Thymocid®, a Standardized Black Cumin (Nigella sativa) Seed Extract, Modulates Collagen Cross-Linking, Collagenase and Elastase Activities, and Melanogenesis in Murine B16F10 Melanoma Cells.

Black cumin (Nigella sativa) seed extract has been shown to improve dermatological conditions, yet its beneficial effects for skin are not fully elucidated. Herein, Thymocid®, a chemically standardized black cumin seed extract, was investigated for its cosmeceutical potential including anti-aging properties associated with modulation of glycation, collagen cross-linking, and collagenase and elastase activities, as well as antimelanogenic effect in murine melanoma B16F10 cells. Thymocid® (50, 100, and 300 µg/mL) inhibited the formation of advanced glycation end-products (by 16.7-70.7%), collagen cross-linking (by 45.1-93.3%), collagenase activity (by 10.4-92.4%), and elastases activities (type I and III by 25.3-75.4% and 36.0-91.1%, respectively). In addition, Thymocid® (2.5-20 µg/mL) decreased melanin content in B16F10 cells by 42.5-61.6% and reduced cellular tyrosinase activity by 20.9% (at 20 µg/mL). Furthermore, Thymocid® (20 µg/mL for 72 h) markedly suppressed the mRNA expression levels of melanogenesis-related genes including microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TYRP1), and TYRP2 to 78.9%, 0.3%, and 0.2%, respectively. Thymocid® (10 µg/mL) also suppressed the protein expression levels of MITF (by 15.2%) and TYRP1 (by 97.7%). Findings from this study support the anti-aging and antimelanogenic potential of Thymocid® as a bioactive cosmeceutical ingredient for skin care products.

Collagen gel formation in the presence of a carbon nanobrush.

Type I, bovine skin collagen was allowed to gel in the presence of various concentrations of a carbon nanotube material covered with a polystyrene/polyaniline copolymer, called a carbon nanobrush (CNB). The rate of collagen gelation was enhanced by the presence of the CNB in a dose dependent manner. The extent of collagen gelation was due to the concentration of collagen and not the amount of CNB. Collagen D-periodicity, and average fibril diameter were unchanged by the CNB material as seen in transmission electron micrographs. Gel tensile strength was reduced by the presence of the CNB in a dose related manner. The collagen-CNB mixture may have a role in the repair and reconstruction of wounds or degenerated connective tissue.

Carbon nanobrush-containing poloxamer hydrogel composites for tissue regeneration.

The objective of this study was to examine potential uses for electrically conductive hydrogel composites in tissue engineering and tissue regeneration, and to explore the composites as a growth matrix for clinically relevant cell lines. The composite was comprised of carbon nanobrushes embedded in a biocompatible poloxamer gel. In this study, we assessed the ability of such composite gels to support the growth of fibroblasts and myocytes and eventually serve as a matrix to stimulate wound closure. In such a model, fibroblasts and myocytes are seeded on the hydrogel and bathed in culture medium. The experimental model assesses the ability of fibroblasts and myocytes to grow into and adhere to the gel. The results of this study demonstrate that carbon nanobrushes can be dispersed within poloxamer gels and that fibroblasts and myocytes can proliferate within homogenously dispersed carbon nanobrush-containing poloxamer gels. We also examined the effects of carbon nanobrush content on the rheological properties of the poloxamer gel matrix; improvement occurred in several areas in the presence of carbon nanobrushes. Our future studies will investigate the effects of design parameters such as carbon nanobrush content and matrix structure on wound healing, as well as the growth of tendons and other cell lines within the hydrogel composites. In general, this work has relevance for tissue and cellular engineering and tissue regeneration in clinical medicine.

Adjuvant radiation therapy increases overall survival in node-positive gastric cancer patients with aggressive surgical resection and lymph node dissection: a SEER database analysis.

OBJECTIVES: To determine the outcomes of postoperative radiation therapy on survival in gastric cancer. METHODS: An analysis of patients with surgically resected and nonmetastatic gastric cancer from the Surveillance, Epidemiology, and End Results database from 1990 to 2003 was carried out. Survival curves were calculated according to the Kaplan-Meier method. Multivariate analysis was carried out by the Cox proportional hazard model. RESULTS: We identified 11,630 patients who met inclusion criteria. Radiation therapy was associated with increased survival in patients with American Joint Committee on Cancer stage IB to IV. The median survival for stage IB and II patients treated with radiation was 96 months and 37 months, respectively, versus 56 months and 23 months for patients who did not receive adjuvant radiation (P=0.0281 for stage IB and <0.0001 for stage II). The 5-year overall survival for node-positive patients treated with radiation was 30.4% versus 21.4% for patients who did not receive adjuvant radiation (P<0.0001). The survival benefit of radiation therapy was maintained even if ≥15 lymph nodes were removed for N1 and N2 disease and if ≥30 lymph nodes were removed for N3 disease. For node-positive patients with ≥15 lymph nodes removed, adjuvant radiation was linked to increase survival in patients who underwent partial gastrectomy, total gastrectomy, and en bloc gastrectomy with other organs removed. Radiation was a strong independent factor for survival on multivariate analysis. CONCLUSIONS: There is a correlation between survival and radiation therapy in node-positive gastric cancer patients and is independent of the extent of surgical resection and lymph node dissection.

Improved survival in patients with lymph node-positive gastric cancer who received preoperative radiation: an analysis of the Surveillance, Epidemiology, and End Results database.

