Human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium.

PURPOSE: To investigate human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium (CM). METHODS: A human corneal epithelial cell line (HCE-T), human corneal fibroblasts (HCF) and keratoconus fibroblasts (KC-HCF) have been used. Twenty-four hours after RB-PDT (0.001% RB concentration, 565 nm wavelength illumination, 0.17 J/cm2 fluence) cell migration rate using scratch assay and growth factor concentrations in the cell culture supernatant using ELISA have been determined. In addition, the effect of CM has been observed. RESULTS: RB-PDT significantly reduced migration rate in all cell types, compared to controls (p≤0.02). Migration rate of HCE-T cultures without RB-PDT (untreated) was significantly higher using HCF CM after RB-PDT, than using HCF CM without RB-PDT (p<0.01). Similarly, untreated HCF displayed a significantly increased migration rate with HCE-T CM after RB-PDT, compared to HCE-T CM without treatment (p<0.01). Furthermore, illumination alone and RB-PDT significantly decreased keratinocyte growth factor (KGF) concentration in HCF and KC-HCF supernatant, and RB-PDT significantly decreased soluble N-Cadherin (SN-Cad) concentration in HCF supernatant, compared to controls (p<0.01 for all). In HCE-T CM, RB-PDT increased hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGFb) concentration (p≤0.02), while decreasing transforming growth factor ß (TGF-ß) concentration (p<0.01). FGFb concentration increased (p<0.0001) and TGF-ß concentration decreased (p<0.0001) in HCF CM, by RB-PDT. Epidermal growth factor (EGF), HGF, and TGF-ß concentration decreased (p≤0.03) and FGFb concentration increased (p<0.01) in KC-HCF CM, using RB-PDT. CONCLUSIONS: HCE-T, HCF and KC-HCF migration rate is reduced 24 hours after RB-PDT. In contrast, HCE-T migration is enhanced using HCF CM after RB-PDT, and HCF migration rate is increased through HCE-T CM following RB-PDT. Modulation of EGF, KGF, HGF, FGFb, TGF-ß and N-Cadherin secretion through RB-PDT may play an important role in corneal wound healing.

Short communication: Clinical evaluation of pea sprout extract in the treatment of hair loss.

Hair loss affects millions of people worldwide, but currently available treatment options are often dissatisfying due to side effects or limited efficacy. Pea sprout extract has been shown to improve hair density when applied topically, but its mode of action and effectiveness upon oral administration remain unknown. Our study has now shown that the application of a fluid containing 2% pea sprout extract on a defined scalp zone of 10 volunteers enhances the expression of defined genes relevant for hair, namely fibroblast growth factor-7 (FGF7) and noggin, by 56 and 85%, respectively. Additionally, a subsequent pilot nutrition intervention study in 21 volunteers proved that pea sprout extract is also effective when consumed as dietary supplement. The daily intake of 100 mg pea sprout extract (AnaGain™ Nu) for 8 weeks significantly reduced hair loss already after 28 days of treatment (p < 0.002). No adverse events were reported. Consequently, pea sprout extract may be an effective means to safely promote hair growth and reduce hair loss in individuals experiencing excessive hair shedding.

Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines.

PURPOSE: The aim of this study was to update the clinical practice guidelines for the use of agents for the prevention and/or treatment of gastrointestinal mucositis (GIM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers across 13 interventions were examined of which 25 were included in the final review. No new guidelines were possible for any agent due to inadequate and/or conflicting evidence. Existing guidelines for probiotics and hyperbaric oxygen were unchanged. CONCLUSIONS: Of the agents studied for the prevention and treatment of GIM, the evidence continues to support use of probiotics containing Lactobacillus spp. for prevention of chemoradiotherapy and radiotherapy-induced diarrhea in patients with pelvic malignancy, and hyperbaric oxygen therapy to treat radiation-induced proctitis. Additional well-designed research is encouraged to enable a decision regarding palifermin, glutamine, sodium butyrate, and dietary interventions, for the prevention or treatment of GIM.

Eclipta prostrata promotes the induction of anagen, sustains the anagen phase through regulation of FGF-7 and FGF-5.

