Inhibition of bleomycin-induced pulmonary fibrosis in SD rats by sea cucumber peptides.

BACKGROUND: Pulmonary fibrosis (PF) is the terminal manifestation of a type of pulmonary disease, which seriously affects the respiratory function of the body, and with no effective cure for treatment. This study evaluated the effect of sea cucumber peptides (SCP) on bleomycin-induced SD rat PF. RESULTS: SCP can inhibit the PF induced by bleomycin. PF and SCP did not affect the food intake of rats, but PF reduced the body weight of rats, and SCP could improve the weight loss. SCP reduced lung index in PF rats in a dose-dependent manner. SCP significantly reduced IL-1ß, IL-6, TNF-α, α-SMA and VIM expression levels in lung tissue (P < 0.05), significantly decreased TGF-ß1 expression level in serum (P < 0.01) and the LSCP group and MSCP group had better inhibitory effects on PF than the HSCP group. Histomorphological results showed that SCP could ameliorate the structural damage of lung tissue, alveolar wall rupture, inflammatory cell infiltration, fibroblast proliferation and deposition of intercellular matrix and collagen fibers caused by PF. The improvement effect of the MSCP group was the most noteworthy in histomorphology. Metabolomics results showed that SCP significantly downregulated catechol, N-acetyl-l-histidine, acetylcarnitine, stearoylcarnitine, d-mannose, l-threonine, l-alanine, glycine, 3-guanidinopropionic acid, prostaglandin D2 and embelic acid d-(-)-ß-hydroxybutyric acid expression levels in lung tissue. CONCLUSION: SCP ameliorate bleomycin-induced SD rat PF. KEGG pathway analysis proved that SCP intervened in PF mainly via the lysosome pathway, with d-mannose as the key factor. © 2023 Society of Chemical Industry.

miRNA-331-3p Affects the Proliferation, Metastasis, and Invasion of Osteosarcoma through SOCS1/JAK2/STAT3.

MicroRNAs (miRNAs) are regulatory small noncoding RNAs that play a key role in several types of cancer. It has been reported that miR-331-3p is involved in the development and progression of various cancers, but there are few reports regarding osteosarcoma (OS). The public GEO database was used to analyze the survival difference of miR-331-3p in OS organizations. The level of cell proliferation assay was assessed by CCK-8 and colony formation. First, transwell and wound-healing assays were used to detect the transfer and invasion ability of miR-331-3p in OS. Second, TargetScan, miRDBmiR, TarBase, and dual-luciferase reporter gene assays were used to determine SOCS1 as a targeted regulator. Third, Western blot and immunohistochemistry were used to detect the expression of protein levels. Finally, a mouse model of subcutaneously transplantable tumors is used to evaluate the proliferation of OS in vivo. The low expression of miR-331-3p was negatively correlated with the overall survival of OS patients. Overexpression of miR-331-3p significantly inhibited cell proliferation, metastasis, and invasion. Moreover, miR-331-3p affected the occurrence and development of osteosarcoma by targeting the SOCS1/JAK2/STAT3 signaling pathway. Therefore, miR-331-3p reduces the expression of SOCS1 by combining with its 3'UTR, thereby activating the JAK2/STAT3 signaling pathway to regulate the progression of OS. This provides a new theoretical basis for the treatment of osteosarcoma.

Sea cucumber peptides inhibit the malignancy of NSCLC by regulating miR-378a-5p targeted TUSC2.

Lung cancer is a common cancer with high mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for the majority. The clinical treatment effect of NSCLC is not ideal. The aim of this study was to investigate the inhibitory effect of sea cucumber peptide (SCP) on NSCLC and its mechanism. The results showed that SCP could effectively inhibit the proliferation, migration and invasion of A549 cells. In addition, SCP can also inhibit the formation of pleural effusion and tumor growth in lung cancer mice, reduce liver and kidney injury, increase the levels of IL-2 and IL-12, decrease the levels of IL-6 and TNF-α, and prolong the survival time of mice. The microRNA sequencing and immunohistochemistry of mouse tumors showed that the tumor suppressor gene TUSC2 targeted by miR-378a-5p was involved in the inhibition of tumor growth by SCP. This study provides an experimental basis for the further development of SCP as an anti-tumor nutritional supplement, and provides a new idea for exploring the molecular mechanism of food derived active peptides in anti-tumor applications.

The Reference Intervals and Roles of GIR, HOMA and QUICKI Indexes to Judge Insulin Resistance/Insufficiency for Newly Diagnosed Diabetes Mellitus.

