The effect of mesenchymal stem cell conditioned medium incorporated within chitosan nanostructure in clearance of common gastroenteritis bacteria in-vitro and in-vivo.

Gastroenteritis infection is a major public health concern worldwide, especially in developing countries due to the high annual mortality rate. The antimicrobial and antibiofilm activity of human mesenchymal stem cell-derived conditioned medium (hMSCsCM) encapsulated in chitosan nanoparticles (ChNPs) was studied in vitro and in vivo against common gastroenteritis bacteria. The synthesized ChNPs were characterized using Zeta potential, scanning electron microscopy (SEM), and dynamic light scattering (DLS) techniques. HMSC-derived conditioned medium incorporated into chitosan NPs (hMSCsCM-ChNPs) composite was fabricated by chitosan nanoparticles loaded with BM-MSCs (positive for CD73 and CD44 markers). The antimicrobial and antibiofilm activity of composite was investigated against four common gastroenteritis bacteria (Campylobacter jejuni ATCC29428, Salmonella enteritidis ATCC13076, Shigella dysenteriae PTCC1188, and E. coli ATCC25922) in-vitro and in-vivo. Majority of ChNPs (96%) had an average particle size of 329 nm with zeta potential 7.08 mV. The SEM images confirmed the synthesis of spherical shape for ChNPs and a near-spherical shape for hMSCsCM-ChNPs. Entrapment efficiency of hMSCsCM-ChNPs was 75%. Kinetic profiling revealed that the release rate of mesenchymal stem cells was reduced following the pH reduction. The antibacterial activity of hMSCsCM-ChNPs was significantly greater than that of hMSCsCM and ChNPs at dilutions of 1:2 to 1:8 (P < 0.05) against four common gastroenteritis bacteria. The number of bacteria present decreased more significantly in the group of mice treated with the hMSCsCM-ChNPs composite than in the groups treated with hMSCsCM and ChNPs. The antibacterial activity of hMSCsCM against common gastroenteritis bacteria in an in vivo assay decreased from > 106 CFU/ml to approximately (102 to 10) after 72 h. Both in vitro and in vivo assays demonstrated the antimicrobial and antibiofilm activities of ChNPs at a concentration of 0.1% and hMSCsCM at a concentration of 1000 µg/ml to be inferior to that of hMSCsCM-ChNPs (1000 µg/ml + 0.1%) composite. These results indicated the existence of a synergistic effect between ChNPs and hMSCsCM. The designed composite exhibited notable antibiofilm and antibacterial activities, demonstrating optimal release in simulated intestinal lumen conditions. The utilization of this composite is proposed as a novel treatment approach to combat gastroenteritis bacteria in the context of more challenging infections.

Advances in inorganic nanoparticles-based drug delivery in targeted breast cancer theranostics.

Theranostic nanoparticles (NPs) have the potential to dramatically improve cancer management by providing personalized medicine. Inorganic NPs have attracted widespread interest from academic and industrial communities because of their unique physicochemical properties (including magnetic, thermal, and catalytic performance) and excellent functions with functional surface modifications or component dopants (e.g., imaging and controlled release of drugs). To date, only a restricted number of inorganic NPs are deciphered into clinical practice. This review highlights the recent advances of inorganic NPs in breast cancer therapy. We believe that this review can provides various approaches for investigating and developing inorganic NPs as promising compounds in the future prospects of applications in breast cancer treatment and material science.

ZnO/chitosan nanocomposites as a new approach for delivery LL37 and evaluation of the inhibitory effects against biofilm-producing Methicillin-resistant Staphylococcus aureus isolated from clinical samples.

Modification surface of chitosan nanoparticles using ZnO nanoparticles is important interest in drug delivery because of the beneficial properties. In this study, we proposed a chitosan/ZnO nanocomposite for the targeted delivery of antibacterial peptide (LL37). Synthesized LL37-loaded chitosan/ZnO nanocomposite (CS/ZnO/LL37-NCs) was based on the ionotropic gelation method. The antibacterial activity of the synthesized platform versus Methicillin-resistant Staphylococcus aureus (MRSA) was determined by the microdilution method in 10 mM sodium phosphate buffer. The biofilm formation inhibitory was also evaluated using microtiter plate method. In addition, the ability of CS/ZnO/LL37-NCs on the icaA gene expression level was assessed by the Real-Time PCR. The loading and release investigations confirmed the suitability of CS/ZnO-NCs for LL37 encapsulation. Results showed 6 log10 CFU/ml reduction in MRSA treated with the CS/ZnO/LL37-NPs. Moreover, CS/ZnO/LL37-NCs showed 81 % biofilm formation inhibition than LL37 alone. Also, icaA gene expression decreased 1-fold in the face of CS/ZnO/LL37-NCs. In conclusion, the modification surface of chitosan nanoparticles with ZnO nanoparticles is a suitable chemical platform for the delivery of LL37 that could be used as a promising nanocarrier for enhancing the delivery of antibacterial peptide and improving the antibacterial activity of LL37.

