The synergistic effect of phototherapy and active substances on hair growth.

Androgenic alopecia (AGA) typically manifests post-puberty, resulting in decreases in hair density, disruptions in the hair growth cycle, and alterations in hair follicle micro structure. Dihydrotestosterone (DHT) is a key hormone implicated in hair loss, especially on male. In this study, we found that each of arginine (Arg), arterial extract (AE) or biotin tripeptide-1 (BT-1), when combined with low level light therapy (LLLT, at 630 nm, 2 J/cm2), showed the efficacy in enhancing mitochondrial functions, cell proliferation and collagen synthesis in fibroblasts. Additionally, CARRIPOWER (the complexes of AE, BT-1, Arg, and Diaminopyrimidine derivatives), in conjunction with LLLT (630 nm, 2 J/cm2), showed promising results in dermal papilla cells (DPCs). The promising results contained not also inflammatory cytokines (IL-1ß and IL-6) and cell pro apoptotic factor (TGF-ß2) reduction, but also Wnt pathway inhibition by decreasing DKK1 level, and pro-hair growth factors (vascular endothelial growth factor (VEGF) and ß-catenin) increase. This innovative combination therapy offers a potential solution for the treatment of AGA, addressing both hormonal and cellular factors involved in hair loss.

Low-level laser activates Wnt/ß-catenin signaling pathway-promoting hair follicle stem cell regeneration and wound healing: Upregulate the expression of key downstream gene Lef 1.

BACKGROUND: The objective of this study is to investigate the mechanism by which low-level laser stimulation promotes the proliferation of intraepithelial hair follicle stem cells (HFSCs) in wounds. This research aims to expand the applications of laser treatment, enhance wound repair methods, and establish a theoretical and experimental foundation for achieving accelerated wound healing. METHODS: The experimental approach involved irradiating a cell model with low-level laser to assess the proliferation of HFSCs and examine alterations in the expression of proteins related to the Wnt/ß-catenin signaling pathway. A mouse back wound model was established to investigate the effects of low-level laser irradiation on wound healing rate, wound microenvironment, and the proliferation of HFSCs in relation to the Wnt/ß-catenin signaling pathway. RESULTS: The research findings indicate that low-level laser light effectively activates the Wnt signaling pathway, leading to the increased accumulation of core protein ß-catenin and the upregulation of key downstream gene Lef 1. Consequently, this regulatory mechanism facilitates various downstream biological effects, including the notable promotion of HFSC proliferation and differentiation into skin appendages and epithelial tissues. As a result, the process of wound healing is significantly accelerated. CONCLUSION: Low levels of laser activates the Wnt signalling pathway, promotes the regeneration of hair follicle stem cells and accelerates wound healing.

Carbon Dioxide Fractional Laser Treatment Induces Lgr5+ Stem Cell Activation and Hair Regrowth Through the Canonical Wnt/ß-Catenin Pathway.

BACKGROUND: Different types of alopecia have negative impacts on patients. Recently, some kinds of laser or light therapies have been reported to effectively alleviate hair loss. Carbon dioxide fractional laser (CO2FL) treatment is one of the most effective laser treatments, but its beneficial effects and exact mechanism in hair regrowth have not been reported in detail. The purpose of this study was to investigate the effect and molecular mechanism further. METHODS: C57 and Lgr5-Cre: Rosa-mTmG mouse models of hair regrowth were established by CO2FL treatment, and the parameters that induced the best effect were determined. Tissues were harvested on the day prior to the treatment day and on days 3, 5, 7, 10 and 14 after CO2FL. H&E and immunofluorescence staining, RNA sequencing (RNA-seq), quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and related inhibitor were used to determine the molecular mechanism underlying the effect of CO2FL treatment on the hair cycle and hair regrowth. In clinical trial, five participants were treated three sessions at 1-month intervals to obverse the effects. RESULTS: Hair regrew and covered the treatment area on the tenth day after CO2FL treatment with the best parameters, while the control group showed signs of hair growth on the 14th day. H&E and immunofluorescence staining showed that the transition of hair follicles (HFs) from telogen to anagen was accelerated, and the rapid activation and proliferation of Lgr5+ hair follicle stem cells (HFSCs) were observed in the treatment group. The RNA-seq, qPCR and WB results indicated that the Wnt pathway was significantly activated after CO2FL treatment. Improvement achieved with CO2FL treatment in clinical trial. CONCLUSIONS: The results of this study suggest that CO2FL treatment can promote hair regrowth by activating Lgr5+ HFSCs and upregulating the Wnt/ß-catenin pathway. Clinical trial results demonstrated that CO2FL treatment will be a promising therapeutic regimen for alopecia. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice.

