Minocycline Improves Memory by Enhancing Hippocampal Synaptic Plasticity and Restoring Antioxidant Enzyme Activity in a Rat Model of Cerebral Ischemia-Reperfusion.

Introduction: Oxidative stress plays a crucial role in the impairment of synaptic plasticity following cerebral ischemia, ultimately resulting in memory dysfunction. Hence, the applying antioxidant agents could be beneficial in managing memory deficits after brain ischemia. Minocycline is a tetracycline antibiotic with antioxidant effect. The main objective of this work was to assess the minocycline effect on the impairment of synaptic plasticity and memory after cerebral ischemia-reperfusion in rats. Methods: Transient occlusion of common carotid arteries was used to induce ischemiareperfusion injury in rats. Single or multiple (once daily for 7 days) dose(s) of minocycline were administered before (pretreatment) or after (treatment) brain ischemia. Seven days after ischemia-reperfusion, passive avoidance performance, long-term hippocampal potentiation, and the activity of antioxidant enzymes were assessed. Results: The passive avoidance test showed that minocycline (20 and 40 mg/kg) significantly increased step-through latency while reducing the duration of staying in a dark chamber in the treatment (but not pretreatment) group. In electrophysiological experiments, the rats treated (but not pretreated) with minocycline (40 mg/kg) showed a significant increase in the amplitude of the field excitatory postsynaptic potentials in the dentate gyrus area of the hippocampus. The treatment (but not pretreatment) with minocycline (20 and 40 mg/kg) resulted in a significant increase in the activity of catalase, glutathione peroxidase, and superoxide dismutase in the hippocampus. Conclusion: It was determined that minocycline attenuates memory dysfunction after cerebral ischemia-reperfusion in rats by improving hippocampal synaptic plasticity and restoring antioxidant enzyme activity. Highlights: Minocycline enhances passive avoidance memory after cerebral ischemia-reperfusion.Minocycline increases enzymatic antioxidant capacity in hippocampal formation.Minocycline improves synaptic plasticity in perforant path-granule cell synapse. Plain Language Summary: Stroke is a common neurological disease with a relatively high mortality rate and disabilities worldwide. More than half of the patients who have had an episode of stroke suffer from the impairment of sensorimotor function and language problems as well as learning and memory disorders. Oxidative stress plays an important role in memory impairment following brain ischemia. Hence, the application of antioxidant agents could be beneficial in managing memory deficits after stroke. Minocycline is a tetracycline antibiotic that is used for the treatment of infectious diseases; it can also function as a potent antioxidant medication. Hence, we hypothesized that minocycline could attenuate memory impairment after brain ischemia. We examined this hypothesis in a rat model of brain ischemia. In this model, the main arteries that supply the brain with oxygenated blood were occluded to induce brain ischemia in the rats. Then, minocycline was administered to the rats, which were subjected to brain ischemia. Seven days later, memory function in the rats was evaluated. The results showed that minocycline could enhance the activity of antioxidant enzymes in the brain, which physiologically fight off oxidative stress. This property of minocycline protects brain cells against ischemic injury and thereby increases the transmission of neuronal signals from one cell to another cell in the memory centers in the brain. These effects ultimately increase the memory function of rats, which was evident in the behavioral memory test. Overall, the study results suggest that minocycline can be considered a memory enhancer drug in patients who suffer from learning and memory disorders following a stroke.

Astaxanthin ameliorates serum level and spinal expression of macrophage migration inhibitory factor following spinal cord injury.

Astaxanthin (AST) is a lipid-soluble carotenoid with antioxidant and anti-inflammatory properties. Previous reports demonstrated the promising effects of AST on spinal cord injury (SCI)-induced inflammation and sensory-motor dysfunction. Macrophage migration inhibitory factor (MIF), as a cytokine, plays a critical role in the inflammatory phase of SCI. The aim of this study was to evaluate the effects of AST on post-SCI levels of MIF in serum and spinal cord. The possible correlation between MIF and mechanical pain threshold was also assessed. Adult male rats were subjected to a severe compression spinal injury and 30 min later were treated with AST (Intrathecal, 2 nmol) or vehicle. Neuropathic pain was assessed by von Frey filaments before the surgery, and then on days 7, 14, 21, and 28 post-SCI. Western blot and ELISA were used to measure the serum level and spinal expression of MIF following SCI in the same time points. AST treatment significantly attenuated the SCI-induced dysregulations in the serum levels and tissue expression of MIF. A negative correlation was observed between mechanical pain threshold and serum MIF level (r = -0.5463, P < 0.001), as well as mechanical pain threshold and spinal level of MIF (r = -0.9562; P < 0.001). AST ameliorates SCI-induced sensory dysfunction, probably through inhibiting MIF-regulated inflammatory pathways.

