Oral spirochetes: Pathogenic mechanisms in periodontal disease.

Periodontitis is an infectious inflammatory disease resulting from infection of biofilm forming bacteria. Several bacterial factors regulate inflammatory response and cause to tissue damage and loss of connection between gingival and tooth. Since bacterial virulence factors and also host immune responses have role, understanding of periodontal disease is complex, in overall we can say that in this disease epithelium is deleted by bacteria. Oral spirochetes are related to periodontitis, among them, Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis. This review will analyse mechanisms of pathogenesis of spirochetes in periodontitis. Microorganisms cause destruction of gingival tissue by two mechanisms. In one, damage results from the direct action of bacterial enzymes and cytotoxic products of bacterial metabolism. In the other, only bacterial components have role, and tissue destruction is the inevitable side effect of a subverted and exaggerated host inflammatory response to plaque antigens.

The critical role of Faecalibacterium prausnitzii in human health: An overview.

Faecalibacterium prausnitzii (F. prausnitzii) is one of the most abundant bacterial species in the colon of healthy human adults and representing more than 5% of the total bacterial population. Recently, it has been known as a major actor in human intestinal health and a biosensor. Changes in this species population richness and quantity have been observed in many illnesses and several investigations have reported that abundance of F. prausnitzii is reduced in different intestinal disorders. In the current review, we aim to consider literature from various library databases and electronic searches (Science Direct, PubMed, and Google Scholar) which were randomly collected and serve as an overview of different features of F. prausnitzii including metabolites, anti-inflammatory action, and correlation of dysbiosis of this bacterium with various complications in human.

Risk of gastric cancer in association with Helicobacter pylori different virulence factors: A systematic review and meta-analysis.

INTRODUCTION: It has been proposed that specific analysis of Helicobacter pylori virulence factors can be suitable for predicting of post H. pylori infection disorders like gastric cancer (GC). The present study was designed to evaluate the association between different virulence factors of H. pylori and GC. METHODS: Studies investigated the association between virulence factors of H. pylori and GC were collected from the several databases. All analysis was performed by Comprehensive Meta-Analysis V2.2 software (Biostat, Englewood, NJ, USA). RESULTS: Based on a comprehensive literature search, 25 eligible studies were included for meta-analyses. Infection with cagA- and vacA s1m1-positive H. pylori strains were significantly associated with increased risk of GC (OR of [2.82 (95% CI 1.96-4.06), P < 0.001]) and ([1.75 (95% CI 1.04-2.96), P 0.034)], respectively. CONCLUSIONS: Infection by H. pylori strains with positive vacA s1m1 and the cagA genes can significantly increase the risk of GC. The association between the vacA s1m1 and the cagA and GC, suggests that screening of these genes may be helpful for identifying populations at higher risk for GC.

The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.

The metabolic, protective, and immune functions of Akkermansia muciniphila.

Numerous studies have almost proven the beneficial effects of gut microbiota in various aspects of human health, and even the gut microbiota is known as a new and forgotten organ. Akkermansia muciniphila, as a member of the gut microbiota, is considered a bacterium with probiotic properties; consequently, it has a remarkable position in microbiome research. This bacterium accounts for about 1-4 % of the total fecal microbiota population and is also considered a health marker. The accumulated evidence has shown a significant association between A. muciniphila and several disorders and diseases, such as obesity, fatty liver disease, diabetes, and even behavioral disorders. On the other hand, the beneficial effects of A. muciniphila in different studies have shown, such as protective role against pathogenic agents, antitumor properties, tight junctions' improvement, reduction of inflammation, gut permeability, and boosting adaptive immune responses. In this review, based on the available evidence and the latest research, we comprehensively evaluated the impact of A. muciniphila on host health from three points of view: metabolic, protective, and immune functions, as well as the possible mechanisms of each process.

Severe acute respiratory syndrome coronavirus 2 infection: Role of interleukin-6 and the inflammatory cascade.

Since December 2019, a novel coronavirus that represents a serious threat to human lives has emerged. There is still no definite treatment for severe cases of the disease caused by this virus, named coronavirus disease 2019 (COVID-19). One of the most considered treatment strategies targets the exaggerated immune regulator, and interleukin (IL)-6 is a crucial pro-inflammatory mediator. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases show an elevated level of IL-6 related to disease severity. IL-6 activity can be inhibited by the following: IL-6 itself, IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription (JAK-STAT), gp130, IL-6R, and downstream activated ILs, such as IL-17 and IL-6 cytokine. Currently, according to these studies and their results, IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate. JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-α and IL-6 and have shown various results in clinical trials. IL-6 induces IL-17 secretion, and IL-17 is involved in the pathogenesis of inflammatory processes. Clinical trials of anti-IL-17 drugs are currently recruiting, and anti-gp130 antibody is preclinical. However, this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2. This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.

