BACKGROUND Androgenetic alopecia(AGA)is a common form of hair loss that can be influenced by psychological factors.AIM To investigate the impact of mental stress on neurotrophic factors in patients with AGA and correl...BACKGROUND Androgenetic alopecia(AGA)is a common form of hair loss that can be influenced by psychological factors.AIM To investigate the impact of mental stress on neurotrophic factors in patients with AGA and correlate the findings with the progression of AGA.METHODS A total of 120 patients with AGA were analyzed in this study,which were divided into a non-stress group(n=30)and a stress group(n=90)on the basis of the presence or absence of psychological stress confirmed by Depression Anxiety Stress Scale-21 scale.The baseline demographic characteristics,serum cortisol levels,hair growth parameters,neurotrophic factors,and AGA progression scores between the non-stress and stress groups were compared.Correlation analyses were conducted to assess the relationships among stress,neurotrophic factors,hair loss progression,and AGA progression.RESULTS This study revealed significantly higher cortisol levels throughout the day in the stress group than in the non-stress group.The stress group exhibited lower levels of nerve growth factor,brain-derived neurotrophic factor,and glial cell linederived neurotrophic factor and higher expression levels of neurotrophin(NT)-3 and NT-4 than the non-stress group.Hair parameters indicated lower hair diameter,decreased hair density,and more severe AGA grading in the stress group,whereas follicle count and terminal/vellus hair ratio showed no significant differences between the two groups.After 1 year of treatment with 5%minoxidil,efficacy was observed to be lower but AGA progression was notably more pronounced in the stress group than in the non-stress group.Disease progression was positively correlated with high stress and NT-4 levels.CONCLUSION This study provides compelling evidence of the influence of mental stress on neurotrophic factors and its correlation with the progression of AGA.The findings underscore the need for a comprehensive approach to the management of AGA that considers the physiological and psychosocial aspects.Further research is warranted to validate the findings and explore targeted therapeutic interventions for individuals with stress-related AGA.展开更多
Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic al...Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic alopecia.Methods:From July 2022 to July 2023,120 male patients with androgenetic alopecia were selected from our Department of Dermatology and randomly divided into Control Group 1,Control Group 2,Observation Group 1,and Observation Group 2,with 30 patients in each group.Control Group 1 was treated with ketoconazole shampoo,Control Group 2 with 5%minoxidil foam,Observation Group 1 with ketoconazole shampoo combined with Chuzhi Shengfa Tablets,and Observation Group 2 with 5%minoxidil foam combined with Chuzhi Shengfa Tablets.Hair density,hair diameter,scalp oil secretion(using oil secretion scoring),and adverse reactions were compared before and after treatment across the four groups.Results:After treatment,hair density and hair diameter significantly increased in all four groups compared to before treatment,while scalp oil secretion scores significantly decreased(P<0.05).The improvements in Observation Groups 1 and 2 were significantly better than those in Control Groups 1 and 2(P<0.05).No significant differences in the incidence of adverse reactions were observed among the four groups(P>0.05).Conclusion:Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam are both effective and safe for treating male androgenetic alopecia.These combinations can significantly improve hair growth and are worthy of clinical promotion.展开更多
Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admi...Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admitted to our Department of Dermatology between January 2022 and January 2024 were randomly divided into two groups,with 30 patients in each group.The control group was treated with finasteride,while the observation group received a combination of Chuzhi Shengfa tablets and finasteride.The clinical efficacy and adverse reactions in both groups were compared.Results:The overall effectiveness rate in the observation group was 93.33%(28/30),significantly higher than the control group’s 73.33%(22/30),with a statistically significant difference(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The combination of Chuzhi Shengfa tablets and finasteride shows good clinical efficacy in treating male androgenetic alopecia.Additionally,Chuzhi Shengfa tablets are convenient to administer and effectively improve efficacy,significantly improving patients’conditions,and demonstrating good clinical application value.展开更多
Studies have shown that platelet concentrates can induce the proliferation of the dermal papilla and the vascularization of the perifollicular tissue, as well as accelerate the telogen-to-anagen transition, thereby pr...Studies have shown that platelet concentrates can induce the proliferation of the dermal papilla and the vascularization of the perifollicular tissue, as well as accelerate the telogen-to-anagen transition, thereby promoting the regrowth of hair improving the appearance of hair loss. Herein, we report on the application of a new, modified form of platelet concentrates, namely, concentrated growth factors (CGFs), in 15 cases of androgenetic alopecia (AGA). 15 cases of androgenetic alopecia were treated with the use of monthly, subcutaneous injections of autologous CGF in the scalp. A total of 3 injections were administered 4 weeks apart, and the patients were followed up for 6 months. Assessments were performed before the treatments and at 4, 8, 12 and 24 weeks after the first treatment. The treatment outcomes were assessed by taking macroscopic photographs and trichoscopic photomicrographs, as well as by using the Global Aesthetic Improvement Scale (GAIS) and the patient satisfaction survey. In order to determine the safety of the treatment, the injection area was observed for signs of infection or mass evaluation. The photographs showed significant improvement in hair appearance after injections of CGF. The hair photomicrographs showed that CGF promoted the regrowth of hair in balding areas, with an increased hair density and an increased ratio of terminal to vellus hair. The GAIS suggested that CGF treatments were effective in treating AGA, and the majority of patients were satisfied with their improvement. In addition, treatments resulted in a faster rate of hair growth and a decrease in the greasy and unpleasant sensation of the hair of the patients. At the last visit, none of the 15 patients reported experiencing side-effects during the follow-up period. To conclude, the application of CGF can be an effective method in the treatment of androgenetic alopecia.展开更多
