Hair Follicle Cell Proliferation Research Articles

Cedrol in ginger (Zingiber officinale) as a promising hair growth drug: The effects of oral and external administration on hair regeneration and its mechanism

Ginger is an important cooking spice and herb worldwide, and scientific research has gradually confirmed the effect of ginger on preventing hair loss. Cedrol (CE) is a small sesquiterpene molecule in ginger and its external administration (EA) has shown hope in promoting hair growth, and alternative administration mode has become a potential treatment scheme to improve the efficacy of CE. The purpose of this study is to evaluate the effects of oral administration (OA) and EA of CE on hair regeneration of C57BL/6 alopecia areata (AA) mice induced by cyclophosphamide (CP) and to clarify the potential hair growth mechanism of CE in AA model in vitro and in vivo. The results showed that CE-OA has a shorter hair-turning black time and faster hair growth rate, and can lessen hair follicle damage induced by CP and promote hair follicle cell proliferation. Its effect is superior to CE-EA. At the same time, CE can increase the cytokines IFN-γ, IL-2, and IL-7 in the serum of mice, and decrease the expression of adhesion factors ICAM-1 and ELAM-1, thus alleviating the immunosuppression induced by CP. Mechanism research shows that CE regulates the JAK3/STAT3 signaling pathway, activates the Wnt3α/β-catenin germinal center, and ameliorates oxidative stress induced by CP, thus promoting the proliferation of hair follicle cells and reversing AA. These results provide a theoretical basis for understanding the anti-AA mechanism of CE-OA, indicating that CE can be used as raw material for developing oral hair growth drugs.

Can Plant Extracts Help Prevent Hair Loss or Promote Hair Growth? A Review Comparing Their Therapeutic Efficacies, Phytochemical Components, and Modulatory Targets

This narrative review aims to examine the therapeutic potential and mechanism of action of plant extracts in preventing and treating alopecia (baldness). We searched and selected research papers on plant extracts related to hair loss, hair growth, or hair regrowth, and comprehensively compared the therapeutic efficacies, phytochemical components, and modulatory targets of plant extracts. These studies showed that various plant extracts increased the survival and proliferation of dermal papilla cells in vitro, enhanced cell proliferation and hair growth in hair follicles ex vivo, and promoted hair growth or regrowth in animal models in vivo. The hair growth-promoting efficacy of several plant extracts was verified in clinical trials. Some phenolic compounds, terpenes and terpenoids, sulfur-containing compounds, and fatty acids were identified as active compounds contained in plant extracts. The pharmacological effects of plant extracts and their active compounds were associated with the promotion of cell survival, cell proliferation, or cell cycle progression, and the upregulation of several growth factors, such as IGF-1, VEGF, HGF, and KGF (FGF-7), leading to the induction and extension of the anagen phase in the hair cycle. Those effects were also associated with the alleviation of oxidative stress, inflammatory response, cellular senescence, or apoptosis, and the downregulation of male hormones and their receptors, preventing the entry into the telogen phase in the hair cycle. Several active plant extracts and phytochemicals stimulated the signaling pathways mediated by protein kinase B (PKB, also called AKT), extracellular signal-regulated kinases (ERK), Wingless and Int-1 (WNT), or sonic hedgehog (SHH), while suppressing other cell signaling pathways mediated by transforming growth factor (TGF)-β or bone morphogenetic protein (BMP). Thus, well-selected plant extracts and their active compounds can have beneficial effects on hair health. It is proposed that the discovery of phytochemicals targeting the aforementioned cellular events and cell signaling pathways will facilitate the development of new targeted therapies for alopecia.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Retracted: ERK1/2 Pathway Is Involved in the Enhancement of Fatty Acids from Phaeodactylum tricornutum Extract (PTE) on Hair Follicle Cell Proliferation.

[This retracts the article DOI: 10.1155/2020/2916104.].

