Identification of HTRA1, DPT and MXRA5 as potential biomarkers associated with osteoarthritis progression and immune infiltration.

BACKGROUND: Our study aimed to identify potential specific biomarkers for osteoarthritis (OA) and assess their relationship with immune infiltration. METHODS: We utilized data from GSE117999, GSE51588, and GSE57218 as training sets, while GSE114007 served as a validation set, all obtained from the GEO database. First, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were performed to identify hub modules and potential functions of genes. We subsequently screened for potential OA biomarkers within the differentially expressed genes (DEGs) of the hub module using machine learning methods. The diagnostic accuracy of the candidate genes was validated. Additionally, single gene analysis and ssGSEA was performed. Then, we explored the relationship between biomarkers and immune cells. Lastly, we employed RT-PCR to validate our results. RESULTS: WGCNA results suggested that the blue module was the most associated with OA and was functionally associated with extracellular matrix (ECM)-related terms. Our analysis identified ALB, HTRA1, DPT, MXRA5, CILP, MPO, and PLAT as potential biomarkers. Notably, HTRA1, DPT, and MXRA5 consistently exhibited increased expression in OA across both training and validation cohorts, demonstrating robust diagnostic potential. The ssGSEA results revealed that abnormal infiltration of DCs, NK cells, Tfh, Th2, and Treg cells might contribute to OA progression. HTRA1, DPT, and MXRA5 showed significant correlation with immune cell infiltration. The RT-PCR results also confirmed these findings. CONCLUSIONS: HTRA1, DPT, and MXRA5 are promising biomarkers for OA. Their overexpression strongly correlates with OA progression and immune cell infiltration.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway.

BACKGROUND: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. METHODS: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. RESULTS: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. CONCLUSION: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Influence of increasing acclimation temperature on growth, digestion, antioxidant capacity, liver transcriptome and intestinal microflora of Ussruri whitefish Coregonus ussuriensis Berg.

For effective restoration, conservation of Ussruri whitefish Coregonus ussuriensis Berg and coping with global climate change, effects of environmental temperature on Ussruri whitefish urgently need to be explored. In current study, the effects of different acclimation temperatures on the growth, digestive physiology, antioxidant ability, liver transcriptional responses and intestinal microflora patterns of Ussruri whitefish were investigated. Ussruri whitefish (15.20 g ± 1.23 g) were reared for 42 days under different acclimation temperatures, i.e., 10, 13, 16, 19, 22 and 25 °C, respectively. Result first determined 28 °C as the semi-lethal temperature in order to design the temperature gradient test. Highest main gain rate (MGR) and specific growth rate (SGR) were observed in fish group having acclimation temperature of 19 °C. Significantly decrease (P < 0.05) in triglyceride (TG) content appeared at 19 °C as compared to the 10 °C and 13 °C temperature groups. 19 °C notablely increased protease activities of stomach and intestine and intestinal lipase and amylase activities. 19 °C group obtained the highest activities of chloramphnicol acetyltransferase (CAT) and total antioxidant capacity (T-AOC) and higher activities of superoxide dismutase (SOD). The intestinal microflora composition was most conducive to maintaining overall intestinal health when the temperature was 19 °C, compared to 10 °C and 25 °C. Ussruri whitefish exposed to 10 °C and 25 °C possessed the lower Lactobacillus abundance compared to exposure to 19 °C. Temperature down to 10 °C or up to 25 °C, respectively, triggered cold stress and heat stress, which leading to impairment in intestinal digestion, liver antioxidant capacity and intestinal microflora structure. Liver transcriptome response to 10 °C, 19 °C and 25 °C revealed that Ussruri whitefish might require the initiation of endoplasmic reticulum stress to correct protein damage from cold-temperature and high-temperature stress, and it was speculated that DNAJB11 could be regarded as a biomarker of cold stress response.Based on the quadratic regression analysis of MGR and SGR against temperature, the optimal acclamation temperature were, respectively, 18.0 °C and 18.1 °C. Our findings provide valuable theoretical insights for an in-depth understanding of temperature acclimation mechanisms and laid the foundation for conservation and development of Ussruri whitefish germplasm resources.

