Chimeric antigen receptor (CAR) T cells and natural killer (NK) cells are genetically engineered immune cells that can detect target antigens on the surface of target cells and eliminate them following adoptive transfer. Recent progress in CAR-based therapies has led to outstanding clinical success in certain patients with leukemias and lymphomas and offered therapeutic benefits to those resistant to conventional therapies. The universal approach to stable CAR transgene delivery into the T/NK cells is the use of viral particles. Such approaches mediate semi-random transgene insertions spanning the entire genome with a high preference for integration into sites surrounding highly-expressed genes and active loci. Regardless of the variable CAR expression level based on the integration site of the CAR transgene, foreign integrated DNA fragments may affect the neighboring endogenous genes and chromatin structure and potentially change a transduced T/NK cell behavior and function or even favor cellular transformation. In contrast, site-specific integration of CAR constructs using recent genome-editing technologies could overcome the limitations and disadvantages of universal random gene integration. Herein, we explain random and site-specific integration of CAR transgenes in CAR-T/NK cell therapies. Also, we tend to summarize the methods for site-specific integration as well as the clinical outcomes of certain gene disruptions or enhancements due to CAR transgene integration. Also, the advantages and limitations of using site-specific integration methods are discussed in this review. Ultimately, we will introduce the genomic safe harbor (GSH) standards and suggest some appropriate safety prospects for CAR integration in CAR-T/NK cell therapies.

Background: Acinetobacter baumannii is a pathogen responsible for nosocomial infections, especially in patients with burns and ventilator‐associated pneumonia (VAP). The aims of this study was to compare the biofilm formation capacity, antimicrobial resistance patterns and molecular typing based on PFGE (Pulsed‐Field Gel Electrophoresis) in A. baumannii isolated from burn and VAP patients.Materials and Methods: A total of 50 A. baumannii isolates were obtained from burn and VAP patients. In this study, we assessed antimicrobial susceptibility, biofilm formation capacity, PFGE fingerprinting, and the distribution of biofilm‐related genes (csuD, csuE, ptk, ataA, and ompA).Results: Overall, 74% of the strains were multidrug resistant (MDR), and 26% were extensively drug‐resistant (XDR). Regarding biofilm formation capacity, 52%, 36%, and 12% of the isolates were strong, moderate, and weak biofilm producers. Strong biofilm formation capacity significantly correlated with XDR phenotype (12/13, 92.3%). All the isolates harbored at least one biofilm‐related gene. The most prevalent gene was csuD (98%), followed by ptk (90%), ataA (88%), ompA (86%), and csuE (86%). Harboring all the biofilm‐related genes was significantly associated with XDR phenotype. Finally, PFGE clustering revealed 6 clusters, among which cluster No. 2 showed a significant correlation with strong biofilm formation and XDR phenotype.Conclusion: Our findings revealed the variable distribution of biofilm‐related genes among MDR and XDR A. baumannii isolates from burn and VAP patients. A significant correlation was found between strong biofilm formation capacity and XDR phenotype. Finally, our results suggested that XDR phenotype was predominant among strong‐biofilm producer A. baumannii in our region.

Encapsulation of amoxicillin (AMX) for drug delivery against Helicobacter pylori infection and aspirin-induced ulcers in rat’s stomachs was performed using docosahexaenoic acid (DHA)-loaded chitosan/alginate (CA) nanoparticles (NPs) developed by ionotropic gelation method. The physicochemical analyses of the composite NPs were performed by scanning electron microscopy, Fourier transform infrared spectroscopy, zeta potential, X-ray diffraction, and atomic force microscopy. The encapsulation efficiency of AMX was increased to 76% by incorporating DHA, which resulted in a reduction in the particle size. The formed CA-DHA-AMX NPs effectively adhered to the bacteria and rat gastric mucosa. Their antibacterial properties were more potent than those of the single AMX and CA-DHA NPs as demonstrated by the in vivo assay. The composite NPs attained higher mucoadhesive potential during food intake than during fasting (p = 0.029). At 10 and 20 mg/kg AMX, the CA-AMX-DHA showed more potent activities against H. pylori than the CA-AMX, CA-DHA, and single AMX. The in vivo study showed that the effective dose of AMX was lower when DHA was included, indicating better drug delivery and stability of the encapsulated AMX. Both mucosal thickening and ulcer index were significantly higher in the groups receiving CA-DHA-AMX than in the groups receiving CA-AMX and single AMX. The presence of DHA declines the pro-inflammatory cytokines including IL-1β, IL-6, and IL-17A. The synergistic effects of AMX and the CA-DHA formulation increased the biocidal activities against H. pylori infection and improved ulcer healing properties.

The frequent metastasis of gastric cancer (GC) complicates the cure and therefore the development of effective diagnostic and therapeutic approaches is urgently necessary. In recent years, lncRNA has emerged as a drug target in the treatment of GC, particularly in the areas of cancer immunity, cancer metabolism, and cancer metastasis. This has led to the demonstration of the importance of these RNAs as prognostic, diagnostic and therapeutic agents. In this review, we provide an overview of the biological activities of lncRNAs in GC development and update the latest pathological activities, prognostic and diagnostic strategies, and therapeutic options for GC-related lncRNAs.