AP collagen peptides improve hair growth and quality by promoting human hair cell proliferation and keratin synthesis

Hair is an essential protective and health-maintaining covering for the body, especially the scalp. It is also important esthetically in modern society, where hair loss, whether caused by the severe scalp condition androgenic alopecia or other internal or external factors, has societal and psychological impacts. Preventing the apoptosis of human hair follicle cells, including hair follicle dermal papilla cells (HFDPCs) and human hair follicle keratinocytes (HHFKs), is crucial for hair production, alongside hair strengthening, which is essential in combatting hair loss. Given the structural importance of collagen peptides in the skin matrix and tissues surrounding hair follicles, we studied the function of AP collagen peptides (APCP) as a hair growth and quality improvement agent. APCP was found to stimulate the proliferation of hair follicle cells and counteract H2O2-induced apoptosis. It also significantly suppressed the expression of dickkopf-1 (DKK1) and bone morphogenetic protein 6 (BMP6), which induce hair cell apoptosis in the presence or absence of UVA/B irradiation. Moreover, APCP induced expression of the antioxidant enzymes, catalase and superoxide dismutase 1 (SOD1), while enhancing hair keratin expression in HHFKs. Mechanistically, APCP facilitated hair growth by elevating GAS6 expression and activating PKA and AKT/ERK signaling pathways. Notably, APCP increased levels of phosphor-?-catenin (Ser552/Ser675) as well as total ?-catenin, as demonstrated by Western blotting and immunocytochemistry. Lastly, we showed that APCP increased expression of the hair cuticle type I keratins, keratin-32 and 42, in HHFKs. Overall, these findings propose APCP as a promising candidate for safeguarding hair follicle cells and mitigating hair loss by improving hair growth and quality.

Cell-free fat extract restores hair loss: a novel therapeutic strategy for androgenetic alopecia

BackgroundAndrogenetic alopecia (AGA) is one of the most common hair loss diseases worldwide. However, current treatments including medicine, surgery, and stem cells are limited for various reasons. Cell-free fat extract (CEFFE), contains various cell factors, may have potential abilities in treating AGA. This study aims to evaluate the safety, effectiveness and the underlying mechanism of CEFFE in treating AGA.MethodsSex hormone evaluation, immunogenicity assay and genotoxicity assay were conducted for CEFFE. In vivo study, male C57BL/6 mice were injected subcutaneously with dihydrotestosterone (DHT) and were treated with different concentration of CEFFE for 18 days (five groups and n = 12 in each group: Control, Model, CEFFELow, CEFFEMiddle, CEFFEHigh). Anagen entry rate and hair coverage percentage were analyzed through continuously taken gross photographs. The angiogenesis and proliferation of hair follicle cells were evaluated by hematoxylin–eosin, anti-CD31, and anti-Ki67 staining. In vitro study, dermal papilla cells (DPCs) were incubated with different concentrations of CEFFE, DHT, or CEFFE + DHT, followed by CCK-8 assay and flow cytometry to evaluate cell proliferation cycle and apoptosis. The intracellular DHT level were assessed by enzyme-linked immunosorbent assay. The expression of 5α-reductase type II, 3α-hydroxysteroid dehydrogenase and androgen receptor were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or/and western blot.ResultsIn CEFFE-treated mice, an increase in the anagen entry rate and hair coverage percentage was observed. The number of CD31-positive capillaries and Ki67-positive cells were increased, suggesting that CEFFE promoted the proliferation of DPCs, modulated the cell cycle arrest, inhibited apoptosis caused by DHT, reduced the intracellular concentration of DHT in DPCs, and downregulated the expression of AR.ConclusionsCEFFE is a novel and effective treatment option for AGA through producing an increased hair follicle density and hair growth rate. The proposed mechanisms are through the DHT/AR pathway regulation and regional angiogenesis ability.

Melatonin promotes the development of the secondary hair follicles by regulating circMPP5

