this link is useful

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236724/

regards

Hassan Nima Thank you

Amended on 25 September 2018

I would like to recommend quantitative PDMD (protein-direct-microsequencing-deciphering) method (please see file; HepG2 Fucoidan). Please, do not utilize non-quantitative ELISA method (please compare the two papers; Fucoidan ELISA and JCB Fucoidan transport). Interestingly, HPLC-photometric method gives c.a. 2,000-fold higher values than notorious ELISA method and/or RIA method. Similarly, notorious Real-time PCR method is also non quantitatve method.

Expression of Growth Factors seems to be important for biology, and I have searched expression of Growth Factors in my protein database.

Interestingly, nerve growth factor (NGF) is not found among my human protein database. This may be due to species differences. Dr. Rita Levi-Montalcini (Italy) has found it in mouse or chicken. Dr. Claudio De Felice has found that biotinidase excretion into urine is differently occurring between European and Asian (please see file; Race Urine BIN).

Insulin-like growth factor (IGF);

Serum of 12mo girl (with common cold) has Insulin-like growth factor 1A/IGF-IA at 6.7 μg/mg of serum protein (0.519 mg/mL; total serum protein of this serum is 77.4 mg/mL as determined by HPLC-photometric method: please see file; HPLC-Surf-SEC protein determination method).

LC tissue (named as No.6) has Insulin-degrading enzyme/Insulinase/IDE at 4.0 μg/mg of tissue protein.

HCC tissue (named as No.6) has CI Man-6-P receptor/IGF2R/Insulin-like growth factor 2 receptor at 27.0 μg/mg of tissue protein, and Insulin-degrading enzyme/Insulinase/IDE at 13.3 μg/mg of tissue protein.

Hepatoma HepG2 (cultured without fucoidan) has Insulin receptor substrate 2/IRS-2 at 15.0 μg/mg of cell protein.

Liver tissue (with pseudo liver cancer) has Insulinoma-associated protein 1 at 0.44 μg/mg of tissue protein.

LC tissue (with leprosy) has Insulin-like growth factor-binding protein 5/IGFBP-5/IBP-5 at 3.0, and Insulin-like growth factor binding-protein 3/IGFBP-3/IBP-3 at 0.7 μg/mg of tissue protein, respectively.

Serum of 1y11mo girl (with excess biotin) has Insulin-responsive sequence DNA-binding protein 1/IRE-BP1/SNED1/Sushi, nidogen and EGF-like domain-containing protein 1 at 2.4 μg/mg of serum protein.

Epidermal growth factor (EGF);

Serum of GSD-1b patient (after 2 mo of liver transplantation) has Epidermal growth factor receptor/EGF receptor at 3.6 μg/mg of serum protein. This gene expression seems to be due to transplantation, and not to be due to HCoV.

Serum of 1y11mo girl (excess biotin, anorexia) has Pro-epidermal growth factor/Urogastrone (1036-1207 a.a.) at 1.2 μg/mg of serum protein (0.071 mg/mL; total serum protein of this serum is 59.0 mg/mL as determined by HPLC-photometric method). This Urogastrone has no EGF activity, since EGF activity is present at 971-1023 a.a. portion.

Serum of Gait disorder patient (with biotin deficiency) has Epidermal growth factor receptor 5/EGFR-5/Proto-oncogene c-ErbB-1 at 1.5 μg/mg of serum protein and Epidermal growth factor-like 2/Flamingo homolog 3 at 5.9 μg/mg of serum protein.

Healed hepatocyte HepG2 (cultured with fucoidan) has Multiple epidermal growth factor-like domains 9 at 0.41 μg/mg of cell protein and Stabilin-1/Fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor 1 at 10.1 μg/mg of cell protein.

Transforming growth factor (TGF）;

Hepatoma HepG2 (cultured without fucoidan) has Transforming growth factor beta receptor type 3/TGF-beta receptor type III/Betaglycan at 2.7 μg/mg of cell protein and Transforming growth factor alpha/TGF-alpha at 0.2 μg/mg of cell protein. It is noteworthy that other 2 liver cancer tissues (HCC tissue with PBC and HCC tissue (named as No.6)) have no TGF-related proteins.

Granulocyte-macrophage-colony stimulating factor (GM-CSF);

Liver tissue (with pseudo liver cancer) has Granulocyte-macrophage colony-stimulating factor receptor alpha chain/GM-CSF-R at 3.0 μg/mg of tissue protein.

