MicroRNAs: Synthesis, mechanism, function, and recent clinical trials

AbstractMicroRNAs (miRNAs) are a class of small, endogenous RNAs of 21–25 nucleotides (nts) in length. They play an important regulatory role in animals and plants by targeting specific mRNAs for degradation or translation repression. Recent scientific advances have revealed the synthesis pathways and the regulatory mechanisms of miRNAs in animals and plants. miRNA-based regulation is implicated in disease etiology and has been studied for treatment. Furthermore, several preclinical and clinical trials have been initiated for miRNA-based therapeutics. In this review, the existing knowledge about miRNAs synthesis, mechanisms for regulation of the genome, and their widespread functions in animals and plants is summarized. The current status of preclinical and clinical trials regarding miRNA therapeutics is also reviewed. The recent findings in miRNA studies, summarized in this review, may add new dimensions to small RNA biology and miRNA therapeutics

A NATURAL PRODUCT DECURSIN ENHANCES THE RADIOSENSITIZATION OF IONIZING RADIATION AGAINST DMBA-INDUCED TUMOR

Objective: Radiation therapy has gained significant attention for the treatment and prevention of solid and malignant human tumors. However, after periodical exposures, radiation therapy losses its efficacy against cancer cells displaying radio-resistant phenotypes. Therefore, decursin might improve the efficiency of radiotherapy against a variety of human cancers. Methods: The chemopreventive efficacy of decursin was evaluated against B16F10 cancer cell lines and DMBA/croton oil-induced skin carcinogenesis in BALB/c mice. Decursin was administered intraperitoneal at the dose of 20 mg/kg/day for 8 weeks following exposure to 5 Gy of ionizing radiation (IR) after 1 month of DMBA application. Western blot was performed for underlying mechanism of radioresistance. Results: Decursin suppressed the proliferation and viability of melanoma cancer cell lines in a concentration- and time-dependent manner. The in vivo data collected from mice model revealed that decursin reduced the precancerous skin lesions and the incidence of tumor bearing in radiation-exposed mice. Decursin also enhanced the effect of IR by downregulation of Akt/NFκB pathway through activation of IκBα. Conclusion: Our results suggest that the activation of Akt/NFκB establishes a pro-survival response to radiation that may account for the development of radioresistance. Decursin blocks the abnormal expression of these proteins and potentiates the radiotherapeutic effect

Synthesis, characterization and antibacterial activity of silver nanoparticles using Rhazya stricta

Background Green synthesis of metallic nanoparticles has gained significant attention in the field of nanomedicine as an environment-friendly and cost-effective alternative in comparison with other physical and chemical methods. Several metals such as silver, gold, iron, titanium, zinc, magnesium and copper have been subjected to nanoformulation for a wide range of useful applications. Silver nanoparticles (AgNPs) are playing a major role in the field of nanomedicine and nanotechnology. They are widely used in diagnostics, therapeutic and pharmaceutical industries. Studies have shown potential inhibitory antimicrobial, anti-inflammatory and antiangiogenesis activities of AgNPs. Methods AgNPs have been synthesized using silver nitrate and methanolic root extract of Rhazya stricta that belongs to the Apocynaceae family. Stability and dispersion of nanoparticles were improved by adding xylitol. Synthesized nanoparticles were characterized by UV–Vis spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, X-ray diffractometer and Fourier transforms infrared spectroscopy. Furthermore, the antibacterial effect of the plant extract and the nanoparticles were evaluated against gram-positive (Bacillus subtilis) and gram-negative (Escherichia coli) bacteria. Results The average size of AgNPs synthesized, was 20 nm with the spherical shape. Rhazya stricta based nanoparticles exhibited improved antibacterial activity against both gram-positive and negative strains

Multifactorial role of flavonoids in prevention and treatment of various cancers

Bioactive compounds isolated from plants have gained a lot of attention in recent years. Among them flavonoids, which consist of a large group of polyphenolic compounds, are at the forefront in the treatment of various diseases including cancer. Flavonoids possess anti-cancer properties and they exert their curative effect by modulating different cell-signalling pathways like the Nf-kB pathway, PI3K/AKT/mTOR pathway and the JAK/STAT pathway. Flavonoids also possess anti-oxidant activity and they regulate the redox status and prevent damage caused by oxidative stress. Chemokines and cytokines play a key role in mediating the inflammatory response in a cell. Consequently, more inflammatory markers are recruited to the site of inflammation that leads to increased ROS and cause damage at the site of accumulation. The present review covers the recent studies, in vitro and in vivo, that highlight the promising potential of flavonoids in treating cancer.