BackgroundThe quality and yield of cashmere fibre are closely related to the differentiation and development of secondary hair follicles in the skin of cashmere goats. The higher the density of secondary hair follicles, the higher the quality and yield of cashmere from the fleece. Development of secondary hair follicles commences in the embryonic stage of life and is completed 6 months after birth. Preliminary experimental results from our laboratory showed that melatonin (MT) treatment of goat kids after their birth could increase the density of secondary hair follicles and, thus, improve the subsequent yield and quality of cashmere. These changes in the secondary hair follicles resulted from increases in levels of antioxidant and expression of anti-apoptotic protein, and from a reduction in apoptosis. The present study was conducted to explore the molecular mechanism of MT-induced secondary hair follicle differentiation and development by using whole-genome analysis.ResultsMT had no adverse effect on the growth performance of cashmere kids but significantly improved the character of the secondary hair follicles and the quality of cashmere, and this dominant effect continued to the second year. Melatonin promotes the proliferation of secondary hair follicle cells at an early age. The formation of secondary hair follicles in the MT group was earlier than that in the control group in the second year. The genome-wide data results involved KEGG analysis of 1044 DEmRNAs, 91 DElncRNAs, 1054 DEcircRNAs, and 61 DEmiRNAs which revealed that the mitogen-activated protein kinase (MAPK) signaling pathway is involved in the development of secondary hair follicles, with key genes (FGF2, FGF21, FGFR3, MAPK3 (ERK1)) being up-regulated and expressed. We also found that the circMPP5 could sponged miR-211 and regulate the expression of MAPK3.ConclusionsWe conclude that MT achieves its effects by regulating the MAPK pathway through the circMPP5 sponged the miR-211, regulating the expression of MAPK3, to induce the differentiation and proliferation of secondary hair follicle cells.In addition there is up-regulation of expression of the anti-apoptotic protein causing reduced apoptosis of hair follicle cells. Collectively, these events increase the numbers of secondary hair follicles, thus improving the production of cashmere from these goats.

Triton modified polyethyleneimine conjugates assembled with growth arrest-specific protein 6 for androgenetic alopecia transdermal gene therapy.

Androgenetic alopecia is an androgen-dependent skin disorder that commonly affects hair follicle growth and hair loss. Gene therapy that can promote the proliferation and survival of hair follicle cells can be a potential choice for its cure. While transdermal application of therapeutic functional nucleic acids across the stratum corneum is quite difficult. Here, we first develop a transdermal agent for functional nucleic acid delivery using Triton X-100-modified low molecular weight polyethyleneimine (PEI-Triton-N, N​=​6 or 8). In vitro cell experiments demonstrate that the PEI-Triton-N conjugates can stably encapsulate and efficiently deliver plasmid DNA to hard-to-transfect keratinocyte HaCaT cells. Further mouse model studies show that PEI-Triton-6 can encapsulate and deliver growth arrest-specific protein 6 (Gas6) plasmid through transdermal administration. The transfected Gas6 prolongs the anagen status, inhibits the apoptosis of hair follicle cells, and further promotes the proliferation and differentiation of hair follicle cells. The PEI-Triton-6/pDNAGas6 complexes can obviously alleviate hair loss in androgenetic alopecia mice and provides a promising strategy for gene therapy via transdermal administration.

Wnt/β-catenin signaling activator restores hair regeneration suppressed by diabetes mellitus

Diabetes mellitus is one of the most prevalent diseases in modern society. Many complicationssuch as hepatic cirrhosis, neuropathy, cardiac infarction, and so on are associated with diabetes. Although a relationship between diabetes and hair loss has been recently reported, the treatment of diabetic hair loss by Wnt/β-catenin activators has not been achieved yet. In this study, we found that the depilation-induced anagen phase was delayed in both db/db mice and high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice. In diabetic mice, both hair regrowth and wound-induced hair follicle neogenesis (WIHN) were reduced because of suppression of Wnt/β-catenin signaling and decreased proliferation of hair follicle cells. We identified that KY19382, a small molecule that activates Wnt/β-catenin signaling, restored the capabilities of regrowth and WIHN in diabetic mice. The Wnt/β-catenin signaling activator also increased the length of the human hair follicle which was decreased under high glucose culture conditions. Overall, the diabetic condition reduced both hair regrowth and regeneration with suppression of the Wnt/β-catenin signaling pathway. Consequently, the usage of Wnt/β-catenin signaling activators could be a potential strategy to treat diabetes-induced alopecia patients. [BMB Reports 2022; 55(11): 559-564].

