2019-03-20 11:35:09 来源：网络 点击：
发现：uncover; give insight into; Disclosed
引起，导致，出现、发生：causing; leading to; result in; occur; exhibited
改变、影响： change; alter; vary; influence; impact; affect; effect
The vibrissal follicle in this respect differs in manyways from the pelage follicle
与...相反: in contract of; in contract to; conversely
comprises a complex assortment of proteins;
Hair follicle cycling including anagen , catagen ,tolegen , and exogen;
such as intactblood vessels or nerves;
Other molecules that could serve asanagen-supporting signals include insulin-like growth factor I receptor(IGF-IR), KGF, and HGF, which are downregulated, and BDNF, NT-4, NT-3,and TGF-b1, which are upregulated upon catagen initiation.
ALP is referred as an excellent marker of DPCs
放置，放入..之中，放在与…一起：placed free-floating in serum -free medium;
方法，方式：by means of
维持，保持：retained; remains; maintain
... 在场的情况下： in the presence of; major pathways involved...
In the hair follicle, telomerase is only weaklyexpressed in the area of the bulge and strongly expressed in thelower bulb cells
表达上调；下调：upregulated by; downregulated by; influenceby molecules
必要的，重要的角色：the imperative role of ; The important role of; undoubtedly play; a critical role in; be Essential to
its role is thought to serve predominately as asupport for the
方式、治疗方式：method; way; type; mode; application forX therapy;
a novel therapeutic target for gene therapy
a potential innovative strategy for
be considered as an agent for clinical application.
offering new mechanistic insight
许多的，各种各样的：multiple; diversity;various; several; a number of
显著地：significantly; dramatic; signally; observably; markedly; memorably
联系、关系: correlation; is linked to; relate to; in correlation with;
新的模式，治疗方法：a novelmode for;
a promising approach;
a novel therapeutic target for;
is considered an effective approach to improving
provide insights into possible cosmetic and therapeutic applications.
然而、转折：while; nevertheless; However;Whereas; but
导致、结果：resulting in；leadingto；as a result of; Resultform; As; So; Because; So as to; Sothat
另外：Moreover；Furthermore；Besides； Inaddition； additionally； at the outset； it is obvious to; above all；Moreover；Naturally；Even within
Prep:In spite of ；In despite of
换句话说,另一方面：in otherword；On the other hand
因为：due to + n
exact mechanisms…are not yet known;
have not yet been elucidated;
No convincing explanation has yet been proposed for thisdecline in hair follicle density;
How the cycle spreads in waves is not clear, but experimentalstudies suggest that;
However, what ... Is debated;
.... Is not yet clear;
Although their function is not yetclear, a group of molecular markers of the anagen follicle bulb/matrix has beendescribed;
知道现象，不知道具体机制：Although we now know their expression pattern, we knowvery little about how any of these adhesion molecules act in anageninitiation, development, or hair cycle control;
What in thesebaceous gland/sebum is responsible for sheath dissociation is undercurrent study;
For this reason;
but experimental studies suggest that;
猜想： hypothesis for；
it is tempting to speculate that;
has been documented;
Studies have also shown the imperativerole of;
Transgenic mouse studies have demonstratedthat;
similar results have been found by;
It has been found that;
This observation suggests that;
It is also notable that;
Such studies indicate that;
Evidence suggesting that;
It is generally hold that;
Direct evidence for this conclusion is found experimentallywhere;
This finding supports the idea that;
Recent work has found that;
限制…的行为：restrict the action of…by preventing
leading to the destabilization of MITFmRNA；
…result in, … that occurs due to a …
These disordersare poorly controlled and cannot currently be effectively treated, mainlydue to our lack of understanding of hair follicle function.
研究目的，提出问题：In this section we focus on thecell lineages making up the cycling portion of the follicle. We would liketo know from where each of the follicular layers arises and what controlstheir differentiation. Although the answers we have are still unsatisfactory,some basic principles are clear
It has recently been demonstrated that several long non-coding RNAs,such as TINCR and ANKR, are involved in the control of epidermaldifferentiation and stratification；
Thus, miRNAs are involved in theregulation of diverse biological functions during development, differentiationand pathological conditions
相同条件下，存在某种物质和不存在某种物质，所产生的影响不同：Whenwhole follicles (sheep, horse,human) are cultured in the presence of their own sebaceousgland/mid-follicle region, the shaft grows out free of sheath. When the samepreparation is grown in the absence of the sebaceous gland/mid-follicleregion, the shaft grows out with the sheath
MITF is paramount for melanocyte developmentand melanoma pathogenesis.
在...领域：Indeed, inthe field of skin tissue engineering, despite the variety of approachesproposed, none allows the formation of hair follicles in in vitro cultures
Support for the unique and conserved character of a givenfollicle is most powerfully demonstrated by transplantation
相同现象，可能相同机制：The similarity of the early anagen finger invading intothe dermis to invasive basal or squamous carcinomas suggests a commonmechanism between the down-growing follicle and invasive skin tumors
机制不明：Theseparadoxical effects of androgens on human hair growth have long been a mystery.
