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Recent studies have found that the mechanistic target of rapamycin (mTOR) signaling pathway affects the growth and development of hair follicles, and is closely related to hair growth cycle. This review summarizes the effect of mTOR signaling pathway on the hair growth cycle, and provides new ideas for the treatment of hair diseases.
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A 65-year-old male patient, who had a history of chronic lymphocytic leukemia for 3 years, presented with erythematous swelling of the right cheek for 20 days and scattered papules on the back and upper extremities for 10 days. Twenty days prior to the presentation, the patient was hospitalized for disseminated herpes zoster. Skin examination showed diffuse dark red swollen plaques in the facial area under the right eyelid as well as on the right auricle and external acoustic meatus, with a sense of infiltration on palpation; scattered brown crusts were left behind at the sites of healed herpes zoster lesions, and scattered depressed scars were observed among these crusts; scattered infiltrative, mung bean- to soybean-sized, light red papules with a smooth surface were seen on the back of the neck, back and upper limbs. Histopathological examination of the facial skin lesions revealed nodular infiltration of epithelioid cells, lymphocytes and many multinucleated giant cells in the dermis and subcutaneous adipose tissue; immunohistochemical staining showed positive staining for CD68, CD20, CD79a, CD3, CD2, CD10, CD5 and Bcl-2, scattered positive staining for Ki-67, and negative staining for CD23, cyclin D1, Bcl-6, multiple myeloma oncogene 1, CD21, CD35 and myeloperoxidase. The patient was diagnosed with Wolf′s isotopic response manifesting as granulomatous inflammation after disseminated herpes zoster. The patient was treated with intravenous drips of methylprednisolone at a dose of 40 mg/d, and the skin lesions were gradually improved and subsided. No recurrence was observed during 4 years of follow-up.
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Objective:To investigate the relationship of antinuclear antibody (ANA) status with clinical features and malignancy risk in adult patients with dermatomyositis.Methods:A retrospective analysis was performed to analyze clinical data from 101 inpatients with dermatomyositis in Department of Dermatology, the First Affiliated Hospital of Soochow University from April 2008 to April 2018. These patients were divided into ANA-positive group and ANA-negative group, and differences in myopathy and malignancy risks as well as other clinical features were analyzed between the 2 groups. A 2-year follow-up was undertaken among 92 patients. Chi-square test was used to analyze and compare clinical features between the 2 groups, and a multivariate regression model was used to analyze the relationship of ANA status with amyopathic dermatomyositis and malignancies.Results:Among the 101 patients with dermatomyositis, there were 42 males and 59 females, aged 55.13 ± 14.63 years; 14 patients had amyopathic dermatomyositis, 6 patients had hypomyopathic dermatomyositis, and 81 patients had myopathic dermatomyositis; 42 (41.58%) cases were positive for ANA, and 59 (58.41%) were negative for ANA. Compared with the ANA-negative group, the ANA-positive group showed significantly decreased incidence of cervical erythema (33.33% vs. 59.32%, P=0.010) and shawl sign (14.28% vs. 35.59%, P=0.017) . Twenty-eight (27.72%) patients with dermatomyositis were complicated by malignancies. Malignancies were found in 5 (11.9%) of ANA-positive patients, and in 23 (38.98%) of ANA-negative patients. Univariate analysis showed that ANA-negative patients with dermatomyositis had a higher risk of malignancies compared with ANA-positive patients with dermatomyositis, with an odds ratio of 7.52 (95% CI: 1.62-13.78, P=0.003) . In the multivariate regression model, the absence of ANA ( OR=4.34, 95% CI: 1.37-13.72, P=0.012) and cervical erythema ( OR=3.27, 95% CI: 1.20-8.91, P=0.020) were associated with high incidence of malignancies, while the absence of ANA was not significantly correlated with the occurrence of amyopathic dermatomyositis ( OR=0.99, 95% CI: 0.32-2.99, P=0.980) . Conclusions:ANA-negative adult dermatomyositis patients with cervical erythema had an increased risk of malignancies. Thus, close follow-up and regular tumor screening are necessary in these patients.
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Objective To evaluate effects of angiogenin on the expression of type Ⅰ collagen and fibronectin in dermal papilla cells from androgenetic alopecia areas,and to explore its possible mechanisms.Methods Dermal papilla cells were isolated from androgenetic alopecia areas and cultured.Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of androgen receptor in dermal papilla cells of different passages,and cell counting kit-8 (CCK-8) assay to evaluate the effect of angiogenin at different concentrations of 0,10,20,40,80,160 μg/L on the proliferative activity of the dermal papilla cells cultured in a medium with or without 0.1 nmol/L dihydrotestosterone.The confluent first-passage dermal papilla cells were divided into 3 groups:control group receiving no treatment,dihydrotestosterone group treated with 0.1 nmol/L dihydrotestosterone,and dihydrotestosterone + angiogenin group treated with 0.1 nmol/L dihydrotestosterone and 80 μg/L angiogenin.After 48-hour treatment,realtime fluorescence-based quantitative PCR was conducted to measure the mRNA expression of type Ⅰ collagen gene,fibronectin and transforming growth factor-β1 (TGF-β1),and Western blot analysis to determine the protein expression of type Ⅰ collagen,fibronectin,TGF-β1,phosphorylated Smad2 (p-Smad2) and p-Smad3.Statistical analysis was done by one-way analysis of variance (ANOVA),least significant difference (LSD)-t test and t test for two independent samples.Results The mRNA expression of androgen receptor significantly decreased during the subcultivation of in vitro cultured dermal papilla cells from androgenetic alopecia areas (P ＜ 0.05).Cell proliferation assay showed that 20-160 μg/L angiogenin could evidently antagonize the inhibitory effect of 0.1 nmol/L dihydrotestosterone on the proliferation of dermal papilla cells (all P ＜ 0.05).Compared with the control group,the dihydrotestosterone group showed significantly higher mRNA expression of type Ⅰ collagen gene,fibronectin and TGF-β1.However,the mRNA expression of type Ⅰ collagen gene,fibronectin and TGF-β1 was significantly lower in the dihydrotestosterone + angiogenin group than in the dihydrotestosterone group (type Ⅰ collagen gene:1.563 ± 0.143 vs.4.329 ± 0.165;fibronectin:1.290 ± 0.063 vs.2.156 ± 0.115;TGF-β1:1.136 ± 0.098 vs.1.707 ± 0.100;all P ＜ 0.05).Moreover,angiogenin could obviously suppress the expression of type Ⅰ collagen,fibronectin,TGF-β1,p-Smad2 and p-Smad3 protein by dihydrotestosterone-induced dermal papilla cells (all P ＜ 0.05).Conclusion Angiogenin can inhibit the expression of type Ⅰ collagen and fibronectin in dermal papilla cells from androgenetic alopecia areas in vitro,which may be associated with the downregulated expression of TGF-β1 and inhibition of TGF-β1/Smad signaling pathway.
