This article presents an inexpensive method to fabricate gelatin, as a natural polymer, into monofilament fibers or other appropriate forms. Through the wet spinning method, gelatin fibers are produced by smooth extrusion in a suitable coagulation medium. To increase the functional surface of these gelatin fibers and their ability to mimic the features of tissues, gelatin can be molded into a tube form by referring to this concept. Examined by in vitro and in vivo tests, the gelatin tubes demonstrate a great potential for application in tissue engineering. Acting as a suitable filling gap material, gelatin tubes can be used to substitute the tissue in the damaged area (e.g., in the nervous or cardiovascular system), as well as to promote regeneration by providing a direct replacement of stem cells and neural circuitry. This protocol provides a detailed procedure for creating a biomaterial based on a natural polymer, and its implementation is expected to greatly benefit the development of correlative natural polymers, which help to realize tissue regeneration strategies.
Excellent wound dressing is essential for effective wound repair and regeneration. This chapter aims to evaluate the effectiveness of bacterial cellulose (BC) and type I collagen (COL) scaffolds conjugated with resveratrol (RSV) for wound management. BC and COL are biodegradable and renewable attractive polymers for medical applications which has a strong affinity for materials containing hydroxyl groups, meanwhile RSV has a 4'-hydroxyl group and exhibits good biocompatibility and no cytotoxicity. The results demonstrated that RSV was effectively released from the BC and COL scaffolds in vitro, and immunofluorescence staining showed that both scaffolds were highly biocompatible and regenerated epithelia. Additionally, Masson’s trichrome staining showed that the both scaffolds preserved the normal collagen-bundling pattern and induced re-epithelialization in defective rat epidermis. These results indicate that RSV-conjugated BC or COL scaffold created a biocompatible environment for stem cell attachment and growth and promoted epithelial regeneration during wound healing.
A new 5-tiered grading grouping system has recently been endorsed for reporting of prostate cancer (PCa) grade to better reflect escalating risk of progression and cancer death. While several validations of the new grade groupings have been undertaken, most have involved centralised pathological review by specialist urological pathologists. Participants included 4268 men with non-metastatic PCa diagnosed between 2006 and 2013 from the multi-institutional South Australia Prostate Cancer Clinical Outcomes Collaborative registry. PCa-specific survival and biochemical recurrence-free survival were compared across the five grade groups using multivariable competing risk regression. For the entire cohort, risk of PCa death increased with increasing grade groups (at biopsy) Adjusted subdistribution-hazard ratios [sHR] and 95% confidence intervals [95%CI] were: 2.2 (1.5–3.6); 2.5 (1.6–4.2); 4.1 (2.6–6.7) and 8.7 (4.5–14.0) for grade groups II (pattern 3 + 4), III (pattern 4 + 3), IV (total score 8) and V (total score 9–10) respectively, relative to grade group I (total score < =6). Clear gradients in risk of PCa death were observed for radical prostatectomy (RP), but were less clear for those who had radiotherapy (RT) with curative intent and those who were managed conservatively. Likewise, risk of biochemical recurrence increased across grade groups, with a strong and clear gradient for men undergoing RP [sHR (95%CI): 2.0 (1.4–2.8); 3.8 (2.9–5.9); 5.3 (3.5–8.0); 11.2 (6.5–19.2) for grade groups II, III, IV and V respectively, relative to grade group I], and a less clear gradient for men undergoing RT. In general, the new five-tiered grade groupings distinguished PCa survival and recurrence outcomes for men with PCa. The absence of a clear gradient for RT may be due to heterogeneity in this patient group.
