Exploring the role of trifarotene against RAR-α: an investigation of expression pattern and clinicopathological significance of RAR-α in breast cancer.

Introduction: The members retinoic acid receptors (RARs) (α, ß, and γ) and retinoid X receptors (RXRs) (α, ß, and γ) belong to the retinoid receptor family. They regulate the biological action of classical retinoids through nuclear retinoid receptors, a transcription factor that is regulated by ligands. Through the binding of particular retinoic acid-responsive elements (RAREs) located in target gene promoters, RARs and members of the RXRs form heterodimers. By binding to its nuclear receptors and triggering the transcription of the target genes downstream, retinoic acid (RA) mediates the expression of certain genes. Retinoids so mainly control gene expression to carry out their biological actions. RARs are essential for many biological processes, such as development, immunity, reproduction, organogenesis, and homeostasis. Apart from their physiological functions, RARs are also linked to pathologies and tumors due to mutations, protein fusions, changes in expression levels, or abnormal post-translational changes that lead to aberrant functions and homeostasis breakdown. The oncogenic development of animal tissues or cultured cells is linked to altered expression of retinoid receptors. The RAR-α is over-expressed in several malignancies. Increased invasion and migration in several cancer forms, including HNSC carcinoma, pediatric low-grade gliomas, lung adenocarcinoma, and breast cancer, have been linked to its upregulated expression. Numerous approved therapeutic regimens targeting RAR-α have been developed, improving patient survival rates. Objective: This study's main objective was to identify novel RAR-α-targeting drugs and evaluate the expression patterns of RAR-α in breast cancer patients. Methodology: In-silico investigation using a variety of bioinformatics tools like UALCAN, TISCH, TIMER 2.0, ENRICHR, and others were employed to examine the expression of RAR-α. Further we evaluated in-silico inhibition of RAR-α with trifarotene and also tested the cytotoxicity of trifarotene in breast cancer cells. Results: Our research indicates that RAR-α is upregulated in several malignancies including Breast Cancer. It regulates granulocyte differentiation and has an association with the retinoic acid receptor signaling pathway and cellular response to estrogen stimulus. Furthermore, trifarotene was found as a potential synthetic compound that targets RAR-α through in silico and in-vitro study. Discussion: Overall, this research indicates that elevated expression of RAR-α enhances the onset of breast cancer. Using trifarotene medication to target RAR-α will significantly boost the response of breast cancer individuals to treatment and delay the development of resistance to drugs.

Development of Germinated-Brown-Rice-Based Novel Functional Beverage Enriched with γ-Aminobutyric Acid: Nutritional and Bio-Functional Characterization.

γ-aminobutyric acid (GABA), recognized as a primary inhibitory neurotransmitter within the brain, serves a crucial role in the aging process and in neurodegenerative conditions such as Alzheimer's disease. Research has demonstrated the beneficial effects of GABA, particularly for elderly individuals. Given that elderly individuals often encounter challenges with swallowing food, beverages designed to address dysphagia represent a preferable option for this demographic. Among the different processing techniques, the germination process triggers biochemical changes, leading to an increase in certain nutrients and bioactive compounds (e.g., GABA). Therefore, we attempted to develop a novel functional beverage utilizing germinated brown rice enriched with GABA and studied its nutritional and bio-functional characterization. The optimal conditions (X1, X2, X3 and X4.) were determined: powdered sugar (40 g), chocolate powder (20 g), sodium carboxymethyl cellulose (0.5 g), GBR (220 g), and water (440 mL). The results of storage studies indicated that the germinated-brown-rice-based beverage exhibited favorable nutritional attributes, including increased γ-oryzanol (52.73 ± 1.56%), total phenolic content (26.68 ± 1.56 mg GAE/100 g), niacin (5.17 ± 0.14%), and GABA (42.12 ± 0.63 mg/100 g) levels. Additionally, the beverage demonstrated notable antioxidant activity (74.23 ± 2.37 µmol TE/100 g), suggesting potential health-promoting effects. Sensory evaluation revealed satisfactory acceptability among consumers, highlighting its palatability. Overall, this study elucidates the development of a novel functional beverage utilizing germinated brown rice enriched with GABA, offering promising nutritional and bio-functional characteristics for health-conscious consumers.

