The Prognostic Value and Clinical Significance of lncRNA SNHG5 Expression in Patients with Multiple Malignancies: A Bioinformatic and Meta-Analysis.

BACKGROUND: Long non-coding RNA small nucleolar RNA host gene 5 (lncRNA SNHG5) has been identified as both a promising target for treatment and a predictor of prognosis in diverse types of cancer. The objective of this study was to assess whether lncRNA SNHG5 expression can be utilized as a prognostic biomarker for human cancer. METHODS: To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases. RESULTS: In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC). CONCLUSION: These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.

Age-specific reference intervals for liver function tests in healthy neonates, infants, and young children in Iran.

BACKGROUND: The reference intervals (RIs) for liver function tests (LFTs) were determined in Iranian children for the first time. METHODS: A total of 344 healthy pediatrics aged 3 days to 30 months old were recruited. Serum levels of ALT, AST, ALP, direct bilirubin, and total bilirubin were measured. RIs were determined using CLSI Ep28-A3 guidelines. RESULTS: All analytes demonstrated age-specific differences except AST. ALT and ALP demonstrated significantly elevated levels in infants 0 to <5 months relative to the remainder of the age range. Direct and total bilirubin demonstrated markedly elevated levels in early life with mean of 0.28 mg/dL and 1.64 mg/dL observed for direct and total bilirubin, respectively, decreasing by ~50% in the adjacent partition. CONCLUSION: These novel data will help improve the clinical interpretation of biochemical test results in young Iranian neonates and children and can be of value to clinical laboratories with similar populations.

Age-specific reference intervals for routine biochemical parameters in healthy neonates, infants, and young children in Iran.

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age-specific RIs for 7 laboratory biochemical parameters. This cross-sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high-sensitivity C-reactive protein (hs-CRP) were measured using an Alpha classic-AT plus auto-analyser. We determined age-specific RIs using CLSI Ep28-A3 and C28-A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs-CRP, which remained relatively constant throughout the age range. Age-specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer.

The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

Therapeutic Effects of Polyphenols on the Treatment of Colorectal Cancer by Regulating Wnt ß-Catenin Signaling Pathway.

Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide in terms of both its rates of incidence and mortality. Due to serious side effects associated with conventional chemotherapeutic treatments, many natural products with fewer adverse side effects have been considered as potential treatment options. In fact, many natural products have widely been used in various phases of clinical trials for CRC, as well as in in vitro and in vivo preclinical studies. Curcumin (CUR) and resveratrol (RES) are classified as natural polyphenolic compounds that have been demonstrated to have anticancer activity against CRC and are associated with minimal side effects. By regulating select target genes involved in several key signaling pathways in CRC, in particular, the Wnt ß-catenin signaling cascade, the course of CRC may be positively altered. In the current review, we focused on the therapeutic effects of CUR and RES in CRC as they pertain to modulation of the Wnt ß-catenin signaling pathway.

Clinical Importance of Wnt5a in the Pathogenesis of Colorectal Cancer.

Wnt5a is one of the potent signaling molecules that initiates responses involved in cancer through activation of both canonical and noncanonical signaling cascades. Wnt5a both directly and indirectly triggers cancer-associated signaling pathways based on the cancer type. In colorectal cancer (CRC), altering Wnt5a expression can influence several cellular processes of tumor cells, including proliferation, differentiation, migration, invasion, and metastasis. This review summarizes the molecular mechanisms and clinical importance of Wnt5a in the pathogenesis of CRC for better understanding the pathogenesis and its potential role as a prognostic marker and as an appropriate therapeutic target in the treatment of this disease in the future.

Crocin as a novel therapeutic agent against colitis.

Ulcerative colitis is a chronic inflammatory bowel disease with high incidence and prevalence worldwide. To investigate the therapeutic potency of crocin, as a pharmacologically active component of saffron, in dextran sodium sulfate (DSS)-induced colitis mice model. Experimental colitis was induced by 7-day administration of DSS dissolved in water at a concentration of 1.5% (w/v). The animals were randomly divided into four groups (n»6 for each group). (1) Control group received regular drinking water for four weeks, (2) the second group of mice received regular drinking water for three weeks and then received DSS for one week, (3) and (4) the other two groups received 50-ppm or 200-ppm crocin for three weeks, respectively, and then treated with DSS for one week. Our results showed that Crocin attenuates colitis disease activity index including body weight loss, diarrhea, rectal bleeding, and colon shortening in crocin pre-tread mice. Comparison of histology of colon tissues between groups showed that crocin significantly decreases colon histopathological score, at least partially, by eliciting anti-inflammatory responses in DSS-induced colitis mice. These results clearly showed that crocin is a novel therapeutic agent with low toxicity as well as great clinical significance in treatment of colitis.

Role of Wnt3a in the pathogenesis of cancer, current status and prospective.

