scholarly journals Suppression of FGF5 and FGF18 Expression by Cholesterol-Modified siRNAs Promotes Hair Growth in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Jungang Zhao ◽  
Haojie Lin ◽  
Lusheng Wang ◽  
Keke Guo ◽  
Rongrong Jing ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Topical Application ◽  
Inhibitory Effect ◽  
Intradermal Injection ◽  
Hair Follicles ◽  
Anagen Phase ◽  
A Cell ◽  
Hair Follicle Cycle

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

Antinociceptive properties of shikonin: in vitro and in vivo studies

2016 ◽  
Vol 94 (7) ◽  
pp. 788-796 ◽  
Author(s):  
Bhawana Gupta ◽  
Sabyasachi Chakraborty ◽  
Soumya Saha ◽  
Sunita Gulabsingh Chandel ◽  
Atul Kumar Baranwal ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Inhibitory Effect ◽  
Pain Modulation ◽  
In Vivo Studies ◽  
Channel Modulation ◽  
Pain Models ◽  
A Cell ◽  
Dose Dependent

Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.

HERBAL CREAMS OF REISHI EXTRACT AND TEA TREE OIL FOR HIRSUTISM–AN IN VIVO STUDY

2020 ◽  
pp. 106-110
Author(s):  
SANGEETA CHOUDHURY ◽  
BLR MADHAVI
Keyword(s):  
Topical Application ◽  
Hair Growth ◽  
Ethanolic Extract ◽  
Hair Follicles ◽  
In Vivo Studies ◽  
Control Group ◽  
Tea Tree Oil ◽  
Tea Tree

Objective: The aim of this work to formulate, evaluate and compare the effectiveness of herbal creams containing extract of reishi and tea tree oil for treating hirsutism. Methods: Herbal ingredients were authenticated. Cream base was initially formulated. Three formulations of herbal cream were prepared. Reishi ethanolic extract, tea tree oil, and combination of tea tree oil and reishi extract were added to the cream base and formulated cream were named as RHC, THC and RTC respectively. In vitro evaluations on herbal creams were done for the physicochemical characteristics. In vivo studies were carried out on female Swiss Albino mice for the activity against hair growth by topical application of cream to shaved skin. The histological and morphometric evaluation was carried out. Skin irritancy study was conducted. Results: The herbal creams showed desirable physicochemical properties like pH, viscosity and spreadability. Statistical analysis for the length of hair was performed by using one way ANOVA followed by DUNNET’S post hoc test where THC and RTC were found to be significant whereas RHC showed no significant reduction of hair growth compared to control. RTC showed a significant effect at p<0.05 and hair growth reduction was significant for THC at p<0.001 compared to the control group. RTC and THC showed mild to moderate reduction in the size of the hair follicles with a reduction of sebaceous gland size in the histological analysis. Conclusion: Topical application of herbal creams to mice showed that hair growth was fastest in group RHC and was slowest in group THC and intermediate with RTC. It can be concluded that these herbal actives can be used as an effective treatment against hirsutism. Within the study period, tea tree oil was found to be more effective than reishi extract and the combination product. Further formulation studies and in vivo studies need to be carried out on reishi to assess its effectiveness against hirsutism.

scholarly journals Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

2020 ◽  
Vol 6 (30) ◽  
pp. eaba1685 ◽  
Author(s):  
Shiqi Hu ◽  
Zhenhua Li ◽  
Halle Lutz ◽  
Ke Huang ◽  
Teng Su ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Paracrine Signaling ◽  
Hair Regrowth ◽  
Study Results ◽  
Anagen Phase ◽  
Hair Follicle Cycle

The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

The effect of IGF-I on the growth of secondary hair follicles of the Cashmere goat in vitro

1997 ◽  
Vol 1997 ◽  
pp. 170-170
Author(s):  
H. Galbraith ◽  
D. Sims ◽  
D. Hazlerigg
Keyword(s):  
Growth Factors ◽  
Hair Follicle ◽  
Human Hair ◽  
Hair Follicles ◽  
Cashmere Goat ◽  
Igf I ◽  
Hair Follicle Cycle ◽  
Insulin Like Growth Factors

Factors regulating the growth of Cashmere fibre and the hair follicle cycle are poorly understood. Insulin-like growth factors (IGFs) or insulin at higher concentrations, have been shown to stimulate in vitro growth of human hair follicles (Philpott et al, 1994). The role of such mitogens in the production of cashmere fibre by the Cashmere goat has not been previously investigated. The objective the study reported here was to investigate the growth of hair follicles in the absence and presence of insulin or IGF-I using our established in vitro technique.