CONTEXT: Eclipta prostrata L. (Asteraceae) (EP) has been widely used for the treatment of skin disease in Asian traditional medicine. OBJECTIVE: This study investigates the potency of EP in promoting hair growth in vivo and in vitro. MATERIALS AND METHODS: C57BL/6N mice were divided into four groups (n = 4) as follows: control (topical treatment of normal saline), topical 3% minoxidil to the dorsal skin of mice for 14 days, and low (1 mg/day) and high (10 mg/day) doses of EP orally administered once a day for 14 days. Dorsal hairs of C57BL/6N mice were depilated to synchronize anagen induction. Hair growth activity was evaluated by gross and microscopic observations. Sections of dorsal skin were stained with haematoxylin and eosin. We also treated the various concentrations of EP (5, 10 and 50 µg/mL) for 24 h on the human dermal papilla cells (HDPs) and examined the effects of EP on the expression of FGF-7 and mTOR signalling. RESULTS: EP enhanced the induction of anagen in the dorsal skin of mice, characterized by the appearance of inner root sheath along with hair shaft, the emergence of hair shaft through the epidermis. EP increased the expression of FGF-7, while decreased the level of FGF-5 in C57/BL6 mice. EP also increased the expression of FGF-7, activated the mTOR signalling in HDPs. DISCUSSION AND CONCLUSIONS: These results suggest that EP has a potency to enhance the growth of hair follicle, promoting hair growth through regulation of FGF-7 and FGF-5.

Alveolus-like organoid from isolated tip epithelium of embryonic mouse lung.

Embryonic lungs were obtained from embryonic day 13.5 ICR mice. The lung-tip epithelium isolated using dispase treatment was embedded in low-growth factor Matrigel, cultured in DMEM/F12 medium containing 0.1% bovine serum albumin, supplemented with insulin, transferrin, and selenium (ITS), with or without fibroblast growth factor 7 (FGF7), and were observed for 14 days. With the addition of FGF7, the tip epithelium grew to form a cyst by culture day 7. Then, tubular tufts-like alveolus appeared around the cyst surface. Reverse transcription-polymerase chain reaction revealed that, with the addition of FGF7, the cultured lung explants expressed alveolar-type 1 cell markers, such as HopX and Aquaporin5, and type 2 cell markers, such as Lamp3 and Surfactant apoproteins (Sftp) C and D. Paraffin-embedded sections were stained with hematoxylin and eosin, and alveolar structures at culture day 14 were composed of squamous and cuboidal epithelial cells. Immunohistochemical studies showed that the squamous epithelial cells were positive for HopX, and the cuboidal epithelial cells were positive for pro-SftpC. Furthermore, transmission electron microscopic observation confirmed that the squamous epithelial cells were alveolar-type 1 cells and the cuboidal cells were type 2 cells, because they had many lamellar inclusion bodies. Embryonic lung-tip epithelium forms an alveolus-like organoid through the self organization with the aid of Matrigel, ITS, and FGF7. This method to make alveolus-like organoid in vitro is easy, reproducible, and economical. This method could have potential to solve many issues in alveolar epithelial cells in normal and pathological conditions.

Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model.

Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.

Effects of all-trans retinoic acid on goat dermal papilla cells cultured in vitro

Background: All-trans retinoic acid (ATRA), a vitamin A-derived active metabolite, exerts important functions in hair biology. Previous studies indicated that excess ATRA hampered hair follicle morphogenesis and cyclic regeneration in adulthood, but other studies stated that ATRA promoted hair growth. Dermal papilla (DP), a cluster of specialized fibroblasts, plays pivotal roles in controlling development and regeneration of hair follicle. Several lines of evidence indicated that DP might be the target cells of ATRA in the hair follicle. To confirm this hypothesis, the present study was performed to explore the biological effects of ATRA on goat dermal papilla cells (DPCs) and clarify the roles of ATRA in hair biology. Results: Our experimental results indicated that key signaling transducers of ATRA were dynamically expressed in distinct stages of goat cashmere growth cycle, and high-dose ATRA treatment (10-5 M) significantly impaired the viability of goat DPCs and lowered the ratio of proliferating cells. Otherwise, goat DPCs were stimulated to enter apoptosis and their cell cycle progression was severely blocked by ATRA. Moreover, the expression of fibroblast growth factor 7 (Fgf7), one of the potent hair growth stimulators secreted by DPCs, was transcriptionally repressed following ATRA treatment. Conclusion: DPCs are the targets of ATRA in the hair follicle, and ATRA negatively regulates hair growth by the targeted suppression of cell viability and growth factor expression of goat DPCs. Through these observations, we offer a new mechanistic insight into the roles of ATRA in hair biology.

Pharmacological modulation of radiation-induced oral mucosal complications.

