Estrogen alleviates liver fibrosis and restores metabolic homeostasis in ovariectomy-induced liver injury and carbon tetrachloride (CCl4) exposure.

AIM: Given estrogen's recognized regulatory influence on diverse metabolic and immune functions, this study sought to explore its potential impact on fibrosis and elucidate the underlying metabolic regulations. METHODS: Female mice underwent ovary removal surgery, followed by carbon tetrachloride (CCl4) administration to induce liver injury. Biochemical index analysis and histopathological examination were then conducted. The expression levels of alpha-smooth muscle actin (α-SMA), transforming growth factor-ß (TGF-ß), and collagen type 1 alpha 1 chain (COL1A1) were assessed using western blotting to further elucidate the extent of liver injury. Finally, metabolite extraction and metabolomic analysis were performed to evaluate metabolic changes. RESULTS: Ovary removal exacerbated CCl4-induced liver damage, while estrogen supplementation provided protection against hepatic changes resulting from OVX. Furthermore, estrogen mitigated liver injury induced by CCl4 treatment in vivo. Estrogen supplementation significantly restored liver damage induced by OVX and CCl4. Comparative analysis revealed significant alterations in pathways including aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism, lysine degradation, and taurine and hypotaurine metabolism in estrogen treatment. CONCLUSION: Estrogen supplementation alleviates liver injury induced by OVX and CCl4, highlighting its protective effects against fibrosis and associated metabolic alterations.

Alloferon Mitigates LPS-Induced Endometritis by Attenuating the NLRP3/CASP1/IL-1ß/IL-18 Signaling Cascade.

Endometritis is an inflammatory reaction of the uterine lining that can lead to infertility. Alloferon, a linear non-glycosylated oligopeptide, has been recognized for its potent anti-inflammatory and immunomodulatory effects. In light of these attributes, this study aims to explore the potential therapeutic effects of alloferon in alleviating endometrial inflammation induced by lipopolysaccharide (LPS), while elucidating the underlying protective mechanisms. Two conditions representing pre- and post-menopause states were simulated using an ovariectomized (Ovx) murine model. The findings underscore alloferon's remarkable capacity to alleviate cardinal signs of endometritis, including redness, swelling, and congestion, while concurrently restoring the structural integrity of the endometrial tissue. Moreover, alloferon effectively modulates the expression of key inflammatory mediators, such as nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease 1 (CASP1), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18). In vitro experiments were conducted to further corroborate and validate these findings. In conclusion, alloferon shows promising potential in mitigating LPS-induced inflammation by attenuating the NLRP3/CASP1/IL-1ß/IL-18 signaling cascade.

Study of alloferon, a novel immunomodulatory antimicrobial peptide (AMP), and its analogues.

Antimicrobial peptides (AMPs) are widely distributed throughout the biosphere and represent a class of conserved peptide molecules with intrinsic antimicrobial properties. Their broad-spectrum antimicrobial activity and low risk to induce resistance have led to increased interest in AMPs as potential alternatives to traditional antibiotics. Among the AMPs, alloferon has been addressed due to its immunomodulatory properties that augment both innate and adaptive immune responses against various pathogens. Alloferon and its analogues have demonstrated pharmaceutical potential through their ability to enhance Natural Killer (NK) cell cytotoxicity and stimulate interferon (IFN) synthesis in both mouse and human models. Additionally, they have shown promise in augmenting antiviral and antitumor activities in mice. In this article, we provide a comprehensive review of the biological effects of alloferon and its analogues, incorporating our own research findings as well. These insights may contribute to a deeper understanding of the therapeutic potential of these novel AMPs.

Protective Effects of Lactobacillus gasseri against High-Cholesterol Diet-Induced Fatty Liver and Regulation of Host Gene Expression Profiles.

Fatty liver is one of the most pervasive liver diseases worldwide. Probiotics play an important role in the progression of liver disease, but their effects on host regulation are poorly understood. This study investigated the protective effects of lactobacillus gasseri (L. gasseri) against high-cholesterol diet (HCD)-induced fatty liver injury using a zebrafish larvae model. Liver pathology, lipid accumulation, oxidative stress and hepatic inflammation were evaluated to demonstrate the changes in a spectrum of hepatic injury. Moreover, multiple indexes on host gene expression profiles were comprehensively characterized by RNA screening. The results showed that treatment with L. gasseri ameliorated HCD-induced morphological and histological alterations, lipid regulations, oxidative stress and macrophage aggregation in the liver of zebrafish larvae. Furthermore, the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed that the core pathways of L. gasseri regulation were interleukin-17 (IL-17) signaling, phosphoinositide 3-kinase (PI3K)-AKT signaling pathway, the regulation of lipolysis and adipocytes and fatty acid elongation and estrogen signaling. The genes at key junction nodes, hsp90aa1.1, kyat3, hsd17b7, irs2a, myl9b, ptgs2b, cdk21 and papss2a were significantly regulated by L. gasseri administration. To conclude, the current research extends our understanding of the protective effects of L. gasseri against fatty liver and provides potential therapeutic options for fatty liver treatment.