Evaluation of the inhibitory effects of TiO2 nanoparticle and Ganoderma lucidum extract against biofilm-producing bacteria isolated from clinical samples.

The emergence of multidrug-resistant pathogens leads to treatment failure. So, the need for new antibacterial drugs is urgent. We evaluated the antibacterial and antibiofilm effects of titanium dioxide (TiO2) nanoparticles (NPs) and Ganoderma extract against biofilm-producing Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) by microbroth dilution and crystal violet assays. The combined effect of these compounds was studied using the checkerboard method. The OD260 was measured to assess the destruction of the membrane permeability. The expression of biofilm-related genes (iacA and algD) was investigated by real-time PCR. MRSA isolate was more susceptible to test compounds. The OD260 increased and algD gene was down-regulated after treatment with TiO2 NPs and a combination of TiO2 NPs and Ganoderma extract. iacA gene did not affect by test compounds. Overall, these findings revealed that nanoparticles and natural substances might represent the potential candidates to develop promising antibacterial agents, especially against Gram-positive bacteria.

Molecular typing of clinical and environmental isolates of Klebsiella pneumoniae producing ESBLs by PFGE.

Objectives: Klebsiella pneumoniae is the common cause of pneumonia in hospitalized patients, particularly in intensive care units (ICU). The infection can transfer by medical equipment such as mechanical ventilators. This study aimed to investigate the molecular typing of the extended-spectrum beta-lactamase-producing K. pneumoniae isolates recovered from Beheshti Hospital, Kashan, Iran. Materials and Methods: K. pneumoniae isolates producing ESBLs have been collected from the samples obtained from Shahid Beheshti hospital, Kashan, Iran. Antimicrobial susceptibility was determined using the Kirby Bauer disk diffusion method. The presence of ESBLs was evaluated using CLSI for ESBL screening by the double-disk diffusion method. Molecular typing was conducted by pulsed-field gel electrophoresis (PFGE). In total, 89 K. pneumoniae isolates were recovered, of which 47.1% were ESBL producers. Results: Results showed that all of the clinical and environmental isolates were resistant to ceftriaxone, meropenem, cefazolin, cefotaxime, cephalothin, and piperacillin-tazobactam. All isolates were grouped under four clusters (A-D). The major cluster was related to the C cluster with 22 isolates (19 clinical and 3 environmental). Seventy-two percent of isolates were from the ICU ward. There was no correlation between antibiotic resistance patterns and PFGE clusters (P=0.2). Conclusion: We observed a common molecular signature among both clinical and environmental K. pneumoniae isolates, indicating a similar genotype and likely a common origin for ESBL producer isolates found in different hospital wards. Therefore, hospitals need to implement an effective infection control system to decrease the spreading of ESBL strains within the hospitals and subsequently the transmission of the infection to patients.

Hyaluronic Acid-Based Nanomaterials as a New Approach to the Treatment and Prevention of Bacterial Infections.

Bacterial contamination of medical devices is a great concern for public health and an increasing risk for hospital-acquired infections. The ongoing increase in antibiotic-resistant bacterial strains highlights the urgent need to find new effective alternatives to antibiotics. Hyaluronic acid (HA) is a valuable polymer in biomedical applications, partly due to its bactericidal effects on different platforms such as contact lenses, cleaning solutions, wound dressings, cosmetic formulations, etc. Because the pure form of HA is rapidly hydrolyzed, nanotechnology-based approaches have been investigated to improve its clinical utility. Moreover, a combination of HA with other bactericidal molecules could improve the antibacterial effects on drug-resistant bacterial strains, and improve the management of hard-to-heal wound infections. This review summarizes the structure, production, and properties of HA, and its various platforms as a carrier in drug delivery. Herein, we discuss recent works on numerous types of HA-based nanoparticles to overcome the limitations of traditional antibiotics in the treatment of bacterial infections. Advances in the fabrication of controlled release of antimicrobial agents from HA-based nanosystems can allow the complete eradication of pathogenic microorganisms.