scholarly journals β-Catenin-Dependent and -Independent Effects of ΔN-Plakoglobin on Epidermal Growth and Differentiation

2004 ◽  
Vol 24 (19) ◽  
pp. 8649-8661 ◽  
Author(s):  
J. Teulière ◽  
M. M. Faraldo ◽  
M. Shtutman ◽  
W. Birchmeier ◽  
J. Huelsken ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Glycogen Synthase ◽  
Mouse Skin ◽  
Hair Follicles ◽  
Epidermal Differentiation ◽  
Follicular Tumors

ABSTRACT Both β-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. β-Catenin is known to associate with Lef/Tcf factors and to participate directly in transactivation in vivo, whereas the role of plakoglobin in transcriptional regulation has been less studied. To analyze the functions of plakoglobin in vivo, we generated transgenic mice expressing in the epidermis N-terminally truncated plakoglobin (ΔN122-PG) lacking the glycogen synthase kinase 3β phosphorylation sites and therefore protected against degradation (transgenic line K5-ΔN122-PG). The expression of ΔN122-PG led to the formation of additional hair germs, hyperplastic hair follicles, and noninvasive hair follicle tumors, a phenotype reminiscent of that induced by expression of N-terminally truncated β-catenin. However, if expressed in β-catenin-null epidermis, ΔN122-PG did not induce new hair follicle germs and follicular tumors. Thus, ΔN122-PG cannot substitute for β-catenin in its signaling functions in vivo and the phenotype observed in K5-ΔN122-PG mouse skin must be due to the aberrant activation of β-catenin signaling. On the other hand, the expression of ΔN122-PG in β-catenin-null skin significantly increased the survival rate of mutant mice, rescued differentiation, and limited excessive proliferation in the interfollicular epidermis, suggesting that plakoglobin may be involved in the intracellular signaling events essential for epidermal differentiation.

Human hair growth in vitro

1990 ◽  
Vol 97 (3) ◽  
pp. 463-471
Author(s):  
M.P. Philpott ◽  
M.R. Green ◽  
T. Kealey
Keyword(s):  
Hair Follicle ◽  
Human Hair ◽  
Subcutaneous Fat ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Anagen Hair ◽  
Scalpel Blade ◽  
Thymidine Autoradiography

We report for the first time the successful maintenance and growth of human hair follicles in vitro. Human anagen hair follicles were isolated by microdissection from human scalp skin. Isolation of the hair follicles was achieved by cutting the follicle at the dermo-subcutaneous fat interface using a scalpel blade. Intact hair follicles were then removed from the fat using watchmakers' forceps. Isolated hair follicles maintained free-floating in supplemented Williams E medium in individual wells of 24-well multiwell plates showed a significant increase in length over 4 days. The increase in length was seen to be attributed to the production of a keratinised hair shaft, and was not associated with the loss of hair follicle morphology. [methyl-3H]thymidine autoradiography confirmed that in vitro the in vivo pattern of DNA synthesis was maintained; furthermore, [35S]methionine labelling of keratins showed that their patterns of synthesis did not change with maintenance. The importance of this model to hair follicle biology is further demonstrated by the observations that TGF-beta 1 has a negative growth-regulatory effect on hair follicles in vitro and that EGF mimics the in vivo depilatory effects that have been reported in sheep and mice.

scholarly journals Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer

2012 ◽  
Vol 109 (38) ◽  
pp. 15312-15317 ◽  
Author(s):  
Paola Tucci ◽  
Massimiliano Agostini ◽  
Francesca Grespi ◽  
Elke K. Markert ◽  
Alessandro Terrinoni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Data Set ◽  
Mesenchymal Transition ◽  
Metastatic Behavior ◽  
A Cell

p63 inhibits metastasis. Here, we show that p63 (both TAp63 and ΔNp63 isoforms) regulates expression of miR-205 in prostate cancer (PCa) cells, and miR-205 is essential for the inhibitory effects of p63 on markers of epithelial–mesenchymal transition (EMT), such as ZEB1 and vimentin. Correspondingly, the inhibitory effect of p63 on EMT markers and cell migration is reverted by anti–miR-205. p53 mutants inhibit expression of both p63 and miR-205, and the cell migration, in a cell line expressing endogenous mutated p53, can be abrogated by pre–miR-205 or silencing of mutated p53. In accordance with this in vitro data, ΔNp63 or miR-205 significantly inhibits the incidence of lung metastasis in vivo in a mouse tail vein model. Similarly, one or both components of the p63/miR-205 axis were absent in metastases or colonized lymph nodes in a set of 218 human prostate cancer samples. This was confirmed in an independent clinical data set of 281 patients. Loss of this axis was associated with higher Gleason scores, an increased likelihood of metastatic and infiltration events, and worse prognosis. These data suggest that p63/miR-205 may be a useful clinical predictor of metastatic behavior in prostate cancer.

