Tamarix chinensis Lour. (T. chinensis) is a traditional herb with functions for releasing the exterior to promote the eruption of rashes, among other ailments. However, these function-related pharmacological effects, such as anti-complement, anti-oxidative, and anti-inflammatory, remain unclear. This study aims to reveal the aforementioned effects and the molecular mechanisms of the ethanol extract of T. chinensis (TCE). Our results demonstrated that TCE inhibited classical- and lectin-mediated complement activation, reduced intracellular ROS via NADPH oxidase inhibition, and directly scavenged DPPH radicals and superoxide anions. By using lipopolysaccharide (LPS)-stimulated macrophages, along with LPS-induced acute lung injury (ALI) and endotoxemia mice, the anti-inflammatory activity and the underlying molecular mechanisms of TCE were deeply investigated. In LPS-activated macrophages, it suppressed iNOS, CCL2, IL-6 and IL-1β transcriptionally and translationally. Mechanistically, TCE inhibited NF-κB signaling by blocking IκBα phosphorylation and p65 nuclear translocation, as well as suppresses AP-1 signaling by reducing ERK and JNK phosphorylation. In vivo, TCE lowered serum multiple pro-inflammatory cytokines of endotoxemic mice and alleviated lung injury of ALI mice. Collectively, our results demonstrated that TCE possesses anti-complement and anti-oxidative activities and exerts anti-inflammatory effects through inhibiting NF-κB and AP-1 signaling. These findings provide scientific evidence for supporting the traditional use of T. chinensis.
BACKGROUND:To explore unhealthy diet and lifestyle factors associated with female androgenetic alopecia (FAGA) in a community-based study. METHODS:A total of 3,008 participants were recruited from the Jidong community (Tangshan, Hebei, China). FAGA was assessed by the Savin scale. Data collection was conducted through structured questionnaires. Univariate and multivariate logistic regression analyses were employed to identify potential factors. Multivariable models were built by selecting covariates with P < 0.05 in univariable analyses and removing collinear variables identified by a variance inflation factor > 5. The predictive performance was evaluated using the receiver operating characteristic curve. RESULTS:The prevalence of FAGA in this study was 6.85% (206/3008). Sleep snoring (adjusted odds ratio [AOR] = 1.398, 95% confidence interval [CI] 1.032-1.894, P = 0.031), frequent consumption of bacon and preserved meat (AOR = 2.205, 95% CI 1.181-4.118, P = 0.013), frequently drinking unboiled water (AOR = 1.984, 95% CI 1.156-3.406, P = 0.013), age (AOR = 1.063, 95% CI 1.050-1.076, P < 0.001) and suboptimal health status score (AOR = 1.033, 95% CI 1.020-1.047, P < 0.001) were identified as independent factors associated with FAGA. CONCLUSIONS:In conclusion, our data suggest that females who snore during sleep, frequently consume bacon and preserved meats, and regularly drink unboiled water are more susceptible to androgenetic alopecia. Additionally, our analysis revealed that age and suboptimal health status score are significantly correlated with FAGA.
Strategies aimed at targeting fungal extracellular heat shock protein 90 (eHsp90) using vaccines and antibodies have demonstrated encouraging potential in the prevention and management of invasive fungal diseases (IFDs). However, the precise underlying mechanism by which eHsp90 contributes to the heightened virulence of Candida albicans (C. albicans) remains an enigma, awaiting further elucidation. In our current research, we have found that the 47-kDa fragment of C. albicans Hsp90 (CaHsp90), which serves as the primary antigenic determinant, is not degraded within C. albicans cells. Moreover, we have discovered that extracellular CaHsp90 (eCaHsp90) is derived from the components of lysed C. albicans cells. We also generated recombinant CaHsp90 in Escherichia coli, and found that eCaHsp90 spreads beyond the initial C. albicans colonization site, thereby enhancing the overall virulence of the organism. Our results further clarify that eCaHsp90 activates the nuclear factor kappa-B (NF-κB) signaling pathway and upregulates the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3). This upregulation results in the activation of Gasdermin D (GSDMD) and subsequent macrophage pyroptosis, ultimately increasing the virulence of C. albicans. This study provides valuable insights into the mechanism by which eCaHsp90 contributes to the virulence of C. albicans, offering a pharmacological basis for antifungal strategies targeting fungal eHsp90.
