Emerging and traditional 5-α reductase inhibitors and androgen receptor antagonists for male androgenetic alopecia.

INTRODUCTION: Androgenetic alopecia (AGA) is the most prevalent cause of male hair loss, often requiring medical and/or surgical intervention. The US FDA has approved topical minoxidil and oral finasteride for male AGA treatment. However, some AGA patients fail to respond satisfactorily to these FDA-approved treatments and/or may experience side effects, based on their individual profiles. To mitigate the shortcomings of these treatments, researchers are now exploring alternative treatments such as newer 5-α reductase inhibitors (5-ARIs) and androgen receptor antagonists (ARAs). AREAS COVERED: This article reviews the safety and effectiveness of well-known 5-α reductase inhibitors (5-ARIs) like finasteride and dutasteride, as well as the newer 5-ARIs, emerging androgen receptor antagonists (ARAs), and natural products such as saw palmetto and pumpkin seed oil in the treatment of male AGA. EXPERT OPINION: Although several newer 5-ARIs, ARAs, and natural products have exhibited promise in clinical trials, additional research is essential to confirm their safety and efficacy in treating male AGA. Until additional evidence is available for these agents, the preferred treatment choices for male AGA are the FDA-approved treatments, topical minoxidil, and oral finasteride.

Clinical presentation and outcomes of care in adults with diabetic ketoacidosis pre-COVID-19 and during-COVID-19 at a tertiary, referral hospital in Nairobi, Kenya.

BACKGROUND: Prognosis of DKA has improved over time with the availability of evidence-based protocols and resources. However, in Kenya, there are limited resources for the appropriate diagnosis and management of DKA, mostly limited to tertiary-level referral facilities. This study aimed to review the clinical presentation, management, and outcomes of adult patients admitted with DKA and assess differences in these parameters before and during the COVID-19 pandemic. METHODS: This was a retrospective study of DKA admissions from January 2017 to December 2021. Patient data were retrieved from the medical records department using ICD-10 codes, and individual details were abstracted on clinical presentation, management, and outcomes of DKA. Comparisons were made between pre-COVID-19 and during COVID-19 durations. RESULTS: 150 patients admitted with DKA were included (n = 48 pre- COVID-19, n = 102 during COVID-19 (n = 23 COVID-19 positive, n = 79 COVID-19 negative)). Median age was 47 years (IQR 33.0, 59.0), median HbA1C was 12.4% [IQR 10.8, 14.6]), and most patients had severe DKA (46%). Most common DKA precipitants were infections (40.7%), newly diagnosed diabetes (33.3%) and missed medication (25.3%). There was a significant difference in pulmonary infections as a DKA precipitant, between the pre- COVID and during COVID-19 pandemic (21.6% during COVID-19 versus 6.3% pre- COVID-19; p = 0.012). Median total insulin dose used was 110.0 units [IQR 76.0, 173.0], and a 100% of patients received basal insulin. Median length of hospital stay was 4.0 days [IQR 3.0, 6.0] and time to DKA resolution was 30.0 h [IQR 24.0, 48.0]. There were 2 deaths (1.3%), none directly attributable to DKA. Severity of DKA significantly differed between pre- COVID-19, COVID-19 positive and COVID-19 negative DKA (52.2% of COVID-19 positive had moderate DKA compared to 26.6% of COVID-19 negative and 22.9% of Pre-COVID-19 (p = 0.006)). CONCLUSION: Even in developing regions, good outcomes can be achieved with the appropriate facilities for DKA management. Clinician and patient education is necessary to ensure early detection and prompt referral to avoid patients presenting with severe DKA. Exploratory studies are needed to assess reasons for prolonged time to DKA resolution found in this study.

Effectiveness of Platelet-Rich Plasma in the Treatment of Androgenic Alopecia: A Meta-Analysis.