BACKGROUND: Several trials have been conducted to determine the feasibility of preoperative radiotherapy (RT) for gastric cancer. However, the absolute benefit from radiotherapy remains to be defined. In this study, the authors examined the use of preoperative RT (Pre-RT) and postoperative RT (PORT) in patients with gastric cancer from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: The overall survival of patients who had nonmetastatic, resected gastric cancer between 2000 and 2006 was analyzed from the SEER database. Kaplan-Meier survival curves comparing Pre-RT, PORT, and no RT (No-RT) were analyzed using the log-rank test. A multivariate analysis (MVA) was conducted using Cox proportional hazards regression. RESULTS: The authors identified 10,251 patients. There was no survival benefit for patients who received Pre-RT or PORT compared with No-RT patients for the entire cohort. Conversely, among lymph node-positive patients, there was a significant survival benefit from both Pre-RT and PORT compared with No-RT (log-rank test: PORT, P < .0001; Pre-RT, P = .0261). The median survival and 5-year overall survival among lymph node-positive patients were 22 months and 24%, respectively, for Pre-RT;29 months and 34%, respectively, for PORT; and 19 months and 20%, respectively, for No-RT. MVA demonstrated that Pre-RT, PORT, and removing ≥ 15 lymph nodes were independent predictors of improved survival, whereas tumor classification, lymph node status, tumor size, and tumor location were independent predictors of death. CONCLUSIONS: The current results supported the use of Pre-RT in select patients with gastric cancer. However, additional trials will be needed to confirm these findings.

Significance of micrometastases on the survival of women with T1 breast cancer.

BACKGROUND: The most important factor in predicting survival among women with newly diagnosed breast cancer is the status of the axillary lymph nodes. Although straightforward to define, the impact of micrometastases on survival remains to be completely determined. METHODS: A review of data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute was performed using 43,921 cases diagnosed from January 1988 through December 2001. Among women with invasive breast carcinomas

Risk of malignancy in scleroderma: a population-based cohort study.

OBJECTIVE: To determine the incidence of cancer in patients with scleroderma (systemic sclerosis) and to compare those rates with cancer rates in the local population. METHODS: Cancer risk in scleroderma patients in the Detroit metropolitan area was assessed by linking patient identification codes of the Michigan Scleroderma Registry to the Metropolitan Detroit Cancer Surveillance System database. Patients were screened between the years 1973 and 2002, with additional followup to 2004. Standardized incidence ratios (SIRs) were calculated for selected malignancies (lung, liver, colon, breast, cervical, and prostate cancers, and non-Hodgkin's lymphomas), with stratification by sex and race. RESULTS: Of 934 patients in the Scleroderma Registry, 538 were included in the study based on tri-county residency (436 females and 102 males). Of these, 45 first malignancies were noted (37 females and 8 males). Lung cancer (10 cases) was found to be the most common cancer in scleroderma patients. However, its incidence was not significantly different from that in the general population of metropolitan Detroit (SIR 1.23). Other types of cancer were examined, and no significant differences were found as compared with the rates in the local population, with 1 exception: black females with scleroderma had significantly higher rates of liver cancer (SIR 45.8). CONCLUSION: Contrary to previous studies, this study did not find statistical evidence of an increased incidence of cancer in scleroderma patients, except for liver cancer. One possible reason is the high background rates of certain cancers in the metropolitan Detroit area. It may be necessary to consider local cancer rates when comparing different scleroderma cohorts.

Piriformis syndrome: diagnosis, treatment, and outcome--a 10-year study.

OBJECTIVES: To validate an operational definition of piriformis syndrome based on prolongation of the H-reflex with hip flexion, adduction, and internal rotation (FAIR) and to assess efficacy of conservative therapy and surgery to relieve symptoms and reduce disability. DESIGN: Before-after trial of cohorts identified by operational definition. SETTING: Outpatient departments of 2 hospitals and 4 physicians' offices. Surgery performed at 3 hospitals. PATIENTS: Consecutive sample of 918 patients (1014 legs) with follow-up on 733. INTERVENTION: Patients with significant (3 standard deviations [SDs]) FAIR tests received injection, physical therapy, and serially reported pain and disability assessments. Forty-three patients (6.47%) had surgery. MAIN OUTCOME MEASURES: Likert pain scale. Subjective estimates of disablement in activities of daily living and instrumental activities of daily living. RESULTS: At 3 SDs, the FAIR test had sensitivity and specificity of.881 and.832, respectively. Seventy-nine percent (514/655) of FAIR test positive (FTP) patients improved 50% or more from injection and physical therapy at a mean follow-up of 10.2 months. Average improvement was 71.1%. Of 385 FTP patients with disability data, mean disability fell from 35.37% prestudy (SD =.2275) to 12.96% poststudy (SD =.1752), a 62.8% improvement. Twenty-eight surgical FTP patients (68.8%) showed 50% or greater improvement; mean improvement was 68% at a mean follow-up of 16 months. Surgery reduced the mean FAIR test to 1.35 +/- 2.17 months postoperatively. FTP patients generally improved 10% to 15% more than others after conservative treatment. CONCLUSIONS: The FAIR test correlates well with a working definition of piriformis syndrome and is a better predictor of successful physical therapy and surgery than the working definition. The FAIR test, coupled with injection and physical therapy and/or surgery, appears to be effective means to diagnose and treat piriformis syndrome.