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Background Diabetic foot ulcers (DFUs) are a severe complication of diabetes, often leading to infections caused by multidrug-resistant (MDR) bacteria, which complicate treatment and increase amputation risks. Bacteriophage (phage) therapy, targeting specific bacterial pathogens, has re-emerged as a promising alternative to antibiotics. This systematic review evaluates the efficacy of phage therapy for DFUs. Methods A comprehensive search was conducted in PubMed, Scopus, Web of Science, and Embase up to October 29, 2024, using keywords such as \"phage therapy,\" \"diabetic foot ulcers,\" and \"bacteriophages.\" Included were original English-language studies investigating phage therapy for DFUs, while reviews and non-English articles were excluded. Data extraction and quality assessment were performed independently by two reviewers. Results Twenty-one studies demonstrated phage therapy’s effectiveness against key DFU pathogens, including  Staphylococcus aureus ,  Pseudomonas aeruginosa ,  Enterococcus faecalis , and  Klebsiella pneumoniae . Phage cocktails showed superior efficacy in preventing bacterial regrowth and overcoming resistance compared to single phages. Synergistic effects with antibiotics (e.g., ciprofloxacin) were observed, enhancing biofilm penetration and bacterial eradication. Case studies reported high tolerability and clinical resolution, even in antibiotic-resistant infections. However, evidence remains limited to small-scale studies. Conclusion Phage therapy is a viable, safe option for MDR DFU infections, particularly due to its biofilm-disrupting properties and synergy with antibiotics. The lack of large randomized controlled trials (RCTs) underscores the need for standardized protocols, broader phage cocktails for polymicrobial infections, and optimized delivery methods. Future research should prioritize RCTs to establish efficacy, safety, and regulatory pathways for clinical adoption.

Background Antibiotic-resistant bacteria pose an urgent health threat as mutations have led to resistant strains that evade treatment. These bacteria form biofilms, complicating infection management. Bacteriophages are being recognized for their potential in phage therapy due to their effectiveness in rapidly targeting and eliminating bacterial hosts. Materials and methods This systematic review examined the effectiveness of bacteriophages against biofilms created by antibiotic- and drug-resistant staphylococcal strains. A thorough search of the Embase, Web of Science, PubMed, and Scopus databases was conducted for studies published from 2012 to October 29, 2024, focusing on relevant research while excluding irrelevant studies. Results This systematic review assesses the effectiveness of phage-derived enzymes, including endolysins and depolymerases, as well as whole bacteriophages, in degrading biofilms and clearing bacteria. It also highlights how combining phages with antibiotics or other agents can improve biofilm removal. The review explores the potential applications of phage therapy in various contexts, such as infections related to milk, silicone surfaces, synovial fluid, and prosthetic joint materials. Overall, while phage therapy shows promise as an alternative to antibiotics, additional research is necessary to refine treatment methods and ensure safety. Conclusions Bacteriophages hold potential as a standalone treatment and a complementary option to traditional antibiotics for managing S. aureus biofilms, but further research is needed to understand their clinical potential. Additional studies on phage selection, dosing, and administration methods are necessary, along with exploration of phage–antibiotic synergy mechanisms and assessment of the safety and environmental impacts of phage therapy.

Hypervirulent Klebsiella pneumoniae (hvKp) has emerged as a clinically significant pathogen that can cause severe infections, even in immunocompetent hosts. Unlike classical K. pneumoniae (cKp), hvKp exhibits enhanced virulence characterized by hypermucoviscosity and the presence of key genetic determinants. Its increasing detection in hospital settings, particularly in intensive care units (ICUs), raises concerns regarding nosocomial transmission and antibiotic resistance. A total of 187 K. pneumoniae isolates from patients at the Imam Reza Hospital, Mashhad, Iran, were screened phenotypically and genotypically. The hypermucoviscous phenotype was assessed using the string test and PCR was used to detect virulence genes ( rmpA , rmpA2 , and iucA ). Antimicrobial susceptibility testing and extended-spectrum β-lactamase (ESBL) detection were conducted, and statistical analyses were performed to compare the hvKp and cKp isolates. hvKp accounted for 9.63% of all isolates. These strains were significantly associated with the presence of rmpA , rmpA2 , and iucA genes. Although no statistically significant differences in antimicrobial resistance were observed between hvKp and cKp , the hvKp strains exhibited relatively lower resistance rates. A slightly higher but non-significant ESBL production rate was noted among the hvKp isolates. Diabetes and renal failure emerged as significant risk factors for hvKp infection, whereas age showed no such association. The detection of hvKp in ICU settings, coupled with its virulence potential and relative antibiotic susceptibility, underscores the urgent need for enhanced surveillance, infection control, and targeted antimicrobial stewardship. Future research should focus on the genomic evolution of hvKp and its interplay with host factors to develop effective prevention and treatment strategies.