Bacillus amyloliquefaciens RWL-1 as a New Potential Strain for Augmenting Biochemical and Nutritional Composition of Fermented Soybean

Soybean (Glycine max L.) is a good source of natural antioxidants and commonly consumed as fermented products such as cheonggukjang, miso, tempeh, and sufu in Asian countries. The aim of the current study was to examine the influence of novel endophytic bacterial strain, Bacillus amyloliquefaciens RWL-1 as a starter for soybean fermentation. During fermentation, the cooked soybeans were inoculated with different concentrations (1%, 3%, and 5%) of B. amyloliquefaciens RWL-1. The changes in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, total phenolic contents, isoflavones (Daidzin, Genistin, Glycitin, Daidzein, Glycitein, and Genistein), amino acids (aspartic acid, threonine, serine, glutamic acid, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, and proline) composition, and minerals (calcium, copper, iron, potassium, magnesium, manganese, sodium, nickel, lead, arsenic, and zinc) were investigated. The level of antioxidants, total phenolic contents, isoflavones, and total amino acids were higher in fermented soybean inoculated with 1% B. amyloliquefaciens RWL-1 after 60 h of fermentation as compared to control, 3% and 5% B. amyloliquefaciens RWL-1. Additionally, fermented soybean inoculated with 5% B. amyloliquefaciens RWL-1 showed the highest values for mineral contents. Changes in antioxidant activities and bioactive compounds depended on the concentration of the strain used for fermentation. From these results, we conclude that fermented soybean has strong antioxidant activity, probably due to its increased total phenolic contents and aglycone isoflavone that resulted from fermentation. Such natural antioxidants could be used in drug and food industries and can be considered to alleviate oxidative stress

Methanolic Extract of Artemia salina Eggs and Various Fractions in Different Solvents Contain Potent Compounds That Decrease Cell Viability of Colon and Skin Cancer Cell Lines and Show Antibacterial Activity against Pseudomonas aeruginosa

Artemia salina, crustaceans of class Branchiopoda and order Anostraca, are living and reproducing only in highly saline natural lakes and in other reservoirs where sea water is evaporated to produce salt. Artemia salina eggs can be purchased from pet stores, where they are sold as tropical fish food and a ready source for hatching shrimp. In the current study, methanolic crude extracts and various fractions of Artemia salina eggs extracted in other solvents were tested for effects on cell viability of human colorectal cancer cells (HCT116) and melanoma cells (B16F10) using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. A methanolic crude extract of eggs was obtained by cold maceration, followed by fractionation to obtain hexane, chloroform, ethyl acetate, n-butanol, and aqueous fractions. The methanolic crude extract decreased cell viability of HCT-116 and B16F10 cell lines at higher concentrations. The other fractions were evaluated using a cell viability assay, and chloroform and hexane showed the highest activity at significantly lower concentrations than did the methanolic fraction. Full scan profiles of the methanolic crude extract and the chloroform and hexane fractions were obtained by gas chromatography mass spectrometry (GC-MS), and the resultant compounds were identified by comparing their spectral data to those available in spectral matching libraries. ROS generation assay, flow cytometry, and western blot analysis provided supporting evidence that the hexane and chloroform fractions induced cell death in HCT116 and B16-F10 cell lines. All fractions were further tested for antibacterial activity against Pseudomonas aeruginosa, among which the hexane fraction showed the highest zone of inhibition on LB nutrient agar plates. This study demonstrated promising anticancer and antibacterial effects of Artemia salina egg extracts. Our results suggest that pure bioactive compounds obtained from Artemia salina eggs can provide new insights into the mechanisms of colon and skin cancer, as well as Pseudomonas aeruginosa inhibition

Challenges in the development of drugs for the treatment of tuberculosis

Tuberculosis infection is a serious human health threat and the early 21st century has seen a remarkable increase in global tuberculosis activity. The pathogen responsible for tuberculosis is Mycobacterium tuberculosis, which adopts diverse strategies in order to survive in a variety of host lesions. These survival mechanisms make the pathogen resistant to currently available drugs, a major contributing factor in the failure to control the spread of tuberculosis. Multiple drugs are available for clinical use and several potential compounds are being screened, synthesized, or evaluated in preclinical or clinical studies. Lasting and effective achievements in the development of anti-tuberculosis drugs will depend largely on the proper understanding of the complex interactions between the pathogen and its human host. Ample evidence exists to explain the characteristics of tuberculosis. In this study, we highlighted the challenges for the development of novel drugs with potent bacteriostatic or bactericidal activity, which reduce the minimum time required to cure tuberculosis infection

Diagnostic and Therapeutic Potential of Circulating-Free DNA and Cell-Free RNA in Cancer Management

Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances in applying molecular testing involve circulating-free DNA (cfDNA)- and cell-free RNA (cfRNA)-based liquid biopsies for the diagnosis, prognosis, prediction, and treatment of cancer. Both cfDNA and cfRNA are sensitive and specific biomarkers for cancer detection, which have been clinically proven through multiple randomized and prospective trials. These help in cancer management based on the noninvasive evaluation of size, quantity, and point mutations, as well as copy number alterations at the tumor site. Moreover, personalized detection of ctDNA helps in adjuvant therapeutics and predicts the chances of recurrence of cancer and resistance to cancer therapy. Despite the controversial diagnostic values of cfDNA and cfRNA, many clinical trials have been completed, and the Food and Drug Administration has approved many multigene assays to detect genetic alterations in the cfDNA of cancer patients. In this review, we underpin the recent advances in the physiological roles of cfDNA and cfRNA, as well as their roles in cancer detection by highlighting recent clinical trials and their roles as prognostic and predictive markers in cancer management