Tuberculosis challenges: Resistance, co-infection, diagnosis, and treatment.

Early diagnosis of tuberculosis (TB), followed by effective treatment, is the cornerstone of global TB control efforts. An estimated 3 million cases of TB remain undetected each year. Early detection and effective management of TB can prevent severe disease and reduce mortality and transmission. Intrinsic and acquired drug resistance of Mycobacterium tuberculosis (MTB) severely restricted the anti-TB therapeutic options, and public health policies are required to preserve the new medications to treat TB. In addition, TB and HIV frequently accelerate the progression of each other, and one disease can enhance the other effect. Overall, TB-HIV co-infections show an adverse bidirectional interaction. For HIV-infected patients, the risk of developing TB disease is approximately 22 times higher than for persons with a protective immune response. Analysis of the current TB challenges is critical to meet the goals of the end TB strategy and can go a long way in eradicating the disease. It provides opportunities for global TB control and demonstrates the efforts required to accelerate eliminating TB. This review will discuss the main challenges of the TB era, including resistance, co-infection, diagnosis, and treatment.

Chitin and chitosan as tools to combat COVID-19: A triple approach.

The progressive and fatal outbreak of the newly emerged coronavirus, SARS-CoV-2, necessitates rigorous collaboration of all health care systems and researchers from all around the world to bring such a devastating pandemic under control. As there is so far no officially approved drug or ideal vaccine for this disease, investigations on this infectious disease are actively pursued. Chitin and chitosan have shown promising results against viral infections. In this review, we first delve into the problematic consequences of viral pandemics followed by an introduction on SARS-CoV-2 taxonomical classification. Then, we elaborate on the immunology of COVID-19. Common antiviral therapies and their related limitations are described and finally, the potential applicability of chitin and chitosan to fight this overwhelming viral pandemic is addressed.

Analgesic effects of cuminic alcohol (4-isopropylbenzyl alcohol), a monocyclic terpenoid, in animal models of nociceptive and neuropathic pain: Role of opioid receptors, L-arginine/NO/cGMP pathway, and inflammatory cytokines.

Cuminic alcohol (4-isopropylbenzyl alcohol; 4-IPBA) is a monocyclic terpenoid found in the analgesic medicinal plants Cuminum cyminum and Bunium persicum. The current study assessed the analgesic effects of 4-IPBA in different animal models of pain. Hot plate, formalin, and acetic acid tests were used to evaluate nociceptive pain in mice. The involvement of opioid receptors and the L-arginine/NO/cGMP/K+ channel pathway in 4-IPBA effects were investigated. Allodynia and hyperalgesia were assessed following peripheral neuropathy induced by chronic constriction of the sciatic nerve in rats. The spinal levels of inflammatory cytokines were measured using the ELISA method. The drugs and compounds were administered intraperitoneally. The results showed that 4-IPBA (200 and 400 mg/kg) significantly prolonged the hot plate latency. This effect was antagonized by naloxone (2 mg/kg). 4-IPBA (25-100 mg/kg) also significantly attenuated formalin- and acetic acid-induced nociceptive pain. L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg) reversed while L-NAME (30 mg/kg) and methylene blue (20 mg/kg) potentiated the antinociceptive effects of 4-IPBA in the writhing test. Glibenclamide (10 mg/kg) and tetraethylammonium chloride (4 mg/kg) did not have any influence on the 4-IPBA effect. Furthermore, 4-IPBA (6.25-25 mg/kg) significantly relieved mechanical allodynia, cold allodynia, and hyperalgesia in rats. The concentrations of TNF-α and IL-1ß in the spinal cord of rats were decreased by 4-IPBA. No evidence of 4-IPBA-induced toxicity was found in behavioral or histopathological examinations. These results demonstrate that 4-IPBA attenuates nociceptive and neuropathic pain through the involvement of opioid receptors, the L-arginine/NO/cGMP pathway, and anti-inflammatory functions.