Metronomic chemotherapy and drug repurposing: A paradigm shift in oncology.

Cancer represents a significant global health and economic burden due to its high mortality rates. While effective in some instances, traditional chemotherapy often falls short of entirely eradicating various types of cancer. It can cause severe side effects due to harm to healthy cells. Two therapeutic approaches have risen to the forefront to address these limitations: metronomic chemotherapy (MCT) and drug repurposing. Metronomic chemotherapy is an innovative approach that breaks from traditional models. It involves the administration of chemotherapeutic regimens at lower doses, without long drug-free intervals that have previously been a hallmark of such treatments. This method offers a significant reduction in side effects and improved disease management. Simultaneously, drug repurposing has gained considerable attraction in cancer treatment. This approach involves utilizing existing drugs, initially developed for other therapeutic purposes, as potential cancer treatments. The application of known drugs in a new context accelerates the timeline from laboratory to patient due to pre-existing safety and dosage data. The intersection of these two strategies gives rise to a novel therapeutic approach named 'Metronomics.' This approach encapsulates the benefits of both MCT and drug repurposing, leading to reduced toxicity, potential for oral administration, improved patient quality of life, accelerated clinical implementation, and enhanced affordability. Numerous clinical studies have endorsed the efficacy of metronomic chemotherapy with tolerable side effects, underlining the potential of Metronomics in better cancer management, particularly in low- and middle-income countries. This review underscores the benefits and applications of metronomic chemotherapy and drug repurposing, specifically in the context of breast cancer, showcasing the promising results of pre-clinical and clinical studies. However, we acknowledge the necessity of additional clinical investigations to definitively establish the role of metronomic chemotherapy in conjunction with other treatments in comprehensive cancer management.

Clinicopathological Significance and Expression Pattern of Bcl2 in Breast Cancer: A Comprehensive in silico and in vitro Study.

B-cell lymphoma/leukemia gene-2 (Bcl-2) is the primary proto-oncogene that has been shown to work by preventing apoptosis/programmed cell death. Bcl-2 combines a variety of cell-generated signals associated to the survival and death of cells. In glioma, lung, and breast cancer, Bcl-2 over-expression has been linked to an increase in invasion and migration. Many treatment regimens that target Bcl2 have been established and approved, and thus increasing the survival rates of the patients. The primary goal of this research was to recognize new therapeutic compounds that target Bcl2 and assess Bcl2 expression pattern in BC patients. We used various bioinformatic tools as well as several in vitro assays to look out the expression and inhibition of Bcl2 in BC. Our study depicted that Bcl2 had a strong connection with tumour stroma, notably with suppressor cells originating from myeloid tissues. Moreover, in vitro and in silico research identified Paclitaxel as a promising natural substance that targets Bcl2. Overall, this work shows that Bcl2 overexpression accelerates the development of BC, and that targeting Bcl2 in combination with other drugs will dramatically improve BC patient's response to treatment and prevent the emergence of drug resistance.

Targeting breast cancer stem cells through retinoids: A new hope for treatment.

