Effects of therapeutic probiotics on modulation of microRNAs.

Probiotics are beneficial bacteria that exist within the human gut, and which are also present in different food products and supplements. They have been investigated for some decades, due to their potential beneficial impact on human health. Probiotics compete with pathogenic microorganisms for adhesion sites within the gut, to antagonize them or to regulate the host immune response resulting in preventive and therapeutic effects. Therefore, dysbiosis, defined as an impairment in the gut microbiota, could play a role in various pathological conditions, such as lactose intolerance, gastrointestinal and urogenital infections, various cancers, cystic fibrosis, allergies, inflammatory bowel disease, and can also be caused by antibiotic side effects. MicroRNAs (miRNAs) are short non-coding RNAs that can regulate gene expression in a post-transcriptional manner. miRNAs are biochemical biomarkers that play an important role in almost all cellular signaling pathways in many healthy and disease states. For the first time, the present review summarizes current evidence suggesting that the beneficial properties of probiotics could be explained based on the pivotal role of miRNAs. Video Abstract.

Therapeutic effect of curcumin in gastrointestinal cancers: A comprehensive review.

Gastrointestinal (GI) cancers with a high global prevalence are a leading cause of morbidity and mortality. Accordingly, there is a great need to develop efficient therapeutic approaches. Curcumin, a naturally occurring agent, is a promising compound with documented safety and anticancer activities. Recent studies have demonstrated the activity of curcumin in the prevention and treatment of different cancers. According to systematic studies on curcumin use in various diseases, it can be particularly effective in GI cancers because of its high bioavailability in the gastrointestinal tract. Nevertheless, the clinical applications of curcumin are largely limited because of its low solubility and low chemical stability in water. These limitations may be addressed by the use of relevant analogues or novel delivery systems. Herein, we summarize the pharmacological effects of curcumin against GI cancers. Moreover, we highlight the application of curcumin's analogues and novel delivery systems in the treatment of GI cancers.

Role of exosomes in malignant glioma: microRNAs and proteins in pathogenesis and diagnosis.

Malignant gliomas are the most common and deadly type of central nervous system tumors. Despite some advances in treatment, the mean survival time remains only about 1.25 years. Even after surgery, radiotherapy and chemotherapy, gliomas still have a poor prognosis. Exosomes are the most common type of extracellular vesicles with a size range of 30 to 100 nm, and can act as carriers of proteins, RNAs, and other bioactive molecules. Exosomes play a key role in tumorigenesis and resistance to chemotherapy or radiation. Recent evidence has shown that exosomal microRNAs (miRNAs) can be detected in the extracellular microenvironment, and can also be transferred from cell to cell via exosome secretion and uptake. Therefore, many recent studies have focused on exosomal miRNAs as important cellular regulators in various physiological and pathological conditions. A variety of exosomal miRNAs have been implicated in the initiation and progression of gliomas, by activating and/or inhibiting different signaling pathways. Exosomal miRNAs could be used as therapeutic agents to modulate different biological processes in gliomas. Exosomal miRNAs derived from mesenchymal stem cells could also be used for glioma treatment. The present review summarizes the exosomal miRNAs that have been implicated in the pathogenesis, diagnosis and treatment of gliomas. Moreover, exosomal proteins could also be involved in glioma pathogenesis. Exosomal miRNAs and proteins could also serve as non-invasive biomarkers for prognosis and disease monitoring. Video Abstract.

Streptococcal bacterial components in cancer therapy.

The incidence rate of cancer is steadily increasing all around the world, and there is an urgent need to develop novel and more effective treatment strategies. Recently, bacterial therapy has been investigated as a new approach to target cancer, and is becoming a serious option. Streptococcus strains are among the most common and well-studied virulent bacteria that cause a variety of human infections. Everyone has experienced a sore throat during their lifetime, or has been asymptomatically colonized by streptococci. The ability of Streptococcus bacteria to fight cancer was discovered more than 100 years ago, and over the years has undergone clinical trials, but the mechanism is not yet completely understood. Recently, several animal models and human clinical trials have been reported. Streptococcal strains can have an intrinsic anti-tumor activity, or can activate the host immune system to fight the tumor. Bacteria can selectively accumulate and proliferate in the hypoxic regions of solid tumors. Moreover, the bacteria can be genetically engineered to secrete toxins or enzymes that can specifically attack the tumors.

New epigenetic players in stroke pathogenesis: From non-coding RNAs to exosomal non-coding RNAs.