PURPOSE: Radiation triggers cell death events through signaling proteins, but the combined mechanism of these events is unexplored The Wnt canonical pathway, on the other hand, is essential for cell regeneration and cell fate determination. AIM: The relationship between the Wnt pathway's response to radiation and its role in radiotoxicity is overlooked, even though it is a critical molecular control of the cell. The Wnt pathway has been predicted to have radioprotective properties in some reports, but the overall mechanism is unknown. We intend to investigate how this combined cascade works throughout the radiation process and its significance over radiotoxicity. MATERIALS AND METHODS: Thirty adult mice were irradiated with electron beam radiation, and 5 served as controls. Mice were sacrificed after 24 h and 30 days of irradiation. We assessed DNA damage studies, oxidative stress parameters, mRNA profiles, protein level (liver, kidney, spleen, and germ cells), sperm viability, and motility. OBSERVATION: The mRNA profile helps to understand how the combined cascade of the Wnt pathway and NHEJ work together during radiation to combat oxidative response and cell survival. The quantitative examination of mRNA uncovers unique critical changes in all mRNA levels in all cases, particularly in germ cells. Recuperation was likewise seen in post-30 day's radiation in the liver, spleen, and kidney followed by oxidative stress parameters, however not in germ cells. It proposes that reproductive physiology is exceptionally sensitive to radiation, even at the molecular level. It also suggests the suppression of Lef1/Axin2 could be the main reason for the permanent failure of the sperm function process. Post-irradiation likewise influences the morphology of sperm. The decrease in mRNA levels of Lef1, Axin2, Survivin, Ku70, and XRCC6 levels suggests radiation inhibits the Wnt canonical pathway and failure in DNA repair mechanisms in a coupled manner. An increase in Bax, Bcl2, and caspase3 suggests apoptosis activation followed by the decreased expression of enzymatic antioxidants. CONCLUSION: Controlled several interlinked such as the Wnt canonical pathway, NHEJ pathway, and intrinsic apoptotic pathway execute when the whole body is exposed to radiation. These pathways decide the cell fate whether it will survive or will go to apoptosis which may further be used in a study to counterpart and better comprehend medication focus on radiation treatment.

Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/ß-catenin signaling.

Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. In the present study, we aimed to explore the potential function of SFRP2 in tumorigenesis and radioresistance of glioma. The RNA sequencing data of TCGA glioma samples were downloaded and analyzed. SFRP2 expression in 166 glioma patients was evaluated by qRT-PCR. The potential functions of SFRP2 in glioma were evaluated by loss-of-function assays and gain-of-function assays in glioma cell lines. We found that SFRP2 was downregulated in radiotherapy-treated glioma patients, and low SFRP2 expression was correlated with advanced tumor stage and poor prognosis. CRISP/Cas9-meidated SFRP2 knockdown promoted soft agar colony formation, cancer stemness and radioresistance of glioma cells, while enforced SFRP2 expression exhibited opposite effects. Moreover, Wnt/ß-catenin signaling was activated in radiotherapy treated glioma patients. SFRP2 knockdown activated Wnt/ß-catenin signaling in glioma cell lines, while overexpression of SFRP2 inhibited Wnt/ß-catenin activation. Besides, pharmacological inhibition of Wnt/ß-catenin signaling by XAV-939 abrogated the effects of SFRP2 knockdown on cancer stemness and radioresistance of glioma cells. Our data for the first time demonstrated a role of SFRP2 in radioresistance of glioma cells, and suggested that inhibition of Wnt/ß-catenin signaling might be a potential strategy for increasing radiosensitivity of glioma patients.

Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development.

Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn , identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931 .

Effect of magnetic graphene oxide on cellular behaviors and osteogenesis under a moderate static magnetic field.

