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


提高,促进: improve

混合:mixed; blended

The vibrissal follicle in this respect differs in manyways from the pelage follicle

...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 ofundoubtedly play; a critical role inbe 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

potential mechanism;

provide insights into possible cosmetic and therapeutic applications.

如前所述:previously described 

潜在的代偿机制:potentialcompensatory mechanism


然而、转折:while; nevertheless; However;Whereas; but

导致、结果:resulting inleadingtoas a result ofResultform; As; So; Because; So as to; Sothat

另外:MoreoverFurthermoreBesides Inaddition additionally at the outset it is obvious to; above allMoreoverNaturallyEven within


Prep:In spite of In despite of

换句话说,另一方面:in otherwordOn 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 ANKRare 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.

...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

方面有提高,进步:these patients also demonstratedsignificant improvement in facial wrinkles

举例: such as后只加一个thethose 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.

自上而下:top down

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... ... 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dividintoThe 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 notresolvedInitial 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