Delivery LL37 by chitosan nanoparticles for enhanced antibacterial and antibiofilm efficacy.

In this study, the fabrication of LL37-loaded chitosan nanoparticles (CS/LL37-NPs) was based on an ionotropic gelation method between sodium tripolyphosphate (TPP) and chitosan. Synthesized chitosan nanoparticles (CS-NPs) were approved by Fourier Transform Infrared (FTIR), UV-vis spectroscopy, Dynamic Light Scattering (DLS), Scanning Electron Microscope (SEM), and Transmission Electron Microscopy (TEM). The encapsulation efficiency of LL37 in this delivery system (CS/LL37-NPs) was 86.9%. According to in vitro release profile, the release of LL37 from CS/LL37-NPs was almost complete after 5 days. Additionally, CS/LL37-NPs can cause an increase in the half-life and prolonged LL37 antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA). This delivery system demonstrated 68% biofilm formation inhibition compared to the LL37 alone. Also, icaA gene expression in the face of CS/LL37-NPs was significantly decreased. This study showed the important role of delivery systems in enhancing LL37 antibacterial and antibiofilm activity which can be suggested as a promising agent in the inhibition of bacterial growth and the prevention of biofilm formation.

Cellulose-Based Nanofibril Composite Materials as a New Approach to Fight Bacterial Infections.

Antibiotic resistant microorganisms have become an enormous global challenge, and are predicted to cause hundreds of millions of deaths. Therefore, the search for novel/alternative antimicrobial agents is a grand global challenge. Cellulose is an abundant biopolymer with the advantages of low cost, biodegradability, and biocompatibility. With the recent growth of nanotechnology and nanomedicine, numerous researchers have investigated nanofibril cellulose to try to develop an anti-bacterial biomaterial. However, nanofibril cellulose has no inherent antibacterial activity, and therefore cannot be used on its own. To empower cellulose with anti-bacterial properties, new efficient nanomaterials have been designed based on cellulose-based nanofibrils as potential wound dressings, food packaging, and for other antibacterial applications. In this review we summarize reports concerning the therapeutic potential of cellulose-based nanofibrils against various bacterial infections.

Genetic Diversity, Antimicrobial Resistance Pattern, and Biofilm Formation in Klebsiella pneumoniae Isolated from Patients with Coronavirus Disease 2019 (COVID-19) and Ventilator-Associated Pneumonia.

INTRODUCTION: Patients with acute respiratory distress syndrome caused by coronavirus disease 2019 (COVID-19) are at risk for superadded infections, especially infections caused by multidrug resistant (MDR) pathogens. Before the COVID-19 pandemic, the prevalence of MDR infections, including infections caused by MDR Klebsiella pneumoniae (K. pneumoniae), was very high in Iran. This study is aimed at assessing the genetic diversity, antimicrobial resistance pattern, and biofilm formation in K. pneumoniae isolates obtained from patients with COVID-19 and ventilator-associated pneumonia (VAP) hospitalized in an intensive care unit (ICU) in Iran. METHODS: In this cross-sectional study, seventy K. pneumoniae isolates were obtained from seventy patients with COVID-19 hospitalized in the ICU of Shahid Beheshti hospital, Kashan, Iran, from May to September, 2020. K. pneumoniae was detected through the ureD gene. Antimicrobial susceptibility testing was done using the Kirby-Bauer disc diffusion method, and biofilm was detected using the microtiter plate assay method. Genetic diversity was also analyzed through polymerase chain reaction based on enterobacterial repetitive intergenic consensus (ERIC-PCR). The BioNumerics software (v. 8.0, Applied Maths, Belgium) was used for analyzing the data and drawing dendrogram and minimum spanning tree. Findings. K. pneumoniae isolates had varying levels of resistance to antibiotics meropenem (80.4%), cefepime-aztreonam-piperacillin/tazobactam (70%), tobramycin (61.4%), ciprofloxacin (57.7%), gentamicin (55.7%), and imipenem (50%). Around 77.14% of isolates were MDR, and 42.8% of them formed biofilm. Genetic diversity analysis revealed 28 genotypes (E1-E28) and 74.28% of isolates were grouped into ten clusters (i.e., clusters A-J). Clusters were further categorized into three major clusters, i.e., clusters E, H, and J. Antimicrobial resistance to meropenem, tobramycin, gentamicin, and ciprofloxacin in cluster J was significantly higher than cluster H, denoting significant relationship between ERIC clusters and antimicrobial resistance. However, there was no significant difference among major clusters E, H, and J respecting biofilm formation. CONCLUSION: K. pneumoniae isolates obtained from patients with COVID-19 have high antimicrobial resistance, and 44.2% of them have genetic similarity and can be clustered in three major clusters. There is a significant difference among clusters respecting antimicrobial resistance.