Background: Progressing androgenetic alopecia (AGA), in both sexes, can result in severe distress. Treatments with the capacity to slow down the progression of AGA, or even to bring it to a halt, and at the same time ...Background: Progressing androgenetic alopecia (AGA), in both sexes, can result in severe distress. Treatments with the capacity to slow down the progression of AGA, or even to bring it to a halt, and at the same time don’t come with side effects are consequently highly sought for. Therefore this study investigates the effect of an over-the-counter nutritional supplement and a similarly formulated topical hair lotion on the progression of AGA. Methods: Seventy-nine healthy study participants of both sexes, who were diagnosed with AGA were divided into 4 study groups. The subjects of the first group were treated with the nutritional supplement, the subjects of the second group with the topical hair lotion, the subjects of the third group with both products, and the subjects of the fourth group served as a no-treatment control. At the beginning and at the end of this nine-month study, the participants were evaluated for their hair loss status. They also answered a questionnaire for self-assessment. A part of the subjects from each study group were further analysed by phototrichography, in order to measure the number of anagen and telogen hairs. Results: It turned out that the supplement, the lotion as well as the treatment with both products not only lead to a reduction in hair loss but also to an increased anagen to telogen hair ratio, whereas no such effects could be measured for the control group. Conclusion: The results show that a systemic delivery via a nutritional supplement, as well as a follicular delivery via a topically applied lotion, both resulted in a reduced hair loss rate as well as in an increased anagen to telogen hair ratio. This demonstrates that the tested formulation is effectively slowing down the progression of AGA.展开更多
Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS wh...Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.展开更多
Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the...Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients.In this study,a hyaluronic acid(HA)based hydrogel-formed microneedle(MN)was designed,referred to as V-R-MNs,which was simultaneously loaded with vascular endothelial growth factor(VEGF)and the novel hair loss drug Ritlecitinib,the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates(PHAs)nanoparticles(R-PHA NPs)for minimally invasive AGA treatment.The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency.Due to the biosafety,mechanical strength,and controlled degradation properties of HA hydrogel formed microneedles,V-R-MNs can effectively penetrate the skin’s stratum corneum,facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive,painless and long-term sustained release manner.V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells,but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis.In comparison to the clinical drug minoxidil for AGA treatment,the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase,improved hair quality,and greater coverage.This introduces a new,clinically safer,and more efficient strategy for AGA treatment,and serving as a reference for the treatment of other related diseases.展开更多
Androgenetic alopecia(AGA)is a common clinical condition,affecting over 200 million people globally each year.For decades,Minoxidil(Mi)tincture has been the primary treatment for this disease,but its low utilization r...Androgenetic alopecia(AGA)is a common clinical condition,affecting over 200 million people globally each year.For decades,Minoxidil(Mi)tincture has been the primary treatment for this disease,but its low utilization rate and significant side effects necessitate new therapeutic strategies.Nitric oxide(NO)is a signaling molecule in various physiological processes,including vasodilation,immune responses,and cell proliferation.Herein,we constructed a hyaluronic acid liposome(HL)complex as a novel transdermal delivery system(HL@Mi/NONOate)for NO and Mi,which displayed promising transdermal and hair-regrowth effects.In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy.First,NO promoted capillary dilation and accelerated blood flow,thus achieving efficient penetration of Mi.Due to the structural advantage of liposomes,the residence time of the Mi in the skin was prolonged.Moreover,HL@Mi/NONOate promoted cell proliferation and angiogenesis,and upregulated the expression of regulatory factors involved in follicle stem cell differentiation.In the AGA model,HL@Mi/NONOate down-regulated the expression of inflammatory factors,inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth.Concurrently,HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues,inducing follicle regeneration and development,ultimately achieving the synergistic multimodal AGA therapy.展开更多
Androgenetic alopecia(AGA)is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment,leading to cell apoptosis and eventual loss of hair follicles(HFs)...Androgenetic alopecia(AGA)is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment,leading to cell apoptosis and eventual loss of hair follicles(HFs).Traditional therapeutic formulations,such as Minoxidil(MXD)tincture,have limitations in reshaping the perifollicular microenvironment and exhibit limited effectiveness.Here,we report a multi-synergistic therapeutic platform for high-performance hair regeneration therapy.The platform combines microneedle(MN)patches loaded with MXD-encapsulated nanostructured lipid carriers(MXD-NLC-MNs)and cold atmospheric plasma(CAP).The MNs’mechanical strength enables efficient transdermal delivery of MXD to the targeted dermal papilla cells,promoting cell proliferation.Furthermore,in collaboration with MXD,the mechanical stimulation exerted by MN application synergistically upregulates the expression of vascular endothelial growth factor,leading to neoangiogenesis.Meanwhile,the transient microchannels in the skin created by MNs facilitate the transdermal delivery of CAPgenerated nitric oxide(NO)to the sites of HF lesions,whereby the synergistic interaction between MXD and NO boosts perifollicular vasodilation.Consequently,the perifollicular microenvironment can be effectively reshaped to accelerate hair regeneration in AGA murine models.This multi-synergistic combination therapy strategy would hold great promise for effectively treating AGA and promoting hair regrowth.展开更多
The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,...The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,a system enabling long-term maintenance of imprints in ESCs has proven challenging.Here,we report that the use of a two-step a2i(alternative two inhibitors of Src and Gsk3β,TSa2i)derivation/culture protocol results in the establishment of androgenetic haploid ESCs(AG-haESCs)with stable DNA methylation at paternal DMRs(differentially DNA methylated regions)up to passage 60 that can efficiently support generating mice upon oocyte injection.We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations.Furthermore,we demonstrate that TSa2itreated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation.Strikingly,AGhaESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells,in part through the enhanced proliferation of H19-DMR hypermethylated cells.Together,we establish AG-haESCs that can longterm maintain paternal imprints.展开更多
