P(LP) conditions. Morphological and metabolic responses to P deficiency were investigated. P deficiency inhibited shoot growth but promoted root growth of rice seedlings in all three varieties. Moreover, P deficiency led to decreased cytosolic phosphate(Pi) and total P concentrations in both shoot and root tissues. The subsequent reduction in internal P concentration enhanced the accumulation of phenolic compounds in both shoot and root tissues of the seedlings. Subsequently, allelopathy-based inter-and intra-specific interactions were assessed using water extracts from seedlings of the three varieties grown under HP and LP conditions. These extracts were tested on seeds of lettuce, the weed Dactyloctenium aegyptium, and the same rice variety. The shoot and root extracts from P-deficient seedlings reduced the germination of all recipient plants. Specifically, the shoot extract from P-deficient KDML105 seedlings reduced the germination index(GI) of lettuce seeds to 1%, while those from P-deficient RB and JHN seedlings produced GIs of 32% and 42%, respectively. However, when rice seeds were exposed to their own LP shoot and root extracts, their GIs increased up to 4-fold, compared with the HP extracts. Additionally, the shoot extracts from P-deficient plants also stimulated the germination of D. aegyptium by about 2–3-fold, whereas the root extracts did not have this effect. Therefore, P starvation led to the accumulation and exudation of phenolics in the shoots and roots of rice seedlings, altering their allelopathic activities. To adapt to P defici

关键词： phosphorus deficiency non-pigmented and black-pigmented rice phenolics extract allelopathy

Basic regulatory science behind drug substance and drug product specifications of monoclonal antibodies and other protein therapeutics

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Journal of pharmaceutical Analysis 2024年第6期14卷 785-804页

作者： Patanachai K.Limpikirati Sorrayut Mongkoltipparat Thinnaphat Denchaipradit Nathathai Siwasophonpong Wudthipong Pornnopparat Parawan Ramanandana Phumrapee Pianpaktr Songsak Tongchusak Maoxin Tim Tian Trairak Pisitkun Department of Food and pharmaceutical Chemistry Faculty of Pharmaceutical SciencesChulalongkorn UniversityPathumwanBangkok10330Thailand pharmaceutical Sciences and Technology(PST)Graduate Program Faculty of Pharmaceutical SciencesChulalongkorn UniversityPathumwanBangkok10330Thailand Center of Excellence in Systems Biology(CUSB) Faculty of MedicineChulalongkorn UniversityPathumwanBangkok10330Thailand Department of pharmaceutical Chemistry Faculty of Pharmaceutical SciencesHuachiew Chalermprakiet UniversityBang PhliSamut Prakan10540Thailand division of research Affairs Faculty of MedicineChulalongkorn UniversityPathumwanBangkok10330Thailand

In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and *** specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered *** of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance *** attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the *** criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric *** in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial *** are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.

关键词： Biopharmaceutical analysis Biopharmaceutical quality control Biopharmaceutical specifications Monoclonal antibodies Protein therapeutics Regulatory science

Camouflaging attenuated Salmonella by cryo-shocked macrophages for tumor-targeted therapy

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Signal Transduction and Targeted Therapy 2024年第2期9卷 709-723页

作者： Leyang Wu Zengzheng Du Lin Li Liyuan Qiao Shuhui Zhang Xingpeng Yin Xiaoyao Chang Chenyang Li Zichun Hua The State Key Laboratory of pharmaceutical biotechnology and Department of Neurology of Nanjing Drum Tower Hospital School of Life Sciences and The Affiliated Hospital of Nanjing University Medical SchoolNanjing UniversityNanjing 21008 JiangsuChina Nanjing Generecom biotechnology Co. LtdNanjing 210023China Changzhou High-Tech research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc Changzhou 213164 JiangsuChina School of Biopharmacy China Pharmaceutical UniversityNanjing 210023 JiangsuChina

Live bacteria-mediated antitumor therapies mark a pivotal point in cancer ***,the difficulty in reconciling the safety and efficacy of bacterial therapies has limited their *** bacterial tumor-targeted delivery while maintaining biosafety is a critical hurdle for the clinical translation of live microbial therapy for ***,we developed“dead”yet“functional”Salmonella-loaded macrophages using liquid nitrogen cold shock of an attenuated Salmonella typhimurium VNP20009-contained macrophage cell *** obtained“dead”macrophages achieve an average loading of approximately 257 live bacteria per 100 *** engineered cells maintain an intact cellular structure but lose their original pathogenicity,while intracellular bacteria retain their original biological activity and are delay freed,followed by ***“Trojan horse”-like bacterial camouflage strategy avoids bacterial immunogenicity-induced neutrophil recruitment and activation in peripheral blood,reduces the clearance of bacteria by neutrophils and enhances bacterial tumor enrichment efficiently after systemic ***,this strategy also strongly activated the tumor microenvironment,including increasing antitumor effector cells(including M1-like macrophages and CD8+Teffs)and decreasing protumor effector cells(including M2-like macrophages and CD4+Tregs),and ultimately improved antitumor efficacy in a subcutaneous H22 tumor-bearing mouse *** cryo-shocked macrophage-mediated bacterial delivery strategy holds promise for expanding the therapeutic applications of living bacteria for cancer.

