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Because of the rise in antibiotic resistance and the control of pathogenicity, polymicrobial bacterial biofilms exacerbate wound infections. Since bacterial quorum sensing (QS) signals can dysregulate biofilm development, they are interesting therapeutic treatments. In this study, Pseudomonas Quinolone Signal (PQS) was used to treat an animal model of a wound that had both Staphylococcus aureus and Pseudomonas aeruginosa co-infection. S. aureus and P. aeruginosa mono- and co-infection models were developed in vitro on the L-929 cell line and in an animal model of wound infection. Moreover, PQS was extracted and purified using liquid chromatography. Then, the mono- and co-infection models were treated by PQS in vitro and in vivo. RT-PCR analysis was used to look into changes in biofilm, QS, tissue regeneration, and apoptosis genes after the treatment. PQS significantly disrupted established biofilm up to 90% in both in vitro and in vivo models. Moreover, a 93% reduction in the viability of S. aureus and P. aeruginosa was detected during the 10 days of treatment in comparison to control groups. In addition, the biofilm-encoding and QS-regulating genes were down-regulated to 75% in both microorganisms. Also, fewer epithelial cells died when treated with PQS compared to control groups in both mono- and co-infection groups. According to this study, PQS may facilitate wound healing by stimulating the immune system and reducing apoptosis. It seems to be a potential medication to use in conjunction with antibiotics to treat infections that are difficult to treat. [ABSTRACT FROM AUTHOR]

Nano pharmacology is considered an effective, safe, and applicable approach for drug delivery applications. Solid lipid nanoparticle (SLNs) colloids contain biocompatible lipids which are capable of encapsulating and maintaining hydrophilic or hydrophobic drugs in the solid matrix followed by releasing the drug in a sustained manner in the target site. SLNs have more promising potential than other drug delivery systems for various purposes. Nowadays, the SLNs are used as a carrier for antibiotics, chemotherapeutic drugs, nucleic acids, herbal compounds, etc. The SLNs have been widely applied in biomedicine because of their non-toxicity, biocompatibility, and simple production procedures. In this review, the complications related to the optimization, preparation process, routes of transplantation, uptake and delivery system, and release of the loaded drug along with the advantages of SLNs as therapeutic agents were discussed. [ABSTRACT FROM AUTHOR]

Abstract Brucellosis is an important zoonotic disease caused by different species of genus Brucella that are pathogenic for humans and a variety of animals. Accurate detection of Brucella spp. infection is important for control of disease. The aim of this study was to comparison of molecular genotyping of Brucella strains by Pulsed-field gel electrophoresis (PFGE) and polymerase chain reaction -Restriction Fragment Length Polymorphism (PCR-RFLP) techniques. Twenty- seven Brucella spp. were isolated from human and animal samples. The isolates identified by conventional microbiological methods and confirmed using PCR for amplification of omp2a gene. Molecular typing of Brucella strains carried out by PCR-RFLP after PstI and PFGE of chromosomal DNA after XbaI enzyme digestion. The omp2a gene PCR Products with different patterns of PCR-RFLP were sequenced. The omp2a gene amplification of all human and animal Brucella isolates were positive for 1100 bp fragment. By PCR-RFLP analysis two genotypes/patterns for human isolates and four genotypes for animal isolates were obtained. In PFGE analysis totally, 7 common clones/clusters and 3 single clones were obtained. The results of this study showed the PFGE method is the more reliable and useful assay for molecular typing of Brucella strains and is more preferred to PCR-RFLP in determination of genetic similarity among human and animal Brucella isolates. The presented data showed PCR-RFLP analysis was not able to differentiate between B. melitensis biovars and vaccine strain. [ABSTRACT FROM AUTHOR]