Antisense Agents against Antibiotic-resistant Bacteria.

The dramatically increasing levels of antibiotic resistance are being seen worldwide and are a significant threat to public health. Antibiotic and drug resistance is seen in various bacterial species. Antibiotic resistance is associated with increased morbidity and mortality and increased treatment costs. Antisense-related technologies include oligonucleotides that interfere with gene transcription and expression; these oligonucleotides can help treat antibiotic-resistant bacteria. The important oligonucleotides include Peptide Nucleic Acids (PNAs), Phosphorodiamidate Morpholino Oligomers (PPMOs), and Locked Nucleic Acids (LNAs). Typically, the size of these structures (oligonucleotides) is 10 to 20 bases. PNAs, PPMOs, and LNAs are highlighted in this review as targets for genes that cause the gene to be destroyed and impede bacterial growth. These results open a new perspective for therapeutic intervention. Future studies need to examine different aspects of antisense agents, such as the safety, toxicity, and pharmacokinetic properties of antisense agents in clinical treatment.

Association of specific haplotype of tumor necrosis factor-α and interleukin-1ß polymorphisms with Helicobacter pylori infection and gastric carcinogenesis.

INTRODUCTION: The Helicobacter pylori infection and cytokine-mediated inflammatory responses play significant roles in the pathogenesis of gastric cancer (GC). This study was performed to determine the association between the risk of GC and genetic polymorphisms in interleukin (IL)-1ß and tumor necrosis factor-alpha (TNF-α). METHODS: The polymorphisms of IL-1ß and TNF-α genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 290 patients who underwent endoscopy. Infection with H. pylori was diagnosed by histological analysis, rapid urease test, and PCR of gastric biopsy samples. Quantitative real-time PCR was performed to determine the relative mRNA expression levels. RESULTS: No significant difference was detected in allele frequency and genotype of all studied polymorphisms between chronic gastritis (CG), GC and healthy individuals. IL-1ß mRNA was down-regulated in both gastritis (relative quantification (RQ)=0.447) and the GC groups (RQ=0.151). In contrast, the expression of TNF-α was up-regulated in the GC group (RQ=2.817) compared to the gastritis group (RQ=0.861). CONCLUSIONS: The studied single-nucleotide polymorphisms are not risk factors for development of CG and GC. However, H. pylori infection causes a huge increase in the TNF-α expression in GC patients.

The Association of the Phylogenetic Typing of the Klebsiella pneumoniae Isolates with Antibiotic Resistance.

Klebsiella pneumoniae complex (KPC) accounts for approximately one-third of all Gram-negative infections. Moreover, it is highly resistant and can taxonomically be distributed into KpI, KpII, and KpIII phylogroups. This study aimed to investigate the distribution of phylogenetic groups and the relationship between them and antibiotic resistance patterns. For this purpose, we collected KPC isolates from Tabriz, Iran, between 2018 and 2020. Antimicrobial susceptibility testing was performed by disk diffusion agar, and phylogenetic groups were then examined using gyrA restriction fragment length polymorphism (RFLP) and parC PCR methods. A total of 100 KPC isolates were obtained from the clinical specimens (urine, respiratory secretion, blood, wounds, and trachea). The enrolled patients included 47 men and 53 women aged from 1 to 91 years old. The highest sensitivity was found related to fosfomycin as 85%, followed by amikacin as 66%. The three phylogenetically groups by the RFLP-PCR method were found in KPC, 96% (96 isolates) as KpI, 3% (3 isolates) as KpII, and 1% (1isolate) as KpIII. The highest antibiotic resistance was observed in KpI. It was shown that a valid identification of three phylogenetic groups of KPC can be done by combining both gyrA PCR-RFLP and parC PCR. Of note, the KpI group was also observed as the dominant phylogenetic group with the highest resistance to antibiotics.

Management of antibiotic-resistant Helicobacter pylori infection: current perspective in Iran.