IntroductionCandidiasis, mainly caused by Candida albicans, poses a serious threat to human health. The escalating drug resistance in C. albicans and the limited antifungal options highlight the critical need for novel therapeutic strategies.MethodsWe evaluated 12 machine learning models on a self-constructed dataset with known anti-C. albicans activity. Based on their performance, the optimal model was selected to screen our separate in-house compound library with unknown anti-C. albicans activity for potential antifungal agents. The anti-C. albicans activity of the selected compounds was confirmed through in vitro drug susceptibility assays, hyphal growth assays, and biofilm formation assays. Through transcriptomics, proteomics, iron rescue experiments, CTC staining, JC-1 staining, DAPI staining, molecular docking, and molecular dynamics simulations, we elucidated the mechanism underlying the anti-C. albicans activity of the compound.ResultAmong the evaluated machine learning models, the best predictive model was an ensemble learning model constructed from Random Forests and Categorical Boosting using soft voting. It predicts that Dp44mT exhibits potent anti-C. albicans activity. The in vitro tests further verified this finding that Dp44mT can inhibit planktonic growth, hyphal formation, and biofilm formation of C. albicans. Mechanistically, Dp44mT exerts antifungal activity by disrupting cellular iron homeostasis, leading to a collapse of mitochondrial membrane potential and ultimately causing apoptosis.ConclusionThis study presents a practical approach for predicting the antifungal activity of com-pounds using machine learning models and provides new insights into the development of antifungal compounds by disrupting iron homeostasis in C. albicans.
The regulatory mechanisms by which cholesterol influences hair regeneration remain incompletely understood. This study investigates the effects of cholesterol on hair follicle stem cells (HFSCs) proliferation and hair regeneration, with a focus on the underlying molecular mechanisms. Subcutaneous cholesterol injections in C57BL/6 mice significantly enhanced hair regeneration by promoting HFSCs proliferation. Hematoxylin and eosin (HE) staining revealed a greater number of hair follicles in the anagen phase in the cholesterol-treated group compared to controls. Immunofluorescence (IF) and BrdU labeling further confirmed that cholesterol significantly stimulated HFSCs proliferation. Mechanistically, cholesterol activated the PKA signaling pathway, leading to the phosphorylation of tyrosine hydroxylase (TH) at the serine 40 residue, which subsequently stimulated the sympathetic nervous system (SNS). SNS activation enhanced HFSCs proliferation and increased the proportion of hair follicles in the anagen phase. Furthermore, sympathetic nerve ablation significantly attenuated the hair regeneration-promoting effects of cholesterol, highlighting the critical regulatory role of SNS in this process. These findings provide key insights into the molecular mechanisms by which cholesterol regulates hair regeneration via the PKA-tyrosine hydroxylase-SNS pathway. Moreover, they suggest potential therapeutic applications targeting cholesterol-mediated signaling pathways to promote hair regeneration.
Androgenetic alopecia (AGA) is a common type of hair loss in men and efficacy and safety of current medical treatment remain limited. Therefore, the present study aimed to investigate the efficacy and safety of botulinum toxin type A (BTA) combined with Minoxidil in patients with AGA. 60 male patients were included in this study and control group received topical 5
Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.
Onychomycosis, a fungal nail infection, is primarily caused by dermatophytes, yeasts, and non-dermatophyte moulds (NDMs). The incidence of this disease and the predominance of specific pathogens vary across different regions and evolve. This study aimed to elucidate the epidemiology of onychomycosis and the pattern of causative pathogens in Beijing, and to ascertain the in vitro antifungal susceptibility profiles of Trichophyton rubrum against itraconazole (ITR), terbinafine (TER), and fluconazole (FLU). Involving 245 patients of onychomycosis with positive fungal culture results, the study implemented internal transcribed spacer (ITS) sequencing of ribosomal DNA (rDNA) on all collected samples. The mean age of the participants was 37.93 ± 13.73 years, with a male-to-female ratio of 1.53:1. The prevalence of toenail infections was significantly higher than that of fingernails. Distal and lateral subungual onychomycosis (DLSO) were the most frequent clinical classifications. PCR results indicated that dermatophytes were the most prevalent pathogens, followed by yeasts and NDMs, among which T. rubrum was the most dominant dermatophyte. TER demonstrated high sensitivity to T. rubrum. However, in clinical settings, some patients with onychomycosis exhibit a poor response to TER treatment. The relationship between in vitro antifungal sensitivity and clinical effectiveness is complex, and understanding the link between in vitro MIC values and clinical efficacy requires further investigation.