The Wnt signaling pathway plays a critical role in initiation, progression, invasion and metastasis of cancer. Wnt3a as a canonical Wnt ligand is strongly implicated in the etiology and pathology of a number of diseases including cancer. Depending on cancer type, Wnt3a enhances or suppresses metastasis, cell proliferation and apoptosis of cancer cells. This review summarizes the role of Wnt3a in the pathogenesis of different cancers including colorectal, prostate, hepatocellular, lung and leukemia, for promoting greater understanding and clinical management of these diseases.

Therapeutic potency of crocin in the treatment of inflammatory diseases: Current status and perspective.

Crocin is the major component of saffron, which is used in phytomedicine for the treatment of several diseases including diabetes, fatty liver, depression, menstruation disorders, and, of special interest in this review, inflammatory diseases. Promising selective anti-inflammatory properties of this pharmacological active component have been observed in several studies. Saffron has been shown to exert anti-inflammatory properties against several inflammatory diseases and can be used as a novel therapeutic agent for the treatment of inflammatory diseases either alone or in combination with other standard anti-inflammatory agents. This review summarizes the protective role of saffron and its pharmacologically active constituents in the pathogenesis of inflammatory diseases including digestive diseases, dermatitis, asthma, atherosclerosis, and neurodegenerative diseases for a better understanding and hence a better management of these diseases.

Role of thrombin in the pathogenesis of atherosclerosis.

Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.

Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate cancer, current status and perspectives.

Prostate cancer is a major cause of cancer-related death in males. Wnt/ß-catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease.

The clinical impact of exosomes in cardiovascular disorders: From basic science to clinical application.

Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of a valid biomarker that accurately predicts the risk of developing CVD, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, messenger RNAs, noncoding RNA, and nucleic acid contents that are important players in intercellular communication, and that act via long-range signals or cell-to-cell contact. The discovery of exosomes provides potential strategies for the diagnosis and treatment of CVD. In the current review, we have explored the potential impact of exosomes on cardiovascular physiology, and their therapeutic potential in cardiovascular disorders with an emphasis on the existing preclinical studies.

The prognostic potential of long noncoding RNA HOTAIR expression in human digestive system carcinomas: A meta-analysis.

Homeobox transcript antisense intergenic RNA (HOTAIR), one of the well-known long noncoding RNAs (lncRNAs), plays an important role in initiation and development of various tumors. Elevated level of HOTAIR is associated with metastatic behavior of primary tumor and poor outcome in several cancers. Therefore, we conducted a meta-analysis to clearly measure the prognostic impact of HOTAIR in patients with digestive system carcinomas. Fourteen studies including 2,666 patients with five different type of digestive system cancers were selected to be entered in meta-analysis. Finding demonstrated that HOTAIR overexpression could predict unfavorable outcome in digestive system carcinomas (hazard ratio [HR] = 2.4, 95% confidence interval [CI]: 2.0-2.9; p < 0.001; fixed-effect model). In stratified analysis, increased level of HOTAIR predicted poor overall survival in gastric cancer (HR = 2.1, 95% CI: 1.6-2.9; p < 0.001), colorectal cancer (HR = 4.1, 95% CI: 1.6-10.2; p = 0.002), esophageal squamous cell carcinoma (HR = 2.3, 95% CI: 1.7-3.0; p < 0.001), and hepatocellular carcinoma (HR = 3.4, 95% CI: 1.9-6.1; p < 0.001). Our meta-analysis results clearly support the prognostic value of HOTAIR to predict unfavorable prognostic outcomes in diverse digestive system carcinomas.

Role of the transforming growth factor-ß signaling pathway in the pathogenesis of colorectal cancer.

The transforming growth factor-ß (TGF-ß) signaling pathway plays an important role in cancer cell proliferation, growth, metastasis, and apoptosis. It has been shown that TGF-ß acts as a tumor suppressor in the early stages of the disease, and as a tumor promoter in its late stages. Mutations in the TGF-ß signaling components, the TGF-ß receptors and cytoplasmic signaling transducers, are frequently observed in colorectal carcinomas. Exploiting specific TGF-ß receptor agonist and antagonist with antitumor properties may be a way of controlling cancer progression. This review summarizes the regulatory role of TGF-ß signaling in the pathogenesis of colorectal cancer.

Role of Wnt5a in the Pathogenesis of Inflammatory Diseases.

Wnt5a initiates pro-inflammatory responses through activation of non-canonical Wnt signaling pathway. Pro-inflammatory functions of Wnt5a trigger pro-inflammatory signaling cascades and increase secretion of pro-inflammatory cytokines and chemokines. Wnt5a as a potent signaling molecule is strongly implicated in a number of diseases including cancer, diabetes, metabolic disorders, and of special interest in this review, inflammatory diseases. This review summarizes the role of Wnt5a in the pathogenesis of inflammatory diseases including atherosclerosis, rheumatoid arthritis, psoriasis vulgaris and sepsis, promoting greater understanding, and clinical management of these diseases. J. Cell. Physiol. 232: 1611-1616, 2017. © 2016 Wiley Periodicals, Inc.