Non-coding RNAs (ncRNAs) have critical role in the pathophysiology as well as recovery after ischemic stroke. ncRNAs, particularly microRNAs, and the long non-coding RNAs (lncRNAs) are critical for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. Moreover, exosomes have been considered as nanocarriers capable of transferring various cargos, such as lncRNAs and miRNAs to recipient cells, with prominent inter-cellular roles in the mediation of neuro-restorative events following strokes and neural injuries. In this review, we summarize the pathogenic role of ncRNAs and exosomal ncRNAs in the stroke.

Coumarins and Gastrointestinal Cancer: A New Therapeutic Option?

Cancers of the gastrointestinal (GI) tract are often life-threatening malignancies, which can be a severe burden to the health care system. Globally, the mortality rate from gastrointestinal tumors has been increasing due to the lack of adequate diagnostic, prognostic, and therapeutic measures to combat these tumors. Coumarin is a natural product with remarkable antitumor activity, and it is widely found in various natural plant sources. Researchers have explored coumarin and its related derivatives to investigate their antitumor activity, and the potential molecular mechanisms involved. These mechanisms include hormone antagonists, alkylating agents, inhibitors of angiogenesis, inhibitors of topoisomerase, inducers of apoptosis, agents with antimitotic activity, telomerase inhibitors, inhibitors of human carbonic anhydrase, as well as other potential mechanisms. Consequently, drug design and discovery scientists and medicinal chemists have collaborated to identify new coumarin-related agents in order to produce more effective antitumor drugs against GI cancers. Herein, we summarize the therapeutic effects of coumarin and its derivatives against GI cancer.

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches.

Over the years, conventional cancer treatments, such as chemotherapy with only a limited specificity for tumors, have undergone significant improvement. Moreover, newer therapies such as immunotherapy have undergone a revolution to stimulate the innate as well as adaptive immune responses against the tumor. However, it has been found that tumors can be selectively colonized by certain bacteria, where they can proliferate, and exert direct oncolytic effects as well as stimulating the immune system. Bacterial-mediated cancer therapy (BMCT) is now one example of a hot topic in the antitumor field. Salmonella typhimurium is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. This species has been designed and engineered in order to be used in cancer-targeted therapeutics. S. typhimurium can be used in combination with other treatments such as chemotherapy or radiotherapy for synergistic modification of the tumor microenvironment. Considerable benefits have been shown by using engineered attenuated strains for the diagnosis and treatment of tumors. Some of these treatment approaches have received FDA approval for early-phase clinical trials. This review summarizes the use of Salmonella bacteria for cancer therapy, which could pave the way towards routine clinical application. The benefits of this therapy include an automatic self-targeting ability, and the possibility of genetic manipulation to produce newly engineered attenuated strains. Nevertheless, Salmonella-mediated anticancer therapy has not yet been clinically established, and requires more research before its use in cancer treatment.

Meta-Analysis of Biofilm Formation, Antibiotic Resistance Pattern, and Biofilm-Related Genes in Pseudomonas aeruginosa Isolated from Clinical Samples.

Resistant microorganisms such as Pseudomonas aeruginosa grow by developing biofilms in hospitals. We aimed to investigate the biofilm formation and the frequencies of biofilm-related genes and their associations with antibiotic resistance pattern in P. aeruginosa isolated from Iranians' clinical samples. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a systematic literature search in scientific databases using medical subject heading terms, including "Pseudomonas aeruginosa," "biofilm formation," "biofilm-related genes," "antibiotic resistance," and "prevalence," to obtain related articles published from 1st January, 2000, to 30th March, 2019. The studies reporting the prevalence of biofilm formation, the frequencies of biofilm-related genes, and the antibiotic resistance pattern in P. aeruginosa retrieved from Iranian patients were included. Meta-analysis was performed using the Comprehensive Meta-Analysis software. The pooled rate of biofilm formation was calculated as 86.5% (95% confidence interval [CI]: 79-91.6). The combined frequencies of strong, moderate, and weak biofilms were 51% (95% CI: 37.4-64.4), 29.2% (95% CI: 20.9-39.1), and 25.4% (95% CI: 11.5-47.2), respectively. The pooled prevalence of laslR, algD, algU, ppyR, and pelF genes were 93.6% (95% CI: 88.1-96.6), 91.4% (95% CI: 80.8-96.4), 89.3% (95% CI: 85.2-92.3), 98.7% (95% CI: 96.5-99.6), and 93% (95% CI: 82.7-97.3), respectively. The highest combined antibiotic resistance rates of P. aeruginosa isolates were against piperacillin/tazobactam (90%). This study showed that biofilm formation was higher in multidrug-resistant (MDR) P. aeruginosa than non-MDRs. A significant correlation was observed between biofilm formation and antibiotic resistance in 50% of studies included in this review.