Effects of Ammonia and Salinity Stress on Non-Volatile and Volatile Compounds of Ivory Shell (Babylonia areolata).

In this study, the flavor compounds of ivory shell (Babylonia areolata) and their changes caused by ammonia and salinity stresses were studied. Ammonia stress improved the contents of free amino acids (FAAs), 5'-adenosine monophosphate (AMP), citric acid, and some mineral ions such as Na+, PO43-, and Cl-. The FAA contents decreased with increasing salinity, while the opposite results were observed in most inorganic ions (e.g., K+, Na+, Mg2+, Mn2+, PO43-, and Cl-). Hyposaline and hypersaline stresses increased the AMP and citric acid contents compared to the control group. The equivalent umami concentration (EUC) values were 3.53-5.14 g monosodium glutamate (MSG)/100 g of wet weight, and the differences in EUC values among treatments were mainly caused by AMP. Hexanal, butanoic acid, and 4-(dimethylamino)-3-hydroxy- and (E, E)-3,5-octadien-2-one were the top three volatile compounds, and their profiles were significantly affected when ivory shells were cultured under different ammonia and salinity conditions.

Dietary Taurine Intake Affects the Growth Performance, Lipid Composition, and Antioxidant Defense of Juvenile Ivory Shell (Babylonia areolata).

In this study, an eight-week feeding trial was performed to investigate the effects of different taurine supplementation levels (0.0% as control, 1.0%, 1.5%, 2.0%, 2.5%, and 3.0%) on the growth performance, lipid composition, and antioxidant ability in juvenile ivory shells Babylonia areolata. The results showed that taurine supplementation significantly improved the specific growth rates (SGRs) and survival rates of ivory shell (except the survival rate in the 3.0% taurine diet group) (p < 0.05). The SGRs showed an increasing and then decreasing tendency with increasing dietary taurine supplementation, and the highest value was observed in the 2.0% taurine diet (2.60%/d). The taurine content in the muscle of ivory shells fed taurine-supplemented diets significantly increased when compared to the control group (p < 0.05). The profiles of C22:2n6 in the muscle of ivory shells fed taurine-supplemented diets were significantly higher than in the control group (p < 0.05), and the highest values were observed in the 2.0% taurine supplementation group. The high-density lipoprotein cholesterol (HDL-C) content in the hepatopancreas showed an increasing and then decreasing tendency with increasing dietary taurine supplementation, while the low-density lipoprotein cholesterol (LDL-C) concentration showed a decreasing tendency. Furthermore, the activities of pepsin and lipase in both the intestine and hepatopancreas significantly increased at moderate taurine supplementation levels compared to the control group (p < 0.05). Accordingly, obvious increases in the histological parameters in the intestine of ivory shells fed taurine-supplemented diets were also found. As for the antioxidant ability, the activities of the total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) showed an increasing and then decreasing tendency with increasing dietary taurine supplementation, and the highest values were observed in the 1.0% and 1.0-2.0% taurine supplementation groups, respectively; the malondialdehyde (MDA) contents significantly decreased with increasing dietary taurine supplementation (p < 0.05). The taurine intake affected the expression of four appetite-related genes in the hepatopancreas, in which orexin and NPY showed an increasing and then decreasing tendency, while leptin and cholecyatoklnin decreased with increasing dietary taurine supplementation. In conclusion, moderate taurine supplementation in an artificial diet (about 1.5-2.0%) could improve the growth performance and antioxidant ability and change the lipid composition of juvenile ivory shells.

CS-NO suppresses inhibits glycolysis and gastric cancer progression through regulating YAP/TAZ signaling pathway.