Radiation-induced mucositis is a common toxicity, especially in patients with head and neck cancers. Despite recent technological advances in radiation therapy, such as intensity-modulated radiotherapy, radiation-induced mucositis is still causing treatment disruptions, negatively affecting patients' long and short term quality of life, and impacting medical resources use with economic consequences. The objective of this article was to review the latest updates in the management of radiation-induced mucositis, with a focus on pharmaceutical strategies for the prevention or treatment of mucositis. Although numerous studies analysing the prevention and management of oral radiation-induced mucositis have been conducted, there are still few reliable data to guide daily clinical practice. Furthermore, most of the tested drugs have shown no (anti-inflammatory cytokine, growth factors) or limited (palifermin) effect. Therapies for acute oral mucositis are predominantly focused on improving oral hygiene and providing symptoms control. Although low-level laser therapy proved efficient in preventing radiation-induced oral mucositis in patients with head and neck cancer, this intervention requires equipment and trained medical staff, and is therefore insufficiently developed in clinical routine. New effective pharmacological agents able to prevent or reverse radio-induced mucositis are required.

Hair growth is promoted by BeauTop via expression of EGF and FGF­7.

Minoxidil and finasteride have been approved to treat hair loss by the Food and Drug Administration. However, the further elucidation of treatments for hair loss, including those using Chinese herbal medicine, remains important clinically. BeauTop (BT) is a health food supplement which contains Ginseng radix, Astragali radix, Radix Angelicae sinensis, Ligustri fructus, Rehmannia glutinosa and Eclipta prostrata (Linn). Susbsequent to oral administration of BT at 0.6 g/kg/day to wax/rosin­induced alopecia in C57BL/6 mice, BT significantly induced hair growth at day 8 compared with control treatment (P<0.05). The expression levels of epidermal growth factor (EGF), and fibroblast growth factor (FGF)­7 were increased compared with control animals on day 8. In contrast, levels of FGF­5 of the BT group were reduced compared with the control on day 12. There were no effects on the expression of insulin­like growth factor 1. The results demonstrated that the mechanism of BT improving alopecia is potentially associated with modulation of EGF and FGF­7 levels. Taken together, it is suggested that BT may have a potential effect of the promotion of hair growth.

LLLT Effects on Oral Keratinocytes in an Organotypic 3D Model.

Several in vitro studies evaluated the cellular and molecular events related to interactions between phototherapy and target tissues, including oral keratinocytes and fibroblasts, providing elucidative data about phototherapy-induced healing. However, these interactions were limited to the application of a bidimensional cell culture model of oral mucosal cells. Thus, thisstudy evaluated the use of an organotypic oral epithelium model to elucidate the morphological and phenotypic responses of cells subjected to low-level laser therapy (LLLT). Oral keratinocytes were seeded in the ex vivo-produced oral mucosal equivalent (EVPOME) model, with a porcine acellular dermal matrix. LLLT was applied by means of the LaserTABLE device (780 nm, 25 mW) at 0.5, 1.5 and 3 J cm-2 . After three irradiations, morphology, proliferation and gene expression of growth factors were assessed. LLLT and control groups presented similar morphological features, characterized by the formation of a stratified, differentiated and keratinized epithelium. LLLT enhanced the cell proliferation and gene expression of keratinocytes (hKGF) as well as epidermal (hEGF) growth factors. In general, analysis of these data shows that the three-dimensional cell culture model can be applied for phototherapy studies and that the positive effects of LLLT were confirmed by the use of an organotypic model.

6-Gingerol inhibits hair cycle via induction of MMP2 and MMP9 expression.

6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-ß participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-ß concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.

6-Gingerol inhibits hair cycle via induction of MMP2 and MMP9 expression

ABSTRACT 6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-β participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-β concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.

Advances in the understanding and management of mucositis during stem cell transplantation.