The biological behaviors of magnetic graphene oxide (MGO) in a static magnetic field (SMF) are unknown. The current study is to investigate the cellular behaviors, osteogenesis and the mechanism in BMSCs treated with MGO combined with an SMF. Results showed that the synthetic MGO particles were bio-compatible and could significantly improve the osteogenesis of BMSCs under SMFs, as verified by elevated alkaline phosphatase activity, mineralized nodule formation, and expressions of mRNA and protein levels. Under SMF at the same intensity, the addition of graphene oxide to Fe3O4 could increase the osteogenic ability of BMSCs. The Wnt/ß-catenin pathway was indicated to be related to the MGO-driven osteogenic behavior of the BMSCs under SMF. Taken together, our findings suggested that MGO under an SMF could promote osteogenesis in BMSCs through the Wnt/ß-catenin pathway and hence should attract more attention for practical applications in bone tissue regeneration.

A Wnt-mediated phenotype switch along the epithelial-mesenchymal axis defines resistance and invasion downstream of ionising radiation in oral squamous cell carcinoma.

BACKGROUND: Dynamic transitions of tumour cells along the epithelial-mesenchymal axis are important in tumorigenesis, metastasis and therapy resistance. METHODS: In this study, we have used cell lines, 3D spheroids and tumour samples in a variety of cell biological and transcriptome analyses to highlight the cellular and molecular dynamics of OSCC response to ionising radiation. RESULTS: Our study demonstrates a prominent hybrid epithelial-mesenchymal state in oral squamous cell carcinoma cells and tumour samples. We have further identified a key role for levels of E-cadherin in stratifying the hybrid cells to compartments with varying levels of radiation response and radiation-induced epithelial-mesenchymal transition. The response to radiation further entailed the generation of a new cell population with low expression levels of E-cadherin, and positive for Vimentin (ECADLow/Neg-VIMPos), a phenotypic signature that showed an enhanced capacity for radiation resistance and invasion. At the molecular level, transcriptome analysis of spheroids in response to radiation showed an initial burst of misregulation within the first 30 min that further declined, although still highlighting key alterations in gene signatures. Among others, pathway analysis showed an over-representation for the Wnt signalling pathway that was further confirmed to be functionally involved in the generation of ECADLow/Neg-VIMPos population, acting upstream of radiation resistance and tumour cell invasion. CONCLUSION: This study highlights the functional significance and complexity of tumour cell remodelling in response to ionising radiation with links to resistance and invasive capacity. An area of less focus in conventional radiotherapy, with the potential to improve treatment outcomes and relapse-free survival.

Amelioration of bone fragility by pulsed electromagnetic fields in type 2 diabetic KK-Ay mice involving Wnt/ß-catenin signaling.

Type 2 diabetes mellitus (T2DM) results in compromised bone microstructure and quality, and subsequently increased risks of fractures. However, it still lacks safe and effective approaches resisting T2DM bone fragility. Pulsed electromagnetic fields (PEMFs) exposure has proven to be effective in accelerating fracture healing and attenuating osteopenia/osteoporosis induced by estrogen deficiency. Nevertheless, whether and how PEMFs resist T2DM-associated bone deterioration remain not fully identified. The KK-Ay mouse was used as the T2DM model. We found that PEMF stimulation with 2 h/day for 8 wk remarkably improved trabecular bone microarchitecture, decreased cortical bone porosity, and promoted trabecular and cortical bone material properties in KK-Ay mice. PEMF stimulated bone formation in KK-Ay mice, as evidenced by increased serum levels of bone formation (osteocalcin and P1NP), enhanced bone formation rate, and increased osteoblast number. PEMF significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. PEMF exerted beneficial effects on osteoblast- and osteocyte-related gene expression in the skeleton of KK-Ay mice. Nevertheless, PEMF exerted no effect on serum biomarkers of bone resorption (TRAcP5b and CTX-1), osteoclast number, or osteoclast-specific gene expression (TRAP and cathepsin K). PEMF upregulated gene expression of canonical Wnt ligands (including Wnt1, Wnt3a, and Wnt10b), but not noncanonical Wnt5a. PEMF also upregulated skeletal protein expression of downstream p-GSK-3ß and ß-catenin in KK-Ay mice. Moreover, PEMF-induced improvement in bone microstructure, mechanical strength, and bone formation in KK-Ay mice was abolished after intragastric administration with the Wnt antagonist ETC-159. Together, our results suggest that PEMF can improve bone microarchitecture and quality by enhancing the biological activities of osteoblasts and osteocytes, which are associated with the activation of the Wnt/ß-catenin signaling pathway. PEMF might become an effective countermeasure against T2DM-induced bone deterioration.NEW & NOTEWORTHY PEMF improved trabecular bone microarchitecture and suppressed cortical bone porosity in T2DM KK-Ay mice. It attenuated T2DM-induced detrimental consequence on trabecular and cortical bone material properties. PEMF resisted bone deterioration in KK-Ay mice by enhancing osteoblast-mediated bone formation. PEMF also significantly suppressed osteocytic apoptosis and sclerostin expression in KK-Ay mice. The therapeutic potential of PEMF on T2DM-induced bone deterioration was associated with the activation of Wnt/ß-catenin signaling.

