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N-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probes

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 64-71 doi: 10.1007/s11705-021-2048-8

摘要： Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity. They play an important role in the design of new structural entities for medical applications. Similarly, indoles and their derivatives are found widely in nature. Amino acids, alkaloids and auxin are all derivatives of indoles, as are dyes, and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents. In this work, we combine these two groups organically to construct a rapid response site (within 30 s) for H S, and at the same time, a ratiometric fluorescence response is presented throughout the process of H S detection. As such, the lower detection limit can reach 55.7 nmol/L for H S. In addition, cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H S. Finally, this probe application was verified by imaging H S in nude mice.

关键词： heterocyclic compound     hydrogen sulfide     ratiometric     mitochondrial targeted    

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hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 92-102 doi: 10.1007/s11705-021-2063-9

摘要： Mitochondrial DNA has a special structure that is prone to damage resulting in many serious diseases, such as genetic diseases and cancers. Therefore, the rapid and specific monitoring of mitochondrial DNA damage is urgently needed for biological recognition. Herein, we constructed an in situ hydrophobic environment-triggering reactive fluorescence probe named MBI-CN. The fluorophore was 2-styrene-1H-benzo[d]imidazole, and malononitrile was introduced as a core into a molecule to initiate the hydrolysis reaction in the specific environment containing damaged mitochondrial DNA. In this design, MBI-CN conjugates to mitochondrial DNA without causing additional damages. Thus, MBI-CN can be hydrolyzed to generate MBI-CHO in an in situ hydrophobic environment with mitochondrial DNA damage. Meanwhile, MBI-CHO immediately emitted a significative fluorescence signal changes at 437 and 553 nm within 25 s for the damaged mitochondria DNA. Give that the specific and rapid response of MBI-CN does not cause additional damages to mitochondrial DNA, it is a potentially effective detection tool for the real-time monitoring of mitochondrial DNA damage during cell apoptosis and initial assessment of cell apoptosis.

关键词： hydrolysis reaction     mitochondrial DNA damage     in situ hydrophobic environment trigger     fluorescence probe     apoptosis    

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Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

《医学前沿（英文）》 2022年 第16卷 第2期   页码 216-226 doi: 10.1007/s11684-022-0920-7

摘要： Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

关键词： tsRNA     biomarker     hepatocarcinoma    

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Conserved gene arrangement in the mitochondrial genomes of barklouse families Stenopsocidae and Psocidae

Xiaochen LIU, Hu LI, Yao CAI, Fan SONG, John-James WILSON, Wanzhi CAI

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 358-365 doi: 10.15302/J-FASE-2017158

摘要： Substantial variation in gene organization and arrangement has been reported for sequenced mitochondrial (mt) genomes from the suborders of the insect order Psocoptera. In this study we sequenced the complete mt genome of , the first representative of the family Stenopsocidae from the suborder Psocomorpha. Relative to the ancestral pattern, rearrangements of a protein-coding gene ( ) and five tRNA genes ( , , , , ) were found. This pattern was similar to that of two barklice from the family Psocidae, with the exception of the translocation of , and Based on comparisons of pairwise breakpoint distances of gene rearrangements, gene number and chromosome number, it was concluded that mt genomes of Stenopsocidae and Psocidae share a relatively conserved pattern of gene rearrangements; mt genomes within the Psocomorpha have been generally stable over long evolutionary history; and mt gene rearrangement has been substantially faster in the booklice (suborder Troctomorpha) than in the barklice (suborders Trogiomorpha and Psocomorpha). It is speculated that the change of life history and persistence of unusual reproductive systems with maternal inheritance contributed to the contrasting rates in mt genome evolution between the barklice and booklice.

关键词： gene rearrangement     mitochondrial genome     Psocoptera     Stenopsocidae     TDRL model    

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Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission

《医学前沿（英文）》 doi: 10.1007/s11684-023-0983-0

摘要： Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca homeostasis in a murine model of HFpEF

关键词： mitochondrial fission Ca     Berberine alleviates myocardial     murine model HFpEF    

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Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

Bo PENG BA , Jinnong ZHANG MD , Jamile S. WOODS MD , Wei PENG MD, PhD

《医学前沿（英文）》 2009年 第3卷 第3期   页码 245-255 doi: 10.1007/s11684-009-0044-3

摘要： Lung cancer is one of the most common human cancers and the number one cancer killer in the United States. In general, lung cancer includes small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), but NSCLC accounts for approximately 90% of lung cancer. The early diagnosis and therapy of lung cancer still presents a big challenge because validated screening tools, which can improve current early detection to reduce mortality from lung cancer, do not exist. Over the last decade, molecular genetic abnormalities have been described in NSCLC, including chromosomal aberrations, overexpression of oncogenes, and deletion and/or mutations in tumor suppressor genes. These molecular markers in NSCLC demonstrated close associations with the development of lung cancer such as Ras, the epidermal growth factor receptor (EGFR, or c-erbB-1), HER2 (c-erbB-2), c-Met, and Bcl-2. Therefore, this information may be applied for early cancer detection, classification, novel targeted therapy, and prognosis in NSCLC. Recent clinical data have revealed that targeted therapy might be the second-line therapy as an alternative approach. Currently, the targeted therapies are mainly focused on two lung cancer pathways, the EGFR and the vascular endothelial growth factor (VEGF) pathways. Some clinical trials are very encouraging, but some of them are not. However, these trials have not identified a subgroup of NSCLC with biomarkers. Therefore, it is very important to select NSCLC patients with biomarkers to match targeted agents so that we can further identify effectiveness of targeted therapy in the future.