MicroRNAs(miRNAs) are a class of highly conserved small non-coding RNA molecules that play a pivotal role in several cellular functions.In this study,miRNA and messenger RNA(mRNA) profiles were examined by Illumin...MicroRNAs(miRNAs) are a class of highly conserved small non-coding RNA molecules that play a pivotal role in several cellular functions.In this study,miRNA and messenger RNA(mRNA) profiles were examined by Illumina microarray in mouse embryonic stem cells(ESCs) derived from parthenogenetic,androgenetic,and fertilized blastocysts.The global analysis of miRNA-mRNA target pairs provided insight into the role of miRNAs in gene expression.Results showed that a total of 125 miRNAs and 2394 mRNAs were differentially expressed between androgenetic ESCs(aESCs) and fertilized ESCs(fESCs),a total of 42 miRNAs and 87 mRNAs were differentially expressed between parthenogenetic ESCs(pESCs) and fESCs,and a total of 99 miRNAs and 1788 mRNAs were differentially expressed between aESCs and pESCs.In addition,a total of 575,5 and 376 miRNA-mRNA target pairs were observed in aESCs vs.fESCs,pESCs vs.fESCs,and aESCs vs.pESCs,respectively.Furthermore,15 known imprinted genes and 16 putative uniparentally expressed miRNAs with high expression levels were confirmed by both microarray and real-time RT-PCR.Finally,transfection of miRNA inhibitors was performed to validate the regulatory relationship between putative maternally expressed miRNAs and target mRNAs. Inhibition of miR-880 increased the expression of Peg3,Dyrklb,and Prrg2 mRNA,inhibition of miR-363 increased the expression of Nfat5 and Soatl mRNA,and inhibition of miR-883b-5p increased Nfat5,Tacstd2,and Ppapdc1 mRNA.These results warrant a functional study to fully understand the underlying regulation of genomic imprinting in early embryo development.展开更多
Objective:Androgenetic alopecia (AA) is a progressive hair loss disorder mediated by systemic androgens and genetic factors. A variety of AA treatments have been investigated. Currently, there is emerging evidence and...Objective:Androgenetic alopecia (AA) is a progressive hair loss disorder mediated by systemic androgens and genetic factors. A variety of AA treatments have been investigated. Currently, there is emerging evidence and growing interest in the use of platelet-rich plasma (PRP) for AA. This study describes a single-center experience using PRP to treat AA in women.Methods:A retrospective observational study design was employed. The study cohort comprised 20 women >18 years of age who were diagnosed with AA. PRP was prepared using a commercially available PRP kit. Each patient received six PRP treatment sessions at 4-week intervals. The severity of alopecia tool (SALT) scoring system was used to measure the severity of alopecia, and a paired t-test was used to calculate significance levels. Results:The mean pre-intervention and post-intervention total SALT score was 27.5 ± 6.35 and 9.41 ± 3.71, respectively. The difference in the total mean SALT score was 18.33 ± 1.64 and the effect size was 3.52. The scalp area with the largest effect size was the vertex (Cohen d= 2.53). The effect size was similar across other scalp areas (Cohen d= 1.91-2.09). There were no serious adverse effects of the treatment;only mild transient adverse effects were reported. Conclusion:The present study demonstrated the efficacy and safety of PRP injections in treating AA in women. However, these findings require confirmation in well-designed studies using standardized treatment protocols and evaluation methods.展开更多
Androgens have an intense consequence on the human scalp and body hair.Scalp hair sprouts fundamentally in awol of androgens whereas the body hair hike is vulnerable to the activity of androgens.Androgenetic alopecia(...Androgens have an intense consequence on the human scalp and body hair.Scalp hair sprouts fundamentally in awol of androgens whereas the body hair hike is vulnerable to the activity of androgens.Androgenetic alopecia(AGA)invoked as males emulate Alopecia due to the cause of the dynamic reduction of scalp hair.Androgens are medium of terminus growth of hair although the body.Local and system androgens convert the extensive terminal follicles into lesser vellus like structure.The out start of this type of alopecia is intensely irregular and the reason behind this existence of enough circulating steroidal hormones androgens and due to genetic predisposition.Effective treatments are available in the market as well as under clinical and preclinical testing.Many herbal formulations are also available but not FDA approved.Different conventional and NDDS formulations are already available in the market.To avoid various systemic side effects of both Finasteride and Minoxidil,topical formulations and natural products(nutrients,minerals,vitamins)now a days are being widely used to treat Androgenic alopecia.CAM(complementary and alternative medicine)provides the option to elect favorable,low-risk,adjuvant and alternative therapies.Herein,we offer a widespread review of topical marketed formulations,natural products,and CAM treatment options for AGA.展开更多
The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulga...The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulgaris.Hair follicle-targeting drug delivery systems allow for controlled drug release and enhance therapeutic efficacywithminimal side effects,exerting a promising method for themanagement of hair follicle-associated dysfunctions.Therefore,they have obtained much attention in several fields of research in recent years.This review gives an overviewof potential follicle-targeting drug delivery formulations currently applied based on the particularities of the hair follicles,including a comprehensive assessment of their preclinical and clinical performance.展开更多
Chimerism is defined as the presence in a subject of more than one stable and genetically distinct cell line;cases reported so far include both patients with ambiguous genitalia and healthy subjects. The biological me...Chimerism is defined as the presence in a subject of more than one stable and genetically distinct cell line;cases reported so far include both patients with ambiguous genitalia and healthy subjects. The biological mechanisms, which may give origin to chimeras, are complex, and can be understood by analyzing DNA samples of the patients and their parents using molecular techniques. The objective of this study is to identify the mechanism of origin for the 2 cases we report. The first patient is a phenotipically normal girl with normal (external and internal) genitalia;the second patient had ambiguous genitalia and underwent surgery. DNA was purified from blood samples and, limited to Patient 1, from a sample of biliary cyst. Short tandem repeat polymorphisms were analyzed in order to identify the relative parental contribution to the patients. Molecular analyses carried out on the first patient are not fully informative because of two possible explanations (i.e. parthenogenetic and andrognetic chimera), while in the second case the presence of four alleles at some markers allowed us to identify a tetragametic chimera originnated from the fusion of two distinct embryos. Studies carried on one single tissue may not always be conclusive as they do not allow the precise identification of the mechanism of origin. In these cases, studies on more tissues are strongly suggested.展开更多
Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genet...Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genetic variants of HSPG2 in 10%cases compared to only 4%in controls among a cohort of 369 NTDs.Endorepellin,a peptide cleaved from the domain V of Perlecan,is known to promote angiogenesis and autophagy in endothelial cells.The roles of enderepellin in neurodevelopment remain unclear so far.Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo.Through the endocytic pathway,the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker,which is necessary for normal neural tube closure.We created knock-in(KI)mouse models with human-derived HSPG2 variants,using sperm-like stem cells that had been genetically edited by CRISPR/Cas9.We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos.Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases.Furthermore,we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation.Therefore,autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.展开更多
Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate th...Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches.Recently,mouse haploid embryonic stem(haES)cells have been successfully isolated from parthenogenetic and androgenetic embryos,providing an ideal tool for genetic analyses.In these studies,mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination.In particular,haES cells from androgenetic embryos can be employed as novel,renewable form of fertilization agent for yielding live-born mice via injection into oocytes,thus showing the possibility that genetic analysis can be extended from cellular level to organism level.展开更多
Diploidy is the typical genomic mode in all mammals.Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploi...Diploidy is the typical genomic mode in all mammals.Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic scale.To date,a multitude of haploid stem cell types from mouse,rat,monkey and humans have been derived,as more are in development.They have been applied in high-throughput genetic screens and mammalian assisted reproduction.Here,we review the generation,unique properties and broad applications of these remarkable cells.展开更多
Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrat...Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors(5ARIs)increases the risk of PFS-like adverse effects.A search of studies published until May 10,2020,was performed using PubMed,EMBASE,and the Cochrane Library.We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia(BPH)or androgenetic alopecia(AGA),and identified 34 studies from 28 articles that met our eligibility criteria.In the random-effects model,the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial(95%confidence interval[CI]:1.64-2.14).Regarding specific types of adverse effects,the use of 5ARIs had a 1.89-fold risk of sexual adverse effects(95%CI:1.74-2.05)and was associated with an increased risk of physical adverse effects(relative risk[RR]:1.31,95%CI:0.80-2.15),albeit without statistical significance.This meta-analysis helped to better define the adverse effects caused by 5ARIs.We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment.Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.展开更多
Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-ce...Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration,which include local growth factors,immune and neuroendocrine signals,and dietary and environmental factors.This is better suited for clinical applica-tion in multiple forms of hair disorders:in male pattern hair loss,the stem cells are largely preserved,but androgen signaling diminishes hair growth;in alopecia areata,an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability.Genome-wide association studies further revealed the genetic bases of these disorders,although the precise pathological mechanisms of the identified loci remain largely unknown.By analyzing the dysregulation of hair regeneration under pathological conditions,we can better address the complex interactions among stem cells,the differentiated progeny,and mesenchymal components,and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration.The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.展开更多
基金Supported by Precision Medicine Joint Fund Cultivation project of Hebei Province,No.H2021206253.
文摘BACKGROUND Androgenetic alopecia(AGA)is a common form of hair loss that can be influenced by psychological factors.AIM To investigate the impact of mental stress on neurotrophic factors in patients with AGA and correlate the findings with the progression of AGA.METHODS A total of 120 patients with AGA were analyzed in this study,which were divided into a non-stress group(n=30)and a stress group(n=90)on the basis of the presence or absence of psychological stress confirmed by Depression Anxiety Stress Scale-21 scale.The baseline demographic characteristics,serum cortisol levels,hair growth parameters,neurotrophic factors,and AGA progression scores between the non-stress and stress groups were compared.Correlation analyses were conducted to assess the relationships among stress,neurotrophic factors,hair loss progression,and AGA progression.RESULTS This study revealed significantly higher cortisol levels throughout the day in the stress group than in the non-stress group.The stress group exhibited lower levels of nerve growth factor,brain-derived neurotrophic factor,and glial cell linederived neurotrophic factor and higher expression levels of neurotrophin(NT)-3 and NT-4 than the non-stress group.Hair parameters indicated lower hair diameter,decreased hair density,and more severe AGA grading in the stress group,whereas follicle count and terminal/vellus hair ratio showed no significant differences between the two groups.After 1 year of treatment with 5%minoxidil,efficacy was observed to be lower but AGA progression was notably more pronounced in the stress group than in the non-stress group.Disease progression was positively correlated with high stress and NT-4 levels.CONCLUSION This study provides compelling evidence of the influence of mental stress on neurotrophic factors and its correlation with the progression of AGA.The findings underscore the need for a comprehensive approach to the management of AGA that considers the physiological and psychosocial aspects.Further research is warranted to validate the findings and explore targeted therapeutic interventions for individuals with stress-related AGA.
