Multi-Drug Resistant (MDR) Pseudomonas aeruginosa is one of the most important bacterial pathogens that causes infection with a high mortality rate due to resistance to different antibiotics. This ...bacterium prompts extensive tissue damage with varying factors of virulence, and its biofilm production causes chronic and antibiotic-resistant infections. Therefore, due to the non-applicability of antibiotics for the destruction of P. aeruginosa biofilm, alternative approaches have been considered by researchers, and phage therapy is one of these new therapeutic solutions. Bacteriophages can be used to eradicate P. aeruginosa biofilm by destroying the extracellular matrix, increasing the permeability of antibiotics into the inner layer of biofilm, and inhibiting its formation by stopping the quorum-sensing activity. Furthermore, the combined use of bacteriophages and other compounds with anti-biofilm properties such as nanoparticles, enzymes, and natural products can be of more interest because they invade the biofilm by various mechanisms and can be more effective than the one used alone. On the other hand, the use of bacteriophages for biofilm destruction has some limitations such as limited host range, high-density biofilm, sub-populate phage resistance in biofilm, and inhibition of phage infection via quorum sensing in biofilm. Therefore, in this review, we specifically discuss the use of phage therapy for inhibition of P. aeruginosa biofilm in clinical and in vitro studies to identify different aspects of this treatment for broader use.
A novel modified carbon ionic liquid electrode (CILE) is prepared as an electrochemical sensor for simultaneous determination of levodopa (l-Dopa) and melatonin (Mel). The experimental results ...suggest that a carbon ionic liquid electrode modified with multi-walled carbon nanotubes and cobalt hydroxide nanoparticles accelerates the electron transfer reactions of l-Dopa and Mel. The fabricated sensor revealed some advantages such as convenient preparation, good stability and high sensitivity. The DPV data in 0.1M phosphate buffer solution (PBS) (pH 7.5) allowed a method to be developed for the determination of l-Dopa and Mel concentrations in the ranges 0.1–300 and 0.01–50μM, with the detection limits of 0.075 and 0.004μM, respectively. The proposed method was successfully applied to determinations of these compounds in some pharmaceutical and human urine samples.
Helicobacter pylori, the most frequent pathogen worldwide that colonizes around 50% of the world's population, causes important diseases such as gastric adenocarcinoma, chronic gastritis, and gastric ...mucosa-associated lymphoid tissue (MALT) lymphoma. In recent years, various studies have reported that H. pylori biofilm may be one of the critical barriers to the eradication of this bacterial infection. Biofilms inhibit the penetration of antibiotics, increase the expression of efflux pumps and mutations, multiple therapeutic failures, and chronic infections. Nanoparticles and natural products can demolish H. pylori biofilm by destroying the outer layers and inhibiting the initial binding of bacteria. Also, the use of combination therapies destroying extracellular polymeric substances decreases coccoid forms of bacteria and degrading polysaccharides in the outer matrix that lead to an increase in the permeability and performance of antibiotics. Different probiotics, antimicrobial peptides, chemical substances, and polysaccharides by inhibiting adhesion and colonization of H. pylori can prevent biofilm formation by this bacterium. Of note, many of the above are applicable to acidic pH and can be used to treat gastritis. Therefore, H. pylori biofilm may be one of the major causes of failure to eradication of infections caused by this bacterium, and antibiotics are not capable of destroying the biofilm. Thus, it is necessary to use new strategies to prevent recurrent and chronic infections by inhibiting biofilm formation.
Background. Serum desmoglein enzyme-linked immunosorbent assay (ELISA) is used for the diagnosis and monitoring of pemphigus diseases. Objectives. To compare the diagnostic accuracy of salivary ...antidesmoglein (Dsg) 1 and 3 ELISA in the diagnosis of pemphigus vulgaris (PV) patients with that of serum desmogleins ELISA. Methods. Eighty-six untreated PV patients and 180 age- and sex-matched PV-free controls were recruited in this case-control study. PV was diagnosed based on clinical, histopathological, and direct immunofluorescence findings. After processing, serum and salivary anti-Dsg 1 and 3 were measured by the ELISA method using Euroimmun kit (Lübeck, Germany). Results. Using the cut-off point of 20 relative units (RU)/mL, the serum anti-Dsg 1 and 3 ELISA were positive in 62 (72.1%) and 83 (96.5%) patients, respectively, and the salivary anti-Dsg 1 and 3 ELISA were positive in 31 (36.1%) and 63 (73.3%) patients, respectively. The specificity of salivary anti-Dsg 1 and anti-Dsg 3 were both 98.9%. Optimal cut-off values of 7.7 and 13.4 RU/mL were determined for the salivary anti-Dsg 1 and anti-Dsg 3 ELISA, respectively. Conclusion. Salivary anti-Dsg 1 and 3 ELISA with high specificities (98.9%) could be suggested as safe and noninvasive methods for the diagnosis of PV when obtaining a blood sample is difficult.
Exosomes are nano-sized structures with lipid bilayer membranes that can be secreted by cancer cells. They play an important role in the biology of the tumor extracellular matrix. Exosomes may ...contain and transfer tumor antigens to dendritic cells to trigger T cell-mediated anti-tumor immune responses.
BALB/c mice bearing CT26 colorectal cancer were treated subcutaneously with purified exosomes from analogous tumor cells. The mice were analyzed with respect to tumor size, survival, and anti-tumor immunity responses, including gene expression of cytokines and flowcytometry analysis of T lymphocytes.