The chemical chaperon 4-phenyl butyric acid restored high-fat diet- induced hippocampal insulin content and insulin receptor level reduction along with spatial learning and memory deficits in male rats.

This study assessed the effect of a chronic high-fat diet (HFD) on plasma and hippocampal insulin and corticosterone levels, the hippocampus insulin receptor amount, and spatial learning and memory with or without receiving 4-phenyl butyric acid (4-PBA) in male rats. Rats were divided into high-fat and normal diet groups, then each group was subdivided into dimethyl sulfoxide (DMSO) and 4-PBA groups. After weaning, the rats were fed with HFD for 20 weeks. Then, 4-PBA or DMSO were injected for 3 days. Subsequently, oral glucose tolerance test was done. On the following day, spatial memory tests were performed. Then the hippocampus Bip, Chop, insulin, corticosterone, and insulin receptor levels were determined. HFD increased plasma glucose, leptin and corticosterone concentrations, hippocampus Bip, Chop and corticosterone levels, food intake, abdominal fat weight and body weight along with impaired glucose tolerance. It decreased plasma insulin, and insulin content, and its receptor amount in hippocampus. HFD lengthened escape latency and shortened the duration spent in target zone. 4-PBA administration improved the HFD- induced adverse changes. Chronic HFD possibly through the induction of endoplasmic reticulum (ER) stress and subsequent changes in the levels of hippocampal corticosterone, insulin and insulin receptor along with possible leptin resistance caused spatial learning and memory deficits.

Attenuating effect of paroxetine on memory impairment following cerebral ischemia-reperfusion injury in rat: The involvement of BDNF and antioxidant capacity.

Memory impairments are frequently reported in patients suffering from brain ischemic diseases. Oxidative/nitrosative stress, synaptic plasticity, and brain-derived neurotrophic factor (BDNF) are involved in the physiopathology of brain ischemia-induced memory disorders. In the present study, the effect of paroxetine as an efficacious antidepressant medication with antioxidant properties was evaluated on passive avoidance memory deficit following cerebral ischemia in rats. Transient occlusion of common carotid arteries was applied to induce ischemia-reperfusion injury in male Wistar rats. Paroxetine (5, 10, 20 mg/kg) was administered intraperitoneally once daily before (for 3 days) or after (for 7 days) the induction of ischemia. A week after ischemia-reperfusion injury, passive avoidance memory, long-term potentiation (LTP), BDNF levels, total antioxidant capacity, the activity of antioxidant enzymes (including catalase, glutathione peroxidase, and superoxide dismutase), the concentration of malondialdehyde (MDA), and nitric oxide (NO) were investigated in the hippocampus. In the passive avoidance test, paroxetine significantly increased the step-through latency and decreased the time spent in the dark compartment. This affirmative function of paroxetine on the passive avoidance memory was accompanied by the improvement of hippocampal LTP and an obvious augmentation in the BDNF contents. Besides, paroxetine caused a significant rise in the total antioxidant capacity and antioxidant enzyme activity; while decreased the hippocampal levels of NO and MDA. It was ultimately attained that paroxetine attenuates cerebral ischemia-induced passive avoidance memory dysfunction in rats by the enhancement of hippocampal synaptic plasticity and BDNF content together with the suppression of oxidative/nitrosative stress.

Phenotypic and Genotypic Prevalence of Extended-Spectrum ß-Lactamase-Producing Escherichia coli: A Systematic Review and Meta-Analysis in Iran.

Background: Despite the existence of discrete and varied studies regarding extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) in Iran, a comprehensive analysis on the prevalence of ESBL-EC has not yet been carried out. The current study analyzed published data regarding ESBL-EC in different regions of Iran to gain insight into this significant subject. Methods: A meta-analysis was performed using Comprehensive Meta-Analysis Software (version 2.2; Biostat) to determine the prevalence of ESBL-EC in Iran. A web-based search was conducted in electronic databases, including PubMed, Scopus, and Web of Sciences. The eligibility of articles published between 2008 and 2018 was assessed, and relevant data were extracted for statistical analysis. A random-effects model was used based on the heterogeneity test. Publication bias was determined using Begg's rank correlation and Egger's weighted regression methods. Results: Among 31,135 studies examined, 61 met inclusion criteria and were included for review. Iran's overall pooled proportion of ESBL-EC was 43.2% (confidence interval [95% CI] 39.2-47.3), and the overall heterogeneity (I2) between studies was significantly high (93.5%, p = 0.00). The most prevalent of ESBLs in E. coli was CTX-M and TEM, with prevalence of 31.2% (95% CI 25.4-37.6), 27.6% (95% CI 22.7-33.2), respectively. Conclusion: The available studies show a high rate of ESBL-EC in Iran. This result highlights a need for appropriate and rapid methods for estimating ESBL infection, which can help our understanding of the actual epidemiology of ESBL and provide protocols for the prevention and control of infection.

