Exploring the therapeutic potential of quercetin in cancer treatment: Targeting long non-coding RNAs.

The escalating global incidence of cancer, which results in millions of fatalities annually, underscores the pressing need for effective pharmacological interventions across diverse cancer types. Long noncoding RNAs (lncRNAs), a class of RNA molecules that lack protein-coding capacity but profoundly impact gene expression regulation, have emerged as pivotal players in key cellular processes, including proliferation, apoptosis, metastasis, cellular metabolism, and drug resistance. Among natural compounds, quercetin, a phenolic compound abundantly present in fruits and vegetables has garnered attention due to its significant anticancer properties. Quercetin demonstrates the ability to inhibit cancer cell growth and induce apoptosis-a process often impaired in malignant cells. In this comprehensive review, we delve into the therapeutic potential of quercetin in cancer treatment, with a specific focus on its intricate interactions with lncRNAs. We explore how quercetin modulates lncRNA expression and function to exert its anticancer effects. Notably, quercetin suppresses oncogenic lncRNAs that drive cancer development and progression while enhancing tumor-suppressive lncRNAs that impede cancer growth and dissemination. Additionally, we discuss quercetin's role as a chemopreventive agent, which plays a crucial role in mitigating cancer risk. We address research challenges and future directions, emphasizing the necessity for in-depth mechanistic studies and strategies to enhance quercetin's bioavailability and target specificity. By synthesizing existing knowledge, this review underscores quercetin's promising potential as a novel therapeutic strategy in the ongoing battle against cancer, offering fresh insights and avenues for further investigation in this critical field.

Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer.

Colorectal neoplasms are one of the deadliest diseases among all cancers worldwide. Thymoquinone (TQ) is a natural compound of Nigella sativa that has been used in traditional medicine against a variety of acute/chronic diseases such as asthma, bronchitis, rheumatism, headache, back pain, anorexia, amenorrhea, paralysis, inflammation, mental disability, eczema, obesity, infections, depression, dysentery, hypertension, gastrointestinal, cardiovascular, hepatic, and renal disorders. This review aims to present a detailed report on the studies conducted on the anti-cancer properties of TQ against colorectal cancer, both in vitro and in vivo. TQ stands as a promising natural therapeutic agent that can enhance the efficacy of existing cancer treatments while minimizing the associated adverse effects. The combination of TQ with other anti-neoplastic agents promoted the efficacy of existing cancer treatments. Further research is needed to acquire a more comprehensive understanding of its exact molecular targets and pathways and maximize its clinical usefulness. These investigations may potentially aid in the development of novel techniques to combat drug resistance and surmount the obstacles presented by chemotherapy and radiotherapy.

The Potential Preventive and Therapeutic Roles of NSAIDs in Prostate Cancer.

Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.

The Critical Function of microRNAs in Developing Resistance against 5-Fluorouracil in Cancer Cells.

Although there have been significant advancements in cancer treatment, resistance and recurrence in patients make it one of the leading causes of death worldwide. 5-fluorouracil (5-FU), an antimetabolite agent, is widely used in treating a broad range of human malignancies. The cytotoxic effects of 5-FU are mediated by the inhibition of thymidylate synthase (TYMS/TS), resulting in the suppression of essential biosynthetic activity, as well as the misincorporation of its metabolites into RNA and DNA. Despite its huge benefits in cancer therapy, the application of 5-FU in the clinic is restricted due to the occurrence of drug resistance. MicroRNAs (miRNAs) are small, non-coding RNAs that act as negative regulators in many gene expression processes. Research has shown that changes in miRNA play a role in cancer progression and drug resistance. This review examines the role of miRNAs in 5-FU drug resistance in cancers.

Flavonoids nanostructures promising therapeutic efficiencies in colorectal cancer.

Colorectal cancer is among the frequently diagnosed cancers with high mortality rates around the world. Polyphenolic compounds such as flavonoids are secondary plant metabolites which exhibit anti-cancer activities along with anti-inflammatory effects. However, due to their hydrophobicity, sensitivity to degradation and low bioavailability, therapeutic effects have shown poor therapeutic effect. Nano delivery systems such as nanoliposomes, nanomicelles, silica nanoparticles have been investigated to overcome these difficulties. This review provides a summary of the efficiency of certain flavonoids and polyphenols (apigenin, genistein, resveratrol, quercetin, silymarin, catechins, luteolin, fisetin, gallic acid, rutin, and curcumin) on colorectal cancer models. It comprehensively discusses the influence of nano-formulation of flavonoids on their biological functions, including cellular uptake rate, bioavailability, solubility, and cytotoxicity, as well as their potential for reducing colorectal cancer tumor size under in vivo situations.