CONTEXT: Gastric cancer (GC) is a significant contributor to global mortality and is recognized for its elevated prevalence and fatality rates. Nitric Oxide (NO) plays a role in multiple aspects of cancer metastasis and progression. CS-NO is a polysaccharide-based biomaterial with NO-releasing properties that shows promising therapeutic potential. Nonetheless, the action mechanism of CS-NO in GC is still largely unclear. METHODS: The present study employed various experimental techniques, including CCK-8 assay, colony formation assay, EdU staining, and transwell assays, to evaluate the proliferation, migration, and invasion of GC cells. Additionally, ELISA was utilized to measure glucose uptake, lactate production, and cellular ATP levels in GC cells. In vivo investigations on nude mice were conducted to validate the in vitro results. OBJECTIVE: The present study aimed to examine the potential anti-tumor properties of CS-NO on GC through in vitro and in vivo investigations, while also exploring the underlying mechanisms involved. RESULTS: Our data suggested that CS-NO might prevent GC cell invasion and migration. Decreased expressions of GLUT1, HK2, and LDHA further demonstrated that CS-NO significantly suppressed aerobic glycolysis in GC cells. The administration of CS-NO resulted in a significant reduction of YAP and TAZ levels in GC cells. Our data further show that CS-NO treatment could inhibit GC cancer growth in mice, consistent with the significant decrease in Ki67, GLUT1 and YAP expression levels. DISCUSSION AND CONCLUSION: These findings could reveal the good effects of CS-NO therapy on inhibiting GC.

Co3O4 nanocrystals as matrices for the detection of amino acids, harmful additives and pesticide residues by MALDI-TOF MS.

Research of detection of low molecular weight compounds on human health and biological systems become increasingly important. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), a soft ionization equipment, is a rapid, reliable, high-sensitivity, high-throughput and simple test instrument. However, the application of MALDI-TOF MS in the analysis of small molecules (<500 Da) has become a great challenge because of the interference from the conventional matrices in low mass region when using conventional matrices. In this research, tricobalt tetraoxide (Co3O4) nanocrystals with rich surface hydroxyl groups were synthesized and served as novel matrices for the detection of small molecules by MALDI-TOF MS. In comparison with conventional organic matrices, the use of as-prepared Co3O4 nanocrystal matrices showed little matrix background interference, good reproducibility and high signal intensity in the analyses of amino acids, harmful additives and pesticide residues. For the detection of most amino acids, Co3O4 nanocrystal matrices have good detection performance both in the positive and negative ion modes and have a unique decarboxylation peak in the positive ion mode, which is conducive to the identification of amino acids. In addition, Co3O4 nanocrystals are completely feasible to test triadimefon, pirimicarb and other pesticide residues, as well as additives such as bisphenol A and melamine in the positive ion mode. It is also feasible to detect small molecule compounds in practical samples using Co3O4 nanocrystals as matrices. We believe the work provides an alternative approach for the detection of small molecules and expands the application scope of Co3O4 nanocrystals.

Dihydroartemisinin alleviates high glucose-induced vascular smooth muscle cells proliferation and inflammation by depressing the miR-376b-3p/KLF15 pathway.

Inflammation and the proliferation of vascular smooth muscle cells (VSMCs) are seen to play critical roles in the development of vascular complications induced by diabetes and hyperglycemia. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the effect of DHA on high glucose (HG)-induced inflammation and proliferation of VSMCs remains unknown. Therefore, this study aims to show that DHA significantly inhibited the proliferation of VSMCs and that expression of the inflammatory cytokines IL-1ß and TNF-α was induced by HG in a dose-dependent manner. Additionally, we were able to determine that KLF15 played a critical role in HG-induced VSMC proliferation and inflammation, confirming its protective effects observed after DHA treatment in the HG-induced inflammatory response of VSMCs. DHA was observed to directly depress the HG-induced expression of miR-376b-3p, which targeted the 3'-UTR of KLF15 and inhibited its expression. These results suggested that DHA plays a protective role in HG-induced VSMC proliferation and associated inflammation by inhibiting the miR-376b-3p/KLF15 axis. Our findings provide new evidence of the mechanisms of DHA and its critical role in treating the pathogenesis of diabetic vascular complications.