BACKGROUND: Androgenetic alopecia (AGA) is a common yet difficult-to-treat condition, which is an important psychosocial problem. Platelet-rich plasma (PRP) therapy has been considered as a promising treatment for AGA. However, the current evidence on the efficacy of PRP for treating AGA is still controversial. This study evaluated the efficacy of PRP monotherapy in the treatment of AGA. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science to collect randomized controlled trials on use of PRP in AGA for a meta-analysis. RESULTS: Ten trials with a total 555 treatment units were identified. The hair density in PRP group was significantly higher than control group [MD = 25.09, 95%CI: 9.03-41.15, p = 0.002], but there was no significant difference in hair diameter between two groups [SMD = 0.57, 95%CI: - 0.23 to 1.38, p = 0.16]. Subgroup analyses indicated that hair density was significantly higher among the male-only trials than in the mixed-sex samples (p = 0.02). In addition, neither the split-head design nor the year of publication affected hair density (p = 0.05, p = 0.06). However, hair density was significantly higher in trials with a sample size less than 30 (p = 0.0004). CONCLUSIONS: PRP treatment increased hair density in participants with AGA, but not hair diameter. In terms of hair density, PRP elicits stronger effects in male patients. There was a trend toward differed treatment effect by gender with PRP injection, which warrants further investigation. Especially in the case of female. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway.

BACKGROUND: Despite the advancement in chemotherapeutic drugs for colon cancer treatment, it is still a life-threatening disease worldwide due to drug resistance. Therefore, an urgently needed to develop novel drugs for colon cancer therapies. AGA is a combination of traditional Chinese medicine Antler's extract (A), Ganoderma lucidum (G), and Antrodia camphorata (A); it contains a lot of biomolecules like polysaccharides, fatty acids, and triterpenoids that are known to exerting anti-oxidative, anti-inflammatory, anti-microbial and anti-tumor activities in oral cancer. In this study, we investigate AGA anti-proliferative, anti-metastatic and apoptotic activity to explore its anti-cancer activity against colon cancer cells and its underlying mechanism. METHOD: Here, in-vitro studies were performed to determine the antiproliferative activity of AGA through MTT and colony formation assays. Wound healing and transwell migration assay were used to evaluate the metastasis. Flow cytometry and protein expression were used to investigate the involved molecular mechanism by evaluating the cell cycle and apoptosis. The in-vivo anti-cancerous activity of AGA was assessed by xenograft mice model of colon cancer cells. RESULTS: We found that AGA significantly inhibited the proliferative capacity and metastasis of colon cancer cells in-vitro. In addition, AGA induced cell cycle arrest in the sub-G1 phase through upregulating p21 and downregulating CDK2, CDK6 in SW620, and CDK4 in SW480 and HT29, respectively. Annexin-v assay indicated that colon cancer cells had entered early and late apoptosis after treatment with AGA. Furthermore, a mechanistic protein expressions study revealed that AGA in p53-dependent and independent regulated the apoptosis of colon cancer by downregulating the p53 protein expression in SW620 and SW480 cells but upregulating in a dose-dependent manner in HT29 cells and increasing the expression of Bax and caspase-9 to inhibit the colon cancer cells. In vivo study, we found that AGA significantly reduced the xenograft tumor growth in NOD/SCID mice with no adverse effect on the kidney and liver. CONCLUSION: Collectively, AGA has the potential to inhibit colon cancer through inhibiting proliferation, migration, and cell cycle kinase by upregulating p21 protein expression and promoting the apoptotic protein in a p53-dependent and independent manner.

The importance of the cerebroplacental ratio for the prognosis of neonatal outcome in AGA fetuses.

PURPOSE: As a Doppler sonographic parameter, the cerebroplacental ratio (CPR) provides information about fetal hemodynamics and the redistribution of fetal blood volume in response to a metabolic change. The present study was undertaken to determine the extent to which CPR can be used as a valid parameter in routine obstetric assessment. We investigated whether CPR can be used to assess the neonatal outcome in appropriate for gestational age (AGA) fetuses and its association with secondary cesarean section due to fetal distress. METHODS: In this retrospective analysis 1739 pregnant women were admitted to the University Women's Clinic Magdeburg, Germany, between January 2016 and December 2017. Of them, 710 AGA fetuses were eligible for analysis. SGA fetuses with an estimated fetal weight < 10th percentile were excluded from the study. The AGA fetuses were divided in two groups based on the CPR: 669 fetuses showed a normal CPR ≥ 1.08; 41 fetuses showed a decreased CPR < 1.08. RESULTS: In our study cohort decreased CPR in AGA fetuses was associated with threefold increased rate of cesarean sections due to fetal distress (p < 0.001). Our data suggested that low CPR is a reliable predictor of an impaired neonatal outcome in AGA fetuses in terms of a lower birth weight, transfer to neonatology, longer length of hospitalization, and the presence of severe morbidity. CONCLUSION: Decreased CPR in AGA fetuses correlated with impaired neonatal outcome and secondary cesarean section due to fetal distress. The potential role of CPR for obstetric screening should be investigated in further studies.