PURPOSE OF REVIEW: Mucositis is a severe and common side effect of anticancer treatments, with an incidence of between 40 and 80% depending on the cytotoxic regimen used. The most profound mucositis burden is experienced during conditioning regimens for hematopoietic stem cell transplant (HSCT), where the use of highly mucotoxic agents with or without total body irradiation leads to serious damage throughout the alimentary tract. Currently, the assessment and management of both oral and gastrointestinal mucositis lack authoritative guideline, with recommendations only achieved in narrow clinical scenarios. This review provides a brief overview of current management guidelines for mucositis in both adult and pediatric patients receiving HSCT, highlights recent advances in mucositis prevention and discusses future research avenues. RECENT FINDINGS: The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines for the prevention of mucositis in HSCT are scarce, with low level laser therapy (photobiomodulation) and palifermin only recommended for oral mucositis. Loperamide and octreotide remain gold-standard for the treatment of diarrhea, despite poor efficacy. Although several interventions have been trialled in pediatric cohorts, no recommendations currently exist for children receiving high-dose chemotherapy or total body irradiation for HSCT. SUMMARY: HSCT continues to be associated with mucositis, which impacts on patients' ability and willingness to receive engraftment, and worsens clinical outcome. Research into the prevention and treatment of mucositis in this setting remains limited, with an overwhelming amount of small, single-center studies that fail to achieve a sufficient level of evidence that warrant recommendation(s). As such, our ability to manage mucotoxic side effects of high-dose chemotherapy and irradiation is limited, particularly in children.

Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy.

BACKGROUND: Salivary gland dysfunction is an 'umbrella' term for the presence of either xerostomia (subjective sensation of dryness), or salivary gland hypofunction (reduction in saliva production). It is a predictable side effect of radiotherapy to the head and neck region, and is associated with a significant impairment of quality of life. A wide range of pharmacological interventions, with varying mechanisms of action, have been used for the prevention of radiation-induced salivary gland dysfunction. OBJECTIVES: To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 14 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8) in the Cochrane Library (searched 14 September 2016); MEDLINE Ovid (1946 to 14 September 2016); Embase Ovid (1980 to 14 September 2016); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 14 September 2016); LILACS BIREME Virtual Health Library (Latin American and Caribbean Health Science Information database; 1982 to 14 September 2016); Zetoc Conference Proceedings (1993 to 14 September 2016); and OpenGrey (1997 to 14 September 2016). We searched the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials, irrespective of their language of publication or publication status. Trials included participants of all ages, ethnic origin and gender, scheduled to receive radiotherapy on its own or in addition to chemotherapy to the head and neck region. Participants could be outpatients or inpatients. We included trials comparing any pharmacological agent regimen, prescribed prophylactically for salivary gland dysfunction prior to or during radiotherapy, with placebo, no intervention or an alternative pharmacological intervention. Comparisons of radiation techniques were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 39 studies that randomised 3520 participants; the number of participants analysed varied by outcome and time point. The studies were ordered into 14 separate comparisons with meta-analysis only being possible in three of those.We found low-quality evidence to show that amifostine, when compared to a placebo or no treatment control, might reduce the risk of moderate to severe xerostomia (grade 2 or higher on a 0 to 4 scale) at the end of radiotherapy (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.19 to 0.67; P = 0.001, 3 studies, 119 participants), and up to three months after radiotherapy (RR 0.66, 95% CI 0.48 to 0.92; P = 0.01, 5 studies, 687 participants), but there is insufficient evidence that the effect is sustained up to 12 months after radiotherapy (RR 0.70, 95% CI 0.40 to 1.23; P = 0.21, 7 studies, 682 participants). We found very low-quality evidence that amifostine increased unstimulated salivary flow rate up to 12 months after radiotherapy, both in terms of mg of saliva per 5 minutes (mean difference (MD) 0.32, 95% CI 0.09 to 0.55; P = 0.006, 1 study, 27 participants), and incidence of producing greater than 0.1 g of saliva over 5 minutes (RR 1.45, 95% CI 1.13 to 1.86; P = 0.004, 1 study, 175 participants). However, there was insufficient evidence to show a difference when looking at stimulated salivary flow rates. There was insufficient (very low-quality) evidence to show that amifostine compromised the effects of cancer treatment when looking at survival measures. There was some very low-quality evidence of a small benefit for amifostine in terms of quality of life (10-point scale) at 12 months after radiotherapy (MD 0.70, 95% CI 0.20 to 1.20; P = 0.006, 1 study, 180 participants), but insufficient evidence at the end of and up to three months postradiotherapy. A further study showed no evidence of a difference at 6, 12, 18 and 24 months postradiotherapy. There was low-quality evidence that amifostine is associated with increases in: vomiting (RR 4.90, 95% CI 2.87 to 8.38; P < 0.00001, 5 studies, 601 participants); hypotension (RR 9.20, 95% CI 2.84 to 29.83; P = 0.0002, 3 studies, 376 participants); nausea (RR 2.60, 95% CI 1.81 to 3.74; P < 0.00001, 4 studies, 556 participants); and allergic response (RR 7.51, 95% CI 1.40 to 40.39; P = 0.02, 3 studies, 524 participants).We found insufficient evidence (that was of very low quality) to determine whether or not pilocarpine performed better or worse than a placebo or no treatment control for the outcomes: xerostomia, salivary flow rate, survival, and quality of life. There was some low-quality evidence that pilocarpine was associated with an increase in sweating (RR 2.98, 95% CI 1.43 to 6.22; P = 0.004, 5 studies, 389 participants).We found insufficient evidence to determine whether or not palifermin performed better or worse than placebo for: xerostomia (low quality); survival (moderate quality); and any adverse effects.There was also insufficient evidence to determine the effects of the following interventions: biperiden plus pilocarpine, Chinese medicines, bethanechol, artificial saliva, selenium, antiseptic mouthrinse, antimicrobial lozenge, polaprezinc, azulene rinse, and Venalot Depot (coumarin plus troxerutin). AUTHORS' CONCLUSIONS: There is some low-quality evidence to suggest that amifostine prevents the feeling of dry mouth in people receiving radiotherapy to the head and neck (with or without chemotherapy) in the short- (end of radiotherapy) to medium-term (three months postradiotherapy). However, it is less clear whether or not this effect is sustained to 12 months postradiotherapy. The benefits of amifostine should be weighed against its high cost and side effects. There was insufficient evidence to show that any other intervention is beneficial.

Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation.

PURPOSE: To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT). METHODS: The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence of severe oral mucositis. The Grades of Recommendation, Assessment, Development and Evaluation approach was used to describe quality of evidence and strength of recommendations. RESULTS: We suggest cryotherapy or LLLT may be offered to cooperative children receiving chemotherapy or HSCT conditioning with regimens associated with a high rate of mucositis. We also suggest KGF may be offered to children receiving HSCT conditioning with regimens associated with a high rate of severe mucositis. However, KGF use merits caution as there is a lack of efficacy and toxicity data in children, and a lack of long-term follow-up data in paediatric cancers. No other interventions were recommended for oral mucositis prevention in children. CONCLUSIONS: All three specific interventions evaluated in this clinical practice guideline were associated with a weak recommendation for use. There may be important organisational and cost barriers to the adoption of LLLT and KGF. Considerations for implementation and key research gaps are highlighted.

Formation of keratinocyte multilayers on filters under airlifted or submerged culture conditions in medium containing calcium, ascorbic acid, and keratinocyte growth factor.

Three-dimensional (3D) cell culture is a powerful in vitro technique to study the stratification and differentiation of keratinocytes. However, culture conditions, including culture media, supplements, and scaffolds (e.g., collagen gels with or without fibroblasts), can vary considerably. Here, we evaluated the roles of calcium, L-ascorbic acid phosphate magnesium salt n-hydrate (APM), and keratinocyte growth factor (KGF) in a chemically defined medium, EpiLife, in 3D cultures of primary human epidermal keratinocytes directly plated on polycarbonate filter inserts under airlifted or submerged conditions. Eight culture media containing various combinations of these three supplements were examined. Calcium was necessary for the stratification and differentiation of keratinocytes based on the localization of keratins and involucrin. However, the localization patterns of keratins and integrin ß4 were partially disrupted and Ki67-positive basal cells almost disappeared 3 weeks after airlift. The addition of KGF, but not APM, prevented these changes. Further addition of APM markedly improved the tissue architecture, including basal cell morphology and the appearance of keratohyalin granules and localized involucrin in the upper suprabasal cells, even after 1 week. Although the submerged culture also formed cornified epithelium-like multilayers, involucrin was localized in the cornified layer, where nuclei were often found. Based on these results, it is most effective to culture keratinocytes at the air-liquid interface in EpiLife medium supplemented with calcium, APM, and KGF to form well-organized and orthokeratinized multilayers as skin analogues.

Hominis Placenta facilitates hair re-growth by upregulating cellular proliferation and expression of fibroblast growth factor-7.