BACKGROUND: To establish the reference intervals of GIR, HOMA, and QUICKI index and to identify the clinical value of the three indexes for newly diagnosed diabetes mellitus. METHODS: The results of fasting glucose and insulin were acquired for 123 healthy individuals using Roche cobas-8000 to establish reference intervals of GIR, HOMA, and QUICKI based on Clinical and Laboratory Standards Institute (CLSI) EP28-A3. Meanwhile, 36 newly diagnosed type 1 and type 2 diabetes mellitus (DM) patients were enrolled to judge the effect of insulin resistance/insufficiency using the three indexes based on clinical initial treat-ment procedures. All the data were acquired from Wangjing Hospital, China Academy of Traditional Chinese Medicine. RESULTS: The reference intervals of GIR, HOMA, and QUICKI were 5.83 - 21.15, 0.87 - 4.22, and 0.309 - 0.392, respectively. Concerning to GIR, HOMA, and QUICKI, there were 57.7% (15/26), 80.8% (21/26), and 80.8% (21/26) outside of the reference limit among type 2 DM patients, respectively; The area under the curve (AUC) of the GIR > 10.937, HOMA < 5.436, and QUICKI > 0.299 were 0.937 (95% CI 0.681 - 1.000), 0.689 (95% CI 0.510 - 0.868), and 0.689 (95% CI 0.510 - 0.868) by ROC curves when insulin insufficiency was judged based on whether insulin was included in initial treatment procedures. There concordance rates were 77.8% (28/36), 50% (18/36), and 50% (18/36) using the three indexes, GIR, HOMA, and QUICKI, respectively. CONCLUSIONS: We established reference intervals for GIR, HOMA, and QUICKI. HOMA and QUICKI were more reliable indexes to identify insulin resistance among type 2 DM patients, but GIR was a more reliable index to identify insulin relatively or absolutely insufficiency than HOMA and QUICKI among DM patients.

Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance.

Platycodin D is a major pharmacological constituent of Platycodi Radix with immunomodulatory activity. The present study was designed to investigate how platycodin D (PLD) reveals liver injury in diabetic mice and its mechanism. Fifty mice were divided into five groups randomly: control group, model group, rosiglitazone (ROG, 10 mg/kg) group, PLD (50 mg/kg) group, and PLD (100 mg/kg) group. Diabetes was induced with the injection of alloxan monohydrate (150 mg/kg) subcutaneously, and animals with blood glucose level of ≥250 mg/dl were considered as diabetic mice. After the first day of diabetes induction, the treatments were performed for 8 weeks. Then the animals were anaesthetized, and blood and liver samples were also collected for further assay. PLD significantly decreased the serum levels of glucose, insulin, interleukin-6 (IL-6), interleukin-1ß, tumor necrosis factor-α (TNF-α), and interleukin (IL)-17A and increased IL-10 level in serum. PLD effectively downregulated aspartate transaminase (AST), alanine aminotransferase (ALT), total cholesterol (TC), and triglycerides (TG) in liver. PLD also attenuated liver histological change. In addition, PLD significantly attenuated IL-17A and IL-10 levels in vitro, flow cytometry (FCM) studies also showed that PLD remarkably inhibited Th17 cells and significantly increased Treg cells in liver tissues and spleen cells. Western blot demonstrated PLD inhibited the phosphorylation of JAK and STAT-3 and the expression of RORγt and increased the expression of Foxp3. The findings showed that PLD exerts beneficial effects on alloxan-induced liver injury in mice.

Effects of diethylhexyl phthalate (DEHP) given neonatally on spermatogenesis of mice.

We previously demonstrated that the effects of diethylhexyl phthalate (DEHP) alter reproduction function on male mice. Immature male mice were treated daily with DEHP from postnatal day 7-21, 7-35, 7-49, in a dose-dependent manner. As results, both the quality and quantity of spermatozoa were decreased in 60-day-old mice. The results by RT-PCR analysis indicated that DDx3Y, Usp9Y, RBM, E1F1AY, EGF, FSHR and EGFR genes were down-regulated, and LHR, Cyp17a1 and Cyp19a1 were down-regulated in response to DEHP. These genes were selected based on their markedly increased or decreased expression levels. However, DEHP had no effect on the meiotic process and recombination levels in male mouse germ cells. Treatment with DEHP induced histopathological changes in the testes. Taken together, these results provide a new insight into the molecular mechanisms underlying the detrimental impacts of DEHP in humans and wildlife.