scholarly journals Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingmei Liu ◽  
Xiangguang Shi ◽  
Yue Zhang ◽  
Yan Huang ◽  
Kai Yang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Hair Growth ◽  
Ex Vivo ◽  
Cell Activity ◽  
Hair Follicles ◽  
Androgenetic Alopecia ◽  
Pcr Analysis

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged &gt; 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.

THE DRUNKEN HAIR: INTRODUCING IN VIVO DEMONSTRATION OF INCREASED BLOOD ALCOHOL CONCENTRATION TEMPORARY DISRUPTING HUMAN HAIR FOLLICLES EMISSION OF ELECTROMAGNETIC RADIATION

2020 ◽  
Vol 8 (10) ◽  
pp. 123-130
Author(s):  
Abraham A. Embi
Keyword(s):  
Electromagnetic Radiation ◽  
Hair Follicle ◽  
Human Hair ◽  
Blood Alcohol Concentration ◽  
Physical Symptoms ◽  
Alcohol Concentration ◽  
Hair Follicles ◽  
Blood Alcohol

The human hair consists of a follicle a.k.a root penetrating the skin and an outer skin structure commonly called the shaft. The hair follicle has been classified as a miniorgan having its own cells divisions; aging stages and also demonstrated to be an energy emitter in the form of electromagnetic radiation. The intent of this manuscript is to introduce documentation from in vivo experiments showing the deleterious effect of alcohol consumption on the previously documented hair follicle intrinsic and orderly emission of energy a.k.a. Electromagnetic Radiation (EMR). This was possible by a minor modification of a tabletop optical microscopy technique introduced in 2015 and designed to display plant and animals tissue EMR. In vitro control experiments had shown that a drop of white wine covering a human hair follicle placed on a glass slide caused what appeared to be a disruption on the hair follicle EMR emissions; the addition of chemicals to the wine during manufacturing could have caused that effect. The answer could lie in an in vivo alcohol drinking approach by increasing only the blood alcohol concentration (BAC). In this manuscript two in vitro and two in vivo are presented where the author, a non-alcohol drinker, purposely and during fasting underwent two binge-drinking episodes aimed to increase his BAC and investigate its impact on hair follicles. Several black beard hair samples were plucked via tweezers as controls; additional samples were also plucked and processed at approximately peak alcohol physical symptoms such cheek numbness and dizziness which occurred between 35 and 45 minutes post two episodes of wine or wine and beer binges. Images and video-recordings are presented.

Free fatty acids and pancreatic function in the duck

1986 ◽  
Vol 112 (1) ◽  
pp. 100-104 ◽  
Author(s):  
R. Gross ◽  
P. Mialhe
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Inhibitory Effect ◽  
Feedback Mechanism ◽  
Pancreatic Function ◽  
Morphological Evidence ◽  
A Cell ◽  
Glucagon And Insulin

Abstract. The isolated perfused duck pancreas was used to study the effect of free fatty acids (FFA) on pancreatic function in vitro and to determine whether the FFA-glucagon negative feedback mechanism resulted from a direct inhibitory effect of FFA on the pancreatic A cell. Oleate, 2 mmol/l, increased the output rates of pancreatic somatostatin, glucagon and insulin. As there is poor morphological evidence in the duck for somatostatin to act as a paracrine intra-islet modulator, we reproduced in the pancreatico-duodenal artery, the rise in somatostatin level obtained in the pancreatic effluent after oleate. In these conditions the rises in glucagon and insulin secretions after oleate treatment were, respectively, reversed and suppressed, thereby reproducing observations previously made in vivo. Consequently, we may assume that the negative FFA-glucagon feedback mechanism that operates in vivo for physiological FFA variations does not result from a direct effect of FFA on the A cell, but may rather be mediated by an increase in pancreatic somatostatin secretion.

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