A structural vaccinology approach for in silico designing of a potential self-assembled nanovaccine against Leishmania infantum.

Visceral leishmaniasis (VL) remains a major public health problem across 98 countries. To date, VL has no effective drug. Vaccines, as the most successful breakthroughs in medicine, can promise an effective strategy to fight various diseases. More recently, self-assembled peptide nanoparticles (SAPNs) have attracted considerable attention in the field of vaccine design due to their multivalency. In this study, a SAPN nanovaccine was designed using various immunoinformatics methods. High-ranked epitopes were chosen from a number of antigens, including Leishmania-specific hypothetical protein (LiHy), Leishmania-specific antigenic protein (LSAP), histone H1, and sterol 24-c-methyltransferase (SMT). To facilitate the oligomerization process, pentameric and trimeric coiled-coil domains were employed. RpfE, a resuscitation-promoting factor of Mycobacterium tuberculosis, was added to induce strong immune responses. Pentameric and trimeric coiled-coil domains as well as eight immunodominant epitopes from antigenic proteins of Leishmania infantum, the causative agent of VL, were joined together using appropriate linkers. High-quality 3D structure of monomeric and oligomeric structures followed by refinement and validation processes demonstrated that the designed nanovaccine could be considered to be a promising medication against the parasite; however, experimental validation is essential to confirm the effectiveness of the nanovaccine.

A new multi-epitope peptide vaccine induces immune responses and protection against Leishmania infantum in BALB/c mice.

Visceral leishmaniasis (VL) is a tropical and subtropical disease which is endemic in more than eighty countries around the world. Leishmania infantum is one of the main causative agents of VL disease. Currently, there is no approved-to-market vaccine for VL therapy. In this study, we evaluated cellular and humoral immune responses induced by our newly designed multi-epitope vaccine in BALB/c mice. Four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP) were chosen for the prediction of potential immunodominant epitopes. Moreover, to enhance vaccine immunogenicity, two toll-like receptors 4 (TLR4) agonists, resuscitation-promoting factors of Mycobacterium tuberculosis (RpfE and RpfB), were employed as the built-in adjuvants. Immunization with the designed multi-epitope vaccine elicited a robust Th1-type immune response, compared to other groups, as shown by increased levels of IL-2, IFN-γ, TNF-α, and IgG2a. Furthermore, a significant decrease was observed in Th-2-type-related cytokines such as IL-4 in immunized mice. The designed construct also induced a significant reduction in parasite load (p < 0.0001), conferring protection against L. infantum challenge. This study could be promising in gaining insight towards the potential of peptide epitope-based vaccines as effective protective approaches against Leishmania species.

Characterization of Gut Microbiota in Hospitalized Patients with Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is one of the most common causes of nosocomial diarrhea in developed countries and the main cause in healthcare settings. This case-control study was designed to evaluate the composition of the gut microbiota dominant bacterial groups in patients with CDI compared to the healthy control subjects. A total of 100 adult subjects involving 50 inpatients with CDI and 50 healthy persons were enrolled in the study. C. difficile isolates were characterized according to the anaerobic culture and presence of toxin genes with multiplex PCR. An ecological analysis was performed real-time quantitative PCR for bacterial elements. The abundances of Enterococcus spp., Lactobacillus spp., Escherichia coli, C. difficile, and Akkermansia muciniphila were higher in group CDI compared with group HC (P < 0.05). The abundances of Bacteroides spp., Bifidobacterium spp., and Faecalibacterium prausnitzii were lower in group CDI than in group HC (P < 0.05). No significant difference was observed in the copy number of Prevotella genus between the CDI and HC subjects (P-value = 0.087). We observed that economic status and income levels were reduced at patients with CDI, however, there was no significant difference between CDI and HC group results and other variables, such as age, BMI, and educational level. These findings showed a reduction in butyrate-producing bacteria and increase in lactic acid-producing bacteria was seen in CDI status. Overrepresentation of Akkermansia may be a predictive marker for the development of nosocomial diarrhea can result in a worse CDI prognosis.