Dual Lewis Acid-Base Sites Regulate Silver-Copper Bimetallic Oxide Nanowires for Highly Selective Photoreduction of Carbon Dioxide to Methane.

Highly selective photoreduction of CO2 to valuable hydrocarbons is of great importance to achieving a carbon-neutral society. Precisely manipulating the formation of the Metal1 ⋅⋅⋅C=O⋅⋅⋅Metal2 (M1 ⋅⋅⋅C=O⋅⋅⋅M2 ) intermediate on the photocatalyst interface is the most critical step for regulating selectivity, while still a significant challenge. Herein, inspired by the polar electronic structure feature of CO2 molecule, we propose a strategy whereby the Lewis acid-base dual sites confined in a bimetallic catalyst surface are conducive to forming a M1 ⋅⋅⋅C=O⋅⋅⋅M2 intermediate precisely, which can promote selectivity to hydrocarbon formation. Employing the Ag2 Cu2 O3 nanowires with abundant Cu⋅⋅⋅Ag Lewis acid-base dual sites on the preferred exposed {110} surface as a model catalyst, 100 % selectivity toward photoreduction of CO2 into CH4 has been achieved. Subsequent surface-quenching experiments and density functional theory (DFT) calculations verify that the Cu⋅⋅⋅Ag Lewis acid-base dual sites do play a vital role in regulating the M1 ⋅⋅⋅C=O⋅⋅⋅M2 intermediate formation that is considered to be prone to convert CO2 into hydrocarbons. This study reports a highly selective CO2 photocatalyst, which was designed on the basis of a newly proposed theory for precise regulation of reaction intermediates. Our findings will stimulate further research on dual-site catalyst design for CO2 reduction to hydrocarbons.

Transcription factor FOXC1 positively regulates SFRP1 expression in androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from -100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.

Natural products for male androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common cause of hair loss in men, often requiring medical attention. The US FDA approved topical minoxidil and oral finasteride to treat AGA. Topical minoxidil requires a long-term application to observe improvement; oral finasteride may cause undesirable side effects. Therefore, natural products may be an alternative when patients are skeptical about these two conventional treatments. Physicians may also suggest natural products in conjunction with topical minoxidil or oral finasteride to enhance clinical outcomes. This article reviews the prospect of natural products in treating male AGA. A systematic search was conducted in PubMed, CINAHL, Scopus, Web of Science, and EMBASE (Ovid) on July 19, 2021. In addition, the bibliographies of selected articles were hand-searched to identify relevant studies. After deduplication and screening, 11 clinical studies meet the criteria for detailed review. The selected clinical studies suggest that saw palmetto, caffeine, melatonin, marine extracts, rosemary oil, procyanidin, pumpkin seed oil, and cannabidiol oil might be considered in male AGA treatment.

Pre-clinical Gene Therapy with AAV9/AGA in Aspartylglucosaminuria Mice Provides Evidence for Clinical Translation.

Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disease caused by loss of the enzyme aspartylglucosaminidase (AGA), resulting in AGA substrate accumulation. AGU patients have a slow but progressive neurodegenerative disease course, for which there is no approved disease-modifying treatment. In this study, AAV9/AGA was administered to Aga-/- mice intravenously (i.v.) or intrathecally (i.t.), at a range of doses, either before or after disease pathology begins. At either treatment age, AAV9/AGA administration led to (1) dose dependently increased and sustained AGA activity in body fluids and tissues; (2) rapid, sustained, and dose-dependent elimination of AGA substrate in body fluids; (3) significantly rescued locomotor activity; (4) dose-dependent preservation of Purkinje neurons in the cerebellum; and (5) significantly reduced gliosis in the brain. Treated mice had no abnormal neurological phenotype and maintained body weight throughout the whole experiment to 18 months old. In summary, these results demonstrate that treatment of Aga-/- mice with AAV9/AGA is effective and safe, providing strong evidence that AAV9/AGA gene therapy should be considered for human translation. Further, we provide a direct comparison of the efficacy of an i.v. versus i.t. approach using AAV9, which should greatly inform the development of similar treatments for other related lysosomal storage diseases.

