Lung cancer is the leading cause of cancer-related death worldwide. Early detection and appropriate treatment for cancerous lesions of patients can reduce the risk of death and improve the quality of life (QOL). Histopathological diagnosis of a lesion is necessary for physicians to decide on a therapeutic plan for a patient. Lung cancer is generally classified into two categories: small cell carcinoma (SC), and non-small cell carcinoma. This information reflects the characteristic of the tumor: SC is usually more aggressive with poorer differentiation potential than non-small cell carcinoma. Cancerous tissue of non-small lung cancer is further classified into three major types according to histological tissue pattern: adenocarcinoma (AD), squamous cell carcinoma (SQ), and large cell carcinoma (LC).^{1, 2, 3} Information on tissue morphology and cancer cell type is important for confirming a diagnosis. Raman spectroscopy is a type of vibrational spectroscopy that provides useful information for estimating the molecular composition of a sample. If the molecular composition changes in cancer tissues, its Raman spectrum must reflect those changes.

Members of the transforming growth factor-β (TGF-β) family, including TGF-βs, activin and bone morphogenetic proteins (BMPs), are multifunctional proteins that regulate a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. TGF-β family signalling is mainly mediated by membranous serine/threonine kinase receptors and intracellular Smad proteins. This signalling is tightly regulated by various post-translational modifications including ubiquitination. Several E3 ubiquitin ligases play a crucial role in the recognition and ubiquitin-dependent degradation of TGF-β family receptors, Smad proteins and their interacted proteins to regulate positively and negatively TGF-β family signalling. In contrast, non-degradative ubiquitin modifications also regulate TGF-β family signalling. Recently, in addition to protein ubiquitination, deubiquitination by deubiquitinating enzymes has been reported to control TGF-β family signalling pathways. Interestingly, more recent studies suggest that TGF-β signalling is not only regulated via ubiquitination and/or deubiquitination, but also it relies on ubiquitination for its effect on other pathways. Thus, ubiquitin modifications play key roles in TGF-β family signal transduction and cross-talk between TGF-β family signalling and other signalling pathways. Here, we review the current understandings of the positive and negative regulatory mechanisms by ubiquitin modifications that control TGF-β family signalling.

Purpose: Raman spectroscopy could potentially be used as a diagnostic tool for the detection of meibomian gland dysfunction by measuring the composition, conformation, and amount of meibum lipid on the lid margin. Toward this goal and to test our studies of meibum lipid using infrared spectroscopy, we measured the Raman spectra of samples from human donors with and without meibomian gland dysfunction. Materials and Methods: Human meibum was expressed from the eyelids and collected on a spatula. Meibum was placed onto an AgCl window for analysis using a Raman spectrometer. Results: Raman spectra of human meibum closely resembled that of wax. The Raman band intensity ratio, 1303/1267 cm⁻¹, was used to calculate a saturation level CH₂/=CH of 12 for meibum from normal donors and 11.8 for meibum from donors with meibomian gland dysfunction. Human meibum was found to fit well in the linear relationships between lipid saturation and lipid order at physiological temperature and between lipid saturation and the lipid phase transition temperature. The CH stretching band region predominates the Raman spectra of human meibum. If sample temperature could be controlled, the CH stretching bands could be used to calculate the lipid structural order in terms of trans and gauche rotomer levels. Raman spectra indicate that carotenoid-like bands decrease from the equivalent of about 90 μg carotenoid per gram of meibum wax at 19 years of age to about 0 at 80 years of age in samples from patients with meibomian gland dysfunction. The carotenoids may serve as antioxidants. Conclusions: Principal component analysis shows that a component containing carotenoid-like bands may be a promising spectral feature that could be used to distinguish differences between the Raman spectra of donors from normal and those with meibomian gland dysfunction. This study demonstrates the wealth of structural and compositional information that Raman spectra of human meibum provide.

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Bone mineral density (BMD) is a commonly used diagnostic indicator for bone fracture risk in osteoporosis. Along with low BMD, bone fragility accounts for reduced bone quality in addition to low BMD, but there is no diagnostic method to directly assess the bone quality. In this study, we investigated changes in bone quality using the Raman spectroscopic technique. Sciatic neurectomy (NX) was performed in male C57/BL6J mice (NX group) as a model of disuse osteoporosis, and sham surgery was used as an experimental control (Sham group). Eight months after surgery, we acquired Raman spectral data from the anterior cortical surface of the proximal tibia. We also performed a BMD measurement and micro-CT measurement to investigate the pathogenesis of osteoporosis. Quantitative analysis based on the Raman peak intensities showed that the carbonate/phosphate ratio and the mineral/matrix ratio were significantly higher in the NX group than in the Sham group. There was direct evidence of alterations in the mineral content associated with mechanical properties of bone. To fully understand the spectral changes, we performed principal component analysis of the spectral dataset, focusing on the matrix content. In conclusion, Raman spectroscopy provides reliable information on chemical changes in both mineral and matrix contents, and it also identifies possible mechanisms of disuse osteoporosis.