Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.

Purpose: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. Conclusion: In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

Genetic diversity of Mycobacterium tuberculosis isolates from northwest of Iran during COVID-19 era.

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

Comparing proteome changes involved in biofilm formation by Streptococcus mutans after exposure to sucrose and starch.

Streptococcus mutans is a main organism of tooth infections including tooth decay and periodontitis. The aim of this study was to assess the influence of sucrose and starch on biofilm formation and proteome profile of S. mutans ATCC 35668 strain. The biofilm formation was assessed by microtiter plating method. Changes in bacterial proteins after exposure to sucrose and starch carbohydrates were analyzed using matrix-assisted laser desorption/ionization mass spectrometry. The biofilm formation of S. mutans was increased to 391.76% in 1% sucrose concentration, 165.76% in 1% starch, and 264.27% in the 0.5% sucrose plus 0.5% starch in comparison to biofilm formation in the media without sugars. The abundance of glutamines, adenylate kinase, and 50S ribosomal protein L29 was increased under exposure to sucrose. Upregulation of lactate utilization protein C, 5-hydroxybenzimidazole synthase BzaA, and 50S ribosomal protein L16 was formed under starch exposure. Ribosome-recycling factor, peptide chain release factor 1, and peptide methionine sulfoxide reductase MsrB were upregulated under exposure to sucrose in combination with starch. The results demonstrated that the carbohydrates increase microbial pathogenicity. In addition, sucrose and starch carbohydrates can induce biofilm formation of S. mutans via various mechanisms such as changes in the expression of special proteins.

Gut Microbiota and Colorectal Cancer Risk Factors.

Colorectal cancer is a type of gut cancer originating either from the rectum or colon. Genetic and environmental factors, such as the gut microbiome, play pivotal roles in colorectal cancer incidence rates. Therefore, we aimed to review the risk factors of CRC comprising gut bacteriomes and their intra-interactions with each other in the context of CRC development. Gut microbiota alteration, especially bacteriome alteration as the dominant player, seems to be the common feature amongst all risk factors. Although it is not quite obvious whether these alterations are the causes or the consequences of the tumorigenesis risk factors, they are common and almost universal among CRC-affected individuals. In addition, bacterial genotoxicity, biofilm formation, oxidative stress, bacterial metabolome, and dysbiosis are assessed in CRC development. The present study suggests that gut microbial alterations could be the key intermediate, as a cause or a consequence, between most risk factors of CRC and the way they promote or contribute to CRC development.

Acute hepatitis (Non Hepa A-E) of unknown origin among pediatrics.

Several clusters and individual cases of acute hepatitis have been reported in the US, Europe and recently in Asia and Central America since October 2021. A laboratory investigation of the common viral hepatitis agents (HAV, HBV, HCV, HDV and HEV) yielded negative results prompting the use of the term "acute non HepA-E hepatitis" to describe this condition. As of 24 June of 2022, WHO have reported 920 probable cases of severe acute hepatitis of unknown origin among pediatrics in 33 countries in five WHO regions. Since the previous reports on 27 May 2022, 270 new probable cases have been increased, including from four new countries, some of whom were also found to be positive for SARS-CoV-2. All the patients showed symptoms such as vomiting, diarrhea, jaundice, and abdominal pain. The patients' liver enzymes were remarkably increased. No connection with SARS-CoV-2 or its vaccine has been found so far. However, the suspected cause is adenovirus, including its genomic variations, because its pathogenesis and laboratory investigations have been positively linked. Until further evidence emerges, hygiene precautions could be helpful to prevent its spread.

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.

Gut Microbiota and Human Body Interactions; Its Impact on Health: A Review.