Fibroblast growth factor (FGF）;

Healed hepatocyte HepG2 (cultured with fucoidan) has Fibroblast growth factor 23 at 0.32 μg/mg of cell protein.

Serum of 4mo boy (with biotin deficiency) has Antisense basic fibroblast growth factor B/Nucleoside diphosphate-linked moiety X motif 6/FGF2AS at 6.4 μg/mg of serum protein. This protein may have been upregulated by FCoV.

Serum of 7mo1w boy (the same boy as above; biotin deficiency has been healed by biotin therapy, but has vitamin K deficiency) has Antisense basic fibroblast growth factor B/Nucleoside diphosphate-linked moiety X motif 6/FGF2AS at 6.4 μg/mg of serum protein. This protein may have been upregulated by +ssRNA bacteriophage of Chlamydophila caviae (of guinea pig), which is present in this serum.

Serum of 8mo girl (with gastritis) has Fibroblast growth factor 13/Fibroblast growth factor homologous factor 2 at 4.0 μg/mg of serum protein (0.234 mg/mL; total serum protein of this serum is 58.4 mg/mL as determined by HPLC-photometric method).

HCC tissue (named as No.6) has Fibroblast growth factor receptor 1/FGFR-1/BFGFR at 1.0 μg/mg of tissue protein and Fibroblast growth factor receptor 2/FGFR-2/Keratinocyte growth factor receptor/KGFR at 1.0 μg/mg of tissue protein.

Hepatocyte growth factor (HGF);

Healed hepatocyte HepG2 (cultured with fucoidan) has Hepatocyte growth factor-regulated tyrosine kinase substrate at 1.9 μg/mg of cell protein.

Transforming growth factor (TGF);

Healthy serum of 1y4mo girl has Growth differentiation factor 8/GDF8/Myostatin at 11.9 μg/mg of serum protein.

LC tissue (with leprosy) has TGF-beta receptor type-1/Serine/threonine-protein kinase receptor R4/ALK-5 at 4.4 μg/mg of tissue protein.

HCC tissue (named as No.6) has Transforming growth factor beta receptor type 3/TGF-beta receptor type III/TGFR-3 at 5.0 μg/mg of tissue protein.

Bone morphogenetic protein (BMP);

Serum of 22y female (with light Gait disorder) has Cartilage-derived morphogenetic protein 1/Growth differentiation factor 5/Bone morphogenetic protein 14 at 8.6 μg/mg of tissue protein (0.714 mg/mL; total serum protein of this serum is 83.0 mg/mL as determined by HPLC-photometric method).

Liver tissue (with pseudo liver cancer) has Bone morphogenetic protein 7/Osteogenic protein 1 at 21.3 μg/mg of tissue protein.

LC tissue (with leprosy) has Bone morphogenetic protein 1/BMP-1 at 5.0 μg/mg of tissue protein.

LC tissue (named No.6) has Bone morphogenetic protein 8B/BMP8B at 0.52 μg/mg of tissue protein.

HCC tissue (No.6) has Bone morphogenetic protein 2 at 8.9 μg/mg of tissue protein.

Glial cell line derived neurotrophic factor (GDNF);

Serum of 7mo1w boy (biotin deficiency has been healed by biotin therapy, but has vitamin K deficiency) has GDNF-inducible zinc finger protein 1 at 1.8 μg/mg of serum protein.

Interestingly, expression of Growth factors seems to be up-regulated by HCoV, Feline infectious peritonitis virus/FCoV, Canine coronavirus/CCoV, and Avian infectious bronchitis virus/IBV/ACoV.

Further, I have recently found that insulin-related proteins are up-regulated by HIV-1, HIV-2 and SIV (reported in this RG). Therefore, I have estimated that human pancreatic cancer is caused by the co-infection of HIV-1 and HCoV (also reported in this RG).

Furthermore, I have also recently estimated that human cervical cancer is caused by the co-infection of HIV-1 and animal coronavirus (such as Murine coronavirus/MCoV, Canine coronavirus/CCoV, or Avian infectious bronchitis virus/IBV/Avian cornavirus/ACoV). This conclusion clearly denies the hypothesis that cervical cancer is caused by human papillomavirus/HPV (non-enveloped, dsDNA virus).