- Detection of Sentinel Lymph Nodes with Near-Infrared Imaging in Malignancies. [Review]
- MIMol Imaging Biol 2019; 21(2):219-227
- Optical molecular imaging, a highly sensitive and noninvasive technique which is simple to operate, inexpensive, and has the real-time capability, is increasingly being used in the diagnosis and trea…
Optical molecular imaging, a highly sensitive and noninvasive technique which is simple to operate, inexpensive, and has the real-time capability, is increasingly being used in the diagnosis and treatment of carcinomas. The near-infrared fluorescence dye indocyanine green (ICG) is widely used in optical imaging for the dynamic detection of sentinel lymph nodes (SLNs) in real time improving the detection rate and accuracy. ICG has the advantages of low scattering in tissue absorbance, low auto-fluorescence, and high signal-to-background ratio. The detection rate of axillary sentinel lymph nodes biopsy (SLNB) in breast cancers with ICG was more than 95 %, the false-negative rate was lower than 10 %, and the average detected number ranged from 1.75 to 3.8. The combined use of ICG with nuclein or blue dye resulted in a lower false-negative rate. ICG is also being used for the sentinel node detection in other malignant cancers such as head and neck, gastrointestinal, and gynecological carcinomas. In this article, we provide an overview of numerous studies that used the near-infrared fluorescence imaging to detect the sentinel lymph nodes in breast carcinoma and other malignant cancers. It is expected that with improvements in the optical imaging systems together with the use of a combination of multiple dyes and verification in large clinical trials, optical molecular imaging will become an essential tool for SLN detection and image-guided precise resection.
- Nano-Assembly of Pamitoyl-Bioconjugated Coenzyme-A for Combinatorial Chemo-Biologics in Transcriptional Therapy. [Journal Article]
- BCBioconjug Chem 2018 04 18; 29(4):1419-1427
- Pathogenesis, the biological mechanism that leads to the diseased state, of many cancers is driven by interruptions to the role of Myc oncoprotein, a regulator protein that codes for a transcription …
Pathogenesis, the biological mechanism that leads to the diseased state, of many cancers is driven by interruptions to the role of Myc oncoprotein, a regulator protein that codes for a transcription factor. One of the most significant biological interruptions to Myc protein is noted as its dimerization with Max protein, another important factor of family of transcription factors. Binding of this heterodimer to E-Boxes, enhancer boxes as DNA response element found in some eukaryotes that act as a protein-binding site and have been found to regulate gene expression, are interrupted to regulate cancer pathogenesis. The systemic effectiveness of potent small molecule inhibitors of Myc-Max dimerization has been limited by poor bioavailability, rapid metabolism, and inadequate target site penetration. The potential of gene therapy for targeting Myc can be fully realized by successful synthesis of a smart cargo. We developed a "nuclein" type nanoparticle "siNozyme" (45 ± 5 nm) from nanoassembly of pamitoyl-bioconjugated acetyl coenzyme-A for stable incorporation of chemotherapeutics and biologics to achieve remarkable growth inhibition of human melanoma. Results indicated that targeting transcriptional gene cMyc with siRNA with codelivery of a topoisomerase inhibitor, amonafide caused ∼90% growth inhibition and 95% protein inhibition.