Background Emergence of new variants mainly variants of concerns (VOC) is caused by mutations in main structural proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, we aimed to investigate the mutations among structural proteins of SARS-CoV-2 globally. Methods We analyzed samples of amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins from the declaration of the coronavirus 2019 (COVID-19) as pandemic to January 2022. The presence and location of mutations were then investigated by aligning the sequences to the reference sequence and categorizing them based on frequency and continent. Finally, the related human genes with the viral structural genes were discovered, and their interactions were reported. Results The results indicated that the most relative mutations among the E, M, N, and S AASs occurred in the regions of 7 to 14, 66 to 88, 164 to 205, and 508 to 635 AAs, respectively. The most frequent mutations in E, M, N, and S proteins were T9I, I82T, R203M/R203K, and D614G. D614G was the most frequent mutation in all six geographical areas. Following D614G, L18F, A222V, E484K, and N501Y, respectively, were ranked as the most frequent mutations in S protein globally. Besides, A-kinase Anchoring Protein 8 Like (AKAP8L) was shown as the linkage unit between M, E, and E cluster genes. Conclusion Screening the structural protein mutations can help scientists introduce better drug and vaccine development strategies.

BackgroundLongitudinal studies provide insights into the outcomes of medical training curriculum. However, few educational cohort studies have been conducted in Iran. This study aims first to evaluate the impact of the current curriculum on medical students' medium- and long-term academic and career outcomes and, second, to identify medical students' characteristics and how they change through the doctor of medicine programme.Methods and analysisThis protocol outlines a multi-phase, prospective cohort study that will take place in Mashhad, Iran. The study will implement the Kirkpatrick model, investigating medical students' knowledge, skills, behaviour and professionalism development over 10 years. Approximately 1000 medical students will be recruited through peer invitations and social networks. Data will be collected through baseline and follow-up questionnaires, academic performance records and comprehensive test scores throughout the Doctor of Medicine (MD) programme.The data from the questionnaires will be reported using a Likert scale. Quantitative data will be described using means and SD, while qualitative variables will be presented as frequencies and percentages. We will evaluate the relationship between quantitative variables using correlation coefficients and the relationship between qualitative variables via the χ2 or Fisher exact test. All tests will be two-sided, with a significance level set as p<0.05.Ethics and disseminationAll participants will complete written informed consent before data collection. All students can withdraw from the study at any time with no consequences. Results of this study will be presented at relevant conferences and will be submitted for publication in peer-reviewed journals. This study was approved by the Ethics Committee of Mashhad University of Medical Sciences.Study registration numberIR.MUMS.REC.1400.311.

In the present study, a novel chimeric peptide was derived from camel lactoferrin designed with a considerable anti-HCV activity and its neutralization mechanism was predicted by molecular modelling tools. A novel anti-HCV peptide derived from camel lactoferrin (cLF36) was designed and expressed it recombinantly in HEK-293-T cells. Anti-viral activity of this peptide was evaluated against hepatitis C virus by Real-time PCR assay in vitro. Finally, to have a better insight into the mode of action of peptide on HCV entry inhibition, we examined the interaction of cLF36 with envelope glycoprotein E2 by molecular dynamic simulation. This chimeric peptide had significant inhibitory effects on both HCV entry (44 µg/mL) and viral replication (88 µg/mL) under in vitro (p > 0.01). Moreover, cLF36 peptide was not toxic to HEK cells as a normal cell at twofold of its anti-viral concentrations for HCV entry and even at concentrations as high as 250 µg/mL exhibited minimal hemolysis (2.5%) against human RBCs (red blood cells). The results of in silico analysis showed that cLF36 interacted with β-sandwich and front layer of E2 protein as two potential CD81 binding sites. We generated and characterized a new camel lactoferrin derived HCV inhibitors. This peptide blocked HCV entry and also intracellular HCV replication in cell culture experiment.