Vitiligo is the most frequently diagnosed depigmentation disease, affecting nearly 0.5–2
您或许对"红皮病"这个名字很陌生,但提到它的外号——"红人综合征",是不是脑海里就自动有画面了?没错,病如其名!红皮病又称剥脱性皮炎,是一种以全身皮肤潮红、脱屑为特征的严重炎症性皮肤病.其病因较复杂,可继发于其他皮肤病,如皮炎、银屑病、药物反应、恶性肿瘤等原发疾病.红皮病不仅会对患者的容貌造成不良影响,还会影响心理健康,甚至身体健康,下面就带您了解一下红皮病.
Background Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth in vitro and in vivo for potentially treating immune-mediated alopecia and further exploring the underlying mechanism. Methods Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established in vivo; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real‐time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq). Results ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF-α signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/β-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice. Conclusion ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/β-catenin signaling pathway, and the TNF-α signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.
雄激素性脱发是一种常见的慢性进行性脱发疾病.治疗雄激素性脱发的目的在于减少头发脱落,促进头发生长,但目前治疗方法比较有限,常用的非手术疗法包括药物治疗、注射治疗、激光治疗和中医中药等.本文概述了目前非手术疗法治疗雄激素性脱发的研究进展,为雄激素性脱发的治疗提供参考.
Background:Health-related quality of life (HRQoL) of androgenetic alopecia patients has become increasingly important, but the influencing factors associated with the different domains are poorly understood.Objective:This study aimed to investigate the influencing factors in HRQoL of androgenetic alopecia patients and identify its strongly associated domains.Patients and Methods:We enrolled 170 androgenetic alopecia patients. HRQoL was measured using the World Health Organization Quality of Life Brief Version (WHO-BREF), and Hairdex.Results:HRQoL was significantly impaired in patients <30 years, (WHO-BREF: P=0.022, Hairdex: P=0.004), less educated (WHO-BREF: P=0.021, Hairdex: P=0.003), single patients (Hairdex: P=0.023), and urban residence (Hairdex: P=0.043). By domains, those <30 years were impaired by physical health (P=0.038) and psychological (P=0.030) by WHO-BREF, and symptoms (P=0.002) and emotions (P=0.002) by Hairdex. Singles were impaired by symptoms (P=0.020), and emotions (P=0.009) by Hairdex. Less-educated individuals had impaired all domains in the WHO-BREF and Hairdex, except for physical health. Women had impaired symptoms (P=0.013) and stigmatization (P=0.041) in Hairdex.Conclusion:Androgenetic alopecia is associated with significantly reduced HRQoL in young, less educated, and single patients. Dermatologists should inquire about Quality of Life and appropriately support androgenetic alopecia patients.