Effects of propolis supplementation on glycemic status, lipid profiles, inflammation and oxidative stress, liver enzymes, and body weight: a systematic review and meta-analysis of randomized controlled clinical trials.

The aim of meta-analysis was to assess the effects of propolis on markers of oxidative stress, lipid profiles, inflammation and glycemic control, liver enzymes, and weight control. The heterogeneity between the included studies was indicated using the Cochrane's Q test and I-square (I2) statistic. 14 trials were included in this meta-analysis. Our meta-analysis indicated a significant reduction in fating glucose (WMD: -17.00; 95% CI: -30.88, -3.11), HbA1C (WMD: -0.42; 95% CI: -0.75, -0.10), and insulin (WMD: -1.75; 95% CI: -3.24, -0.26) and a marginally significant reduction in insulin resistance (WMD: -0.60; 95% CI: -1.20, 0.00) following propolis supplementation in 10, 8, 6, and 5 studies, respectively. Pooling 5 effect sizes, a significant reduction was seen in ALT (WMD: -5.63; 95% CI: -10.59, -0.67) and aspartate aminotransferase (AST) (WMD: -3.09; 95% CI: -5.15, -1.03) following propolis. A significant beneficial effect was observed for CRP (WMD: -1.11; 95% CI: -1.92, -0.29), TNF-α (WMD: -6.71; 95% CI: -9.44, -3.98) and interleukin-6 (IL-6) (WMD: -17.99; 95% CI: -35.56, -0.42) concentrations after propolis supplementation. This study demonstrated the beneficial effects of propolis on FPG, HbA1c, insulin, CRP, TNF-α and liver enzymes levels. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-020-00696-w.

Designing an Outer Membrane Protein (Omp-W) Based Vaccine for Immunization against Vibrio and Salmonella: An in silico Approach.

BACKGROUND: Cholera triggered by Vibrio cholerae remains the main reason for morbidity and mortality all over the world. In addition, salmonellosis is regarded as an infectious disease that makes it essential for the identification and detection of Salmonella. With a beta-barrel structure consisting of eight non-parallel beta strands, OmpW family is widely distributed among gram-negative bacteria. Moreover, OmpW isolated from S. typhimurium and Vibrio cholerae can be used in vaccine design. METHODS: Topology prediction was determined. T-cell and B-cell epitopes were selected from exposed areas, and sequence conservancy was evaluated. The remaining loops and inaccessible residues were removed to prepare OmpW-1. High antigenicity peptides were detected to replace inappropriate residues to obtain OmpW-2. Physicochemical properties were assessed, and antigenicity, hydrophobicity, flexibility, and accessibility were compared to the native Omp-W structure. Low score areas were removed from the designed structure for preparing the OmpW-3. To construct OmpW-4, TTFrC was used as T-CD4+ cell-stimulating factor and CTB as adjuvant to the end of the C-terminal of this sequence, which can increase the antigenicity and sequence density. The sequences were re-analyzed to delete the unfavorable residues. Besides, the solubility of the mature OmpW and the designed structure were predicted while overexpressed in E. coli. RESULTS: The designed vaccine is a stable protein that has immune cells recognizing epitopes and is considered as an antigen. The construct can be overexpressed in an E. coli. CONCLUSION: The multi-epitope vaccine is a suitable stimulator for the immune system and would be a candidate for experimental research. Recent patents describe numerous inventions related to the clinical facets of vaccine peptide against human infectious disease.

Association of rs12487066, rs12044852, rs10735781, rs3135388, rs6897932, rs1321172, rs10492972, and rs9657904 Polymorphisms with Multiple Sclerosis in Iranian Population.

OBJECTIVES: Multiple sclerosis (MS) is a chronic disease of the central nervous system. The pathogenesis of MS is best described by a multifactorial model incorporating interactions between genetic and environmental factors with the role of genetic factors increasingly taken into account. The main goal of this study was to investigate the associations of rs12487066, rs12044852, rs10735781, rs3135388, rs6897932, rs1321172, rs10492972, and rs9657904 polymorphisms with MS in the Iranian population. METHODS: A total of 83 patients with MS (82.0% female and 18.0% male; mean age = 35.2±8.6 years) and 100 physically and mentally healthy subjects (81.0% female and 19.0% male; mean age = 40.4±6.4 years) were selected using convenient sampling. A 5 mL blood sample was taken from each case and control patient. We used the tetra-primer ARMS-PCR method to genotype the desired polymorphisms. The associations between polymorphisms and the disease were studied based on codominant, dominant, recessive, and overdominant models. RESULTS: The rs10735781 polymorphism was codominantly (p = 0.029), overdominantly (p = 0.008), and dominantly (p = 0.009) associated with the disease. The rs6897932 was also found to be codominantly (p = 0.012), dominantly (p = 0.019), and recessively (p = 0.011) associated with the disease. CONCLUSIONS: We found an association between the rs10735781 and rs6897932 polymorphisms on the EVI5 and IL7RA genes, respectively, with increased MS in the Iranian population. Therefore, single nucleotide polymorphisms in the EVI5 and IL7RA genes can be considered a prognostic marker of MS.