关键词： lung cancer     carcinoma     non-small cell lung cancer     molecular markers     targeted therapy    

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Influence of Survivin-targeted siRNA on the biological features of colorectal carcinoma cells

XIONG Ying, GUO Wen, LI Ting, LI Ke

《医学前沿（英文）》 2007年 第1卷 第3期   页码 304-307 doi: 10.1007/s11684-007-0058-7

摘要： The transient transfection of survivin-targeted siRNA to Lovo cells and its influence on the biological features were studied. Two pairs of 19 base pairs (bp) siRNA-specific targeted survivin gene were designed and synthesized by transcription (Survivin-1, Survivin-2). After transient transfection of the two survivin-targeted siRNAs to Lovo cells by Lipofectamine™ 2000, the expression of survivin mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis was detected by flow cytometry and cell proliferation was evaluated by MTT assay. We found that the expression levels of survivin mRNA of the two RNAi groups (Survivin-1 group and Survivin-2 group) respectively decreased by 70% and 39.1% compared with the control Lovo’s. Seventy-two hours after transfection, apoptosis rates of the two RNAi groups were 21.51% and 26.28%, both of which were higher than control Lovo’s (9.03%). The results at 72 h after transfection were that the optical density (OD) at 490 nm of the two RNAi groups was 0.581±0.070 and 0.681±0.104, both of which were much lower than the control Lovo’s (2.060±0.272). Based on the results, we can draw a conclusion that the two survivin-targeted siRNAs successfully suppressed the expression of survivin mRNA, inhibited cell growth and induce cell apoptosis. It provides a powerful evidence for colorectal carcinoma gene therapy.

关键词： control     therapy     influence     Survivin-1     colorectal carcinoma    

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A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics

Wen-Can Huang,Wenjie Wang,Wei Wang,Yanan Hao,Changhu Xue,Xiangzhao Mao,

《工程（英文）》 doi: 10.1016/j.eng.2023.05.024

摘要： Transplantation of probiotics to the intestine can positively regulate the gut microbiota, thereby promoting the immune system and treating various diseases. However, the harsh gastrointestinal environment and short retention time in the gastrointestinal tract significantly limit the bioavailability and intestinal colonization of probiotics. Herein, we present a double-layer polysaccharide hydrogel (DPH) in the form of a double-layer structure composed of a carboxymethyl cellulose (CMCL) supramolecular inner layer and a dialdehyde alginate (DAA) cross-linked carboxymethyl chitosan (CMCS) outer layer. This double-layer structure allows DPH to encapsulate and deliver probiotics in a targeted manner within the body. In the stomach, the cage structure of the DPH is closed, and the outer layer absorbs surrounding liquids to form a barrier to protect the probiotics from gastric fluids. In the intestine, the cage structure opens and disintegrates, releasing the probiotics. Thus, DPH endows probiotics with excellent intestine-targeted delivery, improved oral bioavailability, enhanced gastrointestinal tract tolerance, and robust mucoadhesion capacity. The encapsulated probiotics exhibit almost unchanged bioactivity in the gastrointestinal tract before release, as well as improved oral delivery. In particular, probiotics encapsulated by DPH exhibit 100.1 times higher bioavailability and 10.6 times higher mucoadhesion than free probiotics in an animal model 48 h post-treatment. In addition, with a remarkable ability to survive and be retained in the intestine, probiotics encapsulated by DPH show excellent in vitro and in vivo competition with pathogens. Notably, DAA-mediated dynamic crosslinking not only maintains the overall integrity of the hydrogels but also controls the release timing of the probiotics. Thus, it is expected that encapsulated substances (probiotics, proteins, etc.) can be delivered to specific sites of the intestinal tract by means of DPH, by controlling the dynamic covalent crosslinking.

关键词： Polysaccharides     Chitosan     Hydrogels     Oral delivery     Intestine-targeted    

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NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 177-184 doi: 10.1007/s11684-010-0038-1

摘要： Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, five individuals showed 73€A→G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV 2, which might contribute to the development of LD.