Background Colistin resistance in P. aeruginosa (CRPA) is due to the appearance of superbug strains. As this pathogen gains more transferrable resistance mechanisms and continues to adapt to acquire additional resistance mechanisms during antimicrobial therapy rapidly, we face the growing threat of CRPA in bloodstream infections (BSI). This study designed to evaluate the frequency of CRPA strains producing different β-lactamases by the High-Resolution Melting Curve Analysis (HRMA) method in BSI and to characterize the different types by multilocus sequence typing (MLST). Sixty-nine (69) P. aeruginosa isolates were collected from blood culture. MIC E-test methods examined the antimicrobial susceptibilities of the bacterial isolates. Detection of resistant strains performed by using HRMA assay. The strains resistant to amikacin (n = 11; 15.94%) and colistin (n = 10; 14.49%) were the least abundant and the gentamicin (n = 56; 82.6%) and ciprofloxacin (n = 67; 97.10%) resistant strains were the most frequent. Also, 39 isolates (56.52%) considered as multidrug-resistant (MDR), 20 isolates (28.98%) as extensively drug resistant (XDR), and 11 isolates (15.94%) as Pandrug Resistance (PDR). Further, 32 isolates (46.37%) considered as AmpC producer, and 28 isolates (40.57%) were considered an MBL producer. According to HRMA results, the bla SPM gene was detected in 19 isolates (27.53%), bla NDM gene in 11 isolates (15.94%), bla FOX gene in 31 isolates (44.92%), mcr-1 gene in 10 isolates (14.49%), bla ACC and bla VIM genes in 27 isolates (39.13%), and bla TEM gene was reported in 20 isolates (28.98%). Furthermore, P. aeruginosa PASGNDM699, ST3340, and ST235 identified in 1.44%, 11.59% and 17.39% isolates, respectively. CRPA strains play an essential role in the spread of antibiotic resistance in BSI. Likewise, the HRMA method was sensitive and specific for the detection of superbugs. Moreover, MLST analysis of a diverse collection of P. aeruginosa from blood culture suggests that particular strains or clonal complexes are associated with antibiotic resistance profile. • Pseudomonas aeruginosa gains more transferable resistance mechanisms and capable to acquire additional resistance. • P. aeruginosa PASGNDM699, ST3340, and ST235 identified as superbug strains causing BSI. • The phenotypic and HRMA results confirmed a significant relationship between colistin resistance and the abundance of β-lactamase enzymes in BSI. • CRPA strains play an essential role in the spread of antibiotic resistance in BSI. [ABSTRACT FROM AUTHOR]

Bacterial infection of the wound could potentially cause serious complications and an enormous medical and financial cost to the rapid emergence of drug-resistant bacteria. Nanomaterials are an emerging technology, that has been researched as possible antimicrobial nanomaterials for the inhibition of wound infection and enhancement of wound healing. Graphene is 2-dimensional (2D) sheet of sp2 carbon atoms in a honeycomb structure. It has superior properties, strength, conductivity, antimicrobial, and molecular carrier abilities. Graphene and its derivatives, Graphene oxide (GO) and reduced GO (rGO), have antibacterial activity and could damage bacterial morphology and lead to the leakage of intracellular substances. Besides, for wound infection management, Graphene-platforms could be functionalized by different antibacterial agents such as metal-nanoparticles, natural compounds, and antibiotics. The Graphene structure can absorb near-infrared wavelengths, allowing it to be used as antimicrobial photodynamic therapy. Therefore, Graphene-based material could be used to inhibit pathogens that cause serious skin infections and destroy their biofilm community, which is one of the biggest challenges in treating wound infection. Due to its agglomerated structure, GO hydrogel could entrap and stack the bacteria; thus, it prevents their initial attachment and biofilm formation. The sharp edges of GO could destroy the extracellular polymeric substance surrounding the biofilm and ruin the biofilm biomass structure. As well as, Chitosan and different natural and synthetic polymers such as collagen and polyvinyl alcohol (PVA) also have attracted a great deal of attention for use with GO as wound dressing material. To this end, multi-functional polymers based on Graphene and blends of synthetic and natural polymers can be considered valid non-antibiotic compounds useful against wound infection and improvement of wound healing. Finally, the global wound care market size was valued at USD 20.8 billion in 2022 and is expected to expand at a compound annual growth rate (CAGR) of 5.4% from 2022 to 2027 (USD 27.2 billion). This will encourage academic as well as pharmaceutical and medical device industries to investigate any new materials such as graphene and its derivatives for the treatment of wound healing. [ABSTRACT FROM AUTHOR]

Brucellosis is considered one of the most important infectious diseases affecting any tissue and organ in the human body. Due to the intracellular pathogenesis of Brucella species, the use of conventional antibiotics for managing chronic brucellosis has several limitations. Therefore, the study focused on the use of solid lipid nanoparticles (SLN) to deliver streptomycin (STR) for intracellular infection, with or without the combination of hydroxychloroquine (HCQ) to evaluate if there might be a boost in the antibiotic effect when using the STR or STR-NPs alone. We used the double emulsion technique to synthesize Nano drug carriers; afterward, the physicochemical characteristics of synthesized Nano drug carriers were determined. The in vitro antibacterial activity of free drugs and Nano drug carriers were evaluated using well diffusion, broth microdilution assays (BMD), and murine macrophage-like cells cell line J774A.1. Additionally, acute and chronic phases of brucellosis were inducted into Wistar rats, and healing capacity of Nano drug carriers on liver and spleen tissues was compared with free drugs. The zeta potential of nanoparticles, means of size, Polydispersity Index (PDI), drugs loading, and encapsulation efficiency were 15.2 mV, 312.5 ± 26 nm, 0.433 ± 0.09, 16.6% and 89.5%, respectively. Well diffusion and BMD methods did not show a significantly differ between free drugs and nano drug carriers. However, the Nano drug carriers remarkably decreased the number of bacteria in the cell line compared to the free drugs. STR/HCQ-SLN enhanced the healing processes of the liver and spleen after brucellosis induction. STR/HCQ-SLN showed better inhibitory effects against the chronic phase of B. abortus infection in comparison to the STR-SLN, but this difference was not statistically significant. Using nanoplatforms to enhance conventional anti-brucellosis agents is promising, green and safe. Due to the continuous release of drugs, drugs increase their accumulation at the site of infection, causing a more significant effect on the chronic and acute phases of brucellosis. • Relapse of the brucellosis is one of the most important challenges. The most important reason for the relapse of brucellosis is the survival of the bacteria inside the macrophages. • Solid lipid nanoparticle (SLN) is drug carriers that can control drug release and enhance the chemical stability of the trapped drugs. • Due to the continuous release of drugs, drugs increase their accumulation at the site of infection, causing a more significant effect on the chronic and acute phases of brucellosis. [ABSTRACT FROM AUTHOR]