IntroductionThe stump site of amputees is clinically vulnerable and prone to various skin diseases. Data regarding the impact on quality of life (QoL) of amputees with amputation stump skin disease (ASSD) and risk factors of ASSD and stump fungal infection in the Shanghai area are yet unknown.ObjectiveThis study aims to evaluate the QoL of amputees with ASSD and explore the risk factors of ASSD and stump fungal infection in the Shanghai area.MethodologyA total of 104 amputees from Shanghai Hebin Rehabilitation Hospital, Otto Bock (China) Industries Co., Ltd., Shanghai Tongji Hospital, and Shanghai Rehabilitation and Vocational Training Center for the Disabled were enrolled in this study. We collected demographic, clinical, and skin fungal examination data from these amputees from April 2015 to May 2021. Dermatology life quality index (DLQI) questionnaire was used to evaluate the QoL. The risk factors for ASSD and fungal skin infection were analyzed by the univariate analyses.ResultsThe median age of the 104 amputees was 57.9 ± 11.9 years with an average amputation time of 17.7 ± 15.1 years, and 73% of cases were men. The mean DLQI score of amputees with ASSD was13.6, suggesting the severe impairment of QoL. Among amputees, 41 (39.4%) had confirmed ASSD, of whom 24 (58.5%) suffered from fungal skin infection and the remaining were subjected to intertriginous dermatitis and eczema (22%), cutaneous keratosis (12.2%), and others (7.3%). Aspergillus (50.0%) was the most common species. The other fungal organisms included Trichophyton rubrum (33.3%), Candida krusei (8.3%), T. mentagrophytes (4.2%), and C. albicans (4.2%). ASSD rather than non-ASSD was more common in men (80.4%) and summer (46.3%). Summer (OR = 3.31, 95% CI = 1.19–9.17) was an established risk factor for ASSD compared to spring. The daily artificial limb wearing time > 8 h was associated with stump fungal infection.ConclusionThe QoL of amputees with ASSD was severely affected and the ASSD was characterized by fungal infection (tinea), intertriginous dermatitis, eczema, and skin keratosis. Summer and daily prosthesis wearing > 8 h was a risk factor for ASSD. Aspergillus was the most common fungal species, especially when the stump was exposed in summer.
目的 通过观察大黄灵仙方调控TLR4/NF-κB/MAPK信号通路相关因子基因及蛋白的影响,探讨其对胆管细胞炎性反应的作用.方法 采用大鼠胆总管注射脂多糖(lipopolysaccharide,LPS)构建原发性胆管结石胆管慢性炎症状态,取大鼠肝内胆管内皮细胞,通过qPCR技术同时结合使用信号通路阻断剂,观察胆管细胞炎性状态下TLR4/NF-κB/MAPK信号通路相关因子基因及蛋白影响变化及大黄灵仙方的干预作用.结果 ①Myd88、p-p38、TLR4、NF-κB mRNA变化情况:与空白组比较,L组、L+P组、L+S组、L+P+S组的各指标,均增加明显,剩余各组则降低明显,差异均具统计学意义(P<0.05).与L组比较,L+P组、L+S组、L+P+S组的各指标有所降低,但差异无统计学意义(P>0.05),L+T组、L+P+T组、L+S+T组、L+P+S+T组则降低明显,差异均具统计学意义(P<0.05);与L+T组比较,L+P+T组、L+S+T组、L+P+S+T组的各指标有所降低,差异无统计学意义(P>0.05).②Myd88、p-p38、TLR4、NF-κB蛋白变化情况:变化趋势与mRNA相同.结论 大黄灵仙方可有效逆转胆管细胞炎性反应过程中存在的TLR4/NF-κB/MAPK信号通路相关因子及蛋白表达异常现象,其机制可能与NF-κB、MAPK信号阻断有关.
X线胸片报告的自动生成是计算机辅助诊断研究的热点,X线胸片中65%以上的疾病与肺部相关.针对肺部描述中文报告生成,提出基于语义标签的层级长短期记忆网络模型.首先,分析异常胸片报告,提取高频关键词作为图像语义标签.再加入异常二分类模块,用于修正语义标签分类结果.最后,融合语义标签与图像特征,加强二者的关联映射.实验表明,文中模型在通用和领域指标的评价上均较优,能有效提高胸片报告生成的性能.
Androgenetic alopecia is a patterned hair loss disorder affecting approximately 73% of men and 57% of women in their lifetime, this affection can cause psychological effects like low self-stem and depression diminishing the quality of life. Currently, finasteride and minoxidil are the only two drugs approved by the food and drug administration (FDA), and devices of low-level laser therapy are FDA cleared. Alternative therapies for androgenetic alopecia treatment include a drug like dutasteride, botulinum toxin A, cell-based therapies like adipose-derived stem cell-conditioned medium and platelet-rich plasma protocols. A combination of two or more therapies can be found in the literature, the general consent indicates that any combination has higher efficiency than a single therapy. Finasteride is in less use due to the related sexual side effects, some adjuvant techniques have emerged to improve the delivery and effectiveness of minoxidil, i.e. micro needling. The surgical approach is mainly focused on hair transplant surgery, which offers relatively less invasive procedures and is a more suitable option for long time results, however, it is expensive. Recently, drug-assisted delivery techniques have emerged to improve the efficiency of conventional drugs; transdermal drug delivery through ultrasound pressure waves means creating diffusion channels, increasing skin permeability and stimulating cell differentiation and growth factor utilization along with minoxidil absorption. Another approach for drug-assisted delivery is the embodiment of finasteride in polymer-based microspheres aiming for a sustained and controlled delivery, which can be beneficial to reduce the regular doses decreasing adverse effects.
