Clinical and immunological comparison of COVID-19 disease between critical and non-critical courses: a systematic review and meta-analysis.

Introduction: Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which appeared in 2019, has been classified as critical and non-critical according to clinical signs and symptoms. Critical patients require mechanical ventilation and intensive care unit (ICU) admission, whereas non-critical patients require neither mechanical ventilation nor ICU admission. Several factors have been recently identified as effective factors, including blood cell count, enzymes, blood markers, and underlying diseases. By comparing blood markers, comorbidities, co-infections, and their relationship with mortality, we sought to determine differences between critical and non-critical groups. Method: We used Scopus, PubMed, and Web of Science databases for our systematic search. Inclusion criteria include any report describing the clinical course of COVID-19 patients and showing the association of the COVID-19 clinical courses with blood cells, blood markers, and bacterial co-infection changes. Twenty-one publications were eligible for full-text examination between 2019 to 2021. Result: The standard difference in WBC, lymphocyte, and platelet between the two clinical groups was 0.538, -0.670, and -0.421, respectively. Also, the standard difference between the two clinical groups of CRP, ALT, and AST was 0.482, 0.402, and 0.463, respectively. The odds ratios for hypertension and diabetes were significantly different between the two groups. The prevalence of co-infection also in the critical group is higher. Conclusion: In conclusion, our data suggest that critical patients suffer from a suppressed immune system, and the inflammation level, the risk of organ damage, and co-infections are significantly high in the critical group and suggests the use of bacteriostatic instead of bactericides to treat co-infections.

Stem cell-conditioned medium is a promising treatment for Alzheimer's disease.

BACKGROUND AND AIM: Alzheimer's disease (AD), a prevalent progressive neurodegenerative disease, is mainly characterized by dementia, memory loss, and cognitive disorder. Rising research was performed to develop pharmacological or non-pharmacological approaches to treat or improve AD complications. Mesenchymal stem cells (MSCs) are stromal cells that can self-renew and exhibit multilineage differentiation. Recent evidence suggested that some of the therapeutic effects of MSCs are mediated by the secreted paracrine factors. These paracrine factors, called MSC- conditioned medium (MSC-CM), may stimulate endogenous repair, promote angio- and artery genesis, and reduce apoptosis through paracrine mechanisms. The current study aims to systematically review the advantages of MSC-CM to the development of research and therapeutic concepts for AD management. MATERIAL AND METHODS: The present systematic review was performed using PubMed, Web of Science, and Scopus from April 2020 to May 2022 following the "Preferred Reporting Items for Systematic Reviews" (PRISMA) guidelines. The keywords, including "Conditioned medium OR Conditioned media OR Stem cell therapy" AND "Alzheimer's," was searched, and finally, 13 papers were extracted. RESULTS: The obtained data revealed that MSC-CMs might positively affect neurodegenerative diseases prognosis, especially AD, through various mechanisms, including a decrease in neuro-inflammation, reduction of oxidative stress and Aß formation, modulation of Microglia function and count, reduction of apoptosis, induction of synaptogenesis and neurogenesis. Also, the results showed that MSC-CM administration could significantly improve cognitive and memory function, increase the expression of neurotrophic factors, decrease the production of pro-inflammatory cytokines, improve mitochondrial function, reduce cytotoxicity, and increase neurotransmitter levels. CONCLUSION: While inhibiting the induction of neuroinflammation could be considered the first therapeutic effect of CMs, the prevention of apoptosis could be regarded as the most crucial effect of CMs on AD improvement.

Red-light radiation: does it enhance memory by increasing hippocampal LRP-1 and TRPA-1 genes expression?

PURPOSE: Despite the extensive efforts to treat the leading cause of neurodegenerative diseases (ND), a little progress has been reported. Red light might affect ND through many specific mechanisms. The purpose of this investigation is to explore the effect of red light on the expression of low-density lipoprotein receptor-1 (LRP-1) and transient receptor potential ankyrin-1 (TRPA-1) gene in the hippocampus, and the serum melatonin level (SML) of the lipopolysaccharide (LPS)-induced neuro-inflammated rats. MATERIALS AND METHODS: Red-light therapy was implemented using a wavelength 630 nm under different light conditions and the passive avoidance (PA) and Y-Maze tests were employed to assess memory performance. To evaluate the LRP-1 and TRPA-1 genes expression, quantitive real-time polymerase chain reaction was performed. To measure the SML, ELISA was performed before and after the red-light radiation. RESULTS: LPS caused memory impairment in both behavioral tests. Red-light therapy improved PA memory in all light conditions (p < .001). However, in Y-maze, only the red-light radiation during light and dark cycles, improved memory (p < .01 and p < .001, respectively). In addition, red-light radiation caused significant increase in SML (p < .05). The LRP-1 and TRPA-1 genes expression increased significantly during the dark phase in the red light radiated group compared to non-radiated group (p < .001). CONCLUSIONS: Taken together, the results suggest that red-light therapy can reduce the complications of memory impairment in rats. This study has found that red-light therapy demonstrates higher effect during the period of dark phase compared to light phase. No doubt, further experimental studies would help us to establish a greater degree of accuracy on this matter.

