2025年 · 第08卷第02期

The objective of this study was to formulate a niosomal in situ gel of sertraline hydrochloride for the treatment of depression. Sertraline hydrochloride is a Biopharmaceutical Classification System class II drug with low solubility and high permeability. This research aims to improve the bioavailability of drugs by increasing their solubility by encapsulation in niosomal vesicles incorporated into an in situ gel. Niosomes were prepared via the ether injection method using a 3² full factorial design. Sertraline hydrochloride in situ gel was prepared via the cold method by using Poloxamer 407 and PVP K 30. One factor was evaluated at 3 levels, and the concentrations of surfactant Span 60 (X₁) and of cholesterol (X₂) were selected as independent variables. The F8 batch of niosomes out of 9 formulations was found to be optimized. The average vesicle size of the niosomal suspension in the optimized F8 batch was 167.5 nm, with a zeta potential of -31.4 mV. The entrapment efficiency across the 9 batches varied from 79.6% to 90.5%, while the drug content ranged between 91.2% and 98.5%. The entrapment efficiency and drug content of the optimized batch were 90.5% and 98.5%, respectively. In vitro drug release for these batches was between 86.32% and 91.33%. The in vitro drug release and ex vivo permeation rates of the optimized batch were 88.03% and 81.74%, respectively. Thus, the application of niosomes has proven potential for intranasal delivery of sertraline hydrochloride over conventional gel formulations, and intranasal drug delivery for sertraline hydrochloride has been successfully developed.

NPM1 is a protein-coding gene that encodes the nucleophosmin 1 (NPM1) protein. The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes, such as centrosome duplication, protein chaperoning, and DNA repair. Mutations of the NPM1 gene are associated with human acute myeloid leukemia (AML). AML is a complex hematopoietic cell disorder characterized by excessive proliferation of hematopoietic cells of the myeloid lineage in the bone marrow. This study aimed to predict highly damaging missense single-nucleotide polymorphism (SNPs) in the human NPM1 gene that may be associated with AML. In this investigation, we employed a range of in silico tools to analyze the functional and structural consequences of missense SNPs in the human NPM1 gene. The missense SNPs of the NPM1 gene were retrieved from the Ensembl database. We evaluated the functional and structural impacts of missense SNPs using bioinformatics tools, specifically SIFT, PROVEAN, PolyPhen-2, I-Mutant 3.0, MUpro, and MutPred2. The secondary structure was predicted with PSIPRED. The 3-dimensional structure of the NPM1 protein was obtained from AlphaFold, visualization along with mutant models was generated using PyMOL, and all information about physiological properties was taken from the HOPE project. The protein–protein interactions of the NPM1 protein were investigated using STRING. In silico analysis revealed 8 missense mutations (K54N, I59T, L79S, P152A, K193R, K193N, A283G, and I284F) in the human NPM1 gene. These mutations lead to structural alterations in the protein, which disrupt its normal function and may contribute to the development of AML in humans.

The present study aimed to develop a film-forming spray containing an epigallocatechin-3-gallate:Dexolve complex (FFS-EGCG:Dexolve) for site-specific treatment of throat cancer using newer excipients.

EGCG was used to treat throat cancer. The permeability of EGCG was improved by amalgamating with Kleptose/Dexolve. The screened complex was loaded into a film-forming spray solution. Quality by design (QbD) was utilized to develop FFS-EGCG:Dexolve, including HPMC E5 and Lycoat. A risk estimation matrix (REM) was utilized to scrutinize critical quality attributes (CQAs) and critical material attributes (CMAs), and a correlation was developed via a Box–Behnken design (BBD). FFS-EGCG:Dexolve was characterized for its in vitro and ex vivo characteristics.

EGCG:Dexolve (1:3) had excellent physical properties and 90.83 ± 0.07% permeability. Through an REM, the film formation time and %EGCG released were screened as CQAs, whereas the amounts of HPMC E5, Lycoat, and Dexolve were chosen as CMAs. The amounts of HPMC E5, Lycoat, and Dexolve were considered crucial for designing FFS-EGCG:Dexolve, as determined by the BBD. FFS-EGCG:Dexolve formed instant films, covered a relatively large surface area, and had a long residence time, and controlled EGCG release was achieved for >6 h. The optimal batch comprising HPMC E5 (11.98 mg), Lycoat (10.09 mg), and Dexolve (163.5 mg) had excellent spray characteristics, formed a film in 82 s, and released 85.39% EGCG in a controlled manner.

A novel FFS-EGCG:Dexolve complex was developed to explore the novel excipients Lycoat, HPMC E5, and Dexolve. The throat-targeted film-forming spray developed a film quickly and released >85% EGCG in 6 h. The novel FFS-EGCG:Dexolve complex was formulated for site specificity and intelligent technologies to achieve better therapeutic efficacy. Patient-centric formulations have excellent industrial and social impacts.