Fatal Invasive Pulmonary Aspergillosis in COVID-19 Patient with Acute Myeloid Leukemia in Iran.

Although patients with severe immunodeficiency and hematological malignancies has been considered at highest risk for invasive fungal infection, patients with severe pneumonia due to influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV) are also at a higher risk of developing invasive pulmonary aspergillosis (IPA). Recently, reports of IPA have also emerged among SARS-CoV-2 infected patients admitted to intensive care units (ICUs). Here, we report a fatal case of probable IPA in an acute myeloid leukemia patient co-infected with SARS-CoV-2 and complicated by acute respiratory distress syndrome (ARDS). Probable IPA is supported by multiple pulmonary nodules with ground glass opacities which indicate halo sign and positive serum galactomannan results. Screening studies are needed to evaluate the prevalence of IPA in immunocompromised patients infected with SARS-CoV-2. Consequently, testing for the presence of Aspergillus in lower respiratory secretions and galactomannan in consecutive serum samples of COVID-19 patients with timely and targeted antifungal therapy based on early clinical suspicion of IPA are highly recommended.

Current status of COVID-19 pandemic; characteristics, diagnosis, prevention, and treatment.

Humans have always been encountered to big infectious diseases outbreak throughout the history. In December 2019, novel coronavirus (COVID-19) was first noticed as an agent causing insidious pneumonia in Wuhan, China. COVID-19 was spread rapidly from Wuhan to the rest of the world. Until late June 2020, it infected more than 10,000,000 people and caused more than 500,000 deaths in almost all of countries in the world, creating a global crisis worse than all previous epidemics and pandemics. In the current review, we gathered and summarized the results of various studies on characteristics, diagnosis, treatment, and prevention of this pandemic crisis.

Clostridium difficile isolated from faecal samples in patients with ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is widely identified worldwide. This study aimed to investigate the phenotypic characterization and molecular typing of Clostridium difficile isolates among patients with UC at an inflammatory bowel disease clinic in Iran. METHODS: In this cross-sectional study, conducted from April 2015 to December 2015, 85 UC patients were assessed for C.difficile infection (CDI). C. difficile isolates were characterized based on their toxin profile and antimicrobial resistance pattern. Multi-locus sequence typing analysis (MLST) and PCR ribotyping were performed to define the genetic relationships between different lineages of toxigenic strains. RESULTS: The prevalence of C. difficile isolates was 31.8% (27/85) in patients, of those 15 patients (17.6%) had CDI. Three different sequence types (STs) identified based on MLST among the toxigenic isolates, that is ST54 (33.3%), ST2 (53.3%), and ST37 (13.6%). C. difficile strains were divided into four different PCR-ribotypes (012, 014, 017 and IR1). The most common ribotype was 014 accounting for 48.3% (7/15) of all strains. The strains isolated during the first episode and recurrence of CDI usually belonged to PCR ribotype 014 (ST2). A high rate of CDI recurrence (14.1%, 12/85) experienced in UC patients. Colonization of the gastrointestinal tract with non-toxigenic C. difficile strains was frequent among patients with mild disease. All C. difficile isolates were susceptible to metronidazole, and vancomycin, 86 and 67% of isolates were resistant to clindamycin and erythromycin respectively. There was no correlation between the toxin type and antibiotic resistance (p > 0.05). CONCLUSION: Overall CDI is rather prevalent in UC patients. All patients with CDI experienced moderate to severe disease and exposed to different antimicrobial and anti-inflammatory agents. Close monitoring and appropriate management including early detection and fast treatment of CDI will improve UC outcomes.

Novel biotechnology approaches in colorectal cancer diagnosis and therapy.

With ever-increasing molecular information about colorectal cancer (CRC), there is an expectation to detect more sensitive and specific molecular markers for new advanced diagnostic methods that can surpass the limitations of current screening tests. Moreover, enhanced molecular pathology knowledge about cancer has led to the development of targeted therapies, designed to interfere with specific aberrant biological pathways in cancer. Furthermore, biotechnology has opened a new window in CRC diagnosis and treatment by introducing different application of antibodies, antibody fragments, non-Ig scaffold proteins, and aptamers in targeted therapy and drug delivery. This review summarizes the molecular diagnostic and therapeutic approaches in CRC with a focus on genetic and epigenetic alterations, protein and metabolite markers as well as targeted therapy and drug delivery by Ig-scaffold proteins, non-Ig scaffold proteins, nanobodies, and aptamers.

