A Review of Flow Characterization of Metallic Materials in the Cold Forming Temperature Range and Its Major Issues

We focus on the importance of accurately describing the flow behaviors of metallic materials to be cold formed; we refer to several valuable examples. We review the typical experimental methods by which flow curves are obtained, in addition to several combined experimental-numerical methods. The characteristics of four fundamental flow models including the Ludwik, Voce, Hollomon, and Swift models are explored in detail. We classify all flow models in the literature into three groups, including the Ludwik and Voce families, and blends thereof. We review the experimental and numerical methods used to optimize the flow curves. Representative flow models are compared via tensile testing, with a focus on the necking point and pre- or post-necking strain hardening. Several closed-form function models employed for the non-isothermal analyses of cold metal forming are also examined. The traditional bilinear C-m model and derivatives thereof are used to describe the complicated flow behaviors of metallic materials at cold forming temperatures, particularly in terms of their applications to metal forming simulations and process optimization.     

Evaluation of dermal thermal damage by multiphoton autofluorescence and second-harmonic-generation microscopy

We attempt to characterize the degree of skin thermal damage by using multiphoton microscopy to characterize dermal thermal damage. Our results show that dermal collagen and elastic fibers display different susceptibility to thermal injury. Morphologically, dermal collagen starts to denature at 60 degrees C while fracture and aggregation of elastic fibers do not occur until 65 degrees C. With increasing temperatures, the structures of both elastic and collagen fibers deteriorate. While second-harmonic-generation (SHG) imaging is helpful in identifying the denaturation temperature of collagen, autofluorescence (AF) imaging can help to identify the structural alternations of tissue at higher temperatures when SHG signals have decayed. We also employ a ratiometric approach based on the AF-to-SHG index of dermis (ASID) to characterize the degree of dermal thermal damage. Use of the ASID index can bypass the difficulty in analyzing inhomogeneous dermal fibers and show that dermal collagen starts to denature at 60 degrees C. Our results suggest that with additional developments, multiphoton microscopy has potential to be developed into an effective in vivo imaging technique to monitor and characterize dermal thermal damage.     

Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells

Ethnopharmacological relevance

The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway.

Aims of the study

Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231.

Methods

The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway.

Results

The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK1/2 inhibitor).

Conclusion

Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.     

Meniscal tear configurations: categorization with MR imaging

OBJECTIVE: The purpose of this study was to evaluate the accuracy of MR imaging for categorizing the configuration of meniscal tears of the knee. MATERIALS AND METHODS: Fast spin-echo MR images obtained at 1.5 T from 110 patients who had meniscal tears identified at arthroscopy were retrospectively and independently classified by two reviewers into five configurations: horizontal, longitudinal, radial, oblique, and complex. MR imaging categorization was compared with arthroscopic results as the standard of reference. Data were also analyzed with longitudinal and oblique tears combined because these usually are reparable, and with horizontal, radial, and complex tears combined because these usually are not reparable. Interobserver and intraobserver agreements were calculated using kappa coefficients. RESULTS: At arthroscopy, meniscal tears were categorized as horizontal (n = 44), longitudinal (n = 34), complex (n = 22), radial (n = 11), and oblique (n = 5). Sensitivity, specificity, and accuracy of each reviewer for the reparable tears were 82%, 92%, and 89%; and 59%, 97%, and 84%, respectively. Interobserver agreements were fair between reviewer 1 and the first and second interpretations of reviewer 2 (kappa = 0.25, p < 0.005; and kappa = 0.21, p < 0.05, respectively). Intraobserver agreement was substantial (kappa = 0.71, p < 0.001). CONCLUSION: MR imaging was accurate for predicting reparable meniscal tears and was sensitive for the determination of nonreparable tears.     