文摘Objective:To investigate the clinical efficacy and safety of Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam in the treatment of male androgenetic alopecia.Methods:From July 2022 to July 2023,120 male patients with androgenetic alopecia were selected from our Department of Dermatology and randomly divided into Control Group 1,Control Group 2,Observation Group 1,and Observation Group 2,with 30 patients in each group.Control Group 1 was treated with ketoconazole shampoo,Control Group 2 with 5%minoxidil foam,Observation Group 1 with ketoconazole shampoo combined with Chuzhi Shengfa Tablets,and Observation Group 2 with 5%minoxidil foam combined with Chuzhi Shengfa Tablets.Hair density,hair diameter,scalp oil secretion(using oil secretion scoring),and adverse reactions were compared before and after treatment across the four groups.Results:After treatment,hair density and hair diameter significantly increased in all four groups compared to before treatment,while scalp oil secretion scores significantly decreased(P<0.05).The improvements in Observation Groups 1 and 2 were significantly better than those in Control Groups 1 and 2(P<0.05).No significant differences in the incidence of adverse reactions were observed among the four groups(P>0.05).Conclusion:Chuzhi Shengfa Tablets combined with ketoconazole shampoo and Chuzhi Shengfa Tablets combined with 5%minoxidil foam are both effective and safe for treating male androgenetic alopecia.These combinations can significantly improve hair growth and are worthy of clinical promotion.
文摘Objective:To explore the clinical efficacy and safety of Chuzhi Shengfa tablets combined with finasteride in the treatment of male androgenetic alopecia(AGA).Methods:Sixty male patients with androgenetic alopecia admitted to our Department of Dermatology between January 2022 and January 2024 were randomly divided into two groups,with 30 patients in each group.The control group was treated with finasteride,while the observation group received a combination of Chuzhi Shengfa tablets and finasteride.The clinical efficacy and adverse reactions in both groups were compared.Results:The overall effectiveness rate in the observation group was 93.33%(28/30),significantly higher than the control group’s 73.33%(22/30),with a statistically significant difference(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The combination of Chuzhi Shengfa tablets and finasteride shows good clinical efficacy in treating male androgenetic alopecia.Additionally,Chuzhi Shengfa tablets are convenient to administer and effectively improve efficacy,significantly improving patients’conditions,and demonstrating good clinical application value.
文摘Studies have shown that platelet concentrates can induce the proliferation of the dermal papilla and the vascularization of the perifollicular tissue, as well as accelerate the telogen-to-anagen transition, thereby promoting the regrowth of hair improving the appearance of hair loss. Herein, we report on the application of a new, modified form of platelet concentrates, namely, concentrated growth factors (CGFs), in 15 cases of androgenetic alopecia (AGA). 15 cases of androgenetic alopecia were treated with the use of monthly, subcutaneous injections of autologous CGF in the scalp. A total of 3 injections were administered 4 weeks apart, and the patients were followed up for 6 months. Assessments were performed before the treatments and at 4, 8, 12 and 24 weeks after the first treatment. The treatment outcomes were assessed by taking macroscopic photographs and trichoscopic photomicrographs, as well as by using the Global Aesthetic Improvement Scale (GAIS) and the patient satisfaction survey. In order to determine the safety of the treatment, the injection area was observed for signs of infection or mass evaluation. The photographs showed significant improvement in hair appearance after injections of CGF. The hair photomicrographs showed that CGF promoted the regrowth of hair in balding areas, with an increased hair density and an increased ratio of terminal to vellus hair. The GAIS suggested that CGF treatments were effective in treating AGA, and the majority of patients were satisfied with their improvement. In addition, treatments resulted in a faster rate of hair growth and a decrease in the greasy and unpleasant sensation of the hair of the patients. At the last visit, none of the 15 patients reported experiencing side-effects during the follow-up period. To conclude, the application of CGF can be an effective method in the treatment of androgenetic alopecia.
文摘Background: Progressing androgenetic alopecia (AGA), in both sexes, can result in severe distress. Treatments with the capacity to slow down the progression of AGA, or even to bring it to a halt, and at the same time don’t come with side effects are consequently highly sought for. Therefore this study investigates the effect of an over-the-counter nutritional supplement and a similarly formulated topical hair lotion on the progression of AGA. Methods: Seventy-nine healthy study participants of both sexes, who were diagnosed with AGA were divided into 4 study groups. The subjects of the first group were treated with the nutritional supplement, the subjects of the second group with the topical hair lotion, the subjects of the third group with both products, and the subjects of the fourth group served as a no-treatment control. At the beginning and at the end of this nine-month study, the participants were evaluated for their hair loss status. They also answered a questionnaire for self-assessment. A part of the subjects from each study group were further analysed by phototrichography, in order to measure the number of anagen and telogen hairs. Results: It turned out that the supplement, the lotion as well as the treatment with both products not only lead to a reduction in hair loss but also to an increased anagen to telogen hair ratio, whereas no such effects could be measured for the control group. Conclusion: The results show that a systemic delivery via a nutritional supplement, as well as a follicular delivery via a topically applied lotion, both resulted in a reduced hair loss rate as well as in an increased anagen to telogen hair ratio. This demonstrates that the tested formulation is effectively slowing down the progression of AGA.
文摘Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle.
