MicroRNAs and JAK/STAT3 signaling: A new promising therapeutic axis in blood cancers.

Blood disorders include a wide spectrum of blood-associated malignancies resulting from inherited or acquired defects. The ineffectiveness of existing therapies against blood disorders arises from different reasons, one of which is drug resistance, so different types of leukemia may show different responses to treatment. Leukemia occurs for a variety of genetic and acquired reasons, leading to uncontrolled proliferation in one or more cell lines. Regarding the genetic defects, oncogene signal transducer and activator of transcription (STAT) family transcription factor, especially STAT3, play an essential role in hematological disorders onset and progress upon mutations, dysfunction, or hyperactivity. Besides, microRNAs, as biological molecules, has been shown to play a dual role in either tumorigenesis and tumor suppression in various cancers. Besides, a strong association between STAT3 and miRNA has been reported. For example, miRNAs can regulate STAT3 via targeting its upstream mediators such as IL6, IL9, and JAKs or directly binding to the STAT3 gene. On the other hand, STAT3 can regulate miRNAs. In this review study, we aimed to determine the role of either microRNAs and STAT3 along with their effect on one another's activity and function in hematological malignancies.

Cell cycle involvement in cancer therapy; WEE1 kinase, a potential target as therapeutic strategy.

Mitosis is the process of cell division and is regulated by checkpoints in the cell cycle. G1-S, S, and G2-M are the three main checkpoints that prevent initiation of the next phase of the cell cycle phase until previous phase has completed. DNA damage leads to activation of the G2-M checkpoint, which can trigger a downstream DNA damage response (DDR) pathway to induce cell cycle arrest while the damage is repaired. If the DNA damage cannot be repaired, the replication stress response (RSR) pathway finally leads to cell death by apoptosis, in this case called mitotic catastrophe. Many cancer treatments (chemotherapy and radiotherapy) cause DNA damages based on SSBs (single strand breaks) or DSBs (double strand breaks), which cause cell death through mitotic catastrophe. However, damaged cells can activate WEE1 kinase (as a part of the DDR and RSR pathways), which prevents apoptosis and cell death by inducing cell cycle arrest at G2 phase. Therefore, inhibition of WEE1 kinase could sensitize cancer cells to chemotherapeutic drugs. This review focuses on the role of WEE1 kinase (as a biological macromolecule which has a molecular mass of 96 kDa) in the cell cycle, and its interactions with other regulatory pathways. In addition, we discuss the potential of WEE1 inhibition as a new therapeutic approach in the treatment of various cancers, such as melanoma, breast cancer, pancreatic cancer, cervical cancer, etc.

Bacterial Proteomics and its Application in Pathogenesis Studies.

Bacteria build their structures by implementing several macromolecules such as proteins, polysaccharides, phospholipids, and nucleic acids, which preserve their lives and play an essential role in their pathogenesis. There are two genomic and proteomic methods to study various macromolecules of bacteria, which are complementary methods and provide comprehensive information. Proteomic approaches are used to identify proteins and their cell applications. Furthermore, macromolecules are utilized to study bacteria's structures and functions. These proteinbased methods provide comprehensive information about the cells, such as the external structures, internal compositions, post-translational modifications, and mechanisms of particular actions, including biofilm formation, antibiotic resistance, and adaptation to the environment, promoting bacterial pathogenesis. These methods use various devices such as MALDI-TOF MS, LC-MS, and two-dimensional electrophoresis, which are valuable tools for studying different structural and functional proteins of the bacteria and their mechanisms of pathogenesis, causing rapid, easy, and accurate diagnosis of the infections.

Corrigendum to "Antibacterial Properties of Aloe vera on Intracanal Medicaments against Enterococcus faecalis Biofilm at Different Stages of Development".

[This corrects the article DOI: 10.1155/2020/8855277.].

A Comprehensive Study on the Antimicrobial Properties of Resveratrol as an Alternative Therapy.