BACKGROUND: Hominis Placenta (HP) known as a restorative medicine in Traditional Chinese Medicine (TCM), has been widely applied in the clinics of Korea and China as an anti-aging agent to enhance the regeneration of tissue. This study was conducted to investigate whether topical treatment of HP promotes hair regrowth in the animal model. METHODS: The dorsal hairs of 8-week-old C57BL/6 mice were depilated to synchronize hair follicles to the anagen phase. HP was applied topically once a day for 15 days. Hair growth was evaluated visually and microscopically. The incorporation of bromodeoxyuridine (BrdU) and expression of proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7) in dorsal skin tissue was examined by immunohistochemical analysis. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of FGF-7. RESULTS: HP exhibited potent hair growth-promoting activity in C57BL/6 mice. Gross examination indicated that HP markedly increased hair regrowth as well as hair density and diameter. Histologic analysis showed that HP treatment enhanced the anagen induction of hair follicles. Immunohistochemical analysis revealed that BrdU incorporation and the expressions of PCNA were increased by treatment of HP. HP treatment significantly increased the expression of FGF-7, which plays pivotal roles to maintain anagen phase both protein and mRNA levels. CONCLUSIONS: Taken together, our results indicate that HP has a potent hair growth-promoting activity; therefore, it may be a good candidate for the treatment of alopecia.

Thymus: the next (re)generation.

As the primary site of T-cell development, the thymus plays a key role in the generation of a strong yet self-tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. As the importance of the role of the thymus has grown, so too has the understanding that it is extremely sensitive to both acute and chronic injury. The thymus undergoes rapid degeneration following a range of toxic insults, and also involutes as part of the aging process, albeit at a faster rate than many other tissues. The thymus is, however, capable of regenerating, restoring its function to a degree. Potential mechanisms for this endogenous thymic regeneration include keratinocyte growth factor (KGF) signaling, and a more recently described pathway in which innate lymphoid cells produce interleukin-22 (IL-22) in response to loss of double positive thymocytes and upregulation of IL-23 by dendritic cells. Endogenous repair is unable to fully restore the thymus, particularly in the aged population, and this paves the way toward the need for exogenous strategies to help regenerate or even replace thymic function. Therapies currently in clinical trials include KGF, use of the cytokines IL-7 and IL-22, and hormonal modulation including growth hormone administration and sex steroid inhibition. Further novel strategies are emerging in the preclinical setting, including the use of precursor T cells and thymus bioengineering. The use of such strategies offers hope that for many patients, the next regeneration of their thymus is a step closer.

Bee Venom Promotes Hair Growth in Association with Inhibiting 5α-Reductase Expression.

Alopecia is an important issue that can occur in people of all ages. Recent studies show that bee venom can be used to treat certain diseases including rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we investigated the preventive effect of bee venom on alopecia, which was measured by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors responsible for hair growth were analyzed by quantitative real-time PCR and Western blot analysis using mice skins and human dermal papilla cells (hDPCs). Bee venom promoted hair growth and inhibited transition from the anagen to catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase mice, hair growth was increased dose dependently compared with controls. Bee venom inhibited the expression of SRD5A2, which encodes a type II 5α-reductase that plays a major role in the conversion of testosterone into dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee venom-treated hDPCs dose dependently compared with the control group. In conclusion, bee venom is a potentially potent 5α-reductase inhibitor and hair growth promoter.

Phosphatidylcholine kinetics in neonatal rat lungs and the effects of rhuKGF and betamethasone.

Surfactant, synthesized by type II pneumocytes (PN-II), mainly comprises phosphatidylcholine (PC) and is essential to prevent neonatal respiratory distress. Furthermore, PC is essential to lung tissue growth and maintenance as a membrane component. Recent findings suggest that the lung contributes to systemic lipid homeostasis via PC export through ABC-A1 transporter expression. Hence it is important to consider pharmacological interventions in neonatal lung PC metabolism with respect to such export. Five-day-old rats were treated with carrier (control), intraperitoneal betamethasone, subcutaneous recombinant human keratinocyte growth factor (rhuKGF), or their combination for 48 h. Animals were intraperitoneally injected with 50 mg/kg [D9-methyl]choline chloride 1.5, 3.0, and 6.0 h before death at day 7, and lung lavage fluid (LLF) and tissue were harvested. Endogenous PC, D9-labeled PC species, and their water-soluble precursors (D9-)choline and (D9-)phosphocholine were determined by tandem mass spectrometry. Treatment increased secreted and tissue PC pools but did not change equilibrium composition of PC species in LLF. However, all treatments increased specific surfactant components in tissue. In control rats, peak D9-PC in lavaged lung was reached after 3 h and was decreased at 6 h. Only 13% of this net loss in lavaged lung was found in LLF. Such decrease was not present in lungs treated with betamethasone and/or with rhuKGF. D9-PC loss at 3-6 h and PC synthesis calculated from D9 enrichment of phosphocholine indicated that daily synthesis rate is higher than total pool size. We conclude that lung tissue contributes to systemic PC homeostasis in neonatal rats, which is altered by glucocorticoid and rhuKGF treatment.