Pulmonary arterial hypertension (PAH) is a severe disorder of lung vasculature that causes right heart failure. Homoeostatic effects of flow-activated transcription factor Krüppel-like factor 2 (KLF2) are compromised in PAH. Here, we show that KLF2-induced exosomal microRNAs, miR-181a-5p and miR-324-5p act together to attenuate pulmonary vascular remodelling and that their actions are mediated by Notch4 and ETS1 and other key regulators of vascular homoeostasis. Expressions of KLF2, miR-181a-5p and miR-324-5p are reduced, while levels of their target genes are elevated in pre-clinical PAH, idiopathic PAH and heritable PAH with missense p.H288YKLF2mutation. Therapeutic supplementation of miR-181a-5p and miR-324-5p reduces proliferative and angiogenic responses in patient-derived cells and attenuates disease progression in PAH mice. This study shows that reduced KLF2 signalling is a common feature of human PAH and highlights the potential therapeutic role of KLF2-regulated exosomal miRNAs in PAH and other diseases associated with vascular remodelling.

Cancer is a threatening disease that needs strong therapy with fewer side effects. A lot of different types of chemotherapy or chemo-drugs are used in cancer treatments but have many side effects. The increasing number of antibiotic-resistant microorganisms requires more study of new antimicrobial compounds and delivery and targeting strategies. This work aims to isolate and identify Azotobacter sp., and extract alginate from Azotobacter sp. As well as fabricating selenium nanoparticles using ascorbic acid as reducing agent (As/Se-NPs), and loading extracted alginate with selenium nanoparticles (Alg-Se-NCMs). The As/Se-NPs and Alg-Se-NCMs were categorized by TEM, EDX, UV–Vis spectrophotometry, FT-IR, and zeta potential. The antifungal activities of both As/Se-NPs and Alg-Se-NCMs were investigated against some human pathogen fungi that cause skin infection such as Aspergillus niger (RCMB 002005), Aspergillus fumigatus (RCMB 002008), Cryptococcus neoformans (RCMB 0049001), Candida albicans (RCMB 005003), and Penicillium marneffei (RCMB 001002). The anticancer activities were determined against HCT-116 colorectal cancer and Hep G2 human liver cancer cells. UV spectra of As/Se-NPs and Alg-Se-NCMs confirmed a surface plasmon resonance at 269 and 296 nm, and zeta potential has negative charges −37.2 and −38.7 mV,. Both As/Se-NPs and Alg-Se-NCMs were hexagonal, size ranging from 16.52 to 97.06 and 17.29 to 44.2. Alg-Se-NCMs had anticancer activities against HCT-116 and HepG2. The Alg-Se-NCMs possessed the highest antifungal activities against Cryptococcus neoformans, followed by Aspergillus niger, but did not possess any activities against Penicillium marneffei. Alginate-capped selenium nanoparticles can be used as antifungal and anticancer treatments.

Gold nanoparticles (Au-NPs) have several uses for nanobiotechnologists because of their beneficial biomedical properties. Alginates have various biomedical and industrial applications. The aim of this study is to extract alginate from Azotobacter chroococcum , synthesize chemical Au-NPs (Ch/Au-NPs), and load the NPs with the extracted alginate to form Azotobacter alginate gold nanocomposites (Azto/Alg-Au-NCMs). The Ch/Au-NPs and Azto/Alg-Au-NCMs were characterized by UV-spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), zeta potential, and transmission electron microscopy (TEM). The anticancer activities were determined using the breast cancer cell line MCF-7, human lung cancer cell line H1299, and Vero cell line. The results obtained by UV-spectroscopy exhibited a surface plasmon resonance that was clearly noticeable at 530 nm, and the EDS analysis proved that gold was present in percentages of 50.11 and 28.08 in the Ch/Au-NPs and Azto/Alg-Au-NCMs, respectively. There were several similarities between the alginic acid and the alginate extracted from A. chroococcum, and small modifications were proved by FT-IR spectroscopy. Negative charges were shown by the zeta potential. Crystalline and cubic NPs were shown by XRD analysis and TEM. TGA demonstrated the purity of the Ch/Au-NPs and the existence of organic compounds in the Azto/Alg-Au-NCMs. Both the Ch/Au-NPs and Azto/Alg-Au-NCMs had antibacterial activities against Staphylococcus aureus ATCC 25923, Proteus mirabilis , Enterobacter sp., and Pseudomonas aeruginosa and possessed anticancer activities against MCF-7 and H1299.