Resveratrol is a polyphenolic antioxidant whose possible health benefits include anticarcinogenic, antiaging, and antimicrobial properties that have gained significant attention. The compound is well accepted by individuals and has been commonly used as a nutraceutical in recent decades. Its widespread usage makes it essential to study as a single agent as well as in combination with traditional prescription antibiotics as regards to antimicrobial properties. Resveratrol demonstrates the action of antimicrobials against a remarkable bacterial diversity, viruses, and fungus. This report explains resveratrol as an all-natural antimicrobial representative. It may modify the bacterial virulence qualities resulting in decreased toxic substance production, biofilm inhibition, motility reduction, and quorum sensing disturbance. Moreover, in conjunction with standard antibiotics, resveratrol improves aminoglycoside efficacy versus Staphylococcus aureus, while it antagonizes the deadly function of fluoroquinolones against S. aureus and also Escherichia coli. The present study aimed to thoroughly review and study the antimicrobial potency of resveratrol, expected to help researchers pave the way for solving antimicrobial resistance.

The Role of Janus Kinase/STAT3 Pathway in Hematologic Malignancies With an Emphasis on Epigenetics.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway has been known to be involved in cell growth, cellular differentiation processes development, immune cell survival, and hematopoietic system development. As an important member of the STAT family, STAT3 participates as a major regulator of cellular development and differentiation-associated genes. Prolonged and persistent STAT3 activation has been reported to be associated with tumor cell survival, proliferation, and invasion. Therefore, the JAK-STAT pathway can be a potential target for drug development to treat human cancers, e.g., hematological malignancies. Although STAT3 upregulation has been reported in hematopoietic cancers, protein-level STAT3 mutations have also been reported in invasive leukemias/lymphomas. The principal role of STAT3 in tumor cell growth clarifies the importance of approaches that downregulate this molecule. Epigenetic modifications are a major regulatory mechanism controlling the activity and function of STAT3. So far, several compounds have been developed to target epigenetic regulatory enzymes in blood malignancies. Here, we discuss the current knowledge about STAT3 abnormalities and carcinogenic functions in hematopoietic cancers, novel STAT3 inhibitors, the role of epigenetic mechanisms in STAT3 regulation, and targeted therapies, by focusing on STAT3-related epigenetic modifications.

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.

Alteration of Liver Biomarkers in Patients with SARS-CoV-2 (COVID-19).

INTRODUCTION: Coronavirus disease 2019 (COVID-19) emerged in China and spread worldwide. In this study, we assessed the characteristics of markers of the liver in patients with COVID-19 to provide new insights in improving clinical treatment. PATIENTS AND METHODS: We recruited 279 patients who confirmed COVID-19 and the data of liver biomarkers and complete blood count of patients were defined as the day onset when the patients admitted to the hospital. RESULTS: The average of LDH value was 621.29 U/L in all patients with COVID-19, and CPK was 286.90 U/L. The average AST was 44.03 U/L in all patients, and ALT was 31.14 U/L. The AST/ALT ratio was 1.64 in all patients. The measurement of CRP was increased by 79.93% in all patients. Average ALT and AST values of patients with elevated ALT were significantly increased in comparison to patients with normal ALT (P-value = 0.001), while AST/ALT ratio was significantly decreased compared to patients with normal ALT (P-value= 0.014). In addition, the average LDH of patients with elevated ALT was significantly increased compared to patients with normal ALT (P-value = 0.014). CONCLUSION: Hepatic injury and abnormal liver enzymes related to COVID-19 infection is an acute non-specific inflammation alteration.

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.

Study of combining virtual screening and antiviral treatments of the Sars-CoV-2 (Covid-19).