ACE2: Its potential role and regulation in severe acute respiratory syndrome and COVID-19.

COVID-19, a new disease caused by the 2019-novel coronavirus (SARS-CoV-2), has swept the world and challenged its culture, economy, and health infrastructure. Forced emergence to find an effective vaccine to immunize people has led scientists to design and examine vaccine candidates all over the world. Until a vaccine is developed, however, effective treatment is needed to combat this virus, which is resistant to all conventional antiviral drugs. Accordingly, more about the structure, entry mechanism, and pathogenesis of COVID-19 is required. Angiotensin-converting enzyme 2 (ACE2) is the gateway to SARS-CoV and SARS-CoV-2, so our knowledge of SARS-CoV-2 can help us to complete its mechanism of interaction with ACE2 and virus endocytosis, which can be interrupted by neutralizing small molecules or proteins. ACE2 also plays a crucial role in lung injury.

Prevalence, Genetic Diversity, and Temporary Shifts of Inducible Clindamycin Resistance Staphylococcus aureus Clones in Tehran, Iran: A Molecular-Epidemiological Analysis From 2013 to 2018.

The prevalence of Staphylococcus aureus as an aggressive pathogen resistant to multiple antibiotics causing nosocomial and community-acquired infections is increasing with limited therapeutic options. Macrolide-lincosamide streptogramin B (MLSB) family of antibiotics represents an important alternative therapy for staphylococcal infections. This study was conducted over a period of five years from August 2013 to July 2018 to investigate the prevalence and molecular epidemiology in Iran of inducible resistance in S. aureus. In the current study, 126 inducible methicillin-resistant S. aureus (MRSA) (n = 106) and methicillin-sensitive S. aureus (MSSA) (n = 20) isolates were characterized by in vitro susceptibility analysis, resistance and virulence encoding gene distribution, phenotypic and genotypic analysis of biofilm formation, prophage typing, S. aureus protein A locus (spa) typing, staphylocoagulase (SC) typing, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing. Of the 126 isolates, 76 (60.3%) were classified as hospital onset, and 50 (39.7%) were classified as community onset (CO). Biofilm formation was observed in 97 strains (77%). A total of 14 sequence types (STs), 26 spa types, 7 coagulase types, 9 prophage types, 3 agr types (no agr IV), and 9 clonal complexes (CCs) were identified in this study. The prevalence of the inducible MLSB (iMLSB) S. aureus increased from 7.5% (25/335) to 21.7% (38/175) during the study period. The iMLSB MRSA isolates were distributed in nine CCs, whereas the MSSA isolates were less diverse, which mainly belonged to CC22 (7.95%) and CC30 (7.95%). High-level mupirocin-resistant strains belonged to ST85-SCCmec IV/t008 (n = 4), ST5-SCCmec IV/t002 (n = 4), ST239-SCCmec III/t631 (n = 2), and ST8-SCCmec IV/t064 (n = 2) clones, whereas low-level mupirocin-resistant strains belonged to ST15-SCCmec IV/t084 (n = 5), ST239-SCCmec III/t860 (n = 3), and ST22-SCCmec IV/t790 (n = 3) clones. All the fusidic acid-resistant iMLSB isolates were MRSA and belonged to ST15-SCCmec IV/t084 (n = 2), ST239-SCCmec III/t030 (n = 2), ST1-SCCmec V/t6811 (n = 1), ST80-SCCmec IV/t044 (n = 1), and ST59-SCCmec IV/t437 (n = 1). The CC22 that was predominant in 2013-2014 (36% of the isolates) had almost disappeared in 2017-2018, being replaced by the CC8, which represented 39.5% of the 2017-2018 isolates. This is the first description of temporal shifts of iMLSB S. aureus isolates in Iran that identifies predominant clones and treatment options for iMLSB S. aureus-related infections.