关键词： shock holds maintain

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM Department of Medical biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan pharmaceutical biotechnology research Center Zanjan University of Medical SciencesZanjanIran Nanotechnology research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell *** and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 *** nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical ***,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer *** anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized *** revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation *** can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

Advances in DNA methylation and its role in cytoplasmic male sterility in higher plants

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Journal of Integrative Agriculture 2024年第1期23卷 1-19页

作者： Atiqur Rahman Hasan Sofiur Rahman Shakil Uddin Naima Sultana Shirin Akhter Ujjal Kumar Nath Shamsun Nahar Begum Mazadul Islam Afroz Naznin Nurul Amin Sharif Ahmed Akbar Hossain Department of Genetics and Plant Breeding Bangladesh Agricultural UniversityMymensingh 2202Bangladesh Plant Breeding division Bangladesh Institute of Nuclear AgricultureMymensingh 2202Bangladesh Tuber Crop research Centre Bangladesh Agricultural Research Institute(BARI)Joydebpur 1701Bangladesh Horticulture research Centre Bangladesh Agricultural Research Institute(BARI)Joydebpur 1701Bangladesh biotechnology division Bangladesh Agricultural Research Institute(BARI)Joydebpur 1701Bangladesh International Rice research Institute Bangladesh OfficeDhaka 1213Bangladesh division of Soil Science Bangladesh Wheat and Maize Research InstituteDinajpur 5200Bangladesh

The impact of epigenetic modifications like DNA methylation on plant phenotypes has expanded the possibilities for crop *** methylation plays a part in the regulation of both the chromatin structure and gene expression,and the enzyme involved,DNA methyltransferase,executes the methylation process within the plant *** regulating crucial biological pathways,epigenetic changes actively contribute to the creation of the ***,epigenome editing may assist in overcoming some of the drawbacks of genome editing,which can have minor off-target consequences and merely facilitate the loss of a gene’s *** drawbacks include gene knockout,which can have such off-target *** review provides examples of several molecular characteristics of DNA methylation,as well as some plant physiological processes that are impacted by these epigenetic changes in the *** also discuss how DNA alterations might be used to improve crops and meet the demands of sustainable and environmentally-friendly farming.

关键词： DNA methylation epigenetics CMS male sterility chromatin architecture gene expression higher plants

New pharmacological tools:the use of diterpenes to promote adult hippocampal neurogenesis

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Neural Regeneration research 2024年第8期19卷 1629-1630页

作者： Ricardo Gomez-Oliva Pedro Nunez-Abades Carmen Castro Department of Biomedicine Biotechnology and Public HealthDivision of PhysiologyUniversity of CadizCadizSpain Biomedical research and Innovation Institute of Cadiz(INiBICA) CadizSpain Department of Physiology University of SevilleSevilleSpain

Tissue regeneration maintains homeostasis and preserves the functional features of each ***,not all tissues show a strong repairing *** is the case of the central nervous *** is now well established that the generation of new functional neurons from stem cells in the adult brain occurs in specific regions of the brain of different species such as rodents,birds,primates,and humans(Eriksson et al.,1998).

关键词： capacity maintain preserve

Thermal stability improvement and microstructure optimization of high cobalt content Nd-Fe-B magnets via terbium grain boundary diffusion

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Journal of Rare Earths 2024年第8期42卷 1531-1538,I0004页

作者： Jiyuan Xu Ruiyang Meng Jing Liu Jiateng Zhang Rui Han Yikun Fang Shengzhi Dong Wei Li division of Functional Materials research Central Iron and Steel Research InstituteBeijing100081China

The substitution of Fe by Co in the 2:14:1 phase is an effective method to increase the Curie temperature and enhance the thermal stability of the Nd-Fe-B ***,the accumulation of Co ele ment at the grain boundaries(GBs) changes the GBs from nonmagnetic to ferromagnetic and causes the thinlayer GBs to become rare,In this paper,the method of diffusing Tb element was chosen to improve the microstructure and temperature stability of high-Co *** original sintered Nd_(28.5)Dy_(3)-CO_(x)e_(bal)M_(0.6)B_(i)(x=0,6 wt%,12 wt%;M = Cu,Al,Zr) magnets with different Co contents were diffused with Tb by grain boundary diffusion(GBD).After GBD,high-Co magnets exhibit more continuously distributed thin-layer GBs,and their thermal stability is significantly *** high-Co magnets(x=6 wt%),the absolute value of the temperature coefficient of coercivity decreases from 0.603%/K to0.508%/K in the temperature range of 293-413 K,that of remanence decreases from 0.099%/K to 0.091%/K,and the coercivity increases from 18.44 to 25.04 *** electron microscopy(TEM)characterization reveals that there are both the 1:2 phase and the amorphous phase in the high-Co magnet before and after GBD,EDS elemental analysis shows that Tb element is more likely to preferentially replace the rare earth elements in the 2:14:1 main phase than in the 1:2 phase and the amorphous *** concentration of Tb at the edge of the main phase is much higher than that in the 1:2phase and amorphous phase,which is beneficial to the improvement of the *** preferential replacement of Tb elements at the edge of the 2:14:1 phase and thin-layer GBs with a more continuous distribution are synergistically responsible for improving the thermal stability of high-Co *** study indicates that GBD is an effective method to improve the microstructure and thermal stability of high-Co magnets.

关键词： Nd-Fe-B magnets Coercivity Grain boundary diffusion Thermal stability Micro structure Rare earths