The recent epidemic outbreak of a novel human coronavirus called SARS-CoV-2 and causing the respiratory tract disease COVID-19 has reached worldwide resonance and a global effort is being undertaken to characterize the molecular features and evolutionary origins of this virus. Therefore, rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Additionally, general treatments, coronavirus-specific treatments, and antiviral treatments useful in fighting COVID-19 are addressed. This review sets out to shed light on the SARS-CoV-2 and host receptor recognition, a crucial factor for successful virus infection and taking immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein of SARS-CoV-2. A variety of improved or new approaches also have been developed. It is anticipated that this will assist researchers and clinicians in developing better techniques for timely and effective detection of coronavirus infection. Moreover, the genomic sequence of the virus responsible for COVID-19, as well as the experimentally determined three-dimensional structure of the Main protease (Mpro) is available. The reported structure of the target Mpro was described in this review to identify potential drugs for COVID-19 using virtual high throughput screening.

Clinical manifestation, diagnosis, prevention and control of SARS-CoV-2 (COVID-19) during the outbreak period.

The novel coronavirus SARS-CoV-2 (Covid-19), spreading from Wuhan, China, is one of the causes of respiratory infections that can spread to other people through respiratory particles, and can cause symptoms such as fever, dry cough, shortness of breath, anorexia, fatigue and sore throat in infected patients. This review summarizes current strategies on the diagnosis. Additionally, treatments, infection prevention and control of the SARS-CoV-2 are addressed. In addition to the respiratory system, this virus can infect the digestive system, the urinary system and the haematological system, which causes to observe the virus in the stool, urine and blood samples in addition to throat sample. The SARS-CoV-2 causes changes in blood cells and factors and makes lung abnormalities in patients, which can be detected by serological, molecular, and radiological techniques by detecting these changes and injuries. Radiological and serological methods are the most preferred among the other methods and the radiological method is the most preferred one which can diagnose the infection quickly and accurately with fewer false-negatives, that can be effective in protecting the patient's life by initiating treatment and preventing the transmission of infection to other people.

Antibacterial Properties of Aloe vera on Intracanal Medicaments against Enterococcus faecalis Biofilm at Different Stages of Development.

BACKGROUND: Use of herbal compounds as an intracanal medicament in the field of endodontics has become noteworthy, one of which is the Aloe vera compound whose antibacterial effect has already been proven in the planktonic form of Enterococcus faecalis. The purpose of this study is to evaluate the antibacterial effect of Aloe vera on E. faecalis biofilms at the 4th and 6th week of development. MATERIALS AND METHODS: 130 single root canal teeth without anomalies and caries were used. They were divided into two groups of 65 teeth for four and six weeks of biofilm production. Five samples of each group were examined for confirmation of biofilm formation under an electron microscope. Study groups were investigated with an antimicrobial agent as an intracanal medicament including 20 samples treated with Aloe vera, calcium hydroxide, and phosphate-buffered saline, and biofilm and survival of pathogens were investigated. Dentin chip suspensions were used for colony-forming unit (CFU) counting to estimate remaining E. faecalis counts. RESULTS: The CFU mean in the 4th week subgroup in Aloe vera, phosphate-buffered saline, and calcium hydroxide was 0, 69166.66 ± 31688.58, and 25000 ± 30822.07, and in the 6th week, it was 136.36 ± 323.33, 95000 ± 12247.44, and 27501.66 ± 36570.34, respectively, which showed a significant difference between the used materials (p < 0.05). CONCLUSION: Aloe vera, in contrast to calcium hydroxide, eliminated 4th and 6th week biofilms and showed remarkable antibacterial properties against E. faecalis biofilm. These results support potency of Aloe vera to use as a natural antimicrobial material in the intracanal medicament.

Microbial balance in the intestinal microbiota and its association with diabetes, obesity and allergic disease.