Fabrication and Evaluation of 3D Printed Poly(l-lactide) Scaffold Functionalized with Quercetin-Polydopamine for Bone Tissue Engineering.

Quercetin (Qu), a bioflavonoid, has been reported to positively affect bone metabolism. For the first time, Qu with different concentrations was utilized to functionalize 3D-printed poly(l-lactide) (PLLA) scaffold with the aid of a polydopamine (PDA) layer through a convenient and effective way in this study. Results revealed that the coexistence of PDA and Qu can capacitate the 3D-printed PLLA scaffold to possess rougher surface, as well as better hydrophilicity and compressive properties. The resulting PDA- and Qu-modified PLLA scaffolds (Qu/PD-PLLA) can sustainably release Qu to some extent, which is more beneficial to the proliferation and attachment of MC3T3-E1 cells, upregulating ALP activity and calcium nodules as well as promoting the expression of related osteogenic genes and proteins. More significantly, such a positive impact of the Qu on the cell affinity and osteogenic activity played in a dose-dependent manner. This study revealed the potential of the 3D-printed Qu/PD-PLLA scaffolds with a certain amount of Qu as bone-repair materials.

Fabrication, antibacterial activity and cytocompatibility of quaternary ammonium chitooligosaccharide functionalized polyurethane membrane via polydopamine adhesive layer.

In this study, to enhance the antibacterial activity and cytocompatibility of the electrospinning polyurethane (PU) fibrous membrane, quaternary ammonium chitooligosaccharide (G-COS) was immobilized on the fibrous membrane surface via an intermediate layer of polydopamine (PDOPA) to obtain the G-COS functionalized PU (G-C-D-PU), as a control, chitooligosaccharide (COS) functionalized PU fibrous membrane (C-D-PU) was prepared, too. Surface composition, morphology, hydrophilicity and surface energy of the original and modified PU fibrous membranes were characterized, which revealed that the surface roughness and hydrophilicity of the PU fibrous membrane were obviously increased by modified with COS and G-COS, respectively. Antibacterial experiment against E. coli and S. aureus indicated that antibacterial activity of the G-C-D-PU fibrous membrane was markedly superior to that of pure PU and C-D-PU fibrous membranes. In vitro cells culture experiments revealed that the adhesion and proliferation of NIH-3T3 cells on the PU fibrous membrane were improved by successively immobilized with PDOPA and COS as well as G-COS with the concentration of 2 g/L and 6 g/L. Moreover, the G-C-D-PU fibrous membranes with relative high G-COS content were more beneficial to the enhancement of antibacterial activity, but on the contrary, those with relative low G-COS content were more in favor of cell attachment and proliferation.

Preparation of Icariin and Deferoxamine Functionalized Poly(l-lactide)/chitosan Micro/Nanofibrous Membranes with Synergistic Enhanced Osteogenesis and Angiogenesis.

Osteogenesis is tightly complemented with angiogenesis during the bone regeneration process. In this study, to synergistically enhance the osteogenesis and angiogenesis of poly(l-lactide) (PLLA), PLLA/chitosan (PLLA/CS) composite fibrous membrane was prepared first by combining electrospinning and thermally induced phase separation technologies. Then, with the aid of polydopamine (PDA) coating, two types of bioactive molecules of icariin (ICA) and deferoxamine (DFO) were chosen to singly or simultaneously surface modify the as-prepared PLLA/CS-PDA membrane, thereby fabricating PLLA/CS-PDA/ICA, PLLA/CS-PDA/DFO, and PLLA/CS-PDA/ICA/DFO membranes. The morphology and properties of the pristine and modified PLLA fibrous membranes were studied, which revealed that the modified PLLA membrane's own hierarchical fibrous structure improved hydrophilicity and had better tensile properties by introducing PDA and ICA or DFO. On account of the synergetic contributions of ICA and DFO as well as the hierarchical fibrous structure, the PLLA/CS-PDA/ICA/DFO membrane exhibited superior cytocompatibility and osteogenic activity of MC3T3-E1 cells compared to other membranes, which was confirmed by the enhanced cell adhesion, proliferation, osteogenic differentiation, and mineralization. Besides, compared with those without or single immobilization of ICA or DFO, the PLLA/CS-PDA/ICA/DFO membrane with ICA and DFO together could significantly promote the growth and expression of angiogenic-related factors of HUVECs. Particularly, ICA not only exhibits favorable osteogenic activity but also shows superior angiogenic activity even compared to DFO. On the contrary, DFO possesses well-known angiogenic activity but manifests a better osteogenic activity compared with ICA. Overall, our study demonstrated that the PLLA/CS-PDA/ICA/DFO membrane exerts synergistic effects on osteogenesis and angiogenesis, thereby holding great potentials as a substitute for bone repair.