两种功能并列表达：Paradoxically, this patterning gene plays a structuralfunction in the mature follicle in addition to its patterning rolein early development
在…方面有提高，进步：these patients also demonstratedsignificant improvement in facial wrinkles
举例： such as后只加一个the：those with larger vessels may also requiretreatment with a continuous-wave laser, such as the krypton, argon,or normal mode Nd:YAG lasers
As mentioned above, the cycling portion of the anagen follicle is asolid epithelial cylinder made of embedded,concentric, unique cylindrical layers
Another major skin chromophore is hemoglobin in the red blood cells；
列举、总结生长期的各个方面：In understanding anagen we will haveto acquire greater insight into the controls of tissue regeneration,the signals initiating anagen growth and stem cell arousal, the characterof the molecular system controlling follicle/shaft character, themechanism of shaft outward movement, and shaft sheath dissociation
列举因子上调下调表达：Other molecules that could serve asanagen-supporting signals include insulin-like growth factor I receptor(IGF-IR), KGF, and HGF (297), which are downregulated, and BDNF,NT-4,NT-3, and TGF-b1,which are upregulated upon catagen initiation.
持续时间：persist as long as；
常用的两种方式：There are two types of resurfacinglasers in common use: erbium: YAG and CO2.
相同点与不同点同时表达：Although these two processes sharemany features, they differ from one another in at least one fundamental way: in the one a whole structuregenerates from a primitive epidermis (morphogenesis), and in the other,a partial structure generates from adult tissues
An inverse correlation between MITF and miR-218 expression was found inhuman primary skin melanocytes and melanoma cell lines
It is ... That 句型： it is important to recognize anddistinguish the fect that ...
迫切的需求：A cosmeticapplication of a laser is very demanding
最重要的功能：Its most obvious and perhaps mostimportant function is to provide a protective covering for the restof the body and an interface with the environment.
Not only... Butalso+名词的用法：Thus the growth phase of the shaft,anagen VI, not only serves as the mainproduction period for the fiber but also as a system for transportingskin secretions, debris, and parasites/microorganisms from the pilary canal tothe skin surface
Recent developments in pharmacological approaches to manipulate miRNAlevels in vivo, including tissue-specific delivery, hold great promise fornovel therapeutic approaches to treat cancer, including metastaticmelanoma;
引用别人文章基础，提出假设：Because homeobox gene transcriptionfactors play a pivotal role in body and limb development and are expressed in the follicle, it isreasonable to assume that they also impact hair character.
通过下游基因发挥作用：they act by orchestracting theexpression of many downstream genes.
下定义：... 结构把... 从... 分开；同位语：The outermost cylinder, the ORS, separates the whole hair shaftfactory from the dermis and subcutis.
主语从句，宾语从句，同位语：That the ORS produces catagenproducing growth factors, likeFGF5 and neurotrophins, supports the idea that the ORS plays animportant role in regulating the cycle
毛干的定义：The hair shaft is essentially aproduct of proliferating and terminally differentiating keratinocytes thatdiffer substantially from epidermal keratinocytes in their biochemical andkeratin gene expression
退行期八个亚期dividinto：The catagen stage of the hair cyclehas been divided
into eight subphases beginning with late anagen and ending in early telogen(357, 542).
Hair follicledevelopment and its postnatal regeneration are characterized by dramaticchanges in its microanatomy and cellular activity, which are controlled bymultiple signalling pathways, transcription factors and epigenetic regulators, includingmicroRNAs (miRNAs)
Our focus in this review is on the matureand its contorls. Weattempt here to integrate ...whichwar pretty well known,except for, we do not ...because . Ourgoal is to;
It is important to appreciate that there is an;
it is believed;
实验现象或结果描述：Transcriptional activation, theearliest observed changes of anagen, occurs in the cells of the papilla and thesecondary hair germ
现在：More recently, mature whole skin from mice and humans has beenused to study the hair cycle
转折，不足之处：Although these follicles continue to grow for ;9 days inculture and are thus useful for studying the anagen phase and the onset ofcatagen, they do not traverse the full hair cycle and do not generate newfollicles
No such system is now available;
For this reason
Before we explore the importance of miRNAs for HF biology, we would like tofurther address additional and very basic questions relating to miRNAfunction.
What is the reasonfor such a largenumber of post-transcriptional regulators
Indeed, miRNA profiling studiesin the HF during morphogenesis and cycling revealed the spatio- temporalexpression of a large number of miRNAs (24–26), which indicates the significanceof miRNAs in gene expression regulatory circuits of a complex mini-organ suchas the hair follicle.
