Characteristics and Applications of Peptide Nucleic Acid in the Treatment of Infectious Diseases and the Effect of Antimicrobial Photodynamic Therapy on Treatment Effectiveness.

Antibiotic resistance is a growing global problem, so there is an urgent need for new antimicrobial agents and strategies. Peptide nucleic acid (PNA) oligomers could be designed and utilized as gene-specific oligonucleotides to target any infectious agents. Selectivity and high-affinity binding are the main properties of PNA. However, in therapeutic applications, intracellular delivery of peptide nucleic acids is still a challenge. In photodynamic therapy (PDT), which could be a useful adjunct to mechanical and antibiotics in removing pathogenic agents, low-power lasers are used in appropriate wavelength for killing the microorganisms that have been treated with a photosensitizer drug. Antimicrobial photodynamic therapy (aPDT) in combination with lipid-charged nanoparticles of PNA is a promising alternative therapy proposed to control infectious diseases. This review summarizes progress in the uptake of peptide nucleic acids at intracellular targets. In addition, we focus on recent nanoparticle- based strategies to efficiently deliver conventional and chemically modified peptide nucleic acids. The likely impact of using two treatment methods simultaneously, i.e., PNP and PDT, has already been discussed.

Association Between Inflammatory Bowel Disease and Viral Infections.

Chronic inflammatory gastrointestinal diseases such as Crohn's disease (CD) and ulcerative colitis (UC) are known as inflammatory bowel disorders (IBD). Patients with inflammatory bowel illnesses are more susceptible to viral infections. In people with IBD, viral infections have emerged as a significant issue. Viral infections are often difficult to identify and have a high morbidity and fatality rate. We reviewed studies on viral infections and IBD, concentrating on Cytomegalovirus (CMV), SARS-CoV-2, Epstein-Barr virus (EBV), enteric viruses, and hepatitis B virus (HBV). Also, the effect of IBD on these viral infections is discussed. These data suggest that patients with IBD are more likely to get viral infections. As a result, practitioners should be aware of the increased risk of viral infections in inflammatory bowel disease patients.

Therapeutic effects, immunogenicity and cytotoxicity of a cell penetrating peptide-peptide nucleic acid conjugate against cagA of Helicobacter pylori in cell culture and animal model.

BACKGROUND AND OBJECTIVES: Helicobacter pylori causes several gastrointestinal diseases, including asymptomatic gastritis, chronic peptic ulcer, duodenal ulcer, lymphoma of the mucosa-associated lymphoid tissue (MALT), and gastric adenocarcinoma. In recent years, failure to eradicate H. pylori infections has become an alarming problem for physicians. It is now clear that the current treatment strategies may become ineffective, necessitating the development of innovative antimicrobial compounds as alternative treatments. MATERIALS AND METHODS: In this experimental study, a cell-penetrating peptide-conjugated peptide nucleic acid (CPP-PNA) was used to target the cagA expression. cagA expression was evaluated using RT-qPCR assay after treatment by the CPPPNA in cell culture and animal model. Additionally, immunogenicity and toxicity of the CPP-PNA were assessed in both cell culture and animal models. RESULTS: Our analysis showed that cagA mRNA levels reduced in H. pylori-infected HT29 cells after treatment with CPPPNA in a dose-dependent manner. Also, cagA expression in bacterial RNA extracted from stomach tissue of mice treated with PNA was reduced compared to that of untreated mice. The expression of inflammatory cytokines also decreased in cells and tissue of H. pylori-infected mice after PNA treatment. The tested CPP-PNA showed no significant adverse effects on cell proliferation of cultured cells and no detectable toxicity and immunogenicity were observed in mice. CONCLUSION: These results suggest the effectiveness of CPP-PNA in targeting CagA for various research and therapeutic purposes, offering a potential antisense therapy against H. pylori infections.

Evaluation of cell-penetrating peptide-peptide nucleic acid effect in the inhibition of cagA in Helicobacter pylori.

Helicobacter pylori is the most common cause of chronic infection in human and is associated with gastritis, peptic ulcer disease, and adenocarcinoma of mucosa-associated lymphoid tissue cells. Peptide nucleic acid (PNA) is a synthetic compound, which can inhibit the production of a particular gene. This study aimed to investigate the effect of PNA on inhibiting the expression of cagA. After confirmation of the desired gene by polymerase chain reaction (PCR), the antisense sequence was designed against cagA gene. The minimum inhibitory concentrations of conjugated PNA against H. pylori was determined. The effect of the compound on the expression level of the cagA was investigated in HT29 cell culture using real-time PCR. The results showed 2 and 3 log reduction in bacterial count after 8- and 24-h treatment with 4 and 8 µM of the compound, respectively. The lowest expression level of the cagA gene was observed at a concentration of 8 µM after 6 h. The results of this study showed that cell-penetrating peptide antisense can be employed as effective tools for inhibiting the target gene mRNA for various purposes. Moreover, further research is necessary to assess the potency, safety, and pharmacokinetics of CPP-PNAs for clinical prevention and treatment of infections due to H. pylori.