Detection of quinolone-resistance mutations of parC gene in clinical isolates of Acinetobacter baumannii in Iran.

BACKGROUND: The purpose of this study was to screen of parC gene mutations in clinical isolates of Acinetobacter baumannii from intensive care units (ICUs) of Alzahra Hospital, Isfahan, Iran. MATERIALS AND METHODS: Seventy isolates of A. baumannii between March 2011 and June 2012 were studied. Susceptibility test was established by E-test method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing was performed for detection of parC gene mutation. RESULTS: 77.1% of specimens were highly resistant. Mutation at position 80 in parC was observed in 93% of isolates. CONCLUSION: High proportion of A. baumannii isolates had a mutation in parC that can play an important role in increased incidence of these isolates.

Detection of colistin sensitivity in clinical isolates of Acinetobacter baumannii in Iran.

BACKGROUND: Nosocomial infection caused by Acinetobacter baumannii has emerged as a serious problem world-wide. Finding the suitable drug is an important priority. The aim of this study was to determine colistin (polymyxin E) resistance in clinical isolates of A. baumannii from intensive care units (ICUs) of Al Zahra Hospital. MATERIALS AND METHODS: Sixty isolates of A. baumannii from patients hospitalized in ICU (Al Zahra Hospital, Isfahan University of Medical Sciences [IUMS]) were studied. All isolates of A. baumannii were tested for colistin susceptibility by Eopsilometer test (E-test). RESULTS: Of the 60 isolates 57, (95%) were multidrug resistant (MDR) and 76.6% (46/60) were highly resistant. The rate of colistin resistant with the E-test method was 11.6% (7/60). CONCLUSION: As the frequency of resistance to colistin is low, it can be used as an easily available drug for treatment of MDR A. baumannii strains, which are susceptible to colistin.

Hepatitis A seropositivity among newly admitted medical students of Isfahan, Kermanshah, and Hamedan: A seroprevalence study.

BACKGROUND: Health science students are at an increased risk of hepatitis A virus (HAV) infection even under accidental infection. The aims of this study were to assess the seroprevalence of HAV in 1(st) year medical students and to determine the risk factors of HAV vaccination program among this population. MATERIALS AND METHODS: A cross-sectional study was conducted in autumn 2010. A total of 1028 newly admitted medical students in Isfahan, Kermanshah and Hamedan were included in the study. Participant data were obtained through predesigned data collection sheets. A serum sample was obtained for serologic testing for the presence of IgG anti-HAV using a commercially available enzyme-linked immunosorbent assay kit. Descriptive statistics, Chi-square and logistic regression tests were performed for statistical analysis and P < 0.05 was considered as significant. RESULTS: The prevalence of HAV was detected in Isfahan, Hamedan, and Kermanshah newly admitted students 67.5%, 79.2%, and 50.6% respectively. There were significant relations between anti-HAV (IgG) positivity in drinking water and medical students provinces (P < 0.001, RR = 0.58 and 0.65 respectively). The household size did not significantly influence the anti-HAV (IgG) positivity in studied subjects (P = 0.09, RR = 1.26). CONCLUSION: Our results indicate that more than one-third of the medical students in all three faculties were seronegative for IgG anti-HAV and hence at an increased risk of developing HAV infection as a result of occupational exposure. Therefore, we suggest students in a health care set up should undergo vaccination against HAV after prevaccination immunity screening.