Efficacy assessment for low-level laser therapy in the treatment of androgenetic alopecia: a real-world study on 1383 patients.

Low-level laser therapy (LLLT) has been a treatment modality by many androgenetic alopecia (AGA) patients in recent years. It remained unclear as to how long the treatment regime should be maintained, and which characteristics of patients should this be recommended. A real-world study was carried out with an FDA-cleared low-level laser helmet for 1383 patients. Ordinal logistic regression analysis with propensity score matching (PSM) was used to investigate the factors related to efficacy assessment. More than 80% of users were between 18 and 40 years old. The median use times were 133 for mild AGA patients and 142 for moderate-to-severe AGA patients, which equated to 38 weeks and 40 weeks, respectively. The overall clinical effectiveness was nearly 80%. PSM analysis revealed that gender (P = 0.002), use period (P = 0.068), scalp conditions with dandruff, rash, and itchy symptoms were associated with the grading of efficacy assessment. Male users (ordinal OR: 1.35, CI: (1.01, 1.79)); use for more than 180 times or use period for 1 year (ordinal OR: 1.40, CI: (1.11, 1.96)); and those with scalp dandruff (ordinal OR: 1.34, CI: (1.01, 1.87)), rash (ordinal OR: 1.47, CI: (1.04, 2.07)), and itchy symptoms (ordinal OR: 1.51, CI: (1.12, 2.03)) had better efficacy assessments. The recommended treatment regime with low-level laser helmet was more than 1 year or 180 use times. Male patients with dandruff, rash, and itchy symptoms in scalps tended to have a better efficacy assessment.

Unrevealing the Potential of Sansevieria trifasciata Prain Fraction for the Treatment of Androgenetic Alopecia by Inhibiting Androgen Receptors Based on LC-MS/MS Analysis, and In-Silico Studies.

Androgenetic Alopecia (AGA) occurs due to over-response to androgens causing severe hair loss on the scalp, and requires the development of new and efficient drugs to treat this condition. This study explores and identifies secondary metabolites from Sansevieriatrifasciata Prain using the LC-MS/MS and in-silico method. The inhibitory activity of bioactive compounds from S. trifasciata Prain against androgen receptors (PDB ID: 4K7A) was evaluated molecularly using docking and dynamics studies by comparing their binding energies, interactions, and stability with minoxidil. The results of the LC-MS/MS analysis identified Methyl pyrophaeophorbide A (1), Oliveramine (2), (2S)-3', 4'-Methylenedioxy-5, 7-dimethoxyflavane (3), 1-Acetyl-ß-carboline (4), Digiprolactone (5), Trichosanic acid (6) and Methyl gallate (7) from the leaves subfraction of this plant. Three alkaloid compounds (compounds 1, 3, and 4), and one flavonoid (compound 2), had lower docking scores of -7.0, -5.8, -5.2, and -6.3 kcal/mol, respectively. The prediction of binding energy using the MM-PBSA approach ensured that the potency of the four compounds was better than minoxidil, with energies of -66.13, -59.36, -40.39, and -40.25 kJ/mol for compounds 1, 3, 2, and 4, respectively. The dynamics simulation shows the stability of compound 1 based on the trajectory analysis for the 100 ns simulation. This research succeeded in identifying the compound and assessing the anti-alopecia activity of Sansevieria trifasciata Prain. Seven compounds were identified as new compounds never reported in Sansevieria trifasciata Prain. Four compounds were predicted to have better anti-alopecia activity than minoxidil in inhibiting androgen receptors through an in silico approach.

Global Surgery Hackathons: A Case Study From Pakistan.