Niosome-encapsulated tobramycin reduced antibiotic resistance and enhanced antibacterial activity against multidrug-resistant clinical strains of Pseudomonas aeruginosa.

In the current study, niosome-encapsulated tobramycin based on Span 60 and Tween 60 was synthesized and its biological efficacies including anti-bacterial, anti-efflux, and anti-biofilm activities were investigated against multidrug resistant (MDR) clinical strains of Pseudomonas aeruginosa. The niosomal formulations were characterized using scanning electron microscopy, transmission electron microscopy, and dynamic light scattering measurement. The encapsulation efficiency was found to be 69.54% ±; 0.67. The prepared niosomal formulations had a high storage stability to 60 days with small changes in size and drug entrapment, which indicates that it is a suitable candidate for pharmaceutical applications. The results of biological study showed the anti-bacterial activity via reduction of antibiotic resistance, enhanced anti-efflux and anti-biofilm activities by more folds in comparison to free tobramycin. In addition, niosome encapsulated tobramycin down-regulated the MexAB-OprM efflux genes, pslA and pelA biofilm related genes in MDR P. aeruginosa strains. The anti-proliferative activity of formulation was evaluated against HEK293 cell lines, which exhibited negligible cytotoxicity against HEK293 cells. The finding of our study shows that encapsulation of tobramycin in niosome enhanced the antibacterial activity and reduced antibiotic resistance in MDR strains of P. aeruginosa comparing to free tobramycin and it can be considered as a favorable drug delivery system.

Tympanosclerosis and atherosclerosis plaques: a comparative analytical study on some new microbiological and immunohistochemical aspects.

PURPOSE: The aim of this study was to compare chemical contents, expression of BMP-8a, and the presence of Mycoplasma and ExoS-ExoU exotoxins producing Pseudomonas aeruginosa in tympanosclerosis (TS) and atherosclerosis (AS) plaques. METHODS: Thirty-six cases with TS and AS plaques (18 each) were selected and examined for chemical, immunohistochemical, and microbial analysis. SPSS ver. 21 and t test analysis were used for comparing the findings, and the level of significance was considered as p < 0.05. RESULTS: TS plaques showed lower carbon, higher calcium, and phosphorous contents compared to AS plaques (p value < 0.05). Chlorine was detected in AS plaques (1.8 w%) which could probably be due to the presence of myeloperoxidase (MPO) in atherosclerotic artery. Contrary to spherical shape of the surface of TS plaques, AS plaques were needle shaped. BMP-8a expression in TS plaques (59.5%) was significantly higher (p value < 0.0001) than AS plaques (20%). Of the 18 TS specimens, 12, 14, and 3 were positive for ExoS, ExoU Pseudomonas aeruginosa, and Mycoplasma genes, respectively, while of the 18 AS specimens, 2, 2, and 3 were positive for ExoS, ExoU Pseudomonas aeruginosa, and Mycoplasma genes, respectively. CONCLUSION: TS plaques are different from AS plaques in terms of elemental components, surface morphology, and BMP-8a expression. Therefore, different calcification process and pathogenesis may be responsible for these two diseases. The results of our study showed that both TS and AS plaques have genetic footprint of Mycoplasma, but the level of calcium concentration-dependent exotoxins genes was found only in TS plaques.

Enriched environment effect on lipopolysaccharide-induced spatial learning, memory impairment and hippocampal inflammatory cytokine levels in male rats.

Neuro-inflammation is responsible for cognitive impairments and neurodegenerative diseases such as Alzheimer's disease. In this study, we aimed to investigate the enriched environment (EE) effect on learning and memory impairment as well as on pro-inflammatory cytokines changes induced by lipopolysaccharide (LPS). LPS injection (1 mg/kg/i.p, days 1, 3, 5, and 7) was used to develop the animal model of neuro-inflammation. Twenty-eight male Wistar rats were used in the experiment and randomly divided into 4 groups: 1) sham (S), 2) sham + enriched environment (SE), 3) LPS (L), and 4) LPS + EE (LE). Two different housing conditions, including standard environment (SE) and enriched environment, were used. The Morris Water Maze (MWM) test was used to examine animals learning and memory. IL-1ß, IL-10, and TNF-α levels were measured in the brain using ELISA. We found that LPS significantly impaired learning and memory (p < 0.05) in the MWM task, but EE could significantly improve learning and memory impairment (p < 0.05). IL-1 and IL-10 levels dramatically increased in the LPS group (P < 0.05), whereas EE could decrease and increase IL-1ß and IL-10 values in the LPS + EE group (P < 0.05), respectively. TNF-α levels were traced but had not detectable values in the hippocampus. Thus, we can conclude that EE has healing effects on LPS induced neuro-inflammation and can improve learning and memory deficit; however, further studies are needed to support the findings of our study.

