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Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.

Atopic dermatitis (AD) is a recurrent allergic skin disease caused by genetic and environmental factors. Patients with AD may experience immune imbalance, increased levels of mast cells, immunoglobulin (Ig) E and pro-inflammatory factors (Cyclooxygenase, COX-2 and inducible NO synthase, iNOS). While spilanthol (SP) has anti-inflammatory and analgesic activities, its effect on AD remains to be explored. To develop a new means of SP, inflammation-related symptoms of AD were alleviated, and 2,4-dinitrochlorobenzene (DNCB) was used to induce AD-like skin lesions in BALB/c mice. Histopathological analysis was used to examine mast cells and eosinophils infiltration in AD-like skin lesions. The levels of IgE, IgG1 and IgG2a were measured by enzyme-linked immunosorbent assay (ELISA) kits. Western blot was used for analysis of the mitogen-activated protein kinase (MAPK) pathways and COX-2 and iNOS protein expression. Topical SP treatment reduced serum IgE and IgG2a levels and suppressed COX-2 and iNOS expression via blocked mitogen-activated protein kinase (MAPK) pathways in DNCB-induced AD-like lesions. Histopathological examination revealed that SP reduced epidermal thickness and collagen accumulation and inhibited mast cells and eosinophils infiltration into the AD-like lesions skin. These results indicate that SP may protect against AD skin lesions through inhibited MAPK signaling pathways and may diminish the infiltration of inflammatory cells to block allergic inflammation.

The skin provides protection against environmental stress. However, intrinsic and extrinsic aging causes significant alteration to skin structure and components, which subsequently impairs molecular characteristics and biochemical processes. Here, we have conducted an immunohistological investigation and established the proteome profiles on nude mice skin to verify the specific responses during aging caused by different factors. Our results showed that UVB-elicited aging results in upregulation of proliferating cell nuclear antigen and strong oxidative damage in DNA, whereas chronological aging abolished epidermal cell growth and increased the expression of caspase-14, as well as protein carbonylation. Network analysis indicated that the programmed skin aging activated the ubiquitin system and triggered obvious downregulation of 14-3-3 sigma, which might accelerate the loss of cell growth capacity. On the other hand, UVB stimulation enhanced inflammation and the risk of skin carcinogenesis. Collectively, functional proteomics could provide large-scale investigation of the potent proteins and molecules that play important roles in skin subjected to both intrinsic and extrinsic aging.

Cervix cancer is the second most common cancer among women worldwide, whereas paclitaxel, the first line chemotherapeutic drug used to treat cervical cancer, shows low chemosensitivity on the advanced cervical cancer cell line. Tanshinone IIA (Tan IIA) exhibited strong growth inhibitory effect on CaSki cells (IC50 = 5.51 μM) through promoting caspase cascades with concomitant upregulating the phosphorylation of p38 and JNK signaling. Comprehensive proteomics revealed the global protein changes and the network analysis implied that Tan IIA treatment would activate ER stress pathways that finally lead to apoptotic cell death. Moreover, ER stress inhibitor could alleviate Tan IIA caused cell growth inhibition and ameliorate C/EBP-homologous protein as well as apoptosis signal-regulating kinase 1 mediated cell death. The therapeutic interventions targeting the mitochondrial-related apoptosis and ER stress responses might be promising strategies to conquer paclitaxel resistance.

Background Today, various heavy metals are widespread in the ecosystem and have become important environmental contaminants. Exposure to these hazardous metals such as chromium usually results in cytotoxicity and large-scale protein changes which reflect pathologic states. Methods We used a comprehensive proteomic tool to survey changes in plasma proteins elicited by two chromium species (Cr6 + and Cr3 +). RT-PCR was applied to evaluate levels of cytokines associated with adverse responses. Lectin blotting was used to investigate the contents of fucosylated proteins. Results Protein profiles revealed statistically significant changes in the intensity of 12 proteins. The network analysis implied that Cr6 + application strongly induced the IL-6-stimulated inflammatory pathway. mRNA levels of specific cytokines were also correlated with inflammatory events. Increased IL-6 modulation of the fucosylation of haptoglobin was also identified in Cr6 +-treated samples. Conclusions These results suggest that Cr6 + may induce IL-6-mediated inflammatory responses which result in hepatic injury. This paper highlights the applications of functional proteomics of plasma profiles and fucosylated glycoproteins as a predictive tool to monitor human health in contact with chromium.