Discogenic lumbar pain: association with MR imaging and CT discography

OBJECTIVE: To correlate MR and CT discography findings with pain response at provocative discography in patients with discogenic back pain. MATERIALS AND METHODS: Forty-seven patients aged 25-54 years who underwent MR imaging and subsequent CT discography (97 discs) were included in this study. MR images were retrospectively evaluated regarding disc degeneration, endplate abnormalities, facet joint osteoarthritis, and high intensity zone. During discography concordant pain was regarded as positive, whereas discordant pain and no pain were regarded as negative. MR and CT discographic findings were analyzed on the base of concordant pain using the Chi-square test. RESULTS:: Concordant pain was significantly common in the following (P < 0.05): grade 4 or 5 disc degeneration [88% (30/34) in concordant pain versus 48% (30/63) in discordant pain and no pain], high intensity zone [56% (19/34) versus 30% (19/63)], combination of above two findings [53% (18/34) versus 25% (16/63)], fissured and ruptured disc at discogram [94% (32/34) versus 57% (36/63)], and contrast beyond inner annulus at CT discogram [97% (33/34) versus 57% (36/63)]. CONCLUSION: Typical MR findings with concordant pain at discography include grade 4 or 5 disc degeneration and presence of a high intensity zone. Typical CT discography findings with concordant pain were fissured/ruptured discs and contrast extending into/beyond the outer annulus on CT.     

Treatment with a sclerostin antibody increases cancellous bone formation and bone mass regardless of marrow composition in adult female rats

The current report describes the skeletal effects of a sclerostin monoclonal antibody (Scl-AbIII) treatment at a yellow (fatty) marrow skeletal site in adult female rats. Ten-month-old female Sprague–Dawley rats were treated with vehicle or Scl-AbIII at 5 or 25 mg/kg, twice per week by s.c. injection for 4 weeks. Trabecular bone from a yellow (fatty) marrow site, the 5th caudal vertebral body (CVB), was processed undecalcified for quantitative bone histomorphometric analysis. Compared to vehicle controls, Scl-AbIII at both doses significantly increased bone formation parameters and trabecular bone volume and thickness and decreased bone resorption parameter in the trabecular bone of the CVB. As a reference, we also found that the Scl-AbIII at both doses significantly decreased bone resorption and increased bone formation and bone volume in a red (hematopoietic) marrow site, the 4th lumber vertebral body (LVB). It appears that the percentage of increase in trabecular bone volume induced by Scl-AbIII treatment was slightly larger in the LVB than in the CVB. In summary, these preclinical findings show that antibody-mediated sclerostin inhibition has significant bone anabolic effects at both red and yellow marrow skeletal sites.     

Flurbiprofen-induced stimulation of periosteal bone formation and inhibition of bone resorption in older rats

The skeletal effects of flurbiprofen (Fb), a nonsteroidal antiinflammatory drug, was studied by histomorphometry in 9-month-old retired female breeder, Sprague-Dawley rats. Flurbiprofen was given subcutaneously at 0, 0.2, 0.1, 0.5, 2.5, or 5 mg/kg/d for 21 days. Flurbiprofen had no effect on longitudinal growth, but stimulated radial growth (+200%) over controls. In the tibial shaft, Fb stimulated the mineral apposition rate (+25%), mineral bone formation rate (+100%), and periosteal labeling length (+64%) at the 2.5 and 5.0 mg Fb/kg dose levels, and had no effect on marrow cavity size compared to controls. However, these changes were insufficient to increase cortical bone mass. In the proximal tibial metaphysis, Fb suppressed osteoclasts/mm² of metaphyseal tissue (-47%), osteoclasts/mm of bone surface (-46%), and the osteoclast/osteoblast ratio (-50%), increased the calcified cartilage core population (+100%), and had no effect on osteoblast numbers at all dose levels. There was an insignificant increase in metaphyseal cancellous bone mass. The current study leads to the conclusion that flurbiprofen-stimulated periosteal bone growth was due to direct stimulation of osteoblast recruitment and activity independent of longitudinal bone growth. Further, it confirms early findings in young rats that flurbiprofen induced depressed bone resorption without lowering bone formation. However, because of insufficient treatment time, the older rat did not accumulate bone as the young rats did.     

Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha‐2‐HS‐glycoprotein

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2‐HS‐glycoprotein gene (AHSG) and its protein, fetuin‐A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA‐dependent manner. In HepG2 cells treated with 300 μmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 μmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA‐overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid‐induced ER stress markers, CHOP, Bip, ATF‐6, XBP‐1, ATF‐4, and PERK. In addition, in the high‐fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one‐third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p‐AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.