microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/ß-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

ITGB1BP1, a Novel Transcriptional Target of CD44-Downstream Signaling Promoting Cancer Cell Invasion.

Breast cancer (BC) is the most common malignancy worldwide and has a poor prognosis, because it begins in the breast and disseminates to lymph nodes and distant organs. While invading, BC cells acquire aggressive characteristics from the tumor microenvironment through several mechanisms. Thus, understanding the mechanisms underlying the process of BC cell invasion can pave the way towards the development of targeted therapeutics focused on metastasis. We have previously reported that the activation of CD44 receptor with its major ligand hyaluronan (HA) promotes BC metastasis to the liver in vivo. Next, a gene expression profiling microarray analysis was conducted to identify and validate CD44-downstream transcriptional targets mediating its pro-metastatic function from RNA samples collected from Tet CD44-induced versus control MCF7-B5 cells. We have already validated a number of novel CD44-target genes and published their underlying signaling pathways in promoting BC cell invasion. From the same microarray analysis, Integrin subunit beta 1 binding protein 1 (ITGB1BP1) was also identified as a potential CD44-target gene that was upregulated (2-fold) upon HA activation of CD44. This report will review the lines of evidence collected from the literature to support our hypothesis, and further discuss the possible mechanisms linking HA activation of CD44 to its novel potential transcriptional target ITGB1BP1.

The Impact of ACE Gene Variants on Acute-Phase Reactants in Children with Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is the most important sequela of upper respiratory group A Streptococcus (GAS) infection. The role of the common angiotensin-converting enzyme (ACE) insertion/deletion (I/D) variant in the disease and its subtypes remains uncertain. The acute-phase reactants (APRs) C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) form part of the Jones criteria for diagnosing RHD, and genetic factors are known to influence baseline CRP and ESR levels. Therefore, here, we investigated the relationship between the ACE I/D polymorphism and APR levels in RHD. A total of 268 individuals were recruited, including 123 RHD patients and 198 healthy controls. There was a trend toward a higher D allele frequency in RHD patients. The ACE I/D polymorphism genotype frequency and DD+ID allelic carriage were significantly associated with a high APR level (p = 0.04 and p = 0.02, respectively). These results highlight the importance of ACE I/D polymorphisms in RHD for disease stratification, but not for disease predisposition. Further studies in larger cohorts and different populations are now required to confirm this association and to explore the mechanism of this effect.

Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications.

Neurodegenerative disorders include different neurological conditions that affect nerve cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination, and mental functioning. The molecular mechanisms underpinning neurodegenerative disease pathogenesis are still unclear. Nonetheless, there is experimental evidence to demonstrate that the perturbation of mitochondrial function and dynamics play an essential role. In this context, mitochondrial biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number, plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell division and variations in energy demand in response to extracellular stimuli; therefore, it may represent a promising therapeutic target for developing new curative approaches to prevent or counteract neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have been proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various tissues, including the nervous tissue, and an ever-growing number of studies highlight its neurotherapeutic potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT, TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in the context of neurodegenerative diseases.

SIRT1, a novel transcriptional downstream target of CD44, linking its deacetylase activity to tumor cell invasion/metastasis.

Our tetracycline-off-inducible CD44 expression system previously established in mouse model, revealed that activation of CD44 with its major ligand hyaluronan (HA) promoted breast cancer (BC) metastasis to the liver. To identify the mechanisms that underpin CD44-promoted BC cell invasion, microarray gene expression profiling using RNA samples from (Tet)-Off-regulated expression system of CD44s in MCF7 cells, revealed a set of upregulated genes including, nuclear sirtuin-1 (SIRT1 also known as NAD-dependent deacetylase), an enzyme that requires NAD+ as a cofactor to deacetylate several histones and transcription factors. It stimulates various oncogenic pathways promoting tumorigenesis. This data suggests that SIRT1 is a potential novel transcriptional target of CD44-downstream signaling that promote BC cell invasion/metastasis. This review will discuss the evidence supporting this hypothesis as well as the mechanisms linking SIRT1 to cell proliferation and invasion.

PCF11, a Novel CD44-Downstream Transcriptional Target, Linking Its 3'-End Polyadenylation Function to Tumor Cell Metastasis.

