察爾斯大夫 美麗殿堂 Dr. Charles Meridien Palace

Phenotype表現型：Expression of an organism's Genes

Phenotype（from Greek phainein, 'to show' + typos, 'type'）is the composite of an organism's observable characteristics or traits, such as its morphology, development, biochemical or physiological properties, phenology, behavior, and products of behavior.

Phenotypes result from the expression of an organism's genes as well as the influence of environmental factors and the interactions between the two. When two or more clearly different phenotypes exist in the same population of a species, it is called polymorph.

The genotype of an organism is the inherited instructions it carries within its genetic code. Not all organisms with the same genotype look or act the same way because appearance and behavior are modified by environmental and developmental conditions. Likewise, not all organisms that look alike necessarily have the same genotype.

This genotype-phenotype distinction was proposed by Wilhelm Johannsen in 1911 to make clear the difference between an organism's heredity and what that heredity produces. The distinction is similar to that proposed by August Weismann, who distinguished between germ plasm (heredity) and somatic cells (the body). The genotype-phenotype distinction should not be confused with Francis Crick's central dogma of molecular biology, which is a statement about the directionality of molecular sequential information flowing from DNA to protein, and not the reverse.

一個基因的不同形式（例如S或s），稱為「對偶基因」（alleles）。當產生「配子」（gamate）時，這兩個對偶基因會分開。一個來自花粉的配子和一個來自柱頭的配子授粉後產生「合子」（zygote）。如果合子的對偶基因相同，則為「同基因合子」（homozygote），例如SS與ss。如果結合子的對偶基因不同，則為「異基因合子」（heterozygote），例如Ss。

後來出現「基因型」（genotype）和「表現型」（phenotype）這兩個名詞。外在表現的特徵稱為表現型，而表現型是由基因型來決定。SS與Ss雖擁有不同的基因型，卻有相同的表現型。我們如何能夠分辨SS和Ss呢？讓它們和ss（皺皮）種交配。交配得到的後代應該是平滑（Ss）與皺皮（ss）的比例各佔一半。這種鑑定基本型的方法稱為Testcross。

Epigenetics 表觀遺傳學

In biology, and specifically genetics, epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence; it also can be used to describe the study of stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. Unlike simple genetics based on changes to the DNA sequence（the genotype）, the changes in gene expression or cellular phenotype of epigenetics have other causes.

The name epi-（Greek: επί- over, outside of, around）-genetics.

The term also refers to the changes themselves：functionally relevant changes to the genome that do not involve a change in the nucleotide sequence. Examples of mechanisms that produce such changes are DNA methylation and Histone modification, each of which alters how genes are expressed without altering the underlying DNA sequence. Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA.

These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave or "express themselves" differently.

One example of an epigenetic change in eukaryotic biology is the process of Cellular differentiation. During morphogenesis, totipotent stem cells become the various pluripotent cell lines of the embryo, which in turn become fully differentiated cells. In other words, as a single fertilized egg cell – the zygote – continues to divide, the resulting daughter cells change into all the different cell types in an organism, including neurons, muscle cells, epithelium, endothelium of blood vessels, etc., by activating some genes while inhibiting the expression of others.

In 2011, it was demonstrated that the Methylation of mRNA plays a critical role in human energy homeostasis. The Obesity-associated FTO gene is shown to be able to demethylate N6-methyladenosine in RNA. This discovery launched the subfield of RNA epigenetics.

表觀遺傳學（Epigenetics），又稱「擬遺傳學」、「表遺傳學」、「外遺傳學」以及「後遺傳學」（Epigenetics），在生物學和特定的遺傳學領域，其研究的是在不改變DNA序列的前提下，通過某些機制引起可遺傳的基因表達或細胞表現型的變化。

表觀遺傳學是20世紀80年代逐漸興起的一門學科，是在研究與經典的孟德爾遺傳學遺傳法則不相符的許多生命現象過程中逐步發展起來的。

表觀遺傳現象包括DNA甲基化、RNA干擾、組蛋白修飾等。與經典遺傳學以研究基因序列影響生物學功能為核心相比，表觀遺傳學主要研究這些「表觀遺傳現象」建立和維持的機制。其研究內容主要包括兩類，一類為基因選擇性轉錄表達的調控，有DNA甲基化、基因印記、組蛋白共價修飾和染色質重塑；另一類為基因轉錄後的調控，包括基因組中非編碼RNA、微小RNA、反義RNA、內含子及核糖開關等。

表觀遺傳學指基因組相關功能改變而不涉及核苷酸序列變化。例如DNA甲基化和組蛋白修飾，兩者均能在不改變DNA序列的前提下調節基因的表達；阻遏蛋白通過結合沉默基因從而控制基因的表達。這些變化可能可以通過細胞分裂而得以保留，並且可能持續幾代。這些變化都僅是非基因因素導致的生物體基因表現（或「自我表達」）的不同，由於目前尚不清楚組蛋白的化學修飾是否可遺傳，有人對於用此術語描述組蛋白化學修飾提出了異議。