Hypertrophic scarring is related to persistent activation of transforming growth factor-β (TGF-β)/Smad signaling. In the TGF-β/Smad signaling cascade, the TGF-β type I receptor (TGFBRI) phosphorylates Smad proteins to induce fibroblast proliferation and extracellular matrix deposition. In this study, we inhibited TGFBRI gene expression via TGFBRI small interfering RNA (siRNA) to reduce fibroblast proliferation and extracellular matrix deposition. Our results demonstrate that downregulating TGFBRI expression in cultured human hypertrophic scar fibroblasts significantly suppressed cell proliferation and reduced type I collagen, type III collagen, fibronectin, and connective tissue growth factor (CTGF) mRNA, and type I collagen and fibronectin protein expression. In addition, we applied TGFBRI siRNA to wound granulation tissue in a rabbit model of hypertrophic scarring. Downregulating TGFBRI expression reduced wound scarring, the extracellular matrix deposition of scar tissue, and decreased CTGF and α-smooth muscle actin mRNA expression in vivo. These results suggest that TGFBRI siRNA could be applied clinically to prevent hypertrophic scarring. Hypertrophic scarring is related to persistent activation of transforming growth factor-β (TGF-β)/Smad signaling. In the TGF-β/Smad signaling cascade, the TGF-β type I receptor (TGFBRI) phosphorylates Smad proteins to induce fibroblast proliferation and extracellular matrix deposition. In this study, we inhibited TGFBRI gene expression via TGFBRI small interfering RNA (siRNA) to reduce fibroblast proliferation and extracellular matrix deposition. Our results demonstrate that downregulating TGFBRI expression in cultured human hypertrophic scar fibroblasts significantly suppressed cell proliferation and reduced type I collagen, type III collagen, fibronectin, and connective tissue growth factor (CTGF) mRNA, and type I collagen and fibronectin protein expression. In addition, we applied TGFBRI siRNA to wound granulation tissue in a rabbit model of hypertrophic scarring. Downregulating TGFBRI expression reduced wound scarring, the extracellular matrix deposition of scar tissue, and decreased CTGF and α-smooth muscle actin mRNA expression in vivo. These results suggest that TGFBRI siRNA could be applied clinically to prevent hypertrophic scarring. connective tissue growth factor extracellular matrix human hypertrophic scar fibroblasts scar elevation index α-smooth muscle actin transforming growth factor-β transforming growth factor-β type I receptor transforming growth factor-β type II receptor small interfering RNA Vancouver scar scale
Objective. Postinfarction transneuronal degeneration refers to secondary neuronal death that occurs within a few days to weeks following the disruption of input or output to synapsed neurons sustaining ischemic insults. The thalamus receives its blood supply from the posterior circulation; however, infarctions of the middle cerebral arterial may cause secondary transneuronal degeneration in the thalamus. In this study, we presented the areas of ischemia and associated transneuronal degeneration following MCAo in a rat model. Materials and Methods. Eighteen 12-week-old male Sprague-Dawley rats were randomly assigned to receive middle cerebral artery occlusion surgery for 1, 7, and 14 days. Cerebral atrophy was assessed by 2,3,5-triphenyltetrazolium hydrochloride staining. Postural reflex and open field tests were performed prior to animal sacrifice to assess the effects of occlusion on behavior. Results. Myelin loss was observed at the lesion site following ischemia. Gliosis was also observed in thalamic regions 14 days following occlusion. Differential degrees of increased vascular endothelial growth factor expression were observed at each stage of infarction. Increases in myelin basic protein levels were also observed in the 14-day group. Conclusion. The present rat model of ischemia provides evidence of transneuronal degeneration within the first 14 days of occlusion. The observed changes in protein expression may be associated with self-repair mechanisms in the damaged brain.
[6]-Shogaol is the main biologically active component of ginger. Previous reports showed that[6]-shogaol has several pharmacological characteristics, such as antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic properties. However, the effects of[6]-shogaol on melanogenesis remain to be elucidated. The study aimed to evaluate the potential skin whitening mechanisms of[6]-shogaol. The effects of[6]-shogaol on cell viability, melanin content, tyrosinase activity, and the expression of the tyrosinase and microphthalmia-associated transcription factor (MITF) were measured. The results revealed that[6]-shogaol effectively suppresses tyrosinase activity and the amount of melanin and that those effects are more pronounced than those of arbutin. It was also found that[6]-shogaol decreased the protein expression levels of tyrosinase-related protein 1 (TRP-1) and microphthalmia-associated transcriptional factor (MITF). In addition, the MITF mRNA levels were also effectively decreased in the presence of 20 μ M[6]-shogaol. The degradation of MITF protein was inhibited by the MEK 1-inhibitor (U0126) or phosphatidylinositol-3-kinase inhibitor (PI3K inhibitor) (LY294002). Further immunofluorescence staining assay implied the involvement of the proteasome in the downregulation of MITF by[6]-shogaol. Our confocal assay results also confirmed that[6]-shogaol inhibited α -melanocyte stimulating hormone- ( α -MSH-) induced melanogenesis through the acceleration of extracellular responsive kinase (ERK) and phosphatidylinositol-3-kinase- (PI3K/Akt-) mediated MITF degradation.
The dynamic translocation of androgen receptors (ARs) in prostate cancer cells after hormone conversion was studied. The prostate cancer cell line LNCaP was converted into androgen-independent sublines after long-term treatment with 5α-reductase inhibitor and steroid-depleted medium. Immunohistochemical, immunofluorescent staining and laser scanning microscopy were used to observe the redistribution and serial translocation of ARs in these tumor cells. The androgen-independent tumor cells (LNCaP/Fin and LNCaP/HR) grew slower than native cells with fibroblastic-like characteristics. On immunohistochemical and immunofluorescent double staining, translocation and exocytosis of ARs were noted in androgen- independent tumor cells much more markedly than in native cells. Furthermore, laser-scanning microscopy revealed serial image changes of AR vesicle shifting and exocytosis in androgen-converted tumor cells. Translocation and exocytosis processes were observed in androgen-independent prostate cancer cells. ARs lose partly normal cellular biologic role during hormone manipulation.
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