Activated Beta-Catenin Signaling Ameliorates Radiation-Induced Skin Injury by Suppressing Marvel D3 Expression.

Radiation-induced skin injury remains a serious concern for cancer radiotherapy, radiation accidents and occupational exposure, and the damage mainly occurs due to apoptosis and reactive oxygen species (ROS) generation. There is currently no effective treatment for this disorder. The ß-catenin signaling pathway is involved in the repair and regeneration of injured tissues. However, the role of the ß-catenin signaling pathway in radiation-induced skin injury has not been reported. In this study, we demonstrated that the ß-catenin signaling pathway was activated in response to radiation and that its activation by Wnt3a, a ligand-protein involved in the ß-catenin signaling pathway, inhibited apoptosis and the production of ROS in irradiated human keratinocyte HaCaT cells and skin fibroblast WS1 cells. Additionally, Wnt3a promoted cell migration after irradiation. In a mouse model of full-thickness skin wounds combined with total-body irradiation, Wnt3a was shown to facilitate skin wound healing. The results from RNA-Seq revealed that 24 genes were upregulated and 154 were downregulated in Wnt3a-treated irradiated skin cells, and these dysregulated genes were mainly enriched in the tight junction pathway. Among them, Marvel D3 showed the most obvious difference. We further found that the activated ß-catenin signaling pathway stimulated the phosphorylation of JNK by silencing Marvel D3. Treatment of irradiated cells with SP600125, a JNK inhibitor, augmented ROS production and impeded cell migration. Furthermore, treatment with Wnt3a or transfection with Marvel D3-specific siRNAs could reverse the above effects. Taken together, these findings illustrate that activated ß-catenin signaling stimulates the activation of JNK by negatively regulating Marvel D3 to ameliorate radiation-induced skin injury.

Irradiation by high-intensity red light-emitting diode enhances human bone marrow mesenchymal stem cells osteogenic differentiation and mineralization through Wnt/ß-catenin signaling pathway.

Photobiomodulation therapy (PBMT) using a light-emitting diode (LED) has been employed for various photomedicine studies. The aim of this study was to determine the effects of a high-intensity red LED on the proliferation and osteogenic differentiation of human bone marrow mesenchymal stem cells (BMSCs) and the related mechanism. BMSCs were subjected to high-intensity red LED (LZ1-00R205 Deep Red LED) irradiations for 0 to 40 s with energy densities ranging from 0 to 8 J/cm2. The distance from the LED to the cell layer was 40 mm. The spot size on the target was 4 cm2. Cell proliferation was measured at 3, 24, 48, and 72 h. The effects of LED irradiation on osteogenic differentiation and mineralization were examined with a particular focus on the Wnt/ß-catenin signaling pathway. The high-intensity red LED irradiations did not alter BMSC proliferation after 72 h. LED exposure of 6 J/cm2 (30 s) led to significant enhancements of osteogenic differentiation and mineralization. Additionally, the high-intensity LED irradiation induced activation of Wnt/ß-catenin. The effects of the high-intensity LED irradiation on BMSC osteogenic differentiation and mineralization were suppressed by treatment with the Wnt/ß-catenin inhibitor XAV939. P < 0.05 was considered significant. The results indicate that high-intensity red LED irradiation increases BMSC osteogenic differentiation and mineralization via Wnt/ß-catenin activation. Therefore, short duration irradiation with a portable high-intensity LED may be used as a potential approach in hard tissue regeneration therapy.