Gut-Lung Microbiota Characterization in Patients with Non-Small Cell Lung Carcinoma and COVID-19 Coinfection.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with COVID-19 have an excessive chance of morbidity and mortality. The fecal-nasopharyngeal microbiota compositions of NSCLC patients were assessed in this study. METHODS: In total, 234 samples were collected from 17 NSCLC patients infected with COVID-19, 20 NSCLC patients without confirmed COVID-19, 40 non NSCLC patients with COVID-19, and 40 healthy individuals. RESULTS: In lung microbiota, the abundance of Streptococcus spp. in NSCLC patients with confirmed COVID-19 was significantly higher than the two control groups. Pseudomonas aeruginosa and Staphylococcus aureus were listed as the most frequent pulmonary bacterial groups that colonized COVID-19 patients. In fecal specimens, the numbers of Bacteroidetes, Firmicutes, and Actinobacteria phyla were significantly higher amongst NSCLC patients with COVID-19. NSCLC patients infected with COVID-19 showed lower levels of Lactobacillus spp., Akkermansia muciniphila, and Bifidobacterium spp. The counts of Streptococcus spp., in NSCLC patients with COVID-19 were significantly higher than those of healthy individuals (8.49±0.70 log CFU/g wet feces vs 8.49±0.70 log CFU/g wet feces). Prevotella spp. were enriched in the gut and respiratory tracts of COVID-19 patient groups. The unbiased analysis showed an increment in Enterococcus spp., Streptococcus spp., and Prevotella spp. CONCLUSION: Eventually, it was found that compared to control groups, COVID-19 patients with NSCLC showed diminished gut bacteria diversity and increase in Lactobacillus spp., A. muciniphila, and Bifidobacterium spp. The overgrowth of Enterococcus spp., Streptococcus spp., and Prevotella spp. could be potential predictive biomarkers in the gut-lung axis of NSCLC patients with COVID-19.

Graphene oxide as novel vaccine adjuvant.

To improve antigen immunogenicity and promote long-lasting immunity, vaccine formulations have been appropriately supplemented with adjuvants. Graphene has been found to enhance the presentation of antigens to CD8+ T cells, as well as stimulating innate immune responses and inflammatory factors. Its properties, such as large surface area, water stability, and high aspect ratio, make it a suitable candidate for delivering biological substances. Graphene-based nanomaterials have recently attracted significant attention as a new type of vaccine adjuvants due to their potential role in the activation of immune responses. Due to the limited functionality of some approved human adjuvants for use, the development of new all-purpose adjuvants is urgently required. Research on the immunological and biomedical use of graphene oxide (GO) indicates that these nanocarriers possess excellent physicochemical properties, acceptable biocompatibility, and a high capacity for drug loading. Graphene-based nanocarriers also could improve the function of some immune cells such as dendritic cells and macrophages through specific signaling pathways. However, GO injection can lead to significant oxidative stress and inflammation. Various surface functionalization protocols have been employed to reduce possible adverse effects of GO, such as aggregation of GO in biological liquids and induce cell death. Furthermore, these modifications enhance the properties of functionalized-GO's qualities, making it an excellent carrier and adjuvant. Shedding light on different physicochemical and structural properties of GO and its derivatives has led to their application in various therapeutic and drug delivery fields. In this review, we have endeavored to elaborate on different aspects of GO.

Impact of Selenium Nanoparticle-Enriched Lactobacilli Feeding Against Escherichia coli O157:H7 Infection of BALB/c Mice.

The effectiveness of selenium nanoparticle (SeNP)-enriched Lactiplantibacillus plantarum and Lactobacillus acidophilus was studied against Shiga toxin-producing Escherichia coli O157:H7 infection on the intestinal fragments and kidney tissue of BALB/c mice. Gut microbiota-targeted bacteria and E. coli O157:H7 counts were obtained by qPCR and PCR. Histology of ileum, colon, and kidney tissues and Stx secretions were analyzed until one-week post-infection. Mice fed with SeNP Lpb. plantarum in the preinfection feeding groups have lower E. coli O157:H7 counts and lower intestinal damage than those in the infected group. The lowest mean fecal probiotic counts were in the L. acidophilus group (7.61 log 10). In pretreatment groups of SeNP L. acidophilus and L. acidophilus, the mean counts of bacteria decreased to 104 CFU/g by day 7. The lowest Stx copy number was demonstrated in SeNP Lpb. plantarum feeding groups' day 7 (P < 0.05). Feeding groups with SeNP Lpb. plantarum had significantly higher members of Lactobacilli in their fecal microbiota than the control group on day 7. It was clarified that Se-enriched Lpb. plantarum and L. acidophilus can be useful as a method of preventing STEC infections. The viability of STEC infection exposure to selenium-enriched Lactobacillus spp. was decreased more than for non-Se-enriched Lactobacillus spp.

