Role of Plastic Surgery in the Treatment of Titanium Mesh Exposure Following Cranioplasty.

BACKGROUND: Titanium mesh cranioplasty is the most common strategy for the repair of skull defects. However, as the frequency of cranioplasty increases, the incidence of titanium mesh exposure following cranioplasty increases as well. This study aimed to investigate the methods and outcomes of plastic surgery in the management of titanium mesh exposure following cranioplasty. METHODS: Patients with titanium mesh exposure following cranioplasty were retrospectively selected from January 2016 to August 2021. Titanium mesh exposure was corrected with reconstructive plastic surgery, including skin grafting, expander insertion, partial removal of the exposed mesh, replacement of the mesh, or flap transplantation. RESULTS: This study included 21 patients with titanium mesh exposure with surgical site infection and a variant of scalp deformity. The age of the patients ranged from 18 to 74 years, with the mean age being 54 years. All patients underwent reconstructive plastic surgery and exhibited complete wound healing. The follow-up period ranged from 17 to 90 months. One patient experienced titanium mesh re-exposure and subsequently underwent an additional procedure for the partial removal of the exposed mesh. No serious complications were observed postoperatively. CONCLUSION: Reconstructive plastic surgery can facilitate wound healing at the titanium mesh exposure site following cranioplasty. However, an individualized treatment strategy is required for each patient, and complications should be managed by adopting standard measures.

The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles.

An increasing number of studies show that vascular endothelial growth factor is an important regulator of hair growth, and involves in processes of hair follicle development by vascularization. Recently, VEGF receptor-2 (VEGFR-2) has been detected in epithelial cells of hair follicles, indicating that it may have a direct role in the biological activity of hair follicles. To explore how VEGFR-2 regulates hair follicle development, we investigated the co-expression pattern of VEGFR-2 with ß-catenin, Bax, Bcl-2, involucrin, AE13 (hair cortex cytokeratin), keratin 16, keratin 14, and Laminin 5 by immunofluorescence double staining in anagen hair follicles of normal human scalp skin. The results of double staining immunofluorescence showed a strong overlapping and similar expression pattern for VEGFR-2 with ß-catenin and Bcl-2, and revealing associated expression pattern with involucrin, AE13, keratin 14, keratin 16, and Laminin 5. These results elucidated that VEGFR-2 activation may participate in hair follicle differentiation, proliferation, and apoptosis in vivo.

Co-Expression Pattern of Artemis Serine 516 Phosphorylation with Indicators Involving in Differentiation, Proliferation and Apoptosis of Human Anagen Hair Follicles: An Immunofluorescence Double-Staining Study.

BACKGROUND: Artemis belongs to the SNM1 gene family, and plays a role in repairing ionizing-radiation-induced DNA double-strand breaks and variable (diversity) joining recombination. S534, S538, S516, S645 represent four most rapid phosphorylation sites in Artemis, and serine phosphorylation at amino acid 516 is closely associated with activation. Artemis mutation is perceived as contributing to Omenn syndrome, which manifest features of severe combined immunodeficiency disease, associated with lymphadenopathy, hepatosplenomegaly, erythroderma and baldness. In addition, Artemis phosphorylated at serine 516 (Artemis S516-P) was expressed in scalp hair follicles (HF) as well as other skin appendages, and its expression level is important to mouse hair cycling. However, whether Artemis participated in the regulation of HF growth still unclear. METHODS: Using immunofluorescence double-staining, we assessed the association between Artemis S516-P with proliferation, apoptosis, and differentiation markers in normal adult anagen scalp HF. RESULTS: The results of double-staining immunofluorescence revealed overlapping expression pattern for Artemis S516-P and keratin16, similar pattern for c-myc and p21, while presenting opposite trends for keratin 10, phospho-p53, Bax, Bcl-2 and keratin 14. CONCLUSIONS: Our study provides the clues that Artemis may play roles in regulation of differentiation, proliferation, apoptosis and cell cycling during HF growth and development.

Liposomal C6 Ceramide Activates Protein Phosphatase 1 to Inhibit Melanoma Cells.

Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes. Molecularly, liposomal C6 activated protein phosphatase 1 (PP1) to inactivate Akt-mammalian target of rapamycin (mTOR) signaling in melanoma cells. On the other hand, PP1 shRNA knockdown or exogenous expression of constitutively activate Akt1 (CA-Akt1) restored Akt-mTOR activation and significantly attenuated liposomal C6-mediated cytotoxicity and apoptosis in melanoma cells. Our results suggest that liposomal C6 activates PP1 to inhibit melanoma cells.

Compound 13, an α1-selective small molecule activator of AMPK, potently inhibits melanoma cell proliferation.