In silico identification of novel lncRNAs with a potential role in diagnosis of gastric cancer.

Gastric cancer (GC) is the second leading cause of cancer-related deaths in the world. Due to the shortage of adequate symptoms in the early stages, it is diagnosed when the tumor has spread to distant organs. Early recognition of GC enhances the chance of successful treatment. Molecular mechanisms of GC are still poorly understood. LncRNAs are emerging as new players in cancer in both oncogene and tumor suppressor roles. High-throughput technologies such as RNA-Seq, have revealed thousands of lncRNAs which are dysregulated in GC. In this study, we retrieved lncRNAs obtained by High-throughput technologies from OncoLnc database. Consequently, retrieved lncRNAs were compared in literature-based databases including PubMed. As a result, two lists, including experimentally validated lncRNAs and predicted lncRNAs were provided. We found 43 predicted lncRNAs that had not been experimentally validated in GC, so far. Further Bioinformatics analyses were performed to obtain the expression profile of predicted lncRNAs in tumor and normal tissues. Also, the roles and targets of predicted lncRNAs in GC were identified by related databases. Finally, using the GEPIA database was reviewed the significant relationship of predicted lncRNAs with the survival of GC patients. By recognizing the lncRNAs involved in initiation and progression of GC, they may be considered as potential biomarkers in the GC early diagnosis or targeted treatment and lead to novel therapeutic strategies. Communicated by Ramaswamy H. Sarma.

Effects of a rotational UV-C irradiation system and packaging on the shelf life of fresh pistachio.

BACKGROUND: In this study, fresh pistachio was exposed to UV-C irradiation (2.1 and 4.5 kJ m-2 ) in a rotating cylindrical system with seven germicidal UV-C lamps and immediately packed in perforated and non-perforated polyethylene terephthalate (PET). The fruit were evaluated for weight loss, total phenolic content, enzyme activities, color indices (L*, a*, b* and browning index), and microbial counts during 35 days of storage at 4 °C. RESULTS: UV-C treatment caused a significant decrease (P < 0.05) in the weight loss of fresh pistachios compared to the control. The activity of catalase and peroxidase enzymes was significantly higher (P < 0.05) in irradiated samples packed in non-perforated PET in comparison to those of untreated samples. Irradiation did not inhibit the activity of polyphenol oxidase in treated samples, although a slight decrease in polyphenol oxidase activity was observed in irradiated samples compared to control. The fruit treated with 2.1 kJ m-2 of UV-C and the control packed in non-perforated PET were lighter (L*), redder (a*), and less yellow (b*) compared to 4.5 kJ m-2 treated samples. Furthermore, a dose of 4.5 kJ m-2 UV-C significantly decreased sensory attributes of fresh pistachios compared to the other irradiation level and control. CONCLUSION: UV-C irradiation at a dose of 2.1 kJ m-2 and packing in non-perforated PET are recommended for fresh pistachio preservation based on the physicochemical, microbial, and sensory parameters. © 2019 Society of Chemical Industry.

Some of the effective factors in the pathogenesis of gastro-oesophageal reflux disease.

Oesophageal adenocarcinoma is one of the most fatal tumours to affect the digestive tract and is the eighth most common malignancy worldwide. Gastro-oesophageal reflux has an important role in the incidence of adenocarcinoma of the oesophagus. Gastro-oesophageal reflux disease (GERD) is a multifactorial, acid-peptic disorder that results from the reflux of noxious material from the stomach into the oesophagus. The refluxed material causes the occurrence of oesophageal inflammation which creates a condition that is called reflux oesophagitis. The prevalence of this disease has increased dramatically in recent decades, mostly in the western world, where it affects about 10% to 30% of the population. The aetiology of oesophageal mucosal damage is complicated. Many inflammatory mediators are produced within the gastrointestinal (GI) tract, but their contributions in pathophysiology and disease pathogenesis have not been well investigated. Despite the protective barrier provided by the oesophageal mucosa, refluxed materials can cause oxidative injury and in?ammatory responses that involve the epithelium and immune cells. The analysing cellular events in gastro- oesophageal reflux disease and physiological responses to such conditions are important and necessary for a better grasp of the pathogenesis of GERD and the expansion of new treatments. Therefore, we want to discuss some of the important and key factors of GERD disease in this article.

Evaluation of the effect of polyphenol of escin compared with ibuprofen and dexamethasone in synoviocyte model for osteoarthritis: an in vitro study.