Breast Cancer (BC) is the most common and the major health issue in women worldwide. Metastasis, a multistep process, is the worst aspect of cancer and tumor cell invasion is the defining step. Tumor cell invasion requires cell adhesion molecules (CAMs), and alterations in CAMs is considered as an initiating event in metastasis. Among CAMs, CD44 is a large family of more than 100 isoform, and its precise function was initially controversial in BC. Therefore, we have previously established a (Tet)-off inducible expression system of CD44 in MCF-7 primary BC cell line, and showed that CD44 promoted BC invasion/metastasis both in vitro and in vivo. A microarray gene expression profiling revealed more than 200 CD44-downstream potential transcriptional target genes, mediating its role in BC cell invasion and metastasis. Among these CD44-target genes, the Pre-mRNA cleavage complex 2 protein (PCF11) was upregulated upon the activation of CD44 by its major ligand hyaluronan (HA); This prompted us to hypothesize PCF11 as a potential novel transcriptional target of CD44-promoted BC cell invasion and metastasis. A large body of evidence from the literature supports our hypothesis that CD44 might regulate PCF11 via MAPK/ERK pathway. This review aims to discuss these findings from the literature that support our hypothesis, and further provide possible mechanisms linking CD44-promoted cell invasion through regulation of its potential target PCF11.

Haematococcus pluvialis Microalgae Extract Inhibits Proliferation, Invasion, and Induces Apoptosis in Breast Cancer Cells.

Breast cancer (BC) is the most common malignant cancer in females worldwide. Drug resistance, toxicity, and the failure of current therapies to completely cure BC has challenged conventional medicine. Consequently, complementary alternative medicine has become popular due to its safety and efficacy. Haematococcus pluvialis (H. pulvialis) is a green microalga living in fresh water, and its crude extract is rich of bioactives, including carotenoids, known to inhibit cancer cell growth. In the present study, we investigated the effects of a methanol crude extract called "T1" of H. pulvialis on cell growth and migration/invasion of the BC cell line MDA-MB-231 in comparison to the fibroblast control cells. TI significantly suppressed BC cell growth, inhibited migration and invasion and induced apoptosis. Interestingly, apoptosis was mediated by a significant loss of mutant p53 protein, and increased Bax/Bcl2 ratio. Our findings support our hypothesis that T1 exerts its anti-cancer effects by inhibiting BC invasion and inducing apoptosis mediated, at least, via the p53/Bax/Bcl2 pathway. Ongoing experiments aim to identify the molecular mechanisms underpinning T1-inhibited BC cell invasion using pre-designed metastasis gene-based array method.

Associations between adult attachment and vision-related quality of life in visually impaired individuals.

PURPOSE: An attachment theory framework approach may allow insight into how social and psychosocial factors interact to impact vision-related quality of life (QoL). In this pilot study, we investigated potential associations between adult attachment style and visual function QoL of visually impaired individuals. METHODS: We recruited 38 visually impaired individuals (15 females, 23 males; 51.8 ± 16.0 years). Visual function measures included distance and near visual acuity (VA) and contrast sensitivity. All participants completed: the 25-item National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ 25) and the Experiences in Close Relationships-Relationships Structures questionnaire. RESULTS: Presenting conditions included inherited retinal dystrophy (n = 10), nystagmus (n = 9), glaucoma (n = 7) and other eye conditions (n = 12). There was a statistically significant negative correlation between the NEI-VFQ-25 composite score (45.5 ± 14.7) and attachment-related anxiety (r = -0.352, p = 0.033). The latter correlation still held when controlling for participants' level of vision (r = -0.352, p = 0.035). Despite the range of conditions and wide age range, these were not significantly correlated with any variable of interest in the current study. CONCLUSION: Attachment-related anxiety ought to be taken into account when managing a visually impaired individual. Attachment-based approaches could be used to improve access to support services for visually impaired individuals, as well as self-management of their condition.

Use of Model Predictive Control and Artificial Neural Networks to Optimize the Ultrasonic Release of a Model Drug From Liposomes.

The use of echogenic liposomes to deliver chemotherapeutic agents for cancer treatment has gained wide recognition in the last 20 years. Cancerous cells can develop multiple drug resistance (MDR), in part, due to the drop in concentration of chemotherapeutic agents below the therapeutic levels inside the tumor. This suggests that MDR can be reduced by controlling the level of drug release in the diseased area. In this paper, a model predictive controller based on neural networks is proposed tomaintain a constant chemotherapeutic release at the cancer site. The proposed systemwas able to follow the set point by varying the U.S. intensity within preset constraints. The system simulated model is viable and it showed a high average fit when stimulated with variable input variations, indicating the robustness of the nonlinear model. By maintaining a constant release of the drug so that the concentration level is above a certain threshold, we hope to reduce cancer resistance towards chemotherapeutic agents.