Ghrelin reverts intestinal stem cell loss associated with radiation-induced enteropathy by activating Notch signaling.

BACKGROUD: Exposure to high-dose radiation, such as after a nuclear accident or radiotherapy, elicits severe intestinal damage and is associated with a high mortality rate. In treating patients exhibiting radiation-induced intestinal dysfunction, countermeasures to radiation are required. In principle, the cellular event underlying radiation-induced gastrointestinal syndrome is intestinal stem cell (ISC) apoptosis in the crypts. High-dose irradiation induces the loss of ISCs and impairs intestinal barrier function, including epithelial regeneration and integrity. Notch signaling plays a critical role in the maintenance of the intestinal epithelium and regulates ISC self-renewal. Ghrelin, a hormone produced mainly by enteroendocrine cells in the gastrointestinal tract, has diverse physiological and biological functions. PURPOSE: We investigate whether ghrelin mitigates radiation-induced enteropathy, focusing on its role in maintaining epithelial function. METHODS: To investigate the effect of ghrelin in radiation-induced epithelial damage, we analyzed proliferation and Notch signaling in human intestinal epithelial cell. And we performed histological analysis, inflammatory response, barrier functional assays, and expression of notch related gene and epithelial stem cell using a mouse model of radiation-induced enteritis. RESULTS: In this study, we found that ghrelin treatment accelerated the reversal of radiation-induced epithelial damage including barrier dysfunction and defective self-renewing property of ISCs by activating Notch signaling. Exogenous injection of ghrelin also attenuated the severity of radiation-induced intestinal injury in a mouse model. CONCLUSION: These data suggest that ghrelin may be used as a potential therapeutic agent for radiation-induced enteropathy.

Inhibition of Wnt signaling pathway suppresses radiation-induced dermal fibrosis.

Progressive fibrosis of the dermal tissues is a challenging complication of radiotherapy whose underlying mechanism is not fully understood, and there are few available treatments. The canonical Wnt/ß-catenin signaling pathway plays an important role in fibrosis as well as in the epithelial-to-mesenchymal transition (EMT). We investigated whether inhibition of Wnt/ß-catenin signaling with sLRP6E1E2, a molecule that binds to extracellular Wnt ligands, ameliorated radiation-induced fibrosis both in vitro and in vivo. Radiation with a single dose of 2 Gy not only facilitated fibrosis in cultured human dermal fibroblasts via activation of the Wnt/ß-catenin pathway but also initiated EMT in cultured keratinocytes, developing collagen-producing mesenchymal cells. sLRP6E1E2-expressing adenovirus treatment exerted anti-fibrotic activity in irradiated cultured dermal fibroblasts and keratinocytes. In a mouse model, a single fraction of 15 Gy was delivered to the dorsal skins of 36 mice randomized into three groups: those receiving PBS, those receiving control adenovirus, and those receiving decoy Wnt receptor-expressing adenovirus (dE1-k35/sLRP6E1E2). The mice were observed for 16 weeks, and excessive deposition of type I collagen was suppressed by sLRP6E1E2-expressing adenovirus treatment. These results demonstrate that the modulation of the Wnt/ß-catenin pathway has the potential to decrease the severity of radiation-induced dermal fibrosis.

Arachidonic Acid Promotes Intestinal Regeneration by Activating WNT Signaling.

Intestinal regeneration is crucial for functional restoration after injury, and nutritional molecules can play an important role in this process. Here, we found that arachidonic acid (AA) serves as a direct proliferation promoter of intestinal epithelial cells that facilitates small intestinal regeneration in both three-dimensional cultured organoids and mouse models. As shown in the study, during post-irradiation regeneration, AA positively regulates intestinal epithelial cell proliferation by upregulating the expression of Ascl2 and activating WNT signaling, but negatively regulates intestinal epithelial cell differentiation. AA acts as a delicate regulator that efficiently facilitates epithelial tissue repair by activating radiation-resistant Msi1+ cells rather than Lgr5+ cells, which are extensively considered WNT-activated crypt base stem cells. Additionally, short-term AA treatment maintains optimal intestinal epithelial homeostasis under physiological conditions. As a result, AA treatment can be considered a potential therapy for irradiation injury repair and tissue regeneration.

Impacts of epidural electrical stimulation on Wnt signaling, FAAH, and BDNF following thoracic spinal cord injury in rat.