- History, Discovery, and Classification of lncRNAs. [Historical Article]
- AEAdv Exp Med Biol 2017; 1008:1-46
- The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its cent…
The RNA World Hypothesis suggests that prebiotic life revolved around RNA instead of DNA and proteins. Although modern cells have changed significantly in 4 billion years, RNA has maintained its central role in cell biology. Since the discovery of DNA at the end of the nineteenth century, RNA has been extensively studied. Many discoveries such as housekeeping RNAs (rRNA, tRNA, etc.) supported the messenger RNA model that is the pillar of the central dogma of molecular biology, which was first devised in the late 1950s. Thirty years later, the first regulatory non-coding RNAs (ncRNAs) were initially identified in bacteria and then in most eukaryotic organisms. A few long ncRNAs (lncRNAs) such as H19 and Xist were characterized in the pre-genomic era but remained exceptions until the early 2000s. Indeed, when the sequence of the human genome was published in 2001, studies showed that only about 1.2% encodes proteins, the rest being deemed "non-coding." It was later shown that the genome is pervasively transcribed into many ncRNAs, but their functionality remained controversial. Since then, regulatory lncRNAs have been characterized in many species and were shown to be involved in processes such as development and pathologies, revealing a new layer of regulation in eukaryotic cells. This newly found focus on lncRNAs, together with the advent of high-throughput sequencing, was accompanied by the rapid discovery of many novel transcripts which were further characterized and classified according to specific transcript traits.In this review, we will discuss the many discoveries that led to the study of lncRNAs, from Friedrich Miescher's "nuclein" in 1869 to the elucidation of the human genome and transcriptome in the early 2000s. We will then focus on the biological relevance during lncRNA evolution and describe their basic features as genes and transcripts. Finally, we will present a non-exhaustive catalogue of lncRNA classes, thus illustrating the vast complexity of eukaryotic transcriptomes.
- [The substance of genetic information--nucleic acids]. [Historical Article]
- KOKlin Onkol 2012; 25(5):329-32
- If we look at the history of our knowledge of nucleic acids, we would see in the distant past of 140 years Friedrich Miescher who had identified the acidic substance within the cell nucleus, which he…
If we look at the history of our knowledge of nucleic acids, we would see in the distant past of 140 years Friedrich Miescher who had identified the acidic substance within the cell nucleus, which he called nuclein. About 70 years after his initial observation, this substance was connected with genetic information. This very substantial finding happened during the World War II. This was the impulse that research of nucleic acids received to speed up continuously growing mountain of information, which is more and more difficult to understand. Another eruption of new information about our genome was the result of ten years of intensive cooperation of many manufacturers divided into two competitive blocks which offered us knowledge of nucleotide sequence of all 46 DNA molecules. The year 2000 became the landmark marking the start of the postgenomic era. It did not mean that human genome was totally explored, but the cornerstone has been settled. Since then, we could concentrate our efforts on variability; use of the project of 1,000 genomes brought many important findings, eg. copy number variability (CNV) exceeds the single nucleotide polymophisms (SNP). Also intergenomic relationships, studies on function and pathways began to be much more understandable by elucidation of the genome primary structure. NGS as a tool also accelerated the epigenetic research. All this improved molecular diagnostics by discovering many new markers playing their role in disease and treatment and allowed us to enter the field of multifactorial illnesses including cancer. The progress in diagnostic technologies which has happened during the last decade forced our research teams to include other professions - eg. bioinformatics.
- [DNA: from Miescher to Venter and beyond]. [Historical Article]
- PBPostepy Biochem 2009; 55(3):342-54
- DNA, one of the most famous molecules is 140-years-old. Its history has engaged three centuries of experiments, leading us to a point, where the Homo sapiens genome sequence is known. The "DNA breakt…
DNA, one of the most famous molecules is 140-years-old. Its history has engaged three centuries of experiments, leading us to a point, where the Homo sapiens genome sequence is known. The "DNA breakthrough" is dated on 1953, when James Watson and Francis Crick proposed the model of molecular structure of DNA. But the origin of that great achievement goes back to 1869 and early efforts of Friedrich Miescher, the Swiss doctor, who isolated DNA (than termed nuclein) for the first time. Since that time wealth information on "nuclein", its functions, structure and usage has been collected and formed a basis for modern molecular biology, chemical biology and biotechnology. This article describes the events and circumstances of the most important DNA discoveries since its first isolation up to completing the human genome project and deep DNA sequencing techniques application.
- [Induced differentiation of mouse embryonic stem cell into endothelial cell in vitro]. [Journal Article]
- ZXZhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2007; 21(9):994-8
- CONCLUSIONS: ESC can differentiate into endothelial cells under some conditions, and form vessel-like structure under condition culture, which can provide sources of seed cells for tissue engineered vessel.
- Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. [Historical Article]
- HGHum Genet 2008; 122(6):565-81
- In the winter of 1868/9 the young Swiss doctor Friedrich Miescher, working in the laboratory of Felix Hoppe-Seyler at the University of Tübingen, performed experiments on the chemical composition of …
In the winter of 1868/9 the young Swiss doctor Friedrich Miescher, working in the laboratory of Felix Hoppe-Seyler at the University of Tübingen, performed experiments on the chemical composition of leukocytes that lead to the discovery of DNA. In his experiments, Miescher noticed a precipitate of an unknown substance, which he characterised further. Its properties during the isolation procedure and its resistance to protease digestion indicated that the novel substance was not a protein or lipid. Analyses of its elementary composition revealed that, unlike proteins, it contained large amounts of phosphorous and, as Miescher confirmed later, lacked sulphur. Miescher recognised that he had discovered a novel molecule. Since he had isolated it from the cells' nuclei he named it nuclein, a name preserved in today's designation deoxyribonucleic acid. In subsequent work Miescher showed that nuclein was a characteristic component of all nuclei and hypothesised that it would prove to be inextricably linked to the function of this organelle. He suggested that its abundance in tissues might be related to their physiological status with increases in "nuclear substances" preceding cell division. Miescher even speculated that it might have a role in the transmission of hereditary traits, but subsequently rejected the idea. This article reviews the events and circumstances leading to Miescher's discovery of DNA and places them within their historic context. It also tries to elucidate why it was Miescher who discovered DNA and why his name is not universally associated with this molecule today.
- Some major landmarks in the path from nuclein to human genome (1). [Journal Article]
- TMToxicol Mech Methods 2006; 16(2-3):137-59
- The completion of sequencing of the human genome as well as the genomes of other species is a spectacular achievement of 20th-century biology. It is appropriately regarded as a turning point in biolo…
The completion of sequencing of the human genome as well as the genomes of other species is a spectacular achievement of 20th-century biology. It is appropriately regarded as a turning point in biology and medicine for the 21st century. Knowledge of the human genome will presumably help us understand the genetic instructions that make us human. By learning about the gene sequences, the functional dynamics of the genome as well as the individual genetic differences, scientists hope to understand the molecular basis of the normal state and the diseased state of life on one hand, and develop ways to individualize medicine and nutrition on the other hand. Thus, the science of genomics that has grown out of this genome sequencing effort is expected to revolutionize the future of biology itself. The present article is an attempt to briefly summarize some major landmarks in the path that began with the discovery of "nuclein" and led to the completion of the human genome sequencing.
- Function and significance of very low density lipoprotein receptor subtype II. [Journal Article]
- JHJ Huazhong Univ Sci Technolog Med Sci 2005; 25(3):229-33
- To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constr…
To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype II in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the 1dl-A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type I VLDLR) and the other without the O-linked sugar region (type II VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and beta-VLDL), it was found that surface binding of 25 I-VLDL or 125 I-beta-VLDL of 1dl-A7 cells transfected with type I VLDL R recombinant (1dl-A7-VRI) was more higher than that of 1dl-A7 cells transfected with type II VLDLR recombinant (1dl-A7-VRII). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in 1dl-A7-VR I were much higher than those in 1dl-A7-VR II, and 1dl-A7-VR I could transform into foam cells notably. It was suggested that type I VLDLR binds with relative higher affinity to VLDL and beta-VLDL, and internalizes much more lipoprotein into cells. As a result, we can conclude that type I VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type II VLDLR.
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- Effects of magnolol and honokiol derived from traditional Chinese herbal remedies on gastrointestinal movement. [Journal Article]
- WJWorld J Gastroenterol 2005 Jul 28; 11(28):4414-8
- CONCLUSIONS: The inhibitory effect of magnolol and honokiol on contractility of the smooth muscles of isolated gastric fundus strips of rats and isolated ileum of guinea pigs is associated with a calcium-antagonistic effect. Magnolol and honokiol can improve the gastric emptying of a semi-solid meal and intestinal propulsive activity in mice.