Breast cancer is a complex and diverse disease accounting for nearly 30% of all cancers diagnosed in females. But unfortunately, patients develop resistance to the existing chemotherapeutic regimen, resulting in approximately 90% treatment failure. With over half a million deaths annually, it is imperative to explore new therapeutic approaches to combat the disease. Within a breast tumor, a small sub-population of heterogeneous cells, with a unique ability of self-renew and differentiation and responsible for tumor formation, initiation, and recurrence are referred to as breast cancer stem cells (BCSCs). These BCSCs have been identified as one of the main contributors to chemoresistance in breast cancer, making them an attractive target for developing novel therapeutic strategies. These cells exhibit surface biomarkers such as CD44+, CD24-/LOW, ALDH, CD133, and CD49f phenotypes. Higher expression of CD44+ and ALDH activity has been associated with the formation of tumors in various cancers. Moreover, the abnormal regulation of signaling pathways, including Hedgehog, Notch, ß-catenin, JAK/STAT, and P13K/AKT/mTOR, leads to the formation of cancer stem cells, resulting in the development of tumors. The growing drug resistance in BC is a significant challenge, highlighting the need for new therapeutic strategies to combat this dreadful disease. Retinoids, a large group of synthetic derivatives of vitamin A, have been studied as chemopreventive agents in clinical trials and have been shown to regulate various crucial biological functions including vision, development, inflammation, and metabolism. On a cellular level, the retinoid activity has been well characterized and translated and is known to induce differentiation and apoptosis, which play important roles in the outcome of the transformation of tissues into malignant. Retinoids have been investigated extensively for their use in the treatment and prevention of cancer due to their high receptor-binding affinity to directly modulate gene expression programs. Therefore, in this study, we aim to summarize the current understanding of BCSCs, their biomarkers, and the associated signaling pathways. Retinoids, such as Adapalene, a third-generation retinoid, have shown promising anti-cancer potential and may serve as therapeutic agents to target BCSCs.

Elucidation of interleukin-19 as a therapeutic target for breast cancer by computational analysis and experimental validation.

Interleukin 19 (IL-19) is a cytokine produced by monocytes and belongs to the family of IL-10. The IL-19 protein stimulates fibronectin (FN) expression and assembly, metastasis, and cell division in breast cancer (BC) cells. IL-19, which is connected to breast pathogenesis and has an autocrine action in BC cells, is a key predictor of prognosis for many tumour forms, including breast cancer. Augmented IL-19 expression has been related to poorer clinical outcomes for patients with BC and directly enhances proliferation and migration while also serving as a microenvironment for tumour formation. The main aim of our study was to examine the expression profile, functional role, and prognostic significance of interleukin-19 in BC pathogenesis and also to find out the molecular mechanism of IL-19 in BC. In this work, we used the various computational approach and tools, to evaluate the expression profile and prognostic implication of IL-19 in BC and discover the role of IL-19 in BC pathogenesis. IL-19 was shown to be highly upregulated in BC as compared to other interleukins. Also, its levels were highly overexpressed in liminal BC patients, mostly in 3rd stage groups under the age group of 21-40 years. IL-19 levels were increased in BC and elevated expression of IL-19 was examined to have worse overall survival (OS). The KEGG analysis and gene ontology of IL-19 depict that IL-19 is significantly augmented in cytokine activity and receptor-ligand activity and also in the JAK-STAT signaling pathway. Moreover, IL-19 showed a high correlation with IL20RA, as later is involved with the JAK-STAT signaling pathway. The in-vivo and in-vitro studies have also reflected that upregulation of IL-19 enhances tumor development and affects clinical outcomes in BC patients through several pathways including the JAK TAT signalling pathway. Overall, our study indicates that IL-19 increases tumour growth and that inhibiting it in addition to standard treatments will greatly improve BC patient's therapeutic responses.

Amaranth and quinoa as potential nutraceuticals: A review of anti-nutritional factors, health benefits and their applications in food, medicinal and cosmetic sectors.

Amaranth and quinoa are small-seeded grains with high nutritional and phytochemical profiles that promote numerous health benefits and offer protection against various chronic ailments including hypertension, diabetes, cancer, and cardiovascular disorders. They are classified as pseudocereals and possess significant nutritional benefits due to their abundance of proteins, lipids, fiber, vitamins, and minerals. Moreover, they exhibit an exceptional balance of essential amino acids. Despite having several health benefits, these grains have lost their popularity due to their coarse nature and are neglected in developed countries. Research and development activities are growing to explore these underutilized crops, characterizing and valorizing them for food applications. In this context, this review highlights the latest advancements in use of amaranth and quinoa as nutraceutical and functional foods, covering their bioactive substances, anti-nutritional factors, processing techniques, health benefits, and applications. This information will be valuable for planning novel research for efficient use of these neglected grains.