Use of traditional, complementary and allopathic medicines in Pakistan by cancer patients.

INTRODUCTION: The healthcare systems of developing countries are complex in that they often accommodate a range of disparate and often competing paradigms of care. This is the case in Pakistan where Indigenous traditional medicine (TM) co-exists with Western allopathic medicine and, in theory at least, with 'globalised' complementary and alternative medicines (CAM). To date we know little about what treatments are being chosen and why in this still predominantly rural country. AIM: To gain a preliminary understanding of patterns of usage of traditional medicine and globalised complementary and alternative medicine by cancer patients in Pakistan. METHOD: Structured survey of 362 cancer patients, from diverse regions in the Punjab and North-west Frontier Province provinces, who were being treated in four different hospitals in Lahore, Pakistan. RESULTS: Use of traditional medicine is high amongst cancer patients, with many patients using a combination of different therapeutic modalities. Unlike studies in Western contexts, this study indicated no relationship between cancer type or sex and use of CAM/TM. However level of education was influential in determining usage of particular TM. There is, however, no uniformity in patterns of use of different TM. CONCLUSION: There is less differentiation between social groups in usage of CAM and TM in Pakistan than has been reported in studies of western cancer patients. Differing levels of use for specific TM highlight the need to get beyond monolithic categorizations (such as TM) to understand use patterns for specific indigenous practices (in their social and cultural context).

Toward an understanding of decision making on complementary and alternative medicine use in poorer countries: the case of cancer care in Pakistan.

During the past 2 decades, the study of complementary and alternative medicine (CAM) in general, and the sociological study of CAM in particular, have developed apace in richer countries. In addition to data on use levels and the nature of provision, there is now increasing research on issues such as motivation for use, decision-making processes, and so on. The integration of nonorthodox therapies into cancer care has been an important focus for such work. However, this interest has yet to be matched by work in poorer countries. While the nature of traditional medicine (TM) has long been of interest to anthropologists, the new context (marked by the globalized nature of CAMs existing alongside TM and allopathic treatment) has yet to be examined in any depth. In this article, the authors discuss the structural and cultural context of the first sociological research to be conducted into the role ofCAMandTMin cancer care in Pakistan. They identify some potentially important processes (ie, those identified in the limited existing literature and in anecdotal commentary), which are being tested by the new empirical study. The specific foci of the work are outlined. It is argued that research in poorer countries is essential both to ensure that an existing academic imbalance is addressed and to underpin more informed policy making in complex medically pluralistic (poorer) countries.

Patient assessment of effectiveness and satisfaction with traditional medicine, globalized complementary and alternative medicines, and allopathic medicines for cancer in Pakistan.

BACKGROUND: Virtually no research has been conducted on patient assessments of traditional medicines and allopathic medicines for cancer care in poorer countries marked by pluralistic medical environments. Pakistan represents an excellent case for such a study because of the coexistence of culturally and historically specific indigenous traditional medicine, the strong presence of allopathic medicine, and, to a lesser extent, the availability of some globalized complementary and alternative medicines. AIM: To gain a preliminary understanding of cancer patients' perceptions of effectiveness and satisfaction with traditional medicine, globalized complementary and alternative medicine, and allopathy in the context of a pluralistic medical environment. STUDY DESIGN: Structured survey of 362 cancer patients, from diverse regions in the Punjab province and Northwest Frontier province, who were being treated in 4 different hospitals in Lahore, Pakistan. RESULTS: Use of traditional medicine remains high among cancer patients, with traditional healers used by the majority of those surveyed. Although patients' perceptions of the overall effectiveness of traditional medicines for treating cancer are low, those patients who do use traditional medicines still have high levels of satisfaction with these modalities. This is distinct from levels of satisfaction with, and perceptions of effectiveness of, Western cancer treatments, which were synonymous in this group of patients. Important differences in patient perceptions were found within groups (eg, between different forms of traditional healers) as well as between them. CONCLUSION: This study showed considerable support for complementary and alternative medicine/traditional medicine but also significant variation in usage of and perceptions of local traditional medicines. More research needs to be done to explore the social processes underlying this variation in cancer patients' preferences for particular traditional medicines.