Despite many years ofintensive research into target genes of miRNAs, this issue is notresolved. Initial and serious attempts to address this question indicatethat miRNAs can regulate on average at least 7 (27) to up to 100genes
Experiments withmiRNA knock-out or their overexpression indicate that the impact of the loss ofa miRNA can be broad.
However, there is also somejustification to focus on a very few key target genes (30).
intensive studies in Drosophila by Brenneke et al. (28) showed thattargeting does not need to involve a classical seed sequence.
This may explain why a miRNA is normally around 20 nucleotides long and not justaround 8 nucleotides.
Therefore, this issue is still controversial despite recent comments in Nam et al. (34)that ‘. . . noncanonical site types are either not effective or less effectivethan 6-mer sites’, with 6-mer sites by far the least effective canonical sites,and the clarification of the structural importance of the seed sequence formiRNA function and target recognition
However, the overall relevance of these non-canonical target sitesespecially for ancient and highly conserved miRNAs awaits further studiesand clarification.
The majority of experimentsindicate that one can expect a change in expression of the averagetarget gene on the mRNA and protein level of 20–50%.
Does it matter if a miRNA varies twofold for a buffering function?
In short, all these can be summed up with a conservative rule froma more dogmatic point of view: miRNAs preferentially bind to the 30UTR region ofa mRNA, with the most effective and functional sites recognized be the8-mer seed. This will result in a change in expression of the set of targetgenes of about 15–40% on the mRNA and the protein level.
Therefore, to identify disease- or process-related miRNAs, it seems wise toselect the ones that are massively altered between two states andhave a substantial expression level in one of the states.
In the skin, constitutive surface ectoderm-specific deletion ofmiRNA processors Dicer or Dgcr8 during embryonic development (E14.5–E17.5) resultsin the severe abnormalities in HF development characterized by theinability of the hair follicles to invaginate into the dermis, which leadsto major structural defects and failure to produce a hair shaft
Naturally, miRNAs are essential not only for HF development, but also forits postnatal growth.
In summary, these studies have provided striking evidence on howglobal loss of miRNAs in the embryonic epithelium dramatically changesthe molecular interactions between epithelial and the dermal cells resultingin the failure to form a normal hair follicle, and on how miRNAs arerequired in adult hair follicles for proliferation and apoptosis control.
Even within the hair follicle, major differences in miRNA expression areevident between the bulge, outer root sheath (ORS) and hair matrix cells,while surprisingly high similarities were observed between the miRNAprofile of the bulge and basal epidermal cells
miR-205 and miR-203 can be regarded as the squamous epithelialmiRNAs
It has been shown that miR-125b acts as a repressor of HF stem cell differentiation, andtherefore indispensable for anagen onset
Yi and colleagues have demonstrated that miR-205 is highlyenriched in the epithelial progenitors and stem cells during skindevelopment.
The deletion of miR-205 results in severe developmental defects and aperinatally lethal phenotype, which is very rarely seen in miRNAknockout mice.
Interestingly, vitamin D receptor (VDR) serves as one of the criticaltarget genes of miR-125b in follicular cells, and decreased VDRlevels explain several of the defects in HF differentiation in miR-125btransgenic mice
Constitutive overexpression of miR-24 in proliferating cells duringskin morphogenesis leads to abnormal HF development associatedwith reduced proliferation and premature differentiation.
Tcf3 is the transcription factor expressing in thefollicular stem cells and their progenies in the outer root sheath tomaintain their undifferenti- ated state
E2F2 was identified as one ofthe critical miR-24 targets
How miR-211 is involved in HF pigmentation remains unclear
Apoptosis plays an essential role for proper HF cycling and the maintenanceof homoeostasis
Studies with targeted Dicer and Drosha deletion clearly demonstrated theimportance of miRNAs for the protection of HF cells against apoptosis,because mutant hair follicles undergo massive apoptosis
Catagen induction and apoptosis are significantly reduced in theskin of p53 knockout mice
However, how p53 itself is regulated by miRNAs remains largely unknown
The area of miRNA-mediated gene expression regulation in the HFmesenchyme (dermal papilla and perifollicular connective tissue sheath) remainslargely underinvestigated.
Therefore, many intriguing questions await answers.
However, the functional significance of these findings remains elusive
This will provide new and important insights into fundamental mechanismsthat regulate cellular activity and cell fate decisions inside and outside ofthe skin. Eventually, these findings will be highly important for thedevelopment of novel miRNA-based drugs and therapies.
发挥作用：This indicates that the dermal papilla plays a main rolein androgen- mediated effects in the hair follicles；
Insulin-likegrowth factor-I (IGF-I) is a highly potent mitogen
This review summarizes the roles of miRNAs in the control ofhair follicle development, cycling and hair pigmentation, emphasizes theremaining problems/ unanswered questions, and provides future directions inthis rapidly growing and exciting area of research.