OBJECTIVE: To summarize recent research progress in hydrogel-based growth factors for treatment of intervertebral disc degeneration (IDD). METHODS: The relevant literature on hydrogel-based growth factors for IDD treatment at home and abroad was extensively reviewed, and their advantages and therapeutic effects in repairing IDD were analyzed and summarized. RESULTS: Hydrogels exhibit high hydration, biocompatibility, and biodegradability, enabling targeted delivery and sustained release of growth factors such as growth differentiation factors and transforming growth factors. This facilitates enhanced efficacy in promoting cell proliferation, extracellular matrix synthesis, and reducing inflammatory responses. Consequently, hydrogels demonstrate broad application prospects in the repair of IDD. CONCLUSION Research on hydrogel-based growth factors for treating IDD demonstrates advantages such as avoiding disc damage caused by repeated injections and controlling growth factor release concentrations. However, drawbacks include the limited variety of loaded growth factors and the need to verify the long-term stability and biocompatibility of hydrogels. Therefore, further research is required on aspects such as the types of loaded growth factors and the long-term stability and biocompatibility of hydrogels to establish an experimental foundation for their clinical application.
Intervertebral Disc Degeneration/therapy* ; Hydrogels/chemistry* ; Humans ; Intercellular Signaling Peptides and Proteins/administration & dosage* ; Biocompatible Materials/chemistry* ; Animals ; Tissue Engineering/methods* ; Cell Proliferation/drug effects* ; Drug Delivery Systems

Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.
Administration, Oral* ; Animals ; Dipeptides* ; Elasticity* ; Glycine* ; Humans ; Hyaluronic Acid ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Keratinocytes ; Leucine* ; Mice ; Mice, Hairless* ; Minerals ; Miners ; Pancreatic Elastase ; Peptides ; Placenta ; RNA, Messenger ; Skin* ; Up-Regulation

BACKGROUND: The stem cell-derived secretome has received considerable attention as an alternative to stem cells for therapeutic applications. However, establishing optimal culture conditions is key to obtaining appropriate secretome contents. Here, the optimal culturing environment for achieving a high-efficiency secretome was determined via hypoxic preconditioning of human adipose-derived stem cells (ASC). METHODS: Normoxic conditioned media (NCM) and hypoxic conditioned media (HCM) were obtained after culturing human ASCs under normoxia (20% O2) or hypoxia (1% O2), respectively. Subsequently, both normal and thioacetamide-induced hepatotoxic hepatocytes were treated with NCM or HCM. In addition, partially hepatectomized mice were infused with control saline, NCM, and HCM. The effects on liver regeneration and serum transaminases levels were then compared. RESULTS: Hypoxic preconditioning significantly increased mRNA expression of proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and growth factors (hepatocyte growth factor and vascular endothelial growth factor). In both normal and thioacetamide-induced hepatotoxic hepatocyte (alpha mouse liver 12 [AML12]) cell lines, HCM treatment resulted in the highest cell viability (122% and 95%, respectively), followed by NCM (111% and 78%, respectively). In addition, intravenous administration of HCM to partially hepatectomized mice resulted in substantially enhanced liver regeneration compared with the NCM group (P<0.05). CONCLUSIONS: Taken together, the secretome obtained from ASC with hypoxic preconditioning showed potential to alleviate liver damage both in vitro and in vivo. Hypoxic culture of ASC is expected to play an important role in regenerative medicine by inducing secretome production that is beneficial for improving liver regeneration.
Administration, Intravenous ; Animals ; Anoxia ; Cell Line ; Cell Survival ; Culture Media, Conditioned ; Cytokines ; Hepatocytes ; Humans ; Intercellular Signaling Peptides and Proteins ; Liver Regeneration ; Liver* ; Mice ; Necrosis ; Regenerative Medicine ; RNA, Messenger ; Stem Cells* ; Transaminases