Background. Hackathons aim to solve problems in a selected field by bringing together people from multiple domains and combining their expertise. Global surgery is an emerging field with a huge burden of disease and massive implications for bettering health care. In this study, we describe the first Global Surgery Hackathon held in Pakistan and analyze the impacts of the hack and post-hack incubation. Methods. This research study used data collected from a Hackathon held at the Aga Khan University (AKU) in Karachi, Pakistan, and progress from the post-hack incubation teams. Data were collected from applications, from sign-in attendance, via evaluation forms, and milestone tracking of the incubation teams. A list of factors such as sectors addressed by winning projects and grants received was made. Results. The evaluations provided by the participants were positive, with mean scores of 4.00 (SD = .78) out of 5 on a Likert scale. Pitches made (n = 69, 68%) by the 109 participants were sorted into 5 categories: workplace, access, quality, safety, and design. Fifteen teams were formed, out of which 5 were accepted for incubation. All teams had a minimum viable product at the one-year mark. Conclusion. Hackathons are a reliable way to come up with effective solutions for targeted problems in various areas of health care and using the methodology of a Hackathon, a pool of low-cost, innovative solutions can be generated. These solutions can definitely impact health outcomes, especially for the field of global surgery. Further statistics should be collected to affirm the incubated solutions' impact.

Ectodysplasin-A2 induces dickkopf 1 expression in human balding dermal papilla cells overexpressing the ectodysplasin A2 receptor.

Androgenetic alopecia (AGA) is a common genetic disorder, and a X-chromosomal locus that contains the androgen receptor (AR) and ectodysplasin A2 receptor (EDA2R) genes represents a major susceptibility locus for AGA. In our previous study, we reported that ectodysplasin-A2 (EDA-A2) induces apoptosis in cultured human hair follicle (HF) cells and promotes the regression of HFs in mice. However, the role of the EDA-A2/EDA2R in AGA remains unknown, as the causative gene in this pathway has not yet been identified and potential functional connections between EDA-A2 signaling and the androgen pathway remain unclear. In this study, we investigated the expression of EDA2R in balding HFs and matched with non-balding HFs. The EDA2R level was upregulated in the balding dermal papilla (DP) cells compared with non-balding DP cells derived from patients with AGA. However, EDA2R was strongly expressed in both balding and non-balding outer root sheath (ORS) cells. We screened EDA-A2-regulated genes in balding DP cells and identified dickkopf 1 (DKK-1) as catagen inducer during the hair cycle. The mRNA and protein expression levels of DKK-1 were both upregulated by EDA-A2. In addition, DKK-1 expression was induced by EDA-A2 both in cultured human HFs and in mouse HFs. Moreover, the EDA-A2-induced apoptosis of DP and ORS cells was reversed by the antibody-mediated neutralization of DKK-1. Collectively, our data strongly suggest that EDA-A2 induces DKK-1 secretion and causes apoptosis in HFs by binding EDA2R, which is overexpressed in the bald scalp. EDA-A2/EDA2R signaling could inhibit hair growth through DKK-1 induction, and an inhibitor of EDA-A2/EDA2R signaling may be a promising agent for the treatment and prevention of AGA.

Cross sectional quality of life assessment in patients with androgenetic alopecia.

Assessment of quality of life (QOL) of patients with androgenetic alopecia (AGA) has become increasingly important, both in order to evaluate the influence of the disease on patients and the therapy they require. We aimed to assess QOL in subjects complaining from AGA and evaluated the effects of various sociodemographic factors affecting their QOL. QOL was assessed in 400 patients with AGA and 100 controls using the World Health Organization Quality of life (WHOQOL-BREF) questionnaire. Four domains (physical, psychological, social, and environmental) and two items (overall perception of QOL and health) of the WHOQOL-BREF were the primary end points of this study. Patients had a lower QoL and less general satisfaction in all four domains of assessment than controls. The social impact was significantly higher in patients < 30 years of age (P = .003). Patients with severer form of AGA significantly had higher scores in all domains compared to those with less severe forms. Disease severity negatively impacted all the four domains significantly (P = .021). AGA harmfully affected the patient's QOL which warns the physicians to pay more attention to QOL impairment in patients of AGA for the better understanding of the disease burden on individual patients.