The present work aimed to review the potential mechanisms used by macrophages to kill intracellular bacteria, their entrance to the cell, and mechanisms of escape of cellular immunity and applications of various nanoparticles. Since intracellular bacteria such as Mycobacterium and Brucella can survive in host cells and can resist the lethal power of macrophages, they can cause chronic disease or recur in 10–30% of cases in improved patients Nano drug-based therapeutics are promising tools for treating intracellular bacteria and preventing recurrence of the disease caused by these bacteria. In addition, among their unique features, we can mention the small size and the ability of these compounds to purposefully reach the target location. • Nano drug-based therapeutics are promising tools for treating intracellular bacteria. • In accordance to the bioavailability of the drug causes to prevent of the destruction of the drug. • While reducing the side effects and toxicity associated with the drug, reduce the long course of treatment. • By using of the nanoparticle could reduce the recurrence of the disease. [ABSTRACT FROM AUTHOR]

Memory impairment is determined to be the most well-known symptom of Alzheimer's disease (AD). Although cell therapy seems is an efficient therapeutic strategy to attenuate the AD-related memory impairment, transplanted cells have a short lifespan and do not survive long term in the recipient animals. Herein, we investigated whether the combination therapy of Selenium nanoparticles (SeNPs) and stem cells attenuates the neurotoxicity in an AD animal model. The adipose-derived mesenchymal stem cells (AMSCs) were transplanted in the AD model. In addition to cell injections, the animals also received oral administration of SeNPs (0.4 mg/kg) for one month. Recognition memory, cell survival, and BDNF concentration were assessed using the novel object recognition task, immunofluorescence, and ELISA methods. Our results showed that the combined therapy was more effective in increasing the discrimination index than the administering SeNPs or AMSCs alone. Moreover, SeNPs and stem cells together had the greatest effects in reducing the deposition of Aβ and increasing the concentration of BDNF. Ultimately, the survival and proliferation of transplanted cells were more in the group that received stem cells besides SeNPs. Taken together, it seems that the transplantation of MSCs combined with SeNPs could achieve better results in the neuroprotection in the AD model than a conventional treatment of SeNPs or stem cells alone. [ABSTRACT FROM AUTHOR]

The cooperation of Pseudomonas aeruginosa and Staphylococcus aureus in various infections results in increased pathogenicity and antibiotic resistance. However, the mechanism controlling such a phenomenon is still unclear. In this study, the effects of S. aureus on the metabolism, antibiotic resistance, and pathogenicity of P. aeruginosa were investigated. The biofilm and the planktonic states of growth of P. aeruginosa and S. aureus were investigated using the co-culture method in the L929 cell line. Then, the antibiotic resistance and virulence factors production of the recovered colonies of P. aeruginosa were examined by phenotypic methods. Quantitative Real-Time PCR was used to determine the expression level of crc , lasI/R , and rhlI/R genes. Two way ANOVA test and student's t -test were used to analyze the effect of S.aureus on metabolism, virulence, and resistance of P.aeruginosa. P. aeruginosa strains in a single-species planktonic culture on the L929 cell line indicated higher CFU counts than the biofilm. Conversely, in the biofilm state of co-culture, the CFU counts increased in comparison to the planktonic condition. Also, the expression level of crc increased two fold in the PA-1 and PA-2 strains compared to the single-species cultures on the L929 cell line. However, the PA-3 strain indicated a sharp decrease in the expression of crc (3 fold decrease). Besides, a 3–4 fold increase in susceptibility to amikacin was observed as the expression level of crc declined. The QS-regulated factors were diminished as rhlR and lasI were downregulated in both states of growth. In polymicrobial wound infection, Staphylococcus aureus plays a vital role in the metabolic changes of Pseudomonas aeruginosa. However, the levels of antibiotic susceptibility and pathogenicity of Pseudomonas aeruginosa also changed due to metabolism. • Polymicrobial infections makes treatment more difficult. • Polymicrobial infections are including wound, lung, diabetic foot ulcers, etc. • S.aureus dramatically influences P.aeruginosa metabolism and virulence. • crc, as a global regulator of metabolism in P.aeruginosa , was affected by S.aureus. • Resistance to amikacin remarkably decreased after the co-culture of S.aureus and P.aeruginosa. [ABSTRACT FROM AUTHOR]