Hair growth-promoting effects of Sargassum glaucescens oligosaccharides extracts

Background: Brown algae have been used as food and traditional Chinese medicine for thousands of years and it is known to contain a bioactive component - fucoidan. However, little is known about the effect of fucoidan on cell differentiation and proliferation, particularly in topical application. Given that, this study focused on investigating the effect of different extraction methods of fucoidans on the promotion of human hair growth ability.Methods: Fucoidans from Sargassum glaucescens were extracted by a combination of microwave-assisted high-pressure water or subcritical water. Different molecular weight fractions of fucoidan were separated. The effect of these fractions on the proliferation and hair growth-related genes expression on hair follicle dermal papilla cells (HFDPC) was investigated. Mice models and ex vivo hair follicle culture assays were used to determine the efficacy.Significant Findings: Sargassum glaucescens fucoidan extracts higher than 1 KDa molecular weight demonstrated hair growth-promoting ability. The oligo-fucoidan was more effective in enhancing hair follicle cell proliferation. The effects of fucoidans on the proliferation of HFPDC correlated with IGF-1 and LEF-1 gene expressions. Hair growth-promoting activity was observed in mice models after being treated with Sargassum glaucescens fucoidan extracts. Thus, fucoidan could be a potential topical medicine in alopecia treatment.

Bioactive Small Molecule Enhances Skin Burn Wound Healing and Hair Follicle Regeneration by Activating PI3K/AKT Signaling Pathway: A Preclinical Evaluation in Animal Model

Rational: A bioactive small molecule of precision medicine involves targeted therapies. Shikonin, a herbal extract, is an active small molecule that is traditionally used in wound healing for its anti-tumor and anti-inflammatory properties. Therefore, the present study aims to evaluate the anti-inflammatory role of shikonin in skin burn wound healing and hair follicle regeneration and to identify molecular signaling pathways that promote the regeneration. Method: A secondary skin burn model of mice was established by conventional method. The burn wound was externally treated with shikonin ointment and excipient treated mice were used as controls. Skin samples were taken on the day 3 and 7 after drug treatment and the dosage was unified in the experiments. The wound healing process was observed by histopathological and immunofluorescence (IF) staining. The proliferation of hair follicle cells in wound skin was tracked by 5-Ethynyl-2'-deoxyuridne (EdU) staining. The inflammatory factors at the wound healing site were quantified by polymerase chain reaction (qPCR). The PI3K/Akt, P65, Ki67 signaling proteins and Bax/BCL2 apoptosis proteins were studied by western blot analysis. The functionality of PI3K/Akt signaling pathway was tested using LY294002, an inhibitor of PI3K. Result: Shikonin treated mice group exhibited better and faster skin burn wound healing in comparison with the controls. The proliferation of new skin cells and hair follicle regeneration in the wound site of the shikonin treated group was more active. The recruitment of macrophages in shikonin treated group was inhibited inturn decreased the expression of inflammatory factors. However, LY294002 inhibited the shikonin-mediated PI3K/Akt signaling pathway and affected the wound healing process. Conclusion: In conclusion, this study strengthens the hypothesis that bioactive small molecule, shikonin, inhibits inflammation, promotes wound healing and has a significant protective effect on the deep hair follicles against burn skin injury by activating the PI3K/Akt signaling pathway.

Serum Micronutrient Levels In Premature Canities: A Systematic Review and Meta-analysis.

Background: Premature canities, also known as premature graying of hair, is the graying of hair before 20 years old in Caucasians, before 25 years old in Asians, and before 30 years old in African–Americans. The risk factors for premature canities are multifactorial. The role of micronutrient deficiency has long been suggested to be involved in the etiopathogenesis of premature canities. The management of premature canities remains limited and far from satisfactory; hence, knowing what vitamins and minerals can help in treating premature canities is vital. Aim: This study aims to analyze serum vitamin B12, iron, ferritin, copper, calcium, and zinc levels in premature canities. Methods: The MEDLINE/PubMed electronic database, Cochrane library, ClinicalTrials.gov, EBSCO, Scopus, ProQuest, Cambridge Core, reference lists, conference proceedings, and researchers in fields of eligible studies were searched. Twelve studies (n = 1791 subjects) were included in qualitative analysis of which nine studies (n = 1381 subjects) were included in meta-analysis. Serum levels of micronutrients (vitamin B12, iron, ferritin, copper, calcium, and zinc) were compared in the premature canities and nonpremature canities groups. Result: Pooling of data using fixed-effects model found the overall effect mean difference serum vitamin B12 level was −0.697 ± 0.105 (95% CI = −0.904 to −0.490), p < 0.001. The overall mean difference serum iron level was 0.146 ± 0.105 (95% CI = −0.058 to 0.350), p = 0.161. The overall mean difference serum ferritin level was 0.720 ± 0.071 (95% CI = 0.585 to 0.854), p < 0.001. The overall mean difference serum copper level was 0.230 ± 0.118 (95% CI = −0.003 to 0.463, p = 0.053. The overall mean difference serum calcium level was −0.443 ± 0.114 (95% CI = −0.655 to −0.212), p < 0.001. The overall mean difference serum zinc level was −0.104 ± 0.138 (95% CI = 0.377 to 0.170, p = 0.457. Qualitative analysis showed that vitamin B12 plays an important role in DNA synthesis in the proliferation of hair follicle cells and in melanogenesis. Iron, ferritin, copper, calcium, and zinc also play important roles in stabilizing and increasing tyrosinase activity in several stages of the melanogenesis process. Conclusion: The meta-analysis showed that serum levels of vitamin B12, ferritin, and calcium were significantly lower in premature canities. Although the lower serum iron, copper, and zinc levels were not significantly different in premature canities compared with nonpremature canities. Qualitative analysis found that deficiency of vitamin B12, iron, ferritin, zinc, copper, and calcium can affect the physiology of hair melanogenesis that causing premature canities.