Gut microbiota (GM), as an organ of the human body, has a particular and autonomous function that is related to it. This review aims to investigate human intestinal and gut microbiota interaction and its impact on health. As a creation referable database about this dynamic and complex organ, several comprehensive projects are implemented by using culture-dependent (culturomics), culture- independent methods (e.g., metagenomics, mathematics model), and Gnotobiological together. This study was done by searching PubMed, Scopus and Google scholar database in the gut, health microbiota, and interaction keywords. The first acquired microbiota during pregnancy or childbirth is colonized in the gut by using specific and non-specific mechanisms. Its structure and shape reach relative stability with selection pressure along with host development until adulthood and keeps its resilience against external or internal variables depending on the host's genetics and negative feedback. According to research, individuals have 2 functional group microbiotas, including the core (common between vast majorities human) and flexible (transient population) microbiome. The most important role of the GM in the human body can be summarized in three basic landscapes: metabolic, immune system, and gut-brain axis interaction. So, the loss of microbial population balance will lead to disorder and disease.

Current Advances in DNA Methylation Analysis Methods.

DNA methylation is one of the epigenetic changes, which plays a major role in regulating gene expression and, thus, many biological processes and diseases. There are several methods for determining the methylation of DNA samples. However, selecting the most appropriate method for answering biological questions appears to be a challenging task. The primary methods in DNA methylation focused on identifying the state of methylation of the examined genes and determining the total amount of 5-methyl cytosine. The study of DNA methylation at a large scale of genomic levels became possible following the use of microarray hybridization technology. The new generation of sequencing platforms now allows the preparation of genomic maps of DNA methylation at the single-open level. This review includes the majority of methods available to date, introducing the most widely used methods, the bisulfite treatment, biological identification, and chemical cutting along with their advantages and disadvantages. The techniques are then scrutinized according to their robustness, high throughput capabilities, and cost.

New Insight for the Prognosis of CCHF: Clinical, Laboratory and Sonography Findings.

BACKGROUND: Crimean Congo Hemorrhagic Fever (CCHF) is an acute and fatal disease with various clinical and paraclinical characteristics. INTRODUCTION: In this article, we report data on confirmed CCHF cases from Iran and describe the association between studying factors and outcomes of the disease. METHODS: In the study design, we evaluated demographic characteristics, clinical, laboratory and sonographic findings of 160 CCHF confirmed cases during 2003 and 2012 in Zabol (A city in Sistan and Baluchestan province of Iran). The association between these factors and the fatal outcome were evaluated by regression analysis. RESULTS: The disease had a fatal outcome in 7 (4.4%) patients. Females had more severe symptoms and higher odds for death (odds ratio11.57, p=0.005). Leukocytosis (p<0.001), PT (p<0.001) and PTT (p=0.008) elongation, AST (p=0.010) and ALT (p>0.001) elevation were significantly associated with fatal outcome. CNS related symptoms (odds ratio 5.9, p=0.027) in clinical examination and ascites (odds ratio 38.4, p=0.012) and liquid in the pelvic cavity (odds ratio 24.2, p=0.004) were also identified as risk factors of death in this study. CONCLUSION: Our data suggest that in addition to clinical and laboratory findings practitioners consider sonography for CCHF prognosis.

Study presence of COVID-19 (SARS-CoV-2) in the sweat of patients infected with Covid-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, which started in Wuhan, Chin, has now become a public health challenge in most countries around the world. Proper preventive measures are necessary to prevent the spread of the virus to help control the pandemic. Because, SARS-CoV-2 is new, its transmission route has not been fully understood. In this study, we aimed to investigate the presence of SARS-CoV-2 in the sweat secretion of COVID-19 patients. Sweat specimens of 25 COVID- 19 patients were collected and tested for SARS-CoV-2 RNA by Real-time Polymerase Chain Reaction (RT-PCR) method. After RNA extraction and cDNA amplification, all samples were examined for the presence of ORF-1ab and N genes related to COVID-19. Results annotated by Realtime PCR machines software based on Dynamic algorithm. The results of this study showed the absence of SARS-CoV-2 in the sweat samples taken from the foreheads of infected people. Therefore, it can be concluded that the sweat of patients with COVID- 19 cannot transmit SARS-CoV-2. However they can be easily contaminated with other body liquids.

Proteomic Applications in Antimicrobial Resistance and Clinical Microbiology Studies.

