Methicillin-resistant Staphylococcus aureus (MRSA) has evolved vast antibiotic resistance. These strains contain numerous virulence factors facilitating the development of severe infections. Considering the costs, side effects, and time duration needed for the synthesis of novel drugs, seeking efficient alternative approaches for the eradication of drug-resistant bacterial agents seems to be an unmet requirement. Nickel nanoparticles (NiNPs) have been applied as prognostic and therapeutic cheap agents to various aspects of biomedical sciences. Their antibacterial effects are exerted via the disruption of the cell membrane, the deformation of proteins, and the inhibition of DNA replication. NiNPs proper traits include high-level chemical stability and binding affinity, ferromagnetic properties, ecofriendliness, and cost-effectiveness. They have outlined pleomorphic and cubic structures. The combined application of NiNPs with CuO, ZnO, and CdO has enhanced their anti-MRSA effects. The NiNPs at an approximate size of around 50 nm have exerted efficient anti-MRSA effects, particularly at higher concentrations. NiNPs have conferred higher antibacterial effects against MRSA than other nosocomial bacterial pathogens. The application of green synthesis and low-cost materials such as albumin and chitosan enhance the efficacy of NPs for therapeutic purposes.

The gastrointestinal tract (GIT) environment has an intricate and complex nature, limiting drugs’ stability, oral bioavailability, and adsorption. Additionally, due to the drugs’ toxicity and side effects, renders are continuously seeking novel delivery systems. Lipid-based drug delivery vesicles have shown various loading capacities and high stability levels within the GIT. Indeed, most vesicular platforms fail to efficiently deliver drugs toward this route. Notably, the stability of vesicular constructs is different based on the different ingredients added. A low GIT stability of liposomes and niosomes and a low loading capacity of exosomes in drug delivery have been described in the literature. Bilosomes are nonionic, amphiphilic, flexible surfactant vehicles that contain bile salts for the improvement of drug and vaccine delivery. The bilosomes’ stability and plasticity in the GIT facilitate the efficient carriage of drugs (such as antimicrobial, antiparasitic, and antifungal drugs), vaccines, and bioactive compounds to treat infectious agents. Considering the intricate and harsh nature of the GIT, bilosomal formulations of oral substances have a remarkably enhanced delivery efficiency, overcoming these conditions. This review aimed to evaluate the potential of bilosomes as drug delivery platforms for antimicrobial, antiviral, antifungal, and antiparasitic GIT-associated drugs and vaccines.

Chlamydia trachomatis (C. trachomatis) is an obligate intracellular bacterium which causes eye and sexually transmitted infections. During pregnancy, the bacterium is associated with preterm complications, low weight of neonates, fetal demise and endometritis leading to infertility. The aim of our study was design of a multi-epitope vaccine (MEV) candidate against C. trachomatis. After protein sequence adoption from the NCBI, potential epitopes toxicity, antigenicity, allergenicity, MHC-I and MHC-II binding, cytotoxic T lymphocytes (CTLs), Helper T lymphocytes (HTLs) and interferon-γ (IFN-γ)- induction were predicted. The adopted epitopes were fused together using appropriate linkers. In the next step, the MEV structural mapping and characterization, three-dimensional (3D) structure homology modeling and refinement were also performed. The MEV candidate interaction with the toll-like receptor 4 (TLR4) was also docked. The immune responses simulation was assessed using the C-IMMSIM server. Molecular dynamic (MD) simulation verified the structural stability of the TLR4-MEV complex. The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach demonstrated the MEV high affinity of binding to the TLR4, MHC-I and MHC-II. The MEV construct was also stable and water soluble and had enough antigenicity and lacked allergenicity with stimulation of T cells and B cells and INF-γ release. The immune simulation confirmed acceptable responses of both the humoral and cellular arms. It is proposed that in vitro and in vivo studies are needed to evaluate the findings of this study.Communicated by Ramaswamy H. Sarma.

Infertility is an important issue among couples worldwide which is caused by a variety of complex diseases. Male infertility is a problem in 7% of all men. In vitro spermatogenesis (IVS) is the experimental approach that has been developed for mimicking seminiferous tubules-like functional structures in vitro. Currently, various researchers are interested in finding and developing a microenvironmental condition or a bioartificial testis applied for fertility restoration via gamete production in vitro. The tissue engineering (TE) has developed new approaches to treat male fertility preservation through development of functional male germ cells. This makes TE a possible future strategy for restoration of male fertility. Although 3D culture systems supply the perception of the effect of cellular interactions in the process of spermatogenesis, formation of a native gradient of autocrine/paracrine factors in 3D culture systems have not been considered. These results collectively suggest that maintaining the microenvironment of testicular cells even in the form of a 3D-culture system is crucial in achieving spermatogenesis ex vivo. It is also possible to engineer the testicular structures using biomaterials to provide a supporting scaffold for somatic and stem cells. The insemination of these cells with GFs is possible for temporally and spatially adjusted release to mimic the microenvironment of the in situ seminiferous epithelium. This review focuses on recent studies and advances in the application of TE strategies to cell-tissue culture on synthetic or natural scaffolds supplemented with growth factors.

Background: Klebsiella oxytoca (K. oxytoca) is an opportunistic Gram-negative pathogen that is becoming linked to healthcare-associated infections. The development of carbapenem-resistant strains is a major cause for concern in the clinical setting. Sub-inhibitory concentrations (sub-MICs) of antibiotics have been shown to affect the virulence and the formation of biofilms for bacteria. Objective: This study was designed to assess the effect of sub-MIC levels of meropenem on the expression of some virulence genes in carbapenem-resistant K. oxytoca. Methods: Ten clinical isolates of carbapenem-resistant K. oxytoca were isolated from patients diagnosed with hemorrhagic colitis. Isolates were determined by phenotypic, biochemical, and molecular techniques. Antibiotic susceptibility testing and minimum inhibitory concentration (MIC) determination were done based on the CLSI guidelines. Biofilm formation was measured by using the microtiter plate assay. The expression of virulence-associated genes (mrkA, fimA, pilQ, matB, and npsB) was studied by means of quantitative real-time PCR (RT-qPCR) under planktonic and biofilm growth conditions and after exposure to sub-MIC concentrations of the antibiotic meropenem. Results: All isolates were resistant to multiple drugs but sensitive to colistin, fosfomycin, and nitrofurantoin. Biofilm formation assays showed that all the isolates were moderate producers of biofilm. Gene expression analysis showed that virulence genes were significantly more expressed in biofilm than in planktonic condition, i.e., mrkA (2.6-fold), fimA (2.2-fold), pilQ (1.6-fold), matB (1.4-fold), and npsB (1.2-fold). Exposure to sub-MIC meropenem led to further expression of mrkA (1.8-fold) and fimA (1.6-fold). Conclusions: The results suggest that the expression of virulence-associated genes in carbapenem-resistant K. oxytoca can be increased by biofilm growth and sub-MIC antibiotic exposure. These results call on the potential function of sub-therapeutic levels of antibiotics in modulating the pathogenicity of bacterialpathogens.