Activity of Dipeptidyl Peptidase-IV/CD26 and Aminopeptidase N/CD13 in Secretome of Mesenchymal Stem Cells after Treatment with LPS and PMA.

BACKGROUND: Emerging evidence suggests that secretome of mesenchymal stem cells has many anti-inflammatory and regenerative properties, which makes it a suitable candidate for the treatment of autoimmune and degenerative diseases. Dipeptidyl Peptidase-IV (DPP-IV)/CD26 and Aminopeptidase N (APN)/CD13 are ubiquitous ecto-enzymes which can digest various substrates including some chemokines and neuropeptides that are involved in inflammatory conditions. OBJECTIVE: To evaluate the enzymatic activity of DPP-IV/CD26 and APN/CD13 in MSC conditioned media (MSC-CM). METHODS: The MSCs were isolated from the mouse's abdominal adipose tissues and were cultured with or without preconditioning by adding phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). The levels of interleukin-10 (IL-10), nitric oxide (NO), as well as the enzymatic activities of DPP-IV/CD26 and APN/CD13 were measured in MSC-CM. RESULTS: The level of IL-10 and the enzyme activity of APN/CD13 did not show any changes in the MSC-CM of stimulated and non-stimulated cells. However, NO production was increased after treatment by LPS or PMA; nevertheless, the DPP-IV/CD26 activity was decreased in MSC-CM merely following the stimulation of cells with LPS. CONCLUSION: Our results indicated that MSC-secretome had DPP-IV/CD26 and APN/CD13 activity. The DPP-IV/CD26 activity was decreased following stimulation of MSCs by toll-like receptor 4 agonist. Further studies are needed to reveal the possible contribution of DPP-IV/CD26 and APN/CD13 in the anti-inflammatory functions of MSC-CM.

Antinociceptive and antineuropathic effects of cuminaldehyde, the major constituent of Cuminum cyminum seeds: Possible mechanisms of action.

ETHNOPHARMACOLOGICAL RELEVANCE: In Iranian traditional medicine, Cuminum cyminum is a unique medicinal herb for pain relief. Cuminaldehyde has been distinguished as the major constituent of C. cyminum seeds; even though, the analgesic effect of cuminaldehyde has not yet been examined. AIM OF THE STUDY: The nobility of this study was to assess cuminaldehyde effect on nociceptive and neuropathic pains; furthermore, evaluation of its possible mechanisms of action. MATERIALS AND METHODS: Hot plate, formalin, and acetic acid-induced writhing tests were used to evaluate nociception in mice. Naloxone (opioid receptors antagonist), L-arginine (nitric oxide (NO) precursor), L-NAME (NO synthase inhibitor), sodium nitroprusside (NO donor), methylene blue (guanylyl cyclase inhibitor), sildenafil (phosphodiesterase inhibitor), and glibenclamide (KATP channel blocker) were used to determine the implication of opioid receptors and L-arginine/NO/cGMP/KATP channel pathway. Allodynia and hyperalgesia were investigated in the CCI (chronic constriction injury) model of neuropathic pain in rats. The ELISA method was used to measure the inflammatory cytokines in serum samples of rats. The entire chemicals were intraperitoneally injected. RESULTS: Cuminaldehyde (100 and 200 mg/kg) significantly decreased the latency to nociceptive response in the hot plate test. The outcome of cuminaldehyde was completely antagonized by naloxone (2 mg/kg). Formalin- and acetic acid-induced nociception was significantly inhibited by cuminaldehyde (12.5-50 mg/kg). The antinociceptive effect of cuminaldehyde was reversed in writhing test by L-arginine (200 mg/kg), sodium nitroprusside (0.25 mg/kg), and sildenafil (0.5 mg/kg); however, L-NAME (30 mg/kg) and methylene blue (20 mg/kg) enhanced the effect of cuminaldehyde. Glibenclamide (10 mg/kg) did not alter the antinociceptive effects of cuminaldehyde. In the CCI-induced neuropathy, cuminaldehyde (25-100 mg/kg) significantly alleviated allodynia and hyperalgesia and decreased the serum levels of TNF-α and IL-1ß. CONCLUSION: It was attained magnificently that cuminaldehyde exerts antinociceptive and antineuropathic effects through the involvement of opioid receptors, L-arginine/NO/cGMP pathway, and anti-inflammatory function.

