Age-Dependent Changes in the Plasma Proteome of Healthy Adults.

OBJECTIVE: Human blood plasma is a complex that communicates with most parts of the body and reflects the changes in the state of an organism. Identifying age-related biomarkers can help predict and monitor age-related physiological decline and diseases and identify new treatments for diseases. METHODS AND PARTICIPANTS: In this study, TMT-LC-MS/MS was utilized to screen differentially expressed plasma proteins in 118 healthy adults of different ages. Participants were divided into three groups: 21-30 years of age (Young), 41-50 years of age (Middle) and ≥60 years of age (Old). RESULTS: The number of differentially expressed proteins in the comparisons of Young vs Middle, Middle vs Old and Young vs Old were 82, 22 and 99, respectively. These proteins were involved in numerous physiological processes, such as "negative regulation of smooth muscle cell proliferation" and "blood coagulation". Moreover, when Young was compared with Middle or Old, "complement and coagulation cascades" was the top enriched pathway by KEGG pathway enrichment analysis. Functional phenotyping of the proteome demonstrated that the plasma proteomic profiles of young adults were strikingly dissimilar to those of the middle-aged or older adults. CONCLUSIONS: The results of this study mapped the variation in the expression of plasma proteins and provided information about possible biomarkers/treatments for different age-related functional disorders.

Somatostatin receptors SSTR2 and SSTR5 are expressed in the human thoracic duct.

Somatostatin and its analog octreotide have been used successfully to treat postoperative chylothorax, and it has been shown that octreotide binds with high affinity to somatostatin receptor (SSTR) subtypes 2 and 5. Therefore, we investigated expression of SSTR2 and SSTR5 in the human thoracic duct by immunohistochemistry. Normal rat pancreas was used as a positive control for antibodies against SSTR2 and SSTR5, and Factor VIII-related antigen, SMA, actin, elastin, or collagen type II, III, IV or V antibodies were used to identify cell types and structures within the human thoracic duct. The antibodies against SSTR2 and SSTR5 worked well and yielded positive staining in control rat islets. In the human thoracic duct, SSTR2 was present in smooth muscle cells and some scattered structures which were stained by antibodies against Factor VIII-related antigen, SMA, actin, elastin or collagen type II, III, IV or V. SSTR5 was also present in smooth muscle cells. The presence of SSTR2 and SSTR5 in the human thoracic duct sheds light on the mechanism of somatostatin and octreotide use in the successful treatment of chylothorax and offers new molecular pathways to explore for potential future therapies.

The support of matrix accumulation and the promotion of sheep articular cartilage defects repair in vivo by chitosan hydrogels.

OBJECTIVE: Chitosan has been widely used as an injectable scaffold in cartilage tissue engineering due to its characteristic biocompatibility and biodegradability. In this study, chitosan was used in its hydrogel form as a scaffold for chondrocytes that act to reconstruct tissue-engineered cartilage and repair articular cartilage defects in the sheep model. This study aims to find a novel way to apply chitosan in cartilage tissue engineering. METHODS: Temperature-responsive chitosan hydrogels were prepared by combining chitosan, beta-sodium glycerophosphate (GP) and hydroxyethyl cellulose (HEC). Tissue-engineered cartilage reconstructions were made in vitro by mixing sheep chondrocytes with a chitosan hydrogel. Cell survival and matrix accumulation were analyzed after 3 weeks in culture. To collect data for in vivo repair, reconstructions cultured for 1 day were transplanted to the freshly prepared defects of the articular cartilage of sheep. Then at both 12 and 24 weeks after transplantation, the grafts were extracted and analyzed histologically and immunohistochemically. RESULTS: The results showed that the chondrocytes in the reconstructed cartilage survived and retained their ability to secrete matrix when cultured in vitro. Transplanted in vivo, the reconstructions repaired cartilage defects completely within 24 weeks. The implantation of chitosan hydrogels without chondrocytes also helps to repair cartilage defects. CONCLUSIONS: The chitosan-based hydrogel could support matrix accumulation of chondrocytes and could repair sheep cartilage defects in 24 weeks. This study showcased the success of a new technique in its ability to repair articular cartilage defects.

Evidences for the presence of a somatomedin-like plasma factor(s) in the Japanese eel, Anguilla japonica.

The indirect action of growth hormone (GH) through a somatomedin-like plasma factor(s) on the synthesis of mucopolysaccharides in the ceratobranchial cartilages of the Japanese eel, Anguilla japonica, was studied by monitoring the uptake of [35S]sulfate in vitro. Addition of plasma obtained from intact eels significantly stimulated the sulfate uptake by the cartilages of hypophysectomized eel, whereas plasma from hypophysectomized eels had no effect. On the other hand, the plasma from hypophysectomized eels which had been injected with eel GH significantly stimulated the uptake. The maximal stimulating activity was found in the plasma 24 hr after a single injection of eel GH (2 micrograms/g). This stimulatory activity was dependent on the dose of GH injected. These findings indicate that GH elicits its effect on the cartilages indirectly through a GH-dependent plasma factor(s). The system established in the present study can provide as a biological assay for the somatomedin-like plasma factor(s).

Effects of recombinant eel growth hormone on the uptake of [35S]sulfate by ceratobranchial cartilages of the Japanese eel, Anguilla japonica.

Effects of growth hormone (GH) on the synthesis of mucopolysaccharide by ceratobranchial cartilages of the Japanese eel, Anguilla japonica, were examined by monitoring the in vitro uptake of [35S]sulfate. The [35S]sulfate uptake decreased rapidly to one-third of the initial level during the first 3 days after hypophysectomy, and decreased gradually thereafter. When hypophysectomized eels were injected intramuscularly with recombinant eel GH (2 micrograms/g), the plasma GH concentrations increased maximally after 6 hr, and declined rapidly thereafter. On the other hand, the sulfate uptake increased significantly after 12 hr, and high levels were maintained until 48 hr. The stimulating effect of GH was dose dependent (0.02-2 micrograms/g). However, the addition of eel GH (0.05-5 micrograms/ml) to the culture medium did not affect the sulfate uptake by hypophysectomized eel cartilages, suggesting that the stimulative action of GH on the sulfate uptake by the cartilages is indirect.