Background Fluoroquinolones are broad-spectrum antibiotics that are recommended, and increasingly important, for the treatment of multidrug-resistant tuberculosis (MDR-TB). Resistance to fluoroquinolones is caused by mutations in the Quinolone Resistance Determining Region (QRDR) of gyrA and gyrB genes of Mycobacterium tuberculosis. In this study, we characterized the phenotypic and genotypic resistance to fluoroquinolones for the first time in northeast Iran. Methods A total of 123 Mycobacterium tuberculosis isolates, including 111 clinical and 12 collected multidrug-resistant isolates were studied. Also, 19 WHO quality control strains were included in the study. The phenotypic susceptibility was determined by the proportion method on Löwenstein-Jensen medium. The molecular cause of resistance to the fluoroquinolone drugs ofloxacin and levofloxacin was investigated by sequencing of the QRDR region of the gyrA and gyrB genes. Results Among 123 isolates, six (4.8%) were fluoroquinolone-resistant according to phenotypic methods, and genotypically three of them had a mutation at codon 94 of the gyrA gene (Asp→ Gly) which was earlier reported to cause resistance. All three remaining phenotypically resistant isolates had a nucleotide change in codon 95. No mutations were found in the gyrB gene. Five of the 19 WHO quality control strains, were phenotypically fluoroquinolone-resistant, four of them were genotypically resistant with mutations at codon 90, 91 of the gyrA gene and one resistant strain had no detected mutation. Conclusions Mutation at codon 94 of the gyrA gene, was the main cause of fluoroquinolone resistance among M. tuberculosis isolates in our region. In 3/6 fluoroquinolone-resistant isolates, no mutations were found in either gyrA or gyrB. Therefore, it can be concluded that various other factors may lead to fluoroquinolone resistance, such as active efflux pumps, decreased cell wall permeability, and drug inactivation.

Tuberculosis (TB), a contagious disease caused by ( ), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new TB vaccines could enhance the immunogenicity of antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through intranasal administration in a mice model. In the present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of 2 weeks. Three weeks after the final vaccination, IFN-γ, IL-4. IL-17, and TGF-β concentrations in the supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG1 and IgG2a and sIgA titers in nasal lavage were determined. According to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induce IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of antigens. The results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM, and MPLA after nasal administration in enhancing the immune response against antigens. Both nanoparticles were good adjuvants in order to promote the immunogenicity of TB-fused antigens. So, nasal immunization with these formulations, could induce immune responses and be considered a new TB vaccine or a BCG booster.

Infection with tuberculosis (TB) is regarded as a major health issue. Due to the emergence of antibiotic resistance during TB treatment, prevention via vaccination is one of the most effective ways of controlling the infection. DNA vaccines are developed at a greater pace due to their ability in generating a long-lasting immune response, higher safety compared to the live vaccines, and relatively lower cost of production. In the present study, we evaluated a new DNA vaccine encoding the fusion HspX-PPE44-EsxV antigens, separately, and in combination with Bacillus Calmette-Guérin (BCG) administration, in a prime-boost method in mice. A novel DNA vaccine encoding HspX-PPE44-EsxV fusion antigen of was constructed, and RT-PCR and Western blot analysis were performed to verify the expression of the antigen. Female BALB/c mice were divided into five groups (PBS, BCG, pcDNA3.1 (+) vector, pDNA/HspX-PPE44-EsxV vaccine, and the BCG-prime boost groups). In order to evaluate the immunogenicity of the recombinant vector, BALB/c mice were injected with 100 μg of pDNA at 2-week intervals. Then, cytokine assay was conducted using eBioscience ELISA kits (Ebioscience, AUT) according to manufacturers' instructions to evaluate the concentrations of IL-4, IL-12, TGF-β, and IFN-γ. The concentrations of INF-γ, IL-12, and TGF-beta were significantly increased compared to the control groups ( <0.001). INF-γ and IL-12 production were increased significantly in pDNA/HspX-PPE44-EsxV+BCG group compared to pDNA/HspX-PPE44-EsxV group ( <0.001). This study showed that the present DNA vaccine could induce a high level of specific cytokines in mice. It was also shown that using this DNA vaccine in a BCG prime-boost protocol can produce significant amounts of IFN-γ, IL-12, and TGF-β.

To address a highly mutable pathogen, mutations must be evaluated. SARS-CoV-2 involves changing infectivity, mortality, and treatment and vaccination susceptibility resulting from mutations. We investigated the Asian and worldwide samples of amino-acid sequences (AASs) for envelope (E), membrane (M), nucleocapsid (N), and spike (S) proteins from the announcement of the new coronavirus 2019 (COVID-19) up to January 2022. Sequence alignment to the Wuhan-2019 virus permits tracking mutations in Asian and global samples. Furthermore, we explored the evolutionary tendencies of structural protein mutations and compared the results between Asia and the globe. The mutation analyses indicated that 5.81%, 70.63%, 26.59%, and 3.36% of Asian S, E, M, and N samples did not display any mutation. Additionally, the most relative mutations among the S, E, M, and N AASs occurred in the regions of 508 to 635 AA, 7 to 14 AA, 66 to 88 AA, and 164 to 205 AA in both Asian and total samples. D614G, T9I, I82T, and R203M were inferred as the most frequent mutations in S, E, M, and N AASs. Timeline research showed that substitution mutation in the location of 614 among Asian and total S AASs was detected from January 2020. N protein was the most non-conserved protein, and the most prevalent mutations in S, E, M, and N AASs were D614G, T9I, I82T, and R203M. Screening structural protein mutations is a robust approach for developing drugs, vaccines, and more specific diagnostic tools.