Diphtheria toxoid nanoparticles improve learning and memory impairment in animal model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder involving memory. The present study aimed at evaluating the effects of encapsulated diphtheria toxoid (DT) on behavioral learning impairment, and XBP1 mRNA splicing in AD. METHODS: A DT-loaded nanoparticle (NP) carrier was prepared using the ionic gelation method. Sixty-three rats were divided into nine groups: (1) healthy, (2-4) sham, and (5-9) AD models: (5) AD was induced by intracerebroventricular injection of amyloid beta (Aß) 1-42. (6) The rats received a subcutaneous diphtheria vaccine only 28 days before Aß injection. (7) The rats received an intranasal diphtheria vaccine, in group 8, induced by administering empty chitosan NPs. 9) it was induced by administering chitosan NPs carrying DT. Morris water maze (MWM) test was used to examine the animals' learning and memory. Also, X-box binding protein 1 (XBP-1) mRNA gene splicing was studied in the hippocampus by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: For the first time, chitosan NPs were prepared with an average diameter size of 40 nm and the effectiveness of approximately 70% during DT encapsulation. In comparison with the healthy group, the AD models exhibited significant impairment of learning and memory (P < 0.05), while DT-administrated animals showed significant improvements in learning and memory impairment (P < 0.05). XBP-1 mRNA gene splicing was only detected in an untreated AD group, while encapsulated DT completely inhibited splicing. CONCLUSION: The therapeutic effects of DT chitosan NPs against learning and memory impairment were observed in this study, and XBP1 mRNA splicing was reported in the animal models.

Antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles fabricated from Mespilus germanica extract against multidrug resistance of Klebsiella pneumoniae clinical strains.

The aim of the present work was to investigate the antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles (AgNPs) fabricated from Mespilus germanica extract against multidrug-resistant (MDR) Klebsiella pneumoniae strains. Fifty strains of K. pneumoniae were isolated from various clinical specimens. Biofilm-forming strains were identified using Congo red agar and polymerase chain reaction (PCR) techniques. Subsequently, the antibacterial activity of phytosynthesized AgNPs on MDR K. pneumoniae strains was investigated by broth microdilution assay and agar well-diffusion method. Finally (in the last step), the antibiofilm activity of phytosynthesized AgNPs was determined using microtiter plate assay and real-time PCR (RT-PCR) methods for the analysis of type 3 fimbriae (mrkA) and quorum-sensing system (luxS) gene expression. The results of this study showed that the phytosynthesized AgNPs had a spherical nanostructure with the mean size of 17.60 nm. The AgNPs exhibited dose-dependent antibacterial activity. The results of the microtiter plate and RT-PCR methods show that AgNPs inhibited the biofilm formation in MDR K. pneumoniae strains, and the expressions of mrkA and luxS genes were downregulated significantly in MDR strains after treatment with a subminimum inhibitory concentration of AgNPs. In conclusion, AgNPs effectively prevent the formation of biofilms and kill bacteria in established biofilms, which suggests that AgNPs might be a promising candidate for the prevention and treatment of biofilm-related infections caused by MDR K. pneumoniae strains.

Aptamer-based Targeted Delivery of miRNA let-7d to Gastric Cancer Cells as a Novel Anti-Tumor Therapeutic Agent.

miRNAs as one of the potential therapeutic agents have been recently considered for cancer treatment. AS1411 (aptNCL) is a DNA aptamer specifically binding to nucleolin protein on the cancer cell surface with antiproliferative effect. The aim of the study was to develop a conjugate consisting of aptNCL (as targeted delivery of therapeutic agent) and miRNA let-7d (as a tumor suppressor) using two different linking methods and also to evaluate the potential effect of the conjugates on the proliferation of gastric cancer (MKN-45) cell line compared to negative control cell line of human dermal fibroblast (HDF). Conjugation was performed covalently by SM (PEG)2 as a bifunctional crosslinker (conjugate-1) and noncovalently, using 19bp complementary sticky end sequences (conjugate-2). Nucleolin positive MKN-45 and nucleolin negative HDF cells were cultured and treated with the conjugates. Then, the changes in let-7d expression and cell proliferation were determined using Real-time PCR and MTT methods, respectively. In MKN-45 cells, the conjugates caused significant increase in let7-d uptake compared with HDF cells (P = 0.0001). The conjugate-1, likely due to its higher stability compared with the conjugate-2, led to significantly more increase in intracellular let-7d in MKN-45 cells (30 fold versus 15 fold, respectively, P = 0.0001). The conjugates revealed more potent antiproliferative effect against gastric cancer cells compared with aptNCL alone (P = 0.0001). It was found that the aptNCL-let-7d conjugate efficiently carried let-7d into the cancer cells. Also, it appears that in the setting of aptNCL-let-7d conjugate, let-7d and aptNCL moieties could cooperate and synergistically exhibit the antiproliferative effect on cancer cells.