The role of flavonoids of Echinps latifolius (FELT) in Wnt signaling was investigated in adjuvant arthritis (AA) rats. The therapeutic effects of FELT on AA rats were detected by rat arthritis score and MTT. The effect of FELT gavage treatment on the Wnt signaling key gene β-catenin, C-myc and cyclin D1 in synovium from AA rats was detected by Real-time qPCR, and the effects of FELT gavage treatment on the upstream negative regulation gene SFRP 1,2,4,5 in synovium from AA rats were detected by Real-time qPCR. The results showed that FELT gavage treatment significantly inhibited arthritis score and MTT values in AA rats, significantly inhibited the expression of the Wnt signaling gene β-catenin, C-myc and cyclin D1, significantly up-regulated the expression of the up- stream negative regulation gene SFRP 1,2,4. FELT has a better therapeutic effect for AA rats.
Animals ; Arthritis, Experimental ; drug therapy ; genetics ; metabolism ; Asteraceae ; chemistry ; Disease Models, Animal ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Synovial Membrane ; drug effects ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

This study was aimed to investigate the effect of bortezomib combined with bisphosphonates on serum levels of DKK-1 and RANKL in multiple myeloma patients, and to evaluate its role in the therapy of osteolytic lesion. Fourty-three patients with newly diagnosed and relapsed myeloma were divided into 2 groups. Twenty-three patients were treated with bortezomib combined with bisphosphonates (A group) and 20 patients were treated with bisphosphonates combined with traditional chemotherapy (B group). Serum levels of DKK-1 and RANKL were measured by ELISA before and after 4 cycles of chemotherapy. The results indicated that serum DKK-1 level significantly decreased in patients of A group (43.2 µg/L before vs 30.4 µg/L after 4 cycles of chemotherapy), and so did for serum RANKL level in A group (0.83 pmmol/L before vs 0.45 pmmol/L after 4 cycles of chemotherapy). While there was no significant differences in DKK-1 and RANKL serum level before therapy between A and B groups, but there was significant differences in DKK-1 and RANKL levels after 4 cycles of chemotherapy (P < 0.05). It is concluded that bortezomib combined with bisphosphonates obviously reduce the serum levels of DKK-1 and RANKL, thus has beneficial effect on osteolytic lesion.
Adult ; Aged ; Boronic Acids ; administration & dosage ; therapeutic use ; Bortezomib ; Diphosphonates ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; drug therapy ; Pyrazines ; administration & dosage ; therapeutic use ; RANK Ligand ; blood

OBJECTIVETo explore the difference of effects of two regimens (bortezomib and dexamethasone, BD; and thalidomide and dexamethasone, TD) on bone disease in multiple myeloma (MM).

METHODSForty patients with newly diagnosed and refractory or relapsed MM were treated with BD or TD regimens from Dec 2006 to Sep 2008. Bone pain score and X-ray examination were carried out before and after therapy. Serum levels of DKK-1, sRANKL, OPG and TRACP-5b were measured by ELISA before and 3 months after therapy.

RESULTSSerum TRACP-5b concentration was significantly decreased in patients received TD regimen (5.94 U/L before therapy vs 4.84 U/L 3 months after therapy, P < 0.05), and so did for serum DKK-1 concentration in patients responded to BD regimen (35.11 µg/L before vs 32.03 µg/L 3 months after therapy, P < 0.05); for serum concentration of sRANKL in patients responded to BD regimen (1.05 pmol/L before vs 0.67 pmol/L 3 months after therapy, P < 0.05); and for serum concentration of TRACP-5b in responders to BD regimen (5.57 U/L before therapy vs 4.90 U/L 3 months after therapy, P < 0.05).

CONCLUSIONBortezomib lowers levels of serum DKK-1 and RANKL in responders, thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption. Thalidomide decreases bone resorption regardless of treatment response.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bone Resorption ; drug therapy ; Boronic Acids ; administration & dosage ; Bortezomib ; Dexamethasone ; administration & dosage ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; RANK Ligand ; blood ; Thalidomide ; administration & dosage

OBJECTIVETo evaluate the levels of bone morphogenetic protein-15 (BMP-15) in human follicular fluid (FF) and its association with response to ovarian stimulation.

