Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.

Autosomal dominant polycystic kidney disease is a genetic kidney disease caused by mutations in the genes PKD1 or PKD2. Its course is characterized by the formation of progressively enlarged cysts in the renal tubules bilaterally. The basic genetic explanation for autosomal dominant polycystic kidney disease is the double-hit theory, and many of its mechanistic issues can be explained by the cilia doctrine. However, the precise molecular mechanisms underpinning this condition's occurrence are still not completely understood. Experimental evidence suggests that aquaporins, a class of transmembrane channel proteins, including aquaporin-1, aquaporin-2, aquaporin-3, and aquaporin-11, are involved in the mechanism of autosomal dominant polycystic kidney disease. Aquaporins are either a potential new target for the treatment of autosomal dominant polycystic kidney disease, and further study into the physiopathological role of aquaporins in autosomal dominant polycystic kidney disease will assist to clarify the disease's pathophysiology and increase the pool of potential treatment options. We primarily cover pertinent findings on aquaporins in autosomal dominant polycystic kidney disease in this review.

Morphology and Molecular Phylogeny of the Genus Stigeoclonium (Chaetophorales, Chlorophyta) from China, Including Descriptions of the Pseudostigeoclonium gen. nov.

Stigeoclonium is a genus of green algae that is widely distributed in freshwater habitats around the world. The genus comprises species with variously developed prostrates and erect systems of uniseriate branched filaments and grows attached to a wide range of different surfaces. It holds significant promise for applications in water quality indicators, sewage treatment, and the development of high-value-added products. Nevertheless, our comprehension of Stigeoclonium remains unclear and perplexing, particularly regarding its fundamental systematic taxonomy. Recent molecular analyses have revealed that the morphologically well-defined genus Stigeoclonium is polyphyletic and requires taxonomic revision. Phylogenetic analysis based on a single molecular marker and limited samples is insufficient to address the polyphyletic nature of Stigeoclonium. In the present study, 34 out of 45 strains of Stigeoclonium were newly acquired from China. Alongside the morphological data, a concatenated dataset of three markers (18S rDNA + ITS2 + tufA) was utilized to determine their molecular phylogeny. The phylogenetic analysis successfully resolved the broadly defined Stigeoclonium into three robustly supported clades (Stigeoclonim tenue clade, S. farctum clade, and S. helveticum clade). The morphological characteristics assessment results showed that the cell type of the main axis-producing branch, considered a crucial morphological characteristic of the Stigeoclonium taxonomy, did not accurately reflect the real phylogeny of the genus. A new taxonomical classification of the genus Stigeoclonium was proposed based on zoospores' germination types, which aligned well with the phylogenetic topologies. Species where zoospores showed erect germination (S. helveticum clade) formed a distinct monophyletic clade, clearly separated from the other two clades, with zoospores showing prostrate germination or pseudo-erect germination. Consequently, a new genus, Pseudostigeoclonium gen. nov., is suggested to include all species in the broadly defined Stigeoclonium with zoospores with erect germination. The taxonomic diversity is supported by distinctive morphological differences and phylogenetic divergence within the broadly defined Stigeoclonium identified in this study. Further evaluation of the genus Stigeoclonium is necessary, especially via examining additional specimens and re-evaluating morphological characters under precisely defined laboratory conditions.

Cartilage-targeting poly(ethylene glycol) (PEG)-formononetin (FMN) nanodrug for the treatment of osteoarthritis.

Intra-articular (IA) injection is an efficient treatment for osteoarthritis, which will minimize systemic side effects. However, the joint experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with an average diameter about 218 nm. The in vitro test using IL-1ß stimulated chondrocytes indicated that PCFMN was biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide a reference for clinical OA therapy.

Osteogenic Potential of Electrospun Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/ Poly(ethylene glycol) Nanofiber Membranes.

Nanofibers as niche-biomimetic scaffolds exhibit potential in bone tissue engineering (BTE). Here, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) co-polymer (P34HB)/poly(ethylene glycol) (PEG) nanofiber membranes with a high hydrophilicity and mechanical properties were fabricated by introducing PEG to P34HB via electrospinning. The P34HB/PEG nanofibrous scaffolds were investigated for their potential in the osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells (BMSCs). By adjusting the ratio of PEG to P34HB, three scaffolds, including P34HB, P34HB/10 wt%PEG, and P34HB/30 wt%PEG, were successfully fabricated. The composite P34HB/PEG nanofiber membranes showed an enhanced hydrophilicity, a decreased fiber size, and an increased mechanical strength compared with those of P34HB. In-vitro studies showed that the P34HB/PEG membranes better supported cell adhesion, spreading, and proliferation than those of P34HB. The incorporation of PEG into the P34HB scaffold also promoted the osteoinduction capacity, as evidenced by activation of the alkaline phosphatase activity (ALP) activity, increased gene expression of bone specific markers (such as RUNX2, ALP, Col1a1, OPN, OCN, and BMP2), and mineral nodules formation. Comparatively, P34HB/10 wt%PEG showed a higher hydrophilicity and mechanical properties, as well as a better biological performance than the other membranes. Thus, the electrospun P34HB/PEG nanofiber membranes may be potentially developed as regenerative materials for BTE applications.