Electrical stimulation (ES) has been shown to improve some of impairments after spinal cord injury (SCI), but the underlying mechanisms remain unclear. The Wnt signaling pathways and the endocannabinoid system appear to be modulated in response to SCI. This study aimed to investigate the effect of ES therapy on the activity of canonical/noncanonical Wnt signaling pathways, brain-derived neurotrophic factor (BDNF), and fatty-acid amide hydrolase (FAAH), which regulate endocannabinoids levels. Forty male Wistar rats were randomly divided into four groups: (a) Sham, (b) laminectomy + epidural subthreshold ES, (c) SCI, and (d) SCI + epidural subthreshold ES. A moderate contusion SCI was performed at the thoracic level (T10). Epidural subthreshold ES was delivered to upper the level of T10 segment every day (1 hr/rat) for 2 weeks. Then, animals were killed and immunoblotting was used to assess spinal cord parameters. Results revealed that ES intervention for 14 days could significantly increase wingless-type3 (Wnt3), Wnt7, ß-catenin, Nestin, and cyclin D1 levels, as well as phosphorylation of glycogen synthase kinase 3ß and Jun N-terminal kinase. Additionally, SCI reduced BDNF and FAAH levels, and ES increased BDNF and FAAH levels in the injury site. We propose that ES therapy may improve some of impairments after SCI through Wnt signaling pathways. Outcomes also suggest that BDNF and FAAH are important players in the beneficial impacts of ES therapy. However, the precise mechanism of BDNF, FAAH, and Wnt signaling pathways on SCI requires further investigation.

The effects of the Wnt/ß­catenin signaling pathway on apoptosis in HeLa cells induced by carbon ion irradiation.

The molecular mechanisms underlying the biological effects of carbon ions are unclear. The aim of this study was to explore the Wnt/ß­catenin pathway in regulating carbon ion (12C6+) radiation­induced cellular toxicity. HLY78 is a Wnt­specific small molecular modulator, whose effects on 12C6+ radiation­induced damage are mostly unknown. HLY78, in combination with 12C6+ radiation was investigated on HeLa cell viability, cell cycle progression, DNA damage, and the expression of apoptotic and Wnt­related proteins. 12C6+ radiation suppressed cell viability in a time­dependent manner, whereas the addition of HLY78 to cells significantly reduced this stress. Moreover, after irradiation with 12C6+, HeLa cells exhibited increased cell apoptosis, G2/M phase arrest, and a number of γ­H2AX foci. However, Wnt signaling activation alleviated these effects. Furthermore, when compared with the radiation alone group, supplementation with HLY78 markedly increased the expression of anti­apoptotic and Wnt­related proteins, and significantly decreased the expression of apoptotic proteins. The present results indicated that activation of the Wnt/ß­catenin signaling pathway by HLY78 reduced 12C6+ radiation­induced HeLa cell dysfunction, suggesting that the Wnt/ß­catenin signaling pathway plays an important role in regulating 12C6+ radiation­induced cellular toxicity in HeLa cells.

Acute exposure of 532 nm laser differentially regulates skin tissue transcription factors.

High energy laser, particularly 532 nm, is widely used in defense and medical applications and there is need to address its occupational safety. Thermal and non-thermal effects of 532 nm high energy laser on skin are cause of concern. This study indicates impact of 532 nm laser on rat skin and first of its kind of attempt to understand transcriptional activation of genes as an early response following laser exposure. Skin of experimental rats were exposed to 532 nm radiance at 0.1, 0.25 and 0.50 W/cm2 for 10 sec. Thermographic changes of skin exposed to 532 nm laser exhibited increased Tmax temperature in radiance dependent manner. After thermal imaging, skin of experimental rats was collected 1 h post laser exposure for studying differential gene expression. The skin exposed to lower power density (0.1 W/cm2) did not show significant changes in expression of gene pathways studied. At moderate radiance (0.25 W/cm2), predominantly canonical wnt/B-catenin pathway genes notch1, axin2, ccdn1, wnt5a and redox homeostasis genes; txn1, nqo1 and txnrd1 were expressed. At higher radiance (0.5 W/cm2), significant repression of genes related to wound healing process particularly notch/wnt pathway viz. hes5, wnt1, wn3b with higher expression of dab2 was recorded. The data obtained from these studies would help in drawing safety limits for skin exposure to 532 nm laser. Further, genes expressed at moderate and high level of radiance exposure to skin were distinct and differential and provide new avenue to configure pathway to counteract laser induced delay in tissue injury and hair follicular damage.

Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells.

Cervical cancer is the second most common malignant tumour threatening women's health. In recent years, heavy-ion beam therapy is becoming a newly emerging therapeutic mean of cancer; however, radio-resistance and radiation-induced damage constitute the main obstacles for curative treatment of cervical cancer. Therefore, to identify the radiosensitizers is essential. Here, we investigated the effects of Wnt signalling pathway on the response of 12C6+ radiation in HeLa cells. XAV939, an inhibitor of Wnt signalling pathway, was added two hours before 12C6+ radiation.12C6+ radiation inhibited the viability of HeLa cells in a time-dependent manner, and inhibiting Wnt signalling using XAV939 significantly intensified this stress. Meanwhile, 12C6+ radiation induced a significant increased cell apoptosis, G2/M phase arrest, and the number of γ-H2AX foci. Supplementation with XAV939 significantly increased the effects induced by 12C6+ radiation alone. Combining XAV939 with 12C6+ irradiation, the expression of apoptotic genes (p53, Bax, Bcl-2) was significantly increased, while the expression of Wnt-related genes (Wnt3a, Wnt5a, ß-catenin, cyclin D1 and c-Myc) was significantly decreased. Overall, these findings suggested that blockage of the Wnt/ß-catenin pathway effectively sensitizes HeLa cells to 12C6+ irradiation, and it may be a potential therapeutic approach in terms of increasing the clinical efficacy of 12C6+ beams.

Extremely Low-Frequency Electromagnetic Fields Increase the Expression of Anagen-Related Molecules in Human Dermal Papilla Cells via GSK-3ß/ERK/Akt Signaling Pathway.

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, thereby creating a need for new treatments to control hair loss and prevent balding. Human hair follicle dermal papilla cells (hDPCs), a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions like androgenic alopecia. This study aimed to evaluate the intensity-dependent effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on the expression of anagen-related molecules in hDPCs in vitro. We examined the effect of ELF-EMF on hDPCs to determine whether activation of the GSK-3ß/ERK/Akt signaling pathway improved hDPC activation and proliferation; hDPCs were exposed to ELF-EMFs at a frequency of 70 Hz and at intensities ranging from 5 to 100 G, over four days. Various PEMF intensities significantly increased the expression of anagen-related molecules, including collagen IV, laminin, ALP, and versican. In particular, an intensity of 10 G is most potent for promoting the proliferation of hDPC and expression of anagen-related molecules. Moreover, 10 G ELF-EMF significantly increased ß-catenin and Wnt3α expression and GSK-3ß/ERK/Akt phosphorylation. Our results confirmed that ELF-EMFs enhance hDPC activation and proliferation via the GSK-3ß/ERK/Akt signaling pathway, suggesting a potential treatment strategy for alopecia.

Fractionated head and neck irradiation impacts taste progenitors, differentiated taste cells, and Wnt/ß-catenin signaling in adult mice.

Head and neck cancer patients receiving conventional repeated, low dose radiotherapy (fractionated IR) suffer from taste dysfunction that can persist for months and often years after treatment. To understand the mechanisms underlying functional taste loss, we established a fractionated IR mouse model to characterize how taste buds are affected. Following fractionated IR, we found as in our previous study using single dose IR, taste progenitor proliferation was reduced and progenitor cell number declined, leading to interruption in the supply of new taste receptor cells to taste buds. However, in contrast to a single dose of IR, we did not encounter increased progenitor cell death in response to fractionated IR. Instead, fractionated IR induced death of cells within taste buds. Overall, taste buds were smaller and fewer following fractionated IR, and contained fewer differentiated cells. In response to fractionated IR, expression of Wnt pathway genes, Ctnnb1, Tcf7, Lef1 and Lgr5 were reduced concomitantly with reduced progenitor proliferation. However, recovery of Wnt signaling post-IR lagged behind proliferative recovery. Overall, our data suggest carefully timed, local activation of Wnt/ß-catenin signaling may mitigate radiation injury and/or speed recovery of taste cell renewal following fractionated IR.