ERK1/2 Pathway Is Involved in the Enhancement of Fatty Acids from Phaeodactylum tricornutum Extract (PTE) on Hair Follicle Cell Proliferation.

Extractions from Phaeodactylum tricornutum have been widely studied and evaluated to various biological effects. The aim of this study was to investigate the promotional effect of P. tricornutum extract (PTE) on the ERK1/2 signaling pathway involved in hair follicle cell proliferation. In order to illuminate the enhancement of PTE on hair growth by promoting proliferation of hair follicle cells, the activities of human hair follicle outer root sheath cell (HFORSC), human hair follicle germinal matrix cells (HFGMC), and hair epithelial melanocytes (HEM) were observed under PET treatment. Levels of keratins, PKCζ, ERK1/2, and p38 MAPK in hair follicle cells were determined by Western blotting to illustrate the mechanisms of PTE effects on hair growth. Analyzed by GC-MS, the main polyunsaturated fatty acids which were 9.43% of total fatty acids in PTE were linolenic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid. Melanin content and tyrosinase activity in HEM were measured. The results showed that PTE exhibited remarkable enhancement on cell proliferation. Melanin production was inhibited by PTE treatment, while keratin-14, keratin-15, and keratin-17 levels on hair follicle cells were elevated at different concentrations. The promotions of ERK1/2 and p38 MAPK levels indicated that the ERK1/2 signaling pathway is involved in the proliferation of hair follicle cells. These results are the evidence that PTE potentially deserves further study as a new natural candidate for hair care applications.

Pantothenic acid promotes dermal papilla cell proliferation in hair follicles of American minks via inhibitor of DNA Binding 3/Notch signaling pathway

AimsPantothenic acid (PA) has been applied to treat alopecia, but the underlying mechanism is still unclear. Our study aims to explore the underlying mechanism of PA in regulating hair follicle (HF) growth. Main methodsMink HFs and dermal papilla (DP) cells were isolated and cultured in vitro. HFs and DP cells were treated with 0, 10, 20, 40 μg/ml PA. The effect of PA on HF growth, DP cell proliferation, cell cycle distribution, cell migration, and insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expressions in DP cells was measured. Moreover, the effect of PA on inhibitor of DNA binding 3 (ID3)/Notch signaling pathway was analyzed. Subsequently, ID3 was silenced to validate whether ID3/Notch signaling pathway was involved in regulating DP cell proliferation by PA. Key findingsBoth 20 μg/ml and 40 μg/ml PA promoted HF growth, G1/S transition of DP cells and IGF-1 and VEGF expressions in DP cells, while only 20 μg/ml PA promoted cell viability and the migration of DP cells. Thus 20 μg/ml PA was chosen for the following experiments. PA treatment was found to up-regulate ID3 expression but down-regulate Notch receptor 1 (Notch1) and Notch signaling targets expressions. Furthermore, ID3 knockdown reversed PA-induced cell proliferation and inhibition of Notch1 and Notch signaling targets expressions, indicating that PA-induced DP cell proliferation and inhibition of Notch signaling were mediated via up-regulation of ID3. SignificanceThis study provides an underlying mechanism related to the effect of PA on stimulating DP cell proliferation.