Sequences of the genomes of all-important bacterial pathogens of man, plants, and animals have been completed. Still, it is not enough to achieve complete information of all the mechanisms controlling the biological processes of an organism. Along with all advances in different proteomics technologies, proteomics has completed our knowledge of biological processes all around the world. Proteomics is a valuable technique to explain the complement of proteins in any organism. One of the fields that has been notably benefited from other systems approaches is bacterial pathogenesis. An emerging field is to use proteomics to examine the infectious agents in terms of, among many, the response the host and pathogen to the infection process, which leads to a deeper knowledge of the mechanisms of bacterial virulence. This trend also enables us to identify quantitative measurements for proteins extracted from microorganisms. The present review study is an attempt to summarize a variety of different proteomic techniques and advances. The significant applications in bacterial pathogenesis studies are also covered. Moreover, the areas where proteomics may lead the future studies are introduced.

Chitosan biomaterials application in dentistry.

Chitosan is a natural biopolymer derived from deacetylation of chitin and it has been investigated with interdisciplinary approaches for multitude applications. Chitosan biomaterials possess unique properties such as biocompatibility, biodegradability, non-toxicity, muco-adhesion and a wide range of antibacterial and antifungal activity. Additionally, chitosan is the only cationic polysaccharide in nature and can be chemically modified to derivatives, based on the aim of function and application. The distinctive properties of chitosan and its derivatives have aroused interest in pharmaceutical industries and biomedical fields worldwide. This review discusses the crucial role of chitosan in production of bio-dental materials and accentuates its current profitable utilizations in oral drug delivery system, bone tissue engineering for treatment of periodontitis and dentin-pulp regeneration. Chemical modifications and incorporation of diverse bioactive molecules in order to improve the mechanical and biological characteristics of chitosan have also been discussed.

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.

Antisense peptide nucleic acids againstftsZ andefaA genes inhibit growth and biofilm formation of Enterococcusfaecalis.

Enterococcus faecalis is one of the important causes of nosocomial infections. Nowadays, increasing prevalence of antibiotic-resistant bacteria and slow progress in recognizing new antimicrobial agents has limited the efficiency of conventional antibiotics, which cause to find novel strategies to overcome bacteria. Therefore, in this study, we aimed to assess the role of efaA gene in the biofilm formation and the role of ftsZ gene in the controlling of bacterial growth by the anti-sense PNAs(Peptide Nucleic Acid).E. faecalis ATCC® 29212™was used for the study of PNAs designed to targeting the start codon section of the ftsZ andefaA genes. PNA attachment to RNA was confirmed by blotting. Electroporation technique was used for the intracellular transfer of anti-ftsZ PNAs. The spot-plating method was used to the assessment of alteration in bacterial growth. Biofilm formation assay and real-time PCR were used for detection of biofilm inhibitory effect of cell penetrating peptide (CPP) conjugated to anti-efaA PNAs.ByftsZ PNAs treatment, no growth was seen from the strain in agar by a spot plating method and the inhibition zone of anti-ftsZ PNAs was not seen. PNAs against the efaA gene decreased by 95% the expression of the efaA gene and biofilm formation. In addition, the(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) MTT assay showed no toxicity on MCF7 cells for both of anti-ftsZand anti-efaA PNAs.This study used new genetic and molecular tools to inhibit pathogenicity and infection by E. faecalis. In this study, we suggested that efaA gene plays a critical role in the biofilm formation and anti-efaA PNAs could decrease the formation of biofilm, as well as, anti-ftsZ PNAs could eliminate bacterial growth.

Inhibitory effect of isolated Lactobacillus from oral cavity against bacterial Pathogens and its effect on health promotion / Efecto inhibidor de Lactobacillus aislado de la cavidad oral contra patógenos bacterianos y su efecto en la promoción de la salud