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Objective Psoriasis vulgaris (PV) is easy to prone to recur and hard to cure and little research has been done on combined treatment on PV.The article was to study the clinical effects of total glucosides of paeony capsules (TGP) combined with acitretin and compound flumethasone on PV as well as the peripheral blood cytokine levels.Methods 126 patients with PV who visited our hospital from October 2015 to January 2017 were randomly divided into combined treatment group (63 cases) and control group (63 cases).Both groups were treated with oral acitretin and topical compound flumethasone, what's more, the compound flumethasone group received oral TGP treatment, 8 weeks for a course.The clinical therapeutic effects were evaluated by the levels of peripheral blood IL-17, IL-18, IL-23, TNF-α level, PASI score and percentage of total skin lesions before and after the treatment.Results After the treatment, the concentration of IL-17, IL-18, IL-23 significantly decreased(P<0.05), which was significantly less in combined treatment group compared with control group (IL-17 [61.18±8.91] vs [78.64±7.85], IL-18 [68.56±17.95] vs [79.49±18.64], IL-23 [70.13±12.16] vs [91.18±16.89] pg/ML)(P<0.05).Moreover, the TNF-α level, the PASI score and the percentage of total skin lesions significantly decreased in both groups after treatment(P<0.05), which was significantly less in combined treatment group compared with control group (TNF-α level [14.47±7.53] vs [23.49±8.12]ng/L, PASI score [4.09±1.29] vs [7.29±5.13], the percentage of total skin lesions [6.17±4.59]% vs [8.09±5.18]%) (P<0.05).Conclusion TGP combined with acitretin and compound flumethasone can significantly enhance the clinical therapeutic effects and effectively regulate the levels of the IL-17, IL-18, IL-23 and TNF-α level, which results in treating psoriasis vulgaris.
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Objective To investigate the expression of angiogenin in human hair follicle and evaluate its effect on hair growth. Methods Intact anagen hair follicles were isolated from human occipital scalp ob- tained from brain surgery. Some isolated human hair follicles were directly subjected to RT-PCR and im- munohistochcmical method for the detection of the mRNA expression and protein distribution of angiogenin in, respectively; some were cultured and incubated with angiogenin (0-200 ng/mL), and the measurement of hair follicle length was performed before and after 6-day culture. Human dermal papilla cells were isolated from the remaining hair follicles, cultured, and treated with angiogenin ranging from 0 to 200 ng/mL for 48 hours, then, MTT assay was used to detect the cell proliferation, and flow cytometry to analyze the cell cy- cle. Results RT-PCR showed the mRNA expression of angiogenin in human hair follicles, and angiogenin protein was observed with immunohistochemistry at the hair papilla and dermal sheath. The angiogenin (25-200 ng/mL) stimulated the growth of human hair follicles in a dose-dependent manner in vitro (P < 0.05 ). Also, as flow eytometry revealed, the treatment with 12.5-200 ng/mL of angiogenin significantly pro- moted the proliferation of human dermal papilla cells (P<0.05), and increased the percentage of cells in S phase as well as cell proliferation index (both P<0.05). Conclusion Angiogenin may be a novel stimulus for hair growth.
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Objective To investigate the feasibility of transient transfection of human VEGF165 gene into HaCaT cells and the effects of supernatant from transfected cell culture on pig hair follicles in vitro. Methods PIRES2-EGFP-VEGF165 was transiently transfected into HaCaT cells with lipofectamine?2000. Expression of EGFP( enhanced green fluorescence protein, EGFP) was observed by laser confocal microscopy. VEGF in the supernatant was detected by ELISA. Further,the supernatant was added to pig hair follicles cultured in vitro. The growth and morphologic changes of hair follicles were measured. Results PIRES2-EGFP?VEGF165 was successfully transfected into HaCaT cells, which confirmed by laser confocal microscopy and ELISA. Moreover, the supernatant of HaCaT cells transfected with PIRES2-EGFP-VEGF165 could accelerate the growth of pig hair follicles and prolong their anagen phase. Conclusion PIRES2-EGFP-VEGF165 could be successfully transiently transfected into HaCaT cells, and expressed VEGF could upregulate the growth of pig hair follicles in vitro.