表觀遺傳學在真核生物中主要表現在細胞分化過程。在胚胎形態形成過程中，全能幹細胞將分化成完全不同的細胞，也就是說，一個受精卵細胞分化出各種不同類型的細胞，包括神經細胞、肌肉細胞、上皮細胞、血管內皮細胞等，並通過抑制其他細胞和激活相關基因而進行持續的細胞分裂。

2011年的相關研究已證實，mRNA甲基化對人體內能量平衡發揮著至關重要的作用，對RNA上的N6-甲基腺苷進行脫甲基治療可控制FTO基因相關肥胖症，並因此而開創了RNA表觀遺傳學的相關領域。

PBMC：Peripheral blood mononucleated（mononuclear）cell

A peripheral blood mononucleated cell（PBMC）is any blood cell having a round nucleus（opposed to a lobed nucleus）. For example：a lymphocyte, a monocyte or a macrophage. These blood cells are a critical component in the immune system to fight infection and adapt to intruders.

The lymphocyte population consists of T cells（CD4 and CD8 positive～75%）, B cells and NK cells（～25% combined）.

These cells can be extracted from whole blood using Ficoll™, a hydrophilic polysaccharide that separates layers of blood, which will separate the blood into a top layer of plasma, followed by a layer of PBMCs and a bottom fraction of polymorphonuclear cells (such as neutrophils and eosinophils) and erythrocytes. The polymorphonuclear cells can be further isolated by lysing the red blood cells.

PBMCs are widely used in research and clinical applications.

PBSCT：Peripheral stem cell transplantation周邊血液幹細胞移植

Peripheral blood stem cell transplantation（PBSCT）, also called peripheral stem cell support, is a method of replacing blood-forming stem cells destroyed, for example, by cancer treatment.

PBSCT is now a much more common procedure than its bone marrow harvest equivalent, this is in-part due to the ease and less invasive nature of the procedure.

Studies suggest, that PBSCT has a better outcomes in terms of the number of hematopoietic stem cell（CD34+ cells）yield.[4]

Immature blood cells hematopoietic stem cells in the circulating blood that are similar to those in the bone marrow are collected by apheresis from a potential donor（PBSC collection）. The product is then administered Intravenously to the patient after treatment.

The administered hematopoietic stem cells then migrate to the recipients bone marrow, a process known as Stem cell homing, where the transplanted cells override the previous bone marrow. This allows the bone marrow to recover, proliferate and continue producing healthy blood cells.

The transplantation may be Autologous（an individual's own blood cells saved earlier）, Allogeneic（blood cells donated by someone else with matching HLA）, or Syngeneic（blood cells donated by an identical twin）.

The procedure typically lasts for 4～6 hours, depending on the donors total blood volume.

Granulocyte colony stimulating factor（GCSF）are naturally occurring glycoproteins that stimulate white blood cell proliferation. Filgrastim is a synthetic form of GCSF produced in E.coli.

PBSC donors are given a course of GCSF prior to PBSC collection, this ensures a better outcome, as stem cell proliferation increases, thus increasing the number of peripheral stem cells in circulation. The course is usually given over a 4 day period prior to PBSC collection. Mild bone pain usually results due to the excessive stem cell crowding within the bone marrow.

Since allogeneic PBSCT involves transformation of blood between different individuals, this naturally carries more complications than autologous PBSCT. For example, calculations must be made to ensure consistency in the amount of total blood volume between the donor and recipient. If the total blood volume of the donor is less than that of the recipient（such as when a child is donating to an adult）, multiple PBSCT sessions may be required for adequate collection. Performing such a collection in a single setting could result in risks such as hypovolemia, which could lead to cardiac arrest, thus health care providers must exercise careful precaution when considering donor-recipient matching in allogeneic PBSCT.

何謂周邊血液幹細胞移植？

造血幹細胞（Stem cell）平常在骨髓內負責人體白血球，紅血球及血小板的製造，人類出生之後造血幹細胞主要分佈在人體的骨髓中，而周邊血液的造血幹細胞含量極低，無法分離得到足夠幹細胞作為臨床移植用。但是在病人接受高劑量的化學藥物治療，當白血球回升之際，骨髓中的幹細胞會被釋放至周邊血液中，若合併使用GCSF效果更好，才能抽取足夠的幹細胞，經過收集、分離、保存，然後回輸。

周邊血液幹細胞是在1990年代被發展出來的，主要是因為許多病患接受高劑量的化療或TBI，這些治療的毒性主要發生在骨髓造血細胞，一旦骨髓造血細胞被破壞，就無法被抽取利用；然而如事先收集起來的周邊血幹細胞則不受影響，因此可以用於重建骨髓造血細胞的功能。　