Chitosan/PVA/Doxycycline Film and Nanofiber Accelerate Diabetic Wound Healing in a Rat Model.

In this study, we evaluated the effects of nanofiber and film polymers with doxycycline for treating a wound in a diabetic rat model. 108 male rats were divided into six groups, the control group, the diabetic control, and the groups were diabetic rats receiving different wound dressing. At the 3rd, 7th, and 14th days, macroscopic/histologic imaging and tissue sampling were performed. Tissues were analyzed for IL-1ß, TNF-α, IL-10, TIMP-1, and MMP-2 by using ELISA. Dressings of chitosan, polyvinyl alcohol, and doxycycline increased the rate of wound closure, the volume of collagen, dermal, and epidermis. In addition, it increased the number of fibroblasts and basal cell epidermis cells, vascular length, and decreased the number of neutrophil cells. Inflammatory cytokines and MMP-2 were decreased, and anti-inflammatory IL-10 and TIMP-1 were increased. It was ultimately attained that the combination of chitosan/ polyvinyl alcohol /doxycycline could be a useful dressing for the healing of diabetic wounds.

Attenuating effect of α-pinene on neurobehavioural deficit, oxidative damage and inflammatory response following focal ischaemic stroke in rat.

OBJECTIVES: Oxidative stress and inflammation have a critical role in the pathogenesis of ischaemic stroke. Alpha-pinene is a monoterpenoid molecule with anti-inflammatory and antioxidant properties. The nobility of the present study was to evaluate the neuroprotective effect of α-pinene in ischaemic stroke. METHODS: Ischaemic stroke was induced by transient middle cerebral artery occlusion followed by 24 h reperfusion in male Wistar rats. Alpha-pinene (25, 50 and 100 mg/kg, i.p.) was administered in the beginning of reperfusion. Then, the neurobehavioural function, infarct volume, brain oedema, antioxidant enzyme activity and the concentration of malondialdehyde (MDA), nitric oxide (NO) and interleukin-6 (IL-6) were evaluated by different methods in the brain. KEY FINDINGS: Alpha-pinene (50 and 100 mg/kg) elicited a significant decrease in the brain oedema and infarct size as well as an improvement in the neurobehavioural function. Besides, α-pinene (100 mg/kg) restored the function of superoxide dismutase, catalase and glutathione peroxidase and reduced the concentration of MDA, NO and IL-6 in the hippocampus, cortex and striatum. CONCLUSIONS: It was ultimately attainted that α-pinene exerts neuroprotective effect in ischaemic stroke in rat through the restoration of antioxidant enzymes activity, attenuation of lipid peroxidation and reduction of inflammation in the ischaemic brains.

Genotype Distribution of Panton-Valentine Leukocidin (PVL)-Positive Staphylococcus aureus Strains Isolated from Wound-Related Infections: a Three-Year Multi-Center Study in Tehran, Iran.

The spread of Panton-Valentine leucocidin (PVL)-carrying S. aureus strains in patients with wound infections in both the community and hospitals is increasing in some areas of Iran. In the present study, we determined the molecular characteristics and distribution of PVL-producing S. aureus strains isolated from wound infections. Genes encoding resistance, toxins, and staphylococcal enterotoxins were analyzed by polymerase chain reaction assays. Genotyping was performed using multi-locus sequence typing. Aminoglycoside resistance genes including ant (4')-Ia (57.4%) and aac (6')-Ie/aph (2″) (45.7%) were the most prevalent genes in isolates. Staphylococcal enterotoxin type A, as the most frequent type, was present in 20.2% of isolates. Strains belonged to seven clonal complexes. The most frequent clonal complex was CC30 (ST30) (29.8%), followed by CC22 (ST22) (21.3%), CC8 (ST8 and ST931) (17%), CC88 (ST88) (10.6%), CC59 (ST59 and ST338) (8.5%), CC1 (ST772 and ST1) (7.5%), and CC15 (ST15) (5.3%). Our findings indicated an increasing trend of CC30, carrying a wide range of resistance and toxin genes, which could present an obstacle in the treatment of patients with wound infections. Further studies are required to investigate the carriage of resistance, the antibiotic susceptibility pattern, and toxins encoding genes in different molecular types.

Screening of acetaminophen-induced alterations in epithelial-to-mesenchymal transition-related expression of microRNAs in a model of stem-like triple-negative breast cancer cells: The possible functional impacts.