Prevalence and Antibiotic Resistance of Clostridioides (Clostridium difficile) In Meat and Meat Products: A Systematic Review and Meta-Analysis.

Background: Meat and meat products are introduced as one of the frequent sources of Clostridioides difficile. We aimed to determine the prevalence and antibiotic resistance of C. difficile isolates in meat and meat products using a systematic review and meta-analysis. Methods: A literature search was performed in the primary international and bibliographic databases such as MEDLINE (PubMed), Cochrane Library, Embase, Scopus, and Web of Science to achieve all articles related to the prevalence and antibiotic resistance rates from 2007 to 2022. Results: The 278 retrieved articles were reduced to 54 worldwide eligible studies after screening and matching inclusion/exclusion criteria. C. difficile was examined in different types of samples and its resistance to 10 antibiotics. The pooled prevalence of C. difficile was 3.4% in all samples. C. difficile pooled prevalence was detected in fish, poultry, and red meat groups with 6.9%, 5.2%, and 3.2%, respectively. Regarding antibiotic resistance, the highest pooled prevalence was for ciprofloxacin (86.6%), followed by clindamycin (42.6%) and erythromycin (34%). The lowest pooled prevalence was observed in metronidazole (7.6%), vancomycin (6.6%), and chloramphenicol (6%). Conclusion: Low resistance was found to commonly used drugs for C. difficile infection (CDI) treatment. Since each antibiotic can be predisposing cause for CDI development, this finding possibly will be warning from a One Health viewpoint about the misuse of antibiotics in the chain of farm to fork including agriculture, animal husbandry and the food industry and also their injudicious use in medicine.

Gut microbiota in burned patients with Clostridioides difficile infection.

BACKGROUND: The survival rate of patients with severe burn is positively associated with increasing the incidence of the Clostridioides difficile (C. difficile) infection (CDI). The surviving rate of severe burn patients now has an improved but the incidence of Clostridioides difficile (C. difficile) infection (CDI) has been continues increasing during recent two decades. This study assessed the molecular typing and phenotypic characterization isolates of C. difficile in burn patients with diarrhea, as well as environmental and skin infections with C. difficile spores at a referral burn hospital in Isfahan, Iran. It mainly aimed to evaluate the dominant bacterial structure in the gut microbiome of burned subjects with and without CDI. METHODS: In general, 309 samples were collected from 189 burned patients with hospital-acquired diarrhea and 120 swabs were collected from the healthcare workers' dominant hands, different sites of patients' skin, and medical tools. In addition, C. difficile isolates were characterized considering the existence of antibiotic resistance and toxin genes. Clinical cultures with identification of organisms and antibiotic susceptibility were done. C. difficle isolates were then genotyped and compared to clinical outcomes. Finally, the clinical characteristics of the participants were gathered through their records, and the bacterial targets of the gut microbiome were detected using quantitative real-time polymerase chain reaction (PCR). RESULTS: Based on the findings, 51 C. difficile isolates were detected from 189 severe burn patients hospitalized in the hospital. Further, PCR amplification tcdB and tcdA showed 23 isolates (12.2%) as toxigenic. Overall, 18.3% (22/120) of skin and environment samples demonstrated a positive result for C. difficile colonization. A low concentration of metronidazole and vancomycin (MIC90, 0.5, and 1.2 mg/L) inhibited all toxigenic C. difficile strains. Moreover, these isolates represented the highest rates of resistance to moxifloxacin and clindamycin (MIC90, 0.5, and 1.6 mg/L). A significantly reduced abundance of Clostridium spp., Bacteroidetes, and Bifidobacterium and an increase in the quantity of Firmicutes was observed in the gastrointestinal microbiome of burn patients (P < 0.01). Burn patients with CDI showed a significant decrease in Faecalibacterium prausnitzii (F. prausnitzii) while higher Akkermansia muciniphila (A. muciniphila) loads in comparison with healthy controls (P < 0.001 and P < 0.05). Contrarily, burned cases displayed increased levels of opportunistic pathogenic bacteria including the members of Enterococcus spp. and Escherichia coli (P < 0.05). CONCLUSIONS: Despite appropriate infection control strategies in the burn intensive care unit, CDI remains prevalent in severe burn patients. Eventually, the overgrowth of A. muciniphila and the decreased abundance of F. prausnitzii in burn cases with CDI could be potential predictive microbiome biomarkers in burned patients.

Deep survey for designing a vaccine against SARS-CoV-2 and its new mutations.

The ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has prompted worldwide vaccine development. Several vaccines have been authorized by WHO, FDA, or MOH of different countries. However, issues such as need for cold chain, price, and most importantly access problems have limited vaccine usage in some nations especially developing countries. Moreover, the vast global demand justifies further attempts for vaccine development. Multi-epitope polypeptide vaccines enjoy several key features including safety and lower production and transfer costs and could be designed by in silico tools. Spike protein (S), membrane protein (M), and nucleocapsid protein (N), the three major structural proteins of SARS-CoV-2, are ideal candidates for epitope selection. ORF3a (open reading frame3a), a transmembrane protein with pro-apoptotic functions, could be another proper target. Thus, a novel multi-epitope vaccine against SARS-CoV-2 was designed using these four proteins and LL37, a TLR3 agonist adjuvant, through different immunoinformatics and bioinformatics tools. The proposed multi-epitope vaccine is expected to induce robust humoral and cellular immune responses against SARS-CoV-2 with a population coverage of 76.92 % due to containing different immunodominant epitopes and LL37 adjuvant. Selecting epitopes derived from one functional and three structural proteins suggests the protective ability of the vaccine irrespective of probable virus mutations. The computationally observed proper interaction of LL37 with TLR3 implies its ability to induce immune responses effectively. Besides, it showed acceptable structural and physicochemical properties. The in-silico cloning results predicted its high efficiency production in Escherichia coli. Future experimental studies could further confirm its immunological efficacy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11756-021-00866-y.

Computational Elucidation of Phylogenetic, Functional and Structural Features of Methioninase from Pseudomonas, Escherichia, Clostridium and Citrobacter Strains.

BACKGROUND: L-Methioninase (EC 4.4.1.11; MGL) is a pyridoxal phosphate (PLP)-dependent enzyme that is produced by a variety of bacteria, fungi, and plants. L-methioninase, especially from Pseudomonas and Citrobacter sp., is considered as the efficient therapeutic enzyme, particularly in cancers such as glioblastomas, medulloblastoma, and neuroblastoma that are more sensitive to methionine starvation. OBJECTIVE: The low stability is one of the main drawbacks of the enzyme; in this regard, in the current study, different features of the enzyme, including phylogenetic, functional, and structural from Pseudomonas, Escherichia, Clostridium, and Citrobacter strains were evaluated to find the best bacterial L-Methioninase. METHODS: After the initial screening of L-Methioninase sequences from the above-mentioned bacterial strains, the three-dimensional structures of enzymes from Escherichia fergusonii, Pseudomonas fluorescens, and Clostridium homopropionicum were determined through homology modeling via GalaxyTBM server and refined by GalaxyRefine server. RESULTS AND CONCLUSION: Afterwards, PROCHECK, verify 3D, and ERRAT servers were used for verification of the obtained models. Moreover, antigenicity, allergenicity, and physico-chemical analysis of enzymes were also carried out. In order to get insight into the interaction of the enzyme with other proteins, the STRING server was used. The secondary structure of the enzyme is mainly composed of random coils and alpha-helices. However, these outcomes should further be validated by wet-lab investigations.

Iron nanoparticles as novel vaccine adjuvants.

The poor immunogenicity of peptide vaccines compared to conventional ones re usually improved by applying different adjuvants. As chemical or biological substances, adjuvants are added to vaccines to enhance and prolong the immune response. According to considerable investigations over the recent years in the context of finding new adjuvants, a handful of vaccine adjuvants have been licensed for human use. Recently, engineered nanoparticles (NPs) have been introduced as novel alternatives to traditional vaccine adjuvant. Metallic nanoparticles (MeNPs) are among the most promising NPs used for vaccine adjuvant as well as the delivery system that can improve immune responses against pathogens. Iron NPs, as an important class of MeNPs, have gained increasing attention as novel vaccine adjuvants. These particles have shown acceptable results in preclinical studies. Hence, understanding the physicochemical properties of iron NPs, including size, surface properties, charge and route of administration, is of substantial importance. The aim of this review is to provide an overview of the immunomodulatory effects of iron NPs as novel adjuvants. Furthermore, physicochemical properties of these NPs were also discussed.

Small extracellular vesicles (sEVs): discovery, functions, applications, detection methods and various engineered forms.

INTRODUCTION: Extracellular vesicles (EVs) are cell-created delivery systems of proteins, lipids, or nucleic acids, and means of extracellular communication. Though sEVs were initially considered to be the waste disposal mechanism, today they are at the forefront of research with different biological and pathological functions. Such EVs play a key role in the immunoregulation, CNS development, nervous system physiology, mammary gland development, induction of immunosuppression in pregnancy, the developmental signaling pathways, regeneration of different tissues, inflammation, angiogenesis, coagulation, apoptosis, stem cell differentiation, and extracellular matrix turnover. AREAS COVERED: SEVs contribute to the pathogenesis of different cancers and the progression of various neurodegenerative diseases, infections, as well as metabolic and cardiovascular diseases. Expert Opinion: There is no exact classification for EVs; however, according to size, density, morphological features, content, and biogenesis, they can be categorized into three major classes: microvesicles (ectosomes or microparticles), apoptotic bodies, and sEVs. SEVs, as an important class of EVs, have a crucial role in distinct biological functions. Moreover, shedding light on different structural and molecular aspects of sEV has led to their application in various therapeutic, diagnostic, and drug delivery fields. In this review, we have endeavored to elaborate on different aspects of EVs, especially sEVs.

Intestinal Microbiota in Elderly Inpatients with Clostridioides difficile Infection.

PURPOSE: The incidence of Clostridioides difficile infection (CDI) has been reported as 10-fold higher among the elderly population than in young adults. The aim of this study was to compare the targeted bacteria population in the fecal microbiota in two groups of hospitalized elderly, categorized according to CDI and non-CDI. PATIENT AND METHODS: In this case-control study, 84 fecal samples of the 28 patients with CDI and 56 non-CDI patients (>65 years) were studied. C. difficile isolates were characterized by anaerobic culture and multiplex PCR. Quantitative PCR was used to analyze the bacterial elements. RESULTS: CDI group differed significantly for a prolonged hospital stay, previous surgery, residence in nursing home and exposure to a range of antibiotics including quinolone, clindamycin and cephalosporin. CDI group had significantly fewer members of Bacteroides spp., Clostridium cluster IV, Bifidobacterium spp., Faecalibacterium prausnitzii, and Prevotella spp. in their fecal microbiota than the control group (P < 0.05). The abundances of Akkermansia muciniphila, Lactobacillus spp., Escherichia coli and Klebsiella spp. were higher in group CDI compared with the control group (P < 0.05). CONCLUSION: CDI status is associated with the abundance of some bacterial populations. In this study, an increase in Akkermansia muciniphila, Lactobacillus spp., and Enterobacteriaceae genus was highlighted in CDI patients. A reduction in butyrate-producing bacteria was found in CDI patients. The differences in the composition of fecal microbiota can help to understand how antimicrobial agents impact on gut homeostasis and lead to loss of colonization resistance to C. difficile.