Chitosan-based nanoparticles against bacterial infections.

Chitosan nanomaterials have become a hot topic in biomedicine due to exerting antimicrobial effects with interestingly high levels of biodegradability and biocompatibility without causing toxicity. Regarded as a potential means of wound dressing with antimicrobial activity, chitosan exhibits higher efficiency when it is functionally modified with other natural compounds, metallic antimicrobial particles and antibiotics. Mechanistically, the antibacterial effect of chitosan is mostly, associated with the death-proceeding leakage of intracellular content, induced by malfunction and altered permeability of the negatively charged cell membrane, on which chitosan is adsorbed. Moreover, chitosan nanoparticles (NPs) are endowed with favorable features of NPs (i.e., large surface-to-volume ratio, high functionalization possibilities and a greater capacity for drug loading), as well as that of their chitosan base, thereby possessing strengthened antibacterial potential. In addition, polycations target negatively charged bacterial membranes, so bacteria cells are more strongly affected by polycationic chitosan NPs than pure chitosan.

Pulmonary Nocardiosis in Suspected Tuberculosis Patients: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

BACKGROUND: nocardiosis is an opportunistic infectious disease in immunocompromised patients. The most common form of nocardiosis infection in humans is pulmonary nocrdiosis caused by inhaling Nocardia species from the environment. Thus, this study aimed to evaluate the pulmonary nocardiosis in patients with suspected tuberculosis using systematic review and meta-analysis. METHODS: We conducted a systematic search for cross-sectional studies focused on the pulmonary nocardiosis among patients with pulmonary tuberculosis based on the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) published from January 2001 to October 2019. The search was conducted in MEDLINE/PubMed, Web of Science, Scopus, Cochrane Library, Google Scholar, Science Direct databases, and Iranian databases. Medical subject headings (MeSH) and text words were searched: "pulmonary nocardiosis", "nocardiosis", OR "nocardial infection", "pulmonary nocardial infections/agents", AND "pulmonary tuberculosis", OR "pulmonary TB", AND "Iran". Two of the reviewers enrolled independently articles published in English and Persian languages according to the inclusion and the exclusion criteria. Comprehensive Meta-Analysis software (Version 3.3.070) was used for meta-analysis. RESULTS: Only 4 studies met the eligibility criteria. The pulmonary nocardiosis prevalence varied from 1.7% to 6.7%. The combined prevalence of nocardiosis among patients with suspected pulmonary tuberculosis in Iran was 4.8% (95% CI: 3-7.3, Q=5.8, Z=12.7). No heterogeneity was observed between studies because I2 was 48.3. N. cyriacigeorgica and N. asteroides were reported as the prevalent isolates, respectively. CONCLUSIONS: This review showed in patients suspected TB when they were negative in all diagnosis laboratory tests, nocardiosis cases which be considered.

Effective removal of organic pollution by using sonochemical prepared LaFeO3 perovskite under visible light.

In the present work, LaFeO3 perovskite was prepared via ultrasonic probe with power of 60 W and frequency of 18 KHz. LaFeO3 nanorods were formed when sonication time was 20 min. In this research, green materials including corn, starch, and rice were used to control the size, morphology, and purity of final products. As-prepared LaFeO3 nanostructures were used to purify water containing organic contaminants. LaFeO3 nanostructures prepared by using corn, starch, and rice showed higher photocatalytic activity compare to LaFeO3 nanostructures without natural capping agents. Using corn increased degradation efficiency by 65% under visible light. XRD results show that Fe2O3 appeared as an impurity when starch was used to prepare LaFeO3 nanostructures. This impurity significantly boosts the degradation efficiency under UV light. Fe2O3 under UV light act as co-absorbent and boost efficiency by 43%. LaFeO3 nanostructures were characterized by XRD, EDX, SEM, CV, BET, TEM, DRS and FT-IR.