Aims: To determine the inhibitory effect of oral Lactobacillus against bacterial pathogens and investigate correlation between presence of Lactobacillus strains and health promotion. Method: One hundred saliva samples were collected from oral cavity of domestic dairy consumers and were investigated for the isolation and identification of Lactobacillus strain by conventional culture and sequencing of 16SrRNA. Furthermore, well diffusion assay was performed to determination of antibacterial activity of Lactobacillus strains against bacterial pathogens including Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis and Enterococcus faecium. Finally, association between health condition and isolation of Lactobacillus were investigated and obtained data using questionary form were analysed by chi-square test. Results: Thirty Lactobacillus strains recovered from 100 hundred saliva samples. The most common isolated strain was L. gasseri (n=18) and followed by L. vaginalis (n=3) and L. salivarius (n=3). All Lactobacillus strains demonstrated antibacterial activity against at least one of the investigated pathogens. However, the strongest results were obtained by L. vaginalis against K. pneumonia. The correlation between the presence of thirty Lactobacillus strains and health promotion not found. However, only L. gasseri species has significant positive impact on health in their hosts (P < 0.05). Conclusion: Only some Lactobacillus species have a positive impact on health promotion. Despite of weak activity against the investigated pathogens, L. gasseri has a positive impact on the mental problem (intense anger and depression) of their hosts

Objetivos: Determinar el efecto inhibidor del Lactobacillus aislado de la cavidad oral contra patógenos bacterianos e investigar la correlación entre la presencia de cepas de Lactobacillus y la promoción de la salud. Método: se recolectaron cien muestras de saliva de la cavidad oral de consumidores de productos lácteos y se investigó el aislamiento e identificación de la cepa de Lactobacillus mediante cultivo convencional y secuenciación de 16SrRNA. Además, se realizó un ensayo de difusión en pocillos para determinar la actividad antibacteriana de las cepas de Lactobacillus contra patógenos bacterianos que incluyen Salmonella typhimurium, Klebsiella pneumoniae, Shigella sonnei, Shigella dysenteriae, Enterococcus faecalis y Enterococcus faecium. Finalmente, se investigó la asociación entre el estado de salud y el aislamiento de Lactobacillus y se obtuvieron los datos utilizando el cuestionario mediante la prueba de chi-cuadrado. Resultados: Se aislaron treinta cepas de Lactobacillus de 100 muestras de saliva. La cepa aislada más común fue L. gasseri (n = 18), seguida por L. vaginalis (n = 3) y L. salivarius (n = 3). Todas las cepas de Lactobacillus demostraron actividad antibacteriana contra al menos uno de los patógenos investigados Sin embargo, los resultados más fuertes fueron obtenidos por L. vaginalis contra K. pneumonia. No se encontraron correlación entre la presencia de algunas de las treinta cepas de Lactobacillus y la promoción de la salud. Sin embargo, solo la especie L. gasseri tuvo un impacto positivo significativo en la salud de sus hospedadores (P <0,05). Conclusión: solo algunas especies de Lactobacillus tienen un impacto positivo en la promoción de la salud. A pesar de la actividad débil contra los patógenos investigados, L. gasseri tiene un impacto positivo en el problema mental (ira intensa y depresión) de sus huéspedes

Double strain probiotic effect on Helicobacter pylori infection treatment: A double-blinded randomized controlled trial.

BACKGROUND: A decreased rate of successful helicobacter pylori (H.pylori) infection treatment has revealed serious demand for more effective regimens to eradicate infection. Therefore, probiotics have recently been considered to increase the rate of antibiotic regimens efficacy in H. pylori infections. In current randomized controlled trial, we evaluated the effect of double strain probiotic combination with standard triple therapy (STT), in the eradication rate of H. pylori infection. METHODS: In current randomized placebo-control study, all patients (176 subjects) underwent the STT for 10 days. However, the study group received triple therapy for the eradication of H. pylori with supplement of Lactobacillus probiotic for 4 weeks and placebo was administered to control group, as well. Adverse effects of the antibiotic regimen were recorded for all patients. Six weeks after the cessation of probiotic intake, all patients underwent H. Pylori with fecal antigen of test, followed by a recurrence evaluation six months later. RESULTS: There was no significant difference in demographic data and presenting symptoms between the study groups. The eradication rate of H. pylori infection was significantly higher in probiotic group (78.4%), compared to that of placebo group (64.8%) (P=0.033). In addition, adverse events were significantly less prevalent in patients that received probiotic (P=0.047). Nonetheless, there was no significant difference in terms of infection recurrence during a 6-month follow-up (P=0.07). CONCLUSION: Double strain probiotic in combination with STT increased the eradication rate of H. pylori infection, while the adverse events due to antibiotic therapy decreased.