基金supported by Grants from National Natural Science Foundation of China(Grant No.s 31900950 and 32000944)the Project Supported by Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2024JC-YBMS-706)+1 种基金Collaborative Innovation Project of Zigong Medical Big Data and Artificial Intelligence Research Institute(Grant No.2023-YGY-1-02)Key Science and Technology Plan Project of Zigong(Grant No.2022ZCNKY07)。
文摘Androgenetic alopecia(AGA),the most prevalent clinical hair loss,lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients.In this study,a hyaluronic acid(HA)based hydrogel-formed microneedle(MN)was designed,referred to as V-R-MNs,which was simultaneously loaded with vascular endothelial growth factor(VEGF)and the novel hair loss drug Ritlecitinib,the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates(PHAs)nanoparticles(R-PHA NPs)for minimally invasive AGA treatment.The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency.Due to the biosafety,mechanical strength,and controlled degradation properties of HA hydrogel formed microneedles,V-R-MNs can effectively penetrate the skin’s stratum corneum,facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive,painless and long-term sustained release manner.V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells,but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis.In comparison to the clinical drug minoxidil for AGA treatment,the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase,improved hair quality,and greater coverage.This introduces a new,clinically safer,and more efficient strategy for AGA treatment,and serving as a reference for the treatment of other related diseases.
基金financially supported by the National Natural Science Foundation of China(32171369 and 82102113)2023 cross-research project on basal research fund in central universities(21623410)+1 种基金the Jinan University-Honest Medical Joint Innovation Center(HX20220013)the Pre-study on transdermal technology and product development(ZX20220244)。
文摘Androgenetic alopecia(AGA)is a common clinical condition,affecting over 200 million people globally each year.For decades,Minoxidil(Mi)tincture has been the primary treatment for this disease,but its low utilization rate and significant side effects necessitate new therapeutic strategies.Nitric oxide(NO)is a signaling molecule in various physiological processes,including vasodilation,immune responses,and cell proliferation.Herein,we constructed a hyaluronic acid liposome(HL)complex as a novel transdermal delivery system(HL@Mi/NONOate)for NO and Mi,which displayed promising transdermal and hair-regrowth effects.In-depth mechanistic studies revealed three potential pathways of the synergistic AGA therapy.First,NO promoted capillary dilation and accelerated blood flow,thus achieving efficient penetration of Mi.Due to the structural advantage of liposomes,the residence time of the Mi in the skin was prolonged.Moreover,HL@Mi/NONOate promoted cell proliferation and angiogenesis,and upregulated the expression of regulatory factors involved in follicle stem cell differentiation.In the AGA model,HL@Mi/NONOate down-regulated the expression of inflammatory factors,inhibiting the inflammation of follicle and improving the microenvironment of hair regrowth.Concurrently,HL@Mi/NONOate upregulated the expression of Ki67 and PCNA proteins in follicle tissues,inducing follicle regeneration and development,ultimately achieving the synergistic multimodal AGA therapy.
基金supported by the National Key Research and Development Program of China(Nos.2022YFE0126000(Z.T.C.),and 2020YFA0210800(Z.W.C.))the National Natural Science Foundation of China(Nos.22277011(Z.W.C.),and 22107019(Z.W.C.))+1 种基金the Major Project of Science and Technology of Fujian Province(No.2020HZ06006(Z.W.C.))the Guangdong Basic and Applied Basic Research Foundation(No.2022A1515011129((Z.T.C.)).
文摘Androgenetic alopecia(AGA)is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment,leading to cell apoptosis and eventual loss of hair follicles(HFs).Traditional therapeutic formulations,such as Minoxidil(MXD)tincture,have limitations in reshaping the perifollicular microenvironment and exhibit limited effectiveness.Here,we report a multi-synergistic therapeutic platform for high-performance hair regeneration therapy.The platform combines microneedle(MN)patches loaded with MXD-encapsulated nanostructured lipid carriers(MXD-NLC-MNs)and cold atmospheric plasma(CAP).The MNs’mechanical strength enables efficient transdermal delivery of MXD to the targeted dermal papilla cells,promoting cell proliferation.Furthermore,in collaboration with MXD,the mechanical stimulation exerted by MN application synergistically upregulates the expression of vascular endothelial growth factor,leading to neoangiogenesis.Meanwhile,the transient microchannels in the skin created by MNs facilitate the transdermal delivery of CAPgenerated nitric oxide(NO)to the sites of HF lesions,whereby the synergistic interaction between MXD and NO boosts perifollicular vasodilation.Consequently,the perifollicular microenvironment can be effectively reshaped to accelerate hair regeneration in AGA murine models.This multi-synergistic combination therapy strategy would hold great promise for effectively treating AGA and promoting hair regrowth.
基金This study was supported by Genome Tagging Project and grants from the Chinese Academy of Sciences,the National Key Research and Development Program of Chinathe National Natural Science Foundation of China(2019YFA0109900,2020YFA0509000,XDB19010204,QYZDJ-SSW-SMC023,Facility-based Open Research Program,31821004,32030029,and 31730062).
文摘The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,a system enabling long-term maintenance of imprints in ESCs has proven challenging.Here,we report that the use of a two-step a2i(alternative two inhibitors of Src and Gsk3β,TSa2i)derivation/culture protocol results in the establishment of androgenetic haploid ESCs(AG-haESCs)with stable DNA methylation at paternal DMRs(differentially DNA methylated regions)up to passage 60 that can efficiently support generating mice upon oocyte injection.We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations.Furthermore,we demonstrate that TSa2itreated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation.Strikingly,AGhaESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells,in part through the enhanced proliferation of H19-DMR hypermethylated cells.Together,we establish AG-haESCs that can longterm maintain paternal imprints.