周邊血液幹細胞移植的優點

• 不需住院行全身麻醉抽取幹細胞，因此可免除因抽取導致的疼痛及麻醉的危險。

• 比骨髓移植較不受污染，可降低感染、死亡及住院天數。

• 移植後紅血球、白血球的恢復速度加快，血小板的恢復也比骨髓移植快14天以上，使輸血小板次數減少，降低因輸血的致病率及死亡率。

• 降低成本，且有經濟效益。

周邊血液幹細胞移植的用途

• 固態腫瘤的病患接受高劑量治療後，在癌細胞侵犯骨髓時，採用周邊血液幹細胞可減少癌細胞污染的可能性。

• 曾經接受骨盆腔放射線治療，無法從骨髓抽取足夠造血細胞進行自體骨髓移植者，周邊血液細胞是最好替代來源。

• 異體骨髓移植的骨髓移植捐贈者，因故無法收集骨髓時，也可用周邊血液幹細胞來代替。

Genome

The genome is the entirety of an organism's hereditary information.

The genome is encoded either in DNA or, for many types of viruses, in RNA.

The genome includes both the Genes and the Non-coding sequences of the DNA/RNA.

The term was created in 1920 by Hans Winkler, professor of botany at the University of Hamburg, Germany.

The Oxford English Dictionary suggests the name to be a blend of the words Gene and Chromosome.

A few related -ome words already existed—such as biome, rhizome and, more recently, connectome—forming a vocabulary into which genome fits systematically.

Kisspeptin（formerly known as Metastin）：a protein that in humans is encoded by the KISS1 gene

Kisspeptin（formerly known as Metastin）is a protein that in humans is encoded by the KISS1 gene.

Kisspeptin is a G-protein coupled receptor ligand for GPR54.

Kiss1 was originally identified as a human metastasis suppressor gene that has the ability to suppress melanoma and breast cancer metastasis. It recently became clear that Kisspeptin-GPR54 signaling has an important role in initiating secretion of Gonadotropin-releasing hormone（GnRH）at puberty, the extent of which is an area of ongoing research.

Kisspeptins are a family of peptides encoded by the KiSS-1 gene. This gene is located on the long arm of chromosome 1（1q32）and has four exons of which the 5' and 3' exons are only partly translated. The gene product is a 145 amino acid precursor peptide which is cleaved to 54 amino acids in length, which may be further truncated to 14, 13 or 10 amino acid carboxyl terminal fragments. These N-terminally truncated peptides are known as the Kisspeptins and belong to a larger family of peptides known as RFamides which all share a common arginine-phenylalanine-NH2 motif at their C-terminus.

A polymorphism in the terminal exon of this mRNA results in two protein isoforms. An adenosine present at the polymorphic site represents the third position in a stop codon. When the adenosine is absent, a downstream stop codon is utilized and the encoded protein extends for an additional seven amino acid residues.

DC：Dendritic cell

Dendritic cells（DCs）are Antigen-presenting cells（also known as Accessory cells）of the mammalian immune system.

Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system.

They act as messengers between the Innate and the Adaptive immune systems.

Dendritic cells are present in those tissues that are in contact with the external environment, such as the skin（where there is a specialized dendritic cell type called the Langerhans cell）and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood.

Once activated, they migrate to the lymph nodes where they interact with T cells and B cells to initiate and shape the adaptive immune response.

At certain development stages they grow branched projections, the dendrites that give the cell its name（δένδρον or déndron being Greek for "tree"）. While similar in appearance, these are distinct structures from the dendrites of neurons.

Immature dendritic cells are also called Veiled cells, as they possess large cytoplasmic 'veils' rather than dendrites.

M cells：Microfold cells or Epitheliocytus microplicatus)

M cells（Microfold cells or Epitheliocytus microplicatus）are cells found in the Follicle-associated epithelium of the Peyer's patch as well as in BALT（Bronchus-associated lymphoid tissue）. They transport organisms and particles from the gut lumen to immune cells across the epithelial barrier, and thus are important in stimulating Mucosal immunity.

Unlike their neighbouring cells, they have the unique ability to take up Antigen from the lumen of the Small intestine via Endocytosis or Phagocytosis, and then deliver it via Transcytosis to Dendritic cells（an antigen presenting cell）and T lymphocytes（namely T cells）located in a unique pocket-like structure on their basolateral side.

Prolia®：Denosumab，the first FDA-approved RANK Ligand inhibitor

Prolia® targets and binds to RANK Ligand, inhibiting osteoclast formation, function and survival.

Thus, Prolia® can help keep osteoclasts from resorbing bone.

SVF：Stromal Vascular Fraction

Stromal vascular fraction（SVF）of adipose tissue is a rich source of Preadipocytes, Mesenchymal stem cells（MSC）, Endothelial progenitor cell, T cells, B cells, Mast cells as well as Adipose tissue macrophages.

Stromal Vascular Fraction（SVF）is the product of lipoaspirate which is obtained from liposuction of excess adipose tissue.

The Lipoaspirate, a disposable byproduct of liposuction in cosmetic surgery, contains a large population of stem cells called Adipose derived stem cells （ADSCs）, that shares a number of similarities with the Bone marrow stromal cells, including the multilineage differentiation capacity.