Helicobacter pylori is a common gastric bacterial pathogen implicated in the pathogenesis of many digestive tract disorders. H. pylori infection prevalence has been reported alarmingly in Iran. A plethora of studies have been conducted to evaluate the efficiency of first-line and second-line eradication attempts in patients diagnosed with H. pylori infections in Iran. The present study, was evaluated the efficacy of first-line and second-line therapy in H. pylori infections in Iran. We aimed to consider the literature review of the various library and electronic databases (Science Direct, PubMed, and Google Scholar) until 2020. The frequency of bacterial resistance to tetracycline, ampicillin, trimethoprim, erythromycin, ofloxacin, and metronidazolewas found to be high in Iran, while the most effective antibiotics were clarithromycin, rifampin, rifampicin, tetracycline, amoxicillin, ciprofloxacin, levofloxacin, moxifloxacin, and azithromycin. The therapeutic choice for H. pylori eradication in Iran could be quadruple therapy using two antibiotics amoxicillin and metronidazole/clarithromycin for the first-line regimen, and a combination of furazolidone plus tetracycline/amoxicillin and bismuth plus proton pump inhibitor for the second-line regimen. Due to increased antibiotic resistance in our region, empirical therapy must be replaced by more targeted treatment based on antimicrobial drug resistance profiles obtained from patients. Although we limited our investigation on the H. pylori eradication regimens in Iran, the results can be generalized to any region as long as the patterns of resistance are the same.

EXTENDED-SPECTRUM BETA-LACTAMASE PRODUCING GRAM NEGATIVE BACTERIA IN IRAN: A REVIEW.

BACKGROUND: The emergence and spread of extended spectrum ß-lactamase (ESBL)-producing Gram- negative bacteria (GNB), particularly in Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa, have increased all over the world. ESBLs are characterized by their ability to hydrolyze ß-lactams, early cephalosporins, oxyimino-thiazolyl cephalosporins, and monobactams, but not cephamycins or carbapenems. The rate of nosocomial infections caused by ESBL-producing GNB in Asia Pacific has increased and several studies have identified their prevalence in the region. The aim of this study is to review the prevalence of ESBL-producing GNB in the West Asia and the Middle East with a particular focus on Iran. MATERIALS AND METHODS: The available evidence from various studies (Microbia and clinical studies, retrieved from the PubMed, and Scopus databases) regarding the ESBL producing Gram negative bacteria in Iran were evaluated. RESULTS: In almost all parts of the country, high resistance has been observed, especially in the central part of Iran. Up to 89.8% Escherichia coli, 72.1% Klebsiella pneumonia, 84.2% Acinetobacter baumannii, and 83.8% Pseudomonas aeruginosa isolates are ESBL positive. CONCLUSION: The present study showed the increasing prevalence of ESBLs in different regions of Iran, which could be useful to strategic policy towards reducing reduce their prevalence.

Helicobacter pylori hopQ alleles (type I and II) in gastric cancer.

The Helicobacter pylori (H. pylori) outer membrane protein (HopQ) of is one of the proteins involved in bacterial adherence to gastric mucosa and has been suggested to have a role in the virulence of H. pylori. The aim of the present study was to determine the association between H. pylori virulence types I and II hopQ genotypes and patients with different gastrointestinal diseases. A polymerase chain reaction-based assay was used to determine the presence of type I and type II hopQ genes in 88 H. pylori strains isolated from H. pylori-infected patients. Of the total 88 H. pylori isolates, type I and type II hopQ alleles were detected in 52 (59.1%) and 36 (40.9%), respectively. A significant association was found between type I hopQ gene and gastric cancer [odds ratio, 2.3; 95% confidence interval (CI), 1.3-4.1] and gastric ulcers (odds ratio, 2.5; 95% CI, 1.4-4.3). A significant association was also identified between the type II hopQ gene and gastric cancer (odds ratio, 2.4; 95% CI, 1.1-3.0). The association between hopQ type I and hopQ type II genotypes and clinical status suggest that these genes may be helpful in the universal prediction of specific disease risks.

Malassezia species infection of the synovium after total knee arthroplasty surgery.

Infection is a serious complication after implantation of total knee-prostheses. However, fungal infection is rarely found in periprosthetic joints, and in most reports, the infecting organism is a Candida species. This is a case report of infection after left knee total arthroplasty caused by Malassezia species. The patient is still undergoing antifungal therapy with voriconazole and is still being followed-up. To the authors' knowledge, the present case is the first report of Malassezia species in a patient after total knee arthroplasty.