基金supported by the grants from the NextGeneration BioGreen 21 Program(Nos.PJ009080 and PJ00909801)Rural Development Administration,Republic of Korea
文摘MicroRNAs(miRNAs) are a class of highly conserved small non-coding RNA molecules that play a pivotal role in several cellular functions.In this study,miRNA and messenger RNA(mRNA) profiles were examined by Illumina microarray in mouse embryonic stem cells(ESCs) derived from parthenogenetic,androgenetic,and fertilized blastocysts.The global analysis of miRNA-mRNA target pairs provided insight into the role of miRNAs in gene expression.Results showed that a total of 125 miRNAs and 2394 mRNAs were differentially expressed between androgenetic ESCs(aESCs) and fertilized ESCs(fESCs),a total of 42 miRNAs and 87 mRNAs were differentially expressed between parthenogenetic ESCs(pESCs) and fESCs,and a total of 99 miRNAs and 1788 mRNAs were differentially expressed between aESCs and pESCs.In addition,a total of 575,5 and 376 miRNA-mRNA target pairs were observed in aESCs vs.fESCs,pESCs vs.fESCs,and aESCs vs.pESCs,respectively.Furthermore,15 known imprinted genes and 16 putative uniparentally expressed miRNAs with high expression levels were confirmed by both microarray and real-time RT-PCR.Finally,transfection of miRNA inhibitors was performed to validate the regulatory relationship between putative maternally expressed miRNAs and target mRNAs. Inhibition of miR-880 increased the expression of Peg3,Dyrklb,and Prrg2 mRNA,inhibition of miR-363 increased the expression of Nfat5 and Soatl mRNA,and inhibition of miR-883b-5p increased Nfat5,Tacstd2,and Ppapdc1 mRNA.These results warrant a functional study to fully understand the underlying regulation of genomic imprinting in early embryo development.
文摘Objective:Androgenetic alopecia (AA) is a progressive hair loss disorder mediated by systemic androgens and genetic factors. A variety of AA treatments have been investigated. Currently, there is emerging evidence and growing interest in the use of platelet-rich plasma (PRP) for AA. This study describes a single-center experience using PRP to treat AA in women.Methods:A retrospective observational study design was employed. The study cohort comprised 20 women >18 years of age who were diagnosed with AA. PRP was prepared using a commercially available PRP kit. Each patient received six PRP treatment sessions at 4-week intervals. The severity of alopecia tool (SALT) scoring system was used to measure the severity of alopecia, and a paired t-test was used to calculate significance levels. Results:The mean pre-intervention and post-intervention total SALT score was 27.5 ± 6.35 and 9.41 ± 3.71, respectively. The difference in the total mean SALT score was 18.33 ± 1.64 and the effect size was 3.52. The scalp area with the largest effect size was the vertex (Cohen d= 2.53). The effect size was similar across other scalp areas (Cohen d= 1.91-2.09). There were no serious adverse effects of the treatment;only mild transient adverse effects were reported. Conclusion:The present study demonstrated the efficacy and safety of PRP injections in treating AA in women. However, these findings require confirmation in well-designed studies using standardized treatment protocols and evaluation methods.
文摘Androgens have an intense consequence on the human scalp and body hair.Scalp hair sprouts fundamentally in awol of androgens whereas the body hair hike is vulnerable to the activity of androgens.Androgenetic alopecia(AGA)invoked as males emulate Alopecia due to the cause of the dynamic reduction of scalp hair.Androgens are medium of terminus growth of hair although the body.Local and system androgens convert the extensive terminal follicles into lesser vellus like structure.The out start of this type of alopecia is intensely irregular and the reason behind this existence of enough circulating steroidal hormones androgens and due to genetic predisposition.Effective treatments are available in the market as well as under clinical and preclinical testing.Many herbal formulations are also available but not FDA approved.Different conventional and NDDS formulations are already available in the market.To avoid various systemic side effects of both Finasteride and Minoxidil,topical formulations and natural products(nutrients,minerals,vitamins)now a days are being widely used to treat Androgenic alopecia.CAM(complementary and alternative medicine)provides the option to elect favorable,low-risk,adjuvant and alternative therapies.Herein,we offer a widespread review of topical marketed formulations,natural products,and CAM treatment options for AGA.
文摘The hair follicle is not only a critical penetration route in percutaneous absorption but also has been recognized to be a target for hair follicle-associated disorders,such as androgenetic alopecia(AGA)and acne vulgaris.Hair follicle-targeting drug delivery systems allow for controlled drug release and enhance therapeutic efficacywithminimal side effects,exerting a promising method for themanagement of hair follicle-associated dysfunctions.Therefore,they have obtained much attention in several fields of research in recent years.This review gives an overviewof potential follicle-targeting drug delivery formulations currently applied based on the particularities of the hair follicles,including a comprehensive assessment of their preclinical and clinical performance.
文摘Chimerism is defined as the presence in a subject of more than one stable and genetically distinct cell line;cases reported so far include both patients with ambiguous genitalia and healthy subjects. The biological mechanisms, which may give origin to chimeras, are complex, and can be understood by analyzing DNA samples of the patients and their parents using molecular techniques. The objective of this study is to identify the mechanism of origin for the 2 cases we report. The first patient is a phenotipically normal girl with normal (external and internal) genitalia;the second patient had ambiguous genitalia and underwent surgery. DNA was purified from blood samples and, limited to Patient 1, from a sample of biliary cyst. Short tandem repeat polymorphisms were analyzed in order to identify the relative parental contribution to the patients. Molecular analyses carried out on the first patient are not fully informative because of two possible explanations (i.e. parthenogenetic and andrognetic chimera), while in the second case the presence of four alleles at some markers allowed us to identify a tetragametic chimera originnated from the fusion of two distinct embryos. Studies carried on one single tissue may not always be conclusive as they do not allow the precise identification of the mechanism of origin. In these cases, studies on more tissues are strongly suggested.