Recent studies have been considered to symbiotic interactions of the human gastrointestinal microbiota and human lifestyle-related disorders. The human gastrointestinal microbiota continuously stimulates the immune system against opportunistic and pathogen bacteria from infancy. Changes in gastrointestinal microbiota have been associated with numbers of human diseases such as allergic diseases, autoimmune encephalitis, atherosclerosis, colorectal cancer, obesity, diabetes etc. In this review article, we evaluate studies on the roles of human gastrointestinal microbiota and interference pathogenicity in allergic diseases, obesity, and diabetes. Several studies indicated association between allergic diseases and changes in bacterial balance such as increased of Clostridium spp., some species of Bifidobacterium spp., or decreased of Bacteroidetes phylum and some species of Bifiobacterium spp. and production of specific short-chain fatty acids due to food type, delivery modes of infant, infant evolvement environment and time of getting bacteria at an early-life age. In addition, obesity and diabetes are associated with food type, production of short chain fatty acids undergo fermentation of the intestinal microbiota, metabolic endotoxemia, endocannabinoid system and properties of the immune system. Well-characterized underlying mechanisms may provide novel strategies for using prebiotic and probiotic to prevent and treatment of allergic diseases, obesity, diabetes, and other lifestyle-related disorders.

Synergistic effect of persica mouthwash and Iranian ethanolic extract of propolis against biofilm formation of oral pathogens (in vitro study) / Efecto sinérgico del enjuague bucal persica y del extracto etanólico iraní de propolis contra la formación de biofilm de patógenos orales (estudio in vitro)

Aims: Several pathogens are responsible for oral diseases and dental plaque and their main mechanism is biofilm production. Natural products are point of interest for controlling these infections. persica mouthrinse, propolis and honey are some of these products with considerable antibacterial effects. In this study, we aimed to investigate synergy effect of these products on their antibiofilm and antibacterial effect. Material and Methods: Minimal Inhibitory effect and Minimial Biofilm inhibitory concentration of persica mouthrinse, propolis, honey solely and in combination was calculated against Streptococcus mutans ATCC35668, methicillin-resistant Staphylococcus aureus ATCC 33591, Staphylococcus aureus ATCC 29213, Staphylococcus epidermidis, Enterococcus faecalis ATCC 29212 , Escherichia coli ATCC 25922. Results: Combination of persica and propolis had a better profile in biofilm's inhibition than honey. None of herbal combinations had synergistic effect against studied bacteria; MIC of the persica mouth had the best effect against Streptococcus mutans, which causes caries. Conclusions: There was no synergistic effect of persica and propolis and the best antimicrobial effect was observed on subminimum inhibitory concentration of persica mouthwash. Findings of the present study suggest use of other combination than honey, propolis and persica for improving antimicrobial activity of these components

Objetivos: Varios patógenos son responsables de enfermedades orales y la placa dental y su mecanismo principal es la producción de biofilm. Los productos naturales son puntos de interés para controlar estas infecciones. persica mouthrinse, propolis y miel son algunos de estos productos con considerables efec­tos antibacterianos. En este estudio, se buscó investigar el efecto sinérgico de estos productos sobre su antibiótico y efecto antibacteriano. Material y Métodos: Se calculó el efecto inhibidor mínimo y la concentración inhibitoria mínima de bi­ofilm de enjuague bucal de persica, propóleos, miel únicamente y en combinación, contra Staphylococcus aureus ATCC 29213, S. epidermidis, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922. Resultados: La combinación de persica y propóleo tuvo un mejor perfil en la inhibición de la biopelícula que la miel. Ninguna de las combinaciones de hierbas tuvo efecto sinérgico contra las bacterias estudia­das; La Se calculó el efecto inhibidor mínimo de la boca de la persica tuvo el mejor efecto contra Strepto­coccus mutans, que causa la caries. Conclusiones: No hubo efectos sinérgicos de la persica y el propóleo y se observó el mejor efecto an­timicrobiano en la concentración mínima inhibitoria de enjuague bucal de persica. Los hallazgos del presente estudio sugieren el uso de otra combinación que la miel, el propóleo y la persica para mejorar la actividad antimicrobiana de estos componentes

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.