METHODSWestern blotting was performed to determine the levels of BMP-15 in FF obtained from follicle aspirates in 70 patients undergoing IVF treatment. According to the response to ovarian stimulation the patients were divided into poor responder group and normal responder group.

RESULTBMP-15 levels in FF of poor responders were significantly higher than those in normal responders (1.01 +/- 0.34 vs 0.77 +/- 0.24, P<0.01).

CONCLUSIONIncreased levels of BMP-15 in FF may be associated with poor response to ovarian stimulation.

Adult ; Blotting, Western ; Bone Morphogenetic Protein 15 ; Female ; Follicle Stimulating Hormone ; administration & dosage ; Follicular Fluid ; drug effects ; metabolism ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; Growth Differentiation Factor 9 ; Humans ; Infertility, Female ; metabolism ; Intercellular Signaling Peptides and Proteins ; biosynthesis ; Ovary ; drug effects ; metabolism ; Ovulation Induction

OBJECTIVETo investigate the expression of PC cell-derived growth factor (PCDGF) in the serum of non-small cell lung cancer (NSCLC) patients and healthy adults, and it's correlation with chemotherapeutic sensitivity.

METHODSThe venous blood samples of 44 advanced NSCLC patients and 30 healthy adults were collected, and PCDGF mono-antibody was used for detection in the experiment. A part of specimens were randomly selected for Western-blot, and all specimens were eventually examined by ELISA. Chemotherapeutic response of these patients was recorded in order to analyze the correlation between PCDGF expression level and chemotherapeutic sensitivity.

RESULTSWestern blot results indicated that there was PCDGF expression both in NSCLC patients and healthy adults, and the expressing intensity of PCDGF in NSCLC patients was higher than that in healthy adults. The result of ELISA showed PCDGF expression in the patients whoever was chemoresistant or chemosensitive was significantly higher than that in healthy adults (P < 0.01), However, in chemoresistant patients, it was significantly higher than that in chemosensitive with a borderline statistical difference (P < 0.05).

CONCLUSIONPC cell-derived growth factor is found to be not only expressed in healthy adult but also in NSCLC patient at a high level in the serum, which may indicate metastasis and active proliferation in NSCLC. The intensity of PCDGF expression may be correlated with chemotherapy response and the high level expressing of PCDGF may indicate resistant to platinum-based chemotherapeutic regimen.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Blotting, Western ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; Cisplatin ; administration & dosage ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; blood ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Paclitaxel ; administration & dosage ; Remission Induction ; Vinblastine ; administration & dosage ; analogs & derivatives

Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart
Animals ; Chloramphenicol O-Acetyltransferase/analysis/genetics ; Comparative Study ; Cytomegalovirus/*genetics ; DNA, Viral/*administration & dosage/*genetics ; Endothelial Growth Factors/analysis/*genetics ; *Enhancer Elements (Genetics) ; Gene Expression Regulation, Viral ; Gene Fusion ; *Gene Transfer Techniques ; Genes, Viral ; Genetic Vectors ; Intercellular Signaling Peptides and Proteins/analysis/*genetics ; Lymphokines/analysis/*genetics ; Male ; Myocardium/*metabolism ; Plasmids/genetics ; *Promoter Regions (Genetics) ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart
Animals ; Chloramphenicol O-Acetyltransferase/analysis/genetics ; Comparative Study ; Cytomegalovirus/*genetics ; DNA, Viral/*administration & dosage/*genetics ; Endothelial Growth Factors/analysis/*genetics ; *Enhancer Elements (Genetics) ; Gene Expression Regulation, Viral ; Gene Fusion ; *Gene Transfer Techniques ; Genes, Viral ; Genetic Vectors ; Intercellular Signaling Peptides and Proteins/analysis/*genetics ; Lymphokines/analysis/*genetics ; Male ; Myocardium/*metabolism ; Plasmids/genetics ; *Promoter Regions (Genetics) ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors