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Currently, a large number of people favor meals that are rich in nutraceuticals and phytochemical compounds, which help with the treatment or prevention of chronic diseases. Oral bioavailability is a crucial component of phytochemical bioefficiency, and endogenous mechanisms have a significant impact on how well nutraceuticals and phytochemicals are absorbed by the body. In addition to endogenous variables, exogenous factors that impact the bioavailability of bioactives include the food matrix, food processing, and food storage. Different delivery systems have evolved in this regard, and nanoscale delivery tools have also been created. Delivery methods that use nanostructured lipid carriers show benefits such as enhanced loading capacity, solubility, encapsulation effectiveness, storage stability, bioavailability, and half-life. They also provide safe food systems and regulated release. In this review, the outcomes of recent experimental reports are comprehensively reviewed. In addition, the food processing, storage, gut milieu circumstances, the release process from the food and nano delivery systems in the gastrointestinal tract (GIT) milieu, interactions with other GIT constituents, main delivery systems based on nanostructured lipid carriers for their encapsulation and eventually encapsulating technological barriers, food safety concerns, and regulatory issues of nutraceutical and phytochemical compounds are discussed.

Abstract Background and objective(s) CRISPR-Cas is a prokaryotic adaptive immune system that protects bacteria and archaea against mobile genetic elements (MGEs) such as bacteriophages plasmids, and transposons. In this study, we aimed to assess the prevalence of the CRISPR-Cas systems and their association with antibiotic resistance in one of the most challenging bacterial pathogens, Klebsiella pneumoniae. Materials and methods A total of 105 K. pneumoniae isolates were collected from various clinical infections. Extended-spectrum β-lactamases (ESBLs) phenotypically were detected and the presence of ESBL, aminoglycoside-modifying enzymes (AME), and CRISPR-Cas system subtype genes were identified using PCR. Moreover, the diversity of the isolates was determined by enterobacterial repetitive intergenic consensus (ERIC)-PCR. Results Phenotypically, 41.9% (44/105) of the isolates were found to be ESBL producers. A significant inverse correlation existed between the subtype I-E CRISPR-Cas system’s presence and ESBL production in K. pneumoniae isolates. Additionally, the frequency of the ESBL genes bla CTX−M1 (3%), bla CTX−M9 (12.1%), bla SHV (51.5%), and bla TEM (33.3%), as well as some AME genes such as aac(3)-Iva (21.2%) and ant(2’’)-Ia (3%) was significantly lower in the isolates with the subtype I-E CRISPR-Cas system in comparison to CRISPR-negative isolates. There was a significant inverse correlation between the presence of ESBL and some AME genes with subtype I-E CRISPR-Cas system. Conclusion The presence of the subtype I-E CRISPR-Cas system was correlated with the antibiotic-resistant gene (ARGs). The isolates with subtype I-E CRISPR-Cas system had a lower frequency of ESBL genes and some AME genes than CRISPR-negative isolates.

Microbiota refers to a collection of living microorganisms, including bacteria, yeasts, and viruses, that coexist in various sites of the human body. Microbiota can perform multiple functions in the body, which have an essential effect on human health and homeostasis. For example, the microbiota can digest polysaccharides, produce vitamins, modulate the immune system, and protect the body against pathogens. Various factors can occasionally alter the microbiota population in the human body, a condition known as dysbiosis. Dysbiosis can disrupt the homeostasis of a person's body and cause disease. Recent years have witnessed efforts to restore the microbiota population of an individual's body to its original state and eradicate dysbiosis through microbiota transplantation. The noteworthy point is that different methods such as fecal microbiota transplantation, vaginal microbiota transplantation (VMT), skin microbiota transplantation (SMT), oral microbiota transplantation (OMT), washed microbiota transplantation (WMT), and sinonasal microbiota transplantation (SiMT) are used for microbiota transplantation (MT). According to the results of studies and the usefulness of MT in improving a person's health, the purpose of this study is to investigate different methods of MT to eliminate dysbiosis.

ABSTRACT: Objectives: Plasmid genes, termed mobile colistin resistance-1 (mcr-1) and mobile colistin resistance-2 (mcr-2), are associated with resistance to colistin in Escherichia coli (E. coli). These mcr genes result in a range of protein modifications contributing to colistin resistance. This study aims to discern the proteomic characteristics of E. coli–carrying mcr-1 and mcr-2 genes. Furthermore, it evaluates the expression levels of various proteins under different conditions (with and without colistin). Methods: Plasmid extraction was performed using an alkaline lysis–based plasmid extraction kit, whereas polymerase chain reaction was used to detect the presence of mcr-1 and mcr-2 plasmids. The E. coli DH5α strain served as the competent cell for accepting and transforming mcr-1 and mcr-2 plasmids. We assessed proteomic alterations in the E. coli DH5α strain both with and without colistin in the growth medium. Proteomic data were analysed using mass spectrometry. Results: The findings revealed significant protein changes in the E. coli DH5α strain following cloning of mcr-1 and mcr-2 plasmids. Of the 20 proteins in the DH5α strain, expression in 8 was suppressed following transformation. In the presence of colistin in the culture medium, 39 new proteins were expressed following transformation with mcr-1 and mcr-2 plasmids. The proteins with altered expression play various roles. Conclusion: The results of this study highlight numerous protein alterations in E. coli resulting from mcr-1 and mcr-2–mediated resistance to colistin. This understanding can shed light on the resistance mechanism. Additionally, the proteomic variations observed in the presence and absence of colistin might indicate potential adverse effects of indiscriminate antibiotic exposure on treatment efficacy and heightened pathogenicity of microorganisms.

The blood-brain interface poses formidable obstacles in addressing neurological conditions such as Alzheimer's, Multiple Sclerosis, brain cancers, and cerebrovascular accidents. Serving as a safeguard against potential threats in the blood, this barrier hinders direct drug delivery to affected cells, necessitating specialized transport mechanisms. Within the realm of nanotechnology, the creation of nanoscale carriers, including macromolecules such as polymers, lipids, and metallic nanoparticles, is gaining prominence. These carriers, tailored in diverse forms and sizes and enriched with specific functional groups for enhanced penetration and targeting, are capturing growing interest. This revised abstract explores the macromolecular dimension in understanding how nanoparticles interact with the blood-brain barrier. It re-evaluates the structure and function of the blood-brain barrier, highlighting macromolecular nanocarriers utilized in drug delivery to the brain. The discussion delves into the intricate pathways through which drugs navigate the blood-brain barrier, emphasizing the distinctive attributes of macromolecular nanocarriers. Additionally, it explores recent innovations in nanotechnology and unconventional approaches to drug delivery. Ultimately, the paper addresses the intricacies and considerations in developing macromolecular-based nanomedicines for the brain, aiming to advance the creation and evolution of nanomedicines for neurological ailments.

The emergence and development of antibiotic resistance in bacteria is a serious threat to global public health. Antibiotic resistance genes (ARGs) are often located on mobile genetic elements (MGEs). They can be transferred among bacteria by horizontal gene transfer (HGT), leading to the spread of drug-resistant strains and antibiotic treatment failure. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated genes) is one of the many strategies bacteria have developed under long-term selection pressure to restrict the HGT. CRISPR-Cas systems exist in about half of bacterial genomes and play a significant role in limiting the spread of antibiotic resistance. On the other hand, bacteriophages and other MGEs encode a wide range of anti-CRISPR proteins (Acrs) to counteract the immunity of the CRISPR-Cas system. The Acrs could decrease the CRISPR-Cas system's activity against phages and facilitate the acquisition of ARGs and virulence traits for bacteria. This review aimed to assess the relationship between the CRISPR-Cas systems and Acrs with bacterial antibiotic resistance. We also highlighted the CRISPR technology and Acrs to control and prevent antibacterial resistance. The CRISPR-Cas system can target nucleic acid sequences with high accuracy and reliability; therefore, it has become a novel gene editing and gene therapy tool to prevent the spread of antibiotic resistance. CRISPR-based approaches may pave the way for developing smart antibiotics, which could eliminate multidrug-resistant (MDR) bacteria and distinguish between pathogenic and beneficial microorganisms. Additionally, the engineered anti-CRISPR gene-containing phages in combination with antibiotics could be used as a cutting-edge treatment approach to reduce antibiotic resistance.

Role of clustered regularly interspaced short palindromic repeats (CRISPR)-like sequences in antibiotic resistance and biofilm formation isn't clear. This study investigated association of CRISPR-like sequences with antibiotic resistance and biofilm formation in H. pylori isolates. Thirty-six of H. pylori isolates were studied for existence of CRISPR-like sequences using PCR method and their correlation with biofilm formation and antibiotic resistance. Microtiter-plate technique was utilized for investigating antibiotic resistance profile of isolates against amoxicillin, tetracycline, metronidazole and clarithromycin. Biofilm formation of isolates was analyzed by microtiter-plate-based-method. Out of 23 CRISPR-like positive isolates, 19 had ability of biofilm formation and 7 of 13 CRISPR-like negative isolates were able to form biofilm (Pvalue = 0.445). In CRISPR-like positive isolates, 11 (48%), 18 (78%), 18 (78%) and 23 (100%) were resistant to amoxicillin, tetracycline, metronidazole and clarithromycin, respectively. Since CRISPR-like sequences have role in antibiotic resistance, may be applied as genetic markers of antibiotic resistance. But there was no substantial correlation between biofilm formation and existence of CRISPR-like sequences. These results indicate possible importance of CRISPR-like sequences on acquisition of resistance to antibiotics in this bacterium.

Background: Human intestine microbiota are known to be directly and indirectly altered during some diseases such as kidney complications. Bacteroides is considered as the main and the most abundant phylum among human gut microbiota, which has been classified as enterotype 1. This study aimed to assess the abundance of Bacteroides spp. in fecal flora of end-stage renal disease (ESRD) and chronic kidney disease (CKD) patients and compare it with the Bacteroides composition among fecal flora of healthy individual. Methods: Fresh fecal samples were collected from 20 CKD/ESRD patients and 20 healthy individual without any kidney complications. The pure microbial DNA was extracted by QIAamp Stool Mini Kit from stool samples. MiSeq system was used to analyze the intestinal composition by next generation sequencing method. Results: A number of 651 bacterial strains were isolated and identified from 40 fecal samples of both patients and healthy groups. Bioinformatics analysis defined 18 different types of Bacteroides species which included 2.76% of all strains. Statistical analysis showed no significant difference between study groups (P>0.05). In both healthy and patient groups three species including B. dorei, B. uniformis, and B. ovatus have allocated the most abundance to themselves. The lowest abundance was related to B. eggerthii, A. furcosa and B. barnesiae among CKD/ESRD patients and A. furcosa, B. barnesiae, and B. coprocola had the lowest abundance among healthy people. Conclusion: This study indicates despite all previous evidence of Bacteroides role in gut microbiota, it had no different distribution between healthy persons and CKD/ESRD patients.

Despite the widespread use of the Bacillus Calmette–Guérin (BCG) vaccine, Mycobacterium tuberculosis (MTB) continues to be a global burden. Vaccination has been proposed to prevent and treat tuberculosis (TB) infection, and several of them are in different phases of clinical trials. Though vaccine production is in progress but requires more attention. There are several TB vaccines in the trial phase, most of which are based on a combination of proteins/adjuvants or recombinant viral vectors used for selected MTB antigens. In this review, we attempted to discuss different types of TB vaccines based on the vaccine composition, the immune responses generated, and their clinical trial phases. Furthermore, we have briefly overviewed the effective delivery systems used for the TB vaccine and their effectiveness in different vaccines.

Background. In recent decades, the microbial and plant-derived urease have been used for sand stabilization by the calcium carbonate precipitation method, especially with Sporosarcina pasteurii. However, calcium carbonate precipitation using plant-derived urease has received less attention. Purchasing the extracted and purified commercially available plant-derived urease for the sand improvement is costly. The plant-derived urease-containing crude extract (enzyme substance) is cheaper than purified (commercial) urease. In the present study, the feasibility of sand improvement by enzyme-induced calcium carbonate precipitation method was investigated with urease-containing crude extract (extracted from soybean). Methods. The distilled water, instead of phosphate buffer, was used to provide the main enzyme extraction medium. Also, the effects of temperature, time, and dilution on the activity of the urease-containing crude extract by the electrical conductivity meter were investigated. Results. The results showed that the extraction temperature had a significant effect on the behavior of the enzymes, and according to the results, the temperature range between 19 and 25°C is suitable for the enzyme extraction. The four-layer surface percolation method was used to improve the sand, and 0.75 equimolar (eqM) concentration of urea-CaCl2 cementation solution is suitable for sand improvement using the UCE extracted from soybean seed. Conclusion. Silica sand was successfully improved by the EICP method using the four-layer surface percolation method, and significant unconfined compressive strength and elasticity modulus were obtained. XRD and XRF analysis also confirmed the successful precipitation of calcium carbonate between the sand particles.

Significant advancements have been noticed in cancer therapy for decades. Despite this, there are still many critical challenges ahead, including multidrug resistance, drug instability, and side effects. To overcome obstacles of these problems, various types of materials in biomedical research have been explored. Chief among them, the applications of natural compounds have grown rapidly due to their superb biological activities. Natural compounds, especially polyphenolic compounds, play a positive and great role in cancer therapy. Tannic acid (TA), one of the most famous polyphenols, has attracted widespread attention in the field of cancer treatment with unique structural, physicochemical, pharmaceutical, anticancer, antiviral, antioxidant and other strong biological features. This review concentrated on the basic structure along with the important role of TA in tuning oncological signal pathways firstly, and then focused on the use of TA in chemotherapy and preparation of delivery systems including nanoparticles and hydrogels for cancer therapy. Besides, the application of TA/Fe3+ complex coating in photothermal therapy, chemodynamic therapy, combined therapy and theranostics is discussed.

Abstract Background The emergence of carbapenem-resistant Enterobacterales (CRE) continues to threaten public health due to limited therapeutic options. In the current study the incidence of carbapenem resistance among the 104 clinical isolates of Escherichia coli and the genomic features of carbapenem resistant isolates were investigated. Methods The susceptibility to imipenem, tigecycline and colistin was tested by broth dilution method. Susceptibility to other classes of antimicrobials was examined by disk diffusion test. The presence of bla OXA-48, bla KPC, bla NDM, and bla VIM carbapenemase genes was examined by PCR. Molecular characteristics of carbapenem resistant isolates were further investigated by whole-genome sequencing (WGS) using Illumina and Nanopore platforms. Results Four isolates (3.8%) revealed imipenem MIC of ≥32 mg/L and positive results for modified carbapenem inactivation method and categorized as carbapenem resistant E. coli (CREC). Colistin, nitrofurantoin, fosfomycin, and tigecycline were the most active agents against all isolates (total susceptibility rate of 99, 99, 96 and 95.2% respectively) with the last three compounds being found as the most active antimicrobials for carbapenem resistant isolates (susceptibility rate of 100%). According to Multilocus Sequence Type (MLST) analysis the 4 CREC isolates belonged to ST167 (n = 2), ST361 (n = 1) and ST648 (n = 1). NDM was detected in all CREC isolates (NDM-1 (n = 1) and NMD-5 (n = 3)) among which one isolate co-harbored NDM-5 and OXA-181 carbapenemases. WGS further detected bla CTX-M-15, bla CMY-145, bla CMY-42 and bla TEM-1 (with different frequencies) among CREC isolates. Co-occurrence of NDM-type carbapenemase and 16S rRNA methyltransferase RmtB and RmtC was found in two isolates belonging to ST167 and ST648. A colistin-carbapenem resistant isolate which was mcr-negative, revealed various amino acid substitutions in PmrB, PmrD and PhoPQ proteins. Conclusion About 1.9% of E. coli isolates studied here were resistant to imipenem, colistin and/or amikacin which raises the concern about the outbreaks of difficult-to-treat infection by these emerging superbugs in the future.

Abstract Background Tuberculosis (TB) is considered one of the most infectious diseases in the world. In this study, we intended to examine the epidemiology of tuberculosis by MIRU-VNTR to define the changes that occur in the transmission of tuberculosis in the region during the COVID-19 era. A total of 120 Mycobacterium tuberculosis isolates were collected from sputum samples of patients referred to East Azerbaijan Center TB from December 2020 to August 2021. Demographic information such as age, sex, place of birth, previous TB history, and relevant medical data was collected. The proportion method was performed for drug susceptibility testing, and the PCR-based MIRU-VNTR method was applied to identify molecular epidemiology relationships. Results The isolates were collected from 78 male (65%) and 39 female (32.5%) Iranian patients and 3 (2.5%) Azerbaijani patients. Ninety-three distinct patterns were identified including 15 clustered patterns and 36 unique patterns. The largest cluster was composed of seven isolates. Furthermore, one cluster with 5 members, four clusters with 3 members, and nine clusters with 2 members. In MIRU-VNTR typing, 75 clusters belonged to the Tabriz region and just 3 to the Republic of Azerbaijan. All isolates were sensitive to rifampin, isoniazid, and ethambutol. Conclusions Results of the current study showed COVID-19 pandemic had a direct effect on the transmission and diagnosis of tuberculosis. Less diagnosis and less clustering can indicate public controls and hygiene, and the use of masks had a direct effect on the transmission and diagnosis of tuberculosis. However, misidentification and less focus on other respiratory infections are expected during the pandemic. Studies on the co-infection of COVID-19 and tuberculosis and the role of mask and sanitization against TB are strongly recommended.

Abstract Background Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

Abstract Background To provide effective healing in the wound, various carbohydrate polymers are commonly utilized that are highly potent platforms as wound dressing films. In this work, novel antibacterial flexible polymeric hydrogel films were designed via crosslinking polymeric chitosan (CS) with folic acid-based carbon quantum dots (CQDs). To end this, folic acid as a bio-precursor is used to synthesize CQDs through the hydrothermal technique. The synthesized CQDs as a crosslinking agent was performed at different concentrations to construct nanocomposite hydrogel films via the casting technique. Also, gentamicin (GM), L-Arginine and glycerol were supplemented in the formulation of nanocomposite since their antibiotic, bioactivity and plasticizing ability, respectively. Results The successful construction of films were verified with different methods (FT-IR, UV-Vis, PL, SEM, and AFM analyses). The GM release profile displayed a controlled release manner over 48 h with a low initial burst release in the simulated wound media (PBS, pH 7.4). Antibacterial and in vitro cytotoxicity results showed a significant activity toward different gram-positive and negative bacterial strains (about 2.5 ± 0.1 cm inhibition zones) and a desired cytocompatibility against Human skin fibroblast (HFF-1) cells (over 80% cell viability), respectively. Conclusion The obtained results recommend CQDs-crosslinked CS (CS/CQD) nanocomposite as a potent antimicrobial wound dressing. Graphical Abstract

Chronic kidney disease (CKD) refers to a range of various pathophysiological processes correlated with abnormal renal function and a progressive loss in GFR. Just as dysbiosis and altered pathology of the gut are accompanied with hypertension, which is a significant CKD risk factor. Gut dysbiosis in CKD patients is associated with an elevated levels of uremic toxins, which in turn increases the CKD progression.According to research results, the gut-kidney axis has a role in the formation of kidney stones, also in IgAN. A number of researchers have categorized the gut microbiota as enterotypes, and others, skeptical of theory of enterotypes, have suggested biomarkers to describe taxa that related to lifestyle, nutrition, and disease status. Metabolome-microbiome studies have been used to investigate the interactions of host-gut microbiota in terms of the involvement of metabolites in these interactions and are yielded promising results. The correlation between gut microbiota and CKD requires further multi-omic researches. Also, with regard to systems biology, studies on the communication network of proteins and transporters such as SLC and ABC, can help us achieve a deeper understanding of the gut-liver-kidney axis communication and can thus provide promising new horizons in the treatment of CKD patients. Probiotic-based treatment is an approach to reduce uremic poisoning, which is accomplished by swallowing microbes those can catalyze URS in the gut. If further comprehensive studies are carried out, we will know about the probiotics impact in slowing the renal failure progression and reducing inflammatory markers.

Abstract Background and Aims SARS‐CoV‐2, as a new pandemic disease, affected the world. Short‐chain fatty acids (SCFAs) such as acetic, propionic, and butyric acids are the main metabolites of human gut microbiota. The positive effects of SCFAs have been shown in infections caused by respiratory syncytial virus, adenovirus, influenza, and rhinovirus. Therefore, this study aimed to evaluate the concentration of SCFAs in patients with SARS‐CoV‐2 compared with the healthy group. Methods This research was designed based on a case and control study. Twenty healthy individuals as the control group and 20 persons admitted to the hospital with a positive test of coronavirus disease (COVID‐19) real‐time polymerase chain reaction were included in the study as the patient group from September 2021 to October 2021, in Tabriz, Iran. Stool specimens were collected from volunteers, and analysis of SCFAs was carried out by a high‐performance liquid chromatography system. Results The amount of acetic acid in the healthy group was 67.88 ± 23.09 μmol/g, while in the group of patients with COVID‐19 was 37.04 ± 13.29 μmol/g. Therefore, the concentration of acetic acid in the patient group was significantly (p 0.05). Conclusion This study showed that the concentration of acetic acid as the metabolite caused by gut microbiota is significantly disturbed in patients with COVID‐19. Therefore, therapeutic interventions based on gut microbiota metabolites in future research may be effective against COVID‐19.

Sepsis is a complex clinical disorder with heterogeneous etiological factors. Given its high mortality rate, it is considered a global health issue. Recently, the link between gut microbiota and their metabolites, especially short-chain fatty acids, in the pathophysiology of sepsis has been reported. However, there are few findings to confirm this relationship. This study aimed to evaluate some key gut microbiota members, pathogenic bacteria, and short-chain fatty acids in non-ICU patients with sepsis caused by bacteremia compared to a control group. In this case-control study, 45 stool samples from patients with sepsis and 15 healthy persons were collected from October 2021 to August 2022 in Tabriz, Iran. The position of some gut microbiota members and the main short-chain fatty acids concentration were assessed in the two groups by the Q-PCR and the high-performance liquid chromatography system. Faecalibacterium prausnitzii and Bifidobacterium sp. As bacterial with protective features in non-ICU patients with sepsis decreased significantly. Moreover, the concentrations of acetic acid and propionic acid significantly decreased in this group compared to the healthy volunteers. In contrast, the pathogenic bacteria members such as Enterobacteriaceae and Bacteroides sp. Increased significantly in the patients compared to the healthy individuals. The concentration of butyric acid decreased in the patients, but this change was not significant in the two groups. Protective and immune functions of F. prausnitzii and Bifidobacterium sp., as well as acetate and propionate, are evident. In this investigation, this profile was significantly reduced in non-ICU patients with sepsis compared to the control group.

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue–derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127- Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo–treated PBMCs. The concentration of IL‐10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of Tregs, potentiating its therapeutic effects in COVID-19.

Abstract Background Interleukin (IL)-10 is one of the key interleukins in the immune system. It plays an anti-inflammatory role in body by inhibition of the synthesis of pro-inflammatory cytokines and reducing the expression of major histocompatibility complex II molecules. The single-nucleotide polymorphism in the gene of this interleukin affects its expression level. Thus, this study was conducted to investigate the IL-10 gene polymorphism at position -1082A/G in Azeri population of Iran. Methods Blood samples were taken from 254 healthy and non-relevant Iranian Azeri individuals. After DNA extraction, the frequency of IL-10 genotypes and alleles at -1082A/G position was determined by allele specific-PCR method. Then, q-square test was used to compare allele frequencies and IL-10 genotypes with other populations, and p value of

Multiple sclerosis (MS) is known as a chronic inflammatory disease (CID) that affects the central nervous system and leads to nerve demyelination. However, the exact cause of MS is unknown, but immune system regulation and inhibiting the function of inflammatory pathways may have a beneficial effect on controlling and improving the disease. Studies show that probiotics can alter the gut microbiome, thereby improving and affecting the immune system and inflammatory responses in patients with MS. The results show that probiotics have a good effect on the recovery of patients with MS in humans and animals. The present study investigated the effect of probiotics and possible therapeutic mechanisms of probiotics on immune cells and inflammatory cytokines. This review article showed that probiotics could improve immune cells and inflammatory cytokines in patients with MS and can play an effective role in disease management and control.

Abstract Background Recently, biosensors have become popular analytical tools for small analytes due to their high sensitivity and wide analytical range. In the present work, development of a novel biosensing method based on tungsten disulfide quantum dots (WS2 QDs)-Au for rapidly and selectively detecting c-Met protein is introduced. As a proof of concept, M13 bacteriophage-based biosensors were used for the electrochemical detection of c-Met protein as a colon cancer biomarker. Method The M13 bacteriophage (virus), as the biorecognition element, was immobilized on glassy carbon electrodes which were modified by WS2 QDs-functionalized gold nanoparticles. The stepwise presence of the WS2 QDs, gold nanoparticles, and immobilized phage on glassy carbon electrodes were confirmed by scanning electron microscope (SEM) and square wave voltammetry (SWV) technique. Results The designed biosensor was applied to measure the amount of c-Met protein in standard solutions, and consequently the desirable detection limit of 1 pg was obtained. Finally, as a proof of concept, the developed platform was used for the evaluation of c-Met protein in serum samples of colon cancer-suffering patients and the results were compared with the results of the common Elisa kit. Conclusions As an interesting part of this study, some concentrations of the c-Met protein in colon cancer serum samples which could not be determined by Elisa, were easily analyzed by the developed bioassay system. The developed bioassay system has great potential to application in biomedical laboratories. Graphical Abstract

Abstract Background The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants’ perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness. Methods A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days. Results Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations. Conclusion Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened.

The current study aims to synthesize the gelatin-coated nanostructured lipid carrier (NLC) to encapsulate sage extract and use this nanoparticle to increase the quality parameters of beef burger samples. NLCs were prepared by formulation of gelatin (as surfactant and coating biopolymer), tallow oil (as solid lipid), rosemary essential oil (as liquid lipid), sage extract (as active material or encapsulant), polyglycerol ester and Tween 80 (as low-molecular emulsifier) through the high-shear homogenization–sonication method. The effects of gelatin concentrations and the solid/liquid ratio on the particle size, polydispersity index (PDI), and encapsulation efficiency (EE%) of sage extract-loaded NLCs were quantitatively investigated and optimized using a combined D-optimal design. Design expert software suggested the optimum formulation with a gelatin concentration of 0.1 g/g suspension and solid/liquid lipid ratio of 60/40 with a particle size of 100.4 nm, PDI of 0.36, and EE% 80%. The morphology, interactions, thermal properties, and crystallinity of obtained NLC formulations were investigated by TEM, FTIR, DSC, and XRD techniques. The optimum sage extract-loaded/gelatin-coated NLC showed significantly higher antioxidant activity than free extract after 30 days of storage. It also indicated a higher inhibitory effect against E. coli and P. aeruginosa than free form in MIC and MBC tests. The optimum sage extract-loaded/gelatin-coated NLC, more than free extract, increased the oxidation stability of the treated beef burger samples during 90 days of storage at 4 and −18 °C (verified by thiobarbituric acid and peroxide values tests). Incorporation of the optimum NLC to beef burgers also effectively decreased total counts of mesophilic bacteria, psychotropic bacteria, S. aureus, coliform, E. coli, molds, and yeasts of treated beef burger samples during 0, 3, and 7 days of storage in comparison to the control sample. These results suggested that the obtained sage extract-loaded NLC can be an effective preservative to extend the shelf life of beef burgers.

Background: Colorectal cancer (CRC) is the third most prevalent cancer with approximately 9,000 annual deaths worldwide. However, early detection can provide a high survival rate. The fecal DNA, as a non-invasive method for detecting the genetic markers, such as the TP53 gene, can be conducive to disease diagnosis. In this study, we aimed to investigate the presence of the TP53 mutations in the stool samples and their relationship with somatic mutations in the tissue samples of CRC patients from northwestern Iran. Method: In the present cohort study, tumor and stool samples were obtained from 64 CRC patients (mean age of 60), who were undergoing surgery. Total genomic DNA was extracted from the tissue and stool samples, and TP53 mutations were detected using the PCR-SSCP method, followed by direct sequencing. Differences between mutations were observed in the tumors, and the stools were examined using the McNemar method. Results: Of 64 CRC patients, 19 individuals (30%) demonstrated 27 point mutations in exons 5-7 of the TP53 in the tumor samples. Furthermore, analysis of the stool specimens revealed that the 22 mutations (81.5%) identified in the tumor specimens were also present in the stool of 12 patients (P = 0.063). Conclusion: Based on the results, the DNA from the tissue could be replaced with fecal DNA in the mutation detections for CRC. Given the non-invasive nature of fecal sampling, it can be desirable and acceptable for patients in molecular screening tests as it increases the screening rates and improves timely CRC diagnosis.

Abstract Purpose The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods Mono‐delivery and co‐delivery of SRL and CsA by NLCs (S‐NLCs, C‐NLCs, and S‐C‐NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results Well‐designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co‐delivery by NLCs. Following S‐NLCs and C‐NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro‐inflammatory cytokines (IFN‐γ, TNF‐α, IL‐17, and IL‐21) and their regulators (T‐bet and RORγt), as well as a lower level of an anti‐inflammatory cytokine (IL‐10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S‐C‐NLCs intervention. Conclusions S‐C‐NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first introduced in China in 2019, and it has rapidly spread all around the world. Cryptococcus neoformans is the leading cause of fungal meningitis in human immunodeficiency virus- (HIV-) infected patients. A variety of laboratory tests have been introduced for rapid diagnosis of meningitis. Methods. Here, we report a case of coinfection with COVID-19 and cryptococcal meningitis in a HIV-positive patient with abnormal laboratory findings. In this case, COVID-19 was positive by polymerase chain reaction (PCR) and computerized tomography (CT) scan diagnosis. Cryptococcal antigen testing of CSF was negative, whereas India ink staining and cerebrospinal fluid (CSF) culture confirmed the presence of C. neoformans. Results. Although the patient was in a critical stage of illness, serum and CSF levels of procalcitonin were abnormally low, within normal limits. On the other hand, although initial lumbar puncture had showed elevated protein level, the repeat CSFs presented remarkably reduced protein levels. Our findings indicate that despite COVID-19 infection, procalcitonin level may remain normal in HIV-associated cryptococcal meningitis, and findings of an apparently normal procalcitonin level should not exclude the possibility of infection. Also, antigen testing may present false-negative result, and it should not be the sole laboratory method for diagnosis of infectious meningitis. Consequently, CSF culture and staining is recommended, even when antigen testing of organism is negative and CSF profile is unremarkable. Conclusion. Laboratory information should be combined with a good understanding of clinical manifestations of patient to determine if meningitis is present and confirmed COVID-19 should not ignore possibility of other infections for consideration.

Multiple sclerosis (MS) is a chronic and inflammatory disease of the central nervous system (CNS) that is common in people between the ages of 20 and 40. Although the exact cause of MS is still unknown, evidences shows that genetic and environmental factors have a role in activating immune cells to attack the myelin sheath of the neurons, and causing them to be damaged. In order to control and reduce the disease prevalence, early identification of at risk people and patients in the early stages of the disease is important. Measurement of interferon gamma (IFN-γ), vitamin D, melatonin, neurofilaments, micro RNA-132 (miR-132), miR-155, determination of antibody titer against Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) typing are appropriate methods to diagnose the disease, and ultimately prevent its recurrence.

Introduction: Transmission of bioaerosols through the air is known as an important route for a wide range of nosocomial infections. Therefore, in the present study, we aimed to evaluate the type and diversity of bioaerosols and antibiotic resistance of bacterial bioaerosols in the indoor environments of Sina Educational and Treatment Hospital, Tabriz, Iran. Methods and materials: Bioaerosol samples were collected from February to March (winter) and June to July (summer) 2020 in three periods of daytime (morning, noon and evening). After sampling, fungal and bacterial samples were incubated and the disk diffusion agar method (Kirby-Bauer) was used for assessing the antibiotic resistance. Results: the concentration of bioaerosols varied significantly in different wards. In addition, the concentration of bioaerosols in winter was observed to be higher than in summer. The highest and lowest airborne fungal concentrations were found in burns operating room and men's infectious ward (49 CFU/m3) and children's burns ward (28 CFU/m3), respectively. The predominantly isolated bacteria were Streptococcus spp. (38%) and Staphylococcus spp. (37%). Also, the main isolated fungi belonged to the genera Aspergillus (75.9%) and Penicillium (22.5%). The highest rates of antibiotic resistance were observed for colistin (100%) in Gram-negative and penicillin (84.2%) in Gram-positive. Conclusion: Timely and regular disinfection of hospital wards can affect the density of bioaerosols. Owing to the prevalence of COVID-19 epidemic in the world, the staff and patients often were wearing masks, gloves and special clothing as well as using disinfectants to prevent coronavirus infection in wards during the summer sampling.

Background and Aim: Food is the fundamental need of human life and has nutrients that support growth and be healthy. Gastrointestinal tract (GI) microbiota involves beneficial microorganisms that develop therapeutic effects and are characterize as probiotics. The studies on appropriate probiotic strains have led to the separation and description of specific metabolic byproducts of probiotics named postbiotics. Materials and Methods: A literature review has been performing using PubMed, Medline, and Scopus databases using combinations of search terms “probiotic, postbiotic, immune system, bioactivity, cancer, health-promoting, food, and pharmaceutical industry”. All experimental studies were enrolling for this explanatory review. Articles that did not have a full text were excluded. Results: The probiotics must maintain their survival against inappropriate growth conditions of the processing, storage, distribution, preparation, and digestion system so that they can play their most health effects. Conversely, probiotic metabolites have successfully overcome these unfavorable conditions and maybe a good alternative to probiotics. Due to their specific chemical structure, safe profile, long shelf-life, and the fact that they contain various signaling molecules, postbiotics may have anti-inflammatory, immunomodulatory, antihypertensive, inhibiting abnormal cell proliferation, and antioxidant activities. Conclusions: Postbiotics is mimic the fundamental and clinical role of probiotics, and due to their unique characteristics, can be applied in a delivery system (pharmaceutical/functional foods) to achieve health-promoting, prevention, and treatment purposes.

Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes and susceptibility to MS in the Iranian Azari population. Methods: IL-10-1082 A/G SNP and the CCR5-delta32 were genotyped in 152 patients suffering from MS and 242 healthy non-relatives by allele specific-PCR and simple PCR methods, respectively. Results: The frequencies of AA (37.6%) and AG (55.9%) genotypes of IL-10-1082 were significantly high in the control (p = 0.021) and MS patients (p = 0.015), respectively, with no statistical difference between these groups. There was no significant difference in the CCR5 gene based on the possession of wild/wild and wild/del32 genotypes between MS patients and the control group. The del32/del32 genotype was not seen in any of the investigated groups. Tobacco (cigarettes and hookahs) consumption was higher among the MS patients (p=0.004), and this has the potential to raise the risk of MS in both the individuals and their family. However, it had no significant relation with the frequency of different genotypes of the IL-10-1082 and the CCR5. Conclusion: Our finding conclude on possible role of AA genotype of IL-10 -1082 as a protective factor in MS.

Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are one of the factors which can contribute to limiting the development and evolution of antibiotic resistance in bacteria. There are three genomic loci of CRISPR-Cas in Enterococcus faecalis. In this study, we aimed to assess correlation of the CRISPR-Cas system distribution with the acquisition of antibiotic resistance among E. faecalis isolates. A total of 151 isolates of E. faecalis were collected from urinary tract infections (UTI) and dental-root canal (DRC). All isolates were screened for phenotypic antibiotic resistance. In addition, antibiotic resistance genes and CRISPR loci were screened by using polymerase chain reaction. Genomic background of the isolates was identified by random amplified polymorphic DNA (RAPD)-PCR. The number of multidrug-resistant E. faecalis strains were higher in UTI isolates than in DRC isolates. RAPD-PCR confirmed that genomic background was diverse in UTI and DRC isolates used in this study. CRISPR loci were highly accumulated in gentamycin-, teicoplanin-, erythromycin-, and tetracycline-susceptible strains. In concordance with drug susceptibility, smaller number of CRISPR loci were identified in vanA, tetM, ermB, aac6’-aph(2”), aadE, and ant(6) positive strains. These data indicate a negative correlation between CRISPR-cas loci and antibiotic resistance, as well as, carriage of antibiotic resistant genes in both of UTI and DRC isolates.

Abstract Purpose Alterations in the gut microbiome (dysbiosis) has been associated with increased microbial translocation, leading to chronic inflammation in coronary artery disease (CAD). It has been proposed that modulation of gut microbiota by probiotic might modify metabolic endotoxemia. Therefore, the purpose of this study was to examine the effects of Lactobacillus rhamnosus GG (LGG) on endotoxin level, and biomarkers of inflammation in CAD participants. Methods This study was a 12-weeks randomized, double-blind, and intervention on 44 patients with CAD. Patients were randomly allocated to receive either one LGG capsule 1.6 × 109 colony-forming unit (CFU) or the placebo capsules for 12 weeks. In addition, all the participants were also prescribed a calorie-restricted diet. Serum levels of interleukin-1β (IL-1β), Toll-like receptor 4 (TLR4), interleukin-10 (IL-10), and lipopolysaccharide (LPS), were assessed before and after the intervention. Results A significant decrease in IL1-Beta concentration (− 1.88 ± 2.25, vs. 0.50 ± 1.58 mmol/L, P = 0.027), and LPS levels (− 5.88 ± 2.70 vs. 2.96+ 5.27 mg/L, P = 0.016), was observed after the probiotic supplementation compared with the placebo. Participants who had ≥2.5 kg weight loss showed significantly improved cardiovascular-related factors, compared to patients with

Background and Objectives: Carbapenem treatment for Acinetobacter baumannii‎‎ infections presently faces threats owing to the production of several types of carbapenemase enzymes, prevalence of which varies among different countries. We explored the current trend of antibiotic resistance in A. baumannii clinical isolates from North West Iran, sought the mechanism of carbapenem resistance and addressed the sequence type groups in carbapenem resistant A. baumannii‎‎ (CRAB). Materials and Methods: A. baumannii‎‎ (n=112) isolates were recovered from various clinical specimens of patients admitted in internal, surgery, burn, infectious diseases and various ICUs wards. Genetically confirmed A. baumannii isolates were screened for carbapenem resistance by the Kirby-Bauer and E-test and the presence of blaMBL, blaOXA-like, ISAba1 genes by PCR. Sequence groups were identified by multiplex PCR. Results: Multidrug-resistance (MDR) was a characteristic feature of all A. baumannii isolates. Frequency of oxacillinase genes in combination including blaOXA-51-like/blaOXA-23-like, blaOXA-51-like/blaOXA-24/40-like and blaOXA-51-like/blaOXA-23-like/blaOXA-24/40-like was 82.1%, 36.6% and 25.8% respectively. Blending of oxacillinase and MBL genes was evident in eight blaOXA-23-like positive and 7 blaOXA-24-like positive isolates thereby depicting synchronous etiology of carbapenem resistance. Amongst CRAB isolates, 97.3% contained ISAba1 element and 50.9% belonged to the European clone II. Conclusion: Synchronicity among blaOXA-like with blaMBL and ISAba1 gene was a hallmark of this investigation. Though origin or route of transmission was not elucidated in this study but co-existence among OXA and MBL producing genes is a therapeutic concern demanding strict surveillance strategies and control programs to halt the dissemination of these isolates in the hospital setting.

Background: To end the COVID-19 pandemic, a large part of the world must be immune to the virus by vaccination. Therefore, this study aimed to gauge intent to be vaccinated against COVID-19 among ordinary people and to identify attitudes towards vaccines and barriers for vaccine acceptance. Methods: The study population comprises 1880 people residing in different countries that answer a prepared questionnaire. The questionnaire topics are demographics, historical issues, participants’ attitudes and beliefs regarding vaccines, concerns, and vaccine hesitancy. Results: Attitudes and beliefs relating to vaccines in general, and the COVID-19 vaccine, were ascertained. Overall, 66.81% of the contributors would like to be vaccinated against COVID-19, while %33.19 did not intend to be vaccinated. Reasons for COVID-19 vaccine hesitancy included concern regarding vaccine side effects, fear of getting sick from the uptake of the vaccine, and the absence of accurate vaccine promotion news. Individuals with higher education believe that India (68.6%) produces the best vaccine (P

Background: In spite of Bacillus Calmette-Guerin (BCG) vaccination, still tuberculosis caused by Mycobacterium tuberculosis remains a problematic impediment that requires perspective management. The aim of this study was to evaluate the immunogenicity of chitosan nanoparticles containing recombinant mycobacterial proteins and adjuvant in the Balb/C mice through a non-invasive nasal inhalation delivery route and measure the level of cytokines interferon gamma (IFN-γ), interleukin-4 (IL-4), and IL-17. Methods: Thirty mice in five different groups were vaccinated through inhalation with compounds set in different combinations. Two weeks after the last nasal delivery, IFN-γ, IL-4, and IL-17 were measured in spleen cell culture supernatants. Results: The IFN-γ and IL-17 concentrations were found to increase in the groups that received chitosan nanoparticles containing protein and adjuvant alone or as a BCG booster. Our study showed that the chitosan nanoparticle containing protein and adjuvant induced a Th1 response. However, the groups that first received BCG and then chitosan nanoparticles containing protein and adjuvant had the greatest Th1 response in terms of IFN-γ and IL-17 production in all the groups. Conclusion: Our findings showed that the vaccine designed to be administered through the nasal mucosa well stimulates cellular immunity and enhances the BCG vaccine’s effectiveness.

Coronavirus disease 2019 (COVID-19) dissemination occurred from December 2019 and quickly spread to all countries. Infected patients with COVID-19 have had a wide range of symptoms, ranging from mild to severe illness. The most mortality was observed in patients with underlying disease and over 45 years. World statistics have shown that the COVID-19 outbreak is most expanded in Middle Eastern, West Asian, European, North, and South American countries, and is least expanded in African countries. Therefore, the aim of the paper was the evaluation of six African countries including Mali, Mauritania, Niger, Guinea, Togo, and Djibouti to find why this disease is least expanded in African countries. Study was conducted by Questioner for countries health organizers to define their different aspect exposure and fight with COVID-19 including epidemiology, clinical aspects of the disease, case definitions, diagnosis laboratory confirmation, and referral of cases by the portal of entry, case management, and disease prevention in these countries. According to this opinion review, due to the low international flights and low domestic travel, the spread, and prevalence of COVID-19 was low and the return of the immigrants of these countries has caused the spread of COVID-19 among these countries. Experience, preparation, and impact of previous infections epidemic such as the Ebola virus epidemic would have beneficial, which have promoted certain reflexes among people that cause low dissemination in these countries.

As many investigations have reported, there is a complicated relation between fermented foods, lactic acid bacteria (LAB), and human health. It seems that bioactive components such as prebiotics, probiotics, and postbiotics are key mediators of the complex and direct association between these factors. LAB activity in the matrix of fermented foods and improving their growth by prebiotic compounds ultimately results in the production of bioactive molecules (postbiotics), which possess specific biological and physiological properties. The term "postbiotics" refers to a complex of biological micro- and macromolecules, if consumed in adequate amounts, provides the host with different health-promoting effects. Different reports have suggested that postbiotics possess the ability to moderate the effectiveness of cancer treatment and reduce the side-effects of conventional therapies in cancer patients due to their anti-proliferative, anti-inflammatory and anti-cancer properties. Consequently, postbiotics, for their unique characteristics, have gained great scientific attention and are considered as a novel approach for adjuvant therapy in patients with cancer.

Enterococcus faecalis is one of the important causative agents of nosocomial and life-threatening infections in human. Several studies have demonstrated that the presence of CRISPR-cas is associated with antibiotic susceptibility and lack of virulence traits. In this study, we aimed to assess the phenotypic and genotypic virulence determinants in relation to CRISPR elements from the dental-root canals and hospital-acquired isolates of E. faecalis. Eighty-eight hospital-acquired and 73 dental-root canal isolates of E. faecalis were assessed in this study. Phenotypic screening of the isolates included biofilm formation, and gelatinase and hemolysis activities. Genotypical screening using PCR was further used to evaluate the presence of CRISPR elements and different virulence-associated genes such as efaA, esp, cylA, hyl, gelE, ace, ebpR, and asa1. Biofilm formation, gelatinase, and hemolysis activities were detected in 93.8%, 29.2%, and 19.2% of the isolates, respectively. The most prevalent virulence-associated gene was ace, which was followed by efaA, whereas cylA was the least identified. The presence of CRISPR1-cas, orphan CRISPR2, and CRISPR3-cas was determined in 13%, 55.3%, and 17.4% of the isolates, respectively. CRISPR elements were significantly more prevalent in the dental-root canal isolates. An inverse significant correlation was found between CRISPR-cas loci, esp, and gelE, while direct correlations were observed in the case of cylA, hyl, gelE (among CRISPR-loci 1 and 3), asa1, ace, biofilm formation, and hemolysis activity. Findings, therefore, indicate that CRISPR-cas might prevent the acquisition of some respective pathogenicity factors in some isolates, though not all; so selective forces could not influence pathogenic traits. Abbreviations: BHI: brain-heart infusion agar; CRISPRs: Clustered regularly interspaced short palindromic repeats; Esp: Cell wall-associated protein; ENT: ear-nose-throat; ICU: intensive care units; OD: optical densities; PCR: polymerase chain reaction; SDS: sodium dodecyl sulfate; UTI: urinary tract infection

Background and Objectives: The release of information without scientific basis about the new corona virus (2019) pandemic has now become a global anxiety. The aim of this study was to analyze the performance, planning and flexibility of the Vice Chancellor for Research and Technology of Tabriz University of Medical Sciences in response to the new coronavirus (covid-19) Pandemic crisis to produce and disseminate evidence-based information. Material and Methods: This was an organizational study which was done by descriptive methods. After announcement of a call for Covid-19 research project from the website of Tabriz University of Medical Science (TUOMS), a new policy was arranged for review process. The time and production of evidence were the major factors for this experience. Electronic arbitration methods and virtual discussion were used. Quantitative data was performed in MS Excel version 16 and the results were presented in the form of tables and graphs. Results: Due to the urgency of aggregating the evidence, the review process was done by the scientific team during a maximum of 72 and by the ethical team within 24 hours (excluding the spent time by the principal investigators), 64 research and technological projects were prioritized. The shortest possible review process, the interactive approach of reviewing and problem-based nature of the approved topics were among the most important achievements. Conclusion: This experience showed that cohesive organizational activities in the field of research and flexibility of the processes can play a significant role in dealing with epidemics and crises in order to overcome obstacles, challenges and for production of scientific evidence.

Purpose: In the present study, the poly (ε-caprolactone)/cellulose nanofiber containing ZrO2 nanoparticles (PCL/CNF/ZrO2 ) nanocomposite was synthesized for wound dressing bandage with antimicrobial activity. Methods: PCL/CNF/ZrO2 nanocomposite was synthesized in three different zirconium dioxide amount (0.5, 1, 2%). Also the prepared nanocomposites were characterized by Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). In addition, the morphology of the samples was observed by scanning electron microscopy (SEM). Results: Analysis of the XRD spectra showed a preserved structure for PCL semi-crystalline in nanocomposites and an increase in the concentrations of ZrO2 nanoparticles, the structure of nanocomposite was amorphous as well. The results of TGA, DTA, DSC showed thermal stability and strength properties for the nanocomposites which were more thermal stable and thermal integrate compared to PCL. The contact angles of the nanocomposites narrowed as the amount of ZrO2 in the structure increased. The evaluation of biological activities showed that the PCL/CNF/ZrO2 nanocomposite with various concentrations of ZrO2 nanoparticles exhibited moderate to good antimicrobial activity against all tested bacterial and fungal strains. Furthermore, cytocompatibility of the scaffolds was assessed by MTT assay and cell viability studies proved the non-toxic nature of the nanocomposites. Conclusion: The results show that the biodegradability of nanocomposite has advantages that can be used as wound dressing.

The gold standard method for diagnosis of tuberculosis is the isolation of Mycobacterium tuberculosis through culture, but there is a probability of cross-contamination in simultaneous cultures of samples causing false-positives. This can result in delayed treatment of the underlying disease and drug side effects. In this paper, we reviewed studies on false-positive cultures of M. tuberculosis. Rate of occurrence, effective factors, and extent of false-positives were analyzed. Ways to identify and reduce the false-positives and management of them are critical for all laboratories. In most cases, false-positive is occurring in cases with only one positive culture but negative direct smear. The three most crucial factors in this regard are inappropriate technician function, contamination of reagents, and aerosol production. Thus, to reduce false-positives, good laboratory practice, as well as use of whole-genome sequencing or genotyping of all positive culture samples with a robust, extra pure method and rapid response, are essential for minimizing the rate of false-positives. Indeed, molecular approaches and epidemiological surveillance can provide a valuable tool besides culture to identify possible false positives.

Lactobacillus species and other acid producing bacteria could inhibit aerobic bacteria, normalize the intestinal microbiota and decrease the uremic toxins in patients with chronic kidney disease. Therefore, the aim of this study is assessment of abundance of lactobacillus spp. in fecal flora of End-stage kidney disease (ESKD) and kidney transplanted patients. DNA of 20 fecal samples of ESKD and kidney-transplanted as patients group and 20 fecal samples of non-ESKD and -kidney-transplanted as control group, which were admitted to hospitals, were extracted. Amplified DNA by 16srRNA illumina V3 and V4 primers were sequenced by MiSeq system. Total 651 strains, 37 (5.68%) strains were identified as order Lactobacillales. The strains were classified into six family, nine genus and 37 species. The most abundance genus in both groups are Streptococcus spp. and Lactobacillus spp. and the lowest abundance genus in both groups are Pediococcus and Leuconostoc. Comparing the abundance mean of the strains revealed that there is no significant association between control group and disease group, but the abundance mean of the strains in control group increase in compared to disease group. More diversity was exhibited in lactobacillus spp. in patients with chronic kidney disease compared to control group. Some of the species of Lactobacillaceae family such as L. acidophilus was not found in both patients and control groups. In addition, more of the species of Lactobacillaceae were decreased in patients group, whereas certain species were increased in patients group compared to control group.

Background: Clostridium difficile is known as a prevalent pathogen leading to infections ranging from mild diarrhea to severe disease and death. The aim of the present study was to evaluate the incidence of C. difficile from inpatients with nosocomial diarrhea hospitalized in different wards in the northwest region of Iran. Methods: In this cross-sectional study, 485 diarrheal stool samples were collected from 384 patients referred from different wards of Imam Reza, Sina and Pediatric hospitals, Tabriz and transferred to the laboratory from 25 March 2015 till 1 March 2018. Immuno-chromatographicassay for detection of toxins A and B of C. difficile was used for identification. Results: Clostridium difficile was isolated from 24 (4.7%) out of 485 samples. Fifteen patients(62.5%) were males and 9 were females (37.5%). Twelve positive patients were from the gastrointestinal ward (50%), 5 patients (20.8%) from surgery ward, 3 patients from infectious disease ward (12.5%), 3 patients from rheumatology ward (12.5%) and 1 patient (4.1%) were collected from neurology ward. 95.3% of diarrhea samples had no signs from toxin A and B. Conclusion: These results indicate most of infected patients were from the gastrointestinaland surgery wards which show a different pattern of infection compared to previous studies.The neurology department had the lowest rate of infection. C. difficile is a health threat afterantibiotic consumption and for health promotion, developing strategies for less antibioticconsumption and preventing these emerging infections is critical. The low rate of this infection shows improvement in knowledge and effect of stewardships in physicians.

Erythrasma is a chronic infection of the skin that appears in the body folds as flat copper spots. The causative agent of this infection is Corynebacterium minutissimum (C. minutissimum). Erythrasma can be treated with antiseptics or topical antibiotics. The study aimed to investigate the antibiotics susceptibility patterns, and the presence of the erythromycin resistance gene (ermX and mefA) in C. minutissimum isolates in skin lesions with suspected erythrasma. From July 2020 to May 2022, 278 skin scrub specimens were collected from patients admitted to the hospital of Tabriz University of Medical Sciences. Specimens were incubated on the blood agar plates and isolates were identified by microbiological laboratory methods. The antibiotic susceptibility patterns were determined by the disk diffusion method and resistance genes of ermX and mefA were detected by the PCR method. Out of 278 specimens, 41 C. minutissimum isolates (14.74%) were recovered. The highest frequency of resistance was observed to a penicillin (75.6%) followed by erythromycin and clarithromycin (39.02%), clindamycin (30.05%), tetracycline (24.2%), and gentamicin and neomycin (19.5%). The frequencies of ermX and mefA genes were 75% and 12.5%, respectively. Resistance to antimicrobial drugs was common and worrying. Resistance to erythromycin in C. minutissimum is mainly related to the ermX gene.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been known to be involved in cell growth, cellular differentiation processes development, immune cell survival, and hematopoietic system development. As an important member of the STAT family, STAT3 participates as a major regulator of cellular development and differentiation-associated genes. Prolonged and persistent STAT3 activation has been reported to be associated with tumor cell survival, proliferation, and invasion. Therefore, the JAK-STAT pathway can be a potential target for drug development to treat human cancers, e.g., hematological malignancies. Although STAT3 upregulation has been reported in hematopoietic cancers, protein-level STAT3 mutations have also been reported in invasive leukemias/lymphomas. The principal role of STAT3 in tumor cell growth clarifies the importance of approaches that downregulate this molecule. Epigenetic modifications are a major regulatory mechanism controlling the activity and function of STAT3. So far, several compounds have been developed to target epigenetic regulatory enzymes in blood malignancies. Here, we discuss the current knowledge about STAT3 abnormalities and carcinogenic functions in hematopoietic cancers, novel STAT3 inhibitors, the role of epigenetic mechanisms in STAT3 regulation, and targeted therapies, by focusing on STAT3-related epigenetic modifications.

This work aimed to immobilize silver nanoparticles with catalytic and antibacterial activity (AgNPs) inside of the PEG-based hydrogel through a facile and green design. First, the hybrid hydrogels were prepared under solvent-free conditions based on dianhydride ethylenediamine tetraacetic acid, poly (ethylene glycol) of different molar mass, glycerol, and octa-aminopropyl polyhedral oligomeric silsesquioxane hydrochloride salt as organic and inorganic cross-linker agent. The well-dispersed AgNPs were fabricated in-situ in the polymeric matrix of the hybrid hydrogel through the reduction of Ag+ by NaBH4. The resulting hybrid nanocomposite hydrogels were characterized by various techniques, such as FT-IR spectroscopy, SEM, TEM, EDX, XRD, BET, and TGA. The swelling behavior, the antibacterial activity against the bacteria S. aureus (Gram-positive), and E. coli (Gram-negative), as well as the catalytic efficiency for the reduction reaction of 4-nitrophenol to 4-aminophenol of the nanocomposite hydrogels prepared, were examined. The facile and mass production synthetic method of the nanocomposite hydrogels, excellent dispersion of the AgNPs inside the hydrogel matrix, excellent catalytic recyclability, and antibacterial activity are some of the advantages of this system. The maximum inhibition zone was found to be 17.4 and 15.9 mm against the gram-positive species S. aureus and the gram-negative E. coli, respectively. Besides, the maximum catalytic activity was achieved in a short time period of 30 s.

Background and Objectives: Ceftaroline (CPT) is a novel cephalosporin with potent activity against methicillin-resistant Staphylococcus aureus (MRSA). Despite its recent introduction, CPT resistance in MRSA has been described worldwide. We aimed in the current study to evaluate the in vitro activity of CPT against 91 clinical MRSA and 3 MSSA isolates. Materials and Methods: Susceptibility of isolates to CPT was tested using E-test and disk diffusion (DD) method. The nucleotide sequence of the mecA gene and molecular types of isolates with reduced susceptibility to CPT were further studied to identify resistance conferring mutations in PBP2a and the genetic relatedness of the isolates respectively. Results: Overall, 92.5% of isolates were found to be CPT susceptible (MICs≤1mg/l) and 7 MRSA isolates were characterized with MIC=2mg/l and categorized as susceptible dose dependent. Compared to E-test, DD revealed a categorical agreement rate of 93.6% and the obtained rates for minor, major /very major error were found to be 6.3% and 0% respectively. The MRSA isolates with increased CPT MICs (n=7), belonged to spa types t030 (n=6) and t13927 (n=1) and all carried N146K substitution in PBP2a allosteric domain, except for one isolate which harbored a wild-type PBP2a. Conclusion: While resistance to CPT was not detected we found increased CPT MICs in 7.69% of MRSA isolates. Reduced susceptibility to CPT in the absence of mecA mutations is indicative of contribution of secondary chromosomal mutations in resistance development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was transported from China to Iran via passengers. The virus is transmitted through droplets from coughing, sneezing, talking and contact with infected surfaces. Due to high transmissibility in places such as clinics, medical offices, buses and offices where there are large crowds, it spread rapidly in Iran and caused the mortality of a significant number of people, especially the elderly with underlying disease. Preventing travel and gatherings, as well as applying house quarantine in Apr 2020, reduced COVID-19 somewhat but then due to lack of attention to social distancing, reducing the use of masks by the people and inappropriate decisions by the national committee on combating coronavirus (NCCC), including reducing the working hours of public offices and shops, reducing the staff of government offices, monopoly on the distribution of essential materials and supplies, the presence of overcrowding in clinics of medical centers, hospitals, and private clinics caused the decline of the disease in the country to decrease. Measures can be taken to prevent the spread of the virus as much as possible, including: rapid detection of infected people, their isolation, contact tracing, quarantine of people over 65 and under 15, protection of the elderly, prevention of gatherings, forcing the use of protective equipment in possible gatherings, and electronicizing public services.

Abstract Reinfection with COVID‐19 is possible after exposure to a high dose of the virus. Due to immunity acquired during the previous infection, light symptoms are expected. The finding indicates importance of continuous protection in healthcare workers.