Abstract Background The biosimilar landscape for malignancies continues to grow, with several biosimilars for reference product bevacizumab currently available. Bevacizumab has been shown to be well tolerated; however, the safety of recombinant humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody injection remains unclear. This study aimed to compare the pharmacokinetics (PK), safety, and immunogenicity of recombinant humanized anti-VEGF monoclonal antibody injection to that of Avastin® in healthy Chinese male volunteers. Methods A randomized, double-blind, single-dose, and parallel-group study was performed on 88 healthy men who randomly (1:1) received either the test drug as an intravenous infusion of 3 mg/kg or Avastin®. The primary PK parameter was area under the serum concentration-time curve (AUC) from time zero to last quantifiable concentration (AUC 0–t ). Secondary endpoints included maximum observed serum concentration (C max ), AUC from 0 extrapolated to infinity (AUC inf ), safety, and immunogenicity. Serum bevacizumab concentrations were measured using a validated enzyme-linked immunosorbent assay (ELISA). Results The baseline characteristics were similar among the two groups. The 90% confidence interval (CI) for the geometric mean ratio of AUC 0–t , C max and AUC inf between the test group and reference group were 91.71%–103.18%, 95.72%–107.49% and 91.03%–103.43%, respectively. These values were within the predefined bioequivalence margin of 80.00%–125.00%, demonstrating the biosimilarity of the test drug and Avastin®. Eighty-one treatment-emergent adverse events were reported, with a comparable incidence among the test group (90.91%) and the reference group (93.18%). No serious adverse events were reported. The incidence of ADA antibodies in the two groups was low and similar. Conclusion In healthy Chinese men, PK similarity of recombinant humanized anti-VEGF monoclonal antibody injection to Avastin® was confirmed, with comparable safety and immunogenicity. Subsequent studies should investigate recombinant humanized anti-VEGF monoclonal antibody injection in patients setting. Trial registration Registered 08/10/2019, CTR20191923.
Glycerol is seen in biological systems as an intermediate in lipid metabolism. In recent years, glycerol has been reported to act as a chemical chaperone to correct the conformation of proteins. Here, we investigate the role of glycerol in galectin-7 (Gal-7). The thermal shift and CD assays showed that the thermal stability of Gal-7 increased with glycerol concentration but with little secondary structure changes induced by glycerol. In addition, glycerol can inhibit Gal-7-mediated erythrocyte agglutination. We also solved the crystal structures of human Gal-7 in complex with glycerol in two different conditions. Glycerol binds at the carbohydrate-recognition binding sites of Gal-7, which indicates glycerol as a small ligand for Gal-7. Surprisingly, glycerol can bind a new pocket near the N-terminus of Gal-7, which can greatly reduce the flexibility and improve the stability of this region. Moreover, overexpression of Gal-7 decreased the intracellular triglyceride levels and increased mRNA expression of aquaporin-3 (AQP-3) when HeLa cells were incubated with glycerol. These findings indicate that Gal-7 might regulate glycerol metabolism. Overall, our results on human Gal-7 raise the perspective to systematically explore this so far unrecognized phenomenon for Gal-7 in glycerol metabolism.
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin-like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.
Background With increasing knowledge about the gut – bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of Lactobacillus rhamnosus GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.Results We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.Conclusions Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.
Solar photovoltaic technology is a mature, stable and sustainable energy solution with important social and economic benefits.This study aims to investigate the technical and economic feasibility of installing solar PV systems on the building roofs in the university campus.The techno-economic analysis was carried out under three installation scenarios: PV modules parallel to the pitched roof, PV modules aligned at the optimal tilt angle on flat roof and pitched roof, respectively.The results show that, the flat roof has the potential installed capacity of 3.82 MW with an annual generation capacity of 4.51 GMh, while the pitched roof has the potential installed capacity of 2.45 MW and 2.64 MW with an annual generation capacity of 2.89 GWh and 3.11 GWh depending on two installation orientations and tilt angles, respectively.The economic analysis of the above three scenarios shows that all PV systems are in profit and positive net cash flow in year 5 for PV projects installed at optimal tilt on flat roofs and parallel to the roof on pitched roofs, and positive net cash flow in year 6 for PV projects installed at optimal tilt on pitched roofs.
There is increasing evidence that sex hormones are involved in the development of lung cancer, but the correlation between the reproductive behavior that changes sex hormone levels and lung cancer is not yet clear. Many previous studies have investigated the association between reproductive factors and lung cancer risk, but the results have been inconsistent. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential relationship between age at first sexual intercourse (AFS), age at menarche, and age at menopause, and lung cancer.
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