Potential use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and prevention method in viral infection.

Cellular lipid membranes serve as the primary barrier preventing viral infection of the host cell and provide viruses with a critical initial point of contact. Occasionally, viruses can utilize lipids as viral receptors. Viruses depend significantly on lipid rafts for infection at virtually every stage of their life cycle. The pivotal role that proprotein convertase subtilisin/kexin Type 9 (PCSK9) plays in cholesterol homeostasis and atherosclerosis, primarily by post-transcriptionally regulating hepatic low-density lipoprotein receptor (LDLR) and promoting its lysosomal degradation, has garnered increasing interest. Conversely, using therapeutic, fully humanized antibodies to block PCSK9 leads to a significant reduction in high LDL cholesterol (LDL-C) levels. The Food and Drug Administration (FDA) has approved PCSK9 inhibitors, including inclisiran (Leqvio®), alirocumab (Praluent), and evolocumab (Repatha). At present, active immunization strategies targeting PCSK9 present a compelling substitute for passive immunization through the administration of antibodies. In addition to the current inquiry into the potential therapeutic application of PCSK9 inhibition in human immunodeficiency virus (HIV)-infected patients for hyperlipidemia associated with HIV and antiretroviral therapy (ART), preclinical research suggests that PCSK9 may also play a role in inhibiting hepatitis C virus (HCV) replication. Furthermore, PCSK9 inhibition has been suggested to protect against dengue virus (DENV) potentially and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses. Recent evidence regarding the impact of PCSK9 on a variety of viral infections, including HCV, HIV, DENV, and SARS-CoV-2, is examined in this article. As a result, PCSK9 inhibitors and vaccines may serve as viable host therapies for viral infections, as our research indicates that PCSK9 is significantly involved in the pathogenesis of viral infections.

Deciphering the Role of Exosomal Non-Coding RNA (ncRNA) in Drug Resistance of Gastrointestinal Tumors; an Updated Review.

One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.

Optimization by Box-Behnken design for environmental contaminants removal using magnetic nanocomposite.

In this study, a CoO-Fe2O3/SiO2/TiO2 (CIST) nanocomposite was synthesized and utilized as an adsorbent to remove methylene blue (MB), malachite green (MG), and copper (Cu) from aqueous environments. The synthesized nanocomposite was characterized using field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Input parameters included pH (3-10), contact time (10-30 min), adsorbent amount (0.01-0.03 g), and pollutant concentration (20-60 mg L-1). The effects of these parameters on the removal process efficiency were modeled and optimized using the response surface methodology (RSM) based on the Box-Behnken design (BBD). The RSM-BBD method demonstrated the capability to develop a second-degree polynomial model with high validity (R2 ˃ 0.99) for the removal process. The optimization results using the RSM-BBD method revealed a removal efficiency of 98.01%, 93.06%, and 88.26% for MB, MG, and Cu, respectively, under optimal conditions. These conditions were a pH of 6, contact time of 10 min, adsorbent amount of 0.025 g, and concentration of 20 mg L-1. The synthesized adsorbent was recovered through five consecutive adsorption-desorption cycles using hydrochloric acid. The results showed an approximately 12% reduction from the first to the seventh cycle. Also, MB, MG, and Cu removal from real water samples in optimal conditions was achieved in the range of 81.69-98.18%. This study demonstrates the potential use of CIST nanocomposite as an accessible and reusable option for removing MB, MG, and Cu pollutants from aquatic environments.