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Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galβ1-3/β1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galβ1-3/β1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC.

Rationale: Many external factors can induce the melanogenesis and inflammation of the skin. Salidroside (SAL) is the main active ingredient of Rhodiola , which is a perennial grass plant of the Family Crassulaceae. This study evaluated the effect and molecular mechanism of SAL on skin inflammation and melanin production. It then explored the molecular mechanism of melanin production under ultraviolet (UV) and inflammatory stimulation. Methods: VISIA skin analysis imaging system and DermaLab instruments were used to detect the melanin reduction and skin brightness improvement rate of the volunteers. UV-treated Kunming mice were used to detect the effect of SAL on skin inflammation and melanin production. Molecular docking and Biacore were used to verify the target of SAL. Immunofluorescence, luciferase reporter assay, CO-IP, pull-down, Western blot, proximity ligation assay (PLA), and qPCR were used to investigate the molecular mechanism by which SAL regulates skin inflammation and melanin production. Results: SAL can inhibit the inflammation and melanin production of the volunteers. SAL also exerted a protective effect on the UV-treated Kunming mice. SAL can inhibit the tyrosinase (TYR) activity and TYR mRNA expression in A375 cells. SAL can also regulate the ubiquitination degradation of interferon regulatory factor 1 (IRF1) by targeting prolyl 4-hydroxylase beta polypeptide (P4HB) to mediate inflammation and melanin production. This study also revealed that IRF1 and upstream stimulatory factor 1 (USF1) can form a transcription complex to regulate TYR mRNA expression. IRF1 also mediated inflammatory reaction and TYR expression under UV- and lipopolysaccharide-induced conditions. Moreover, SAL derivative SAL-plus (1-(3,5-dihydroxyphenyl) ethyl-β-d-glucoside) showed better effect on inflammation and melanin production than SAL. Conclusion: SAL can inhibit the inflammation and melanogenesis of the skin by targeting P4HB and regulating the formation of the IRF1/USF1 transcription complex. In addition, SAL-plus may be a new melanin production and inflammatory inhibitor., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)