The relationship between apoptosis and aging

Apoptosis is involved in aging and age-related disease, with respect to aging, apoptosis acting in a celltype-specific manner. The rate of apoptosis is elevated in-most types of aging cell populations and organs. In stable cells and certain continuously dividing cells, apoptosisserves to eliminate presumably dysfunctional cellsthat show homeostatic failure due to oxidative stress, glycation, and DNA damage, thereby maintaining homeostasis in the body. What’smore, apoptosis, at least in part, plays some important role inthe regulation of aging process and anti-tumorigenesis in mammals. Age-enhanced apoptosis may be aninnateprotective mechanism against age-associated tumorigenesis. There is clear evidence to indicate that senescentcells are remarkably resistant to apoptosis. The intensity of global apoptosis and autophagy clearance significantly declines in humans during aging, as aging repress the apoptotic response. In this paper, we will review the relationship between apoptosis and aging, and outline how are they interact each other.

Chinese herbal medicine Yougui Pill reduces exogenous glucocorticoid-induced apoptosis in anterior pituitary cells

Long-term glucocorticoid use may result in sustained suppression of one or more secreted components from the hypothalamo-pituitary-adrenal axis, and often results in apoptosis. Yougui Pill（YGP）, a 10-component traditional Chinese herbal medicine, has been shown to be clinically effective for glucocorticoid-induced suppression of the hypothalamo-pituitary-adrenal axis. However, the pharmacological and molecular mechanisms remain unclear. We hypothesized that YGP would exert an anti-apoptosis effect on dexamethasone-treated anterior pituitary cells. In vivo experiments showed that YGP significantly reduced the number of apoptotic cells, down-regulated m RNA expression of cytochrome c, caspase-3, and caspase-9, and up-regulated m RNA expression of Bcl-2. These findings suggest that YGP reduced glucocorticoid-induced apoptosis in rat anterior pituitary cells by regulating the mitochondria-mediated apoptosis pathway.

Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis

Background: As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis. Methods: WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (w = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline;w = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-10, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6g were investigated by immunohistochemistry (IHC). Results: Acanthosis (98.46±14.12 vs. 222.68土71.10μm, P<0.01) and dermal cell infiltration (572.25±47.45 vs. 762.47土 59.59cells/field, P< 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83±5112.09 vs. 4093.19±2591.88 pirn2, P< 0.01) and scales (100,935.24 ±41,167.77 vs. 41,604.41 ± 14,184.10 μm, P<0.01) as compared with WT mice. In skin lesions ot IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased. Conclusions: IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.

T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes

Background： Atopic dermatitis （AD） is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 （Th 1/Th2） cytokine expression.Filaggrin （FLG） is the key protein to maintaining skin barrier function.Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes.However, the role ofThl/Th2 cytokines on FLG processing is not substantially documented.Our aim was to investigate the impact ofThl/Th2 cytokines on FLG processing.Methods： HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin （IL）-4, 13 or interferon-γ（IFN-γ）.FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor （LEKTI） were measured by both real-time quantitative polymerase chain reaction and Western blotting.Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry.Results： IL-4/13 significantly reduced, while IFN-γsignificantly up-regulated FLG expression.IL-4/13 significantly increased, whereas IFN-γsignificantly decreased the expression ofkallikreins 5 and 7, matriptase and channel-activating serine protease 1.On the contrary, IL-4/13 significantly decreased, while IFN-γincreased the expression of LEKTI and caspase-14.Similar trends were observed in AD lesions.Conclusions： Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes.The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.

High Staphylococcus epidermidis Colonization and Impaired Permeability Barrier in Facial Seborrheic Dermatitis

Background：Seborrheic dermatitis （SD） is a common inflammatory skin condition.The etiology is unclear,although overgrowth of Malassezia on the skin has been suggested to cause SD.This study investigated whether colonization with Staphylococcus plays a role in facial SD,which was not well addressed previously.Methods：The study was conducted from September 1,2011 to February 20,2012 in the First Hospital of China Medical University.In the first phase,the study evaluated the level of transepidennal water loss （TEWL） and the number of colony-forming units （CFU） of Staphylococcus in defined skin areas of SD patients who were human immunodeficiency virus （HIV） seropositive （HIV [＋] SD [＋] group,n =13）,classical SD （HIV [-] SD [＋] group,n =24） patients,H IV seropositive-non-SD （HIV [＋] SD [-] group,n =16） patients,and healthy volunteers （HIV [-] SD [-] group,n 16）.In the second phase,we enrolled another cohort of HIV （-） SD （＋） patients who applied topical fusidic acid （n =15）,tacrolimus （n =16）,or moisturizer （n =12）.Changes in the Seborrheic Dermatitis Area Severity Index （SDASI）,TEWL,and Staphylococcus density were evaluated 2 weeks later.Comparisons of each index were performed using analysis of variance （ANOVA） and least significant difference method.Results：The level of TEWL was greater through lesional sites in the HIV （＋） SD （＋） group than that in HIV （＋） SD （-） and HIV （） SD （-） groups （95% confidence interval [CI]：18.873-47.071,P 〈 0.001 and 95% CI：28.755-55.936,P 〈 0.001,respectively）.The number of CFU of Staphylococcus was greater in the HIV （＋） SD （＋） group than that in HIV （＋） SD （-） and HIV （-） SD （-） groups （95% CI：37.487-142.744,P =0.001 and 95% CI：54.936-156.400,P 〈 0.001,respectively）.TEWL was significantly more improved in patients treated with tacrolimus and fusidic acid than that in those treated with moisturizers （95% CI：7.560 38.987,P =0.004 and 95% CI：4.659-37.619,P =0.01 1,respectively）.Topical tacrolimus and fusidic acid were significantly associated with decreased SDASI as compared with moisturizer （95% CI：0.03-0.432,P =0.025 and 95% CI：0.033 0.44,P =0.024,respectively）.Conclusions：High colonization with Staphylococcus epidermidis,along with impaired skin permeability barrier function,contributes to the occurrence of SD.