Effects of photoperiod on circadian clock genes in skin contribute to the regulation of hair follicle cycling of Inner Mongolia white cashmere goats.

This study investigated how the effects of photoperiod on circadian clock genes in the skin contribute to the regulation of hair follicle cycling of Inner Mongolia white cashmere goats. Twenty-four female (non-pregnant) Inner Mongolia white cashmere goats aged 1-1.5years old with similar live weights (mean, 20.36±2.63kg) were randomly allocated into two groups: a natural daily photoperiod group (NDPP group:10-16hr Light, n=12) and a short daily photoperiod group (SDPP group: 7hr Light:17hr Dark, n=12). All goats were housed in individual pens from May 15 to October 15, 2015 and were fed the same diets. We detected the mRNA expression of brain and muscle arnt-like protein-1 (Bmal1), circadian locomotor output control kaput (Clock), cryptochrome-1 (Cry1), period homolog-1 (Per1) and Rev-erbα genes in the goat skin. ANOVA revealed a significant 24hr (10:00hr, 14:00hr, 18:00hr, 22:00hr, 02:00hr, 06:00hr, 10:00hr) variation between the SDPP and NDPP groups for three months (July, September, and October). In summary, the current results confirm that an intrinsic oscillating molecular clock exists in goat skin, and that the clock is important for potential timing mechanisms at the anagen phase of hair follicles, which would contribute to the regulation mechanisms of hair follicle cell proliferation.

Stromal Vascular Fraction and Platelet-Rich Plasma Upregulate Vascular Endothelial Growth Factor Expression to Promote Hair Growth via the Wnt/β-Catenin Signaling Pathway

Androgenetic alopecia (AGA) is a hair loss disease. At present, use of the stromal vascular fraction (SVF) and platelet-rich plasma (PRP) are thought to be the novel, safe, and effective treatment options of AGA, but the mechanism by which SVF and PRP promote hair growth is unclear. Here, we investigated the mechanism underlying the effects of SVF and PRP on hair growth by in vitro culture and in vivo modeling. SVF and PRP promoted hair growth, as was evident from the observation and counting of hair on the back skin of nude mice using ImageJ software. SVF and PRP promoted hair growth, and SVF worked better. We performed nucleic acid extraction with nanomagnetic beads, and the protein levels were extracted with a bicinchoninic acid protein assay kit. The results of western blot analysis and quantitative polymerase chain reaction (qPCR) showed that both SVF and PRP promoted the expression of anti-apoptotic genes. The effect of SVF was better than that of PRP. The results of EdU and hematoxylin and eosin staining showed that SVF and PRP induced the proliferation of hair follicle cells. SVF exerted better effects on the proliferation of hair follicle cells than PRP. Enzyme-linked immunosorbent assay (ELISA) results showed that the expression of the proteins associated with the Wnt/β-catenin process, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), alkaline phosphatase (ALP), Wnt10b, and β-catenin, significantly increased in the SVF-treated and PRP-treated dermal/epidermal cells as compared with the control cells. Therefore, SVF and PRP increased the expression of VEGF and PDGF through the Wnt/β-catenin signaling pathway to promote hair growth. The effect of SVF on dermal cells/epidermal cells was stronger than that of PRP, and the difference was statistically significant (P < 0.05).

Pre-clinical evidences for the efficacy of tryptanthrin as a potent suppressor of skin cancer.