Targeting p53 misfolding conundrum by stabilizing agents and their analogs in breast cancer therapy: a comprehensive computational analysis.

Cancer continues to be a major global public health concern and one of the foremost causes of death. Delays in the diagnosis and cure may cause an increase in advanced stage disease and mortality. The most common cancer found in women currently is breast carcinoma. Breast carcinoma has surpassed lung carcinoma and currently represents the chief type of cancer diagnosed (2.3 million new cases, which amount to 11.7% of all cancer cases). In addition, by 2040, the incidence will increase by more than 46% as per the estimates of GLOBOCAN. Triple-negative breast cancer (TNBC) represents a highly aggressive and invasive subtype of breast cancer, characterized by rapid progression, short response time to the available treatment, and poor clinical results. Thus, it is very crucial to develop novel diagnostic tools and therapeutics with good efficacy. A majority of cancers display malfunction along the p53 pathway. Moreover, p53 not only loses its function but is also prone to misfolding and aggregation, leading to formation of amyloid aggregates as well. Research is being carried out to find ways to restore the normal action and expression of p53. Here, we have explored PhiKan-083 for its possible stabilizing effect on p53 in order to address the problem with its misfolding. Thus, examining the analogs of PhiKan-083 that have a role in p53 stability will help update our understanding of cancer progression and may expedite the progress of new anticancer treatments. We anticipate that the drug molecules and their analogs targeting p53 aggregation may be used in combination with other anticancer compounds to solve the problem with p53 aggregation. In this study, by employing ADMET analysis, the compounds were screened, and we further examined the chosen compounds with the help of molecular docking. By using databases like UALCAN, TIMER, GEPIA, and PredictProtein, we investigated TP53's expression pattern and prognostic relevance in various cancer settings.

Development of chitosan-based biodegradable films enriched with thyme essential oil and additives for potential applications in packaging of fresh collard greens.

In the present study, chitosan (CH) based biodegradable films were developed enriched with thyme essential oil (TEO) incorporated with different additives including zinc oxide (ZnO), polyethylene glycol (PEG), nano clay (NC), and calcium chloride (CaCl2) and characterize the postharvest quality of 'collard greens' during refrigerated storage. The results indicated that the incorporation of ZnO/PEG/NC/CaCl2 in CH-based films significantly decreased water vapor transmission rate, increased tensile strength, and were water soluble and biodegradable in nature. Moreover, CH-TEO based films incorporated with ZnO/PEG/NC/CaCl2 were significantly effective in reducing physiological weight loss, retained total soluble solids, titratable acidity, and preserved chlorophyll contents as well as showed lesser a* values, suppressed microbial growth, and preserving appearance/sensory quality of collard greens for 24 days than LDPE and other biodegradable films. Our results suggest that CH-based films enriched with TEO and additives such as ZnO/CaCl2/NC/PEG are an ecological, environmental friendly, and effective alternative approach to retain shelf life of collard greens during refrigerated storage.

Preparation of a biodegradable chitosan packaging film based on zinc oxide, calcium chloride, nano clay and poly ethylene glycol incorporated with thyme oil for shelf-life prolongation of sweet cherry.