关键词： nucleoside reverse transcriptase inhibitors     human immunodeficiency virus     mitochondrial DNA     D loop     mutation    

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Molecular classification and molecular targeted therapy of cancer

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 147-149 doi: 10.1007/s11684-013-0274-2

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Microwave-induced high-energy sites and targeted energy transition promising for efficient energy deployment

《能源前沿（英文）》 2022年 第16卷 第6期   页码 931-942 doi: 10.1007/s11708-021-0771-y

摘要： Diverse interactions between microwaves and irradiated media provide a solid foundation for identifying novel organization pathways for energy flow. In this study, a high-energy-site phenomenon and targeted-energy transition mechanism were identified in a particular microwave heating (MH) process. Intense discharges were observed when microwaves were imposed on irregularly sized SiC particles, producing tremendous heat that was 8-fold the amount generated in the discharge-free case. Energy efficiency was thereby greatly improved in the electricity-microwaves-effective heat transition. Meanwhile, the dispersed microwave field energy concentrated in small sites, where local temperatures could reach 2000°C– 4000°C, with the energy density reaching up to 4.0 × 105 W/kg. This can be called a high-energy site phenomenon which could induce further processes or reactions enhancement by coupling effects of heat, light, and plasma. The whole process, including microwave energy concentration and intense site-energy release, shapes a targeted-energy transition mechanism that can be optimized in a controlled manner through morphology design. In particular, the discharge intensity, frequency, and high-energy sites were strengthened through the fabrication of sharp nano/microstructures, conferring twice the energy efficiency of untreated metal wires. The microwave-induced high-energy sites and targeted energy transition provide an important pathway for high-efficiency energy deployment and may lead to promising applications.

关键词： microwave discharge     high-energy sites     targeted-energy transition     morphology design     energy efficiency    

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Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging

Liangqian Tong, Ming Zhao, Shu Zhu, Jing Chen

《医学前沿（英文）》 2011年 第5卷 第4期   页码 379-387 doi: 10.1007/s11684-011-0162-6

摘要： Superparamagnetic iron oxide (SPIO) nanoparticles have become a popular strategy of cancer treatment and molecular imaging because of their versatile properties and biocompatibility. A variety of studies have shown the exciting potential of functionalized SPIO nanoparticles, such as surface-coated, targeted ligand-conjugated, and/or drug-loaded SPIO nanoparticles, as powerful tools for targeted imaging and therapy. Moreover, the applications of SPIO nanoparticles that integrate diagnosis and therapy in SPIO nanoparticles facilitate the monitoring of therapeutic efficacy during treatment. In the present review, we primarily concentrate on the recent advancements in the field of SPIO nanoparticles in terms of synthesis, targeted therapy, and cancer imaging.

关键词： nanoparticles     superparamagnetic iron oxide     targeted therapy     molecular imaging     cancer    

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Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy

《医学前沿（英文）》 2023年 第17卷 第3期   页码 493-502 doi: 10.1007/s11684-022-0946-x

摘要： Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

关键词： ALK fusion     next-generation sequencing     fluorescence in situ hybridization     immunohistochemistry     variant allele frequency     intratumoral heterogeneity     targeted therapy    

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Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 112-120 doi: 10.1007/s11705-021-2075-5

摘要： The design of three novel fatty nitrogen mustard-based anticancer agents with fluorophores incorporated into the alkene structure (CXL 118, CXL121, and CXL122) is described in this report. The results indicated that these compounds are selectively located in lysosomes and exhibit effective antitumour activity. Notably, these compounds can directly serve as both reporting and imaging agents in vitro and in vivo without the need to add other fluorescent tagging agents.

关键词： fluorescent drug     lysosomal     anticancer     zebrafish     nude-mouse tumour imaging    

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标题 作者 时间 类型 操作

N-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probes

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

期刊论文

hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

期刊论文

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

期刊论文

Conserved gene arrangement in the mitochondrial genomes of barklouse families Stenopsocidae and Psocidae

Xiaochen LIU, Hu LI, Yao CAI, Fan SONG, John-James WILSON, Wanzhi CAI

期刊论文

Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission

期刊论文

Molecular markers and pathogenically targeted therapy in non-small cell lung cancer

Bo PENG BA , Jinnong ZHANG MD , Jamile S. WOODS MD , Wei PENG MD, PhD

期刊论文

Influence of Survivin-targeted siRNA on the biological features of colorectal carcinoma cells

XIONG Ying, GUO Wen, LI Ting, LI Ke

期刊论文

A Double-Layer Polysaccharide Hydrogel (DPH) for the Enhanced Intestine-Targeted Oral Delivery of Probiotics

Wen-Can Huang,Wenjie Wang,Wei Wang,Yanan Hao,Changhu Xue,Xiangzhao Mao,

期刊论文

NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文

Molecular classification and molecular targeted therapy of cancer

null

期刊论文

Microwave-induced high-energy sites and targeted energy transition promising for efficient energy deployment

期刊论文

Synthesis and application of superparamagnetic iron oxide nanoparticles in targeted therapy and imaging

Liangqian Tong, Ming Zhao, Shu Zhu, Jing Chen

期刊论文

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy

期刊论文

Novel lysosome-targeted anticancer fluorescent agents used in zebrafish and nude mouse tumour imaging

期刊论文