PANoptosis has been shown to play important pathophysiological roles, particularly in cancer. This review summarizes the composition and functions of PANoptosis and its associated PANoptosomes, including the ZBP1, RIPK1, AIM2, and NLRP12-PANoptosomes. Predictive models based on PANoptosis markers have been developed to guide personalized treatment strategies, highlighting novel therapeutic targets. Research into compounds that modulate PANoptosis pathways is ongoing, with the aim of increasing cancer treatment efficacy and addressing challenges such as drug resistance and immune evasion. This review also summarizes innovative PANoptosis-related prognostic gene signature models and compounds that modulate PANoptosis pathways.

Obesity represents a major health issue linked to various dysfunctions within adipose tissue. The equilibrium between energy storage and expenditure is vital for appropriate fat accumulation and lipid metabolism. A comprehensive understanding of the molecular mechanisms underlying adipogenesis (the formation of fat cells) and thermogenesis (the production of heat) is crucial for sustaining lipid homeostasis and managing fat development. Increasing evidence indicates that long noncoding RNAs (lncRNAs), a category of nonprotein-coding RNAs that are several hundred nucleotides long, play substantial roles in biological processes related to obesity through various regulatory pathways. The increasing incidence of obesity has increased interest in the specific mechanisms that govern adipocyte development. Although numerous mRNAs and microRNAs are recognized for their influences on adipogenesis, the overall expression patterns and functional roles of lncRNAs in this context remain inadequately studied. Adipose tissue is rich in various lncRNAs that have different expression patterns during adipogenesis and are regulated by key transcription factors such as PPARγ (peroxisome proliferator-activated receptor γ) and CEBPα (CCAAT/enhancer binding protein α). For example, ADINR (adipogenic differentiation inducing noncoding RNA) promotes adipogenesis by activating PPARγ, whereas GATA6-AS (GATA6 antisense RNA) affects preadipocyte differentiation through GATA proteins. TUG1 (taurine up-regulated gene 1) regulates the TGFβ (transforming growth factor β)/SMAD pathway, which affects the development of white and brown fat, whereas DLK1/PREF1 (delta-like 1/preadipocyte factor 1) inhibits adipocyte maturation. Functional screens utilizing RNA interference (RNAi) and CRISPR-SpCas9 genome editing have revealed critical lncRNAs that exert diverse effects on adipogenesis. This review focuses on recent research concerning the functions of lncRNAs in the regulation of white and brown adipogenesis, emphasizing their roles in adipocyte differentiation.

Cancer has caused the deaths of millions of people around the world. Negative side effects are associated with the conventional therapies currently used to treat cancer. This finding prompted scientists to investigate novel treatment approaches that offer a better b enefit-to-risk ra tio. Nanoparticles ra nging from 1 to 100 nm in size have emerged as promising tools in cancer therapy. Magnetic nanoparticles, in particular, have garnered attention for their unique magnetic properties and versatile biomedical applications. These goals are pursued by nanotechnology, which provides a vast array of nanoscale systems capable of combining therapeutic and diagnostic capabilities for real-time cancer treatment monitoring. Magnetic nanosystems stand out in the realm of nanotechnology due to their advanced nature and potential for magnetic properties. These qualities enable the application of these constructions in thermal therapy and magnetic resonance imaging. Additionally, because magnetic nanoparticles may be functionalized with therapeutic, contrast, and targeting agents and adjusted for increased specificity and reduced toxicity, they show marked promise as multifunctional nanoplatforms for cancer theranostics. A comprehensive description of the current designs, synthesis procedures, characterization techniques, and roles of magnetic nanoparticles as possible nanotheranostic agents is the aim of the current article.

Dengue virus (DENV) is spread through bites from mosquitos of the Aedes genus. DENV activates antibodies against 4 dengue serotypes, which are identified by the plaque reduction neutralization test of 50%, and the dengue antivirals use nonstructural viral antigens to excite T cells. Dengue vaccines include a live attenuated vaccine, inactivated vaccine, and DNA vaccine, among others. DENV is via dengue enzyme-linked immunosorbent assay (ELISA)-immunoglobulin (Ig). In 2009, the World Health Organization classified patients with DENV according to clinical presentation (dengue fever with rash, headache, eye pain, muscular pain, joint pain, and leukopenia) and positive test results for nonstructural protein 1 and dengue IgM antibodies by ELISA. The Dengvaxia vaccine is in second phase III trials; it was released by Sanofi Pasteur for use in Mexico in 2015 and was being used in more than 20 countries by 2017. After 30 years of research, only the live attenuated vaccine has passed phase III trials. Clinical trials for treating infections with Flavivirus viruses have been conducted in Asia and North and South America. Phase I to phase III trials involving 40,000 volunteers from 16 countries have assessed the vaccine safety, immunogenicity, and protection.