The rate of tumor size growth in the exosome-treated group significantly decreased (
<0.05), and the flow cytometry results showed a significant reduction in the spleen regulatory T cells (Tregs) count of the exosome-treated group, compared with the untreated group (
=0.02). Although the increase in the serum level of interferon-γ (IFN-γ) and the number of cytotoxic CD8 T lymphocytes (CTLs) in the spleen tissue was not significant (
>0.05), the gene expression of IFN-γ increased significantly (
=0.006).
The present results revealed that subcutaneous administration of tumor-derived exosomes could effectively lead to the inhibition of tumor progression by decreasing the number of Treg cells and up-regulation of the IFN-γ gene. Therefore, tumor-derived exosomes can be used as potential vaccines in cancer immunotherapy.
Human rights may feel self-apparent to us, but less than 80 years ago, one of the most advanced countries at the time acted based on an utterly contrary ideology. The view of social Darwinism that ...abandoned the idea of the intrinsic value of human lives instead argued that oppression of the inferior is not only inevitable but desirable. One of the many catastrophic outcomes is the medical data obtained from inhuman experiments at concentration camps. Ethical uncertainty over whether the resulting insights should be a part of the medical literature provides a chance to consider the seemingly irreplaceable social construct of human dignity. Would any medical benefit justify the utilization of this illicit data? Would utilization even qualify as an insult to the dignity of the exploited subjects, or is this a question about intersubjective meaning? This work discusses the wisdom in blind adherence to human dignity, the possibility of retrospective insults, moral complicity, contrary viewpoints, and possible resolutions.
Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we ...evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients.
Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry.
The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05).
Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.
Background. Autoimmune process and immunosuppressive therapy of pemphigus vulgaris would predispose the patients to infections. Aim. We aimed to study the prevalence of infection and pathogenic ...agents in pemphigus vulgaris patients admitted to dermatology service. Material and methods. This retrospective study was conducted on 155 pemphigus vulgaris patients (68 males, 87 females) admitted to dermatology service between 2009 and 2011. In this study, the diagnosis of pemphigus vulgaris was confirmed by light microscopic and direct immunofluorescence findings. Data were collected through a questionnaire. Results. Of 155 pemphigus vulgaris patients, 33 had infection at admission and 9 acquired nosocomial infection. In addition, 37 cases of oral candidiasis and 15 cases of localized herpes simplex were recorded. Totally, 94 cases of infection were recorded. The occurrence of infection was significantly related to the severity of disease, number of hospital admissions, and presence of diabetes mellitus. The most common pathogenic germs isolated from cultures were Staphylococcus aureus and Escherichia coli. Conclusion. Severity of pemphigus vulgaris and diabetes were directly related with tendency to infections. Staphylococcus aureus and Escherichia coli were the most common pathogenic agents. Due to limitations of retrospective study, a prospective study is recommended.
Pemphigus vulgaris is an autoimmune disease, in which the role of Th17 cytokines needs to be further explored. This study was performed to assess serum levels of three interleukins (IL) required for ...Th17 differentiation (IL-1β, IL-6 and IL-23) and two specific Th17 cytokines (IL-17 and IL-22) in a group of patients with pemphigus vulgaris, at baseline, 3 weeks and 6 months after treatment. Correlations between anti-desmogleins and cytokines with disease severity as well as the influence of therapy on the above factors were assessed. Forty-three first-admitted pemphigus vulgaris patients with the active disease entered the study, but only 31 completed the study. Forty-five healthy volunteers were recruited as a control group. The patients were treated with conventional immunosuppressive therapy (oral prednisolone and azathioprine). Cytokines and anti-desmogleins were measured, using enzyme-linked immunosorbent assay. General linear model was used to evaluate the changes over time. In patients at baseline, mean serum level of IL-6 was higher, while mean levels of IL-1β and IL-22 were lower than the controls. After 3 weeks of therapy, IL-1β and IL-6 levels showed a decreasing trend, whereas IL-22 showed an increasing trend. Mean anti-desmogleins 1 and 3 values decreased significantly during the time. Anti-desmoglein values were significantly correlated with disease severity. In conclusion, IL-1β and IL-6 could be involved in the pathogenesis of pemphigus vulgaris. The positive trend of IL-22 is a new finding and should be confirmed by further studies.
The opioid crisis in the United States has had devastating effects on communities across the country, leading many states to pass legislation that limits the prescription of opioid medications in an ...effort to reduce the number of overdose deaths. This study investigates the impact of South Carolina's prescription limit law (S.C. Code Ann. 44-53-360), which aims to reduce opioid overdose deaths, on opioid prescription rates. The study utilizes South Carolina Reporting and Identification Prescription Tracking System (SCRIPTS) data and proposes a distance classification system to group records based on proximity and evaluates prescription volumes in each distance class. Prescription volumes were found to be highest in classes with pharmacies located further away from the patient. An Interrupted Time Series (ITS) model is utilized to assess the policy impact, with benzodiazepine prescriptions as a control group. The ITS models indicate an overall decrease in prescription volume, but with varying impacts across the different distance classes. While the policy effectively reduced opioid prescription volumes overall, an unintended consequence was observed as prescription volume increased in areas where prescribers were located at far distances from patients, highlighting the limitations of state-level policies on doctors. These findings contribute to the understanding of the effects of prescription limit laws on opioid prescription rates and the importance of considering location and distance in policy design and implementation.
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