It is vital to develop new therapeutic agents for the treatment of melanoma. In the current study, we studied the potential effect of Compound 13 (C13), a novel α1-selective AMP-activated protein kinase (AMPK) activator, in melanoma cells. We showed that C13 exerted mainly cytostatic, but not cytotoxic activities in melanoma cells. C13 potently inhibited proliferation in melanoma cell lines (A375, OCM-1 and B16), but not in B10BR melanocytes. Meanwhile, the AMPK activator inhibited melanoma cell cycle progression by inducing G1-S arrest. Significantly, we failed to detect significant melanoma cell death or apoptosis after the C13 treatment. For the mechanism study, we showed that C13 activated AMPK and inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling in melanoma cells through interaction with the α1 subunit. Short hairpin RNA (shRNA)-mediated knockdown of AMPKα1 not only blocked C13-mediated AMPK activation but also abolished its antiproliferative activity against melanoma cells. Together, these results show that C13 inhibits melanoma cell proliferation through activating AMPK signaling. Our data suggest that C13 along with other small molecular AMPK activators may be beneficial for patients with melanoma.

VS-5584, a Novel PI3K-mTOR Dual Inhibitor, Inhibits Melanoma Cell Growth In Vitro and In Vivo.

Melanomas cause over 76% of skin cancer deaths annually. Phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is important for melanoma initiation and progression. In the current study, we evaluated the potential anti-melanoma effect of VS-5584, a novel and highly potent PI3K-mTOR dual inhibitor. We demonstrated that VS-5584 potently inhibited survival and proliferation of established (A375, A-2058 and SK-MEL-3 lines) and primary human melanoma cells, but was non-cytotoxic to non-cancerous human skin keratinocytes and B10BR murine melanocytes. At the meantime, VS-5584 induced caspase-dependent apoptotic death in melanoma cells, and its cytotoxicity was alleviated by the caspase inhibitors. At the molecular level, VS-5584 blocked AKT-mTOR activation and downregulated cyclin D1 expression in melanoma cells, while the expressions of Bcl-xL and Bcl-2 were not affected by VS-5584 treatment. On the other hand, a BH-3 mimetic Bcl-xL/Bcl-2 inhibitor ABT-737, as well as siRNA-mediated knockdown of Bcl-xL or Bcl-2, enhanced the activity of VS-5584 in melanoma cells. In vivo, oral administration of VS-5584 suppressed A375 melanoma xenograft growth in nude mice, and its activity was further enhanced by co-administration of ABT-737. These results provide the rationale for the clinical assessment of VS-5584 in melanoma patients and development of ABT-737 and other Bcl-xL/Bcl-2 inhibitors as the possible adjuvants.

Aging and age-related diseases--from endocrine therapy to target therapy.

Aging represents an important health issue not only for the individual, but also for society in general. Burdens associated with aging are expanding as longevity increases. This has led to an enhanced focus on issues related to aging and age-related diseases. Until recently, anti-aging endocrine-therapy has been largely limited to hormone-replacement therapy (HRT) that is associated with multiple side effects, including an increased risk of cancer. This has greatly limited the application of HRT in anti-aging therapy. Recently, the focus of anti-aging research has expanded from endocrine signaling pathways to effects on regulatory gene networks. In this regard, the GHRH-GH-IGF-1/Insulin, TOR-S6K1,NAD(+)-Sirtuin, P53, Klotho and APOE pathways have been linked to processes associated with age-related diseases, including cancer, cardiovascular disease, diabetes, osteoporosis, and neurodegenerative diseases, all of which directly influence health in aging, and represent key targets in anti-aging therapy.

Immunolocalization of vimentin, keratin 17, Ki-67, involucrin, ß-catenin and E-cadherin in cutaneous squamous cell carcinoma.

Skin squamous cell carcinoma (SCC) is a subtype of very aggressive skin cancers. To investigate if epithelial-mesenchymal transition (EMT), a process for epitheloid cells losing their polarity and cohesiveness and transform into spindle-shaped cells, occurs in skin SCC. By using immunofluorescence, we defined the immunolocalization of vimentin, Keratin 17, ß-catenin, E-cadherin, Ki-67 and involucrin, in SCC samples. Our results show reduced activity of involucrin and E-cadherin, and increased expression of Ki-67, ß-catenin, Keratin 17 and vimentin in SCC. These data propose that EMT really occurs in poorly differentiated SCC and keratin 17 and involucrin may be another two biomarkers for EMT.

Phospholipase D participates in H(2)O(2)-induced A549 alveolar epithelial cell migration.

To investigate the effects of phospholipase D (PLD) on low-concentration hydrogen peroxide (H(2)O(2))-induced growth and migration in alveolar epithelial A549 cells, the cells were exposed to H(2)O(2) (3-100 µM) for 12-48 hours, cell proliferation was determined by MTT assay and cell migration was tested by a modified epithelial wound healing assay. We found that one bolus of H(2)O(2) (10-100 µM) did not affect proliferation, but significantly stimulated migration (143-161% of control) after a 12-hour exposure. Pretreatment with the antioxidants catalase (1000 U/ml), N-acetyl-cysteine (2 mM), or edaravone (10 µM) abolished the migration induced by 30 µM H(2)O(2); the PLD inhibitor 1-butanol (0.5%) also attenuated H(2)O(2)-induced migration to the control level; while exogenous phosphatidic acid (PA) (10(-7)-10(-4) M) mimicked the effects of PLD activation and induced migration in a dose-dependent manner. We suggest that the alveolar epithelial cell migration induced by exposure to low concentrations of H(2)O(2) benefits tissue repair during acute lung injury (ALI) and PLD is involved in the underlying mechanism.