This study includes development of chitosan-based films with incorporated essential thyme oil and different combinations of cross-linkers viz., ZnO, CaCl2, NC, and PEG for the safe storage of sweet cherries. The resulting films stored with sweet cherries were analyzed for different physicochemical and antimicrobial properties. Incorporation of ZnO, CaCl2, NC, and PEG in chitosan-based films maintained fruit quality by conserving higher total soluble solids, titratable acidity, and reduced weight loss. The combined ZnO + CaCl2 + NC + PEG in chitosan-based films also suppressed microbial activity. The sensorial quality of fruits stored with CH + ZnO + CaCl2 + NC + PEG treatment was also stable during storage. In conclusion, the combined CH + ZnO + CaCl2 + NC + PEG with added thyme oil application is an effective approach to maintain the postharvest quality and could be an alternative to increase the shelf life of sweet cherries, besides decreasing environmental impacts of non-biodegradable packages.

Influence of Canning and Storage on Physicochemical Properties, Antioxidant Properties, and Bioactive Compounds of Apricot (Prunus armeniaca L.) Wholes, Halves, and Pulp.

This study aimed to examine the effect of canning and storage on physicochemical, mineral, and antioxidant properties and phenolic composition of apricot wholes, halves, and pulp. The findings for physicochemical properties revealed that the total soluble solids, titratable acidity, total sugars, and ascorbic acid were found higher in apricot pulp (37.15, 1.39, and 20.74% and 7.21 mg/100 g FW, respectively) followed by apricot wholes and halves throughout the storage period. The remarkable contents of potassium, phosphorous, zinc, copper, iron, and manganese were found in the apricot pulp which revealed that canning and storage slightly affected the mineral composition. Bioactive substances were identified and quantified by reversed-phase high-performance liquid chromatography, which indicated a higher presence of chlorogenic acid (34.45 mg/kg FW), quercitin-3-glucoside (16.78 mg/kg FW), neochlorogenic acid (26.52 mg/kg FW), gallic acid (5.37 mg/kg FW), kaempferol (14.22 mg/kg FW), ellagic acid (6.02 mg/kg FW), procyanidin B2 (8.80 mg/kg FW), and epicatechin (9.87 mg/kg FW) in apricot pulp followed by apricot wholes and halves throughout the storage period. The total phenolic content was found highest in apricot pulp (13.76 GAE mg/100 g FW) followed by wholes (8.09 GAE mg/100 g FW) and halves (6.48 GAE mg/100 g FW) which decreased significantly throughout the storage period. Antioxidant properties were assessed by DPPH, ABTS+, MCA, and BCBA, which were found higher in the apricot pulp (92.23 TEAC µg/g DW, 92.33 TEAC µg/g DW, 33.80 TEAC µg/g DW, and 68.40 TEAC µg/g DW, respectively) that is correlated with the higher presence of bioactive compounds. Thus, apricot pulp containing excellent sources of nutrients, minerals, phytochemicals, and antioxidant components could be used for consumption purposes that provide nutraceuticals and antioxidants globally.

Effect of oxalic acid and salicylic acid treatments on the post-harvest life of temperate grown apricot varieties (Prunus armeniaca) during controlled atmosphere storage.

This study aimed at investigating the influence of different postharvest treatments with oxalic acid (OA) and salicylic acid (SA) on quality attributes and postharvest shelf life of temperate grown apricot varieties stored under controlled atmosphere (CA) storage conditions. After each treatment was given, the samples were stored in CA store maintained at a temperature of 0 °C, 90 ± 5% relative humidity, 5% oxygen and 15% carbon dioxide for 30 days. Results indicated that both OA and SA treatments significantly (p ≤ 0.05) retained total soluble solids, titratable acidity, color profile, ascorbic acid content and total phenolic content of apricot varieties and had a positive effect on antioxidant activity and texture of samples compared to control. However, carotenoid content was found to be higher in control. Both the treatments reduced chilling injury index, weight loss and decay percentage of samples. Moreover, it was found that SA treatment was the most effective treatment in maintaining visual color of apricots while OA maintained fruit firmness and effectively decreased the decay percentage and chilling injury index of apricot varieties. In conclusion, it was found that both OA and SA have the potential to extend storage life of apricots and maintain quality attributes of the crop during CA storage.