Biogenic synthesis of AgNPs using Artemisia oliveriana extract and their biological activities for an effective treatment of lung cancer.

Silver nanoparticles (AgNPs) were synthesized using Artemisia oliveriana extract, and their physicochemical characteristics were studied. The antioxidant and antimicrobial activities of the AgNPs, as well as their anticancer effects on the lung cancer cell line (A549), using 1,1-diphenyl-2-picrylhydrazyl (DPPH), MIC and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) techniques respectively demonstrated that the synthesized AgNPs mainly affected the gram-positive bacteria rather than the gram-negative bacteria, and exhibited significant cellular toxicity on the A549 cell line. Further, the cellular uptake of the AgNPs results indicated that the AgNPs accumulated within the cell. Moreover, their impact on the expression of apoptotic genes including Bax, Bcl-2, caspase-3 (CASP3), caspase-9 (CASP9) and miR-192 using real-time PCR demonstrated substantial increase in the expression of all mentioned genes (p<.001). Finally, the apoptotic effects of the AgNPs through DNA fragmentation test, flow cytometry and cell cycle analysis indicated the induction of apoptosis in the A549 cell line. The results revealed that the AgNPs synthesized using A. oliveriana extract have potential biological applications.

Distribution of high-level mupirocin resistance among clinical MRSA.

Mupirocin is a topical antibiotic for methicillin-resistant Staphylococcus aureus (MRSA) decolonization in hospital settings and nursing homes and is used as a highly effective antibiotic against MRSA. In this study, we aimed to evaluate the frequency of high-level mupirocin-resistant (HLMR) strains among the MRSA subtypes. A total of 188 clinical MRSA isolates were collected from 2011 to 2014, and their susceptibility to antimicrobial agents and vancomycin resistance was evaluated using disc diffusion method and micro-dilution method, respectively. Furthermore, the presence of mecA, SSCmec, mupA and mupB was assessed by PCR. All isolates were multi-drug resistant (MDR) but 2 strains (1.06%) were resistant to mupirocin. Minimum inhibitory concentration (MIC) of vancomycin for 8 strains (4.7%) was higher than 2 µg/ml. Of 188 isolates, 188 (100%), 64 (34.04%), 8 (4.3%), 150 (79.8%), 26 (13.8%), 2 (1.06) and 2 (1.06%) isolates possessed mecA, SCCmec types I, II, III, IV, mupA and mupB genes, respectively. Our data showed that despite infection control policy enforced by health care committee, the rate of mupirocin resistance among MRSA strains is continuously rising.

Isolation of a new ssDNA aptamer against staphylococcal enterotoxin B based on CNBr-activated sepharose-4B affinity chromatography.

Staphylococcus aureus are potent human pathogens possessing arsenal of virulence factors. Staphylococcal food poisoning (SFP) and respiratory infections mediated by staphylococcal enterotoxin B (SEB) are common clinical manifestations. Many diagnostic techniques are based on serological detection and quantification of SEB in different food and clinical samples. Aptamers are known as new therapeutic and detection tools which are available in different ssDNA, dsDNA and protein structures. In this study, we used a new set of ssDNA aptamers against SEB. The methods used included preparation of a dsDNA library using standard SEB protein as the target analyte, affinity chromatography matrix in microfuge tubes, SELEX procedures to isolate specific ssDNA-aptamer as an affinity ligand, aptamer purification using ethanol precipitation method, affinity binding assay using ELISA, aptamer cloning and specificity test. Among 12 readable sequences, three of them were selected as the most appropriate aptamer because of their affinity and specificity to SEB. This study presents a new set of ssDNA aptamer with favorable selectivity to SEB through 12 rounds of SELEX. Selected aptamers were used to detect SEB in infected serum samples. Results showed that SEB c1 aptamer (2 µg SEB/100 nM aptamer) had favorable specificity to SEB (kd = 2.3 × 10(-11) ). In conclusion, aptamers can be considered as useful tools for detecting and evaluating SEB. The results showed that affinity chromatography was an affordable assay with acceptable accuracy to isolate sensitive and selective novel aptamers. Copyright © 2016 John Wiley & Sons, Ltd.