Overexpression and characterization of a novel GH16 ß-agarase (Aga1) from Cellulophaga omnivescoria W5C.

OBJECTIVE: To identify and characterize a new ß-agarase from Cellulophaga omnivescoria W5C capable of producing biologically-active neoagarooligosaccharides from agar. RESULTS: The ß-agarase, Aga1, has signal peptides on both N- and C-terminals, which are involved in the type IX secretion system. It shares 75% protein sequence identity with AgaD from Zobellia galactanivorans and has a molecular weight of 54 kDa. Biochemical characterization reveals optimum agarolytic activities at pH 7-8 and temperature 30-45 °C. Aga1 retains at least 33% activity at temperatures lower than the sol-gel transition state of agarose. Metal ions are generally not essential, but calcium and potassium enhance its activity whereas iron and zinc are inhibitory. Finally, hydrolysis of agarose with Aga1 yields neoagarotetraose, neoagarohexaose, and neoagarooctaose. CONCLUSIONS: Aga1 displays unique traits such as moderate psychrophilicity, stability, and synergy with other agarases, which makes it an excellent candidate for biosynthetic production of neoagarooligosaccharides from agar.

Systematic Review of Platelet-Rich Plasma Use in Androgenetic Alopecia Compared with Minoxidil®, Finasteride®, and Adult Stem Cell-Based Therapy.

The number of articles evaluating platelet-rich plasma (PRP) efficacy in androgenic alopecia (AGA) have exponentially increased during the last decade. A systematic review on this field was performed by assessing in the selected studies the local injections of PRP compared to any control for AGA. The protocol was developed in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases was performed to identify studies on hair loss treatment with platelet-rich plasma. Of the 163 articles initially identified, 123 articles focusing on AGA were selected and, consequently, only 12 clinical trials were analyzed. The studies included had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. In total, 84% of the studies reported a positive effect of PRP for AGA treatment. Among them, 50% of the studies demonstrated a statistically significant improvement using objective measures and 34% of the studies showed hair density and hair thickness improvement, although no p values or statistical analysis was described. In total, 17% of the studies reported greater improvement in lower-grade AGA, while 8% noted increased improvement in higher-grade AGA. Only 17% of the studies reported that PRP was not effective in treating AGA. The information analyzed highlights the positive effects of PRP on AGA, without major side effects and thus it be may considered as a safe and effective alternative procedure to treat hair loss compared with Minoxidil® and Finasteride®.

Comparative Evaluation of the Clinical Efficacy of PRP-Therapy, Minoxidil, and Their Combination with Immunohistochemical Study of the Dynamics of Cell Proliferation in the Treatment of Men with Androgenetic Alopecia.

Platelet-rich plasma (PRP) therapy has been considered as a promising treatment for androgenetic alopecia (AGA). The aim of the study was comparative evaluation of the clinical efficacy of PRP-therapy, minoxidil, and their combination in the treatment of men with AGA and to evaluate the effects of PRP on the proliferation of hair follicle (HF) cells in skin biopsy. MATERIALS AND METHODS: The study involved 69 men who were divided into 3 groups who received PRP therapy, minoxidil, and their combination. The clinical efficacy of the therapy was evaluated by the dynamics of morphometric of hairs. To assess cell proliferation antibodies to ß-catenin, CD34, Ki67, and to Dkk-1 were used. RESULTS: PRP treatment was more effective than minoxidil therapy (p = 0.005). Complex therapy turned out to be more effective than minoxidil monotherapy (p < 0.0001) and PRP monotherapy (p = 0.007). After applying PRP the absolute and relative values of the ß-catenin and CD34 expression area increased; an increase in Ki67+ index was also significant. CONCLUSIONS: PRP can be considered as a treatment option for AGA. Combined PRP and minoxidil use seems promising for the treatment of AGA. PRP increase in the proliferative activity of HF cells and improves hair morphology in patients with AGA.

The level of stress and the assessment of selected clinical parameters in patients with androgenetic alopecia.