基金supported by the National Key Research and Development Program of China(2021YFC2701100)the National Natural Science Foundation of China(81930036,32293230 and 8215008)+1 种基金the Commission for Science and Technology of Shanghai Municipality(20JC1418500 and 20ZR1404800)Project supported by Shanghai Municipal Science and Technology Major Project。
文摘Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genetic variants of HSPG2 in 10%cases compared to only 4%in controls among a cohort of 369 NTDs.Endorepellin,a peptide cleaved from the domain V of Perlecan,is known to promote angiogenesis and autophagy in endothelial cells.The roles of enderepellin in neurodevelopment remain unclear so far.Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo.Through the endocytic pathway,the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker,which is necessary for normal neural tube closure.We created knock-in(KI)mouse models with human-derived HSPG2 variants,using sperm-like stem cells that had been genetically edited by CRISPR/Cas9.We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos.Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases.Furthermore,we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation.Therefore,autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.
基金supported by grants from the Ministry of Science and Technology of China(No.2009CB941101 to J.L.)the "Strategic Priority Research Program" of the Chinese Academy of Sciences(No.XDA01010403 to J.L.).
文摘Identification of the function of all genes in the mammalian genome is critical in understanding basic mechanisms of biology.However,the diploidy of mammalian somatic cells has greatly hindered efforts to elucidate the gene function in numerous biological processes by mutagenesis-based genetic approaches.Recently,mouse haploid embryonic stem(haES)cells have been successfully isolated from parthenogenetic and androgenetic embryos,providing an ideal tool for genetic analyses.In these studies,mouse haES cells have already shown that they could be used in cell-based forward or reverse genetic screenings and in generating gene-targeting via homologous recombination.In particular,haES cells from androgenetic embryos can be employed as novel,renewable form of fertilization agent for yielding live-born mice via injection into oocytes,thus showing the possibility that genetic analysis can be extended from cellular level to organism level.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA16030400)the National Basic Research Program of China(Grant No.2014CB964800)+2 种基金the National Natural Science Foundation of China(Grant Nos.31621004,31422038)the National Key Research and Development Program(Grant No.2017YFA0103803)CAS Key Projects(Grant No.QYZDY-SSWSMC022,QYZDB-SSW-SMC002).
文摘Diploidy is the typical genomic mode in all mammals.Haploid stem cells are artificial cell lines experimentally derived in vitro in the form of different types of stem cells,which combine the characteristics of haploidy with a broad developmental potential and open the possibility to uncover biological mysteries at a genomic scale.To date,a multitude of haploid stem cell types from mouse,rat,monkey and humans have been derived,as more are in development.They have been applied in high-throughput genetic screens and mammalian assisted reproduction.Here,we review the generation,unique properties and broad applications of these remarkable cells.
基金the National Natural Science Foundation of China for their support in generating this manuscript(No.81770758 to LW).
文摘Postfinasteride syndrome(PFS)is a term coined to characterize a constellation of reported undesirable sexual,physical,and neuropsychiatric side effects.In the present study,we conducted the meta-analysis to demonstrate whether the use of 5α-reductase inhibitors(5ARIs)increases the risk of PFS-like adverse effects.A search of studies published until May 10,2020,was performed using PubMed,EMBASE,and the Cochrane Library.We included randomized controlled trials with at least one comparison between male patients receiving 5ARIs versus placebo for the treatment of benign prostatic hyperplasia(BPH)or androgenetic alopecia(AGA),and identified 34 studies from 28 articles that met our eligibility criteria.In the random-effects model,the overall use of 5ARIs exhibited a 1.87-fold risk of PFS-like adverse effects during the trial(95%confidence interval[CI]:1.64-2.14).Regarding specific types of adverse effects,the use of 5ARIs had a 1.89-fold risk of sexual adverse effects(95%CI:1.74-2.05)and was associated with an increased risk of physical adverse effects(relative risk[RR]:1.31,95%CI:0.80-2.15),albeit without statistical significance.This meta-analysis helped to better define the adverse effects caused by 5ARIs.We concluded that the overall use of 5ARIs significantly increased the risk of PFS-like adverse effects in men with AGA or BPH during treatment.Enhanced awareness of and education on the PFS-like adverse effects are necessary for clinicians.
基金ZY is supported by the National Natural Science Foundation of China(NSFC 31871468)the Shenzhen University Stable Support Program(20200808172413001).
文摘Hair growth and regeneration represents a remarkable example of stem cell function.Recent progress emphasizes the micro-and macro-environment that controls the regeneration process.There is a shift from a stem cell-centered view toward the various layers of regulatory mechanisms that control hair regeneration,which include local growth factors,immune and neuroendocrine signals,and dietary and environmental factors.This is better suited for clinical applica-tion in multiple forms of hair disorders:in male pattern hair loss,the stem cells are largely preserved,but androgen signaling diminishes hair growth;in alopecia areata,an immune attack is targeted toward the growing hair follicle without abrogating its regeneration capability.Genome-wide association studies further revealed the genetic bases of these disorders,although the precise pathological mechanisms of the identified loci remain largely unknown.By analyzing the dysregulation of hair regeneration under pathological conditions,we can better address the complex interactions among stem cells,the differentiated progeny,and mesenchymal components,and highlight the critical role of macroenvironment adjustment that is essential for hair growth and regeneration.The poly-genetic origin of these disorders makes the study of hair regeneration an interesting and challenging field.