目的 通过观察大黄灵仙方调控NF-κB信号通路相关因子基因的影响,探讨其对胆管细胞炎性反应.方法 采用大鼠胆总管注射LPS构建原发性胆管结石胆管慢性炎症状态,取大鼠肝内胆管内皮细胞,通过CCK-8检测胆管细胞增殖、qPCR技术同时结合使用信号通路阻断剂,观察胆管细胞炎性状态下NF-κB信号通路相关因子基因影响变化,及大黄灵仙方的干预作用.结果 以LPS浓度差异对于胆管细胞进行炎性致敏,后检测细胞增殖效率,结果发现:观察D组的增值率最高,达95%.与空白组比较,LPS对照组、LPS+ PDTC组、LPS+ SB203580组、LPS+ PTDC+ SB203580组的Myd88、TRAF6、TAK1、IKKa、NF-κBmRNA表达,均增加明显,LPS+中药组、LPS+ PDTC+中药组、LPS+ SB203580+中药组、LPS+ PTDC+SB203580+中药组,则降低明显,差异均具统计学意义(P<0.05);与LPS对照组比较,LPS+ PDTC组、LPS+ SB203580组、LPS+PTDC+ SB203580组的Myd88、TRAF6、TAK1、IKKa、NF-κBmRNA表达,有所降低,但无明显差异(P>0.05),LPS+中药组、LPS+ PDTC+中药组、LPS+SB203580+中药组、LPS+PTDC+ SB203580+中药组,则降低明显,差异均具统计学意义(P<0.05);与LPS+中药组比较,LPS+ PDTC+中药组、LPS+ SB203580+中药组、LPS+PTDC+ SB203580+中药组的Myd88、TRAF6、TAK1、IKKa、NF-κBmRNA表达,有所降低,但无明显差异(P>0.05).结论 1mg/ml是大黄灵仙方进行胆管细胞炎性实验的较佳浓度,胆管细胞炎性反应过程中存在NF-κB信号通路相关因子表达异常,NF-κB、MAPK信号阻断剂可延缓NF-κB信号通路相关因子表达,大黄灵仙方可调控NF-κB信号通路相关因子基因.
目的:观察银棱十味散直肠栓剂治疗IIIA型前列腺炎患者的临床疗效.方法:对IIIA型前列腺炎患者90例进行随机分组,分为对照组和观察组各45例.对照组采用邦列安治疗;观察组采用银棱十味散直肠栓剂治疗.观察两组治疗前后前列腺液常规、慢性前列腺炎症状指数(NIH-CPSI)评分及不良反应.结果:两组前列腺常规中的白细胞计数与治疗前比较均有所减少,卵磷脂小体均较治疗前有所增加,但观察组比对照组改善情况较好(P<0.05).两组的NIH-CPSI评分与治疗前相比均有所下降,观察组治疗后的NIH-CPSI评分下降幅度大于对照组(P<0.05).观察组的总有效率为75.86%,优于对照组的66.67%(P<0.05).结论:银棱十味散直肠栓剂治疗IIIA型前列腺炎疗效较好,无明显不良反应,值得临床推广应用.
探讨PBL-LBL双轨模式教学法在壮医学专业课堂教学中的应用,比较PBL-LBL双轨模式、PBL教学模式、LBL教学模式的特点,通过问卷调查评价教学效果.结果显示,PBL-LBL双轨模式教学法在课堂民主性、教学启发性、学习合作性方面均优于PBL、LBL,学生满意度较高.PBL-LBL双轨模式教学法在壮医学专业课堂教学中提高了教学质量,值得推广.