Current protocols for therapy inefficiently targets triple negative breast cancer and barely eradicate cancer stem cells. Elucidation of the pleiotropic effect of clinically proven therapeutics on cancer cells shed light on novel application of old friends. The pleiotropic effect of acetaminophen (APAP) on breast cancer was previously reported. In a cell model of triple negative breast cancer with stem-like CD44high/CD24low phenotype, we screened the impacts of APAP (1 mM, 72 h) on the Epithelial to mesenchymal transition (EMT)-related expression of miRs. APAP significantly overexpressed hsa-miR-130a-3p, 192-5p, 214-3p, 101-3p, 30d-5p, 10a-5p, 99a-5p, 200c-3p, 143-3p, 30b-5p and let-7f-5p showed significant overexpression, but suppressed the expression of hsa-miR-7-5p, 149-3p, 215, 150-5p, 205-5p, 206, 10b-5p, 20b-5p, 145-5p, 26b-5p, 223-3p, 17-5p, 186-5p, 146a-5p and let-7c. It also altered on the expression of selected EMT-related genes, significantly upregulated the expression of KRT19, AKT2, CD24, and TIMP1; but downregulated the expression of MMP2, ALDH1, MMP9, TWIST, NOTCH1, and AKT1. Such shifts in expression profiles increased the population of the cells with CD44high/CD24high, and CD44low/CD24high phenotypes, significantly reduced the Twist protein and shifted the balance of E-cadherin and Vimentin proteins in favor of differentiation. Treated cells showed a significant reduction of in vitro migration and were significantly chemosensitized to Camptothecin. In conclusion, APAP, at a safe clinical dose, induced a set of targeted alterations in the EMT-related miRs which implicate, even in part, significant mitigation in chemoresistance and in vitro migration. Further studies should also be piloted to elucidate the most crucial miRs and to evaluate its clinical effectiveness.

Prevalence of integron classes in Gram-negative clinical isolated bacteria in Iran: a systematic review and meta-analysis.

OBJECTIVES: Integrons, as a potential element in the distribution and maintenance of drug resistance, have thoroughly been established. It is known that the high prevalence of integrons in multidrug-resistant (MDR) clinical isolates has become a serious public health concern. The objective of the present study was to determine the frequency of different classes of integrons in clinical isolates in Iran. MATERIALS AND METHODS: Electronic global databases were systematically searched. The raw data for integrons among bacterial isolates were collected and their prevalence was analyzed using Comprehensive Meta-Analysis V2.0 (Biostat, Englewood, NJ, USA) software. RESULTS: In a comprehensive literature review, 29 eligible studies were determined with their meta-analyses indicating the prevalence of integron class 1 to be 41% (95% CI 36.3-46.1) and integron class 2 as 17.7% (95% CI 13-23.3) in Gram-negative bacteria. The highest prevalence of integron class 1 was reported in Acinetobacter spp (58%) while the highest prevalence of integron class 2 was reported in Shigella isolates (83.7%). The frequencies of class 1 integron in MDR (79%) and non-MDR isolates (41%) were higher than those for class 2 integron in MDR (13.4%) and non-MDR isolates (17.7%). CONCLUSION: The current systematic review demonstrated the significant presence of integrons among clinical isolates. Our analysis showed that measures such as estimates of the prevalence of this transposable element and diligence in continued surveillance might be necessary to prevent its spread.

Genetic Diversity Analysis of Methicillin-resistant Staphylococcus aureus Strains Isolated from Intensive Care Unit in Iran.

OBJECTIVES: Staphylococcus aureus has emerged as a major public health concern. It is a common pathogen in high-risk hospital intensive care units (ICUs). We analyzed the molecular characteristics on the SCCmec and spa genes of S. aureus isolates gathered from ICUs. The antibiotic resistance patterns and carriage of resistance and virulence determinants were also identified. METHODS: In this cross-sectional study, 84 non-duplicated S. aureus strains isolated from ICU patients in were genotyped using SCCmec and spa typing. The Kirby-Bauer disk diffusion and micro-broth dilution methods were used to determine resistance patterns. Virulence and resistance gene profiling were also determined using the polymerase chain reaction technique. RESULTS: All isolates were methicillin-resistant S. aureus and belonged to seven spa types: t388 (36.9%), t852 (14.3%), t924 (13.1%), t790 (11.9%), t064 (10.7%), t037 (9.5%), and t084 (3.6%). They differed in the carriage of resistance and toxin genes. The most common SCCmec type was III detected in 50 isolates (59.5%), followed by type IV in 34 isolates (40.5%). The pvl gene was detected in 14.3% (n = 12) of isolates, of which 66.7% (n = 8) belonged to t852 and 33.3% (n = 4) belonged to t790. Among the tested strains, 9.5% (n = 8) carried the mupA gene and belonged to the t064 spa type. CONCLUSIONS: The data revealed a high resistance rate to antibiotics, which could be a threat to ICU patients. It is necessary to detect antimicrobial resistance and resistance and toxin-encoding of gene profiles in different molecular types.

