Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study.

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.

Exploring the Benefits of Probiotics in Gut Inflammation and Diarrhea-From an Antioxidant Perspective.

Inflammatory bowel disease (IBD), characterized by an abnormal immune response, includes two distinct types: Crohn's disease (CD) and ulcerative colitis (UC). Extensive research has revealed that the pathogeny of IBD encompasses genetic factors, environmental factors, immune dysfunction, dysbiosis, and lifestyle choices. Furthermore, patients with IBD exhibit both local and systemic oxidative damage caused by the excessive presence of reactive oxygen species. This oxidative damage exacerbates immune response imbalances, intestinal mucosal damage, and dysbiosis in IBD patients. Meanwhile, the weaning period represents a crucial phase for pigs, during which they experience pronounced intestinal immune and inflammatory responses, leading to severe diarrhea and increased mortality rates. Pigs are highly similar to humans in terms of physiology and anatomy, making them a potential choice for simulating human IBD. Although the exact mechanism behind IBD and post-weaning diarrhea remains unclear, the oxidative damage, in its progression and pathogenesis, is well acknowledged. Besides conventional anti-inflammatory drugs, certain probiotics, particularly Lactobacillus and Bifidobacteria strains, have been found to possess antioxidant properties. These include the scavenging of reactive oxygen species, chelating metal ions to inhibit the Fenton reaction, and the regulation of host antioxidant enzymes. Consequently, numerous studies in the last two decades have committed to exploring the role of probiotics in alleviating IBD. Here, we sequentially discuss the oxidative damage in IBD and post-weaning diarrhea pathogenesis, the negative consequences of oxidative stress on IBD, the effectiveness of probiotics in IBD treatment, the application of probiotics in weaned piglets, and the potential antioxidant mechanisms of probiotics.

Macro- and microplastic leachates show a slightly toxic effect on seed germination of cotton.

Utilizing degradable mulching film effectively decreases the accumulation of plastic residuals in agriculture fields and their impacts on plant growth. However, the chemical risks to plants raised by leached substances from different microplastics are still unknown. This work determined the characteristics of macro- and microplastic leachates from different degradation (PE, PO, and Bio) and size (1 × 1 cm, 450-600 µm and <355 µm), as well as their impact on the germination of two varieties of cotton seeds. Our study revealed that degradable characteristics of macro-plastic significantly affect its leachates. Leachates of Bio gained higher dissolved organic carbon (DOC) concentration, aromatic, and values of slope ratios (SR) compared with PO and PE. The particle size of Bio macro- and microplastics also influences indicators such as SR, E250/E365, E253/E203, and Fmax value; however, fluctuations of those indicators were significantly lower than that induced by different degradable traits. Leachates of PE, PO, and Bio seem to have little impact on the germination of two varieties of cotton seeds, only mean germination time (MGT) and shoot height were slightly different among each treatment. A slight fluctuation of enzyme activities also indicates that plastic leachate did not generate excessive oxidative stress in cotton during germination. Leachates of macro- and microplastic under the tested concentration exhibited a slight toxic impact on cotton, which has high-stress tolerance. Thus, further studies should concentrate on the effects of plastic leachate on sensitive plants.