Combination therapy with topical minoxidil and nano-microneedle-assisted fibroblast growth factor for male androgenetic alopecia:a randomized controlled trial in Chinese patients

To the Editor:Male androgenic alopecia(MAA)is the most common hair loss disorder characterized by miniaturization of hair follicles and progressive hair loss.[1]Although oral drugs,topical agents,and laser therapy can promote hair growth,minoxidil is the only topical therapy approved by the United States Food and Drug Administration.Fibroblast growth factors(FGFs)have a wide range of biological functions.The basic FGF(bFGF)promotes the growth of the hair follicle in mice,indicating its potential as a therapeutic agent for MAA.[2]The nano-microneedle is a new device that can promote transdermal absorption of topical drugs,[3]and increase drug penetration by up to 10 or 20 times.In this study,we compared the safety and efficacy of topical minoxidil,nano-microneedle-assisted FGF,and a combination of the two.

Proteomic Analysis of the Serum of Patients with Stable Vitiligo and Progressive Vitiligo

To the Editor： Vitiligo is not a fatal disease; however, it can have strong social and psychological impacts on the patients. Genetic susceptibility, autoimmunity, neural dysregulation, melanin self-destruction, and oxidative stress may be involved in the pathogenesis of vitiligo.

Metastatic melanoma misdiagnosed as lipoma manifesting as a subcutaneous soft-tissue mass

To the Editor:Metastatic melanoma is a fatal disease with rapid systemic dissemination and a 5-year survival rate of about 1 7%.[1] More than half of primary metastases involve the skin as nodal,subcutaneous,or distant metastasis.[2] Cutaneous metastases of melanoma occur relatively frequently and can arise in early-or late-stage disease,with a variable clinical appearance and pattern distribution.[3] We describe herein a patient with a large subcutaneous nodule on the arm that we initially diagnosed as a lipoma.After obtaining further clinical history and reviewing the pathologic findings after excision,the nodule was determined to represent metastatic melanoma.

DnaJA4 is involved in responses to hyperthermia by regulating the expression of F-actin in HaCaT cells

Background:Hyperthermia in combination with DnaJA4-knockout(KO)obviously affects the anti-viral immunity of HaCaT cells.The mechanisms of this process are not yet fully explored.However,it is known that DnaJA4 interacts with actin cytoskeleton after hyperthermia.Our aim was to investigate the effects of DnaJA4 on F-actin in HaCaT cells following hyperthermia.Methods:Wild-type(WT)and DnaJA4-KO HaCaT cells were isolated at either 37°C(unheated)or 44°C(hyperthermia)for 30 min followed by testing under conditions of 37°C and assessing at 6,12,and 24 h after hyperthermia.The cytoskeleton was observed with immunofluorescence.Flow cytometry and Western blotting were used to detect the expression of F-actin and relevant pathway protein.Results:DnaJA4-KO and hyperthermia changed the cytoskeleton morphology of HaCaT cells.F-actin expression levels were elevated in DnaJA4-KO cells compared with WT cells(6364.33±989.10 vs.4272.67±918.50,P<0.05).In response to hyperthermia,F-actin expression levels of both WT and DnaJA4-KO cells showed a tendency to decrease followed by an obvious recovery after hyperthermia(WT cells:unheated vs.6 h after hyperthermia or 24 h after hyperthermia:0.34±0.02 vs.0.24±0.01,0.31±0.01,P<0.001,P<0.05;DnaJA4-KO cells:unheated vs.6 h after hyperthermia or 24 h after hyperthermia:0.44±0.01 vs.0.30±0.01,0.51±0.02,P<0.001,P<0.01).WT cells restored to baseline levels observed in the unheated condition,while DnaJA4-KO cells exceeded baseline levels in the recovery.As the upstream factors of F-actin,a similar profile in rho-associated serine/threonine kinase 1(ROCK 1)and RhoA expressions was observed after hyperthermia.While E-cadherin expression was decreased in response to hyperthermia,it was increased in DnaJA4-KO cells compared with WT cells.Conclusions:Hyperthermia affects the expression levels of F-actin in HaCaT cells.DnaJA4 knockout increases the expression of F-actin in HaCaT cells after hyperthermia.DnaJA4 regulates the expressions of F-actin and the related pathway proteins in response to hyperthermia in HaCaT cells.