ObjectiveClinical trials have demonstrated the efficacy of indigo naturalis, a traditional Chinese medicine ingredient, against psoriasis, a skin disease characterized by keratinocyte hyperproliferation and inflammation. The present study investigates the efficacy of tryptanthrin, a bioactive compound in indigo naturalis, against non‐melanoma skin cancer (NMSC) and the signalling events involved.MethodsEfficacy of tryptanthrin against NMSC was assessed using DMBA/PMA‐induced skin carcinogenesis model in Swiss albino mice. Immunostaining for PCNA and ki‐67 was used to mark proliferating cells in tissues. Haematoxylin and eosin staining and toluidine staining were employed to assess inflammation, and TUNEL assay was used to detect apoptosis in tissues. The signalling events were evaluated using Western blot, imunohistochemistry and immunofluorescence staining. MTT assay and clonogenic assay were performed to assess the viability and proliferation of cancer cells, in vitro.ResultsIn mice, topical application of tryptanthrin suppressed skin carcinogenesis. It attenuated inflammation, impeded the proliferation of hair follicle (HF) cells and suppressed the activation of β‐catenin, a major driver of HF cell proliferation. Additionally tryptanthrin suppressed the activation of ERK1/2 and p38, both of which promote β‐catenin activation and lowered the expression of c‐Myc and cyclin‐D1. Tryptanthrin suppressed the proliferation of the human NMSC cell line, A431 and abrogated EGF‐induced activation of β‐catenin and subsequent cytoskeletal rearrangement.ConclusionThe study demonstrates with molecular evidence that tryptanthrin is an effective suppressor of NMSC.

Hot water extract of oriental melon leaf promotes hair growth and prolongs anagen hair cycle: In vivo and in vitro evaluation.

Effects of hot water extracts of oriental melon leaves (OML) on promotion of hair growth were investigated. Topical OML extract administration for hair regeneration was investigated using an in vivo model with C57BL/6 mice. Effects of OML extracts on the human hair growth were investigated using a hair follicle organ culture. OML extracts induced a shortened telogen to anagen conversion and promoted hair growth in the C57BL/6 mouse model. Culture of human hair follicles in the presence of OML extracts for 8 days promoted hair growth and prolonged the anagen duration due to induction of hair follicle cell proliferation in the bulb region. OML extracts exert a hair growth promotion effect and, therefore, can be used as a therapeutic agent for prevention of hair loss.

Effects of a Closed Space Environment on Gene Expression in Hair Follicles of Astronauts in the International Space Station.

Adaptation to the space environment can sometimes pose physiological problems to International Space Station (ISS) astronauts after their return to earth. Therefore, it is important to develop healthcare technologies for astronauts. In this study, we examined the feasibility of using hair follicles, a readily obtained sample, to assess gene expression changes in response to spaceflight adaptation. In order to investigate the gene expression changes in human hair follicles during spaceflight, hair follicles of 10 astronauts were analyzed by microarray and real time qPCR analyses. We found that spaceflight alters human hair follicle gene expression. The degree of changes in gene expression was found to vary among individuals. In some astronauts, genes related to hair growth such as FGF18, ANGPTL7 and COMP were upregulated during flight, suggesting that spaceflight inhibits cell proliferation in hair follicles.

Regulations of Reversal of Senescence by PKC Isozymes in Response to 12-O-Tetradecanoylphorbol-13-Acetate via Nuclear Translocation of pErk1/2.

The mechanism by which 12-O-tetradecanoylphorbol-13-acetate (TPA) bypasses cellular senescence was investigated using human diploid fibroblast (HDF) cell replicative senescence as a model. Upon TPA treatment, protein kinase C (PKC) α and PKCβ1 exerted differential effects on the nuclear translocation of cytoplasmic pErk1/2, a protein which maintains senescence. PKCα accompanied pErk1/2 to the nucleus after freeing it from PEA-15pS104 via PKCβ1 and then was rapidly ubiquitinated and degraded within the nucleus. Mitogen-activated protein kinase docking motif and kinase activity of PKCα were both required for pErk1/2 transport to the nucleus. Repetitive exposure of mouse skin to TPA downregulated PKCα expression and increased epidermal and hair follicle cell proliferation. Thus, PKCα downregulation is accompanied by in vivo cell proliferation, as evidenced in 7, 12-dimethylbenz(a)anthracene (DMBA)-TPA-mediated carcinogenesis. The ability of TPA to reverse senescence was further demonstrated in old HDF cells using RNA-sequencing analyses in which TPA-induced nuclear PKCα degradation freed nuclear pErk1/2 to induce cell proliferation and facilitated the recovery of mitochondrial energy metabolism. Our data indicate that TPA-induced senescence reversal and carcinogenesis promotion share the same molecular pathway. Loss of PKCα expression following TPA treatment reduces pErk1/2-activated SP1 biding to the p21WAF1 gene promoter, thus preventing senescence onset and overcoming G1/S cell cycle arrest in senescent cells.