Topical treatment with vitamin C has been used to treat photoaged skin and as a skin whitener, but no standard procedure exists for percutaneous delivery.To compare skin histology and the permeation of ascorbic acid 2-glucoside (AA2G) after fractional and conventional carbon dioxide (CO(2) ) laser pretreatment.The effect on porcine skin of treatment with different strengths of fractional and conventional CO(2) laser treatment was examined using scanning electron microscopy and transmission electron microscopy. Permeation of AA2G through porcine skin was tested in vitro using a Franz diffusion chamber. In vivo changes in fluorescein thiocyanate permeability in nude mice were examined using confocal laser scanning microscopy.Fractional CO(2) laser treatment with four or fewer passes caused less disruption than conventional laser treatment at the same fluence. AA2G permeation using four passes of fractional laser treatment was similar to that seen with conventional CO(2) laser treatment of the same fluence. Changes in permeability and in depth of permeation were higher with conventional than fractional laser treatment.Fractional CO(2) laser treatment can cause similar transdermal delivery of AA2G to conventional laser treatment with less skin disruption and a different pattern of histologic change.

Lead compounds exhibit a high degree of cytotoxicity and carcinogenicity. We evaluated the impact of lead acetate on the liver by skin exposure as well as the changes in protein profiles reflecting pathogenic processes. Functional proteomic tools showed that the most meaningful protein changes were involved in protein folding, ER stress, and apoptosis in the presence of an organic lead compound. Treatment with lead acetate also elicits intracellular ROS levels as well as carbonyl modification of chaperone proteins, suggesting that lead might trigger the unfolded protein response due to oxidative stress. Lead application induced ER stress, as indicated by the promotion of GRP78 and by increased expression of the transcription factors ATF6, IRE1α, and PERK. Moreover, upregulation of GRP75 may participate in lead-caused hepatic cytotoxicity while abrogation of GRP75 appears to attenuate the inhibition of cell growth. Our findings demonstrate that accumulation of organic lead in the liver can induce oxidative imbalance and protein impairment that may result in ER stress followed by liver injuries. Hepatic proteome profiles delineate a finer picture of protein networks and metabolic pathways primarily involved in lead-initiated hepatic toxicity via skin exposure.

The objective of this study is to investigate the effects of two lasers (erbium:YAG and CO(2)) on the ability to enhance skin permeation of two vitamin C derivatives, 3-O-ethyl ascorbic acid (EAC) and ascorbic acid 2-glucoside (AA2G). The study was taken in the skin of a female nude mouse (Balb/c-nu strain, 8 weeks old) in vitro. The histologic and ultrastructural changes of the nude mouse skin treated by the lasers were examined under light microscopy and transmission electron microscopy, respectively. The in vitro permeation of vitamin C derivatives was performed in Franz cell. The stratum corneum (SC) layer in the skin was partly ablated by erbium:YAG laser treatment, resulting in greater permeation of both vitamin C derivatives. The flux of EAC and AA2G across erbium:YAG laser-treated skin was 105 to 189-fold and 35 to 78-fold higher, respectively, than their flux across intact skin. The increase in enhancement ratio with increase in fluency decreases markedly for both compounds at the last dose escalation (from 5.0 to 6.3 J/cm(2)). Both SC ablation and a thermal effect may contribute to the effect of the CO(2) laser on skin structure. The flux of EAC and AA2G across CO(2) laser-treated skin was 181 to 277-fold and 82 to 117-fold higher, respectively, than their flux across intact skin. We concluded that both erbium:YAG and CO(2) laser pretreatment increased the transdermal flux of two stable vitamin C derivatives, EAC and AA2G. The optimal fluency for the Er:YAG laser was 5 J/cm(2).