Androgenetic alopecia is the most common type of hair loss both in male as well as female patients. It is a type of non-cicatricial hair loss. Pathophysiology of the disease remains largely unknown. It is believed that the occurrence of FPHL (female pattern hair loss) is linked with cellular insensitivity to androgens. Human hair does not only represent beauty, health and youth, but it also has a significant impact on one's self-esteem. For many patients, hair loss is a stigmatizing experience, many of them complain about a lower quality of life, anxiety or even depression. AIM: Aim of the study was to evaluate the levels of selected clinical parameters, including exposure to stress and disease progression based on the Ludwig scale, and of the applied therapies in a group of female patients with androgenetic alopecia. MATERIALS AND METHODS: A group of 106 patients with androgenetic alopecia was analyzed with respect to their age, duration of disease, disease progression based on the Ludwig scale, family history of AGA, exposure to stress (with the level of stress subjectively assessed by the patients using a score of 1 to 10), and treatment modality. Comparison of the results will be carried out with the help of the Statistica software, using the Student's t-test or its non-parametric equivalent. RESULTS: Patients reported very high levels of stress exposure: 7 and 8 on a scale of 1 to 10. The type of treatment applied (local vs. systemic) was of no significance with respect to the alleviation of stress. Disease progression was not found to correlate with the level of stress. When analyzing disease progression, using the Ludwig classification scale, most of the patients met the criteria of type I-2 (24.74%). As regards the comparison of treatment modalities in the study group, a great majority of patients was treated with topical agents in the form of scalp massage liquids (80.00%), while 17.14% of the study population underwent systemic treatment. A small percentage of patients also resorted to esthetic medicine procedures (3.81%), and 22.86% of them used dietary supplements or OTC topical agents. CONCLUSIONS: High levels of stress exposure reported by patients most probably stemmed from the symptoms of the disease itself, as the study population was quite diverse in terms of their levels of professional activity and the type of profession performed.

Development of novel surface display platforms for anchoring heterologous proteins in Saccharomyces cerevisiae.

BACKGROUND: Cell surface display of recombinant proteins has become a powerful tool for biotechnology and biomedical applications. As a model eukaryotic microorganism, Saccharomyces cerevisiae is an ideal candidate for surface display of heterologous proteins. However, the frequently used commercial yeast surface display system, the a-agglutinin anchor system, often results in low display efficiency. RESULTS: We initially reconstructed the a-agglutinin system by replacing two anchor proteins with one anchor protein. By directly fusing the target protein to the N-terminus of Aga1p and inserting a flexible linker, the display efficiency almost doubled, and the activity of reporter protein α-galactosidase increased by 39%. We also developed new surface display systems. Six glycosylphosphatidylinositol (GPI) anchored cell wall proteins were selected to construct the display systems. Among them, Dan4p and Sed1p showed higher display efficiency than the a-agglutinin anchor system. Linkers were also inserted to eliminate the effects of GPI fusion on the activity of the target protein. We further used the newly developed Aga1p, Dan4p systems and Sed1p system to display exoglucanase and a relatively large protein ß-glucosidase, and found that Aga1p and Dan4p were more suitable for immobilizing large proteins. CONCLUSION: Our study developed novel efficient yeast surface display systems, that will be attractive tools for biotechnological and biomedical applications.

The diagnosis of androgenetic alopecia in children: Considerations of pathophysiological plausibility.

Androgenetic alopecia (AGA), one of the most common causes of hair loss in men and women, is an infrequent cause of alopecia in children. In AGA, patients generally start noticing hair thinning after the onset of puberty due to progressive miniaturisation of the hair follicle which leads to vellus transformation of terminal hair. However, the occurrence of prepubertal AGA has rarely been reported in the literature. The pathophysiology of AGA is tightly linked to androgen hormones; prepubertal children do not usually produce significant amounts of adrenal or gonadal androgens. When it does occur, an underlying abnormality should be suspected. Secondary causes of AGA must be excluded when evaluating a patient before the appearance of puberty. Premature puberty, polycystic ovarian syndrome and other causes of hyperandrogenism can present with hair loss in an androgenetic pattern. This article reviews the normal physiology of androgen hormones and their role in the pathophysiology of childhood AGA.