The prevalence of exotoxins, adhesion, and biofilm-related genes in Staphylococcus aureus isolates from the main burn center of Tehran, Iran.

OBJECTIVES: The present study investigated the prevalence of genes encoding for exotoxins, adhesion and biofilm factors in Staphylococcus aureus isolates obtained from samples in a referral burn hospital in Tehran, Iran. MATERIALS AND METHODS: S. aureus isolates obtained from patients, personnel and surfaces in the wards of a burn hospital were identified and confirmed by biochemical and molecular tests, respectively. The susceptibility of isolates was determined using the disk diffusion method. Virulence factors were detected by multiplex PCR. RESULTS: The frequency of hla, hlb, hld, hlg, tst and pvl genes was 92.8%, 34.7%, 89.8%, 11.9%, 10.7%, and 0.5% respectively. The results revealed that the hla gene had the highest frequency among isolates (94.4% for methicillin-resistant S. aureus (MRSA) and 89.8% for methicillin-susceptible S. aureus (MSSA)). The most prevalent adhesion and biofilm-related gene was eno (85.6%). The prevalence of the remaining genes was as follows: fib (71.8%), clfB (70%), cna (59.2 %), fnbB (17.9%), icaA (72.4%), and icaD (85.6%). The incidence of fib, hlb, hlg, and tst genes was significantly higher in MRSA isolates compare to the MSSA isolates. Moreover, the resistance rates for all antibiotics were higher is MRSA isolates except for nitrofurantoin and chloramphenicol antibiotics. CONCLUSION: Data indicate the high prevalence rates of virulence factors among S. aureus isolates, especially MRSA strains in the burn hospital. This should to be taken into account in the development of an effective infection control policy and continuous monitoring of drug resistance in hospitals.

Analgesic effect of α-terpineol on neuropathic pain induced by chronic constriction injury in rat sciatic nerve: Involvement of spinal microglial cells and inflammatory cytokines.

OBJECTIVES: Neuropathic pain is a prevalent and debilitating neurological disorder. Ample evidence indicates that microglial cells and inflammatory cytokines are involved in the pathogenesis of neuropathic pain. Alpha-terpineol is a monoterpenoid alcohol with inhibitory effect on inflammatory cytokines. The main purpose of this study was to evaluate the effect of α-terpineol on neuropathic pain in rats. MATERIALS AND METHODS: Chronic constriction injury (CCI) model was utilized to induce neuropathic pain in male Wistar rats. The rats were randomly divided into control, sham, α-terpineol, and gabapentin groups. Normal saline, α-terpineol (25, 50, and 100 mg/kg), and gabapentin (100 mg/kg) were administered intraperitoneally in the above-mentioned groups once daily for 14 days post-CCI. Behavioral tests, including Von Frey, acetone, and Hargreaves were used to assess mechanical allodynia, cold allodynia, and hyperalgesia in rats. Iba1 immunostaining and ELISA procedures were used to assess the activation of microglial cells and inflammatory cytokines level. RESULTS: The results showed that α-terpineol (50 and 100 mg/kg) significantly attenuated mechanical allodynia, cold allodynia, and hyperalgesia in the neuropathic rats. The analgesic effect of α-terpineol (100 mg/kg) was comparable with that of gabapentin as a standard antineuropathic pain drug. In addition, α-terpineol (25, 50 and 100 mg/kg) significantly decreased the number of Iba1-positive cells and diminished the concentration of IL-1ß and TNF-α in the spinal tissue. CONCLUSION: It was ultimately attained that α-terpineol attenuates neuropathic pain through the suppression of the microglial cells and reduction of inflammatory cytokine levels in the spinal cord of rats.