Persistent infection with metallo-beta-lactamase and extended spectrum ß-lactamase producer Morganella morganii in a patient with urinary tract infection after kidney transplantation.

Organ transplant recipients under immunosuppressive therapy have a highly increased risk of acquiring unusual opportunistic infections. Diagnosis of the etiology of infection may be difficult in clinical manifestations, which need further histological and biological investigations. Here in we report, for the 1(st) time in the Iran, a Morganella morganii isolate harboring blaVIM, blaCTX-M, and blaSHV genes after kidney transplantation with persistent urinary infections.

Pulmonary Tuberculosis Diagnosis: Where We Are?

In recent years, in spite of medical advancement, tuberculosis (TB) remains a worldwide health problem. Although many laboratory methods have been developed to expedite the diagnosis of TB, delays in diagnosis remain a major problem in the clinical practice. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many methods have been developed for direct detection, species identification, and drug susceptibility testing of TB. A good understanding of the effectiveness and practical limitations of these methods is important to improve diagnosis. This review summarizes the currently-used advances in nonmolecular and molecular diagnostics.

Viral infections in patients with acute respiratory infection in Northwest of Iran.

INTRODUCTION: Acute respiratory infection (ARI) is one of the main causes of morbidity and mortality all around the world. The aim of this study was to determine the frequency, mortality and association with clinical entities of influenza virus type A, influenza virus type B, respiratory syncytial virus (RSV), coronavirus, and adenoviruses in patients with ARI. MATERIALS AND METHODS: During September 2014 till May 2015, 143 respiratory inpatients samples for viral testing collected from central Hospital in Northwest of Iran. A real-time reverse transcription-PCR (RT-PCR) assay was done to allow in one test the detection of influenza A and B viruses. Also, RSV and adenovirus were identified by Immunochromatography test. RESULTS: Twenty-four (46%) cases were positive for influenza A, which 11 (46%) of them were subtype H1N1 and 13 (54%) cases were subtype H3N2. Also, 21 (40%) cases were positive for influenza B, 5 (10%) cases were positive for RSV, and 2 (4%) cases were positive for adenovirus. One of the patients was positive for both influenza A and adenovirus. Two of the patients were positive for both influenza A and RSV. None of the patients were positive for coronavirus. CONCLUSIONS: Our findings show the importance of influenza virus type A, influenza virus type B, RSV, and adenoviruses associated with ARI in hospitalized patient and the different epidemiological patterns of the viruses in Tabriz, Iran.

Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review.

AIM: To review previous studies (the last 6 years) about the Helicobacter pylori (H. pylori) antibiotic resistance in order to evaluate the trend in antibiotic resistance. METHODS: In this study, the PubMed, MEDLINE, Science Direct, Google Scholar and Scielo manuscripts were reviewed from 2009 to 2014. RESULTS: On the whole rates of H. pylori antibiotic resistance were 47.22% (30.5%-75.02%) for metronidazole, 19.74% (5.46%-30.8%) for clarithromycin, 18.94% (14.19%-25.28%) for levofloxacin, and 14.67% (2%-40.87%) for amoxicillin, 11.70% (0%-50%) for tetracycline, 11.5% (0%-23%) for furazolidon and 6.75% (1%-12.45%) for rifabutin. The frequency of tetracycline, metronidazole and amoxicillin resistance was higher in Africa, while clarithromycin and levofloxacin resistance was higher in North America and Asian, respectively. CONCLUSION: The most sensitive drug is rifabutin and the lowest sensitive drug is metronidazole in the world. The worldwide H. pylori antibiotic resistance to clarithromycin and levofloxacin has increased during the last 6 years. The present systematic review show alarming results and a novel plan is needed for eradication therapy of H. pylori infections.

Nosocomial oral myiasis in ICU patients: occurrence of three sequential cases.

Myiasis is the infestation of living vertebrates or humans tissues by dipterous larvae. The oral cavity is rarely affected by this infestation and the circumstances which can lead to oral myiasis include persistent mouth opening together with poor hygiene. Such infestations have been reported mainly in developing countries such as in Asia. Although rare, nosocomial myiasis must be noted carefully, especially in case of hospitalized patients. This report describes three cases of nosocomial oral myiasis in hospitalized patients in ICU (intensive care unit) in Tabriz, North West of Iran.