Osteoarthritis (OA) is a chronic degenerative joint disease with inflammatory component. It is associated with progressive histological alterations and disabling symptoms. Today, drugs such as glucocorticoids (GCs) and nonsteroidal anti-inflammatory drugs (NSIADs) are commonly employed for treatment of osteoarthritis, but have serious and life-threatening side effects. The aim of the current study is to evaluate the effects of escin on cyclooxygenase-2 (COX-2, isoform), inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß), interleukin-18 (IL-18), tumor necrosis factor-alpha (TNF-α), and nitric oxide (NO) (1), as well as prostaglandin E2 (PGE2) on inflammatory cells, similar osteoarthritis in synoviocytes, and monocytes/macrophages, and to compare it with dexamethasone (DEX) and ibuprofen (IBP). Synovial cells were isolated from synovial membrane of the radiocarpal joint cartilage of an 8-month-old Holstein cow. THP-1 cells were prepared from Pasteur Institute of Iran. Cells were cultivated and exposed to lipopolysaccharide (LPS) stimulation without, or in the presence of, DEX, IBP, or escin. The gene expressions of IL-1ß, TNF-α, IL-18, COX-2, and iNOS were evaluated by real-time PCR. Concentrations of NO and PGE2 were measured by ELISA methods. Our cells secreted an increased amounts of IL-1ß, TNF-α, IL-18, COX-2, iNOS, NO, and PGE2 in response to LPS stimulation in all conditions. Escin can quench the gene expression of COX-2, iNOS, IL-1ß, IL-18, and TNF-α in synoviocyte cells and production of NO and PGE2 in monocyte/macrophage cells alike DEX and IBP. We can use from escin for the treatment of osteoarthritis as an anti-inflammatory agent in the latter but further studies to support the results from such a model are needed.

Osteogenic differentiation potential of mesenchymal stem cells cultured on nanofibrous scaffold improved in the presence of pulsed electromagnetic field.

Nowadays, tissue engineering by using stem cells in combination with scaffolds and bioactive molecules has made significant contributions to the regeneration of damaged bone tissues. Since the usage of bioactive molecules including, growth factors to induce differentiation is safety limited in clinical applications, and it has also been previously observed that extremely low frequency pulsed electromagnetic fields (PEMF) can be effective in the enhancement of proliferation rate and osteogenic differentiation of stem cells, the aim of this study was investigating the osteoinductive potential of PEMF in combination with Poly(caprolactone) (PCL) nanofibrous scaffold. To achieve this aim, Adipose-derived mesenchymal stem cells (ADSCs) isolated and characterized and then osteogenic differentiation of them was investigated after culturing on the surface of PCL scaffold under treatments of PEMF, PEMF plus osteogenic medium (OM) and OM. Analysis of common osteogenic markers such as Alizarin red staining, ALP activity, calcium content and four important bone-related genes in days of 7, 14, and 21 confirmed that the effects of PEMF on the osteogenic differentiation of ADSCs are very similar to the effects of osteogenic medium. Thus, regarding the immunological concerns about the application of bioactive molecules for tissue engineering, PEMF could be a good alternative for osteogenic medium. Although, results were showed a synergetic effect for simultaneous application of PEMF and PCL scaffold in the osteogenesis process of ADSCs. Taking together, ADSCs-seeded PCL nanofibrous scaffold in combination with PEMF could be a great option for use in bone tissue engineering applications.

Evaluation of iNOS Expression in Esophageal Cancer Patients.

BACKGROUND: Esophageal cancer is a public health concern around the world; this cancer is the sixth leading cause of death of cancer in the world with about 386,000 deaths per year. Its risk factors include environmental factors such as tobacco smoke, gastroesophageal reflux and genetic changes. iNOS is stated by the effect of various inflammatory factors and is thus called inducible NOS. Investigating iNOS expression is a powerful tool for understanding effective molecular parameters at tissue and cellular responses to external factors. In this research work, iNOS expression in patients with esophageal cancer was studied in Iran. MATERIALS AND METHODS: 15 formalin-fixed and paraffin-embedded (FFPE) esophageal cancer tissue samples and 15 normal FFPE samples were collected from various medical centers (Zabol, Zahedan, Kashan) to measure iNOS expression by real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). All PCR reactions were conducted by three replicates for iNOS and internal control (ß-actin) by 2-ΔΔCT (Livak) method. Differences were measured in target gene expression in patients and control group using the t test. All statistical analyses were done using the SPSS software. RESULTS: The results showed that there was no significant difference between iNOS expression in the case and control groups (p > 0.05); however, there was an increase in iNOS expression in the case group. On the other hand, there was a significant difference between iNOS expression in males and females in the two groups of healthy subjects and patients, and it was higher in women than in men. CONCLUSION: Further studies need to be conducted with larger sample sizes and in other populations to validate these findings.